Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: g. pH, Viscosity, Gel strength and Spreadability. The pH, viscosity, gel strength and spreadability of the prepared Cur-Nanogels were found to be optimum at of 0. 3%. The optimized Cur-Nanogel was found to be smooth, translucent, clear, homogenous with good spreadability and consistency. The gels showed good consistency with Viscosity of 20,480 ± 456 cp, which was a desired consistency for patient compatible topical application. The spreadability was found to be 20. 0 ± 1. 6 g/cm2. The gels showed good gel strength of 9. 0 ± 0. 4 g and showed slightly acidic pH at 6. 50 ± 0. 3 which is safe for topical application as shown in Table 3. Drug loading in Cur-nanogelThe drug loading efficiency in the prepared Cur-Nanogel was determined by the HPLC method. Sufficient drug loading of 61. 2 ± 4. 5% was obtained by the method used for preparation of nanogel in the optimized Cur-NS. Stability studiesStability studies of developed formulation were performed according to ICH guidelines for 30 days. From the study it was observed that the optimized formulation exhibited good stability behavior in terms of pH, physical appearance, viscosity, spreadability and drug content as shown in Table 4. No change in properties of the gel is observed for the formulations stored at room temperature, 4 °C and 40 °C. Table 4 Evaluation of Optimized Cur- NS Loaded NanogelFull size tableEx vivo skin permeation studyFrom the ex vivo skin permeation Study using rat skin, Cur-NS-nanogel showed a much controlled permeation with steady state flux of 21. 28 ± 0. 23 µg/cm2/hr in 24 h in comparison to gel which showed higher steady state flux of 36. 38 ± 0. 23 µg/cm2/hr. The permeation coefficients were similarly found to be 2. 031 ± 0. 0064(×103 cm/min) and 3. 6 ± 0. 0064 (×103 cm/min) in Cur-NS-Nanogel and Gel respectively (Table 5).

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: 3100±3310050±20106±3439kDa100101±13100±28100130±2580±36100100±1768±9. 3Table 2. Nature of liposome-specific domains and membrane-specific domain of SecAaaReaction mixtures with 1 µg [35S]SecA were incubated and treated as in Fig. 5. C. The membranes, liposomes and liposomes with N39 (20 µg/ml) and were recovered by centrifugation and re-suspended in 100 μl of TK buffer, 10 mg/ml heparin or 0. 1 M Na2CO3 (pH 11) respectively. After incubation on ice for 30 min, the liposomes and membranes were recovered by centrifugation and were analyzed by SDS-PAGE and autoradiography. The quantities of remaining SecA fragments in liposomes and membranes were determined by software, using these in TK buffer as 100%. All experiments were carried out for 3-5 times. determine whether the formation of these domains and their resistance to trypsin were due to the intrinsic resistance of these domains or due to some protection conferred from being formed in the presence of proteoliposomes or membranes, detergents were added after the formation of SecA domains. The non-ionic detergents, Triton X-100 and malto-dodecylmaltoside, which have previously been shown to maintain SecYEG in soluble form and to allow the formation of an inserted 30-kDa SecA domain [33], were used. Neither conferred the subsequent protection to trypsin digestion, indicating that the M48 and N39 domains are specifically induced and maintained only in the presence of phospholipids (Figure 5C). Structures of Lipid-as Observed by Microscopy (AFM) We have previously demonstrated the ability of SecA to form ring-like pore structures upon its interaction with phospholipids using both electron microscopy and atomic force microscopy [14]. Here we used AFM as the tool of choice to probe overt conformational changes of the SecA domains that could be induced by phospholipids.

Output: corroborate


Input: Claim: Cheetahs can run indefinitely at top speed without tiring. [SEP] Text: The captured adults were sexed. During the field studies, traps were rotated clockwise to eliminate possible bias because of uneven distributions of C. capitata populations. Unbaited traps were used as control. Statistical analyses All statistical tests were performed on 23. Data were checked for homogeneity of variance (Levene test) and the normal distribution of all data (Shapiro–Wilk test; P < 0. 05) before analysis. Data were transformed using log 10 (x + 1) to satisfy normality assumptions prior to analysis of variance (ANOVA). Wind tunnel and olfactometer bioassays were carried out as completely randomized designs with the 4 test dates as replicates. The field study was conducted as a randomized block design with four replications. The behaviors of the adults in the wind tunnel were analyzed using the Chi-square goodness-of-fit 0. 05. Also, to further understand the effect of chemicals, data from females, males, and both were subjected to seperate a one-way ANOVA (chemicals as factors). were followed by TUKEY’s test at P < 0. 05 level. All data in this study are shown as mean ± standard error (SE). ResultsAccording to odor characterization results by SPME and GC-MS, 63 compounds were isolated from apricot (Table 1). A total of 56 compounds were identified from apricot, representing 97. 2% of the total composition. The predominant volatile components were found to be 3-hexen-1-ol, acetate, (Z)-, ethyl acetate, and butanoic acid, 2-hexenyl ester, (E)-. Olfactometer experiments confirmed that 3-hexen-1-ol, acetate, (Z)-, ethyl acetate, and butanoic acid, 2-hexenyl ester, (E)- attracted significantly more flies than the control (Fig. 1) (F = 10. 800; df = 3, 15; P = 0. 001). 3-hexen-1-ol, acetate, (Z)-and ethyl acetate attracted significantly more females than control, but males were not importantly different (female, F = 9. 333; df = 3, 15; P = 0. 002: male, F = 9. 709; df = 3, 15; P = 0. 258).

Output: pass


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Therefore, the presence of curcuminoids, which have substantial antioxidant activity, may be responsible for the DPPH radical scavenging activity of the LKDCH extract. Homogenous nanosuspensions were obtained by the precipitation-sonication method. The precipitation method of nanosuspensions preparation is instantaneous, straightforward and easy [42]. The high drug saturation concentration and the rapid solvent injection into the antisolvent results in such precipitation into nanop0. 2 ± 0. 1, indicating suitable size and distribution. This size range and the homogeneity are because of the method of preparation by precipitation followed by sonication. This decreased size might result in increased surface area which may result in the increased saturation solubility and release of curcumin [54]. From the study, the of the formulations were found to negative that might be due to the surfactant or due to the terminal carboxylic groups. The reduced surface charge reflects better surface coverage due to the use of non ionic surfactant which results in steric stabilization. PVA was used as a steric stabilizer since steric stabilization has several advantages over electrostatic stabilization as the nanop0. 25% and PVA concentration of 0. 6% were considered as optimized variable conditions as shown in Table 3. It was observed that with increasing drug concentration the size and dispersity decreases indicating the impact of supersaturation in the nanoprecipitation. However at higher concentration, above 60 mg/ml the size increases. Similarly, it was observed that the p20. Similar behaviors were reported in previous works on nanosuspension by this method [22, 58]. The concentration of PLGA and stabilizer didn’t show any direct correlation with the size distribution of the precipitated nanop98. 52% ± 0. 2). The high entrapment is because of the precipitation method of preparation of nanosuspensions. In this method technique the drug which is hydrophobic in nature is soluble in organic solvent but is very slightly soluble in water. Nanop0. 3%. The optimized Cur-Nanogel was found to be smooth, translucent, clear, homogenous with good spreadability and consistency. The obtained properties of prepared gel were found suitable, safe for compatible topical application, particularly in wound healing.

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: In agreement with limited proteolysis results, N95 but not C95 (lacking the first 63 N-terminal residues) formed a ring-like structure similar to those formed by wild-type SecA in the presence of phospholipids (Figure 6A), and protein translocation with liposomes (Figure 2E). These results further support the conclusion that the N- terminal, but not the C-terminal, of SecA is required for the formation of lipid-specific domains. We next examined the structure of various SecA domains in lipids. We cloned, overexpressed, and purified the lipid-specific domains of N39 and M48*, as well as the soluble domain of N68 [24]. The lipid-specific domains of N39 and M48* formed imperfect partial ring structures, which appeared to be smaller than those of the intact SecA, while the soluble N68 domain [24] (Figure 6A) and C34 failed to form any ring structures at all (not shown). All ring structures that were observed were only formed in the presence of phospholipid liposomes with no detergents and did not form in the absence of lipids. The N39 ring structure differed from that formed by the M48* domain in that the former appeared to be more anchored on the surface of the lipid-bilayers with an outward amplitude, whereas the partial M48 ring structures showed a much more deeply indented cavity with an inward amplitude at the center of the ring-structure (Figure 6B). The partial pore structures of the N39 and M48 were smaller than SecA: using gold p10. 3 ± 1. 0 nm, 7. 1 ± 0. 4 nm, 6. 2 ± 0. 4 nm, respectively. In addition, sequence analysis showed that N39 possesses more hydrophobic area than M48 does. These data are also consistent with the observations that N39 was resistant to Na 2CO3 treatment, while M48 was removed 50% by the same treatment (Table 2). These data suggest that the lipid-specific domains of N39 and M48* do form part of the characteristic ring-like pore structures of SecA following its interaction with phospholipids, and further suggest that these lipid-specific domains are important components of SecA function in the membrane.

Output: corroborate


Input: Claim: Cheetahs can run indefinitely at top speed without tiring. [SEP] Text: AbstractThe cheetah, Acinonyx jubatus, is the fastest living land mammal. Because of its specialized hunting strategy, this species evolved a series of specialized morphological and functional body features to increase its exceptional predatory performance during high-speed hunting. Using high-resolution X-ray computed micro-tomography (μCT), we provide the first analyses of the size and shape of the vestibular system of the inner ear in cats, an organ essential for maintaining body balance and adapting head posture and gaze direction during movement in most vertebrates. We demonstrate that the vestibular system of modern cheetahs is extremely different in shape and proportions relative to other cats analysed (12 modern and two fossil felid species), including a closely-related fossil cheetah species. These distinctive attributes (i. e. , one of the greatest volumes of the vestibular system, dorsal extension of the anterior and posterior semicircular canals) correlate with a greater afferent sensitivity of the inner ear to head motions, facilitating postural and visual stability during high-speed prey pursuit and capture. These features are not present in the fossil cheetah A. pardinensis, that went extinct about 126,000 years ago, demonstrating that the unique and highly specialized inner ear of the sole living species of cheetah likely evolved extremely recently, possibly later than the middle Pleistocene. Similar content being viewed by others A test of the lateral semicircular canal correlation to head posture, diet and other biological traits in “ungulate” mammals 25. 9–29 m/s1,2. The species usually hunts swift ungulates such as gazelles, antelopes, and impalas by chasing them at high speeds, knocking them over, and biting their throats until they suffocate3,4. Given its lightly-built body compared to other felids, the cheetah captures medium-sized prey, weighing only 23 to 56 kg on average, which limits the risk of injuries and provides enough time for the animal to eat before the arrival of kleptoparasites such as lions, leopards, hyaenas or vultures4,5. Because of this distinctive hunting strategy, the species evolved an array of morphological characteristics related to fast motion and enhanced predatory performance3,6,7,8,9.

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: 11987510. 1016/10. 2147/IJN. S18791810. 1016/j. arabjc. 2017. 05. 01110. 1016/10. 4255/mcpharmacol. 15. 0410. 3390/gels704021310. 1080/22311866. 2020. 180673110. 1016/j. mtcomm. 2023. 10605010. 1186/2008-2231-20-7610. 1007/s13204-012-0188-310. 1016/j. ijpharm. 2009. 11. 00710. 1016/j. matchemphys. 2020. 12289810. 1590/S1984-8250201600030001510. 4103/0250-474X. 5729110. 1590/0001-376520162016016210. 1016/j. ejphar. 2020. 17317210. 1016/10. 1016/j. jsps. 2011. 08. 00110. 1016/10. 1080/10837450802409438193. 2019 Green synthesis of silver nanop10. 1016/10. 1002/aoc. 501610. 1155/2013/97202810. 3390/scipharm8802002610. 1021/acs. oprd. 6b0034710. 1039/c8ra08435a10. 1021/ed077p35910. 3109/0363904980910857110. 1007/s10661-021-09261-110. 1016/j. indcrop. 2019. 04. 02110. 1016/j. jfca. 2004. 11. 00510. 1016/j. foodchem. 2006. 06. 02310. 1007/s10787-016-0264-510. 2174/138920021866617011610355510. 1016/j. biomaterials. 2011. 11. 01110. 1016/j. polymdegradstab. 2010. 08. 01510. 1007/s40199-018-00235-210. 1021/acs. iecr. 9b0474710. 1081/DDC-10010219710. 12968/jowc. 2012. 21. 9. 45710. 1016/j.

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: A Model of SecA as Protein-in the have earlier found that SecA forms ring-like structure upon interaction with E. coli phospholipids [14] and recently we showed that SecA alone can promote protein translocation in liposomes and elicit ion-channel activity [16]. In addition we have also shown that dimeric SecA couples the preprotein translocation in an asymmetric manner [42,43]. This study has demonstrated that SecA, in the presence of liposomes, forms the lipid-specific domains of N39 and M48, with characteristics similar to the membrane-specific domains, in addition to the N68 and C34 domains present in the soluble SecA and membrane SecAS forms [22]. From X-ray structures of soluble E. coli SecA [46], the most likely tryptic cleavage site in SecAS that gives rise to N68 and C34 is 608-609RK, which is in a loop at the surface of the protein and probably lies within the motif of the NBDII region (Figure 6B). As a result of the drastic conformational change with lipids, the cleavage sites for SecAM that give rise to N39 and M48 are probably at 348R in the PBD domain, and 805R in the an α-helix in IRA1 domain (Figure 6B). To account for these observations, we propose a model (Figure 6C) in which the SecA dimer alone functions as the protein conducting-channel in promoting protein translocation and ion channel activity [14,16,17]. In this model SecA adopts an asymmetric dimer configuration in the membrane [42,43], in which the membrane bound subunit SecAM is specific for membrane lipids and plays the structural role of a channel, while the other SecA subunit, SecAS, has essentially the same conformation as it does in its soluble form and functions as the ATPase motor. SecAS has both the ATPase domain of N68 and the regulatory C34 domain, while SecAM is structurally composed of the N39 domain forming the surface part of the ring-pore structure and the M48 domain forming the more aqueous part of the channel (Figure 6C), as well as a small C10 domain that is probably exposed to the periplasmic side [35,37].

Output: corroborate


Input: Claim: Cheetahs can run indefinitely at top speed without tiring. [SEP] Text: The genome sequence of cheetahs also revealed positive selection of genes mediating energy metabolism and regulating muscle contraction, involved in their high-speed adaptations10. No prior study has investigated the sensory capacities of cheetahs through analyses of the anatomy of their intracranial organs, including the inner ear, which facilitates their remarkable capacity of maintaining visual and postural stability while running and capturing prey at high speeds, a key feature in the hunting specialization of the modern cheetah species. The inner ear, located in the petrosal bone at the base of the occipital region, plays a primary role in detecting head movements (accelerations and decelerations in both linear and rotational directions – pitch, yaw, and roll) and directly guiding the eyes and neck muscles in order to maintain posture and stabilize balance and gaze (e. g. , vestibulo-ocular reflex11,12). The bony labyrinth surrounds the soft tissues of the inner ear and can be used as a proxy for investigating the shape and dimensions of this organ. The morphology of the bony labyrinth can be correlated with phylogenetic relationships in some groups13,14,15,16,17,18. The vestibular system within the bony labyrinth, in particular, also can reflect ecological capabilities of vertebrates, especially their locomotor styles19,20,21,22,23,24,25,26. In this paper, we investigate the shape and the dimensions of the bony vestibular system in a number of individual extant cheetahs (taking into account variation that might be present in members of several subspecies) compared to other extant felids, using high-resolution μ-CT data and 3D morphometric analyses. Because of the long evolutionary history of the cheetah lineage27, and to provide greater insights into the timing of its specialized predatory behavior, we studied the fossil ‘giant’ cheetah Acinonyx pardinensis (early-middle Pleistocene) and one of the earliest felids Proailurus lemanensis (Oligo-Miocene of Eurasia28), to assess the ancestral inner ear condition for the cheetah and felid clades (Supplementary Fig. 1; 1–2; see Methods).

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Behavioral tests All rats were subjected to behavioral analysis to assess their motor functions. In the hind limb splay examination [3,5], the hind paws of rats were inked, then the rats were placed in a horizontal position of 30 cm high and dropped onto a white paper. The distance between the center points of right and left heels were recorded as the landing foot spread distance. In the movement initiation test [5, 24], the rat was held by its hind limbs and its torso, one forelimb was lifted above a table in order that the body weight was supported by the other forelimb alone. Then, rat was allowed to initiate stepping movements for one forelimb, and then the other. The averaged time period to initiate one step was recorded as the response latency for each forelimb. In the gait score test [3,5], animals were placed on the table and were observed for 3 min. Gait was scored as follow: 1: normal gait; 2, slightly abnormal gait characterized by slight ataxia, weakness and foot splay; 3, moderately abnormal gait characterized by obvious ataxia and foot splay with limb spread during ambulation; 4, severely abnormal gait characterized by a combination of all the above symptoms, dragging hind limbs and inability to support body weight. Histopathological analysis The collected brain tissues were fixed with 10% neutral-buffered formalin followed by dehydrating and paraffin-embedding. Then, embedded brain sections (5-μm thickness) were stained with hematoxylin and eosin (HE) for histopathological observation. The histopathological changes in cerebral cortex, hippocampal CA1, CA3, and dentate gyrus regions were analyzed. TUNEL assay The apoptotic neurons in the brain sections were detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assay. After deparaffinization and rehydration, the brain sections were permeabilized with proteinase K solution, then exposed to the mixture of biotinylated nucleotide dUTP and recombinant terminal deoxynucleotidyl transferase (TdT) following the instruction manual of (Servicebio, Wuhan, China).

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: In their lipid-dependent structural configuration, neither N39 nor M48 exhibit ATPase activity (data not shown), even though each possesses an adequate nucleotide binding domain (NBDI and NBDII, respectively) with each domain encompassing an intact and B sites (Figure 6B). In this model for SecA-dependent protein translocation, SecAS alone would provide the ATPase activity that is capable of propelling the protein precursor(s) through the SecAM channel. While the proposed model depicted in Figure 6C indicates a clear distinction between the two asymmetric units of the liposome-induced SecA dimer, it is not entirely inconsistent with the possibility of each subunit “flip-flopping” between each other conformation as the protein that is being translocated is propelled into the periplasmic space. DiscussionSecA is present in bacterial cells as both a soluble and a membrane form [26,65,66], and has been suggested to cycle on and off the membrane during protein translocation. A number of studies have shown, however, that SecA inserts deeply into liposomes and, in so doing, undergoes a series of conformational changes [7,32,38,67]. In addition, an earlier study from our laboratory also showed that a significant fraction of SecA remains on the membrane and does not cycle on and off during protein translocation [40]. Consequently, it has been suggested that SecA interacts with membranes, resulting in series of conformational changes that allow it to form part of a protein-conducting channel [22,40]. The specific domains that characterize the membrane bound conformation of SecA are the proteolytic N39 and M48 fragments [22]. This study shows that these membrane-specific domains can be induced by liposomes alone. Formation of the lipid-specific M48 domain (and the corresponding N39 domain) depends on the species and the combination of the phopholipids used. It has been well established that anionic lipids such as PG and CL are required for SecA to function in vitro and in vivo [3,12,14,59,66,68,69], even though overall there are 26 more negatively charged Glu and Asp residues in the E. coli SecA, for example, than there are positively charged Arg and Lys residues [68].

Output: corroborate


Input: Claim: Cheetahs can run indefinitely at top speed without tiring. [SEP] Text: The deviation from orthogonality of the SC has been associated with slower overall head rotations in mammals, with terrestrial running species having canals that are closer to right angles (90var38; e. g. , semicircular canal modifications of semi-aquatic otters and minks26). This finding contradicts the pattern observed between cheetahs and other felids (i. e. , greater angle between ASC and PSC in cheetahs, 6), but it is possible that the greater vertical development of ASC and PSC in cheetahs has a more important influence than their orthogonality on increasing the afferent vestibular sensitivity to roll and pitch head movements (as radius of curvature R, a measure of canal elongation, is still the most common index used to infer an animal’s agility21,37). Moreover, the out-of-plane curvature of ASC and PSC could allow the cheetah to sense accelerations of the head in other directions than the main roll and pitch movements19,33. Further physiological studies on the possible effect of semicircular canal curvature on the canal afferent sensitivity would enhance interpretations of their interrelationships. Postcranial remains of Acinonyx pardinensis suggest that fossil cheetahs already were adapted for fast running since at least the beginning of the Pleistocene39,40,41,42. Nevertheless, the small vestibular system of the fossil cheetah species, and, in particular, the presence of a shorter common crus and less extended ASC and PSC compared to the extant cheetah, indicate a relatively lower afferent sensitivity to angular and linear head movements. In addition to those physiological and functional aspects, the shape patterns of the vestibular system of A. pardinensis closely resemble that of the early fossil felid Proailurus, reflecting the retention of a morphologically primitive, ancestral condition, and emphasizing that postcranial skeleton modifications for higher speed locomotion preceded adaptations in the inner ear sensory system within the cheetah lineage. The extreme enlargement of the vestibular system and elongation of the ASC and PSC exhibited by modern cheetahs thus appears to be a unique and extremely recent key acquisition to fast running within that lineage. It is possibly more recent than the middle Pleistocene (i. e.

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Staining with 4,6-diamino-2-phenyl indole (DAPI) (Sigma, St. Louis, USA) was performed to visualize nuclei. Images were obtained under a fluorescent microscope (). Real-time of brain cerebral cortex tissues was isolated using TRIzol reagent (). The expression levels of TERT mRNA were measured by real-time PCR using all-in-OneTM qPCR master mix AOPR-1200 (). The sequences of primer sets for TERT were 5’-- 3’(forward) and 5’--3’ (reverse). β-actin gene was applied as a reference. Immunohistochemistry Paraffin-embedded brain sections of 5-μm thickness were incubated with a rabbit anti-TERT antibody (Servicebio, Wuhan, China), then a biotinylated goat anti-rabbit secondary antibody (Servicebio, Wuhan, China). Immune complexes were visualized by incubation with 3,3’-diaminobenzidine tetrachloride (DAB) and hematoxylin. Measurement of parameters related to oxidative stress in cerebral homogenates The brain tissue were homogenized with 9 times the volume of PBS on ice and then centrifuged to prepare homogenates. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of SOD and GSH-Px in the cerebral homogenates were measured following the respective manufacturer’s protocols (Bio-Engineering Co. , Ltd. , Nanjing, China). Protein contents in the cerebral homogenates were determined using the bicinchoninic acid assay kit (Bio-Engineering Co. , Ltd. , Nanjing, China). Measurement of IL-1β and TNF-ɑ levels in cerebral homogenates The concentrations of IL-1β and TNF-ɑ in cerebral homogenates were determined using using ELISA kits according to the manufacturer’s instructions (IL-1β: PeproTech Inc. , NJ, USA TNF-ɑ: R&). Statistical analysis All experiments were conducted with two technical replicates.

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: Dapic V, (2000) Distinct membrane binding properties of N- and C-terminal domains of Escherichia coli SecA ATPase. J 275: 25000-25007. doi: PubMed: 10835419. View 24. (1999) A molecular switch in SecA protein couples ATP hydrolysis to protein translocation. 34: 1133-1145. doi: PubMed: 10594836. View 25. (2000) Two independent mechanisms down-regulate the intrinsic SecA ATPase activity. J 275: 33209-33212. PubMed: 10982786. View 26. (1990) Complementation of two overlapping fragments of SecA, a protein translocation ATPase of Escherichia coli, allows ATP binding to its amino-terminal region. J 265: 8760-8765. PubMed: 2160468. View 27. (2001) Lipid and signal peptide-induced conformational changes within the C-domain of Escherichia coli SecA protein. Biochemistry 40: 1835-1843. doi: PubMed: 11327846. View 28. (2003) Nucleotide and phospholipid-dependent control of PPXD and C-domain association for SecA ATPase. Biochemistry 42: 13468-13475. doi: PubMed: 14621992. View 29. Economou A, (1994) SecA promotes preprotein translocation by undergoing ATP-driven cycles of membrane insertion and deinsertion. Cell 78: 835-843. doi: PubMed: 8087850. View 30. (1998) Endogenous SecA catalyzes preprotein translocation at SecYEG. J 273: 21675-21681. doi: PubMed: 9705302. View 31. Eichler J, (1997) Both an N-terminal 65-kDa domain and a C-terminal 30-kDa domain of SecA cycle into the membrane at SecYEG during translocation. 94: 5574-5581. doi: PubMed: 9159114. View 32. (1991) The conformation of SecA, as revealed by its protease sensitivity, is altered upon interaction with ATP, presecretory proteins, everted membrane vesicles, and phospholipids. 266: 5827-5833. View 33.

Output: corroborate


Input: Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: navigation Apply for support FAQ Be involved toggle overview Mission statement PAGES logos fellows Meeting minutes us Supporters and partners Supporters and partners organization Scientific partners -of involved Be involved mailing lists Apply to be on the SSC Write for and education Stakeholder engagement Stakeholder engagement Engaging with stakeholders guidelines Endorsed and affiliated Former initiatives and groups Data stewardship Data guidelines PAGES databases External databases webinars PAGES awardees PAGES awardees Scholarship recipients Early-Guest scientists -Menu layer 3 left side Menu layer 3 right side : : Volcanic eruptions and climate Allegra N. LeGrande and Kevin J. Anchukaitis >Access contents of this issue >Download this 10. 22498/pages. 23. 2. 46 Allegra N. LeGrande1 and Kevin J. Anchukaitis2 Figure 1: Last millennium climate forcing and modeled global mean annual temperature response. (A) Two time series of global annual radiative forcing estimated by scaling global sulfate loading (GRA: Gao et al. 2008 and CEA: Crowley et al. 2008 & Crowley and Untermann 2013) via aerosol optical depth (Schmidt et al. 2012, light lines) and a 10-year Gaussian smooth through these values (thick lines). (B) The full range of estimated PMIP3 annual total solar irradiance (TSI) anomalies (excluding those of Shapiro et al. 2011) relative to a 1976-2006 baseline (Schmidt et al. 2012). (C) Global mean annual average surface air temperature response in the GISS-E2 last millennium (CMIP5) experiment forced with given anthropogenic land use (Pongratz et al. 2008), solar variability (Steinhilber et al. 2009), and with (Crowley and Unterman 2013) or without (red) volcanic forcing. Volcanic eruptions represent some of the most climatically important and societally disruptive short-term events in human history. Large eruptions inject ash, dust, sulfurous gases (e. g. SO2, H2S), halogens (e. g. HCl and HBr), and water vapor into the Earth's atmosphere. Sulfurous emissions principally interact with the climate by converting into sulfate aerosols that reduce incoming solar radiation, warming the stratosphere and altering ozone creation, reducing global mean surface temperature, and suppressing the hydrological cycle.

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: AbbreviationsACR: Acrylamide; GSH: Glutathione; GSH-Px: Glutathione peroxidase; HE: Hematoxylin and eosin; IL-1β: Interleukin-1β; MDA: Malondialdehyde; ROS: Reactive oxygen species; SOD: Superoxide dismutase; TERT: Telomerase reverse transcriptase; TNF-α: Tumor necrosis factor-α; TUNEL: Terminal deoxynucleotidyl transferase mediated dUTP nick end labellingDeclarationsEthics approval and consent to participate Animal experiments were approved by the of Medicine College, of Science and Technology (resolution number 2019078), and accomplished in line with the guidelines of the Council of China. Consent for publication Not applicable. Availability of data and materials The datasets supporting the conclusions of this 57. . Acrylamide in human diet, its metabolism, toxicity, inactivation and the associated legal regulations in food industry. Nutr. 2019 Mar 25:1-16. . Calpeptin is neuroprotective against acrylamide-induced neuropathy in rats. Toxicology. 2018;400-401:1-8. . Neurotoxicity of acrylamide in exposed workers. . 2013; 10(9):3843-54. . Down-regulation of telomerase reverse transcriptase-related anti-apoptotic function in a rat model of acrylamide induced neurobehavioral deficits. Biotech Histochem. 2018;93(7):512-8. . Acrylamide exerts its cytotoxicity in NIH/3T3 fibroblast cells by apoptosis. Health. 2018;34(7):481-9. . Acrylamide-induced apoptosis in rat primary astrocytes and human astrocytoma cell lines. Vitro. 2014;28(4):562-70. . Taurine attenuates acrylamide- induced apoptosis via a PI3K/AKT-dependent manner. Toxicol. 2018;960327118765335. . Roles for Telomerase in the System. Neurosci. 2018;11:160. .

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: Peer review processEditorsReviewer #1Reviewer #2Peer review processNot revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, and public reviews. Read more about eLife’s peer review process. of of Photonic Sciences, Barcelona, SpainReviewer #1 (Public Review): Here the authors discuss mechanisms of ligand binding and conformational changes in GlnBP (a small E Coli periplasmic binding protein, which binds and carries L-glutamine to the inner membrane ATP-binding cassette (ABC) transporter). The authors have distinguished records in this area and have published seminal works. They include experimentalists and computational scientists. Accordingly, they provide comprehensive, high-quality, experimental and computational work. They observe that apo- and holo- GlnBP does not generate detectable exchange between open and (semi-) closed conformations on timescales between 100 ns and 10 ms. Especially, the ligand binding and conformational changes in GlnBP that they observe are highly correlated. Their analysis of the results indicates a dominant induced-fit mechanism, where the ligand binds GlnBP prior to conformational rearrangements. They then suggest that an approach resembling the one they undertook can be applied to other protein systems where the coupling mechanism of conformational changes and ligand binding. They argue that the intuitive model where ligand binding triggers a functionally relevant conformational change was challenged by structural experiments and MD simulations revealing the existence of unliganded closed or semi-closed states and their dynamic exchange with open unbound conformations, discuss alternative mechanisms that were proposed, their merits and difficulties, concluding that the findings were controversial, which, they suggest is due to insufficient availability of experimental evidence to distinguish them. As to further specific conclusions they draw from their results, they determine that a conformational selection mechanism is incompatible with their results, but induced fit is. They thus propose induced fit as the dominant pathway for GlnBP, further supported by the notion that the open conformation is much more likely to bind substrate than the closed one based on steric arguments. Considering the landscape of substrate-free states, in my view, the closed state is likely to be the most stable and, thus most highly populated. As the authors note and I agree that state can be sterically infeasible for a deep-pocketed substrate.

Output: corroborate


Input: Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: In this issue, we focus on the history, processes, and consequences of these large eruptions that inject enough material into the stratosphere to significantly affect the climate system. In terms of the changes wrought on the energy balance of the Earth System, these transient events can temporarily have a radiative forcing magnitude larger than the range of solar, greenhouse gas, and land use variability over the last millennium. In simulations (Fig. 1) as well as modern and paleoclimate observations, volcanic eruptions cause large inter-annual to decadal-scale changes in climate. Active debates persist concerning their role in longer-term (multi-decadal to centennial) modification of the Earth System, however. Societal systems are affected as well, and agriculture and infrastructure can be profoundly disturbed by these severe short-term geological and climate events, even at locations quite distant from the eruptions themselves. For instance, Puma et al. (p. 66) demonstrate an association between volcanic eruptions with some of the worst famines in human history. Despite their importance for both climate and natural hazards, there remain substantial gaps in our knowledge of the physics, magnitude, timing, and impacts of large volcanic eruptions. Robock (p. 68) highlights several persistent climatic mysteries related to volcanoes and uncertainties in our understanding of processes linking eruptions to both short- and long-term changes in the climate system. Historical accounts, geological evidence, and ice cores provide evidence of eruptions in the past that were much larger than those documented and observed since the 19th century, and volcanoes represent the most important forcing in last millennium transient climate simulations, at least until the dawn of the industrial era (Jungclaus et al. 2010). Various groups (Crowley and Unterman 2013; Gao et al. 2008; Sigl et al. 2015) have taken the initiative of estimating volcanic forcing from ice core records using the coherence of sulfate horizons in ice core records to infer volcanic eruptions. Lower (tropical) latitude and higher magnitude eruptions were inferred when there was greater coherence and higher sulfate concentrations across sites.

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: At 24 h after the last administration, all animals were euthanized by CO2 asphyxiation, brain tissues were quickly collected. Behavioral tests All rats were subjected to behavioral analysis to assess their motor functions. In the hind limb splay examination [3,5], the hind paws of rats were inked, then the rats were placed in a horizontal position of 30 cm high and dropped onto a white paper. The distance between the center points of right and left heels were recorded as the landing foot spread distance. In the movement initiation test [5, 24], the rat was held by its hind limbs and its torso, one forelimb was lifted above a table in order that the body weight was supported by the other forelimb alone. Then, rat was allowed to initiate stepping movements for one forelimb, and then the other. The averaged time period to initiate one step was recorded as the response latency for each forelimb. In the gait score test [3,5], animals were placed on the table and were observed for 3 min. Gait was scored as follow: 1: normal gait; 2, slightly abnormal gait characterized by slight ataxia, weakness and foot splay; 3, moderately abnormal gait characterized by obvious ataxia and foot splay with limb spread during ambulation; 4, severely abnormal gait characterized by a combination of all the above symptoms, dragging hind limbs and inability to support body weight. Histopathological analysis The collected brain tissues were fixed with 10% neutral-buffered formalin, subsequently dehydrated and embedded in paraffin. Then, paraffin-embedded brain sections of 5-μm thickness were stained with hematoxylin and eosin (HE) to observe the histopathological changes. The histopathological changes in cerebral cortex, hippocampal CA1, CA3, and dentate gyrus regions were analyzed. TUNEL assay The apoptotic neurons in the brain sections were detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assay.

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: As indeed they also underscore, there is likely to be a range of open states. If the populations of certain states are extremely low, they may not be detected by the experimental (or computational) methods. The free energy landscape of the protein can populate all possible states, with the populations determined by their relative energies. In principle, the protein can visit all states. Whether a particular state is observed depends on the time the protein spends in that state. The frequencies, or propensities, of the visits can determine the protein function. As to a specific order of events, in my view, there isn't any. It is a matter of probabilities which depend on the populations (energies) of the states. The open conformation that is likely to bind is the most favorable, permitting substrate access, followed by minor, induced fit conformational changes. However, a key factor is the ligand concentration. Ligand binding requires overcoming barriers to sustain the equilibrium of the unliganded ensemble, thus time. If the population of the state is low, and ligand concentration is high (often the case in in vitro experiments, and high drug dosage scenarios) binding is likely to take place across a range of available states. This is however a personal interpretation of the data. The paper here, which clearly embodies massive careful, and high-quality work, is extensive, making use of a range of experimental approaches, including isothermal titration calorimetry, single-molecule Förster resonance energy transfer, and surface-plasmon resonance spectroscopy. The problem the authors undertake is of fundamental importance. #2 (Public Review): Summary: The manuscript by Han et al and Cordes is a tour-de-force effort to distinguish between induced fit and conformational selection in glutamine binding protein (GlnBP). It is important to say that I don't agree that a decision needs to be made between these two limiting possibilities in the sense that whether a minor population can be observed depends on the experiment and the energy difference between the states. That said, the authors make an important distinction which is that it is not sufficient to observe both states in the ligand-free solution because it is likely that the ligand will not bind to the already closed state. The ligand binds to the open state and the question then is whether the ligand sufficiently changes the energy of the open state to effectively cause it to close.

Output: corroborate


Input: Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: Through a clever bit of historical work, Stothers (1984) was able to calculate the volcanic aerosol optical depth (AOD) after the 1815 Tambora eruption by digging through newspaper archives and finding mention of visible sunspots at a certain day and time, which indicated a certain minimum aerosol optical depth. Paired with the sulfate horizon observed in ice core records, it is possible to develop a conversion factor between sulfate horizon and AOD. Unsurprisingly, this process can be highly uncertain. And indeed, estimates of both the timing and magnitude of past major volcanic eruptions differ, in some cases substantially, between different ice-core derived calculations of volcanic forcing (Fig. 1; Schmidt et al. 2010). Sigl et al. (p. 48) detail their latest work to establish an improved chronology for volcanic eruptions during the Common Era, in particular an improved 1st millennium record and suggest a reduced magnitude for some of the largest last millennium eruptions, including the 1250s Samalas eruption. Early work following the Mt. Pinatubo 1991 eruption showed that global mean annual surface temperature decreased by ~0. 5°C (Hansen et al. 1996). This and subsequent research on Pinatubo has been important not only because of the insights provided about the response and sensitivity of the climate system to radiative perturbations, but because knowledge of this particular eruption forms a key part of how we model the Earth System’s response to other eruptions in the planet's history. Translating (parameterizing) the observed volcanic perturbation into forcing fields for global climate models (GCMs) has been accomplished, in a variety of ways with varying complexity, from exceptionally simple top-of-the-atmosphere shortwave forcing, to an intermediate complexity estimate of change in the AOD of the atmosphere, and the effective radius of the volcanic aerosol p0. 04-0. 05 mm per day following large eruptions. Focusing on the Asian monsoon region, Gao (p. 58) illustrate the reductions in monsoon rains in the years following an eruption may be an order of magnitude larger than the global average. The papers in this issue collectively represent not just a summary of the current science, but also more importantly a series of implicit and explicit challenges to the modeling, observation, and paleoclimate communities. Robock (p.

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: After deparaffinization and rehydration, the brain sections were permeabilized with proteinase K solution, then exposed to the mixture of biotinylated nucleotide dUTP and recombinant terminal deoxynucleotidyl transferase (TdT) following the instruction manual of (Servicebio, Wuhan, China). Staining with 4,6-diamino-2-phenyl indole (DAPI) (Sigma, St. Louis, USA) was performed to visualize nuclei. Images were obtained under a fluorescent microscope (). Real-time of brain cerebral cortex tissues was isolated using TRIzol reagent (). The expression levels of TERT mRNA were measured by real-time PCR using all-in-OneTM qPCR master mix AOPR-1200 (). The sequences of primer sets for TERT were 5’-- 3’(forward) and 5’--3’ (reverse). β-actin gene was applied as a reference. Immunohistochemistry Paraffin-embedded brain sections of 5-μm thickness were incubated with a rabbit anti-TERT antibody (Servicebio, Wuhan, China), then a biotinylated goat anti-rabbit secondary antibody (Servicebio, Wuhan, China). Immune complexes were visualized using 3,3’-diaminobenzidine tetrachloride (DAB). Then, sections were counter-stained with hematoxylin. Measurement of parameters related to oxidative stress in cerebral homogenates The brain tissue homogenates were made by homogenizing each cerebral cortex tissue with 9 times volume of PBS on ice, then centrifuging. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of SOD and GSH-Px in the cerebral homogenates were measured according to their respective manufacturer’s instructions (Bio-Engineering Co. , Ltd. , Nanjing, China). The protein contents in cerebral homogenates were detected using the bicinchoninic acid assay kit (Bio-Engineering Co. , Ltd. , Nanjing, China).

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: The heatmap and PECA results show example genes: the stress response genes HSPA5 (GRP78, BiP) and HSP90B1, the DNA repair gene RAD51, and the aminoacyl-tRNA synthetase WARS. FDR - false discovery rate. Figure 1—figure supplement 1 Download asset Open asset Overview of the statistical workflow for data analysis (PECA). The schematic illustrates the experimental design that maps multiple layers of regulation in response to stress. RNA and protein abundances were measured using RNA-seq and mass spectrometry, respectively. Ribosome footprinting and protein occupancy profiling were used to map the binding of ribosomes and non-ribosomal proteins along mRNAs, respectively. Time points and genes with significant regulation were extracted from each data type with (PECA)(Teo et al. , 2018; Teo et al. , 2014). For changes in RNA concentration, assuming DNA concentration remains constant, PECA reports on transcription and RNA degradation regulation. After factoring out changes that occur in RNA concentrations, the ribosome footprinting, protein occupancy profiling, and mass spectrometry datasets inform on translation, binding of post-transcriptional regulators, and translation/protein degradation changes, respectively. The figure shows the expression patterns for the ER stress response gene IFRD1 as an example of significant regulatory events identified by PECA; layer one represents the changes in molecular abundance on which layer two levels partially depend (false discovery rate <0. 2 in both biological replicates). Solid lines - replicate 1, dashed lines replicate 2. TRXP - transcription; TRL - translation; RNA-DEG - RNA degradation; PROT-DEG - protein degradation. Figure 2 with 5 supplements Download asset Open asset Tunicamycin elicits stress of the endoplasmic reticulum. (A) Reactive oxygen species (ROS) change in HeLa cells after tunicamycin and hydrogen peroxide (left and right, respectively) treatment, as measured for indicated time points. The cells show basal levels of ROS with minimal increase upon tunicamycin treatment, and substantial increase when treated with hydrogen peroxide, consistent with the relationships shown in Figure 1A. (B) The panels show phosphorylation levels of ER stress markers PERK and eIF2α increase after treatment with tunicamycin (left).

Output: corroborate


Input: Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: 68) directly sets out a series of tantalizing questions, and it is clear that a consilience of simulated and reconstructed temperature response has not yet been achieved. Likely explanations for these differences lie at least in part on our representation of the processes governing the climate consequence of eruptions in state-of-the-art GCMs, including aerosol processes, as well as precise knowledge of the timing and magnitude of past events. Paleoclimate proxies are a filter through which we peer into the past, and thus the biological, chemical, and physical mechanisms that give rise to these records need to be better understood. Addressing these myriad and extant uncertainties will require close coordination between those specializing in paleoclimate reconstruction, modeling, and present observations of the climate system: scientists with domain knowledge in aerosol and particulate behavior in the atmosphere, geologists and ice core specialists with knowledge of both atmospheric processes and geochronology, social scientists and engineers who understand the coupled human and natural systems impacted by eruptions, and climate modelers. Volcanic eruptions and their influence on coupled Earth systems cut across traditional disciplinary boundaries, and will continue to require collaboration and a high degree of international cooperation. PAGES has recently organized the “on Climate and Society” (VICS) working group. The principal aims of this group are to improve radiative forcing; understanding of volcanically induced climate variability; and understanding of societal impacts of volcanic eruptions. The group hopes to extend our current volcanic forcing datasets, largely limited to the last millennium back to the beginning of the Holocene. This work will facilitate model-to-data inter comparisons such as those of SSiRC (and its Role in Climate), PMIP4 (Paleoclimate and Project, Phase 4), and VolMIP (Project on the to Volcanic Forcing). In addition to editors Allegra LeGrande and Kevin Anchukaitis, the working group will be lead by Michael Sigl,. affiliations 1for 2School of Geography and Development and Laboratory of Tree-Ring Research, University of Arizona, Tucson, USA contact Allegra N. LeGrande: allegra. n. legrandenasa. gov 10. 1029/2008JD010239 et al. (1996) 42: 233-272 Jungclaus JH et al. (2010) 6: 723-737 Mann ME et al.

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: AbbreviationsACR: Acrylamide; GSH: Glutathione; GSH-Px: Glutathione peroxidase; HE: Hematoxylin and eosin; IL-1β: Interleukin-1β; MDA: Malondialdehyde; ROS: Reactive oxygen species; SOD: Superoxide dismutase; TERT: Telomerase reverse transcriptase; TNF-α: Tumor necrosis factor-α; TUNEL: Terminal deoxynucleotidyl transferase mediated dUTP nick end labellingDeclarationsEthics approval and consent to participate Animal experiments were approved by the of Medicine College, of Science and Technology (resolution number 2019078), and accomplished in line with the guidelines of the Council of China. Consent for publication Not applicable. Availability of data and materials The datasets supporting the conclusions of this 57. . Acrylamide in human diet, its metabolism, toxicity, inactivation and the associated legal regulations in food industry. Nutr. 2019 Mar 25:1-16. . Calpeptin is neuroprotective against acrylamide-induced neuropathy in rats. Toxicology. 2018;400-401:1-8. . Neurotoxicity of acrylamide in exposed workers. . 2013; 10(9):3843-54. . Down-regulation of telomerase reverse transcriptase-related anti-apoptotic function in a rat model of acrylamide induced neurobehavioral deficits. Biotech Histochem. 2018;93(7):512-8. . Acrylamide exerts its cytotoxicity in NIH/3T3 fibroblast cells by apoptosis. Health. 2018;34(7):481-9. . Acrylamide-induced apoptosis in rat primary astrocytes and human astrocytoma cell lines. Vitro. 2014;28(4):562-70. . Taurine attenuates acrylamide- induced apoptosis via a PI3K/AKT-dependent manner. Toxicol. 2018;960327118765335. . Roles for Telomerase in the System. Neurosci. 2018;11:160. .

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: are conventionally viewed as structurally stabilizing elements in proteins but emerging evidence suggests two disulfide subproteomes exist. One group mediates the well known role of structural stabilization. A second redox-active group are best known for their catalytic functions but are increasingly being recognized for their roles in regulation of protein function. Redox-active disulfides are, by their very nature, more susceptible to reduction than structural disulfides; and conversely, the Cys pairs that form them are more susceptible to oxidation. In this study, we searched for potentially redox-active by scanning the Bank for structures of proteins in alternate redox states. The PDB contains over 1134 unique redox pairs of proteins, many of which exhibit conformational differences between alternate redox states. Several classes of structural changes were observed, proteins that exhibit: disulfide oxidation following expulsion of metals such as zinc; major reorganisation of the polypeptide backbone in association with disulfide redox-activity; order/disorder transitions; and changes in quaternary structure. Based on evidence gathered supporting disulfide redox activity, we propose disulfides present in alternate redox states are likely to have physiologically relevant redox activity. evidence supports the concept of two distinct types of disulfides in protein structures which have different functional roles. 1 The best known group act as structural stabilizers in proteins, significantly lowering the Gibb's free energy of the protein chain by crosslinking it, resulting in proteins that are more resistant to denaturation. The second group are redox-active and best known for their catalytic role in proteins such as thiol-disulfide oxidoreductases. An increasing role for the redox-active group in protein redox regulation is emerging. 1, 2 These disulfides act as redox-sensitive switches and are best viewed as post-translational modifications akin to phosphorylation. It has now been established that oxidative regulation: important in processes such as the cell cycle, apoptosis, and response to oxidative stress; is an important control mechanism in the cytosol. Transient oxidation mediates control of enzymes, signaling pathways, as well as transcriptional and translational control. However, these characterized cytosolic proteins likely only represent the tip of the iceberg. Increasingly, reduction of disulfides is also emerging as a key regulator of protein function in oxidizing environments.

Output: corroborate


Input: Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: Preprints AbstractDiscussion © Author(s) 2024. This work is distributed under the Attribution 4. 0 License. © Author(s) 2024. This work is distributed under the Attribution 4. 0 License. Preprints AbstractDiscussionMetrics 20 Aug 2024 | 20 Aug 2024 Status: this preprint is open for discussion and under review for Climate of the Past (CP). Identifying climate variables that interchange with volcanic eruptions as cooling forces during the Common Era’s ice ages Seip, Øyvind Grøn, and Abstract. Volcanism is known to be an instigating factor for the Age (LALIA, 536–660) and the Age (LIA, 1250–1850), but little is known about when the effect of volcanism ends, and which other mechanisms prolong a cold period that includes the ice-ages’ cold periods, but also continued periods with persistent cooling. Here we show, with a high-resolution lead-lag method, where the stratospheric aerosol optical depth (SAOD) generated by volcanic emissions ceases to precede the summer temperature (NHST). We find that five climate mechanisms cool the (percentage time in parentheses): SAOD (51 %), total solar irradiance (TSI, 2 %), the oscillation (NAO, 11 %), the interdecadal Pacific oscillation (IPO, 28 %) and CO2 (16 %). The last four variables overlap, and altogether the five climate variables cover 89 % of the cold period that includes LALIA and LIA. In contrast, we find an increase in atmospheric CO2 over a brief period just after large volcanic eruptions. During the cold period, the five variables lead NHST, are in a cooling mode, and have sufficient strength to cool the Northern Hemisphere. How to cite. Seip, K. L. , Grøn, Ø. , and Wang, H. : Identifying climate variables that interchange with volcanic eruptions as cooling forces during the Common Era’s ice ages, EGUsphere [preprint], 2024. Received: 21 Jun 2024 – Discussion started: 20 Aug 2024 Publisher's note: remains neutral with regard to jurisdictional claims made in the text, published maps, institutional affiliations, or any other geographical representation in this preprint. The responsibility to include appropriate place names lies with the authors.

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Prasad SN, Muralidhara. Neuroprotective effect of geraniol and curcumin in an acrylamide model of neurotoxicity in Drosophila melanogaster: relevance to neuropathy. J Insect Physiol. 2014;60:7-16. . Tau hyperphosphorylation and P-CREB reduction are involved in acrylamide-induced spatial memory impairment: Suppression by curcumin. Immun. 2018; 71:66-80. . Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviatesmotor deficits induced by 6-OHDA in rats. Neuroscience. 2016;318:157-65. -. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease. Nutr. 2016;115(3):449– Cavallucci V, D'Amelio M. Matter of life and death: the pharmacological approaches targeting apoptosis in brain diseases. Des. 2011;17(3):215-29. . Effects of water extract of Curcuma longa (L. ) roots on immunity and telomerase function. J Med. 2017;14(3). -Soltanahmadi Y, Zarghami N. Adipose Tissue-. (Stuttg). 2018;68(4):213-21. . Curcumin, inflammation, and chronic diseases: how are they linked? Molecules. 2015;20(5):9183-213. . Curcumin: into an against Cancer. Mol Sci. 2019;20(8):1808. . Curcumin-Induced DNA Demethylation in by the DNA-Pathway. Cell Longev. 2020;2020:2543504. Liczbiński P, Michałowicz J, Bukowska B. Molecular mechanism of curcumin action in signaling pathways: Review of the latest research. Phytother Res. 2020;10. 1002/ptr. 6663. . Role of microglial activation and neuroinflammation in neurotoxicity of acrylamide in vivo and in vitro. Arch Toxicol. 2019;93(7):2007-19. TableTable 1.

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: 3-5 Importantly, ageing and several major diseases including neurodegenerative diseases such as Alzheimer's disease, type II diabetes, cancer, and cardiovascular disease have been associated with abnormal redox conditions. Structural and redox-active disulfides can be distinguished by their redox potentials. Disulfide redox potentials measured in thiol-disulfide oxidoreductases range from −120 to −270 mV. 6-9 For disulfides serving structural purposes, the redox potential can be as low as −470 mV. 10 Computational methods for distinguishing the two groups would be a boon. Reactivity of a redox-active Cys is modulated by its immediate protein environment. In addition to the effects of the electrostatic environment, physical stress applied to a disulfide bond both through stretching and twisting enhances its reactivity. These forces can be applied to a protein dynamically11 or may be captured during the protein folding process, rendering the disulfide poised to act upon exposure to variations in redox conditions. 12 Because of their enhanced reactivity, redox-active disulfides are also more susceptible to cleavage/oxidation under nonphysiologic conditions. For instance, redox-active disulfides are prone to cleavage by synchrotron radiation during the process of X-ray structure determination. 13-15 Other factors such as the pH of crystallization or the presence of mutations that change the electrostatic environment near a disulfide may also influence reactivity. Here, we mined the Bank (PDB)16 for highly similar proteins that have been solved in multiple redox states, that is, disulfide-bonded in one structure and reduced in another. We present evidence that most of the disulfides present in our dataset are likely to be physiologically redox-active. Many of the proteins have known thiol-based redox activity, while others have a high likelihood of thiol-based redox activity based on their involvement with redox processes. We also observed and classified types of conformational changes which occur during redox transitions. processes are enriched in the redox pair dataset Pairs dataset contains 18,003 pairs of protein structures consisting of 4333 protein chains, of which 1238 (28. 57%) are high-resolution structures (<2. 2 Å). Many structures are of the same protein solved in different redox environments.

Output: corroborate


Input: Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: Download & links Preprint (PDF, 1209 KB) Supplement (678 KB) Download & links Preprint (1209 KB) Metadata XML Supplement (678 KB) Øyvind Grøn, and Status: open (until 20 Nov 2024) Comment types: AC – author | RC – referee | CC – community | EC – editor | CEC – chief editor | : Report abuse Post a comment Subscribe to comment alert RC1: 'Comment on egusphere-2024-1874', #1, 29 Aug 2024 reply This is the third time I have reviewed this paper, earlier versions of which were submitted to Bulletin of Volcanology and Science of the Total Environment. In both cases I recommended rejection, and my recommendation is the same here. Resubmitting papers without fixing them wastes editors’ and reviewers’ time. This may not even be only the third time, as I may have not been sent other versions to review. The fundamental problem is that a purely statistical approach is not correct for this problem. Such a statistical approach ignores the physics of the system and is confusing. Correlation is not causation. The forcing from volcanic eruptions is very short, but the response has a much larger time scale, and is non-linear. In the case of the Age, a resetting of the state of the Arctic climate prolonged the response for decades and centuries. This is already well known. The authors claim “to our knowledge, few studies examine the timings when the effect of volcanism ceases, and other mechanisms continue the cooling effect. ” But to my knowledge there are many papers that address this. For example, look at papers referenced in this submission such as Miller et al. (2012), the title of which is “Abrupt onset of the Age triggered by volcanism and sustained by sea-ice/ocean feedbacks. ” By ignoring the physical system and its response, it is not possible to understand how climate changes. By treating and CO2 as normalized time series, and not with units and actual radiative forcing, the results are meaningless, particularly as NAO and IPO are internal variability and not forcing. The conclusion that CO2 changes are as important as volcanic eruptions is ridiculous, if you account for the magnitude of their forcings, except for the period since 1850 when CO2 and other greenhouse gases dominate.

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Behavioral tests All rats were subjected to behavioral analysis to assess their motor functions. In the hind limb splay examination [3,5], landing foot spread distance was measured as follow: the hind paws of rats were inked, then the rats were placed in a horizontal position of 30 cm high and dropped onto a white paper. The distance between the center points of right and left heels were recorded. In the movement initiation test [5, 24], the rat was held by its hind limbs and its torso, one forelimb was lifted above a table in order that the body weight was supported by the other forelimb alone. Then, rat was allowed to initiate stepping movements for one forelimb, and then the other. The averaged time period to initiate one step was recorded as the response latency for each forelimb. In the gait score test [3,5], animals were placed on the table and were observed for 3 min. Gait was scored as follow: 1: normal gait; 2, slightly abnormal gait characterized by slight ataxia, weakness and foot splay; 3, moderately abnormal gait characterized by obvious ataxia and foot splay with limb spread during ambulation; 4, severely abnormal gait characterized by a combination of all the above symptoms,dragging hind limbs and inability to support body weight. Histopathological analysis The collected brain tissues were fixed with 10% neutral-buffered formalin, subsequently dehydrated and embedded in paraffin. Then, paraffin-embedded brain sections of 5-μm thickness were stained with hematoxylin and eosin (HE) to observe the histopathological changes. The histopathological changes incerebral cortex, hippocampal CA1, CA3, and dentate gyrus regions were analyzed. TUNEL assay The apoptotic neurons in the brain sections were detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assay following the instruction manual of (Servicebio, Wuhan, China). Real-time PCR The expression levels of TERT mRNA in cerebral Cortex were measured by real-time PCR using all-in-OneTM qPCR master mix AOPR–1200 (GeneCopoeia, Rockville, MD).

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: Key to Groups: A, ion channel, ion pump modifier; B, protein folding, isomerization; C, cell cycle; D, Calvin cycle; E, photosynthesis, respiration, transport, maturation of proteins involved in these processes; F, destruction of oxygen radicals; G, redox metal homeostasis; H, amino acid metabolism; I, sulfur metabolism; J, nucleotide metabolism/homeostasis; K, isoprenoid biosynthesis; L, RNA-interacting; M, proteases; N, DNA repair; O, actin-related; P, carrier proteins; Q, other metabolism; R, NADP+-dependent oxidoreductase; S, other oxidoreductase; T, signaling; U, development; V, cell growth pathways; W, enzyme inhibitors; X, redox homeostasis; Y, ROS generating; Z, apoptosis; a, protein fate; b, cell entry; c, cell adhesion; d, DNA-interacting proteins; e, translation; f, immunity; g, carbohydrate metabolism; h, NAD+-dependent oxidoreductases; i, Ca handling; j, methyltransferase; k, other. To further assess the likelihood that the presence of proteins in the PDB with disulfides in both redox states is an indicator of physiological disulfide redox activity, we looked for (GO) terms overrepresented in the dataset compared to the entire PDB. GO is a dynamic controlled vocabulary of over 16,000 terms used to describe molecular function, process and location of action of a protein in a generic cell. 28 The analysis revealed many GO terms consistent with redox function, including cell redox homeostasis and multiple pathways of cysteine biosynthesis (Table 2). Interestingly, several of the enriched GO terms are linked to proteins mediating cell entry, including bacterial toxins and viral entry proteins. Reduction of disulfides, often accompanied by irreversible conformational changes, have previously been implicated as a general mechanism in cell entry proteins of diverse types. 27 Experimental evidence directly supporting such a general process exists for HIV gp120, Newcastle disease virus, SARS coronavirus and Chlamydia. 29-32 Thus the GO terms support redox roles for proteins in the dataset.

Output: corroborate


Input: Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: The claim on lines 529-530 that “Volcanic eruptions instigated directly or indirectly increases in atmospheric CO2 concentrations for 136 ±42 years” is completely wrong, and based on statistical artifacts of the analysis that have no basis in physics. CO2 emissions from volcanic eruptions for the past 2000 years have been very small. They have been important for massive flood basalt eruptions, but the contribution from eruptions during the period studied is trivial. The authors mix up external forcing and the internal climate system. Oceanic and atmospheric variations (such as the NAO) are internal responses to external forcings, such as volcanic eruptions and solar variations. Some of the 10. 5194/egusphere-2024-1874-RC1 AC1: 'Response to -2024-1874', Knut Seip, 02 Sep 2024 reply R … Resubmitting papers without fixing them wastes editors’ and reviewers’ time. Response. I find the introduction to the review personal, and to me this contrast with the reviewer choosing to be anonymous. Second, we have “fixed” the paper, partly based on the present reviewer’s recommendations. However, there are issues the reviewer pointed to that we do not agree with. We appreciate the opportunity to respond to the reviewer’s – sometimes harsh (the term ridiculous was used! ) –comments. And for the record, there have been other reviewers that have been positive to the study. R The fundamental problem is that a purely statistical approach is not correct for this problem. Such a statistical approach ignores the physics of the system and is confusing. Response. The paper is basically statistical, but we invoke time series, e. g. , the Oscillation (NAO) and other ocean variability series that have been discussed extensively in physical terms. The ocean variability series has been shown to impact global temperature. Wu et al. (2019) is cited in the paper line 537, but a new 235. R. In the case of the Age, a resetting of the state of the Arctic climate prolonged the response for decades and centuries. This is already well known. Response. We are not sure what the reviewer means by “resetting”. There is a large literature on ocean teleconnections across the globe, and changes in the Arctic climate is one element.

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: The sequences of primer sets for TERT were 5’-- 3’(forward) and 5’-–3’ (reverse). β-actin gene was applied as a reference. Immunohistochemistry Paraffin-embedded brain sections of 5-μm thickness were incubated with a rabbit anti-TERT antibody (Servicebio, Wuhan, China), then a biotinylated goat anti-rabbit secondary antibody (Servicebio, Wuhan, China). Immune complexes were visualized using 3,3’-diaminobenzidine tetrachloride (DAB). Then, sections were counter-stained with hematoxylin. Measurement of parameters related to oxidative stress in cerebral homogenates The brain tissue homogenates were made by homogenizing each cerebral cortex tissue with 9 times volume of PBS on ice, then centrifuging. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of SOD and GSH-Px in the cerebral homogenates were measured according to their respective manufacturer’s instructions (Bio-Engineering Co. , Ltd. , Nanjing, China). The protein contents in cerebral homogenates were detected using the bicinchoninic acid assay kit (Bio-Engineering Co. , Ltd. , Nanjing, China). Measurement of IL–1β and TNF-ɑ levels in cerebral homogenates The concentrations of IL–1β and TNF-ɑ in cerebral homogenates were determined using using ELISA kits according to the manufacturer’s instructions (IL–1β: PeproTech Inc. , NJ, USA TNF-ɑ: R&). Statistical analysis All data were expressed as the mean ± SD, and analyzed using one-way analysis of variance (ANOVA) with post hoc Tukey test by SPSS 22. 0 software. P < 0. 05 or P < 0. 01 was considered statistically significant. ResultsEffect of curcumin on ACR-induced body weight and neurobehavioral changes As shown in Fig. 1A, the animals in the ACR group began to show slow growth compared to the normal control group since 2 weeks of exposure (P < 0. 05).

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: Disulfides were tested computationally for likely redox activity by screening the dataset for oxidized structures where the disulfide had particular properties previously associated with redox activity. Flagged disulfides were those (a) with high torsional energies; (b) found in known redox-active sequence motifs; or (c) which disobeyed known rules of protein stereochemistry. 12 Studies of disulfide-bonds in model proteins have shown that those bonds with high torsional energies are more easily cleaved than disulfide-bonds with lower stored energy. 33-36 148 disulfides in 139 proteins have torsional energies >15 kJ mol−1: a conservative threshold associated with redox activity. 27 These are designated by “H” in Table 1. Redox-pair disulfides were also found in sequence motifs previously shown to be associated with redox activity. 67 proteins, designated by “M” in Table S1, contain known redox-active motifs such as the CXXC motif: a redox-active disulfide motif commonly found in the thioredoxin fold, but which has also arisen convergently in other folds. A further 65 proteins, designated by “F” in Table S1, contain disulfides in protein structures that disobey known rules of protein stereochemistry. 37, 38 These disulfides, which we refer to as “forbidden” disulfides, conform to canonical structural motifs. Deformation of the resident structure enhances disulfide reactivity by inducing stress in the protein chain. 37, 38 Forbidden disulfides are proposed to have a functional role through redox activity. 12 In summary, a total of 226 proteins in the dataset contain disulfides predicted to be redox-active by a second independent bioinformatic analysis method. Nonetheless, it is possible that some proteins with alternate Cys-Pair redox states are non-native, that is, not encountered under normal, or abnormal, physiological conditions. We reasoned that proteins demonstrated selective reduction of disulfides were more likely to represent physiological states. Accordingly, for proteins with more than one disulfide, the dataset was partitioned into pairs where all the disulfides were reduced and those where some disulfides were selectively reduced while others remained intact, to further test the likelihood of involvement in physiological redox processes.

Output: corroborate


Input: Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: Other variabilities have also been given prominent roles, like El Niño and the Pacific decadal oscillation. R The authors claim, “to our knowledge, few studies examine the timings when the effect of volcanism ceases, and other mechanisms continue the cooling effect. ” But to my knowledge there are many papers that address this. …” Miller et al. (2012) is given as an example. Response. The study by Miller et al. (2012) identify when summer cold begins (1275), but not when it ends. There are several studies that suggest mechanisms that would continue the cooling effect, but they are generic. et al. (2012, p. 5) study says: “Climate modeling reveals one such possible feedback mechanism. ” Modeling studies have their advantage in being mechanistically driven, but also their drawbacks. Examples on this were given on Line 60. In contrast, the time series we use are observed series, although often based on proxies. R By ignoring the physical system and its response, it is not possible to understand how climate changes. Response. “To understand” is a complex and interesting expression. For example, you understand a phenomenon if you can refer to something well known (freezing water increase in volume, IPO gets warmer) and accepted a causal link between the familiar and what you want to understand (the water bottle breaks, GTA increases). The water bottle example is from Campbell (1952). R. By treating and CO2as normalized time series, and not with units and actual radiative forcing, the results are meaningless. Response. We treat the series in a normalized form to identify correlations and lead-lag relations. We also distinguish components of the series. To convert the series to a common unit is a challenge, but we refer to studies that suggest that e. g. NAO and IPO would have the strength to affect the global temperature, line 535. Presently we could have added a study by Samset et al. (2024) who focus on ocean basins having positive anomalies at the same time and on upwelling of previously stored deeper water with high temperatures. Text will be changed, a reference to Samset et al. (2024) will be added. R particularly as NAO and IPO are internal variability and not forcing. Response.

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Skip to main content Explore journals Get published About BMC My account Search all BMC 0. 1 M PBS (pH 7. 4, final methanol concentration was < 1%) and injected (i. p. , at 50 mg/kg) one a day to mice in groups: and VIII. The same volume of vehicle (PBS) was injected to WT (Group I) and 5xFAD mice (Group-IV), as summarized in Table 1. Table 1 Summary of the different animal groups and treatment regimens used in this studyFull size table Tissue processingAll mice were deeply anaesthetized with an overdose of sodium pentobarbital (i. p. ), and transcardially perfused with 0. 1 M cold PBS at pH 7. 4, followed by 4% paraformaldehyde (diluted in 0. 1 M PBS at pH 7. 4) to fix the brains. The brains were then removed, suspended in 4% paraformaldehyde for 24 h at 4 °C, and transferred to the graded sucrose solutions (10, 20 and 30%). When brains were completely immersed in the 30% sucrose solution, they were stored at 4 °C until being sectioned coronally at 40 µm on a Cryostat (Leica, Germany). Cur and SLCP permeability studyTo investigate whether sufficient amounts of Cur or SLCP crossed the blood brain barrier (BBB) and reached to the regions of interest in the brain, the Cur- and the SLCP-injected 5xFAD mice (Group V–VIII) were sacrificed and their brain tissue was processed, as described above. Coronal sections (40 μM) were cut and imaged using a fluorescent microscope (Leica, Germany) to assess the amount of Cur or SLCP bound to the Aβ plaques, which was confirmed by co-localization of either the Cur or the SLCP to Aβ-specific antibody (6E10) in Aβ-plaques, as described previously [32]. To compare the permeability of Cur and SLCP in vitro, mouse neuroblastoma cells (N2a, ATCC, Catalog no: Neuro2a (ATCC® CCL131™) and the primary hippocampal neurons from a 5xFAD mouse were used.

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: The enriched GO terms for both the partially and fully reduced sets contained terms previously associated with thiol-based redox regulation indicating both the fully and partially reduced sets have likely redox activity (Table 2). Conformational changes associated with redox activity Having established the Redox-Pair dataset is enriched in proteins involved in redox-regulated processes, we studied conformational changes between redox pairs of proteins. For many proteins in the data set there were negligible conformational differences between the SG atoms of each Cys residue of the reduced and oxidized states (see Fig. 2). For this group, other factors may be required for, or preclude, conformational changes in these proteins. Crystal packing forces, for example, may prevent a subsequent conformational change after cleavage of the disulfide by synchrotron radiation. For another group, the small distance changes of 2–4 Å observed are most likely due to rotation of one or both Cys sidechains toward each other to form the SS bond. Some of the proteins exhibiting these small conformational changes are oxidoreductases with catalytic thiols such as thioredoxin, thioredoxin reductase, and protein disulfide isomerase. Figure 2Open in figure viewerPowerin disulfide separation in protein Redox Pairs. Excluding interchain disulfides, around 21% of redox structure pairs have a change of over 1 Å in the sulfur atom separation between the oxidized and reduced structures. Maximal intrachain differences of up to 18. 8 Å were apparent in 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXP reductoisomerase) and the RNA sulfuration enzyme TrmU. 39 For proteins which exhibit major conformational changes, four classes were identified based on the nature of the change. These groups were: proteins that oxidize disulfides following expulsion of metals such as Zn; proteins that exhibited major reorganization or “morphing” of portions of the polypeptide backbone in association with disulfide redox-activity; proteins that exhibited order/disorder transitions; and proteins that exhibited changes in quaternary structure. Redox sites associated with zinc and other metals Redox regulation of proteins that form disulfides following expulsion of Zn is an emerging area of signaling.

Output: corroborate


Input: Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: NAO (indirectly) and IPO show characteristics of surface water temperatures in the Atlantic and the Pacific respectively, but they are also part of a teleconnection system and therefore exert force on other part of the global surface temperature system. (NAO is measured as sea surface pressure difference, but it is associated with sea surface temperatures in the literature). If GTA is restricted to the surface system, the oceanic deep waters will be a force outside this system. However, the referee is right, presently all the ocean waters are treated as one system. Text will be changed. R. The conclusion that CO2changes are as important as volcanic eruptions is ridiculous, if your account for the magnitude of their forcings, except for the period since 1850 when CO2and other greenhouse gases dominate. Response. The role of CO2 in the atmosphere before, say 1850, has been revised in recent literature. It is probably not as small as previously believed. For example, Hansen et al. (2023) states that “We infer from paleoclimate data that aerosol cooling offset GHG warming for several millennia as civilization developed” The authors suggest that the effects of aerosols and GHG were comparable. However, their suggestions are discussed further in subsequent literature. R. The claim on lines 529-530 that “Volcanic eruptions instigated directly or indirectly increases in atmospheric CO2concentrations for 136 ±42 years” is completely wrong and based on statistical artifacts of the analysis that have no basis in physics. Response. We give the source for the time series for CO2 around line 140. To our knowledge, it is developed without 0. 1,2) smoothed version of the raw curve (Line 228, to avoid possible high frequency noise) and the droplines shows volcanic eruptions. KLS remade the calculations the result is correct, and the calculations are available from him. ) We do not know what artefacts the referee refers to. R CO2 emissions from volcanic eruptions for the past 2000 years have been very small. They have been important for massive flood basalt eruptions, but the contribution from eruptions during the period studied is trivial. Response. We quote Werner et al. (2019) and Buono et al. (2023). We should not have restricted the Werner reference to one figure. Did we misunderstand the information in the Werner 401. N. R. (1952). What is science?

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: The N2a cells were grown with minimum essential medium () containing 10% heat-inactivated fetal bovine serum (FBS), and penicillin and streptomycin (100 I. U. /mL and 100 μg/mL). The culture was maintained at 37 °C in a humidified atmosphere at 5% CO2. The primary hippocampal neurons were taken from embryonic-16 (E16) mouse pups and grown in neurobasal media containing B27 supplementation for 7 days in vitro (7-DIV), as described previously [42]. Prior to the experiment, the cells were grown in either in 60 mm Petri dishes or on glass coverslips, using fresh MEM or neurobasal media that lacked growth factors. The cells were then treated with 100 μM of either Cur or SLCP for 2 h, after which the media was removed, and the cells were fixed with 4% paraformaldehyde solution. Microphotographic images were taken using a fluorescent microscope (Leica, Germany) with appropriate excitation/emission filters for analyses. Aβ plaque load in 5xFAD after treatment with Cur or SLCPTo check the effects of acute treatment of Cur or SLCP on Aβ plaque burden, the 5xFAD brain sections were stained with Cur and the number of Aβ plaques were counted in these sections. Cur was used to label Aβ plaques, because it labels plaques as efficiently as Aβ-specific antibody [32]. Using Image-J software ( the total area of each image was measured and the numbers of Aβ plaques were counted manually in PFC and DG area of hippocampus and expressed as number of Aβ plaques per 100 µm2 area. Only clearly visible, large fluorescent signals were considered as Aβ plaques. A minimum of 10 serial sections, with forty different fields were used to count the number of Aβ plaques in each group (n = 4), with the experimenters blinded to the group identity of the specimens analyzed. Neuronal morphology by cresyl violet stainingOne of the aims of this study was to investigate whether short-term treatment of Cur or SLCP can protect the neuronal morphology, especially in hippocampal subfields and in the PFC area. To this end, the tissue from 5xFAD mice that were treated with Cur or SLCP was stained with 0.

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: Further inspection of proteins with likely redox-active Zn sites reveals that two forbidden disulfide motifs, the Disulfide (JSD) and a type of β-diagonal disulfide (BDD),12 are repetitively associated with redox-active Zn-binding sites in the dataset. Oxidized structures that contain a BDD include isoleucyl tRNA synthetase (1ile 180–184, 502–504), the apoptosis-related proteins birc8 and survivin (1xb1, 300–303;1f3h, 57–60), aspartate transcarbamylase (1r0b, 138–141) and the DNA repair enzyme RecR (1vdd, 57–60). Oxidized structures that contain a JSD include the amino-acyl tRNA synthetases for Leu and Ile (1obh, 439–484; 1jzs, 461–502), the enzymes of sulfur metabolism MetH and BHMT (1q7m, 207–273; 1lt7, 217–300) and GTP hydrolase GTPhI (1gtp, 110–181). Morphing transitions in the dataset A large group of proteins in the dataset were observed to undergo plastic deformations involving large scale rearrangements of the polypeptide backbone. We refer to these conformational changes as morphing transitions. These transitions, which typically involve unraveling portions of secondary structure, are illustrated in Figure 4 and in animations in the Supporting Information. The well known redox-sensitive protein OxyR belongs to this group. In OxyR, a protein of 305 residues, significant refolding of the C-terminus occurs involving residues 196–221. 23 In the reduced structure, residues 200–204 form a short 310 helix flanked by regions of coil. Upon oxidation, residues 196–221 adopt a different fold with residues 189–193 and 213–218 forming two parallel β-strands joined by a loop with a disulfide-linkage between Cys199 and Cys208. In the reduced OxyR structure, the two Cys that form the disulfide are separated by almost 13 Å. Cys 199 in OxyR is known to undergo alternate modifications such as glutathionylation.

Output: corroborate


Input: Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: Dover Publications. Cheng, L. J. , Abraham, J. , Trenberth, K. E. , Boyer, T. , Mann, M. E. , Zhu, J. , Wang, F. , Yu, F. J. , Locarnini, R. , Fasullo, J. , Zheng, F. , Li, Y. L. , Zhang, B. ,. . . Lu, Y. Y. (2024). Indicators in 2023. Advances in Atmospheric Sciences, 41(6), 1068-1082. J. E. , Sato, M. , Simons, L. , Nazarenko, L. S. , von Schuckmann, K. , Loeb, N. G. , Osman, M. B. , 9, Gary Russell, Junji Cao, & Li11, J. (2023). Global warming in the pipeline. Climate Change, 3. . , & Trenberth, K. E. (2013). and with the Oscillation. Journal of Climate, 26(18), 7298-7310. G. H. , Geirsdóttir, A. , Zhong, Y. F. , Larsen, D. J. , Otto-. , Björnsson, H. , & Thordarson, T. (2012). Abrupt onset of the Age triggered by volcanism and sustained by sea-ice/ocean feedbacks. Letters, 39. L02708 10. 1029/2011gl050168& Wilcox, L. J. (2024). 2023 temperatures reflect steady global warming and internal sea surface temperature variability. & Environment, 5(1). 460 10. 1038/s43247-024-01637-8Werner, C. , Fischer, T. , Aiuppa, A. , Edmonds, M. , Cardellini, C. , Carn, S. , & Allard, P. (2019). Emissions from Regions: in Review. In B. Orcutt, I. Daniel, & R. Dasgupta (Eds. ), Deep Carbon: Past to Present (2. 18 10.

Output: pass


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: 1% cresyl violet, as described previously [43]. The sections were washed, dehydrated, cleared, mounted, and coverslipped using DePex mounting media (). The slides were dried, after which photomicrographs were taken using a compound light microscope (Olympus, Japan) with 100× objectives (total magnification of 1000×). The number of pyknotic, or tangle-like, cells were counted manually using Image-J software ( and were expressed as number of pyknotic cells per 100 µm2 area. A minimum of 5 serial sections, each with 10 different fields, were used for counting the number of pyknotic cells in each group (n = 4), with the experimenters blinded to the group identity of the specimens being analyzed. Neuroinflammation study by immunohistochemistryTo compare the anti-inflammatory effects of Cur or SLCP in 5xFAD mice, the brain tissue from each mouse was labeled with GFAP and Iba-1, which are the markers for activated astrocytes and microglia, respectively. GFAP-immunohistochemistryA subset of brain sections were rinsed three times with 0. 1 M PBS (pH 7. 4) for 5 min each. The sections were then blocked with 10% normal goat serum for 1 h at room temperature with gentle shaking. The tissue was incubated overnight on a shaker at 4 °C with GFAP antibody (rabbit polyclonal, 1:500). On the next day, the sections were thoroughly washed with PBS, three times, for 10 min each. The sections were incubated with anti-rabbit secondary antibody (1:1000), tagged with Alexa-594 (Molecular Probes, OR), for 30 min at room temperature. Then sections were washed thoroughly with distilled water, dehydrated, cleared and mounted on slides using anti-fading Fluoro-mount aqueous mounting media (Sigma) prior to microscopic examination using a fluorescence microscope (Leica, Germany) with the appropriate excitation/emission filters. Iba-1 immunohistochemistrySimilarly, for Iba-1 immunohistochemistry, another subset of brain section were thoroughly rinsed, three times with 0. 1 M PBS (pH 7. 4) for 5 min each.

Output: pass


Input: Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: coli DNA polymerase III τ 20-1xxh; Rhodobacter capsulatus xanthine dehydrogenase 21-1jrp. Metal in all structures is Zn unless specified otherwise. Metal atoms in structure 21 are Fe atoms in Fe-S cluster. Figure 4Open in figure viewerPowertransitions in protein Redox Pairs. A: A large morphing transition in the chloride channel CLIC1: a protein that forms ion channels by inserting itself into membranes in response to oxidation. B: A smaller morphing transition in cyclic phosphodiesterase (CPDase) a protein involved in the tRNA splicing pathway of yeast, plants and vertebrates. Redox activity of the disulfide modulates access to the active site. 59 Oxidized structures are shown on the left. Reduced structures are on the right. The region of the polypeptide chain between the two redox-active Cys is shown in green in the oxidized structure and red in the reduced structure. Other morphing regions are shown in blue. C: Flocco-Mowbray diagram for CLIC1 (left) and CPDase (right). Y-axis SFMI-Smoothed Flocco-Mowbray Index. The polypeptide chain is coloured according to the corresponding oxidized structure. Redox-active thiols are indicated with open squares. Animations of the conformational changes in CLIC1 and CPDase are included in the Supporting Information. To determine whether the oxidized structure of OxyR is indeed an oddity, or if other proteins exhibit similar conformational changes, we systematically searched for morphing proteins in the dataset by scanning for protein structure pairs that exhibited large differences of the backbone torsional angles over at least seven contiguous residues. Changes in pseudo-dihedral angles calculated using four consecutive Cα atoms exceeding a summed threshold of 1000 degrees over seven consecutive residues were used to detect changes in secondary structure. Twenty-two parents were found in the fully reduced set and four in the partially reduced set (designated m in Table 1). Proteins showing the largest conformational changes are in Table II.

Output: corroborate


Input: Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: These responses are partly dependent on the climate state prior to an eruption, as well as the location of the volcano and the season of eruption (Stevenson et al. 2017). While much attention has focused on short-term variability, less is known about the influence of longer-term changes in the background climate (Zanchettin et al. 2013). The future response to an eruption may be different because of changes in the climate system caused by anthropogenic warming. Aubry et al. (2016) have recently shown that warming-induced changes in the vertical structure of atmosphere (particularly changes in the tropopause height) would impact on the rise of volcanic plumes, but the impact of future changes on the radiative forcing and response to a volcanic eruption has not been quantified. Here we analyse an ensemble of comprehensive model simulations of a large volcanic eruption to evaluate the climate system response to a large volcanic eruption in a future climate state. We performed an ensemble of simulations with the HadGEM2-ES model (HadGEM2 2011; Collins et al. 2011) of a Tambora 1815 -like eruption in pre-industrial (Kandlbauer et al. 2013) and Pathway 6. 0 (RCP 6. 0) conditions for the years AD1860 and AD2045, respectively. Tambora was chosen because it provides a very strong forcing which can be more easily separated from simulated internal variability. 2 MethodsTo simulate the climatic impact of a volcanic eruption we use the 2 (HadGEM2-ES). This a coupled atmosphere-ocean general circulation model (GCM), which includes terrestrial and ocean carbon cycle components, interactive tropospheric aerosols and an interactive tropospheric chemistry scheme (HadGEM2 2011; Collins et al. 2011). The atmospheric resolution of the model is 1. 875 × 1. 25° (longitude-latitude), with 38 vertical levels reaching to just over 39 km, with 11 levels above 15 km and resolving the lower stratosphere. The ocean resolution is 1° horizontally, but this increases in the latitudinal direction to 1/3° in the tropics, and has 40 unequally spaced vertical levels. HadGEM2-ES includes an interactive sulphur cycle as well as representations of biomass burning, sea-salt, mineral dust and fossil fuel black and organic carbon aerosols (Bellouin et al. 2011).

Output: contrast


Input: Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: The sections were then immersed in a solution of 3% hydrogen peroxide and 0. 1 M PBS (pH 7. 4) for 30 min at room temperature to inhibit endogenous peroxidase. Then the sections were rinsed with PBS and blocked with 10% normal goat serum (NGS), which underwent gently shaking for 1 h at room temperature. The tissue was then incubated with Iba-1 antibody (rabbit, monoclonal, 1:4000) with gentle shaking for 4 h at room temperature and then for overnight at 4 °C. On the next day, the sections were thoroughly washed 3 times for 5 min each, and incubated with biotinylated anti-rabbit secondary antibody (1:250) for 1 h at room temperature. Finally, the sections were incubated with peroxidase substrate solution, supplied with the ABC kit (Vector Laboratory, CA), and the signal was developed using diaminobenzidine (DAB) until the desired staining intensity emerged. The tissue was then washed, dehydrated with graded alcohol, cleared with xylene, mounted on slides, coverslipped with DePex (), air dried, and visualized using a compound light microscope (Olympus, Japan) with 20× objectives (total magnification 200×). Quantification of GFAP-IR and Iba-1-IR cellsFor quantification of GFAP-IR and Iba-1-IR cells, the sections were imaged using a fluorescent microscope (Leica, Germany) and a compound light microscope (Olympus, Japan), respectively. The number of GFAP-IR and Iba-1-IR were counted manually using Image-J software ( Briefly, the images were taken from randomly selected regions of the layer IV/V of PFC (bregma +3. 20 mm), striatum (bregma +1. 00 mm), subicular complex, hippocampus (CA1, CA3 and dentate gyrus) at bregma −3. 30 mm, and the entorhinal cortex (bregma −3. 30 mm), using 20× objectives (total magnification at 200×). The total area of each image was measured and the numbers of GFAP-IR and Iba-1-IR cells were counted manually in those areas.

Output: pass