Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: Three areas of interest were chosen to illustrate the appearance of melanophores (C6 to C8: at the top of the head, C11 to C13: above internal organs, and, C20 to C25: close to the caudal peduncle,) and xanthophores (C7 to C8 at the top of the head, C14 to C16 above internal organs and C26: close to the caudal peduncle). (D) Expression patterns of genes encoding for the rhodopsins (rh1) and the visual cone opsins (rh2A, rh2B, rh2C, opnlw, opnsw1, opnsw2A-1, opnsw2A-2, opnsw2B). Gene expression data was generated from whole fish. Expression levels were derived from DESeq2 normalized gene counts. Other TH-regulated biological processes are also activated during grouper metamorphosis Pigmentation changes are often the most visible changes in some teleost species such as clownfish (Salis et al. , 2021). In grouper, the pigmentation changes are accompanied by the regression of the dorsal and pelvic spines. The acquisition of an adult pigmentation pattern is characterized by the formation of brown and white vertical bars in E. malabaricus (Figure 4C, juvenile stage). To reveal the molecular regulations driving these pigmentation changes, we assessed the expression of key pigmentation genes involved in white (iridophore genes), black (melanophore genes), and yellow (xanthophore genes) pigment cells known to be regulated by TH in zebrafish and clownfish (Salis et al. , 2021; Saunders et al. , 2019). The expression level of the iridophore gene flh2a showed a strong increase from D03, followed by a decrease at D32 and a new surge at D60 (Figure 4C). The first increase may correspond to the appearance of iridophores on the ventral cavity whereas the second may coincide with the formation of the white bars. In contrast, its paralogue fhl2b remained relatively stable throughout the development.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Incidence rate of acute myeloid leukemia (AML) has been reported to be significantly increased in a cohort of pilots in comparison to respective Canadian population rates [108]. It has also been found that working a rotating nightshift at least three nights per month for 15 or more years may increase the risk of colorectal cancer in women [109]. Colon cancer patients who have maintained a regular pattern of rest and activity rhythms have shown a fivefold higher survival time than those who have chaotic circadian rhythms [110]. Aberrant expression of clock genes in cancer Several reports have revealed that clock genes are found to be deregulated in various cancers. In comparison with nearby non-cancerous cells, more than 95% of breast cancer cells reveal disturbances in the expression of the three Per genes attributable to methylation of the per gene promoters [111]. Moreover, a structural variation of the Per3 gene has been identified as a potential biomarker for breast cancer in pre-menopausal women [112]. Significantly decreased expression of Per1 has been observed between sporadic breast tumors and normal samples, as well as a further significant decrease between familial and sporadic breast tumors for both Per1 and Per2 suggesting a role for both in normal breast function [113]. It has been demonstrated recently that Per2 is endogenously expressed in human breast epithelial cell lines but is not expressed or is expressed at significantly reduced level in human breast cancer cell lines. Expression of Per2 in these breast cancer cells results in inhibition of cell growth and induction of apoptosis demonstrating the tumor suppressive nature of PER2. Moreover, PER2 activity is found to be significantly enhanced in the presence of its normal clock partner CRY2. Furthermore, Per2 expression in cancer cell lines is associated with a significant decrease in the expression of Cyclin D1 and an up-regulation of p53 [114]. The proliferation in ovarian cancer cells has been found to follow a cyclical pattern of peaks and troughs that is out of phase with the circadian rhythm in proliferation of normal tissues [115,116]. Recently, it has been reported that expression levels of Per1, Per2, Cry2, Clock, and CKIε in ovarian cancers are significantly lower than those in normal ovaries. On the contrary, Cry1 expression is highest followed by Per3 and Bmal1 [117].

Output: corroborate


Input: Claim: Geothermal plants can harness energy from any location on Earth with minimal infrastructure. [SEP] Text: The LCOE for the two cases have been calculated at 2. 93 €-ct/kWh and 16. 94 €-ct/kWh, respectively. Furthermore, the conventional system was found to be capable of meeting the sustainability criteria in almost all cases. These include the operation in an equilibrium between extraction and recharge as well as the technical definition of an operation time between 100 and 300 years. Economic optimization, however, leads to more excessive production schemes in all cases except for a macroeconomic climate dictated by a low interest rate, and thus reflects the behavior of modern-day power plant operations. The enhanced system, in contrast, could not do justice to a sustainable operation in most cases. Nevertheless, in the default case and within some slight variations of various parameter values, it can reach the lower threshold of our technical definition, i. e. , it can operate over a lifetime of 100 years under the given circumstances, but is hardly economical. At this point, however, the question arises as to how useful this definition is for petrothermal systems. Accordingly, one could also argue to use the resource regardless of time. The earth’s heat is inexhaustible from a human point of view, but conductive systems need a considerable time until they reach their pre-production status and are in that sense an exhaustible resource that should not be taken lightly. Concluding, it should be noted that natural geothermal systems can be operated sustainably, but our optimizations show that a more excessive operation is generally economically beneficial. Artificially developed reservoirs for electricity generation that are purely sustained by a conductive heat flow are simply not economically viable or depend on high feed-in tariffs. With the more favorable reservoirs for EGS utilization that are also sustained by a conductive heat flow lying somewhere in between, it can be stated that these could be also operated in a sustainable manner, but again, without external influences, economic incentives would lead to excessive production. Availability of data and materials Data supporting the findings are available from the authors upon request. Change history06 August 2024A Correction to this paper has been published: technical potential for geothermal power generation describes the share of the theoretical potential that can be "technically exploited" taking into account current technical possibilities (Paschen et al. 2003: 23; Rybach 2010: 2; EPA 2007: 2–4).

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: Xanthophores start colonizing the larval body at D10, which may explain the increase of the expression level of two xanthophores markers, gtsm3, and perp6, which play a role in concentrating and trafficking lipophilic pigments (Granneman et al. , 2017). On the other hand, scarb1, which is involved in carotenoid deposition in zebrafish, increased slightly at D03 (Figure 4C). Similarly, melanophore genes are displaying a strong increase in their expression level at D03 and D06 that may be related to the colonization of melanophores on the larval body (tyrp1b, tyr, Figure 4C). During their metamorphosis in the wild, fish larvae also undergo ecological changes such as habitat transition (from ocean to coastal environment) and food habits. It is well known that in many fish species, this ecological transition is accompanied by a change in color vision (Cortesi et al. , 2016). Since TH appeared critical in the regulation of genes involved in vision in salmonids, zebrafish, and clownfish (Roux et al. , 2023; Volkov et al. , 2020; Cheng et al. , 2009; Veldhoen et al. , 2006), we investigated the regulation of genes encoding for visual opsin. We expected to find at least eight visual cone opsin genes in E. malabaricus according to the phylogeny of opsin genes in teleosts (Cortesi et al. , 2015) (opnsw1, opnsw2Aa, opnsw2Ab, opnsw2B, rh2A, rh2B, rh2C, opnlw) and one rhodopsin gene (rh1) (Cortesi et al. , 2015; Musilova et al. , 2021). These genes were indeed expressed in our transcriptomic data. We observed that the medium wavelength opsin (rh2A, rh2B, rh2C), and the long wavelength opsin (opnlw) were highly expressed at the beginning of the larval development (at D03 for rh2B, rh2C, and opnlw, and at D10 for rh2A) (Figure 4D).

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Similarly, significantly decreased expression levels of Per1 as compared to paired non-tumour tissues, have been reported in endometrial carcinoma (EC). The decreased Per1 expression in EC is partly due to inactivation of the Per1 gene by DNA methylation of the promoter and partly due to other factors. This downregulation of the Per1 gene disrupts the circadian rhythm, which might favour the survival of endometrial cancer cells [118]. In another study, the promoter methylation in the Per1, Per2, or Cry1 circadian genes has been detected in about one-third of EC and one-fifth of noncancerous endometrial tissues of 35 paired specimens indicating possible disruption of the circadian clock in the development of EC [119]. Serum-shocked synchronized prostate cancer cells have been found to display disrupted circadian rhythms compared with the normal prostate tissue. Per1 is down-regulated in human prostate cancer samples compared to normal prostates. Moreover, over-expression of Per1 in prostate cancer cells has resulted in significant growth inhibition and apoptosis [120]. CCAAT/enhancer-binding proteins (C/EBPs) are a family of transcription factors that regulate cell growth and differentiation in numerous cell types. The results from a recent study suggest that Per2 is a downstream C/EBPα-target gene involved in acute myeloid leukemia (AML). Its disruption might be involved in initiation and/or progression of AML, as significantly reduced expression of Per2 has been noted in lymphoma cell lines as well as in AML patient samples [121]. The expression of Per1, Per2, Per3, Cry1, Cry2, and Bmal1 is significantly impaired in both chronic phase and blast crisis of chronic myeloid leukemia (CML) samples compared with those in normal samples. Although no mutations have been detected within the coding region of Per3, the CpG islands in its promoter are methylated in all the CML samples. Likewise, the CpG islands of Per2 are also methylated in 40% of cases [122]. Recently, Cryptochrome1 has been found to be a valuable predictor of disease progression in early-stage chronic lymphocytic leukemia (CLL) [123]. More recently, it has been reported that CRY1: PER2 expression ratio is independent prognostic marker in chronic lymphocytic leukemia [124].

Output: corroborate


Input: Claim: Stem cell research holds potential for regenerating damaged tissues and organs. [SEP] Text: Science 287: 1427–1430. 67. Wei, G. , G. Schubiger, F. Harder, A. M. Müller (2000) Stem cell plasticity in mammals and transdetermination in Drosophila: common themes? 18: 409–414. 68. Weiss, S. , C. Dunne, J. Hewson, C. Wohl, M. Wheatley, A. C. Peterson, B. A. Reynolds (1996) Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J Neurosci 16: 7599–7609. 69. Whetton, A. D. G. J. Graham (1999) Homing and mobilization in the stem cell niche. Biol 9: 233–238. 70. Williams, B. P. , J. Price (1995) Evidence for multiple precursor cell types in the embryonic rat cerebral cortex. Neuron 14: 1181–1188. 71. Wu, A. M. , J. E. Till, L. Siminovitch, E. A. McCulloch (1968) Cytological evidence for a relationship between normal hematopoietic colony-forming cells and cells of the lymphoid system. J 127: 455–463. 72. (1996) Distinct developmental patterns of short-term and long-term functioning lymphoid and myeloid precursors defined by competitive limiting dilution analysis in vivo. J Immunol 157: 138–145. © 2002 S. Karger AG, Basel2002Copyright DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions.

Output: pass


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: These surges of expression are followed by the increase of the expression levels of opnsw2B, opnsw2Bb, and opnlw from D32. From D18 the rhodopsin involved in scotopic vision (rh1) increases. The expression level opnsw1 remained low and stable during the entire development (Figure 4D). It is again very interesting to note that these changes coincide with both TH signaling peaks. As these genes are regulated by TH in other species and according to the observed expression patterns, we may assume that this is also the case in E. malabaricus. The timing of cone opsin (opnsw2a1, opsnw2a2, and opnlw) expression in E. malabaricus is similar to E. bruneus (Matsumoto and Ishibashi, 2016), but different from E. akaara where opnsw2 is strongly expressed early and then decreases (Kim et al. , 2019). However, the expression levels of mid-wavelength opsins and opnlw are similar between E. malabaricus and E. akaara, suggesting their involvement in cone photoreceptor differentiation, while rod photoreceptors differentiate during metamorphosis in E. akaara and E. malabaricus larvae. Metamorphosis is accompanied by a metabolic shift Because metamorphosis is known to be energetically demanding and because the ecology of the planktonic larvae and the demersal juveniles are different, we investigated metabolic gene expression. Figure 5 shows the expression profile of the genes encoding for the rate-limiting steps enzymes involved in glycolysis, (phosphofructokinase, pfkma, and pfkmb), and citric acid cycle (citrate synthase, cs; isocitrate dehydrogenase, idh3a; oxoglutarate dehydrogenase complex, ogdhl, dlst2). The expression profile of all the genes associated with these pathways are shown in Figure 5—figure supplement 1. Figure 5 with 1 supplement see all Download asset Open asset Metabolic transition and corticoid expression levels of E. malabaricus. (A) Schematization of the metabolic transition occuring during E. malabaricus larval development showing that young larvae rely on aerobic metabolism whereas older larvae rely on anaerobic metabolism.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: There is also a case report showing that a patient with primary cerebral B-cell non-Hodgkin's lymphoma (NHL) has lost circadian control of sleep [125]. Moreover, genetic association and functional analyses suggest that the circadian gene Cry2 might play an important role in NHL development [126]. Several circadian related genes have been found to be under-expressed in pancreatic cancer indicating that pancreatic tumors have altered circadian rhythms [127]. Recently, Per1 has been identified as a candidate tumor suppressor, epigenetically silenced in nonsmall-cell lung cancer (NSCLC). Per1 expression has been found to be low in a large panel of NSCLC patient samples and in NSCLC cell lines compared to normal lung tissue. The down-regulation of Per1 expression is associated with hypermethylation of the Per1 promoter. Moreover, the study reveals that aberrant acetylation of Per1 promoter is also a potential mechanism for silencing Per1 in cancer [128]. More recently, Bmal1 has been reported to be transcriptionally silenced by promoter CpG island hypermethylation in hematologic malignancies, such as diffuse large B-cell lymphoma and acute lymphocytic and myeloid leukemias. It has been shown that BMAL1 epigenetic inactivation impairs the characteristic circadian clock expression pattern of certain genes including c-Myc, in association with a loss of BMAL1 occupancy in their respective promoters. Furthermore, the DNA hypermethylation-associated loss of BMAL1 also prevents the recruitment of its natural partner, the CLOCK protein, to their common targets, further enhancing the perturbed circadian rhythm of the malignant cells [129]. Epigenetic technologies in cancer studies are helping increase the number of cancer candidate genes and allow us to examine changes in 5-methylcytosine DNA and histone modifications at a genome-wide level. In fact, all the various cellular pathways contributing to the neoplastic phenotype are affected by epigenetic genes in cancer. They are being explored as biomarkers in clinical use for early detection of disease, tumor classification and response to treatment with classical chemotherapy agents, target compounds and epigenetic drugs [130]. The discovery of cancer-relevant gene silencing by epigenetic mechanisms is closely linked to epigenetic drug design and development.

Output: corroborate


Input: Claim: CRISPR can be used to create entirely new human species with superhuman abilities. [SEP] Text: Our research showed that using this SSD activates the visual areas in the brain after lots of practice—showing that these areas are not used only for seeing with the eyes (Figure 3D) [4, 5]! Figure 3 - (A) Bats have evolved the ability to “see” with their ears. They do this using a process called echolocation, in which they emit sounds and detect them as they bounce off objects. (B) Daredevil, the superhero, is blind and uses echolocation to “see” sounds. (C) A device called the EyeMusic SSD allows people to see with sounds. (D) Our research shows that people who have trained using SSDs can accurately identify shapes, objects, locations, and colors [adopted from Abboud et al. [7]]. In 1981, won the for the theory of critical periods, which states that the development of the senses, for example, the development of normal vision or hearing, depends on the experience of visual or auditory stimuli in early childhood. They discovered that if animals did not experience a certain sense in the 1st weeks of life—the critical period—they could not develop that sense later in life. This idea is now being challenged by work done in several labs, including ours. For example, studies on children after cataract removal indicate that vision can be developed at a much older age than once was thought, so maybe there are multiple critical periods instead of only one! Moreover, if people can learn to use alternate senses, for example to “see” with their ears or “hear” through touch, or if people can learn to develop entirely new senses even in adulthood, this indicates that strict critical periods might not exist [6]. It seems that the more we discover about exactly how the brain is wired, the more we uncover fascinating connections between the senses that can be used to improve existing abilities and possibly to create new ones. At the beginning of the twentieth century, American psychologist stated that “We use only a small part of our possible mental and physical resources. ” The race to discover the unused resources in the brain has already begun. Who knows what we will be able to sense in the future? With the help of technology, combined with perceptual learning, we are on the verge of becoming humans with super abilities!

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: Expression levels of genes involved in glycolysis (pfkma, pfkmb), krebs cycle (idh3, dlstb). Gene expression data was generated from whole fish. Expression levels were derived from DESeq2 normalized gene counts. These profiles revealed a clear overall pattern: glycolysis genes are poorly expressed at the very beginning of the larval development while their expression increases throughout the development. This is particularly visible for pfkma which starts to increase from D10 and reaches its highest expression level at D32, likely coinciding with the onset of metamorphosis, and then decreases until the juvenile stage (J) (Figure 5A). The genes involved in the rate-limiting steps of the citric acid cycle (cs, idh3, dlst) are more expressed during early larval stages and then decrease progressively. It is also worth noting that several genes involved in both glycolysis and the TCA cycle are encountering these two peaks of expression during the larval development (gpi1b, aldoaa, gapdh1, pgam1a, pgam1b, pgam2, eno1b, pkma, dlsta, dldh, sdhb, mdh2, 2. Figure 6 Download asset Open asset Expression levels of genes involved in the hypothalamo-pituitary-interrenal axis (HPI) and corticoid synthesis. (A) Expression levels of genes involved in HPI: crha (corticotropin releasing hormone a), crhb (corticotropin releasing hormone b), crhr1a (corticotropin releasing hormone receptor 1 a), crhr1b (corticotropin release hormone receptor 1b), crhr2 (cortico release hormone receptor 2), pomc-a1 (propiomelanocortin a1), pomc-a2 (propiomelanocortin a2), pomc-b (propiomelanocortin b), mr (mineralocorticoid receptor), gr1 (glucocorticoid receptor 1), gr2 (glucocorticoid receptor 2).

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Application of epigenetic therapies in terms of developing drugs that block epigenetic events in cancer is one of the major courses of action that can influence the epigenetic yield. Demethylating agents namely 5-azacytidine (5-aza-CR) and 5-aza-2'-deoxycytidine (5-Aza-CdR) are the only cytidine analogues that have been approved by the U. S. Food and (FDA) for hematological malignancies in non-toxic doses [131,132]. Cancer as a circadian rhythm related disorder Different lines of evidence in mice and humans suggest that cancer may be a circadian-related disorder [133,134]. A number of studies by Filipski et al. indicate that the circadian clock of the host might play an important role in the endogenous control of tumor progression. SCN ablation or exposure to experimental chronic jetlag (CJL) caused alterations in circadian physiology and significantly accelerated tumor growth. CJL suppressed or altered the rhythms of clock gene and cell cycle gene expression in mouse liver. It increased p53 and decreased c-Myc expression, a result in line with the promotion of diethylnitrosamine-initiated hepatocarcinogenesis in jet-lagged mice. The accelerating effect of CJL on tumor growth is counterbalanced by the regular timing of food access over the 24 hours. Meal timing prevented the circadian disruption produced by CJL and slowed down tumor growth. In synchronized mice, meal timing reinforced host circadian coordination, phase-shifted the transcriptional rhythms of clock genes in the liver of tumor-bearing mice and slowed down cancer progression [135]. Recent findings suggest that circadian genes may function as tumor suppressors [133,136] at the systemic, cellular and molecular levels due to their involvement in cell proliferation [82,89], apoptosis [85,91], cell cycle control [69,70,82], and DNA damage response [70,86,97]. The genetic or functional disruption of the molecular circadian clock may result in genomic instability and accelerated cellular proliferation, two conditions that favor carcinogenesis [137]. Thus, aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis thus potentially promoting carcinogenesis.

Output: corroborate


Input: Claim: CRISPR can be used to create entirely new human species with superhuman abilities. [SEP] Text: All values were normalised to the steady-state, DMSO treated condition (bars 1 and 5). Mean ± S. D. (n = 3) and significance are indicated, unpaired Students t-test: **p≤0. 01, ***p≤0. 001, n. s. not significant. Figure 5—figure supplement 2—source data 1 Raw data from qPCR experiment in Figure 5—figure supplement 2B. Download elife-40009-fig5-figsupp2-data1-v1. xlsx Figure 6 with 1 supplement Download asset Open asset Endogenous RNF145 shows sterol-sensitive binding to Insig-1 and HMGCR. (A) Exogenous RNF145 shows sterol-sensitive binding to HMGCR. RNF145 knockout cells stably reconstituted with RNF145-V5 (ΔR145 #4 + R145-V5, as shown in Figure 3—figure supplement 4C, lane 3) were sterol-depleted (SD, 20 hr) and, where indicated, sterols (S) added back for 1 hr in the presence of NMS-873 (10 µM, 1. 5 hr). RNF145-V5 was affinity-purified (AP) and HMGCR detected by immunoblotting. Representative of ≥3 independent experiments. (B - C) Endogenous RNF145 shows sterol-sensitive binding to HMGCR and Insig-1. (B) HeLa WT or ΔRNF145 #4 (∆R) cells were treated as in (A), endogenous RNF145 was immunoprecipitated (IP), and RNF145 and HMGCR detected by immunoblot analysis. Non-specific bands are designated by an asterisk (*). Representative of ≥3 independent experiments. (C) HeLa UBE2G2 knockout cells (ΔUBE2G2 #1) were sterol-depleted (SD, 20 hr) and, where indicated, sterols (S) added for 1 hr. Endogenous RNF145 was affinity-purified and following SDS-PAGE separation, Insig-1 and HMGCR detected by immunoblot analysis. Representative of ≥2 independent experiments.

Output: pass


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: (B) Expression levels of genes involved in corticoids synthesis: star (steroidogenic acute regulatory protein), fdx1 (ferredoxine 1), fdx2 (ferredoxine 2), fdxr (ferredoxine reductase), cyp11a1 (Cytochrome P450 Family 11 Member 1), hsd3b1 (Hydroxysteroid dehydrogenases 3β1), cyp17a1 (Cytochrome P450 Family 17 Member 1), cyp21a2 (Cytochrome P450 Family 21 Member 2), cyp11c1 (Cytochrome P450 Family 11 Member 1), hsd11b1, hsd11b2 (Hydroxysteroid dehydrogenase 11 3β1&2). (C) Cortisol levels (in ng/g of larvae) during early larval development. Three biological replicates consisting of pooled larvae were analysed at each stage (D01 n = 120 larvae per replicate, D03 n = 120 larvae per replicate, D06 n = 60 larvae per replicate, D10 n = 40 larvae per replicate). # indicates that the value is below the quantification limit, and different letters indicate significant differences <0. 05 (one-way ANOVA followed by a Tukey HSD test). Gene expression data was generated from whole fish. Expression levels were derived from DESeq2 normalized gene counts. Most of the genes of this pathway displayed a similar pattern as described previously above with a surge of expression between D03 and D10 and a second one between D32, D60 (crhb, crhr1b, crhr2, pomc-a2, mr, gr1) (Figure 6A). The expression level of the gene encoding for CRHR2 started to increase after D01 and remained relatively stable all along whereas crha was lowly expressed (Figure 6A). A surge of expression was observed for pomc-a1 at D03 followed by a constant decrease until the juvenile stage. High expression of pomc-b was observed at D13, D18, and Juvenile stage. Finally, gr2 expression level increased strongly at D03, then remained stable and increased again at D60.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: As stress-induced senescence has been proposed as one of the mechanisms for tumour suppression [141], the delay in tumorigenesis seen in p53-/- Cry1-/- Cry-/- mice may indicate a switch of DNA damage response to senescence, which in these compound mutants is attributable to insufficiency of Cryptochromes. Cancer chronotherapy Research in chronotherapy, which takes into consideration the biological time to improve treatments, plays an important role in devising new therapeutic approaches for the treatment of cancer [142]. The circadian timing system controls cellular proliferation as well as drug metabolism over 24 hours through molecular clocks, circadian physiology, and the SCN [143]. That is why both the toxicity and efficacy of more than 30 anticancer agents vary by more than 50% as a function of dosing time in experimental models [144]. The administration of a drug at a circadian time when it is best tolerated usually achieves best antitumor activity. This has been reported for antimetabolites, such as arabinofuranosylcytosine, 5-fluorouracil (5-FU), or 5-fluorouracil deoxyribonucleoside (FUDR); for intercalating agents such as doxorubicin; and for alkylating drugs such as melphalan or cisplatin [145]. The results obtained by numerical simulations of automaton model for the cell cycle indicate that the least cytotoxic patterns of 5-FU and l-OHP (oxaliplatin) circadian administration match those used clinically. The model also shows that continuous administration of 5-FU and l-OHP has the same effect as the most cytotoxic circadian pattern of drug delivery. Furthermore, the model helps to identify factors that may contribute to explain why temporal patterns corresponding to minimum cytotoxicity for a population of healthy cells could at the same time prove more cytotoxic toward a population of tumour cells [146]. The clinical relevance of chronotherapy is currently being investigated along these lines for the outcome of patients suffering from metastatic breast and pancreatic cancers. Multicenter clinical trials comparing chronomodulated versus conventional therapy are being planned for the adjuvant treatment of colorectal cancer and for head and neck and biliary duct cancers [146]. More phase III trials will be needed to firmly establish chronotherapy in medical oncology.

Output: corroborate


Input: Claim: CRISPR can be used to create entirely new human species with superhuman abilities. [SEP] Text: The proposed method was used to effectively assess the cultural competence of clinical nurses. The findings of this study serve as a reference for health care providers in the process of designing cultural competence-related education programs to improve clinical nursing care quality. AbbreviationsOSCE: : Survey SPs: standardized patients MOSE: : Index SP: Standardized PatientDeclarationsEthics approval and consent to participate: This study was approved by the of the research hospital (Approval No. 17MMHIS096e). Consent for publication: Not applicable. Availability of data and materials: The datasets used and analysed during the current study are available from the corresponding authors on reasonable request. Competing interests The authors declare no conflict of interest. Funding: of Science and Technology of Taiwan for funding [grant numbers: MOST 105-2511-S-227 -002 -MY2 Authors’ contributions: Lee Yu-Hsia, designed the teaching materials, collected and analyzed the data, and evaluated the learning outcome of this intervention. Lin Shu-Chuan, designed the teaching materials, Wang Pao-Yu, collected and evaluated the learning outcome of this intervention. Lin Mei-Hsiang, designed the teaching materials and evaluated the learning outcome of this intervention, critically revised and approved the final manuscript. Acknowledgements: The authors would like to thank the nurses who participated in this study. 213. doi: 10. 1177/1043659612472059. . Understanding cultural competence in a multicultural nursing workforce: Registered nurses' experience in Saudi Arabia. J Transcult Nurs. 2015; 26:16-23. doi:10. 1177/1043659614523992. Strategies to promote cultural competence in distance education. J. Transcult. Nurs. 2015; 26 (4): 436-440. doi. 10. 1177/1043659614547201. Culturally sensitive communication in healthcare: A concept analysis. Collegian. 2019; 26 (3): 383-391. doi. 10. 1016/j. colegn. 2018. 09. 007. An innovative evaluation in fundamental nursing curriculum for novice nursing students: an observational research. J. Prof. Nurs. 2018; 34 (5): 412-416. doi 10. 1016/j. profnurs. 2018. 05. 002. . The effect of a cultural competence educational intervention for first-year nursing students in Israel.

Output: pass


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: The relatively high expression of the crhr genes may suggest an increase in the sensitivity to CRH to mediate the production of POMC by the pituitary gland, a process that seems to occur twice during E. malabaricus larval development. Concomitantly, a two-step increase in the star is observed: first at D03 and a second at D32. This may suggest an increase in the production of cortisol following the high expression of pomc-a2. Indeed, POMC is the precursor of the adreno cortico trophic hormone (ACTH) which is the pituitary factor stimulating cortisol production by the inter-renal gland (Takahashi and Mizusawa, 2013). The expression levels of genes involved in cortisol production corroborate this hypothesis. Indeed, we observe an increase of expression around D03 and D06 for fdx1, cyp11a1, hsd3b1, cyp11c1, hsd11b1, hsd11b2, as well as a second increase of expression from D32 for fdx1, fdxr, hsd3b1, cyp11c1, hsd11b1, hsd11b2. Interestingly, measurements of cortisol levels during early larval development (between D01 and D10) showed that cortisol concentration starts to increase from D3, coinciding with the expression levels of the star, and is followed by a stronger increase from D10. Those results first indicate that the HPI axis and cortisol production are activated at the beginning of the larval development around the timing of activation of TH pathway genes between D03 and D10. Second, the transcriptomic data also showed an activation of the corticoid pathway genes around D32 as it has been observed for TH pathway genes. There is contrasting evidence of communication between these two pathways during teleost fish larval development with some data suggesting a synergic and other an antagonistic relationship. In terms of synergy, an increase in cortisol levels concomitantly with an increase in TH levels has been observed in flatfish (de Jesus et al. , 1991), golden sea bream (Deane and Woo, 2003), and silver sea bream (Szisch et al. , 2005).

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: A recent study finds that wild-type and circadian mutant mice demonstrate striking differences in their response to the anticancer drug cyclophosphamide (CY). While the sensitivity of wild-type mice varies greatly, depending on the time of drug administration, Clock mutant and Bmal1 knockout mice are highly sensitive to treatment at all times tested. On the contrary, mice with loss-of-function mutations in Cryptochrome (Cry1-/-Cry2-/- double knockouts) were more resistant to CY compared with their wild-type littermates. This indicates that sensitivity of chemotherapeutic drug cyclophosphamide (CY) is directly correlated with the functional status of the major circadian transactivation complex, suggesting that molecular determinants of sensitivity to CY may be directly regulated by CLOCK-BMAL1, which is based on a CLOCK-BMAL1-dependent modulation of target B cell responses to drug-induced toxicity [147]. As discussed earlier, nucleotide excision repair is found to display prominent circadian oscillations in mouse brain reaching at its peak in the afternoon/early evening attributable to circadian oscillation of XPA [97]. It is interesting to note that the peak of DNA repair activity coincide with the previously determined peak of animal's resistance to CY forming a background for important clinical applications. However, further research is required to know whether the damage caused by CY is repaired by nucleotide excision repair mechanism in vivo. Anticancer agents generally produce their cytotoxic effect in both malignant and normal tissues. If we know the circadian rhythm of DNA repair capacity of cancer and normal tissues, we can extrapolate that the most favorable time for drug administration will be when the excision repair activity is low in cancer tissues and when the repair activity is high in normal tissues. Multiple preclinical models with different clock properties are needed for the personalization of cancer chronotherapeutics and the prophecy of optimal chronomodulated drug delivery. The stages where chronotherapeutics will be incorporated into the development of new anticancer drugs will have to be defined, ranging from screening to clinical phases. regulation is important to maintain normal cellular functions, and a disruption of core clock genes can be damaging to the organism's overall well-being. The work is in progress to explicate the cascading interactions of networks of CCGs that connect the clockwork to the expressed rhythms. Results from several epidemiological and genetic studies have shown that disruption of circadian rhythm may lead to cancer.

Output: corroborate


Input: Claim: CRISPR can be used to create entirely new human species with superhuman abilities. [SEP] Text: 1060. 10. 1111/1462-2920. 13058 1340. 26. 160. 273. 406. 248. 1554. 230. 1369. 1884. 335. 5117. 636. 775. 1589. 294. 8760. 92. 797. 34. 3731. 170. 37. 372. 2363. 8208. Download BibTeX Download. RIS Share this 10. 7554/eLife. 08208 Categories and tags Tools and experimental evolution microbial metabolism flux balance analysis model calibration diversity microbial ecology Research organism E. coli Further reading Computational and Genetics and Genomics DGRPool, a web tool leveraging harmonized phenotyping data for the study of complex traits. . . Tools and 21, 2024 Genome-wide association studies have advanced our understanding of complex traits, but studying how a GWAS variant can affect a specific trait in the human population remains challenging due to environmental variability. Drosophila melanogaster is in this regard an excellent model organism for studying the relationship between genetic and phenotypic variation due to its simple handling, standardized growth conditions, low cost, and short lifespan. Panel (DGRP) in particular has been a valuable tool for studying complex traits, but proper harmonization and indexing of DGRP phenotyping data is necessary to fully capitalize on this resource. To address this, we created a web tool called DGRPool (dgrpool. epfl. ch), which aggregates phenotyping data of 1034 phenotypes across 135 DGRP studies in a common environment. DGRPool enables users to download data and run various tools such as genome-wide (GWAS) and phenome-wide (PheWAS) association studies. As a proof-of-concept, DGRPool was used to study the longevity phenotype and uncovered both established and unexpected correlations with other phenotypes such as locomotor activity, starvation resistance, desiccation survival, and oxidative stress resistance. DGRPool has the potential to facilitate new genetic and molecular insights of complex traits in Drosophila and serve as a valuable, interactive tool for the scientific community. Computational and Genetics and metabolic modeling-based framework for predicting trophic dependencies in native rhizobiomes of crop plants Ginatt,. . . Research 1.

Output: pass


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: Cortisol was also shown to enhance in vitro the action of TH on fin ray resorption (a phenomenon occurring during flatfish metamorphosis) in flounder de Jesus et al. , 1990. It has also been shown that cortisol regulates local T3 bioavailability in the juvenile sole via regulation of deiodinase 2 in an organ-specific manner (Arjona et al. , 2011). On the antagonistic side, it has been shown that experimentally induced hyperthyroidism in common carp decreases cortisol levels (Geven et al. , 2006), whereas cortisol exposure decreases TH levels in European eels (Redding et al. , 1986). Given this scattered evidence, the existence of a crosstalk active during teleost larval development and metamorphosis has never been formally demonstrated. The results we obtained in grouper are clearly indicating that the HPI axis is activated during both early development and metamorphosis and that cortisol synthesis is activated during early development. This may suggest that in some aspects, cortisol synthesis could work in concert with TH, as has been shown in several different contexts in amphibians (Sachs and Buchholz, 2019), but functional experiments need to be conducted to confirm this hypothesis. It is worth to note, however, that the increase of the gene encoding POMC-A2 may not only be linked to cortisol synthesis as POMC is also a precursor of other hormones and notably melanocytes-stimulating hormones (Takahashi and Mizusawa, 2013). Those hormones belong to the melanocortin system that is involved in body pigmentation, but also in social behavior, appetite, and stress physiology (Cone, 2006). The increase in pomc-a2 observed during E. malabaricus may thus also be involved in the onset of pigmentation pattern. Taken together, these results brought a first insight into the potential role of corticoids in the larval development of E. malabaricus and call for functional experiments directly testing a possible synergy. Given the results obtained in our study, E. malabaricus could be a good model to investigate the potential role of corticoids and TH in elongate appendages formation during early larval development as well as during metamorphosis and if there is an interplay between the two pathways.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: : [PubMed] Kume, K; Zylka, MJ; Sriram, S; Shearman, LP; Weaver, DR; Jin, X; Maywood, ES; Hastings, MH; 1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop Cell 98: 193–205, DOI: [PubMed] Sato, TK; Yamada, RG; Ukai, H; Baggs, JE; Miraglia, LJ; Kobayashi, TJ; Welsh, DK; Kay, SA; Ueda, HR; Hogenesch, JBFeedback repression is required for mammalian circadian clock function 38: 312–319, DOI: [PubMed] Hirayama, J; Sahar, S; Grimaldi, B; Tamaru, T; Takamatsu, K; Nakahata, Y; Sassone--mediated acetylation of BMAL1 controls circadian function Nature 450: 1086–1090, DOI: [PubMed] Nakahata, Y; Kaluzova, M; Grimaldi, B; Sahar, S; Hirayama, J; Chen, D; Guarente, LP; Sassone-+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control Cell 134: 329–340, DOI: [PubMed] Asher, G; Gatfield, D; Stratmann, M; Reinke, H; Dibner, C; Kreppel, F; Mostoslavsky, R; Alt, FW; 1 regulates circadian clock gene expression through PER2 deacetylation Cell 134: 317–328, DOI: [PubMed] Guillaumond, F; Dardente, H; Giguere, V; Cermakian, NDifferential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors J 20: 391–403, DOI: [PubMed] Sato, TK; Panda, S; Miraglia, LJ; Reyes, TM; Rudic, RD; McNamara, P; Naik, KA; FitzGerald, GA; Kay, SA; Hogenesch, JBA functional genomics strategy reveals Rorα as a component of the mammalian circadian clock Neuron 43: 5

Output: corroborate


Input: Claim: Biotechnology allows people to live forever by continually replacing damaged tissues. [SEP] Text: Skip to main contentScientific AmericanSeptember 1, 201014 min readWhy Can't Forever? As we grow old, our own cells begin to betray us. By unraveling the mysteries of aging, scientists may be able to make our lives longer and healthierKirkwoodIf you were given a free hand to plan how your life will end—your last weeks, days, hours and minutes—what would you choose? Would you, for example, want to remain in great shape right up until the last minute and then go quickly? Many people say they would choose that option, but I see an important catch. If you are feeling fine one moment, the very last thing you would want is to drop dead the next. And for your loving family and friends, who would suffer instant bereavement, your sudden death would be a cruel loss. On the other hand, coping with a long, drawn-out terminal illness is not great either, nor is the nightmare of losing a loved one into the dark wastes of dementia. We all prefer to avoid thinking about the end of life. Yet it is healthy to ask such questions, at least sometimes, for ourselves and to correctly define the goals of medical policy and research. It is also important to ask just how far science can help in efforts to cheat death. We’re is often said that our ancestors had an easier relationship with death, if only because they saw it so much more often. Just 100 years ago life expectancy was shorter by around 25 years in the West. This literal fact of life resulted because so many children and young adults perished prematurely from a whole variety of causes. A quarter of children died of infection before their fifth birthday; young women frequently succumbed to complications of childbirth; and even a young gardener, scratching his hand on a thorn, might be lost to fatal blood poisoning. On supporting science journalismIf you're enjoying this 1977. I believe that the answer, now called the disposable soma theory, goes a long way toward explaining why different species age as they do. Age as theory is best understood by considering the challenges cells and complex organisms face as they try to survive. Cells are damaged all the time—DNA gets mutated, proteins get damaged, highly reactive molecules called free radicals disrupt membranes, and the list goes on. Life depends on the continual copying and translation of genetic data, and we know that the molecular machinery handling all these things, excellent as it may be, is not perfect.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: Such interplay could have relevant consequences in terms of aquaculture and claim for an examination of the role of stress in regulating fish larval development and impacting metamorphosis triggering. Overall, the results obtained in this study revealed a very precocious surge of expression of genes involved in two key hormonal pathways (corticoids and TH) that are known to control ontogenetic transitions, but which are also involved in the regulation of many biological processes (Wada, 2008; Watanabe et al. , 2016). This indicates that the early post-embryonic period in grouper may correspond to such an ontogenetic transition that has been ignored until now and that could be linked to the formation of the specific elongated appendages present in groupers. More generally, the fact that the outcome of metamorphosis is very variable from one species to another (e. g. differences in metamorphosis between clownfish, grouper, flatfish, etc. ) and that it also allows exquisite acclimation of the juveniles to their local environment (Denver, 2021), highlights the capacity of this transitional step, controlled by environmentally connected hormonal systems, to change rapidly in accordance with ecological needs (Zwahlen et al. , 2024). Finally, considering that rearing conditions during larval metamorphosis in an aquaculture context may impact growth and welfare at later life stages, understanding the molecular changes occurring during the development of a species might prove useful to enhance survival rates. Materials and methods Larval husbandry Request a detailed protocol This study was conducted in partnership with the -cho, Okinawa, Japan. Epinephelus malabaricus larvae and juveniles were obtained from various clutches obtained from natural spawning in 2020, 2021, and 2023. Larvae were reared under natural conditions in 50,000 L of natural sea water in circular tanks. Light exposure duration followed natural daylight hours, salinity (approximately 33–34 ppm), and temperature (approximately 27॰C on average) remained relatively stable as the tanks were constantly renewed with natural seawater. Microalgae (Nannochloropsis sp. ) was added from hatching until 15 days post-hatching (dph) to maintain the nutritional value of live-feed organisms and create a green-water environment. sp.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: DOI: [PubMed] Gery, S; Komatsu, N; Baldjyan, L; Yu, A; Koo, D; Koeffler, HPThe circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells 22: 375–382, DOI: [PubMed] Barnes, JW; Tischkau, SA; Barnes, JA; Mitchell, JW; Burgoon, PW; Hickok, JR; Gillette, MURequirement of mammalian Timeless for circadian rhythmicity Science 302: 439–442, DOI: [PubMed] Unsal-Kacmaz, K; Mullen, TE; Kaufmann, WK; Sancar, ACoupling of human circadian and cell cycles by the timeless protein Biol 25: 3109–3116, DOI: [PubMed] Wood, PA; Yang, X; Taber, A; Oh, EY; Ansell, C; Ayers, SE; Al-Assaad, Z; Carnevale, K; Berger, FG; Pena, MM; Hrushesky, WJPeriod 2 mutation accelerates ApcMin/+ tumorigenesis Res 6: 1786–1793, DOI: [PubMed] Yang, X; Wood, PA; Ansell, CM; Ohmori, M; Oh, EY; Xiong, Y; Berger, FG; Pena, MM; Hrushesky, WJBeta-catenin induces beta-TrCP-mediated PER2 degradation altering circadian clock gene expression in intestinal mucosa of ApcMin/+ mice J Biochem 145: 289–297, DOI: [PubMed] Hua, H; Wang, Y; Wan, C; Liu, Y; Zhu, B; Yang, C; Wang, X; Wang, Z; Cornelissen-Guillaume, G; Halberg, FCircadian gene mPer2 overexpression induces cancer cell apoptosis 97: 589–596, DOI: [PubMed] Hua, H; Wang, Y; Wan, C; Liu, Y; Zhu, B; Wang, X; Wang, Z; Ding, JMInhibition of tumorigenesis by intratumoral delivery of the circadian gene mPer2 in C57BL/6 mice Ther 14: 8

Output: corroborate


Input: Claim: Biotechnology allows people to live forever by continually replacing damaged tissues. [SEP] Text: Considering all these challenges, the immortality of the germ line is actually remarkable. Living cells operate constantly under threat of disruption, and the germ line is not immune. The reason that the germ line does not die out in a catastrophe of errors has to do, on the one hand, with its highly sophisticated mechanisms for cellular self-maintenance and repair and, on the other hand, with its ability to get rid of its more serious mistakes through continual rounds of competition. Sperm are produced in vast excess; usually only a good one can fertilize the egg. Egg-forming cells are produced in much greater numbers than can ovulate; stringent quality control eliminates the ones that fail to make the grade. And finally, if errors slip past all these checks, natural selection provides the final arbiter of which individuals are the fittest to transmit their germ line to future generations. After the seemingly miraculous feat of growing a complex body from a single cell—the fertilized egg—it should be relatively straightforward merely to keep a body going indefinitely—as American evolutionist has pointed out. Indeed, for some multicelled organisms, an absence of aging appears to be the rule. The freshwater hydra, for example, shows an extraordinary power of survival. Not only does the hydra apparently not age, in the sense that as it gets older it shows no increase in death rate or decline in fertility, it also appears capable of regrowing a whole new body from even a tiny fragment, if by chance it is cut into pieces. The secret of the hydra’s eternal youth: quite simply, germ cells permeate its body. If the immortal germ line is everywhere, it actually comes as no surprise that an individual hydra can survive without any foreseeable end, presuming it does not succumb to injury or predators. In most multicelled animals, however, the germ line is found only in the tissue of the gonads, where the sperm and eggs form. This arrangement provides great advantages. During the long history of evolution, it freed other cell types to become specialists—nerve, muscle and liver cells, among others, that are required for the development of any complex organism, whether a Triceratops or a human. This division of labor had far-reaching consequences for how organisms age and how long they can live.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: (S type) were enriched with fish oil and distributed twice a day from 1 dph to maintain a concentration of 10 ind/mL until 13 dph. Artemia nauplii were added twice a day from 13 dph to 20 dph. Frozen copepods were given five times a day from 13 dph until 20 dph. Artificial food was given from 20 dph during the daytime by automatic feeding (one distribution every hour). Sample collection and tissue collection Request a detailed protocol In order to assemble and functionally annotate the genome, tissues for DNA sequencing and RNA sequencing were collected on September 8, 2020 from two approximately 4-month-old fish sourced from the Center. The fish were euthanized by cervical dislocation, and immediately dissected. The liver and muscle tissues of one fish were immediately frozen in liquid nitrogen for PacBio HiFi and Hi-C sequencing, respectively. Brain, gill, liver, heart, caudal fin, eye, spleen, stomach, intestine, muscle, skin spinal cord, and spinal nerve tissues were taken from the second fish and stored in RNAlater (ThermoFisher Scientific) for tissue-specific transcriptome sequencing. For the larval developmental analysis, whole larval and juvenile fish were sampled between April 30, 2021 and June 2, 2021, ranging from 1 day post-hatching (dph) to approximately 2 months (Table 4). A total of four clutches spawned in early and late April were sampled during this period and larvae were collected and sorted according to their morphology allowing us to sequence eight developmental stages. Larvae and juveniles were euthanized in the afternoon (between 13:00 and 15:00) with MS222 solution (200 mg/L, Sigma-A5040) before being placed in RNAlater. Larger fish were cut open for improved RNAlater penetration and samples were kept at 4॰C for 2-8 days before being stored at –20॰C until extraction. Larvae for TH and cortisol measurements were sampled in triplicates between June 17, 2023 and June 26, 2023 at D01 (n=120 per replicate), D03 (n=120 per replicate), D06 (n=60 per replicate), and D10 (n=40 per replicate), as described in Roux et al. , 2023 and kept at –80 until analysis.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: 15–818, DOI: [PubMed] Gauger, MA; and Res 65: 6828–6834, DOI: [PubMed] Kondratov, RV; Kondratova, AA; Gorbacheva, VY; Vykhovanets, OV; Antoch, MPEarly aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock 20: 1868–1873, DOI: [PubMed] Antoch, MP; Gorbacheva, VY; Vykhovanets, O; Toshkov, IA; Kondratov, RV; Kondratova, AA; Lee, C; Nikitin, AYDisruption of the circadian clock due to the Clock mutation has discrete effects on aging and carcinogenesis 7: 1197–1204.

Output: corroborate


Input: Claim: Biotechnology allows people to live forever by continually replacing damaged tissues. [SEP] Text: As soon as the specialist cells surrendered the role of continuing the species, they also abandoned any need for immortality; they could die after the body had passed on its genetic legacy through the germ line to the next generation. Ultimate Trade-offsso how long can those specialist cells survive? In other words, how long can we and other complex organisms live? The answer for any given species has a lot to do with the environmental threats its ancestors faced as they evolved and with the energy costs of maintaining the body in good operating order. By far the majority of natural organisms die at relatively young ages because of accidents, predation, infection or starvation. Wild mice, for example, are at the mercy of a very dangerous environment. They are killed rather quickly—it is rare for a wild mouse to see its first birthday. Bats on the other hand are safer because they can fly. Meanwhile maintenance of the body is expensive, and resources are usually limited. Out of the daily intake of energy, some might go to growth, some to physical work and movement, some to reproduction. Some energy, instead, might be stored as fat to protect against famine, but much gets burned just to fix the innumerable faults that arise every second the organism is alive. Another increment of these scarce resources goes to proofread the genetic code involved in the continual synthesis of new proteins and other essential molecules. And still another allocation powers the energy-hungry garbage disposal mechanisms that clear molecular debris out of the way. Here is where the disposable soma theory comes in. The theory posits that, like the human manufacturer of an everyday product—a car or a coat, for example—evolving species have to make trade-offs. It does not pay to invest in allowing indefinite survival if the environment is likely to bring death within a fairly predictable time frame. For the species to survive, a genome basically needs to keep an organism in good shape and enable it to reproduce successfully within that time span. At all stages of life, even to its very end, the body does its utmost to stay alive—in other words, it is programmed not for aging and death but for survival. But under the intense pressure of natural selection, species end up placing higher priority on investing in growth and reproduction—in the perpetuation of the species—than on building a body that might last forever. So aging is driven by the gradual lifelong accumulation of diverse forms of unrepaired molecular and cellular damage.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: TH and cortisol extraction and measurement were outsourced to. , Kanagawa, Japan. Detailed protocols can be found in 12. 5 mm NL/2. 7 mm TLD01Newly hatched larva with a yolk sac; mouth unopened; eyes not pigmented; no pectoral fin32. 7 mm NL/2. 9 mm TLD03Yolk sac remains; the mouth is opened; eyes are pigmented; pectoral fins are formed; large melanophores appear on the ventral cavity and on the second half of the body62. 9 mm NL/3. 1 mm TLD06Yolk sac has been resorbed; dorsal-fin spine starts to form within the fin fold103. 8 mm NL/4. 0 mm TLD10Embryonic fin fold start differentiating in anal and dorsal fin while second spine of dorsal fin and spines of pelvic fins begin to extend with some melanophores colonizing the tips and xanthophores start covering the ventral cavity13–156. 0 mm NL/6. 4 mm TLD13Spines of dorsal and pelvic fins grow. First spine of dorsal fin appears, second spine of dorsal fin and spines of pelvic fins become serrated; head spines appear, caudal-fin rays start to form, tip of the notochord begins to flex; xanthophores continue their expansion18–206. 8 mm SL/8. 3 mm TLD18Notochord post-flexed; hypural bones are formed and in perpendicular position; caudal-fin rays are segmented; soft rays of dorsal and anal fins start to form and both fins start to form their final shape; fin rays are forming on upper part of the pectoral fin; soft rays of pelvic fins began to form; melanophores appeared on the top of the head and on the caudal peduncle30–3210. 0 mm SL/12. 8 mm TLD32Second spine of dorsal fin and spines of pelvic fins start to regress; soft rays in dorsal, anal, and pectoral fins are weakly segmented, caudal fin becomes truncated shape; melanophores are appearing at the basis of dorsal spines and along the notochord, melanophores ventrally on the caudal peduncle disappears; xanthophores start colonizing the caudal peduncle6014.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: [PubMed] Ozturk, N; Lee, JH; Gaddameedhi, S; Sancar, ALoss of cryptochrome reduces cancer risk in p53 mutant mice 106: 2841–2846, DOI: [PubMed] Kang, TH; Reardon, JT; Kemp, M; Sancar, ACircadian oscillation of nucleotide excision repair in mammalian brain 106: 2864–2867, DOI: [PubMed] Schernhammer, ES; Laden, F; Speizer, FE; Willett, WC; Hunter, DJ; Kawachi, I; Colditz, GARotating night shifts and risk of breast cancer in women participating in the nurses' health study J Inst 93: 1563–1568. [PubMed] Hansen, JRisk of breast cancer after night- and shift work: current evidence and ongoing studies in 17: 531–537, DOI: [PubMed] Stevens, RGArtificial lighting in the industrialized world: Circadian disruption and breast cancer Control 17: 501–507, DOI: [PubMed] Davis, S; Mirick, DKCircadian disruption, shift work and the risk of cancer: a summary of the evidence and studies in 17: 539–545, DOI: [PubMed] Keith, LG; Oleszczuk, JJ; Laguens, MCircadian rhythm chaos: a new breast cancer marker Med 46: 238–247. [PubMed] Pushkala, K; Gupta, PDPrevalence of breast cancer in menopausal blind women IJMMS 1: 425–431. Viswanathan, AN; Hankinson, SE; and the Risk of 67: 10618–10622, DOI: [PubMed] Band, PR; Le, ND; Fang, R; Deschamps, M; Coldman, AJ; Gallagher, RP; Moody, JCohort study of pilots: mortality, cancer incidence, and leukemia risk Epidemiol 143: 13–43.

Output: corroborate


Input: Claim: Biotechnology allows people to live forever by continually replacing damaged tissues. [SEP] Text: No biological software program, then, dictates precisely when it is time to die, but growing evidence suggests that certain genes can nonetheless influence how long we live. , working with tiny nematode worms, discovered a gene with such an effect on longevity in the 1980s. Mutation of a gene that the researchers aptly named age-1 produced a 40 percent increase in average life span. Since then, investigators in many laboratories have found numerous other genes capable of increasing nematode life span, and similar mutations have turned up in other animals, from fruit flies to mice. The genes that extend life span mostly alter an organism’s metabolism, the way it uses energy for bodily functions. Often investigators find these genes play a role in the insulin-signaling pathway, pivotal in metabolic regulation. The cascades of molecular interactions constituting this pathway shift the overall level of activity of literally hundreds of other genes responsible for controlling all the intricate processes that carry out cellular maintenance and repair. In effect, it seems that lengthening life span requires changing exactly those processes we know protect the body against buildup of damage. The amount of food available also ratchets metabolism up or down. As long ago as the 1930s, researchers discovered, rather surprisingly, that underfeeding laboratory rodents extends their lives. Once again, modulating metabolism seems to have an effect on the rate of damage accumulation, because mice subjected to dietary restriction increase the activity of a range of maintenance and repair systems. At first glance, it might seem strange that an animal short of food should spend more, not less, energy on bodily maintenance. A period of famine is, however, a bad time to reproduce, and some evidence suggests that during famines certain animals will do better to switch off their fertility, thereby diverting a large fraction of their remaining energy budget to cell maintenance. and Menthis notion of caloric restriction—and its purported ability to extend longevity—has captured the attention of people who wish to live longer. Humans who go hungry in the hope of a longer life should take note, though, that such a mechanism is much less likely to work for us because our slow-paced metabolism differs greatly from that of organisms in which this strategy has already been tested. Dramatic extension of life span has indeed been achieved in worms, flies and mice. These animals, with their short-lived, fast-burn biology, have an urgent need to manage their metabolism in a way that adapts rapidly to changing circumstances.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: 7 mm SL/19. 1 mm TLD60Second spine of dorsal fin and spines of pelvic finscontinue their regression. Soft rays in pectoral and pelvic fins segmented; caudal-fin rays branched; anterior two bands of melanophores start appearing in some individuals: xanthophores are disappearing from the ventral cavity6027. 6 mm SL/34. 6 mm TLJJuvenile stage; scales cover the body surface; second spine of dorsal fin and spines of pelvic fins fully regressed and became plain without hooks; caudal fin reached its final round shape; adult pigmentation pattern is more visible with alternate light and brownish vertical bands making lateral line system fully visible All sampling conducted in this study was done under the approval of the at the of Science and University (approval N°2021–328). DNA extraction and sequencing Request a detailed protocol Genomic DNA was extracted from liver tissue using the extraction kit (Machery-Nagel). Library preparation was carried out with the 2. 0 and primer v2, Sequel II 2. 0, and Sequel II 2. 0 (Pacific Biosciences). Sequencing was done on a Sequel II System, using three SMRT Cell 8 M flow cells through diffusion loading of 60-100pM library. Hi-C library preparation and sequencing was carried out by from muscle tissue using the Kit v3. 0 and sequenced on a Illumina HiSeq 4000 with 150 bp PE. RNA extraction and sequencing Request a detailed protocol For the functional genome annotation, tissue samples were homogenized using a PT1200E Homogenizer and RNA was extracted using the Maxwell RSC simply RNA (Promega: AS1340). Individually barcoded Isolibraries of all 13 tissues were prepared by the using the 2. 0. The libraries were sequenced on a Pac2 across two SMRT Cell 8 M flow cells. For the developmental transcriptomic analysis, samples from 1 to 32 dph were homogenized in thioglycerol using metal beads lysing matrix tubes (MPB) in an automated homogenizer (FastPrep-24 5 G MPB). Bigger samples (60 dph and juveniles) were manually homogenized in thioglycerol using 14 mL round bottom tubes and a tissue grinder (II, Qiagen).

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Pukkala, E; Aspholm, R; Auvinen, A; Eliasch, H; Gundestrup, M; Haldorsen, T; Hammar, N; Hrafnkelsson, J; Kyyrönen, P; Linnersjö, A; Rafnsson, V; Storm, H; Tveten, UCancer incidence among 10,211 airline pilots: a Nordic study 74: 699–706. [PubMed] Kubo, T; Ozasa, K; Mikami, K; Wakai, K; Fujino, Y; Watanabe, Y; Miki, T; Nakao, M; Hayashi, K; Suzuki, K; Mori, M; Washio, M; Sakauchi, F; Ito, Y; Yoshimura, T; Tamakoshi, AStudy of the Risk of among Rotating-Shift Workers: Findings from the 164: 549–555, DOI: [PubMed] Band, PR; Le, ND; Fang, R; Deschamps, M; Coldman, AJ; Gallagher, RP; Moody, JCohort study of pilots: mortality, cancer incidence, and leukemia risk Epidemiol 143: 13–43. Schernhammer, ES; Laden, F; Speizer, FE; Willett, WC; Hunter, DJ; Kawachi, I; Fuchs, CS; Colditz, GANight-and Risk of in the Nurses' 95: 825–828. [PubMed] Mormont, MC; Waterhouse, J; Bleuzen, P; Giacchetti, S; Jami, A; Bogdan, A; Lellouch, J; Misset, JL; Touitou, Y; Levi, Marked 24-h rest/activity rhythms are associated with better quality of life, better response, and longer survival in patients with metastatic colorectal cancer and good performance status Res 6: 3038–3045.

Output: corroborate


Input: Claim: Biotechnology allows people to live forever by continually replacing damaged tissues. [SEP] Text: In nematode worms, for example, most of the more spectacular effects on life span result from mutations that evolved to allow the worms to switch their development to a stress-resistant form whenever they find themselves in a bad environment and potentially required to make a long trek to find better living conditions. We humans, in any case, may not have the same flexibility in altering our own metabolic control. Immediate metabolic effects, of course, occur in humans who undergo voluntary dietary restriction, but only time—and many hungry years—will tell if these have any beneficial impact on the aging process and, in particular, on longevity. The goal of gerontology research in humans, however, is always improving health at the end of life, rather than achieving Methuselean life spans. Answersaging is complicated. It affects the body at all levels, from molecules to cells to organs. It also involves multiple kinds of molecular and cellular damage. And although it is true that, in general, this damage accumulates with age and occurs slower in some cell types than in others (depending on the efficiency of the repair systems), injury to any given cell occurs randomly, and the extent can differ even in two cells of the same type in an individual. Thus, all individuals age and die, but the process varies considerably—more confirmation that aging does not stem from a genetic program that specifies how quickly we become frail and die. To understand aging in enough detail to intervene in a suitably targeted fashion that stops or slows the death of selected kinds of cells, we need to know the nature of the molecular defects that drive the aging process at the cellular level. How many of these flaws must accrue before the cell can no longer function? How many defective cells need to accumulate in a given organ before it shows signs of disease? And if we agree that some organs are more important to target than others, how do we deliver the necessary precision? It may be possible to combat aging by altering important mechanisms that cells use to counteract the buildup of damage. One way that a cell responds to too much wear and tear is simply to kill itself. At one time, scientists viewed this cellular suicide process, technically called apoptosis, as evidence that aging adheres to a genetic program. In aged tissues the frequency of cells killing themselves increases, and this process does indeed contribute to aging.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: Samples from 1 and 3 dph consisted of pools of three larvae in triplicates, while all remaining timepoints consisted of triplicates of single individuals. RNA extraction was then carried out as for the tissue samples using the Maxwell RSC simply RNA (Promega: AS1340). Library preparation was carried out at the using the. The final pooled library was then split into two Seq SP flowcells for sequencing with 150 bp PE reads. Genome assembly, scaffolding, and phasing Request a detailed protocol The genome assembly was carried out using unprocessed PacBio HiFi reads with the diploid aware Assembler ( Sović and Kronenberg, 2020) using default parameters, which resulted in a primary and alternative phase genome. The two-phased genomes were assessed using purge_haplotigs (Roach et al. , 2018) using default parameters to generate a genome-wide read-depth histogram; however, no purging was necessary. Completeness of the final assembly was assessed using BUSCO (V4. 1. 2) (Manni et al. , 2021) with the actinopterygii_odb10 database. Scaffolding and phasing were outsourced to (See 2. 0. 1), RepeatMasker (Tempel, 2012) (V4. 1. 1), the vertebrata library of Dfam (V3. 3) (Storer et al. , 2021), and GenomeTools (V1. 6. 1) (Gremme et al. , 2013). Annotation was done using 2 (Brůna et al. , 2021) and associated programs (Barnett et al. , 2011; Brůna et al. , 2020; Buchfink et al. , 2015; Gotoh, 2008; Hoff, 2019; Hoff et al. , 2016; Iwata and Gotoh, 2012; Li et al. , 2009; Lomsadze et al. , 2014; Lomsadze et al. , 2005; Stanke et al. , 2008; Stanke et al. , 2006). For this, the ISO-seq data from the adult tissue and RNA-seq data from the larval samples (see below for the quality control process) were used together with publicly available protein data (Table 5). Post-processing was carried out as described by Ryu et al.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: [PubMed] Chen, ST; Choo, KB; Hou, MF; Yeh, KT; Kuo, SJ; Chang, JGDeregulated expression of the PER1, PER2 and PER3 genes in breast cancers Carcinogenesis 26: 1241–1246, DOI: [PubMed] Zhu, Y; Brown, HN; Zhang, Y; Stevens, RG; Zheng, TPeriod3 structural variation: a circadian biomarker associated with breast cancer in young women 14: 268–270. [PubMed] Winter, SL; Bosnoyan-Collins, L; Pinnaduwage, D; Andrulis, ILExpression of the Genes Per1 and Per2 in Sporadic and 9: 797–800, DOI: [PubMed] Xiang, S; Coffelt, SB; Mao, L; Yuan, L; Cheng, Q; Hill, SMPeriod-2: a tumor suppressor gene in breast cancer Journal of 6: 4. DOI: [PubMed] Klevecz, RR; Shymko, RM; Blumenfeld, D; Braly, PSCircadian gating of S phase in human ovarian cancer 47: 6267–6271.

Output: corroborate


Input: Claim: Biotechnology allows people to live forever by continually replacing damaged tissues. [SEP] Text: But we now know that apoptosis acts chiefly as a survival mechanism that protects the larger body from injured cells that could potentially cause trouble, notably, ones that have become malignant. Apoptosis happens more in old organs because their cells have suffered more insults. Remember, though, that in nature animals rarely live long enough to grow old. Apoptosis evolved to deal with damaged cells in younger organs, when many fewer would need to be eliminated. If too many cells die, an organ fails or becomes debilitated. So apoptosis is good and bad—good when it deletes potentially dangerous cells, bad when it deletes too many. Nature cares more about survival of the young than managing decline in old age, so not all apoptosis might be strictly necessary in our later years. In some diseases, such as stroke, researchers hope that by suppressing apoptosis in the less damaged tissue, the resulting loss of cells may be reduced, thereby aiding recovery. Instead of dying, hurt cells that are normally able to reproduce may take a less extreme course and simply stop dividing, a fate known as replicative senescence. Fifty years ago Leonard Hayflick, now at the University of California, San Francisco, discovered that cells tend to divide a set number of times—now called the Hayflick limit—and then stop. Later work showed that they often stop dividing when the caps, or telomeres, that protect the ends of chromosomes erode too much. But other details of how cell senescence sets in remained obscure. Recently, though, my colleagues and I have made an exciting discovery. We found that each cell has highly sophisticated molecular circuitry that monitors the level of damage both in its DNA and in its energy-forming units known as mitochondria. When the amount of damage passes some threshold, the cell locks itself into a state where it can still perform useful functions in the body but can never divide again. As with apoptosis, nature’s bias toward the survival of the young probably means that not all these lockdowns are strictly necessary. But if we are to unpick the locks and so restore some division capacity to aged cells, without unleashing the threat of cancer, we need to understand very thoroughly just how cell senescence works.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: , 2022 using the Swiss-Prot protein database (UniProt) (Consortium, 2021) with Diamond (Buchfink et al. , 2015) (V2. 0. 9) and Pfam domains (Mistry et al. , 2021) identified by InterProScan (V5. 48. 83. 0) (Zdobnov and Apweiler, 2001). Gene model statistics were calculated using the get_general_stats. pl script from the eval package (V2. 2. 8) (Keibler and Brent, 2003). Finally, functional annotation was carried out with the filtered gene models produced by. The amino acid sequences were blasted against the non-redundant protein database (downloaded 15. November 2021) using blastp (V2. 10. 0+; parameters: -show_gis -num_threads 10 -evalue 1e-5 -word_size 3 -num_alignments 20 -outfmt 14 -max_hsps 20) (Altschul et al. , 1990). Additionally, protein domains were assigned using InterProScan (V5. 48. 83. 0; parameters: --disable-precalc --goterms --pathways -f xml) (Zdobnov and Apweiler, 2001). The blast and interproscan results were then loaded into OmicsBox (Gotz et al. , 2008; Huerta-Cepas et al. , 2017) for post-processing. Table 5 Origin of protein sequences used for genome annotation in braker2. SpeciesCommon nameNumber of proteinsSourceAmphiprion ocellarisOcellaris clownfish48,668 reriozebrafish88,631 polyacanthusspiny chromis damselfish36,648 niloticusNile tilapia36,648 latipesJapanese medaka47,623 reticulataguppy45,692 salarAtlantic salmon112,302 partitusbicolor damselfish31,760 rubripesJapanese puffer49,529 lanceolatusGiant grouper42,970GCA_005281545.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: [PubMed] Klevecz, RR; Braly, PSCircadian and ultradian rhythms of proliferation in human ovarian cancer 4: 513–523, DOI: [PubMed] Tokunaga, H; Takebayashi, Y; Utsunomiya, H; Akahira, J; Higashimoto, M; Mashiko, M; Ito, K; Niikura, H; Takenoshita, S; Yaegashi, NClinicopathological significance of circadian rhythm-related gene expression levels in patients with epithelial ovarian cancer et Gynecologica 87: 1060–1070, DOI: Yeh, KT; Yang, MY; Liu, TC; Chen, JC; Chan, WL; Lin, SF; Chang, JGAbnormal expression of period I (PERI) in endometrial carcinoma J Pathol 206: 111–120, DOI: [PubMed] Shih, MC; Yeh, KT; Tang, KP; Chen, JC; Chang, JGPromoter methylation in circadian genes of endometrial cancers 45: 732–740, DOI: [PubMed] Cao, Q; Gery, S; Dashti, A; Yin, D; Zhou, Y; Gu, J; Koeffler, HPA Role for the Per1 in 69: 7619–7625, DOI: Gery, S; Gombart, AF; Yi, WS; Koeffler, C; Hofmann, WK; Koeffler, HPTranscription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia Blood 106: 2827–2836, DOI: [PubMed] Yang, MY; Chang, JG; Lin, PM; Tang, KP; Chen, YH; Lin, HY; Liu, TC; Hsiao, HH; Liu, YC; Lin, SFDownregulation of circadian clock genes in chronic myeloid leukemia: Alternative methylation pattern of hPER3 97: 1298–1307, DOI: [PubMed] Lewintre, EJ; Martín, CR; Ballesteros, CG; Montaner, D; Rivera, Rf; Mayans, JR; García-Conde, JCryptochrome-1 expression: a new prognostic

Output: corroborate


Input: Claim: Biotechnology allows people to live forever by continually replacing damaged tissues. [SEP] Text: The demanding science needed to make this discovery required a multidisciplinary team, including molecular biologists, biochemists, mathematicians and computer scientists, as well as state-of-the-art instruments for imaging the damage in living cells. Where such discoveries might lead we do not yet know, but it is through studies of this kind that we can hope to identify novel drugs able to combat age-related diseases in completely new ways and thereby shorten the period of chronic illness experienced at the end of life. The difficulty of this type of basic research means that many years, perhaps decades, may pass before these drugs come to market. Using the science of aging to improve the end of life represents a challenge, perhaps the greatest yet to face medical science. Solutions will not come easily, despite the claims made by the merchants of immortality who assert that caloric restriction or dietary supplements, such as resveratrol, may allow us to live longer. The greatest human ingenuity will be needed to meet this challenge. I believe we can and will develop treatments targeted at easing our final years. But when the end arrives, each of us—alone—will need to come to terms with our own mortality. All the more reason then to focus on living—on making the most of the time of our lives, because no magic elixir will save us. One other thing is also very clear: the longer-lived worms, flies and mice still undergo the aging process. Aging happens because damage still accumulates and in time leads to the breakdown of healthy functions of the body. Therefore, if we want our end to be actually better, we need to look elsewhere. In particular, we need to focus on figuring out how to safely limit or reverse the buildup of damage that leads eventually to age-related frailty, disability and disease. This goal represents a huge challenge and calls for some of the most demanding of today’s interdisciplinary research. Rights & PermissionsMore by Thomas KirkwoodThis 10. 1038/scientificamerican092010-7ekABzRb1j4F6r6HqZVD0with ScienceLearn and share the most exciting discoveries, innovations and ideas shaping our world today.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: 1, RefSeqEpinephelus akaaraRed-spotted grouper23,9234398b9f, DryadTotal aa sequences1,155,478 Differential gene expression analysis Request a detailed protocol The differential gene expression analysis for the larval developmental stages was carried out on the sequencing data from the whole larval and juvenile fish. Before processing, the data from the two lanes were merged per sample. Low-quality bases and adaptor sequences were filtered using (V0. 6. 5) (Krueger, 2015) and cutadapt (V2. 10) (Martin, 2011) using default parameters with the exception of ‘--length 30. ’ Kraken2 (V2. 0. 9-beta) (Wood et al. , 2019) was used to remove bacterial reads using the bacterial and archeal database (V4. 08. 20) and ‘--confidence 0. 3. ’ Cleaned reads were mapped using STAR (V2. 7. 9a) (Dobin et al. , 2013) with ‘--quantMode GeneCounts’ and ‘--out’ using the filtered gff file produced by the braker2 annotation outlined above for the genome indexing (--genomeSAindexNbases 13, --sjdbOverhang 149). The unstranded mapped reads were then loaded into Rstudio (V2022. 02. 4) (Team, 2020) using R (V3. 6. 3) (R Team, 2013). DESeq2 (V1. 36. 0) (Love et al. , 2014) was used for general data analysis, with coseq (V1. 20. 0) (Godichon-Baggioni et al. , 2019; Rau and Maugis-Rabusseau, 2018) being used for cluster analysis. The cluster analysis was carried out on differentially expressed genes only, as determined through likelihood ratio test (LRT) analysis (full model: design = ~dph, reduced model: reduced = ~1, adjusted p-value threshold: 0. 001) in DESeq2. Adjusted p-values and annotations for the group of genes represented in Figure 1B in this study can be found in the Suppl. Data File.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: AbstractThe effect of circadian rhythm (CR) disruption on immune function depends on the method by which CRs are disrupted. Behavioral and thermoregulatory responses induced by lipopolysaccharide (LPS) treatment were assessed in female Siberian hamsters in which circadian locomotor activity (LMA) rhythms were eliminated by exposure to a disruptive phase-shifting protocol (DPS) that sustains arrhythmicity even when hamsters are housed in a light-dark cycle. This noninvasive treatment avoids genome manipulations and neurological damage associated with other models of CR disruption. Circadian rhythmic (RHYTH) and arrhythmic (ARR) hamsters housed in a 16L:8D photocycle were injected with bacterial LPS near the onset of the light (zeitgeber time 1; ZT1) or dark (ZT16) phase. LPS injections at ZT16 and ZT1 elicited febrile responses in both RHYTH and ARR hamsters, but the effect was attenuated in the arrhythmic females. In ZT16, LPS inhibited LMA in the dark phase immediately after injection but not on subsequent nights in both chronotypes; in contrast, LPS at ZT1 elicited more enduring (~4 day) locomotor hypoactivity in ARR than in RHYTH hamsters. Power and period of dark-phase ultradian rhythms (URs) in LMA and Tb were markedly altered by LPS treatment, as was the power in the circadian waveform. Disrupted circadian rhythms in this model system attenuated responses to LPS in a trait- and ZT-specific manner; changes in UR period and power are novel components of the acute-phase response to infection that may affect energy conservation. Immune function is modulated by the circadian pacemaker in the suprachiasmatic nucleus (SCN). Behavioral, thermoregulatory, and cytokine responses to innate immune challenges (acute-phase responses) reflect an interaction between peripheral cytokine production and brain responsiveness to cytokines (Dantzer et al. , 2008). The acute-phase response may be particularly instructive for understanding interactions between the circadian and immune systems. Innate immune responses are robustly modulated by the circadian clock (Franklin et al. , 2003; Marpegan et al.

Output: corroborate


Input: Claim: Biotechnology allows people to live forever by continually replacing damaged tissues. [SEP] Text: Skip to main contentScientific AmericanApril 1, 201514 min readForever? As we grow old, our cells begin to betray usKirkwoodIf you were given a free hand to plan how your life will end—your last weeks, days, hours and minutes—what would you choose? Would you, for example, want to remain in great shape right up until the last minute and then go quickly? Many people say they would choose that option, but I see an important catch. If you are feeling fine one moment, the very last thing you would want is to drop dead the next. And for your loving family and friends, who would suffer instant bereavement, your sudden death would be a cruel loss. On the other hand, coping with a long, drawn-out terminal illness is not great either, nor is the nightmare of losing a loved one into the dark wastes of dementia. We all prefer to avoid thinking about the end of life. Yet it is healthy to ask such questions, at least sometimes, for ourselves and to correctly define the goals of medical policy and research. It is also important to ask just how far science can help in efforts to cheat death. We're living longerIt is often said that our ancestors had an easier relationship with death, if only because they saw it so much more often. Just 100 years ago life expectancy was shorter by around 25 years in the West. This literal fact of life resulted because so many children and young adults perished prematurely from a whole variety of causes. A quarter of children died of infection before their fifth birthday; young women frequently succumbed to complications of childbirth; and even a young gardener, scratching his hand on a thorn, might be lost to fatal blood poisoning. On supporting science journalismIf you're enjoying this 1977. I believe that the answer, now called the disposable soma theory, goes a long way toward explaining why different species age as they do. Why we age as we doThe theory is best understood by considering the challenges cells and complex organisms face as they try to survive. Cells are damaged all the time—DNA gets mutated, proteins get damaged, highly reactive molecules called free radicals disrupt membranes, and the list goes on. Life depends on the continual copying and translation of genetic data, and we know that the molecular machinery handling all these things, excellent as it may be, is not perfect. Considering all these challenges, the immortality of the germ line is actually remarkable.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: Normalization was done in DESeq2, while the following parameters were used for coseq: model = ‘Normal,’ transformation = ‘arcsin,’ seed = 1234, iter = 10,000. Specific genes belonging to clusters where D03 and/or Day 32 showed upregulation and were then re-clustered with the same parameter for visualization. A complete representation of all initial clusters found in this study can be found in Figure 2—figure supplement 1. Pairwise analysis of differentially expressed genes between two-time points was done using the Wald test in DESeq2 (design = ~dph, adjusted p-value threshold: 0. 01, log2FoldChange ≥ ±0. 58). Figures were plotted using ggplot2 (V3. 4. 1) (Wickham, 2009), and the analysis made general use of the tidyverse package (V1. 3. 2) (Wickham et al. , 2019). Lastly, expression levels shown in Figures 3—6 are normalized gene counts produced by DESeq2. Materials and correspondence Request a detailed protocol Correspondence and material requests should be addressed to at either roger. huerlimann@oist. jp or roger. huerlimann@gmail. com. Add a comment + Open annotations. The current annotation count on this page is being calculated. 3. The homogenate sample was denatured with acetonitrile and then, equilibrated for 30 min at room temperature on dark After equilibration, the sample was centrifuged at 3000 rpm for 3 min, and then the supernatant was decanted into a new PP tube which was added to distilled water. The sample was applied to an Oasis MCX cartridge which had been successively conditioned in methanol, distilled water, and 1% acetic acid solution. After the cartridge was washed with distilled water followed by methanol, the thyroid hormones were eluted with methanol/distilled water/ammonia solution (70:30:1,v/v/v). After the sample was evaporated to dryness, the residue was dissolved with methanol/distilled water pyridine solution (40:60:1, v/v/v).

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: , 2009): in many animal models, inflammatory responses to bacterial lipopolysaccharide (LPS) are greater during the interval approaching the onset of the active phase and reduced near the beginning of the rest phase (Curtis et al. , 2014). Conversely, innate immune activation affects circadian timekeeping. LPS elicits SCN c-fos expression and shifts the circadian pacemaker (Marpegan et al. , 2005). Convergent evidence suggests that LPS-induced phase shifts are mediated by proinflammatory cytokines (Marpegan et al. , 2005; Paladino et al. , 2010; Leone et al. , 2012). Thus, time-of-day information derived from the circadian pacemaker modulates responsiveness of the immune system, and conversely, immune mediators modulate clock function. Whereas circadian rhythms provide circa-24-h temporal order, ultradian rhythms (URs) impose essential temporal structure on subcircadian timescales (periods <8 h; Veldhuis, 2008; Yates and Yates, 2008). URs affect diverse aspects of physiology and behavior, including sleep (Mueller et al. , 2012), hormones (Knobil, 1999; Choe et al. , 2013; Lloyd et al. , 2008), food intake (Warner et al. , 2010), and body temperature (Heldmaier et al. , 1989), traits that undergo striking changes during the acute response to infection (Hart, 1988). Despite the ubiquity of physiological and behavioral URs, it is unknown whether the temporal structure of URs, like circadian rhythm (CRs), is affected by immune activation. Induced circadian arrhythmia has been widely used to assess circadian regulation of organismal physiology. Insights regarding circadian influences on immune responses have been gleaned from models of circadian arrhythmia induced by clock gene knockouts (Gibbs et al. , 2012), constant illumination (LL; Deprés-Brummer et al. , 1997), and ablation of the SCN (SCNx; Filipski et al. , 2003; Guerrero-Vargas et al. , 2014), but each of these models has limitations. Clock genes are present in all tissues, and resulting immunophenotypes may reflect either arrhythmia or interference with cellular metabolic processes; LL can elevate immunosuppressive glucocorticoids (Welberg et al.

Output: corroborate


Input: Claim: Biotechnology allows people to live forever by continually replacing damaged tissues. [SEP] Text: Living cells operate constantly under threat of disruption, and the germ line is not immune. The reason that the germ line does not die out in a catastrophe of errors has to do, on the one hand, with its highly sophisticated mechanisms for cellular self-maintenance and repair and, on the other hand, with its ability to get rid of its more serious mistakes through continual rounds of competition. Sperm are produced in vast excess; usually only a good one can fertilize the egg. Egg-forming cells are produced in much greater numbers than can ovulate; stringent quality control eliminates the ones that fail to make the grade. And finally, if errors slip past all these checks, natural selection provides the final arbiter of which individuals are the fittest to transmit their germ line to future generations. After the seemingly miraculous feat of growing a complex body from a single cell—the fertilized egg—it should be relatively straightforward merely to keep a body going indefinitely—as American evolutionist has pointed out. Indeed, for some multicelled organisms, an absence of aging appears to be the rule. The freshwater hydra, for example, shows an extraordinary power of survival. Not only does the hydra apparently not age, in the sense that as it gets older it shows no increase in death rate or decline in fertility, it also appears capable of regrowing a whole new body from even a tiny fragment, if by chance it is cut into pieces. The secret of the hydra's eternal youth: quite simply, germ cells permeate its body. If the immortal germ line is everywhere, it actually comes as no surprise that an individual hydra can survive without any foreseeable end, presuming it does not succumb to injury or predators. In most multicelled animals, however, the germ line is found only in the tissue of the gonads, where the sperm and eggs form. This arrangement provides great advantages. During the long history of evolution, it freed other cell types to become specialists—nerve, muscle and liver cells, among others, that are required for the development of any complex organism, whether a Triceratops or a human. This division of labor had far-reaching consequences for how organisms age and how long they can live. As soon as the specialist cells surrendered the role of continuing the species, they also abandoned any need for immortality; they could die after the body had passed on its genetic legacy through the germ line to the next generation.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: The sample was subjected to an LC-MS/MS system for determination of T4, T3, and rT3. The SRM transitions were m/z 777. 8/731. 6 for T4, 651. 9/605. 8 for T3 and 651. 9/507. 7 for rT3. The measurement ranges were 4–4000 pg/tube for T4 and 0. 5–500 pg/tube for both T3 and rT3. The limits of quantification were 4 pg/tube for T4 and 0. 5 pg/tube for both T3 and rT3. 4. F was extracted with 4 mL of methyl tert-butyl ether. After the organic layer was evaporated to dryness, the extract was dissolved in 0. 5 mL of methanol and diluted with 1 mL of distilled water. The sample was applied to an cartridge which had been successively conditioned with 3 mL of methanol and 3 mL of distilled water. After the cartridge was washed with 1 mL of distilled water, 1 mL of methanol/distilled water/acetic acid (45:55:1,v/v/v), and 1 mL of 1% pyridine solution, the F was eluted with 1 mL of methanol/pyridine (100:1,v/v). After evaporation, the residue was reacted with 50 μL of mixed solution (80 mg of 2-methyl-6-nitrobenzoic anhydride, 20 mg of 4-dimethylaminopyridine, 40 mg of picolinic acid and 10 μL of triethylamine in 1 mL of acetonitrile) for 30 min. at room temperature. After the reaction, the sample was dissolved in 0. 5 mL of ethyl acetate/hexane/acetic acid (15:35:1, v/v) and the mixture was applied to a HyperSep SI cartridge which had been successively conditioned with 3 mL of acetone and 3 mL of hexane. The cartridge was washed with 1 mL of hexane, and 2 mL of ethyl acetate/hexane (3:7, v/v). Steroids was eluted with 2. 5 mL of acetone/hexane (7:3, v/v). After evaporation, the residue was dissolved in 0.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: , 2006) and SCN lesions damage adjacent hypothalamic tissue, increase stress hormones (Buijs et al. , 1993; Kalsbeek et al. , 2012), and generate glial scars and neuroinflammation that persist for months after the insult (Logan et al. , 1992; Silver and Miller, 2004). A general theme emerging from these and other studies is that the circadian system inhibits inflammatory responses and may provide a circadian temporal gating of inflammatory responses (Gibbs et al. , 2012); other reports, however, indicate attenuated inflammatory responses in circadian-disrupted animals (Wachulec et al. , 1997; Liu et al. , 2006; Spengler et al. , 2012). Here we used a noninvasive model of circadian arrhythmia: the disruptive phase-shifted (DPS) hamster, which avoids the aforementioned complications, to examine the consequences of circadian disruption on innate inflammatory responses. DPS hamsters are well suited for translational analyses because, as in humans, dysrhythmia is manifested by genetically and neurologically intact individuals that remain exposed to circadian light-dark cycles. In DPS hamsters, CRs in locomotor activity (LMA), Tb, sleep, hormone secretion, and SCN clock gene expression are eliminated by light treatments administered over the course of 2 days (Ruby et al. , 2004; Fernandez et al. , 2014). The present experiment was conducted on female Siberian hamsters; females are understudied in neuroscience research (Beery and Zucker, 2011; Prendergast et al. , 2014), an impediment to establishing brain-behavior relations applicable to both sexes. Materials and MethodsAnimalshamsters (Phodopus sungorus) were derived from a breeding colony maintained in a long-day, 15L:9D photoperiod (LD) at the University of Chicago. Hamsters were housed in polypropylene cages, with food (Teklad; Harlan; Madison, WI) and filtered tap water provided ad libitum; cotton nesting material was available in the cages. Ambient temperature and relative humidity were held constant at 19 ± 2°C and 53% ± 10%, respectively. All procedures conformed with principles and guidelines in the Guide for the Care and Use of and were approved by the Care and of the University of Chicago.

Output: corroborate