Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: The master clock, as it is often called, is reset by light or photic stimuli [3] as well as by arousal-inducing or non-photic stimuli [4]. Whether the input is photic or non-photic, it reaches the clock through neurotransmitters in nerve terminals. Neurotransmitters are released at the inputs for entrainment, in the clock itself for integration and consolidated output, and in efferent projections for the control of overt rhythms. Several reviews on the neurotransmitters of the SCN have been previously published [5 - 10]. The present review concentrates on studies conducted in the last decade and gives particular attention to neurotransmitters whose involvement in the circadian clock have not been traditionally recognized. About neurotransmitters in general Studies have indicated the presence of a large number of neurotransmitters in the SCN [11 - 15]. However, information about their role individually as well as in combination in the functioning of the clock has been slow to come. It is observed that the presence of neurotransmitters in the afferent and efferent projections of the SCN is equally important for the entrainment of the clock and for the control of overt rhythms. Thus, we have neurotransmitters released at the inputs for entrainment, in the clock itself for the integration and consolidated output, and in the efferent projections for the control of overt rhythms. There have been attempts to categorize the putative neurotransmitters of the SCN on the basis of their origin and function [16] and there have been reports indicating subdivisions of the SCN with relation to neurotransmitter function [17]. Further, it has been reported [18] that the human SCN also have well defined subdivisions with chemically defined neuronal groups comparable to the well defined subdivisions reported in the case of experimental animals, mainly rodents. There are many excellent reviews [19 - 22] highlighting various aspects of the neurotransmitters. From a functional point of view, two important aspects emerge. One is the fact that one particular neurotransmitter may have more than one function and thereby make the prediction of the function more difficult and complex. Another aspect is that the neurotransmitter input from various pathways and their influence may vary (1) by itself and (2) by way of modification of SCN function.

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: find support for two ways that cells segregate mitochondria as they multiply, and show that the decrease in the number of mitochondrial DNA molecules during bottlenecking is flexible. This reconciles a debate amongst previous studies. These findings are confirmed using new experimental data from mice, which are genetically distinct from existing studies, illustrating the generality of the model's findings. Furthermore, an analytic mathematical description that describes in detail how bottlenecking might work is produced. Finally, Johnston et al. provide examples using this new theoretical model to suggest therapeutic strategies for diseases caused by mitochondrial DNA mutations. Future work will need to test these suggestions, and link mathematical understanding of mitochondria with healthcare data. are vital energy-producing organelles within eukaryotic cells, possessing genomes (mitochondrial DNA, mtDNA) that replicate, degrade and develop mutations (Rand, 2001; Wallace and Chalkia, 2013). MtDNA mutations have been implicated in numerous pathologies including fatal inherited diseases and ageing (Lightowlers et al. , 1997; Wallace, 1999; Poulton et al. , 2009; Wallace and Chalkia, 2013). Combatting the buildup of mtDNA mutations is of paramount importance in ensuring an organism's survival. Substantial recent medical, experimental, and media attention has focused on methods to remove (Bacman et al. , 2013) or prevent the inheritance of (Bredenoord et al. , 2008; Poulton et al. , 2009; Craven et al. , 2010; Poulton et al. , 2010; Burgstaller et al. , 2015) mutated mtDNA in humans. One means by which organisms may ameliorate the mtDNA damage that builds up through a lifetime is through a developmental process known as bottlenecking. Immediately after fertilisation, a single oocyte (which may contain >105 individual mtDNAs) may have a nonzero mtDNA mutant load or heteroplasmy (the proportion of mutant mtDNA in the cell). As the number of cells in the developing organism increases, the intercellular population then acquires an associated heteroplasmy variance, that is, the variance in mutant load across the population of cells (Figure 1A), allowing removal of cells with high heteroplasmy and retention of cells with low heteroplasmy. Intense and sustained debate exists as to the mechanism by which this increase of heteroplasmy variance occurs.

Output: pass


Input: Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: Derivation of the. A disease activity index for lupus patients. Arthritis & Rheumatism 35(6):630-640 Bots SH, Van der de. 2016. The influence of baseline risk on the relation between HbA1c and risk for new cardiovascular events and mortality in patients with type 2 diabetes and symptomatic cardiovascular disease. 15(1):101. 2012. Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis. Arthritis & Rheumatism 64(8):2687-2697 Burger D, Dayer JM. 2002. High-density lipoprotein-associated apolipoprotein A-I: the missing link between infection and chronic inflammation. 1(1–2):111-117 Crispín JC, Liossis S-NC, Kis--T, Tsokos GC. 2010. Pathogenesis of human systemic lupus erythematosus: recent advances. Trends in 16(2):47-57 MGM, de Sain-van. 1998. Plasma α2 macroglobulin is increased in nephrotic patients as a result of increased synthesis alone. 54(2):530-535 Galicia G, Ceuppens JL. 2011. Haptoglobin function and regulation in autoimmune diseases. In: Francisco Veas, ed. Proteins—Regulation and Functions of Proteins, Prof. London: InTech. . 2006. Human body fluid proteome analysis. Proteomics 6(23):6326-6353. 2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. 4(1):44-57. 2005. Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein. Molecular & 4(9):1265-1272. 2015. Biomarkers identified from serum proteomic analysis for the differential diagnosis of systemic lupus erythematosus. Lupus 24(6):582-587. 2012. Contribution of mass spectrometry-based proteomics to defining cellular mechanisms and diagnostic markers for systemic lupus erythematosus. & Therapy 14:204-214. 2014. Systemic lupus erythematosus.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: Neurotransmitters like acetylcholine, glutamate, neuropeptide Y (NPY), serotonin, vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and arginine vasopressin (AVP) have been implicated in the functioning of the SCN. Glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP) are indicated as principal neurotransmitters of the retinohypothalamic tract (RHT), although excitatory amino acids like L-aspartate and N-acetyl-aspartylglutamate may also function as neurotransmitters in RHT. also might be a candidate as a neurotransmitter in RHT. Functional studies over the years have given evidence that PACAP alone or in concert with glutamate may be responsible for the light signalling to the clock. The role of AVP in circadian time keeping has been well established. Its role in the control of circadian rhythm of food and water intake has been reported and well documented. Another intrinsic neuropeptide, VIP, acting through VPAC2 receptor (a type of receptor for VIP), participates in both resetting to light and maintenance of ongoing rhythmicity of the SCN. NPY and GABA seem to be the neurotransmitters in the projection from the intergeniculate leaflet to the SCN. Raphe nuclei projections to the SCN contain serotonin. AVP and prokineticin 2 are seen in the outputs from the SCN. The neurotransmitter-dependent molecular basis of the working of the clock is yet to be understood completely. The specific roles of the various neurotransmitters may be based on the response of the neurons of the SCN on application of a neurotransmitter, capacity to phase shift a particular rhythm on application of neurotransmitter, effect of lesions on the entrained and free running rhythms, and disruptions seen in the rhythms after blockade by the antagonist/inhibitors. Possible targets for some of the neurotransmitters are the clock genes per1 and per2, which are induced in the SCN by light or by neurotransmitters, at night. Evidence indicating co-localization of some of the neurotransmitters in the SCN has further complicated the investigations into the role of neurotransmitters in the working of the clock.

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: Several experimental results in mice suggest that, during development, the copy number of mtDNA per cell in the germ cell line drops dramatically to ∼102, reducing the effective population size of mitochondrial genomes (Cree et al. , 2008; Wai et al. , 2008). One postulated bottlenecking mechanism is that this low population size accelerates genetic drift and so increases the cell-to-cell heteroplasmy variance (Bergstrom and Pritchard, 1998; Aiken et al. , 2008; Cree et al. , 2008; Wonnapinij et al. , 2010), which was first observed to generally increase from primordial germ cells through primary oocytes to mature oocytes (Jenuth et al. , 1996). However, independent experimental evidence (Wai et al. , 2008) suggests that heteroplasmy variance increases negligibly during this copy number reduction, though this interpretation has been debated (Samuels et al. , 2010). Wai et al. (2008) shows heteroplasmy variance rising during folliculogenesis, after the mtDNA copy number minimum has been passed. In yet another picture, supported by conflicting experimental results (Cao et al. , 2007, 2009), heteroplasmy variance increases with a less pronounced decrease in mtDNA copy number (a minimum copy number >103 in mice), solely through random effects associated with partitioning at cell divisions. Clearly a consensus on this important mechanism is yet to be reached. Figure 1 Download asset Open asset The mitochondrial bottleneck, and elements of a general model for bottlenecking mechanisms. (A) The mitochondrial DNA (mtDNA) bottleneck acts to produce a population of oocytes with varying heteroplasmies from a single initial oocyte with a specific heteroplasmy value. During development, mtDNA copy number per cell decreases (by a debated amount, which we address; see Main text) then recovers, suggesting a ‘bottleneck’ of cellular mtDNA populations. (B) Cellular mtDNA populations during the bottleneck are modelled as containing wildtype and mutant mtDNAs. MtDNAs can replicate and degrade within a cell cycle, with rates λ and ν respectively. (C) At cell divisions, the mtDNA population is partitioned between two daughter cells either deterministically, binomially, or through the binomial partitioning of mtDNA clusters.

Output: pass


Input: Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: Lancet 384(9957):1878-1888. 2010. Urinary monocyte chemoattractant protein-1 correlates with disease activity in lupus nephritis. 25(11):2283-2288. 2015. Role of hemoglobin/heme scavenger protein hemopexin in atherosclerosis and inflammatory diseases. in Lipidology 26(5):384-387. 1999. Systemic lupus erythematosus, a disease associated with low levels of clusterin/apoJ, an anti-inflammatory protein. Journal of Rheumatology 26:597-603 Pavón EJ, Muñoz án -Rubio J-L, Sola R, Navarro-Pelayo F, Raya-Alvarez E, Ortego-. 2006. Proteomic analysis of plasma from patients with systemic lupus erythematosus: Increased presence of haptoglobin α2 polypeptide chains over the α1 isoforms. Proteomics 6(S1):S282-S292 Pisetsky DS. 1997. Systemic lupus erythematosus. A. Epidemiology, pathology and pathogenesis. In: Klippel JH, ed. Primer on the (11th edition). Georgia: Arthritis Foundation. 246-251. 2012. A comparative proteomic study of sera in paediatric systemic lupus erythematosus patients and in healthy controls usin and LC MS Apolot study. 10:24. 2006. Exploring human plasma proteome strategies: High efficiency in-solution digestion protocol for multi-dimensional protein identification technology. Journal of 1111(2):175-191. 2007. Lipocalin-2, TWEAK, and other cytokines as urinary biomarkers for lupus nephritis. Annals of the Academy of Sciences 1109(1):265-274 Simon JD. 2013. Inflammation and acute phase proteins in hemostasis. In: Janciauskiene S, ed. Proteins. London: InTech.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: It is likely that the functioning of the clock may depend on the presence of a particular neurotransmitter on a mechanism in which co-localized neurotransmitters interact in a functionally significant manner. With more information available on the role of neurotransmitters in the working of the clock, which is involved in so many functions of the body, better opportunity for neurotransmitter-based manipulation of the clock has also been reported. Problems of shift-work insomnia and ill effects of jet lag are among the clock-related functions for which much attention has been given in recent years. Melatonin has been in use with some success in reducing the above effects. However, search for other chronobiotic agents is continuing and it is likely that there may be some new dimensions given to the problem and its solution in future. A report of a close relationship between circadian clock and cell proliferation makes things even more interesting. Investigations into the role of neurotransmitters in the SCN as well as in the afferent and efferent inputs have come a long way with the advent of newer techniques of positron emission transaxial tomography (PET) scan and polymerase chain reaction (PCR). In both plants and animals, circannual rhythms are widely distributed. Endogenous circannual rhythms form the basis for many seasonal rhythms. A number of neuroendocrine mechanisms have been implicated in the regulation of seasonal changes in the physiology and behaviour of animals. Some of these neuroendocrine pathways are necessary for the regulation of particular overt seasonal responses, though they may not be directly linked to the circadian time-keeping system. Photoperiodic input and circannual function may have profound influence on many of the functions of body. Naturally, neurotransmitters are involved not only in circadian function but also in seasonal processes. It has been postulated that heterogeneity of the clocks which are seen within the SCN may be one of the factors that form the basis of seasonal adaptations [23]. A typical example of the close linkage between seasonal rhythms and affective disorders can be seen in a seasonal form of mood disorder, seasonal affective disorder (SAD). Treatment for SAD based on circadian principles includes not only light therapy but also the use of certain drugs, again based on circadian principles involving neurotransmitters. The SCN has been subdivided into a dorsomedial shell and a ventrolateral core.

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: In our case, this goodness-of-fit is computed using a comparison of squared residuals associated with the trajectories of mean mtDNA copy number and normalised heteroplasmy variance (see ‘Materials and methods’ and 0. 006; optimal fits to data generally show 0. 005 < α < 0. 01), and the proportions of loci visible in Wai et al. (2008) are substantially higher than this required 1% value. We show in 40. * denotes measurements in mature oocytes, modelled as 100 dpc (see ‘Materials and methods’). Note: the range in (B) does not correspond to a credibility interval on individual measurements, but rather on an expected underlying (population) variance, from which individual variance measurements are sampled. We thus expect to see, for example, several measurements lower than this range due to sampling limitations (see text). (C) Posterior distributions on mtDNA turnover ν with time. (D) Posterior distribution on min E(m), the minimum mtDNA copy number reached during development. (E) Posterior distribution on σ=∑i=36τ′iνi, a measure of the total amount of mtDNA turnover. Figure 3D shows posterior distributions on the copy number minimum and total turnover (see ‘Materials and methods’) resulting from this process; posteriors on all other parameters are shown in 1. Substantial flexibility exists in the magnitude of the copy number minimum, illustrating that observed heteroplasmy variance can result from a range of bottleneck sizes from ∼200 to >103; going some way towards reconciling the conflict between Cao et al. (2007) and Cao et al. (2009) and Cree et al. (2008) and Wai et al. (2008). The total amount of mtDNA turnover (presented as σ=∑i=36νiτ′i, the product of turnover rate and the time for which this rate applies, summed over quiescent dynamic phases; for example, a turnover rate of 0. 1 hr−1 for 30 days yields σ = 0. 1 × 24 × 30 = 72) is constrained more than the specific trajectory of mtDNA turnover rates, showing that a variety of time behaviours of turnover are capable of producing the observed heteroplasmy behaviour.

Output: pass


Input: Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: Javascript is disabled in your browser. Please enable Javascript to view PeerJ. Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses All reviews of published 2023. Peer reviewers are encouraged (but not required) to provide their names to the authors when submitting their peer review. If they agree to provide their name, then their personal profile page will reflect a public acknowledgment that they performed a review (even if the 2020. The first revision was submitted on March 17th, 2020 and was reviewed by 2 reviewers and the Academic Editor. A further revision was submitted on May 14th, 2020 and was reviewed by the Academic Editor. The 2020. Version 0. 3 (accepted) · Jul 28, 2020 · would like to start this letter with an apology for the delay in my decision. I'm sure you understand that everybody's lives have been disrupted by the pandemic, which has both taken us away from our offices and changed the timing and length of our (remote) meetings. I really wanted to read the manuscript very carefully and assess whether you had revised the manuscript in line with the reviewer's comments. After a careful reading I have reached the conclusion that you have done so; therefore, I feel this version is now acceptable. Please accept my apologies. I hope that things are going well for you during these trying times. [# PeerJ - this decision was reviewed and approved by Paula Soares, a PeerJ covering this Section #] 0. 3 (PDF) Download author's response letter - submitted May 14, 2020 Version 0. 2 Walter de Azevedo Jr. · Apr 8, 2020 · Two reviewers evaluated the revised version of this manuscript. Both reviewers asked for additional corrections. In my view, this manuscript needs a minor revision. [# PeerJ Staff Note: The review process has identified that the English language must be improved. PeerJ can provide language editing services - please contact us at editorial. support@peerj. com for pricing (be sure to provide your manuscript number and title) #] Reviewer 1 · Mar 24, 2020 Basic reporting See attachment Experimental design See attachment Validity of the findings See attachment Additional comments See attachment Annotated reviews are not available for download in order to protect the identity of reviewers who chose to remain anonymous.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: This is based on retinal innervation patterns as well as the observation that these regions are defined by phenotypically distinct cell types [24]. Each nucleus contains about 10,000 neurons, thereby making 20,000 neurons in total. These neurons are characterized by small size and high density [25]. Isolated individual neurons are reported to produce circadian oscillations with periods ranging from 20–28 h [26,27]. Circadian oscillations are generated in the individual neurons of the SCN by a molecular regulatory network. Though individual cells oscillate with periods ranging from 20–28 h, at the tissue level SCN neurons display synchrony indicative of a robust inter-cellular coupling, and neurotransmitters appear to have an important role in the inter-cellular coupling. Gondze and co-workers [28] have introduced a molecular model for the regulatory network underlying the circadian oscillators in the SCN and stated that effective synchronization is achieved when the average neurotransmitter concentration damps the individual oscillators. Cells are effectively synchronized due to global neurotransmitter oscillation. Neither spiking in the neurons of the SCN nor chemically mediated transmission is needed for the pacemaking activity seen in individual cells. However, synchronization of circadian rhythmicity across neurons in the SCN does require neurotransmitters [25,29] and development of action potentials [30]. Before attempting a discussion of the neurotransmitters, it is necessary to identify the afferent projections to the SCN, and neurotransmitters present in it, neurotransmitters intrinsic to the SCN, and efferent projection with its neurotransmitters. The SCN is composed of different neuronal elements, each having its own specific function. Intensive interconnection and interaction among the heterogeneous neuronal elements is responsible for the functional output of the SCN. Different neurons of the SCN contain different neuropeptides, with several neurons having co-localization of neurotransmitters. Thus, we have, for example, gamma amino butyric acid (GABA) and glutamate, GABA and and corticotrophin releasing hormone (CRH), AVP and its carrier protein neurophysin, VIP and peptide histidine isoleucine (PHI), and VIP and somatostatin (SS). Co-localization of different neuropeptides is seen not only in rat SCN but also in human SCN [31 - 33].

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: Following this recursion for n phases of bottlenecking and simplifying the resultant multi-layer fraction gives rise to the solution (54) goverall=h0=A′z+B′C′z+D′, where (55) [A′B′C′D′]=∏i=1n[AiBiCiDi], from which Goverall=goverallm0 follows straightforwardly. The following results will be of assistance: (56) E(m)=ddz(A′z+B′C′z+D′)m0|z=1=m0(A′D′−B′C′)(A′+B′C′+D′)m0−1(C′+D′)2, (57) d2dz2(A′z+B′C′z+D′)m0|z=1=m0(B′C′−A′D′)(A′+B′C′+D′)m0(B′C′(m0+1)+A′(2C′+D′(1−m0)))(A′+B′)2(C′+D′)2, (58) =−(A′+B′C′+D′)(A′+B′)2(B′C′(m0+1)+A′(2C′+D′(1−m0)))E(m).

Output: pass


Input: Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: Cite this review as (2020) #1 of "Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses (v0. 2)". PeerJ Reviewer 2 · Apr 1, 2020 Basic reporting Please see my first report Experimental design Please see my first report Validity of the findings Please see my first report Additional comments The authors have made an effort to introduce the changes and modifications suggested in the previous version. As a consequence, I understand that the overall quality of the manuscript has improved substantially and that now it can be considered acceptable for publication. I would just like to suggest a few minor changes to the text that are detailed below. Line 33: What is exactly the meaning of the expression “an absolute log10 fold change (i. e. , >1. 2 difference)”? It seems confusing to me. Could it be expressed more clearly? Line 48: instead of “The downregulated” Line 83: What does it mean R 2007? Line 127: The expression “All the remaining samples were used” is unclear Line 128: Use "After labeling with iTRAQ" instead of "After labeling". In addition it should be specified the iTRAQ version (4plex? 8plex? ) across the manuscript. Line 134-135: methyl cyanide is correct but very few people use it. It is much popular to use acetonitrile. Line 155: please specify the reference of the kit used Line 156: use "manufacturer instructions" instead of "kit instructions" Line 197: It is more appropriate to use "interact" instead of writing "coordinate with one another" Line 231: the expression "we used ELISA to identify again" is grammatically wrong, but it is also meaningless. Please correct. Line 255: Use "previous evidence" instead of "much evidence" Line 278: Factor VII instead of factor VI? Line 284:" consumes" is inappropriate in this context, please use a more adequate expression.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: The combination of a variety of peptides with or without amino acid neurotransmitters within a single nucleus gives the SCN a variety of signalling properties as well. A set of SCN neurons and their neurotransmitters has the function of conveying the daily light-dark signal to hypothalamic target structures [34 - 36]. Three major incoming pathways have been identified for the SCN. These have been defined as the retinohypothalamic tract (RHT), geniculohypothalamic tract (GHT), and the projection from the raphe nuclei (Figure 1). Photic information is relayed directly from the retina to the SCN by way of the monosynaptic retinohypothalamic tract [37,38]. It is seen that transection of all visual pathways leaving the optic chiasm makes animals blind with no visual reflexes but with perfect normal entrainment of circadian rhythms. This has indicated that RHT is sufficient for entrainment. Also it has been demonstrated that sectioning of RHT abolishes entrainment without affecting visual functions [39]. Although the exact mechanism by which a monophasic stimulus, light, produces either no response or a biphasic response in SCN neurons is unclear at present, Myers and co-workers [40] provided a potential molecular explanation for the phenomenon. Using electron microscopy and immunohistochemistry, they identified the excitatory amino acid glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP) as the main neurotransmitters of the RHT [41 - 43]. Although substance P (SP) was thought of as a neurotransmitter of the RHT, there is now substantial evidence against this possibility [44 - 46]. Figure 1 Afferent inputs and efferent pathways of the SCN. RHT: Retinohypothalamic tract, GHT: Geniculohypothalamic tract, OC: Optic chiasm, 3V: Third ventricle, IGL: Intergeniculate leaflet, DM: : : : Gamma amino butyric acid, PACAP: Pituitary adenylate cyclase-activating polypeptide. Retinohypothalamic tract (RHT) and its neurotransmitters The principal neurotransmitters involved in conveying photic information to the SCN have been identified as glutamate and PACAP.

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: The findings will add another piece to the puzzle of how the brain and nervous has evolved to control the behaviour of these remarkably sophisticated animals. Russell WyethAssociate ProfessorSt. UniversityWillem has conceived an exciting project on the edges of what we know about octopus sensory experience - despite the interest in how octopuses perceive the world, little work has ever been done on how their behavior is tied to the chemical sensory ability. Willem is getting excellent behavioral data and needs the ability to visualize the plumes in the water that the octopuses is tracking. Funds for the laser will allow him to fill in that side of the experimental design, and complete a fascinating study. David ScheelProfessor of think the information discovered from this project will add a very interesting 2017. His primary advisor is Dr. at University who has been studying octopus ecology for more than two decades. For his Willem is investigating octopus odor tracking at the Laboratories. Venkatesh GopalDr. Gopal has extensive experience—including postdoctoral research at of Technology (MIT) and Northwestern University—in classical and quantum optics, quantum information processing, and neuroscience. His current research interests lie in understanding how biological systems process sensory information, with an emphasis on how possibly “optimal” movement strategies emerge to gather information efficiently. Lab Notes6 PostedIn case anyone needed some cool octopus photosApril 17, 202144326Hey everyone! I hope you all are having a fantastic. . . December 30, 202044319New favorite clip! An octopus appears to be tricked by. . . December 18, 202087320The octopus Slaanesh foraging in the dark finds a piece of shrimp from one of three possible locations on the first try. In the flume tank water moves from right to left, the space is in a black out tent and illuminated by near-infrared lamps invisible to the eye but not cameras. Example of what can be tracked by a custom trained markerless pose estimator DeepLabCut model. In the top left you can see the convex hull of the points predicted by the model. Top middle is the convex hull rotated into the reference frame of the octopus. Top right shows a plot of the center of mass velocity on top and the area of the convex hull of the four quadrats around the octopus, forward left, forward right, back left, back right.

Output: contrast


Input: Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: Line 291: Use "support" instead of "add to" Line 339: please use "previous studies have shown that" instead of "a study shows that" Line 340: please use "which is involved" instead of "which involved" line 342: please use "were similar" instead of "was similar" Cite this review as (2020) #2 of "Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses (v0. 2)". PeerJ 0. 2 (PDF) Download author's response letter - submitted Mar 17, 2020 Version 0. 1 (original submission) Walter de Azevedo Jr. · Jan 13, 2020 · Three specialists in the field evaluated your manuscripts. Two of them recommend major revisions. I agree with them - please respond to all the comments. [# PeerJ Staff Note: Please ensure that all review comments are addressed in an appropriate rebuttal letter, and please ensure that any edits or clarifications mentioned in the rebuttal letter are also inserted into the revised manuscript (where appropriate). Direction on how to prepare a rebuttal letter can be found at: #] Reviewer 1 · Dec 10, 2019 Basic reporting No comment. Experimental design The use of small sample (4 per sub-group) size should be justified. Validity of the findings 1. Were the top three differentially expressed proteins equal in all the samples of the sub-groups? 2. LRP1, APOC1, and APOL3 were linked to which gestational sub-group? 3. Whether the differentially expressed proteins are placenta-specific needs be clarified. If not, how do you justify them as a biomarker? 4. Power analysis should be carried out to determine the acceptability of the findings. Cite this review as (2020) #1 of "Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses (v0. 1)". PeerJ Reviewer 2 · Dec 16, 2019 Basic reporting In this manuscript, the authors analyze a set of serum samples obtained either from control individuals or patients diagnosed with early and late preeclampsia.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: Light stimulation of the retina results in direct secretion of glutamate from the RHT into the ventral VIP-containing part of the SCN [47 - 49]. Glutamate as a transmitter at RHT/SCN synaptic connections plays an important and critical role in mediating photic regulation of circadian rhythmicity. RHT terminals innervating the SCN show glutamate immunoreactivity associated with synaptic vesicles [41,50], which confirms the role of glutamate as a neurotransmitter. Different types of glutamate receptors were identified and localized in the SCN using in situ hybridization and immunocytochemistry [51]. PACAP, which is co-localized in a subpopulation of glutamate-containing retinal ganglion cells and also involved in relaying light information, may potentiate the action of glutamate on the SCN [52,53]. Both glutamate and PACAP fulfil the criteria of being located in the RHT, being released on stimulation, affecting the cells of the SCN in a manner similar to light, and having their effects blocked by specific antagonists [20]. Exogenous application of glutamate receptor (GluR) agonists is found to excite SCN neurons [54,55] and cause phase shifts. On the other hand, GluR antagonists block light-induced phase shifts and Fos-induction in the SCN in vivo [56,57]. Nitric oxide (NO) NO appears to be a crucial neuroactive substance for the function of the SCN. Presence of neurons showing nitric oxide synthase (nNOS) immunoreactivity in the SCN of dwarf hamster and rat [58,59] were further confirmed by the studies of Chen and co-workers [60] and Caillol and co-workers [61]. Nitric oxide production in the SCN has been linked to N-methyl D-aspartate (NMDA)-induced cyclic guanosine monophospahate (cGMP) production, and administration of cGMP produces phase shifts of circadian rhythms in vitro [62]. It has also been reported that NOS inhibitors prevent NMDA-induced phase shifts of circadian rhythms in vitro and in vivo [48]. There is also a possibility for an additional source of NO in the SCN from the astrocytes, as a group of cells positive for endothelial NOS (eNOS) was found in rat and hamster [61].

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: -19 PreprintsProtocolsVideosJournalsTools & a 10. 21203/rs. 3. rs-1432758/v1This work is licensed under a CC BY 4. 0 LicenseStatus:Under ReviewVersion 1posted 4You are reading this latest preprint versionAbstractSocial recognition is the ability of individuals in a species to differentiate among conspecifics based on their identity or biologically meaningful demographic. Despite evidence that they have sophisticated brains, complex behavioural repertoires, and acute sensory processing, surprisingly little is known about mechanisms aiding social recognition in cephalopods. This class’s unique chemotactile sense by the ventral arm surfaces gathers considerable information used in predator-prey interactions. Does it also help mediate social interactions? This study utilised 366 hours of focal animal observations to assess the likelihood of Hapalochlaena maculosa, a nocturnal species, to retreat after physically contacting conspecifics based on their sex, familiarity and mating history. Females retreated from both sexes equally, while males were more likely to retreat after contacting female conspecifics. Most conspicuously, males were significantly more likely to retreat after contacting females with which they had already mated. These findings provide the first evidence for chemotactile sex discrimination and mate recognition within cephalopods, and supplement previous observations that male H. maculosa do not appear to detect the sex of conspecifics from a distance. The decision to retreat from or stay with an individual based on their sex or mating history, only after physical contact, emphasises the importance of chemotactile behaviour in octopus sensory ecology and behaviour. Furthermore, male octopuses have limited spermatophore production, and the use of chemotactile social recognition observed here may highlight the importance of reproduction, specifically sperm allocation and avoidance of sexual cannibalism, on the evolution of sensory ecology and cognition within this lineage. 1Figure 2Figure 3Figure 4IntroductionSocial recognition is a generic term used to describe the capacity of individuals to use sensorial or contextual cues to distinguish among conspecifics or in some cases their socially relevant category (e. g. dominance, kinship, neighbour, sex etc. ) (Colgan 1983).

Output: contrast


Input: Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: Differential quantitative proteomics experiments have been carried out using iTRAQ 8-plex isobaric labeling as an experimental approach, followed by LC-MS analysis of the samples. The main objective of this work is to describe proteins differentially expressed between the control and problem (preeclampsia) samples in order to find new clues related to this pathology. This is an objective of great biomedical interest, since preeclampsia has a great impact on the human population, causing high economic and human costs, and for which clear and unambiguous biomarkers useful for diagnosis and prognosis have not yet been found. Both the introduction and, above all, the discussion of the results adequately pose the problem and the experimental context. In addition, the manuscript is well written and easy to understand. For everything mentioned above, it is a manuscript of potential interest for publication. However, significant improvements must be done, particularly in the data presentation format, as described below. Experimental design The experimental design proposed by the authors is not novel, but it is adequate to try to obtain the answers sought, although it could be objected that the number of samples used and representative of each condition is somewhat low. Likewise, it would be advisable to include some experiments to validate at least some of the so-called differentially expressed proteins identified here, either using MRM directed proteomic techniques or other approaches based on the use of antibodies, such as analysis. The validation should ideally be performed on a cohort of samples not related to that used in the first phase. Validity of the findings : The presentation of the experimental data requires further improvement. For example, in the results file corresponding to LOPE, 8 data columns (supposedly corresponding to 4 control samples + 4 LOPE samples) are displayed. However, in the EOPE file, 16 data columns are shown, and apparently it includes all (8) the control samples and both 4 LOPE samples + 4 EOPE samples. Please modify this as it only serves to create confusion. In addition, the authors should indicate in the table which samples correspond either to the control or preeclampsia groups. Lines 135-140: Data processing and protein identification and quantification analysis methodology is confusing and contains some spelling mistakes, for example, writing Unipro instead of UniProt.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: In terms of the functional impact of NO in the working of the SCN, blocking of NO production disrupts light transmission to the SCN [63], thus indicating the possibility of the role of NO in the light-input pathway. NO synthesis is required for phase changes of electrical activity [64]. Intracerebroventricular application of L-NAME (a drug that blocks NOS in hamsters) produces attenuation of light-induced phase-advances of activity rhythms [65]. Reports also indicate interruption in the light-triggered cascade of glutamate release from retinal terminals in the SCN by blockade of NO action in intact animals, which leads to subsequent interruption of NMDA receptor activation [66,67]. Interruption of intracellular increase of calcium, activation of nNOS, augmented production of cyclic guanosine monophosphate (cGMP), activation of protein kinase C, and phosphorylation of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), as well as interruption of the expression of immediate early genes, are other effects of blockade of NO action. Starkey and co-workers [68] provided evidence for the presence of functional type II NOS within the SCN of guinea pig. All isotypes of NO synthase have also been identified in the normal adult mammalian SCN. Contribution by more than one NOS isotype to the regulation of circadian rhythms cannot be ruled out. In this context, it is interesting to note the demonstration by Kriegfeld and co-workers [69] that mice lacking the gene for type I NOS experience no change in the ability to phase-shift or entrain circadian rhythm of locomotor activity. Yet another study, also by Kreigfeld and co-workers [70], has suggested that endothelial isoform of NOS among the three known isoforms may not be necessary for photic entrainment in mice. However, considering the three different forms of NOS identified, until the isoforms of NOS involved in regulating the clock phase by modulating inputs are completely established it is difficult to speculate the exact role of NO. There has been much speculation as to the photopigment mediating light information to the SCN. However, this is not yet known with certainty [71].

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: The overall complexity of social recognition and the underlying mechanisms driving it vary greatly among the animal kingdom and are hypothesised to correlate directly to the life history and sociality of the species (Medvin et al. 1993; Ward et al. 2009). Social recognition is a necessary prerequisite for cooperative behaviours (Wilson 2000), and is thought to have evolved in various forms to facilitate social behaviours including anti-predator defence (Townsend et al. 2011), collaborative hunting (Gazda et al. 2005), resource competition (Jaeger 1981), mate choice (Cheetham et al. 2008), parental care (Medvin et al. 1993) and reciprocal altruism (Seyfarth and Cheney 1984), as well as many others. Social recognition has been studied quite extensively within vertebrate groups (Colgan 1983; Mateo 2004), perhaps because their sensory ecology and mechanisms of social recognition are most relatable to our own as humans (Patullo and Macmillan 2015). However, where studied a diverse range of social recognition has also been reported within invertebrate taxa, leading to valuable insights to the link between social structure and cognitive evolution across distinct phylogenetic lineages (Aquiloni and Tricarico 2015). One invertebrate group for which surprisingly little is still known about the dynamics of social recognition, despite substantial evidence for their relatively sophisticated brains and intricate social behaviours (Amodio et al. 2018; Shigeno et al. 2018), are the cephalopods (Mollusca: Cephalopoda) (Boal 2006). Within this class, the octopuses (Cephalopoda: Octopodidae) are often regarded as one of the most ‘asocial’ (Edsinger and Dölen 2018), and in some cases ‘antisocial’ (O’Brien et al. 2021), of the cephalopod clades, with the vast majority of their intraspecific interactions revolving around the necessary life stage of reproduction (Boal 2006; Huffard et al. 2008; Huffard et al. 2010; Hanlon and Messenger 2018; Morse and Huffard 2019). As such, it might be hypothesised that social recognition in octopuses could be highly specialised from evolutionary pressures of sexual selection to help in facilitating reproductive behaviours such as mate choice and sperm competition.

Output: contrast


Input: Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: It should be explained why using ProteinPilot to analyze the results instead of using other alternatives recommended by Thermo (please note that data were obtained in a mass spectrometer) such as ProteomeDiscoverer. Other common alternatives, and by far more used by the proteomics community, include freely available software like MaxQuant. In addition, there is no coincidence when the proteins found in the result files and the protein numbers mentioned in the text are compared. Thus, 65 and 132 proteins, respectively, are shown in LOPE and EOPE files, values that do not match the total number of proteins identified in both data sets (413 for EOPE, 470 for LOPE) or the proteins described as differentially regulated (70 and 24 for EOPE and LOPE, respectively). I do not understand why quantification values corresponding to all the proteins, either differentially expressed or not, identified in both data groups (EOPE and LOPE) are not shown. I suggest that the authors present the data so that we can: 1) Have the quantification values of all the proteins identified in each data set. 2) highlight the values corresponding to differentially regulated proteins in each data set independently. Regarding the quantification values presented in the table, it is well known that the number of decimal numbers should reflect the accuracy of the technique used. It is not a proper practice to present the data with such a high number of decimal numbers, since differential quantitative proteomic analysis using iTRAQ 8plex is far from reaching such high accuracy. I suggest the authors to use 2 or 3 decimal numbers in the tables, because it will help to better understand the data. : Line 118: dithiothreitol final concentration Line 118: iodoacetamide final concentration Line 120: UA? Please detail Iine 125: 75 micrograms of sample are obtained but the protocol starts with 60 micrograms (line 117): please clarify this point Discussion: I was surprised that the authors did not include in the discussion any mention to the protein “c75401, highly similar to Homo sapiens endoglin”, described as differentially expressed protein in the EOPE dataset, since this protein has been previously described as a putative preeclampsia marker ('. Soluble endoglin contributes to the pathogenesis of preeclampsia Nat. Med. 2006 Jun; 12 (6): 642-9. ).

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: Their studies have shown phase delay on SCN neuron firing during early subjective night and phase advance during late subjective night with no response on application during subjective day. Phase shifts were blocked by a BB2 receptor antagonist, thereby confirming the role of GRP in the participation of photic entrainment. GRP found within calbindin-containing retinorecipient cells and also causing photic-like phase shifts on application directly to the SCN may be a possible neurotransmitter for intra-SCN communication [105]. Acetylcholine (ACh) Acetylcholine (ACh) has the distinction of being identified as the first neurotransmitter for the regulation of circadian rhythms. There is evidence in favour and against acetylcholine as a neurotransmitter in the literature. It was suggested that acetylcholine plays a role in the light-input pathway on the basis of some of the studies [16,106]. Electrophysiological studies indicating excitation of some neurons of the SCN by cholinergic agents [107,108] have supported the role of acetylcholine. Use of the acetylcholine receptor agonist carbachol, a non-specific agonist, to mimic the effects of light [109] also added to the supporting evidence for the role of acetylcholine in the SCN. The effect is mediated by muscarinic receptors of the M1 subtype [110]. Intraventricular administration of carbachol, which caused phase shifts in vivo, could be blocked by GluR antagonists [111]. However, acetylcholine does not appear to be directly involved as a neurotransmitter in the light-input pathway. It may act to modulate the photic information reaching the SCN. Geniculohypothalamic tract The geniculohypothalamic tract (GHT) is a second afferent photic projection from the intergeniculate leaflet (IGL) to the SCN. The IGL receives input directly from the retina via a separate branch of the RHT. The projection from IGL via GHT terminates in the areas of the SCN that overlap the direct RHT-SCN input. GHT provides a secondary, indirect photic input as well as an alternate input which has an important role in entrainment mediated by non-photic stimuli such as motor activity.

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: To date there is conflicting and enigmatic evidence for and against various forms of social recognition among octopuses. The common octopus (Octopus vulgaris) has been observed to recognise familiar conspecifics in the laboratory based on visual cues (Tricarico et al. 2011), and the California two-spot octopus (O. bimaculoides) appears capable of discriminating the sex of conspecifics from a distance based on olfactory signals in the water (Walderon et al. 2011). Distance sex discrimination has also been observed in wild Abdopus aculeatus, and is presumably mediated by sex-specific chromatophore patterning (Huffard et al. 2010). Additionally, the males of two species of octopus, an unidentified pygmy octopus and the southern blue-ringed octopus (Hapalochlaena maculosa), have been observed to adjust their copulation time with females depending on whether or not they were the last male to have mated with them (Cigliano 1995; Morse et al. 2015), suggesting that some octopuses might be capable of mate recognition. However, the prevalence of male-male copulation attempts in the laboratory (Hapalochlaena spp. : Cheng and Caldwell 2000; Morse et al. 2015) suggests some octopuses cannot recognise the sex of their conspecifics accurately, and an interspecific male-male copulation attempt observed in the deep sea demonstrates the inability of some male octopuses to ascertain even their own species (Lutz and Voight 1994). Furthermore, recent studies of H. maculosa indicate that females of this species are likely to discriminate the sex, and possibly identity, of conspecifics via distance chemoreception using olfactory cues in the seawater, but the males do not appear able to do this (Morse et al. 2017). In laboratory focal animal observations with the same species, both males and females approached either sex indiscriminately, leading to either mating attempts, grappling or retreat behaviours (Morse et al. 2015). It seems plausible that there could be a missing piece of the puzzle in our understanding of octopus social recognition and its link to their unique sensory ecology.

Output: contrast


Input: Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: Particularly interesting would be to discuss the presence of this protein in the EOPE but not in the LOPE dataset. Additional comments no comment Cite this review as (2020) #2 of "Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses (v0. 1)". PeerJ Islam · Jan 12, 2020 Basic reporting The manuscript entitled “Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses” by Tu and his co-authors reported the differently expressed serum proteins in early- and late-onset preeclampsia. The manuscript reported some new findings that are associated with preeclampsia. language used is a professional standard. Literature and 0. 1)". PeerJ Submission (PDF) - submitted Nov 26, 2019 All text and materials provided via this peer-review history page are made available under a Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: Serotonin (5HT) A dense, robust serotonergic projection from midbrain raphe nuclei terminating predominantly in the retinorecipient region of the SCN has been reported [127]. A reciprocal projection from the SCN to raphe nuclei is also seen [128]. Both in vitro and in vivo, 5HT receptor agonists are found to cause phase shifts of the SCN when administered at times in the circadian cycle during which light does not cause phase shifts [129,130]. Raphe nuclei lesions reduce the amplitudes or "clarity " of rat's circadian activity rhythm [131] with detectable persistent rhythmicity. Serotonergic projection to the SCN terminate to a great extent on vasoactive intestinal peptide(VIP)-containing neurons in the ventrolateral part of the SCN. There is a close relation between retinal afferents and VIP-containing neurons of the SCN in this area [132]. The major function of the serotonergic projection most probably is the modulation of the pacemaker responses to light. Raphe nuclei receive retinal afferents [133] and hence the raphe-retina projection may be viewed as another indirect photic input to the biological clock. In in vitro studies, serotonin advances the phase of the circadian pacemaker during the day and delays it at night, an action similar to that of GABA [134]. Serotonin is also found to regulate SCN neurons by both pre- and post synaptic inhibitory mechanisms [135]. 5HT and 5HT agonists are also found to inhibit optic nerve-induced field potentials in the SCN brain slice preparation, and light-induced Fos expression and phase shifts of the circadian rhythm of wheel-running activity [136]. It is also reported that 5HT antagonists enhance light-induced increases in the firing rates of SCN neurons [137] and light induced phase shifts [138]. Many of the above studies point towards the hypothesis that the serotonergic innervation of the SCN serves to modulate light-induced glutaminergic input. Considering these facts, there exists a possibility of the involvement of 5HT in tonic inhibition of the light-input pathway to the SCN. There is a suggestion that this serotonergic projection from raphe to the SCN may be the anatomical substrate for affective disorders to alter human circadian system/rhythms.

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: A distinct aspect of cephalopod morphology is that they possess specialised chemosensory and mechanosensory cells on the suckers lining the undersides of each of their arms that separately convey information to the brain about both chemical profiles and texture (Budelmann 1996; van Giesen et al. 2020). Octopuses possess many more of these chemosensory receptors (~ 10,000 cells per sucker in O. vulgaris: Graziadei 1964a) compared to their decapod (Cephalopoda: Decapodiformes) sister taxa (~ 100 cells per sucker in cuttlefish: Graziadei 1964b), and this has been thought to relate to the way in which octopuses reach their arms into holes and crevices while foraging for food (Budelmann 1996). It is also pertinent to note that a tactile phase leading up to copulation has been observed in several octopus species (Wells and Wells 1972; Voight 1991; Morse 2008; Morse et al. 2018a), and the olfactory lobes of octopuses, which are responsible for processing chemical stimuli, are integrated with the parts of the brain that regulate signal molecules involved in both feeding and reproductive behaviours (Polese et al. 2015). It therefore appears straightforward that chemotactile (mechanical and/or chemical) information is a very important tool used by octopuses to interact with their environment (van Giesen et al. 2020) and possibly each other. However, to the best of the authors’ knowledge, the role of chemotactile cues in octopus social behaviour or any cephalopod mating system has never been investigated. The present study aims to provide new context for the interpretation of octopus interactions by evaluating evidence for and against chemotactile-based social recognition in the relatively well-studied H. maculosa. Specifically, this study aims to determine whether H. maculosa of different sex and size are more or less likely to retreat after contacting conspecifics depending on the following three socially-relevant criteria: i) conspecific sex; ii) conspecific novelty; and iii) shared mating history. Evidence for chemotactile recognition at these levels may reveal previously unexplored links among sensory ecology, sexual selection and cognition in cephalopods.

Output: contrast


Input: Claim: Gene expression analysis helps understand cellular responses to stimuli. [SEP] Text: are medically important intracellular parasites that are accountable to cause fatal infections ranging from small cutaneous lesions to more severe and life threatening visceral infections in humans (Holzmuller et al. 2002). Leishmaniasis is a neglected tropical disease that remains to impose a serious public health problems in many countries around the world because of absence of vaccines and limited availability of chemotherapeutic agents in use as of today (Rastrojo et al. 2018). The disease is widespread in tropical and subtropical countries and known to have both zoonotic and human to human transmission patterns with two main clinical forms that include cutaneous and visceral Leishmaniasis (Steverding 2017). The main etiologic agent of cutaneous leishmaniasis is Leishmania major. It is commonly associated with lesions in the area where sandfly bite occurs. Whereas, the cause of visceral leishmaniasis is Leishmania donovani which eventually spreads to internal organs culminating in death (Downing et al. 2011). The transmission of Leshmania donovani, a parasite that kills millions of people in east Africa in general and thousands in Ethiopia in particular was thought to be anthroponotic. However, recent genetic studies have claimed that there are possibilities of zoonotic transmission (Kassahun et al. 2015). Leishmania donovani is an obligate intracellular parasite (Mukherjee, Chakraborty, and Chakrabarti 2016; Singh et al. 2016; Verma, Rastogi, and Mukhopadhyay 2017) that is postulated to inhabit phagolysosomes of the macrophages (Singh et al. 2016). Once the macrophage is inhabited the growth of the parasite will be favored with the help of phagosome mutation regulation which will eventually avoid destruction. As the result, antigen presentation, oxidative damage, apoptosis and immune activation will be depleted and the availability of the nutrients will be favored on the contrary (Podinovskaia and Descoteaux 2015). The parasite almost exclusively multiplies in the phagolysosomes of the infected macrophage and this affects the expression of gen in both the parasite itself and the host cell (Buates and Matlashewski 2001).

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: Differential day-night modulation of GABAergic neurotransmission seen in the SCN may provide a time-dependent gating mechanism to counteract propagation of excitatory signals throughout the biological clock during the day and to promote it at night [152]. GABA does not seem to be synthesized in the SCN in a circadian fashion, but in a diurnal pattern as per GAD m RNA basis [153,154]. A circadian rhythm in GABA transmission in the dorsal part of the mouse SCN, with requirement of VIP for the expression of this rhythm, is reported by Itri and co-workers [155]. While considering the action of GABA in the SCN, whether inhibitory or excitatory, extrinsic GABA sources such as from IGL [116] and release of GABA from SCN terminals implicated in transmission of light information should also be looked into to visualize a clearer picture. GABA receptors and receptor subunits are expressed in the SCN [116,139,140]. Although no variation in concentration of GABA in the SCN has been reported, responsiveness of the SCN undergoes daily variation [156]. Neurotransmitters for intra-SCN communication Integrated output as a result of integrated activity within the SCN in spite of heterogeneity in functional and neurochemical organization explains the efficiency of the SCN, the biological clock. Such a process is likely to involve much coordinated activity, and intra-SCN communication must be strong enough to produce such an action. It is clear that photic information received must be relayed from retinorecipient cells to the oscillator cells in the nucleus. Intra-SCN signals underlying such communication are not known with certainty as yet. The importance of circadian synchrony of the SCN neurons in the normal working of the clock has been highlighted in some animal studies recently [157]. In these studies, loss of coherent daily rhythms has been shown to coincide with loss of circadian synchrony among the constituent neurons [157]. Neurotransmitters have been designated as potential SCN synchronizers and one of them, which is unique since it is expressed by most of the SCN neurons, is GABA. This and other transmitters involved in synchronization, such as and prokineticin 2, have been studied quite extensively. However, the potential of the latter two, GRP and prokineticin 2 as synchronizing factors require further investigation [23].

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: Intriguingly, a prior study of this species indicated that females are able to identify the sex and possibly the identity of conspecifics from chemical signatures in the water, however males have not been observed to be able to do this (Morse et al. 2017). The novelty or familiarity of conspecifics did not influence the probability of an individual to retreat after contact in this study. Therefore, shared mating history rather than familiarity itself was more likely to influence a male’s decision whether to retreat from a conspecific female. Together these results suggest octopuses, particularly male H. maculosa, may use chemotactile information gathered by chemosensory cells on the arms to recognise socially-relevant categories of conspecifics. Male H. maculosa were able to assess the prior mating history of females by touch, but without necessarily inserting the hectocotylus. Male mate recognition may occur in cephalopods that adjust copulation time based on prior mating history of females (Cigliano 1995; Wada et al. 2010; Morse et al. 2015). In all of these cases known previously, males had already initiated copulation, presumably allowing the hectocotylus to assess the presence and potentially the identity of existing sperm. By contrast, H. maculosa males in this study appeared able to assess whether they had already mated with a female prior to mounting her – presumably via tactile chemosense, though mechanosense cannot be discounted. It is unknown whether males remember the scent of their former mates, impart their chemical signature onto females’ skin while mounting to mate (i. e. , scent marking), or whether females emit the chemical signature of their stored sperm. While all of these possibilities merit further exploration, scent-marking, despite being widespread among terrestrial animals (Hurst 2005), is not known to occur in marine systems and therefore seems unlikely. It is more probable in this case that males can remember characteristics about the phenotype or possibly the identity of the females with which they have mated, as occurs broadly across social animals (Mateo 2004). The use of chemotactile cues in social recognition may be widespread among male cephalopods. In numerous reported observations of squids, cuttlefishes, and octopuses, including H. maculosa (Morse et al.

Output: contrast


Input: Claim: Gene expression analysis helps understand cellular responses to stimuli. [SEP] Text: It represents motifs as position dependent letter probability matrices that describe the probability of each possible letter at each position in the pattern. Individual MEME motifs do not contain gaps. Patterns with variable-length gaps are split by MEME into two or more separate motifs. This tool also takes as input a group of sequences and outputs as many motifs as requested. MEME uses statistical modeling techniques to automatically choose the best width, number of occurrences and description for each motif (Bailey and Elkan 1994). The identified motifs were exported to another web-based tool, (Tomtom - Submission form n. d. ); which is used to compare one or more query motifs against one or more databases of target motifs (and their reverse complements when applicable), and reports for each query a list of target motifs, ranked by p-value. The E-value and the q-value of each match is also reported. The q-value is the minimal false discovery rate at which the observed similarity would be deemed significant (Gupta et al. 2007). 2. 3 Gene ontology The identified motifs were also fitted to another motif-based sequence analysis tool, for Motif (GOMo); under MEME suite version 5. 3. 0 to scan all promoters using nucleotide motifs provided to determine if any motif is significantly associated with genes linked to one or more (GO) terms. The significant GO terms can suggest the biological roles of the motifs. The program searches in a set of ranked genes for enriched GO terms associated with high-ranking genes. The genes can be ranked, for example, by applying a motif scoring algorithms on their upstream sequence (Buske et al. 2010a). 2. 4 Identification of CpG islands A server based online CpG islands prediction analysis for genome sequence exploration was used to search for CpG islands (Database of CpG Islands n. d. ). Genomic islands play an important role in medical, methylation and biological studies. CpG islands are springs of characteristically unmethylated DNA with a high content of the Cytosine (C) and Guanine (G); i. e. , high GC content compared to the bulk DNA. If genes are expressed, the CpG islands of promoters are unmethylated whereas when methylation of these sites occurs it is essential in expression of genes.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: Further, it is reported that neurotransmitters released by neurons of the ventral part of the SCN is necessary for maintaining synchrony of the whole SCN [23 ]. Vasoactive intestinal polypeptide (VIP) VIP, a gut polypeptide, has been identified as one of the main neurotransmitters of SCN neurons and participates in SCN function. These SCN neurons are retinorecipient and are found in the core of the SCN. They are activated by light, and exogenous application of VIP can reset the circadian clock in a manner similar to that of light application, both in vitro and in vivo[6]. It is estimated that 9%–24 % of SCN neurons express VIP [26,158]. It appears that in rats there are two types of VIP neuronal components[159], namely a medial GRP-free group and a lateral group containing GRP. Only the lateral group expresses per1 following a light pulse [159]. However, few VIP-containing cells rhythmically express per1 and per2 [160,161]. VIP is synthesized from prepro VIP and further cleavage of the molecule forms VIP and peptide histidine isoleucine (PHI). PHI is found in abundance in the SCN and is co-localized [162,163]. VIP and PHI are structurally related to PACAP. The receptor for 2,also known as Vipr2, is expressed in about 60% of the SCN neurons, which respond to VIP with changes in firing rate [164,165]. VIP acting through VPAC2 can participate in both resetting by light and maintenance of ongoing rhythmicity in the SCN [6]. VIP along with GRP and AVP show circadian variation in the level of mRNA in constant environmental conditions [166]. Some earlier studies [167 - 169] had indicated that VIP and GRP do not show circadian rhythms in DD and only daily rhythms in LD. On the basis of their study, Shinohara et al [168] suggested that changes in the peptide content by light conditions might reflect changes in the synthesis and release of peptides. The release of these peptides also shows circadian variation [170]. It has been reported that treatment of SCN slices with VIP produces phase shifts similar to those induced by light pulses [171].

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: Multi-modal social recognition may be particularly important for nocturnal (e. g. H. maculosa) or eyeless animals (e. g. annelids) for which visual recognition may be difficult or impossible (Aquiloni and Tricarico 2015). Data collection for this study occurred at night, and visual cues were assumed to be limited. Octopuses’ sucker-lined arms sense both textures (Wells and Wells 1957) and chemical signatures (Wells et al. 1965; van Giesen et al. 2020); either of those inputs, or both, may have been used here. It is suspected in this case that dermal hormones, which can vary by both sex and reproductive status (e. g. O. bimaculoides, Chancellor et al. 2021), may be the most likely chemicals assessed and utilised in social recognition here. These chemotactile cues would have complemented other cues (e. g. chemical or possibly visual) sensed from a distance. A prior study of combined visual and tactile learning in O. vulgaris found these modalities operated largely without interaction (Allen et al. 1986), and the neural underpinnings of visual and tactile learning are reported to take place separately within the octopus brain (Wells 1961). Octopus vulgaris uses multiple sensory cues to recognize and discriminate between prey types (Maselli et al. 2020). Individuals offered simultaneous access to both visual and chemical recognition cues in prey discrimination tests performed only slightly, or no better, than those offered either chemical cues only, or conflicting sensory inputs (ibid). In these experiments, individual O. vulgaris were given up to an hour to make those decisions. By contrast, H. maculosa in this study only took seconds to sense, process, and prioritise multiple information channels, and make decisions about retreat based on social recognition. While all individuals in this study had access to the same sensory channels, males (this study) and females (Morse et al. 2017) appeared to use different cues in social recognition, suggesting sex differences in this prioritisation of sensory information in decision-making. In addition to revealing social recognition, patterns of retreat following touch in H. maculosa align with previous assessments of its mating system, and may provide insights into prosocial mechanisms that maintain it.

Output: contrast


Input: Claim: Gene expression analysis helps understand cellular responses to stimuli. [SEP] Text: Majority (40%), of the CpG islands are located in the promoter region. Herein, the CpGPAP platform employs the use of Takai and Jones algorithm. In this algorithm, a DNA sequence with a length of >500bp, GC content >55% in that region and Observed/Expected (O/E) ratio of >0. 65 was considered. The algorithm can successfully exclude false positives from short repetitive sequences (Chuang et al. 2012). ver. 5. 5. 2 (CLC n. d. ) was used to search for the restriction enzyme MspI cutting sites with a fragment selection of 40 to 220pbs having in mind that the region enriches CpG islands. 3. Results3. 1 Number of TSSs and predictive values of L. donovani BPK282A1 genome The TSS of the parasite was predicted among forty putative genes of L. donovani BPK282A1 genome and the important variables such as gene identification number, corresponding promoter region, predictive value and location of the TSS were summarized in table 1. This in silico analysis of L. donovani BPK282A1 genome showed that a single sequence can have as low as one TSS and as high as four TSSs. Where there were two or more TSSs the one with highest predictive score was considered the best TSS location of the gene. In all cases, the TSSs have a predictive score that ranged from 0. 80 to 1. 00. Majority (82. 3%), of the TSSs identified were located below -500bp away from the start codon of the gene being expressed. Surprisingly, the TSS of one gene was located at -1338 which is very apart from the start codon. The number of TSSs were significantly varied between 1 and 4 among the promoter region sequences. The analysis revealed that about forty percent (40%) of the gene had only one TSS while only one gene had four TSSs. On the other hand, the location of the TSS of one sequence (Pro-LDBPK_060-590) was remarkably close to the start codon which was only 2bps away upstream of the respective gene. Table 1 Number, predictive score and location of TSSs in L.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: Nielsen and co-workers [172] showed that VIP induces per1 and per2 gene expression in rat SCN in a phase dependent manner. More recently, VIP has been shown to be necessary for the coordination of the daily rhythms in behaviour and physiology at the level of biological clock in mice [173]. Loss of internal desynchronization and its subsequent restoration were achieved by adding VIP into the mice cells. Thus, VIP signalling through its receptor serves two important functions in the SCN, namely, circadian rhythmicity in a subset of neurons and maintenance of synchrony between intrinsically rhythmic neurons. This may also mean that VIP-expressing neurons themselves are circadian pacemakers in the SCN for establishing and synchronizing rhythmic activity. Vasopressin (AVP) AVP neurons occupy a large part of the SCN, mostly in the dorsomedial part of the SCN and are extensively interconnected [174,175], indicating the capacity of the SCN to produce an integrated output. It is estimated that nearly one third of the SCN neurons in rats synthesize AVP. It is one of the major neuropeptides identified in the SCN [16,176,177]. AVP is synthesized and secreted by the SCN in a circadian pattern. AVP has an important excitatory role by activating V1a receptors [177] to increase the amplitude of firing rates in the SCN during subjective day [178,179] and enhance SCN output [176,177]. Although the presence of AVP at the level of the SCN may not be critical for the expression of some of the circadian rhythms, abnormalities can be seen in some of the expressed rhythms in its absence. AVP-deficient Brattleboro rats have served as an excellent model for the demonstration of the absence of AVP and subsequent disturbances in many of the circadian rhythms. Local application of AVP into the SCN does not affect the free running circadian wheel running rhythm in hamsters[180] or entrained circadian food intake [181] and water intake [182]. A convincing supportive role for vasopressin in SCN circadian function has come from transplantation studies of DeCoursey and Buggy [183] as well as that of Lehman and co-workers [184].

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: Larger females were less likely than smaller females to retreat following contact with conspecifics, regardless of conspecific sex or size. Larger females are also more receptive to mating attempts (Morse et al. 2015). Both of these findings suggest larger female H. maculosa are more likely than smaller females to tolerate the presence of conspecifics. However, cannibalism is an extreme form of social intolerance (Chiara et al. 2019), and sexual cannibalism occurs in the Hapalochlaena genus (Cheng and Caldwell 2000). Where this behaviour has been observed in other octopuses in the wild, it has been expressed by large females (Huffard and Bartick 2015). In order to reproduce successfully, large female octopuses must tolerate males in their presence, and suppress any aggressive motivation to cannibalise before spermatophores have been transferred to the oviduct. It might be that females would be more likely to cannibalise males with which they have already mated, because they have already stored their sperm. If so then this tendency could induce strong selection for males to avoid females that are former mates. Serotonergic neurotransmission may play a role in suppressing aggressive asocial or antisocial tendencies in O. vulgaris, thereby releasing conserved prosocial behaviours (Edsinger and Dölen 2018). If this mechanism is present in H. maculosa as well, then results here suggest it may develop as females grow in size. The evolution of chemotactile social recognition by male H. maculosa may have been influenced by the risk of sexual cannibalism, and mate preference for novel females in the context of significant biological and ecological constraints. In stomatopods, the species with the best social recognition capabilities are also the most aggressive (Vetter and Caldwell 2015). Given the prevalence of cannibalism among octopuses (Ibáñez and Keyl 2010), males have likely evolved the means to recognise those individuals most likely to initiate sexual cannibalism (e. g. large females). This recognition may be especially acute for males that also prefer to mate with large females (e. g. A. aculeatus, Huffard et al. 2008). Male H. maculosa do not share this preference (Morse et al. 2015), but nonetheless appeared more likely to retreat after contacting larger females. It is curious that sex recognition requires male H.

Output: contrast


Input: Claim: Gene expression analysis helps understand cellular responses to stimuli. [SEP] Text: donovani BPK282A1genes Name/gene ID Corresponding promoter region name Number of TSS identified Predictive score at cutoff value of 0. 8 Location of the best TSS from the start codon LDBPK_141460 Pro-LDBPK_141-460 2 0. 84, 0. 99 -385 LDBPK_230300 Pro-LDBPK_230-300 1 0. 88 -835 LDBPK_212210 Pro-LDBPK_212-210 3 0. 85,0. 89, 0. 99 -679 LDBPK_251640 Pro-LDBPK_251-640 1 0. 96 -692 LDBPK_151500 Pro-LDBPK_151-500 3 0. 81,0. 86, 0. 99 -554 LDBPK_340900 Pro-LDBPK_340-900 1 1. 00 -126 LDBPK_262720 Pro-LDBPK_262-720 2 0. 97,0. 99 -513 LDBPK_040440 Pro-LDBPK_040-440 1 0. 94 -159 LDBPK_171020 Pro-LDBPK_171-020 1 0. 88 -1338 LDBPK_151100 Pro-LDBPK_151-100 20. 811. 00 -177 LDBPK_151540 Pro-LDBPK_151-540 3 1. 00,0. 88,1. 00 -106, -697 LDBPK_060590 Pro-LDBPK_060-590 2 0. 99, 0. 87 -2 LDBPK_030760 Pro-LDBPK_030-760 2 0. 97, 1. 00 -132 LDBPK_111140 Pro-LDBPK_111-140 1 0. 99 -366 LDBPK_160580 Pro-LDBPK_160-580 3 0. 86, 0. 89, 0. 92 -898 LDBPK_250780 Pro-LDBPK_250-780 2 0. 97, 0. 92 -85 LDBPK_362640 Pro-LDBPK_362-640 4 0. 88, 0. 94, 0. 99, 0.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: This protocol might be applied before eastward jet travel or for delayed sleep phase syndrome to evoke a phase advance of the circadian clock [208]. In spite of the experimental evidence favouring a very important role for melatonin in the circadian timing system, the exact role of melatonin has not been demonstrated clearly. Melatonin and seasonal rhythms are intimately related in mammals, and this has been well documented [209,210]. Lincoln and co-workers [211] provided evidence for a temporal melatonin-controlled expression of clock genes in specific calendar cells. The retinohypothalamic -pineal (RHP) axis is comparable in animals and humans. In both animals and humans melatonin is secreted exclusively at night. The RHP is capable of detecting changes in night length to make proper adjustments for the duration of nocturnal melatonin secretion so that animals can use this melatonin message to trigger seasonal changes in behaviour [209]. With seasonal changes in night duration, there are parallel changes in the duration of melatonin secretion, and this leads to more secretion as compared to summer. Neurotransmitters in efferent projections The output of the SCN by way of efferent projections serves the purpose of conveying the information to the related centres. Outputs are primarily seen to the nearby hypothalamic and thalamic nuclei from the SCN, particularly to the medial preoptic nucleus, the medial part of the paraventricular nucleus of the hypothalamus, the anterior part of the paraventricular nucleus of thalamus, the medial part of the dorsomedial nucleus of hypothalamus, and principally the subparaventricular zone [212,213]. Projections to the ventrolateral preoptic nucleus from the dorsomedial nucleus, the preoptic nucleus and the subparaventricular zone appear to serve as the anatomical basis for the control of sleep and wakefulness, as the ventrolateral preoptic nucleus is implicated in the control of sleep states [214 - 216]. Efferent projections seem to have mainly AVP and VIP as transmitters. These fibres that originate in the SCN can be seen for long distances within the hypothalamus and have a characteristic morphology. The functional significance of these projections remains to be fully determined, apart from the basic fact that they are necessary for the SCN to exert its overt function. The functional role has been described to some extent earlier [217].

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: mounts and wraps his arms tightly around the female’s mantle (Cheng and Caldwell 2000), possibly interfering with ventilation and oxygenation of the gills. Females sometimes expend significant effort to terminate mating attempts by males (Cheng and Caldwell 2000; Morse et al. 2015). Therefore, individual females that can identify males via olfactory cues from a distance (Morse et al. 2017), and can preclude mating attempts by unpreferred males by avoiding them altogether, may gain a selective advantage. ConclusionSocial recognition in octopuses points to a number of underexplored connections between male mate preference, sensory biology, neural control, and evolutionary ecology. Hapalochlaena maculosa uses multi-channel sensory inputs in rapid decision-making, with apparent sex differences in those mechanisms. The neural templates underpinning sex recognition are likely stable across generations, and therefore unlikely to require learning (Tumulty and Sheehan 2020). By contrast, recognition of former mates is contextual and requires a recognition template to be both learned and updated throughout the lifetime (Tumulty and Sheehan 2020). Hormones may play an important role in this recognition system, both as dermal cues used by males, and by suppressing female aggression allowing for successful conspecific interactions. Finally, the constraints of limited gene flow and reproductive potential of both males and females in this relatively asocial lineage may provide strong selective forces behind the evolution of social recognition and the sensory mechanisms that facilitate it. study was partially funded by the Australia & Foundation and University. These funding bodies and authors have no conflict of interest in the presentation of this study. All international, national and institutional guidelines for the sampling, care and experimental use of organisms for the study have been followed and all necessary approvals have been obtained, with details provided in the methodology. would like to thank Ross and of the Company for the use of their facilities during the course of this study. We would also like to thank João Santos and for their assistance in obtaining H. maculosa from their by-catch. Thank you also to the Australia & Foundation for funding some of the research costs associated with this investigation and to University for funding P. Morse’s stipend while obtaining these data. Thank you also to ReefOneTM for donating the LED lighting used to simulate daylight and moonlight hours during this study. We are also very grateful to Jones who took the time and patience to teach P.

Output: pass


Input: Claim: Gene expression analysis helps understand cellular responses to stimuli. [SEP] Text: 82 -703 LDBPK_280030 Pro-LDBPK_280-030 3 0. 82, 0. 96, 0. 92 -452 LDBPK_131090 Pro-LDBPK_131-090 1 1. 00 -222 LDBPK_040570 Pro-LDBPK_040-570 1 0. 89 -431 LDBPK_303160 Pro-LDBPK_303-160 1 0. 94 -925 LDBPK_180690 Pro-LDBPK_180-690 2 0. 98, 0. 96 -466 LDBPK_180620 Pro-LDBPK_180-620 2 0. 97,. 98 -928 LDBPK_180590 Pro-LDBPK_180-590 3 0. 84, 0. 98, 0. 89 -504 LDBPK_180480 Pro-LDBPK_180-480 1 0. 92 -195 LDBPK_180460 Pro-LDBPK_180-460 2 0. 90, 0. 86 -601 LDBPK_180370 Pro-LDBPK_180-370 1 0. 92 -598 LDBPK_180360 Pro-LDBPK_180-360 2 0. 90, 0. 80 -368 LDBPK_180270 Pro-LDBPK_180-270 1 0. 81 -346 LDBPK_181100 Pro-LDBPK_181-100 2 0. 91, 0. 97 -927 LDBPK_181080 Pro-LDBPK_181-080 2 0. 82, 0. 95 -330 LDBPK_180920 Pro-LDBPK_180-920 1 0. 90 -857 LDBPK_180810 Pro-LDBPK_180-810 2 0. 81, 0. 89 -402 LDBPK_180790 Pro-LDBPK_180-790 1 0. 97 -504 LDBPK_180650 Pro-LDBPK_180-650 1 0. 86 -426 LDBPK_180580 Pro- LDBPK_180-580 3 0. 98, 0. 91, 0. 81 -437 LDBPK_180510 Pro-LDBPK_180-510 1 1.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: Though the various mechanisms used to regulate the activity of other systems of the body is unclear at present, a number of hormones with direct actions on different parts of the body are produced by the SCN. These include and SS. A review by and co-workers [9] describes not only the transmitters of RHT but also the output of the SCN. A long neural signalling pathway from the SCN regulates the pineal gland secretion of melatonin. SCN neurons also stimulate gonadotrophin releasing hormone (GnRH) synthesizing neurons of the preoptic area and thereby affect sex hormone cycles [232]. It is generally seen that outputs of the circadian system are rhythmic but not temperature compensated. In spite of the difficulties to understand the mechanisms by which the SCN regulates a wide range of physiological outputs, it has been agreed that there are two types of signals originating from the SCN. These are hormonal and neural outputs. Transplantation experiments [233] in particular have provided highly useful evidences for the suggestion that hormonaldiffusible factors produced by the SCN act as an important output signal for the circadian system [234]. Quick recovery of behavioural rhythms within 4 days of transplantation of the SCN [184], successful placement of transplants at locations distant from the SCN [184], and transplanted dissociated SCN cells capable of restoring rhythmicity [235] are all in favour of hormonaldiffusible factors as the output signal. It is possible that different physiological systems are controlled by either neural or hormonal output from the SCN. For example, rhythmic secretion of melatonin could be under neural control while locomotor activity might be under hormonal control. Also, a specific physiological function may receive both neural and hormonal signals. As regards to the communication of information from the circadian clock to the centres controlling activity in brain areas, more than one mode is indicated [222,236]. Analysis of the chemoarchitecture of the SCN have shown that, in addition to the above neurotransmitters, the SCN also contain neurons capable of synthesizing a number of other neurochemicals, with the distribution of immunoreactive neurons differing slightly for each neurochemical. A few of these neurochemicals are described here. Somatostatin (SS) SS producing neurons of the SCN are located in both the core and shell portions [237] and form a distinct peptidergic neuronal group.

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: ölen G (2018) A conserved role for serotonergic neurotransmission in mediating social behavior in octopus. 28:3136–3142 e3134 doi. -(2012) The energetic cost of mating in a promiscuous cephalopod. 8:754–756 (2005) A division of labour with role specialization in group-hunting bottlenose dolphins (Tursiops truncatus) off Cedar Key, Florida. Proceedings of the B: 272: 135–140 doi (1964a) Electron microscopy of some primary receptors in the sucker of Octopus vulgaris. Z für Zellforschung und 64:510–522. doi (1964b) Receptors in the sucker of the cuttlefish. Nature 203:384–386. doi (2018) Cephalopod Behaviour. (2015) photogenicus and Octopus cyanea employ asphyxiating ‘constricting’ in interactions with other octopuses. 35:12–16. doi (2008) Mating behavior of Abdopus aculeatus (d’Orbigny 1834) (Cephalopoda: Octopodidae) in the wild. 154:353–362. doi (2010) Male-male and male-female aggression may influence mating associations in wild octopuses (Abdopus aculeatus). J 124:38–46. doi Hurst JL (2005) Scent marking and social communication. In: McGregor PK (ed) Animal communication networks. Press, Cambridge, pp 219–243 Ibáñez CM, (2010) Cannibalism in cephalopods. 20:123–136. doi Jaeger RG (1981) Dear enemy recognition and the costs of aggression between salamanders. 117:962–974. doi (2015) Social recognition in annelids and the evolution of social recognition and cognitive abilities by sexual selection. In: Aquiloni L, (eds) in Invertebrates. Springer, Switzerland, pp 1–15 (1994) Close encounter in the deep. Nature 371:563–563. doi Maselli V, Al-Soudy A-(2020) Sensorial hierarchy in Octopus vulgaris’s food choice: Chemical vs. visual. Animals 10:457.

Output: contrast


Input: Claim: Gene expression analysis helps understand cellular responses to stimuli. [SEP] Text: 00 -559 LDBPK_170660 Pro-LDBPK_170-660 2 0. 99, 1. 00 -796 LDBPK_170610 Pro-LDBPK_170-610 3 1. 00, 0. 97, 1. 00 -586, -837 LDBPK_170890 Pro-LDBPK_170-890 2 086, 1. 00 -422 Results from NNPP tool prediction are considered to be reliable at 0. 8 cutoff values (BDGP: n. d. ) 3. 2 Promoter regions with potential motifs in L. donovani BPK282A1 The spatial distribution and location of the motifs were presented below in figure 1. The motifs were found on both positive and negative strands. The shortest distance of the location of the motif was only 2bps upstream of the TSS while the longest distance was 4941bps upstream of the TSS of the respective gene. Majority, 188 (72. 3%) of the motifs were highly distributed on positive strand than the negative strand. On the other hand, the study also revealed that in about twenty-seven (67. 5%) sequences the location of the first motif was held in the first -500bps upstream of the respective gene. Furthermore, the promoter sequence of gene LDBPK_151500 was exceptionally too long and contains seven motifs among which only one motif was located on the negative strand. The study has also revealed seven candidate motifs in the promoter regions being analyzed using server-based MEME suite motif identifier. The analysis was performed at a cutoff value of 0. 80 and provided and MVII motifs. The minimum site per motif was two while the maximum site per motif was forty. The identified motifs were presented below in table 2 with their respective total number of binding sites and the level of statistical significance (E-values). It was shown that MI was the common promoter motif for all (100%) L. donovani BPK282A1 genes that regulates transcription and translation of the genes being studied. Statistically, it shares at least 85% of the promoters containing each one of the motifs with an E-value of 4. 0e-116. The sequence Logo of the best motif identified was presented in figure 2. Table 2 Common motifs identified in L.

Output: pass


Input: Claim: The suprachiasmatic nucleus (SCN) in the brain is the master clock regulating circadian rhythms. [SEP] Text: These cells are few in the mouse SCN, but are large in size. Part of the SS and (SP) peptides are co-localized [238]. The shell portion of the SCN, which is likely to be involved in the regulation of overt rhythms, projects within the SCN through SS fibres [239]. In an interesting study, Biemans co-workers [240] reported a significant increase in SS and SP immunoreactivity in aged Wistar rats as compared to young ones, thereby indicating that not all SCN neuropeptidergic systems decline with age. However, another study in Syrian hamsters [241] showed that there is no effect of age on SS mRNA. Aging effects of SCN neuropeptide expression, like the circadian profile of peptide expression, may be species specific as far as the SCN is concerned. Further, it has been reported [242] that SS has a role in phase shifting and is able to reset the phase of the clock [243]. Synapse of SS fibres on VIP and AVP neurons and presence of SS receptors in the SCN is suggestive of a regulatory role for SS on other peptidergic neurons. An inhibitory modulating role of SS on VIP rhythmicity is seen [244]. Increase in SS immunoreactivity could explain the observed VIP decrease with aging, and, if enhanced SS immunoreactivity reflects a release deficit, this may lead to reduction in inhibitory action [240]. Calbindin (CalB) Calbindin (CalB) neurons are also found throughout the core and shell subdivisions of the SCN. Silver and co-workers [245] reported the presence of CalB-containing cells in the caudal part of the SCN. CalB cells are densely packed and receive direct retinal synaptic input [246] and respond to photic stimuli. Study of Silver and co-workers [245] indicates that CalB cells are present in the input pathway for photic stimuli reaching the SCN. The CalB subregion of the SCN seems essential for the maintenance of circadian locomotor activity rhythm. This comes from the studies of lesion as well as transplantation. Animals with lesions that destroyed CalB neurons but spared other neurons of the SCN lost rhythmicity of locomotor activity, and transplants of SCN tissue containing CalB cells restored rhythmicity.

Output: corroborate


Input: Claim: Octopuses and snails are biologically identical, differing only in size. [SEP] Text: 1Isotopic niches represented by Standard ellipse area corrected for small sample size (seac) of the land snail species collected in four study sites (A, B, C, D) at least in five individuals per site. Citation: Contributions to Zoology 92, 1 (2023) 10. 1163/18759866-bja10036Download FigureDownload figure as PowerPoint slide Land snail lifestyle was classified according to microhabitat p2. Statistical analysis To analyse variation in species seac in relation to their lifestyle and body sizes, generalised estimating equations (gee) with Gaussian distribution was used (gee-g). The seac and body size of each species were transformed prior the analysis using natural logarithm as the data were not normally distributed (table 2). gee is an extension of the generalised linear models for situations when measurements of the response variable are not independent. In our study there were multiple species collected from the same site, which gave rise to a correlated response per site, so we assumed exchangeable correlation structure in the residuals in order to correct for standard errors of parameter estimates that were too small. As seac value can be expected to increase with increasing sample size, we included the number of analysed individuals per species into the model as the first predictor, to control for variable sample size. gee-g were fitted using a function from the ‘geepack’ package (version 1. 3–2; Højsgaard et al. , 2006). The significance of all predictors was tested by the model, using Wald test. Variation in percentages of overlapping seac for pairwise species combinations was analysed by generalised linear regression model (glm) using quasi-Poisson distribution with log link function (glm-qp) to correct for an overdispersion. We tested whether the overlap in seac is different between study assemblages and types of lifestyle and is changing with body size difference. As the number of analysed individuals varied, sums of individuals in the compared pair of species were the first predictor added into the model. The significance of all predictors was tested by the model, using Chi-square statistic. The size of the overlapping area was transformed using square root transformation to normalise its distribution, the difference in body size was transformed using natural logarithm (table 2). All analyses and graphics were performed in R program, version 4. 0.

Output: pass


Input: Claim: Gene expression analysis helps understand cellular responses to stimuli. [SEP] Text: 97e+00 VRN1 Required for vernalization EGR2 DBD (Zinc finger, C2H2 type, C2H2-type zinc finger, Zinc finger double domain) Homo sapiens 6. 43e+00 EGR2 Early growth response 2 Three-zinc finger Krüppel-related factors Homo sapiens 6. 43e+00 EGR2 Binds specifically to 9-bp target sequences containing two CpG sites that can potentially be methylated at four cytosine bases Three-zinc finger Kruppel-related factors Homo sapiens 6. 70e+00 KLF9 Binding of the encoded protein to a single GC box inhibits mRNA expression while binding to tandemly repeated GC box elements activates transcription EGR2_full (Domain of unknown function (DUF3446), Zinc finger, C2H2 type, C2H2-type zinc finger, Zinc-finger double domain) Homo sapiens 8. 18e+00 EGR2 Early growth response 2 3. 3 Gene ontology Having been compared the common motif using publicly known databases in another server based investigation using GOMo (for Motifs) (Buske et al. 2010b; GOn. d. ) was used to look for GO terms for promoter regions of L. donovani BPK282A1 gene and no significant GO term was associated with the common motif (MI) submitted (Figure 3). 3. 4 Determination of the CpG islands of L. donovani BPK282A1 genome in promotor and gene body regions CpG islands, stretches of DNA that are 500-1500bp long with CG:GC ratio of more than 0. 65% in promoter and gene body regions were determined using two algorithms. First, an online CpG Island finder (Database of CpG Islands n. d. ) that depends on Takai and Jones rigorous criteria where parameters were set as ob/ex ratio of the CpG islands ≥0. 65, GC content of at least 50% and minimal length of ≥500bps was used to identify possible CpG islands present, the number of CpG islands found and the percent of GC contents in each of the promoter and gene body regions (Takai and Jones 2002). Herein, the search revealed that thirty-one (31) promoter regions of the L.

Output: pass