Input: Task: corroborate the claim using the given text. Claim: The impact craters on the Moon provide insights into the history of the solar system. [SEP] Text: 8°E); II Albategnius (11. 7°S, 4. 3°E); III Thebit (22. 0°S, 4. 0°W); IV Cleomedes (27. 7°N, 56°E)Full size image For the profile of craters in group I, the eroded extent of the older crater rim is about 1,300 m, enabling it to still present some of the original morphology. As for the group II profile, the eroded extent of the older crater rim is about 2,500 m, and the overall shape of the older crater has changed significantly. Some of group III has an eroded extent, which is at about 2,500 m, and the depth of the two craters shows a great difference. In group IV, the radius ratio of the younger to older craters was small. The eroded extent of the rim of the older one is about 500 m, and the depth of the younger impact craters is shallow. 5 Discussion5. 1 Inferring the Order of CratersTaking the geological ages of the craters published by IAU ( as standard, the inferred positional relationship results and relative impact timing for many groups of craters are found to agree with the geologic record. Comparative results (Table 4) show that the inferring method in this paper is feasible. Similarly, relative age orders for craters on a geologic setting can be determined. The universal parameters and supplementary methods mentioned above can be used to infer the relative order of impact for most ‘overlapping’ impact craters, but a few anomalous impacts could not be assessed. These include situations where the impacts occurred close together in time and also where there are external influences or interference factors; e. g. , diversity of lunar soil and rock composition, or where depth and rays cannot be distinguished. Furthermore, owing to basalt fill, tectogenesis, isostatic compensation and other impact effects of the lunar surface, thus, shape, size and depth of older craters would gradually change with time of exposure. Infilled by ejecta is one of the mechanisms of crater destruction which leads to a reduction in the depth of these craters. [SEP] Justify:

Output: The text corroborates the claim by discussing how the geological ages of the craters, along with their inferred positional relationships and relative impact timings, agree with the geologic record. It states that methods can be used to infer the relative order of impact for overlapping craters, indicating that the study of these craters can indeed reveal important historical information about the solar system.


Input: Task: pass the claim using the given text. Claim: All plants used historically are still cultivated in modern agriculture. [SEP] Text: Statistical output from a two-way ART-ANOVA for the effects of region and genus on bleaching severity, as well as their interaction. Only genera present in most or all regions were included. Significant (p < 0. 05) factors are bolded. Df. res F value Pr(>F) Region 2 1407 6. 901 0. 001 Genus 19 1407 3. 468 <0. 001 Region * Genus 22 1407 2. 868 <0. 001 DOI: 10. 7717/peerj. 16100/table-1 Figure 5: Coral bleaching severity by genus and region. Violin plots showing the distribution of bleaching severity scores for each common coral genus across the Atlantic, Indian, and (0 = none, 1 = low, 2 = moderate, 3 = high, 4 = severe). The total number of observations by genus and region is indicated above each box. Asterisks indicate genera for which mean bleaching severity varied significantly by region. Download full-size image DOI: 10. 7717/peerj. 16100/fig-5 We also found significant effects of region (p < 0. 001) and morphology (p < 0. 001) on bleaching responses (Table 2). Again, there was a significant interaction between region and morphology indicating that some morphologies responded differently across regions. Specifically, massive (p = 0. 002) and massive/encrusting (p = 0. 004) corals bleached most in the Atlantic, followed by the Indian and (mean bleaching severity scores = 1. 9 ± 0. 1, 1. 5 ± 0. 1, and 1. 4 ± 0. 1, or 1. 9 ± 0. 2, 1. 4 ± 0. 1, and 1. 3 ±0. 1, respectively). In contrast, free-living corals (p = 0. 004) bleached most in the Indian and compared to the Atlantic (mean bleaching severity scores = 1. 8 ± 0. 2, 1. 2 ± 0. 3, and 0. 2 ± 0. 1, respectively). Branching corals showed particularly high variability in bleaching responses within regions (bleaching severity range = 0–4; Fig. 6) but not significantly among regions. Columnar corals (p = 0. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the effects of region and genus on coral bleaching severity and does not mention plants, their historical use, or current agricultural practices. Therefore, it does not provide any supporting or contrasting information regarding the claim.


Input: Task: pass the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: The tube is surrounded by the subarachnoid spaces, which in this discussion are taken to include the basal cisterns. Both ventricles and subarachnoid spaces are filled with cerebrospinal fluid (CSF). The inside of the tube at the IVth ventricle is connected to the outside of the tube at the cisterna magna via the foramina of Magendie and Luschka. The subarachnoid spaces are bounded on their outside by the outer meninges composed of the arachnoid and the dura (see Fig. 2 inset), which are in turn encased by the skull (see [1]). On their inside the subarachnoid spaces are separated from the brain parenchyma by a cell layer, the pia mater or inner meninges, and one or more layers of astrocyte endfeet, the glia limitans. The surfaces of the parenchyma adjacent to the ventricles are covered by a layer of cells, the ependyma (see Fig. 2 inset). Fig. 1Mid-saggital section of the brain showing locations of the ventricles, cerebral aqueduct, subarachnoid spaces (including the basal cisterns) and choroid plexuses. The choroid plexuses are discrete epithelial structures located in the cerebral ventricles that secrete cerebrospinal fluid (CSF) shown in pale blue, which fills the ventricles and subarachnoid spaces. Normally there is net flow of CSF from the ventricles into the cisterna magna and from there to the other subarachnoid spaces of the brain and spinal cord. Reproduced but relabelled with permission from Strazielle et al. [20]Full size image Fig. 2Schematic diagrams of the lateral surface of the brain showing a the arterial supply and b the venous drainage with an inset indicating the relations of the pia, the ependyma and the perivascular spaces to the brain parenchyma. The large vessels run parallel to the surfaces of the brain, with smaller branches that penetrate into the parenchyma more or less perpendicular to the surfaces (see inset). [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the structure of the brain and its associated spaces without mentioning the blood-brain barrier or its function in protecting the brain from harmful substances.


Input: Task: corroborate the claim using the given text. Claim: The impact craters on the Moon provide insights into the history of the solar system. [SEP] Text: It can be assumed that the rate of degradation of craters on Earth must be greater due to erosion, sedimentation and plate tectonics. However, on Earth we can find deeply eroded and buried astroblemes using modern methods of geology and geophysics. Some idea of what preserved large impact craters look like can be obtained from images and topography of craters on Mercury and Mars (Figs. 2, 3). However, the approximately three-times lower gravity on these planets requires additional discussion of the geometry of large craters. The crater profile on Mars (Fig. 3) has been greatly modified by younger geological processes, including the formation of younger craters, but the position of the inner ring is still noticeable. To illustrate what the initial profile of the crater might have been, the dotted line in the lower figure shows the profile of the younger and better-preserved crater Lyot (D ~ 200 km) with a depth of ~4 km, comparable to the depth of the crater on Mercury shown in Fig. 2. Fig. 3. Ancient impact crater Schröter (D ~ 300 km) on Mars (top) and the altitude profile of the surface along the diameter of the crater (bottom, solid line). The dotted line shows the profile of the younger and better preserved Lyot crater (Lyot, D ~ 200 km). The image and altitude profiles were constructed by the author using the publicly available JMars software ( based on the results of several NASA spacecraft flights to Mars ( size imageOften, the search for traces of ancient impact events includes the search for bulk deposits of multiple ejecta from craters (Simonson and Glass, 2004; Johnson and Melosh, 2012; Johnson et al. , 2016; Bottke and Norman, 2017; Schulz et al. , 2017; Lowe and Byerly, 2018). Less common are traces of possible individual impact events in “suspicious” areas. A study of one such site (Maniitsoq in Greenland) was proposed by Garde et al. , (2012). Several years ago, the author took part in the discussion of the Garde hypothesis and carried out a small series of numerical calculations (Garde et al. , 2011). Without the participation of the author, the study of the Garde hypothesis continues (Trowbridge et al. , 2017). [SEP] Justify:

Output: The text supports the claim by discussing the study of impact craters on other celestial bodies such as Mercury and Mars, highlighting the significance of these craters in understanding ancient impact events and geological processes. It mentions that the search for traces of ancient impacts includes analyzing craters, which is relevant to understanding the solar system's history.


Input: Task: pass the claim using the given text. Claim: All plants used historically are still cultivated in modern agriculture. [SEP] Text: Limnology and Oceanography 59:788-797. 2020. Contrasting color loss and restoration in survivors of the 2014–2017 coral bleaching event in the Turks and Caicos Islands. SN 2:1-11. 1996. Bacterial infection and coral bleaching. Nature 380:396. 2018. Systematic revision of Symbiodiniaceae highlights the antiquity and diversity of coral endosymbionts. 28:2570-2580. 2016. Most low-abundance background Symbiodinium spp. , are transitory and have minimal functional significance for symbiotic corals. 71:771-783. 1990. Bleaching in coral reef anthozoans: effects of irradiance, ultraviolet radiation, and temperature on the activities of protective enzymes against active oxygen. 8:225-232. 2018. Assessing the spatial distribution of coral bleaching using small unmanned aerial systems. 37:373-387 -Karger FE, Vega-. 2014. Reef-scale thermal stress monitoring of coral ecosystems: new 5-km global products from NOAA coral reef watch. 6:11579-11606. 2014. Incorporating adaptive responses into future projections of coral bleaching. Biology 20:125-139. 2001. Coral bleaching: the winners and the losers. 4:122-131 Marshall P, Baird A. 2000. Bleaching of corals on the Reef: differential susceptibilities among taxa. 19:155-163 McClanahan T. 2004. The relationship between bleaching and mortality of common corals. 144:1239-1245. 2004. Comparing bleaching and mortality responses of hard corals between southern Kenya and the Reef, Australia. Bulletin 48:327-335. 2014. Coral reefs in a crystal ball: predicting the future from the vulnerability of corals and reef fishes to multiple stressors. in 7:59-64 ’agata. 2020. Large geographic variability in the resistance of corals to thermal stress. and Biogeography 29:2229-2247. 2016. Marine protected areas increase resilience among coral reef communities. 19:629-637. 2007. Real-time PCR reveals a high incidence of Symbiodinium clade D at low levels in four scleractinian corals across the Reef: implications for symbiont shuffling. 26:449-457. 2011. [SEP] Justify:

Output: The text is irrelevant to the claim because it discusses coral bleaching and associated research without any mention of plants or agriculture. Therefore, it does not support or contrast the claim.


Input: Task: pass the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: Points of penetration of the vessels down into the parenchyma are indicated by black dots at the end of vessels. Branching of arteries continues within the parenchyma yielding arterioles and eventually capillaries that then join forming venules and then veins. These merge and drain into the large veins and venous sinuses on the surface. As discussed in the text blood vessels within the parenchyma have associated perivascular spaces that provide preferential routes for materials to enter and leave the parenchyma. Figure drawn by Robert G. Thorne and used with permission. See [639] for a succinct but still thorough description of human anatomy relevant to delivery of substances to the brain and their removal from itFull size image Current evidence indicates that most of the CSF is secreted into the ventricles by the choroid plexuses (see Fig. 1 and for reviews [2,3,4]). While there are to and fro movements of CSF driven by the cardiac and respiratory cycles [5,6,7] and considerable convective mixing of CSF within the ventricles [8, 9], net flow is normally from the choroid plexuses in the ventricles towards the cisterna magna and onwards via the subarachnoid spaces to the various sites of CSF outflow. Most but not all studies show that in the absence of hydrocephalus there is transfer of solutes and fluid through the cerebral aqueduct connecting the IIIrd to the IVth ventricle but only limited transfers from the IVth to the IIIrd ventricle [9,10,11,12,13,14,15,16]. Footnote 1 The cells of the ependymal layer bordering the ventricles are not bound together by tight junctions and the layer is thought to be permeable to small solutes and proteins [17,18,19,20]. However, diffusion in the parenchyma is too slow to transfer material more than several hundred microns within 1–2 hFootnote 2 (see e. g. [17, 21,22,23,24,25]). Thus normally neither transfer across the ependyma nor flow of CSF provides a rapid route for substances to reach the choroid plexuses from most of the parenchyma. [SEP] Justify:

Output: The text discusses the anatomy of blood vessels, the flow of cerebrospinal fluid (CSF), and certain properties of cellular layers near the ventricles but does not directly address or evaluate the protective function of the blood-brain barrier. As such, it is irrelevant to the claim regarding the brain's protection from harmful substances.


Input: Task: corroborate the claim using the given text. Claim: The impact craters on the Moon provide insights into the history of the solar system. [SEP] Text: It seems to us that, more generally, regardless of the verification of the impact origin of the Maniitsoq structure, the results of modeling large terrestrial impact structures are of interest for the search for as yet undiscovered (if they are preserved at all) ancient impact craters with a diameter greater than ~200 km from the currently known Big Three: Vredefort, Sudbury, and Chicxulub. recent years, many papers have been published on numerical simulations of large-scale impacts. This paper uses a software package known as SALEB, described in detail previously (Ivanov et al. , 1997, 2010; Ivanov and Melosh, 2003; Ivanov, 2005). Fitting model parameters to best reproduction of the impact structures is described by Ivanov (2005), where field and laboratory observation data for the crater Vredefort were used to verify the model (Reimold, 1996; Gibson and Reimold, 1999; Lana et al. , 2003a, 2003b). The choice of model parameters is supported by recent 2D and 3D simulations for the Chicxulub crater (Riller et al. , 2018). The models of thermodynamic and strength properties of rocks in the works described above continue to be actively used in the numerical modeling of large terrestrial craters (Allen et al. , 2022; Posiolova et al. , 2022; Allibert et al. , 2023; Huber et al. , 2023). Because the original modeling assumed an impact structure in Greenland, current crustal thickness data (Kumar et al. , 2007) were used, with corrections for possible depth of erosion using the Sudbury and Vredefort structures as examples. With a modern crust thickness of ~35 km, options with an ancient crust thickness of up to 50 km were studied. Recent studies by Steffen et al. (2017) give more detailed values, in southern Greenland the Mohorovičić boundary plunges from a depth of ~30 to >50 km moving from west to east. In the following, when describing numerical modeling, we use the terminology generally accepted in papers on this topic. [SEP] Justify:

Output: The text corroborates the claim by discussing the importance of understanding large terrestrial impact structures, such as those modeled in the study, for the search of ancient impact craters. This indicates the broader relevance of impact craters, including those on the Moon, in uncovering insights about the solar system's history, particularly their formation and the parameters involved in modeling these impact structures.


Input: Task: contrast the claim using the given text. Claim: Archaeobotany can reveal the exact causes of ancient civilization collapses. [SEP] Text: Other types of remains, such as tubers, tissue or fibres, are also inherently morphologically not very distinctive. In all cases, DNA can help to shed light on species diversity during different cultural periods by typing species-specific genomic regions. 2. In all but a few cases, it is unclear whether observed morphological diversity of diaspores can be ascribed to the location of the seed in the flower, to preservation conditions, to being the result of environmental conditions, or whether such differences in morphology are related to genetic diversity which could then point to the presence of landraces of crops. Charred wheat grains are good examples of diverse morphological forms within one taxon (Jacomet et al. 1989). aDNA research can clarify such cases by investigation of genetic diversity within samples of a species from a defined context. 3. The evaluation of the importance of trade versus local agricultural diversity is complicated because it is difficult to establish whether cultivated plants were grown locally, or if they were imported from other regions. This point is particularly interesting at cultural transitions, when new edible plants appear. Examples are the many fruit species found north of the Alps in Roman times. aDNA can help to identify the origin of ancient plant remains through analysis of alleles or haplotypes known to have a geographically structured distribution in a taxon. 4. Understanding the process of domestication is still an important issue in archaeology (e. g. Zeder 2006; Zeder et al. 2006). Some traits of domestication are morphologically visible, such as the brittle rachis in cereals, but many are not. It remains unclear in which order and at which time points these traits were selected, unless they left a visible signature on well-dated archaeological remains. When the genes that have been selected during domestication have been identified, they can be studied in ancient plant remains and help the understanding in more detail of how domestication occurred. Through this analysis information can also be gained on the spread of domesticates and the status of selection of a plant at the onset of its spread. This is also true for the detection of selection for the dietary or medicinal values of plants, which can be studied through the genes important for metabolic pathways or economic traits in archaeological plant remains. Although modern genetic studies have made major contributions to our understanding of, for example, modes of domestication, migrations or biogeography (e. g. Arroyo-Garcia et al. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexities involved in understanding the causes of agricultural diversity and diversity within plant remains. It highlights that while ancient DNA (aDNA) research can help clarify the genetic diversity of crops and the spread of domesticated plants, it does not provide an exact analysis of the causes of ancient civilization collapses, as the evaluation of trade versus local agricultural diversity is particularly complicated. The statement that 'it remains unclear in which order and at which time points these traits were selected' suggests that this uncertainty undermines the ability of archaeobotany to reveal precise causes of societal decline.


Input: Task: corroborate the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: By contrast movement of substances between CSF and parenchyma across the pia/glial layers and ependyma is limited by diffusion in the parenchyma (in the absence of imposed osmotic gradients or infusions of fluid) and, except for regions of parenchyma very close to the surfaces (or to some extent in white matter, see Sect. 3. 1), is much slower than movement via the perivascular spaces. Hence the major routes for efflux of substances from the brain parenchyma are transfer across the blood–brain barrier and movements towards the outer surfaces of the brain via the perivascular spaces. The blood–brain barrier provides a route for efflux of solutes that are sufficiently small and lipid soluble (see Sect. 4. 1) and it also contains specific transporters that can transfer many polar substances. The perivascular route is especially important for the elimination of large or polar solutes for which there are no specific transporters (see Sect. 3). The types of mechanisms present at the blood–brain barrier that allow easy passage of nutrients like glucose and amino acids and wastes like CO2 are shown in Fig. 3 along with indication of the need for expulsion of substances that should not be allowed to enter or accumulate in the brain. Because the gaps between the endothelial cells are occluded by tight junctions that greatly reduce the paracellular passage of solutes even as small as sugars and inorganic ions like Na+, K+ and Cl−,Footnote 4 to enter or leave the brain across the blood–brain barrier almost all substances must pass through the cells, which means they must cross both the luminal and abluminal membranes. Fig. 3Mechanisms for transfers into and out of the brain across the blood–brain barrier and the need for efflux mechanisms. Passive, non-specific transfers can occur via paracellular and transcellular routes, though the rates for paracellular transfer are small. Specific transcellular transport can be passive or active. In addition to the transfers for well-known substances many others are able to enter at various rates, either because they are sufficiently small and lipid-soluble or because barrier mechanisms are not perfect. Substances which enter even though they shouldn’t or are produced “accidentally” by metabolism cannot be allowed to accumulate within the brain. [SEP] Justify:

Output: The text corroborates the claim by describing how the blood-brain barrier functions to limit the movement of harmful substances into the brain. It states that the blood-brain barrier plays a critical role in controlling which substances can pass through, emphasizing the importance of its mechanisms for retaining nutrients while preventing the accumulation of unwanted substances.


Input: Task: corroborate the claim using the given text. Claim: The impact craters on the Moon provide insights into the history of the solar system. [SEP] Text: The formation of a central impact melt basin is reliably observed in simulations of lunar and Martian impact basins (Ivanov et al. , 2010; Potter et al. , 2012). From the many parameters of hot rod geometry observed in the simulation, we selected the simplest parameter—the diameter of the hot rod at the assumed erosion level 20 km below the surface level at the moment of impact (Table 1). The largest craters on Venus, Mars, and Mercury show a limited range of modern depths in the range of 2–3 km. Therefore, it can be assumed that viscous relaxation of the original crater will not radically change the position of the “hot rod. ”Table 1. Model impact parameters: equivalent diameter of the spherical projectile Dpr (D-projectile), type of thermal gradient—cold or hot—and the main final parameters of the simulated impact structureFull size tablework began many years ago in discussion with Adam Garde, who proposed an impact origin for the Maniitsoq structure in Greenland (Garde et al. , 2011, 2012). Recent studies by Yakymchuk et al. (2021) argue against an impact origin of this structure. However, the question of the possibility of detecting terrestrial impact structures with a diameter of more than 200 km and an age of more than 2 billion years remains open. Numerical modeling predicts a long-lived impact melt “lake” in the central part of a fairly large crater; this is partly evidenced by geological structures in the eroded Sudbury crater, Canada (Grieve and Therriault, 2000). Independent numerical simulations of the formation of terrestrial impact craters with a diameter of about 300 km (Trowbridge et al. , 2017) generally confirm the results of this work. In addition, the model results are consistent with the geology of large impact craters observed on Venus, Mercury, and Mars from spacecraft. However, additional research is needed to assess the possibility of preserving the remains of terrestrial impact craters of large size and age more than 2 billion years, taking into account erosion and terrestrial tectonics. 686. L. , Landeau, M. , Röhlen, R. , Maller, A. , Nakajima, M. , and Wünnemann, K. , Planetary impacts: Scaling of crater depth from subsonic to supersonic conditions, J. Geophys. Res. [SEP] Justify:

Output: The text corroborates the claim by discussing the process of impact cratering and its implications for understanding planetary geology. It mentions 'numerical modeling predicts a long-lived impact melt “lake” in the central part of a fairly large crater,' indicating the significance of impact craters in studying both lunar and Martian cratering processes, thereby providing insights into the broader history of impact events in the solar system.


Input: Task: contrast the claim using the given text. Claim: Neuroethologists can instantly determine the intelligence of any animal. [SEP] Text: Given that, a few alternatives have been suggested, such as the “coffee test,” “robot college test” and “flat pack furniture test. ” Taken together, these attempts at tests show our limited understanding of the nature of general intelligence itself. Furthermore, there are many people who could not pass various tests because of physical or cultural differences but otherwise seem to be generally intelligent. And none of these tests seem to address some questions that most children are good at, such as “what will happen next? ” But even with these tests, where would we place a system that can pass the robot college test but is too clumsy to make a cup of coffee? This means that we will continue to argue about whether AGI has been achieved for perhaps a decade after credible experts begin saying that it has been reached. By that time, systems will have surpassed human abilities in so many areas that we will be forced to agree that some sort of AGI has been created. AGI is Inevitable and As we learn more and more about brain function, the only argument against the eventual creation of AGI is that the human mind contains some fundamental “magic” that is outside the scope of physical systems, which we can replicate in nonbiological systems. That position aside, if all of today’s more specialized, individually marketable AI systems were built on a common underlying data structure, they could begin to interact with each other, building a broader context that can actually understand and learn. As these systems become more advanced, they will be able to work together to create a more general intelligence that approaches the threshold for human-level intelligence, then equals it, and eventually surpasses it. Perhaps only then will we humans begin to acknowledge that yes, maybe AGI does exist. It is inevitable because market forces eventually will prevail. All we are waiting for are the insights needed to make it work. When will that happen? Some experts say it will take hundreds of years before we know how the brain works, what its algorithms are and what its capacity is, but I would suggest that it is only a matter of time before we shift from our current dependence on bigger and bigger data sets and recognize that to approach true understanding, we must address the brain knowledge gap. Me to ChatGPT: Are you an AGI? ChatGPT: No, I am not an AGI. [SEP] Justify:

Output: The text contrasts the claim by discussing the challenges in determining intelligence through various tests and suggesting that our understanding of general intelligence is limited. It states that tests like the 'coffee test' or 'robot college test' are inadequate and do not account for the complexity of intelligence, emphasizing that there is still much debate and uncertainty surrounding the concept of intelligence. This indicates that neuroethologists cannot simply or instantly determine intelligence, as the text highlights the nuances and limitations in existing methods.


Input: Task: pass the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: The principles involved in balancing inputs and outputs and what is meant by “clearance” are both considered more fully in Sect. 6. The relationship between rates of elimination, clearances, permeability-area products, volumes of distribution and half-lives together with the units used are described in 3. 2). The exact ways in which perivascular influx and efflux of solutes and water take place have been controversial as considered in some detail in Sect. 3. Tarasoff-Conway et al. [52] have addressed the issue of perivascular clearance with particular regard to one particular solute, amyloid-β. Brinker et al. [53], Hladky and Barrand [41], Simon and Iliff [39], Coles et al. [1], Abbott et al. [40], and Benveniste et al. [54] have summarized the evidence concerning perivascular transport from various perspectives. Transport across the blood–brain barrier is the dominant mechanism for removal of water and CO2 from brain parenchyma (for discussion and 4. 2). Certain larger solutes, e. g. insulin [59], transferrin [60, 61] and β-amyloid [62], may be transported across the blood–brain barrier by transcytosis [36, 63, 64] (see Sect. 4. 3). Many of the transporters found at the blood–brain barrier are capable of mediating not only efflux but also influx and have been studied more thoroughly from this standpoint. Other transporters, e. g. the ABC efflux pumps that are present in the luminal membranes of the endothelial cells (see Sect. 4. 2. 1), transfer many exogenous substances in an outward direction from endothelial cells to blood fuelled by the energy derived from ATP hydrolysis. This outward movement serves to decrease blood-to-brain influx as substances that enter the endothelial cells (or even just the luminal membranes of the cells) are returned to blood before they enter the brain proper. ABC transporters may also promote brain-to-blood efflux if there is some means for the substances to enter the endothelial cells across the abluminal membranes (see Sects. 4. 2. 1 and 4. 2. 2). 3 Perivascular pathways3. [SEP] Justify:

Output: The text is largely focused on the mechanisms of solute transport across the blood-brain barrier and discusses concepts like clearance and efflux/influx of various substances. While it includes information about transporters that influence the movement of substances, it does not explicitly support or contrast the claim that 'the blood-brain barrier protects the brain from harmful substances.' Thus, the text is considered irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: The impact craters on the Moon provide insights into the history of the solar system. [SEP] Text: 1 IntroductionCrater counting is a key tool in the arsenal of planetology. Many planets, moons, asteroids, comets, etc. are pocked to a greater or lesser extent with impact craters, whose areal density and distribution reveals much about the geologic and dynamical history of the target. Impact craters come in two main types: primary and secondary. Primary craters are made by the impact of interplanetary objects, at speeds greater than the target’s escape speed, and produce primary ejecta. Secondary craters are made by the re-impact of ejecta from primary craters, at speeds less than the target’s escape speed, and produce secondary ejecta. An intermediate type also has been described: Dobrovolskis and Lissauer (2004) originally dubbed them “poltorary” craters, after the Slavic word for “one and a half”; but Zahnle et al. (2008) re-labeled them “sesquinary”, after the corresponding Latin term. Sesquinary craters are produced by impacts of circum-planetary debris on planets or their satellites, at speeds greater than the target’s escape speed, but less than the speed of interplanetary bodies. It is often difficult to distinguish among these types of craters. Sometimes primary and secondary craters can be distinguished by morphology; e. g. , ellipticity, depth/diameter ratios, rim sharpness, ejecta blankets, blocks, chains, rays, herringbone patterns, etc. (Melosh (1989)). This paper presents another criterion which may help to distinguish among the different crater populations. This paper shows that the interior of a crater should have a lower density of smaller impact craters per unit area than nearby plains would have, because the impacts are spread out over a larger surface area, and because the crater’s wall partially shields its interior. Inside a crater shaped like a spherical bowl (a spherical cap turned upside-down), smaller primary (and sesquinary) impact craters should be spread uniformly, but the distribution of secondary craters is more complicated, usually concentrated near the center. These results may help to distinguish between populations of primary and secondary craters, and should be of interest for interpreting counts of craters within craters. The next section describes the cratering model used to obtain these results. [SEP] Justify:

Output: The text corroborates the claim by explaining that crater counting is a key tool in planetology, revealing much about the geologic and dynamical history of celestial bodies, including the Moon. It discusses the impact craters' types and their significance, suggesting that their distributions and characteristics can provide insights into the body's history, directly supporting the claim regarding the impacts craters on the Moon.


Input: Task: pass the claim using the given text. Claim: Neuroethologists can instantly determine the intelligence of any animal. [SEP] Text: | Effects of prenatal restraint stress on hypothalamic–pituitary–adrenocortical and sympatho–adrenomedullary axis in neonatal pigs. Crossref | GoogleScholar369. | Placental restriction in multi-fetal pregnancies and between-twin differences in size at birth alter neonatal feeding behaviour in the sheep. Crossref | GoogleScholar612. | Effects of oral doses of corn oil and other factors on preweaning survival and growth of piglets. Crossref | GoogleScholar1306. | Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations. Crossref | GoogleScholar1254. | The effect of birth weight on glucose tolerance in pigs at 3 and 12 months of age. Crossref | GoogleScholar348. | Insulin sensitivity in juvenile and adult pigs of low and high birthweight. Crossref | GoogleScholar868. | Effects of birth weight on growth and carcass composition of swine. Crossref | GoogleScholar70. | Variation of piglets’ birth weight and consequences on subsequent performance. Crossref | GoogleScholar123. | Consequences of birth weight for postnatal growth performance and carcass quality in pigs as related to myogenesis. Crossref | GoogleScholar285. | Effects of maternal nutrition and porcine growth hormone (pGH) treatment during gestation on endocrine and metabolic factors in sows, fetuses and pigs, skeletal muscle development, and postnatal growth. Crossref | GoogleScholar203. | Corticosterone in chicken eggs. Crossref | GoogleScholar141. | The role of maternal nutrition, metabolic function and the placenta in developmental programming of renal dysfunction. Crossref | GoogleScholar1243. | Compensatory growth in runt pigs is not mediated by insulin-like growth factor I. Crossref | GoogleScholar53. | IFPA award in placentology lecture: complicated interactions between genes and the environment in placentation, pregnancy outcome and long term health. Crossref | GoogleScholar1442. | Meat science and muscle biology symposium: developmental programming in cattle: consequences for growth, efficiency, carcass, muscle, and beef quality characteristics. Crossref | GoogleScholar98. | Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Crossref | GoogleScholar440. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses various studies on physiological and developmental aspects related to pigs and chickens without any mention of neuroethology or the ability to determine intelligence in animals. Therefore, it does not provide corroborative or contrasting information regarding the claim.


Input: Task: pass the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: 1 Routes of perivascular effluxSome of the possible routes for perivascular movements of solutes are indicated in Fig. 5. Whether or not actual fluid filled spaces exist around the blood vessels, it is believed that substances can move along preferential routes parallel to the blood vessels. (The description that follows is primarily for grey matter. As suggested originally by Rosenberg et al. in 1980 [65] there are likely to be preferential routes for fluid movement parallel to axons in white matter. It should also be noted that there may be regional variations, see e. g. [66, 67]). The idea that the basement membranes of microvessels can provide a preferential route stems from observations that when horseradish peroxidase is introduced into CSF with consequential influx along arteries the peroxidase is found to be localized in the basement membranes around microvessels. The idea has subsequently been supported by similar observations for other macromolecules (see e. g. [16, 68,69,70,71,72]). However, calculations by Asgari et al. [73] imply that unless the matrix of the microvascular basement membranes has a resistance substantially less than a sleeve of ®Matrigel with the same dimensions, they will not provide a preferential route for fluid flow parallel to the microvessels. A preferential route for movement along the vessels does not conflict with the movements of solutes outward by diffusion into the surrounding interstitial fluid. Regardless of whether or not the microvessel basement membranes provide a route with relatively low resistance, the distance from anywhere in the parenchyma to the nearest larger vessel is still likely to be relatively small, e. g. 100–200 µm. (Striking images of the vascular tree can be seen in [72]). For distances this short, diffusion is expected to be the dominant mechanism of extracellular movement [16, 24, 72, 74,75,76,77,78,79,80,81]. Fig. 5Diagram indicating putative perivascular routes for substances to move into, out of and through the brain parenchyma. [SEP] Justify:

Output: The text discusses various routes of solute movement in and around the brain's microvessels but does not address the claim about the protective function of the blood-brain barrier. It focuses on the mechanics of fluid movement rather than the barrier's role in protecting the brain from harmful substances, making it irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: The number of identified peptides was 122 213. Furthermore, 16 129 identified peptides were analysed using the matching results, 15 436 unique peptides were analysed using the matching results, 2733 identified proteins were analysed using specific peptides, and 1772 identified proteins were quantified using specific peptides. Differential protein screening In total, 313 (156 upregulated and 157 downregulated) differentially expressed proteins were screened using the tear samples. diagram, principal component analysis plot, and differential protein volcano map for protein identification of the two groups of the samples are shown in Fig. 1. GO and KEGG pathway enrichment analyses Figures 2 and 3 show the results of GO and KEGG pathway enrichment analyses for DK-related proteins, respectively. Protein interaction network diagram Figure 4 shows the protein interaction map screened from the top 50 most closely related proteins. Voltage-dependent anion-selective channel protein-3 (VDAC3) was selected as the predicted protein (marked with a green circle). Figure 5 presents the protein interaction network indicating the proteins most closely related to VDAC3. DiscussionWe conducted tear analysis on patients with diabetic retinopathy with and without DK. We identified 16 129 peptides and 2733 proteins through 4D label-free mass spectrometry. After screening, we identified 313 differential proteins, including 156 that were significantly upregulated and 157 that were significantly downregulated. Age,19 sex,20 courses of diabetes,21,22 glycosylated haemoglobin,23 and dry eye24–26 affect the results of tear proteome mass spectrometry. Therefore, we ensured the consistency of these confounding factors between the case and control groups. We identified several differentially expressed proteins related to DK and wound healing, including signal transducer and activator of transcription 3,27,28 epoxide hydrolase 2,29 and lacritin. 30 GO is a vital bioinformatics tool used to uniformly describe the characteristics of genes and gene products in all species. 31 Proteomics analysis is used to describe protein functions and trends in protein data sets. 32 Herein, GO enrichment analysis revealed that the differentially expressed proteins were mainly involved in mRNA catabolism, nuclear transcription, and receptor-mediated endocytosis. Proteomic data often contain a large amount of information; moreover, many protein complexes are involved in pathways and are likely to be regulated by the same mechanism. [SEP] Justify:

Output: The text corroborates the claim by discussing various aspects of proteomics, such as the identification and analysis of peptides and proteins through methodology like mass spectrometry. It mentions the identification of proteins and their roles in specific biological processes, which aligns with the definition of proteomics as the study of the entire set of proteins expressed in a system.


Input: Task: contrast the claim using the given text. Claim: All behaviors can be understood solely through neural circuitry. [SEP] Text: Finally, they also demonstrate that the synaptic assembly is impaired in the sema7a mutant. Overall, the data are of high quality and properly controlled. The availability of Sema7a antibody is a big plus, as it allows to address the endogenous protein localization as well to show the signal absence in the sema7a mutant. The quantification of the arbor topology should be useful to people in the field who are looking at the lateral line as well as other axonal terminals. #3 (Public Review): The data reported here demonstrate that Sema7a defines the local behavior of growing axons in the developing zebrafish lateral line. The analysis is sophisticated and convincingly demonstrates effects on axon growth and synapse architecture. Collectively, the findings point to the idea that the diffusible form of sema7a may influence how axons grow within the neuromast and that the GPI-linked form of sema7a may subsequently impact how synapses form, though additional work is needed to strongly link each form to its' proposed effect on circuit assembly. Comments on latest version: The authors comprehensively and appropriately addressed most of the reviewers' concerns. In particular, they added evidence that hair cells express both Sema7A isoforms, showed that membrane bound Sema7A does not have long range effects on guidance, demonstrated how axons behave close to ectopic Sema7A, and analyzed other features of the hair cells that revealed no strong phenotypes. The authors also softened the language in many, but not all places. Overall, I am satisfied with the study as a whole. #4 (Public Review): ** This study provides direct evidence showing that Sema7a plays a role in the axon growth during the formation of peripheral sensory circuits in the lateral-line system of zebrafish. This is a valuable finding because the molecules for axon growth in hair-cell sensory systems are not well understood. The majority of the experimental evidence is convincing, and the analysis is rigorous. The evidence supporting Sema7a's juxtracrine vs. secreted role and involvement in synapse formation in hair cells is less conclusive. The study will be of interest to cell, molecular and developmental biologists, and sensory neuroscientists. response: The following is the authors’ response to the previous reviews. [SEP] Justify:

Output: The text contrasts the claim by providing evidence that while the findings on Sema7a indicate its role in axon growth and synaptic architecture, it does not assert that all behaviors can be explained solely by neural circuitry. The mention of additional work needed to link Sema7a's effects on circuit assembly to specific behaviors suggests that understanding behavior is more complex and may involve factors beyond neural circuitry alone.


Input: Task: pass the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: The lumens of arteries, arterioles, venules and veins are surrounded by a layer of endothelial cells with a basement membrane, then a layer of vessel wall including smooth muscle, and outside that there may be a further perivascular space with fluid and connective tissue bounded by basement membranes of the smooth muscle, pial and glial cells. Close to the surfaces of the brain these further spaces are often called Virchow-Robin spaces. Movements parallel to the large vessels may be intramural, through the extracellular space of the vessel wall, or extramural either in the outermost basement membranes or, in the opinion of some workers, in a fluid filled space. In this review both intramural and extramural pathways are called perivascular routes. Parallel to microvessels movement may be preferentially within the basement membrane separating the endothelial cells from the glial endfeet or it may be more diffuse through the interstitial spaces between the parenchymal cellsFull size imageMarkers for perivascular transport clearly have perivascular pathways for entry and exit from the parenchyma, but there is controversy as to whether efflux, influx or both occur along arteries and/or veins (for discussion see [16, 39, 41, 52, 72]). Efflux along arteries has been seen in many studies (e. g. [70, 82,83,84,85,86,87,88]) with substances even reaching the large arteries near the circle of Willis [82], and influx has also been seen in many studies [15, 16, 25, 69, 71, 79, 84, 88,89,90,91,92]. Evidence of influx along some vessels was obtained as early as 1960 [93]. Perivenous influx [16] and efflux [25, 69, 84, 94] have been reported. Efflux along unspecified blood vessels has also been seen [79]. The available evidence suggests that both influx and efflux occur along both arteries and veins [41, 78, 95] either via common pathways or separately along parallel pathways [88, 95] (see Proposal 2 below). In Fig. 5 movements are shown as occurring in both directions along both. [SEP] Justify:

Output: The text discusses the structure and function of vascular pathways and blood vessels surrounding the brain, including efflux and influx of substances. However, it does not explicitly address the claim about the role of the blood-brain barrier in protecting the brain from harmful substances. Therefore, it is considered irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: Rapid advances in proteomic technology have led to the identification of several novel protein biomarkers related to both SLE and lupus nephritis (LN); these include monocyte chemoattractant protein-1 (MCP-1) (Marks et al. , 2010), the tumor necrosis factor-like weak inducer (TWEAK) (Schwartz, Michaelson & Putterman, 2007), transferrin (Suzuki et al. , 2007), various interleukins and TNF-α (Almoallim et al. , 2012) proteins. However, these organ-specific biomarkers do not serve only as markers of lupus and of primary organ participation in lupus. Despite tremendous basic and clinical research progress regarding biomarkers discovery, SLE remains an unsolved puzzle due to a lack of appropriate disease monitoring and the absence of predictive/diagnostic biomarkers. Thus the quest for such markers is still continuing. Human serum/plasma holds abundant information on the physiological and pathological states of an individual’s body, and as a result, such samples can provide valuable clinical parameters (Anderson & Anderson, 2002). Consequently, they have enormous potential in terms of revealing disease conditions and they also hold the promise of a revolution in disease diagnosis and therapeutic monitoring. Moreover, plasma is a very rich source of proteins and tissue leakage with the presence of interleukins (Anderson & Anderson, 2002). The protein alterations in a diseased plasma sample may provide clues and potential clinical parameters that should help us to understand both the pathogenesis of a disease, as well as diagnosis. Significant advances in proteomic technologies now allow the comprehensive profiling of protein expression levels in biofluids from patients with a given disease (Hu, Loo & Wong, 2006). Furthermore, mass spectrometry technologies have become a significant approach in clinical proteomics which allows the exploration in depth of an illness and its underlying mechanisms. Tandem mass spectrometry (MS/MS) coupled with multidimensional liquid chromatography (LC) together with database searching has emerged as a robust technique that allows protein identification and characterization. [SEP] Justify:

Output: The text corroborates the claim by discussing significant advances in proteomic technologies that enable comprehensive profiling of protein expression levels in biofluids, which aligns with the definition of proteomics as the study of proteins expressed in a cell. Moreover, it mentions the use of mass spectrometry coupled with other techniques for protein identification and characterization, further supporting the claim's assertion about the focus of proteomics.


Input: Task: contrast the claim using the given text. Claim: All behaviors can be understood solely through neural circuitry. [SEP] Text: eLife assessment Dasgupta and colleagues make a valuable contribution to the understanding how the guidance factor Sema7a promotes connections between mechanosensory hair cells and afferent neurons of the zebrafish lateral line system. The authors provide solid evidence that loss of Sema7a function results in fewer contacts between hair cells and afferents through comprehensive quantitative analysis. Additional work is needed to distinguish the effects of different isoforms of Sema7a to determine whether there are specific roles of secreted and membrane bound forms. Public Reviews: Reviewer #1 (Public Review): Dasguta et al. have dissected the role of Sema7a in fine tuning of a sensory microcircuit in the posterior lateral line organ of zebrafish. They attempt to also outline the different roles of a secreted verses membrane-bound form of Sema7a in this process. Using genetic perturbations and axonal network analysis, the authors show that loss of both Sema7a isoforms causes abnormal axon terminal structure with more bare terminals and fewer loops in contact with presynaptic sensory hair cells. Further, they show that loss of Sema7a causes decreased number and size of both the pre- and post-synapse. Finally, they show that overexpression of the secreted form of Sema7a specifically can elicit axon terminal outgrowth to an ectopic Sema7a expressing cell. Together, the analysis of Sema7a loss of function and overexpression on axon arbor structure is fairly thorough and revealed a novel role for Sema7a in axon terminal structure. However, the connection between different isoforms of Sema7a and the axon arborization needs to be substantiated. Furthermore, the effect of loss of Sema7a on the presynaptic cell is not ruled out as a contributing factor to the synaptic and axon structure phenotypes. These issues weaken the claims made by the authors including the statement that they have identified dual roles for the GPI-anchored verses secreted forms of Sema7a on synapse formation and as a chemoattractant for axon arborization respectively. Reviewer #2 (Public Review): In this work, Dasgupta et al. investigates the role of Sema7a in the formation of peripheral sensory circuit in the lateral line system of zebrafish. [SEP] Justify:

Output: The text contrasts the claim by discussing the role of Sema7a in the formation and function of sensory circuits in zebrafish, indicating that while neural circuitry plays a significant role, the authors acknowledge the need for additional work to understand the contributions of different isoforms of Sema7a. This implies that behaviors may not solely be understood through neural circuitry, as other factors and mechanisms (like the influence of specific proteins and their isoforms) are also crucial, suggesting a more complex interplay beyond just neural circuitry.


Input: Task: pass the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: There has also been disagreement over which of the structural components of the arteries provide the principal routes for periarterial transport with some favouring an extramural, fluid filled perivascular space, possibly containing connective tissue fibres [16], between the vessel walls and the astrocyte endfeet, see e. g. [25, 71, 78, 79, 81, 83,84,85, 87, 92, 96]Footnote 5 while others favour the view that “perivascular spaces” are not fluid filled, free spaces but rather perivascular pathways via basement membranes either within the smooth muscle layer or on the outside surface of the artery [52, 70, 72, 88, 97,98,99] (see Fig. 5). Free spaces may be highly compressible, allowing modest changes in pressure to change their dimensions as envisaged in the proposal that variations in the blood pressure within the vessels somehow drive perivascular movements. By contrast basement membranes are likely to be much less compressible and are likely to offer much greater resistance to flow (see [73, 100, 101]), thus precluding blood pressure variations as the driving force for perivascular flow (see next section). Diem et al. [100] have proposed vasomotion as an alternative. Pizzo et al. [16] have suggested that both basement membrane routes and other, extramural routes exist with their relative importance depending on the size of vessel and the size of the solute. Another proposed variation is a hybrid with an extramural basement membrane route mediating fluxes into the brain and an intramural basement membrane route between smooth muscle cells mediating fluxes outwards [88, 95]. It is quite evident that solutes even as large as amyloid-β have access to the basement membranes between the smooth muscle cells (see e. g. [16, 70, 93, 102]), but it is not known whether the solutes reach these locations via an intramural route with movement along basement membranes as favoured by Carare, Weller, Hawkes and colleagues [70, 88, 95] or via extramural pathways with subsequent penetration from these into the basement membranes within the vessel wall (see Figure 21 in Sect. 5. 7. 1. 2) or some mixture of the two. Arbel-Ornath et al. [SEP] Justify:

Output: The text discusses various structural components of arteries and their roles in perivascular transport but does not directly address the claim about the blood-brain barrier Protections. Therefore, it is irrelevant to the claim.


Input: Task: pass the claim using the given text. Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: The digested plasma samples were run in triplicate and the data were analyzed by ProteinServer 4. 2 software (PLGS; ) (Aggarwal et al. , 2017). Each sample was injected three times to obtain technical triplicates. Label-free quantification To quantify the proteins from the LC-MS/MS, a label-free quantification analysis was performed using 8. 0 (Inc. , ) (Zhang et al. , 2012). Independent samples from each triplicate analysis were studied and compared between patients and the controls. Total raw data files were imported and processed using the Peaks software program for the interpretation of spectra and the retention time was set from 600 to 10,500 s. An in-house constructed Uniprot’s reference database of Homo sapiens (release 03_2014) contained 20,272 entries was added and combined with a decoy database (the sequences were reversed). For label-free quantification the following parameters were specified: enzymatic digestion by trypsin, with two missed cleavages; precursor mass tolerance was 10 ppm; fragment mass tolerance: 0. 7 Da, minimum charge: 2, maximum charge: 3. The specified fixed and variable modification consisted of carbamidomethylation (Cys), oxidation (M), and deamidated (N and Q). To determine the false-positive identification rate, the estimated spectra was used against decoy database. A false discovery rate (FDR) of ≤1%, with a peptide score of −10 log p ≥ 20 was considered adequate for confident protein identification. To determine the relative protein and peptide abundance in the tested samples, peptide feature based quantification was performed. The signal intensity of a peptide is directly proportional to the abundance of the peptide in the sample, therefore, the confidently identified peptide features were matched and the peptide intensity differences between two samples were able to be estimated. Likewise, the area under the curve of the extracted ion chromatograms (XICs) was measured and compared between two analyzed runs. To get the summed cumulative peak area of the protein, only unique peptides that are assigned to particular proteins were selected. The FDR was calculated based on the target/decoy database, and the peptides with an FDR of ≤1% were chosen as true positive hits (considering the risk of having one false positive in 20 observations). [SEP] Justify:

Output: The text provides a detailed description of a method used for protein quantification in samples but does not directly address or support the claim regarding the overall focus of proteomics on studying the entire set of proteins expressed in a cell. The methodologies described are relevant to proteomics but do not explicitly corroborate the claim that proteomics encompasses the entire set of proteins.


Input: Task: contrast the claim using the given text. Claim: All behaviors can be understood solely through neural circuitry. [SEP] Text: They show that Sema7a protein is present during neuromast maturation and localized, in part, to the base of hair cells (HCs). This would be consistent with pre-synaptic Sema7a mediating formation and/or stabilization of the synapse. They use sema7a loss-of-function strain to show that lateral line sensory terminals display abnormal arborization. They provide highly quantitative analysis of the lateral line terminal arborization to show that a number of specific topological parameters are affected in mutants. Next, they ectopically express a secreted form of Sema7a to show that lateral line terminals can be ectopically attracted to the source. Finally, they also demonstrate that the synaptic assembly is impaired in the sema7a mutant. Overall, the data are of high quality and properly controlled. The availability of Sema7a antibody is a big plus, as it allows to address the endogenous protein localization as well to show the signal absence in the sema7a mutant. The quantification of the arbor topology should be useful to people in the field who are looking at the lateral line as well as other axonal terminals. I think some results are overinterpreted though. The authors state: "Our findings demonstrate that Sema7A functions both as a juxtracrine and as a secreted cue to pattern neural circuitry during sensory organ development. " However, they have not actually demonstrated which isoform functions in HCs (also see comments below). In addition, they have to be careful in interpreting their topology analysis, as they cannot separate individual axons. Thus, such analysis can generate artifacts. They can perform additional experiments to address these issues or adjust their interpretations. Reviewer #3 (Public Review): The data reported here demonstrate that Sema7a defines the local behavior of growing axons in the developing zebrafish lateral line. The analysis is sophisticated and convincingly demonstrates effects on axon growth and synapse architecture. Collectively, the findings point to the idea that the diffusible form of sema7a may influence how axons grow within the neuromast and that the GPI-linked form of sema7a may subsequently impact how synapses form, though additional work is needed to strongly link each form to its' proposed effect on circuit assembly. The revised manuscript is significantly improved. The authors comprehensively and appropriately addressed most of the reviewers' concerns. [SEP] Justify:

Output: The text contrasts the claim by discussing the role of the Sema7a protein in neural circuitry and synapse formation, indicating that while there are connections, the data suggest complexities in behavior that may not be solely attributable to neural circuitry. Specifically, the text notes that the interpretation of topology analysis may generate artifacts and highlights the need for additional experiments to clarify the effects on circuit assembly, suggesting that behaviors could involve more factors beyond just neural circuitry.


Input: Task: pass the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: [87] used two-photon imaging to investigate the position of a 3 kDa fluorescent dextran during efflux following injection into the parenchyma. Shortly after injection they saw fluorescence within the parenchyma, in perivascular spaces surrounding small arteries and, at lower concentration, between the smooth muscle cells. There has been controversy about the nature of the connections between the perivascular spaces adjacent to larger blood vessels within the parenchyma, the CSF and the perivascular spaces of the vessels passing through the subarachnoid spaces [1, 16, 25, 54, 71, 72, 81, 103,104,105,106,107,108,109]. However, whatever the exact perivascular pathway used, solutes exiting from the parenchyma along perivascular routes appear to be effluxed partly to CSF in the basal cisterns or subarachnoid spaces and partly to the outer meninges [85] and/or lymphatics [94, 107, 109,110,111,112,113,114,115]. Movement of small solutes and water does take place between fluid in the subarachnoid space and fluid within the perivascular spaces (see Section 4. 1. 1. 1 of [41]). However a substantial proportion of perivascular efflux of large solutes appears to pass to lymph without first appearing in CSF in the cisterna magnaFootnote 6 (see Fig. 6) [16, 39, 52, 82, 83, 94, 96, 105, 107, 111, 115,116,117,118,119]. Fig. 6Schematic diagram indicating possible routes for efflux of large solutes from the parenchyma along perivascular routes. a Large solutes emerging from the parenchyma via intramural or extramural routes along arteries (and possibly veins) may either mix with CSF or continue along the walls of blood vessels. The blood vessels span the subarachnoid space (see Figs. 1 and 6) before leaving the brain to reach the rest of the body. The fluid that continues along these vessels may enter either blood or lymph, but solutes as large as serum albumin will enter only lymph. [SEP] Justify:

Output: The text discusses the movement of substances within the cerebrospinal fluid and perivascular spaces but does not provide information directly supporting or opposing the claim about the blood-brain barrier's protective function. It offers details about the efflux of solutes and their routes but lacks a clear connection to the claim regarding the barrier's protective abilities.


Input: Task: corroborate the claim using the given text. Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: By using this active feature based quantitative approach the detected peptides with p-values <0. 05 and 0. 01 which were identified in at least three observations from the SLE samples compared to control samples were considered. In order to identify the significant protein differential expressions an independent sample T-test was performed. The quantified datasets were normalized using their spectral abundance factor values (the average of the triplicate experiments) and this was used to generate a heat map showing the differentially expressed proteins between the two groups. Quantification of altered proteins by emPAI To acquire confident results from our proteomic study, the widely used exponentially modified protein abundance index (emPAI) was employed as an alternative method in order to quantify the differences in abundances of the identified proteins between the SLE patients and the control subjects. Numerous label-free relative quantification studies have successfully applied the formula derived for emPAI and developed by Ishihama et al. (2005). Specifically, the database results were generated in an Excel file (composed of emPAI, protein description, peptide identifications, the charge states of the peptides, etc. ), and this was uploaded to the freely accessible ( web-based system ( for emPAI evaluation. The following parameters were specified on the emPAI website: IPI_HUMAN database, trypsin digestion as the enzyme, carbamidomethyl (Cys) fixed modifications, mass range 500–3,000 Da, and no retention time filtering. The uploaded sample files were analyzed and the results were exported to a separate file. To estimate the protein abundances, the mean emPAI values of the triplicate MS analyses from patients and controls were calculated and Hochberg and Benjamini calculation of FDR (p < 0. 05) was applied to correct for multiple testing errors. Protein level fold-difference was calculated from the relative means of normalized emPAI values and the fold change differences were estimated from all replicates, with the Student’s t-test (two-tailed, heteroscedastic) applied to the same values. A minimum of three unique peptide sequences in at least three replicates were required for quantification. [SEP] Justify:

Output: The text corroborates the claim by discussing the methods used to analyze and quantify proteins in a proteomic study. It refers to the use of statistical tests and quantification techniques to assess protein expressions in samples, which aligns with the definition of proteomics as the study of the entire set of proteins expressed in a cell.


Input: Task: contrast the claim using the given text. Claim: All behaviors can be understood solely through neural circuitry. [SEP] Text: In particular, they added evidence that hair cells express both Sema7A isoforms, showed that membrane bound Sema7A does not have long range effects on guidance, demonstrated how axons behave close to ectopic Sema7A, and analyzed other features of the hair cells that revealed no strong phenotypes. The authors also softened the language in many, but not all places. Overall, I am satisfied with the study as a whole. Reviewer #4 (Public Review): This study provides direct evidence showing that Sema7a plays a role in the axon growth during the formation of peripheral sensory circuits in the lateral-line system of zebrafish. This is a valuable finding because the molecules for axon growth in hair-cell sensory systems are not well understood. The majority of the experimental evidence is convincing, and the analysis is rigorous. The evidence supporting Sema7a's juxtracrine vs. secreted role and involvement in synapse formation in hair cells is less conclusive. The study will be of interest to cell, molecular and developmental biologists, and sensory neuroscientists. Recommendations for the authors: Reviewer #1 (The Authors): In their revised manuscript, Dasgupta et al. have provided further experiments to address the role of Sema7a (sec and GPI-anchored) in regulating axon guidance in the lateral line system. Specifically, the inclusion of the heat shock controls and FM labeling to show hair cell mechanotransduction were crucial to interpretation of the results. However, there are still concerns about the specificity of the results. My primary concern is if the change in axon patterning is specifically due to loss of Sema7a in the mutant hair cells. These animals are morphologically very abnormal and, in the rebuttal, the authors state that hair cell number is reduced. This is not quantified in the manuscript and should be included. Thank you for this suggestion. We have included the data in the manuscript in lines 137-139, in Figure 2—figure supplement 1B, and in the source data for Figure 2 and Figure 2-figure supplements. If there is not a function for Sema7a in hair cells themselves, why is the number reduced? The sema7a-/- homozygous mutants are not viable and they die by 6 dpf. The loss of Sema7A protein produce other developmental defects including brain edema and a curved body axis. [SEP] Justify:

Output: The text contrasts the claim by detailing a study focused on Sema7A's role in axon growth and sensory circuit formation. It discusses developmental defects such as brain edema and provides evidence that the loss of Sema7A leads to significant morphological abnormalities and affects the viability of mutants. This suggests that behaviors and developmental outcomes cannot be fully understood by neural circuitry alone, as other factors (like gene expression and developmental pathways) are also crucial.


Input: Task: pass the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: b Large solutes that have reached CSF will be taken to sites of CSF outflow including the arachnoid villi, where the solutes will enter venous blood, and the cribriform plate, where they will enter lymph. (Based primarily on data for radio-iodinated serum albumin RISA [82, 83, 125] and on the location of the pia surrounding arteries taken from [103]). The anatomical relations of the pathways or spaces remain controversialFull size imageThose solutes that do reach CSF from the parenchyma can be taken out of the cranium via CSF outflow. Routes for CSF outflow were reviewed comprehensively by Pollay in 2010 [119] This outflow is partly via arachnoid villi, partly via perineural routes including those across the cribriform plate to the nasal mucosa [119,120,121] and possibly also via extra-parenchymal perivascular routes (see Fig. 6) [16, 81, 105, 111, 119, 122,123,124]. Outflow via arachnoid villi leads directly to venous blood while outflow via the cribriform plate may deliver solutes directly to lymphatics or to the extracellular fluid in the nasal mucosa [118, 121, 125]. Small solutes (e. g. lactate) and solutes even as large as inulin may leave the nasal mucosa by entering blood across peripheral capillary walls but larger solutes (e. g. albumin) will leave via lymph flow to cervical lymph nodes [125]. Outflow via other routes leads at least in part to lymph (see e. g. [111]). 3. 2 Mechanisms driving perivascular solute effluxDiffusion is not adequate for perivascular influx because substances added to CSF are found deep in the parenchyma much too quickly for diffusion over the distance involved, a millimeter or more [25, 68, 69, 84]. Similarly diffusion cannot account for efflux from parenchyma to CSF of substances like polyethylene glycol and dextran [126, 127], serum albumin [83], mannitol [25] or inulin [62, 128]. Thus alternative mechanisms have been proposed (see Fig. 7). Fig. [SEP] Justify:

Output: The text discusses the movement of solutes in relation to cerebrospinal fluid (CSF) outflow and pathways but does not directly address or provide evidence about the protective role of the blood-brain barrier against harmful substances. Therefore, it is considered irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: Here, we have attempted to use LC-ESI-MS/MS to identify proteins that show significant alterations in expression levels among 19 SLE patients compared to 12 healthy controls. In order to detect differentially expressed proteins in the individual SLE plasma samples compared to controls, the samples were analyzed in triplicates by LC-ESI-MS/MS with label-free quantitative analysis was performed using 8. 0 software. Apart from the use of this software, an emPAI method by Ishihama et al. was also used manually to obtain highly confident proteomic data. Both the quantitative analysis results were complimentary to each other in terms of protein abundance and the fold change. Table 2 shows the details about the number of MS/MS spectra, peptide and protein identification and quantitation of each SLE patient and healthy sample. The proteins which are identified in at least two of the three technical replicates were selected for the quantitation and statistical analysis. Table 2: Complete LC-MS/MS proteomic analysis details for peptide and protein identification and quantitation in each patient and healthy sample. SLE patients Total spectra* Distinct peptides* FDR spectra FDR distinct peptide (%) P1 169,115 38,918 0. 41 1. 21 P2 176,318 46,186 0. 43 1. 24 P3 165,812 35,981 0. 47 1. 29 P4 126,050 38,843 0. 45 1. 34 P5 169,295 37,918 0. 41 1. 49 P6 173,378 36,186 0. 43 1. 26 P7 165,812 39,991 0. 44 1. 25 P8 126,050 28,843 0. 42 1. 26 P9 149,295 37,918 0. 42 1. 27 P10 173,378 36,186 0. 43 1. 28 P11 161,812 35,881 0. 45 1. 44 P12 126,050 28,843 0. 44 1. 33 P13 169,295 37,918 0. 43 1. 35 P14 183,878 38,186 0. 42 1. 26 P15 165,812 35,981 0. 45 1. 24 P16 136,050 28,843 0. 45 1. 27 P17 169,295 47,918 0. 45 1. [SEP] Justify:

Output: The text corroborates the claim by detailing the use of LC-ESI-MS/MS for identifying proteins that exhibit significant alterations in expression levels among SLE patients and healthy controls. This aligns with the definition of proteomics as the study of the entire set of proteins expressed in a cell, as the text describes analyzing and quantifying various proteins in the samples.


Input: Task: contrast the claim using the given text. Claim: All behaviors can be understood solely through neural circuitry. [SEP] Text: (1) Although the authors say that they added appropriate no plasmid/heatshock-only and plasmid-only/no heatshock controls, these results need to be presented more clearly, as they are separated in the paper and only one was quantified (i. e. 100% of embryos showed no defect). Please just make it clear that no defects were observed in either control for either experiment (both secreted and membrane bound ectopic expression). We have clearly stated this information in lines 297-299 and 343-345. (2) Please add a compass to Fig. 1A to indicate the orientation of the neuromast. It would also be helpful to add labels for developmental ages to all of the figures, rather than making the reader look it up in the legend. We have updated the Figure 1A and the corresponding figure legend in lines 882883. We have denoted the larval age in the figure legends to keep the individual images uncluttered. (3) For the RT-PCR experiments in Figure 1, no negative control was included to show that supporting cell or neuronal genes are not detected in the purified hair cells and v. v. that neither isoform is detected in supporting cells or neurons. I ask only because there is a lot of immune-signal outside of the hair cells and I am curious whether that is secreted or might come from other cell types. For neurons and supporting cells, simply demonstrating absence of Sema7a overall would suffice. We have utilized the transgenic line Tg(myo6b:actb1-EGFP) that expresses the fluorophore GFP specifically in the hair cells of the neuromast. Unfortunately, we do not possess a transgenic line that reliably and specifically labels the support cells in the neuromast. Hence, in our sorting experiment the GFP-negative cells that are collected from the trunk segments of the larvae contain all the non-hair cells including epidermal cells, neuronal cells, and immune cells etc. Such a mixture of varied cellular identity may not serve as a reliable negative control. 7, we have plotted the normalized expression values of the sema7a gene in the neuromast. The plot clearly depicts that the source of Sema7A is the young and the mature hair cells, not the support cells. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations of relying solely on neural circuitry to understand behaviors. It mentions the complexity in determining the source of specific gene expressions and highlights that the presence of various cell types complicates the interpretation. It emphasizes that behaviors cannot solely be understood through neural circuitry, as other cellular types (like epidermal and immune cells) are involved and that a comprehensive understanding requires acknowledging these complexities.


Input: Task: pass the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: 7(Modified from Figure 9 in [41])Proposals to explain rapid transfer of markers via periarterial spaces: a the original proposal; b proposed perivascular convection and interstitial diffusion c the glymphatic proposal. In a the blood–brain barrier secretes fluid which flows out of the parenchyma via preferred routes (here the perivascular routes). In b transport in the perivascular spaces is assisted by convective stirring or mixing. In c (see Figure 5 of Iliff et al. [25]) there is preferential inflow via the space between the arterial wall and the pial sheath and preferential outflow via spaces surrounding veins. Red lines represent pial membranes, grey lines the layer of glial end-feet or glia limitans, black arrows are fluxes of markers carried or assisted by convection, green arrows are primarily diffusion. The location of the pial barriers is based on Zhang et al. [23]. The anatomical basis of the perivascular spaces remains controversialFull size image Proposal 1 The first proposal (Fig. 7a) was that secretion of fluid by the blood–brain barrier provides a small pressure gradient for outflow of ISF along preferential routes (see [83, 126, 127, 129, 130]). These routes could be perivascular spaces or the extracellular spaces parallel to the axons in nerve fibre tracts. When this proposal was put forward more than 30 years ago (see e. g. [83]) it was believed that the half-life for clearance of marker solutes by outflow was of the order of 12 h. However, all of these early studies were performed on animals anaesthetized using barbiturates. Using either conscious animals or those anaesthetized with ketamine/zylazine or halothane, the half-lives are much shorter, 2–4 h [25, 62, 85, 131]. Perivascular efflux of solutes is considerably faster than envisaged by Cserr and coworkers. It should also be pointed out that Proposal 1 does not and was never intended to provide any explanation for the rapid influx of solutes. 1 (and in Proposal 3, see below) the solutes are swept out of the parenchyma by the flow through the perivascular system. [SEP] Justify:

Output: The text does not directly address the claim about the blood-brain barrier's protective role against harmful substances. Instead, it discusses various proposals regarding the fluid dynamics and transport mechanisms across the blood-brain barrier, notably outlining concepts about fluid secretion and solute outflow. While it mentions the blood-brain barrier and its functions, it does not establish or refute its protective capabilities as suggested in the claim.


Input: Task: corroborate the claim using the given text. Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: The complete list of identified proteins and their fold change differences with both the quantitative analysis data among SLE patients and healthy controls were presented in Table S2. software generated a heat map of the differentially expressed proteins by comparing the patients and controls were shown in Fig. 2. The FDR specified for the identified proteins was <1%. The complete comparative proteomic analysis using PEAKS 8. 0 and emPAI quantitative evaluations of the up and down-regulated proteins were presented in Table 3. Figure 1: A representative LC-MS/MS base peak chromatogram. (A) SLE patients compared to (B) healthy controls. Download full-size image DOI: 10. 7717/peerj. 4730/fig-1 Figure 2: An overview of the plasma protein profile of the SLE patients. The heat map was generated using 8. 0 displaying the differentially expressed proteins identified using LC-MS/MS label-free proteomic analysis between SLE patients and controls. The color scale representing the relative expression level of each protein across SLE and controls; red and green colors indicate the higher and lower levels of expressions. The intensity of the color represents the degree of protein up- and down-regulation when SLE patients and controls are compared. Download full-size image DOI: 10. 7717/peerj. 4730/fig-2 Table 3: The list of statistically significantly up and down-regulated proteins (p < 0. 05, 0. 01) between SLE patients and healthy control plasma samples. Protein name Gene name Uniprot accessiona Mascot scoreb Matched peptidesc Msequence coveragee Average area of the triplicate analysisf Fold change SLE/controls EmPAI (triplicates average) EmPAI fold change Protein regulation Up(+), Down (−) Function p-valueg kappa chain C variable region 315_HUMAN 212 77 12. 49 42. 7 81657. 3 ± 30951. 1 28738. 8 ± 2422. 5 2. 84 0. 90 ± 0. 1 0. 382 ± 0. 01 2. 35 + Immune response and regulation 0. 04 Ig heavy chain G4 IGHG4 IGHG4_HUMAN 141 17 35. 4 23. 97 407207. 9 ± 142838. 3 118916. 6 ± 10435. 2 3. 42 0. [SEP] Justify:

Output: The text corroborates the claim by detailing a proteomic analysis, which involves identifying proteins and evaluating their expression levels in SLE patients compared to healthy controls. It mentions the identification of proteins, their differential expression, and heat maps representing protein profiles, all of which are essential elements of proteomics research focused on the entire protein set expressed in cells.


Input: Task: contrast the claim using the given text. Claim: All behaviors can be understood solely through neural circuitry. [SEP] Text: We have clarified this information in lines 310-311. (11) Finally, the discussion contains a statement that is not supported by the data: "We have discovered dual modes of Sema7A function in vivo. " They have discovered evidence that there are two isoforms, that loss of both disrupts connectivity, and that overexpression of only the secreted form can elicit growth from a distance. However, there is no direct evidence that the membrane-bound form is responsible for local effects. It is formally possible still that the phenotypes are a result of dual roles for the secreted form. It is clear that another manuscript is forthcoming that will expand on the role of the transmembrane form, but for this manuscript, the authors should make firm conclusions only about the data presented herein. Thank you for this suggestion. We have modified the manuscript in lines 425-434. Reviewer #4 (The Authors): The authors have made significant changes to the manuscript based on the comments of the reviewers. It is now suitable for publication. [SEP] Justify:

Output: The text contrasts the claim by discussing that, although dual modes of Sema7A function appear to have a role in behavior, there are complexities in understanding these roles. Specifically, the text indicates that the understanding of the function is not straightforward and emphasizes the lack of direct evidence linking the membrane-bound form of Sema7A to local effects, suggesting that behaviors cannot be fully explained by neural circuitry alone.


Input: Task: pass the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: Even the bottom of this range is somewhat more than twice the rate of production of CSF. There is no other reason to suspect that there is a rate of secretion of fluid across the blood–brain barrier that exceeds the rate of fluid secretion by the choroid plexuses (see Section 4. 1 in [4]). The rate of fluid secretion across the blood–brain barrier is very unlikely to be this large and is almost certain to be insufficient to account for perivascular clearance of solutes. Proposal 2 (Fig. 7b) The second suggestion, recently revived, is that convection in the perivascular spaces, arterial and possibly venous, leads to convective mixing of the fluid in the spaces allowing relatively rapid movements of solutes both inwards and outwards [41, 78, 82, 96, 132]. Such mixing probably presupposes that perivascular spaces are compressible. Convective mixing is perhaps better called dispersion [78]. Papisov [133] and Asgari et al. [134] discuss a similar effect in the spinal cord allowing transport of solutes down their concentration gradients against the direction of net flow of CSF and at rates much greater than allowed by diffusion. In this proposal diffusion is taken to be adequate to explain movements within the interstitial spaces in the parenchyma because the distances involved are sufficiently short (see Sect. 3. 2. 1). In this proposal (and in Proposal 3, see below), an important part of the mechanism is thought to be convection in spaces whose dimensions are changed by periodic compression resulting from the changes in blood pressure during the cardiac cycle [13, 25, 70, 82, 96, 132]. The length of space around a cortical vessel that is compressed at one time is as long as the vessel [78, 82]. Bradbury et al. [82] were of the opinion that periodic compression and reexpansion of this space “would cause to-and-fro movement of fluid in and out of the brain” such that “A basis would be provided for substances in solution or suspension to be moved either out of or into the brain depending on the relative concentration in subarachnoid CSF. ” Another variation on this theme may be possible if there are layers of differing compressibility, both connected via relatively low resistance pathways to the brain surface. [SEP] Justify:

Output: The text does not provide any information that directly supports or rebuts the claim regarding the blood-brain barrier's protective function. Instead, it discusses fluid secretion and potential mechanisms for the movement of solutes across the blood-brain barrier, but does not specifically address whether it protects against harmful substances.


Input: Task: corroborate the claim using the given text. Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: Therefore, the identified proteins are likely to play a significant role in SLE disease development and/or pathogenesis. Figure 4: Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis of the proteins identified showing differential expression. The majority of the identified proteins were enriched in relation to the complement and coagulation cascades and acute immune responses. The horizontal bars represent the number of differentially expressed proteins involved in various pathways. Download full-size image DOI: 10. 7717/peerj. 4730/fig-4 Additionally, the network analysis demonstrated a tight PPI network when the medium PPI confidence score of 0. 4 was applied in database, whereas at the high confidence score of 0. 7 a significant association of PPT networks was identified among the differentially expressed proteins as shown in Fig. 5. This PPI network suggests that the identified proteins have strong interactions with the proteins that contribute to numerous BP and have a wide range of MFs. Figure 5: The protein–protein interactions for the differentially expressed proteins identified by LC-MS/MS label-free proteomics were analyzed using software V9. 1. In the network analysis the differentially expressed proteins were represented as nodes. Each color of the lines connecting the nodes indicates strong evidence of the tight network of proteins. (A) The tight protein–protein interaction network obtained when the medium confidence level of 0. 4 was applied. (B) The high confidence (0. 7) PPI network of the identified significant proteins in SLE. Download full-size image DOI: 10. 7717/peerj. 4730/fig-5 comparative mass-based proteomic analysis investigated the proteomic profiles of SLE plasma samples were compared with healthy controls using the LC-ESI-MS/MS technique with label-free quantification. We were able to identify 122 differentially expressed proteins, and among these 19 proteins showed significant changes in expression with 14 of these being up-regulated and five being down-regulated in the SLE samples. When these proteins were subjected to the functional analysis, this protein profile was predominantly enriched with biological regulation, catalytic, and binding activity. [SEP] Justify:

Output: The text corroborates the claim by discussing proteomics in the context of identifying and analyzing the differential expression of proteins in SLE (systemic lupus erythematosus) samples. It highlights the investigative technique of label-free proteomics to study the proteomic profiles, indicating that it explores the entire set of proteins expressed, which aligns with the definition of proteomics.


Input: Task: contrast the claim using the given text. Claim: All behaviors can be understood solely through neural circuitry. [SEP] Text: : 2572-4983 Neonatal and -in-for Manuscript 10. 4172/2572-4983. 1000171 Rewarding the Autistic through Understanding the Neural Cognitive, Emotional, Motor binding Circuitry in the *Specialist in Dermatology, Academy of *Corresponding Author: Michael Chan, Specialist in Dermatology, Academy of : +85221482882, Email: pioneerskin@ymail. com Received: 26-Oct-2018 Accepted Date: 01-Nov-2018 Published Date: 09-Nov-2018 DOI: 10. 4172/2572-4983. 1000171 : Autism spectrum disorder syndrome; Cerebellar corticoemotional motor neural circuits; Reward; Adaptive time delay; Theory of mind; Early detection is a complex spectrum disorder; mostly observed at 2-3 years of age with characteristic anomalous, deviant cognitive, emotional, behavioural and neuro-motor developments till adulthood. Each autistic is different. Increasing prevalence up to 2% in children with a greater association and severity in male gender is noted. Asperger’s syndrome, Rett syndrome, childhood disintegrative disorder, pervasive developmental disorder and autism are all grouped under Disorders (ASD) [1]. ASD sufferers can be readily recognised by their repetitive, sometimes aloof and servant behaviour; echolalia, inappropriate language response and impaired attention to other. The overall consequences deprived the ASD individuals with adaptive learning, social, relationship and communication skills. ASD are frequently stigmatized as mentally insane in our community. Academy of Pediatrics (AAP) recommends children be screened for developmental disorders at wellchild preventive visits before age three [2]. for and Prevention (CDC) of have identified possible clinical alerts or red flags for ASD [1,2] (Table 1). S. N. Alerts or for ASD 1 Not responding to his/her name by 12 months of age 2 Not pointing at objects to show interest by 14 months 3 Not playing "pretend" games by 18 months 4 Avoiding eye contact or preferring to be alone 5 Getting upset by minor changes 6 Flapping their hands, rocking their body or spinning in circles 7 Having unusual and sometimes intense reactions to the way things smell, taste, feel and/or look Table 1: Clinical signs that parents should alert the possibilities of ASD. [SEP] Justify:

Output: The text contrasts the claim by indicating that autism spectrum disorder (ASD) is a complex spectrum disorder that involves a variety of cognitive, emotional, behavioral, and neuro-motor developments. It emphasizes that each autistic individual is different, suggesting that behaviors associated with ASD cannot be solely understood through neural circuitry alone. Additionally, the involvement of social, relationship, and communication skills further suggests that behaviors are influenced by various factors beyond neural circuitry.


Input: Task: pass the claim using the given text. Claim: The blood-brain barrier protects the brain from harmful substances. [SEP] Text: Back-and-forth convective movements in perivascular spaces would only be apparent using techniques with both good spatial resolution and time resolution better than a fraction of a second. Such movements have been observed in perivascular spaces very close to the cortical surface using india ink [84] and in the periarterial spaces at the cortical surfaces using microspheres [108]. But with techniques now available for viewing, if perivascular spaces exist that allow convective back and forth movements, all that would be seen within the parenchyma would be accelerated movement down the concentration gradient regardless of its direction, i. e. the periarterial influxes and effluxes that have been observed. Proposal 3 (Fig. 7c) The third proposal, the glymphatic hypothesis [25, 109, 135,136,137], asserts. There is an inward flow of CSF along periarterial spaces; The flow is driven across the layer of astrocyte endfeet into the parenchyma aided by the presence of Aqp4 in the endfeet; The flow propels the waste products of metabolism into the perivenous space again crossing the layer of endfeet, presumably again aided by the presence of Aqp4; The flow exits the parenchyma by the perivenous route and reaches lymphatic vessels in the neck. As indicated when considering Proposal 1, a flow of ~ 0. 6 µL g−1 min−1 or more would be required to remove the efflux markers at the observed rate. For a 1400 g brain, that is c. 1. 2 L day−1 roughly twice the generally accepted rate of CSF production. Thus even if the rest of this proposal is correct, either the glymphatic flow does not direct ISF out of the brain directly to lymphatic vessels or the rate of CSF production is greater than is generally accepted. [SEP] Justify:

Output: The text does not address the claim about the blood-brain barrier's protective role regarding harmful substances. Instead, it discusses mechanisms like the glymphatic flow and the movement of cerebrospinal fluid (CSF) through perivascular spaces, which do not directly relate to the blood-brain barrier or its functions. Thus, it is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Proteomics studies the entire set of proteins expressed in a cell. [SEP] Text: The AAP proteins which are down-regulated in this study are APOA1 and APOA2, these are major constituents of the high-density lipoprotein (HDL) complex, which has a specific role in lipid metabolism and has anti-inflammatory properties during both acute and chronic inflammation. Moreover, these are known to be immune regulators and suppress the generation of pro-inflammatory cytokines by activated T-cells (Barry et al. , 2004) have been demonstrated in various autoimmune diseases. Furthermore, previous proteomic studies of RA and SLE have reported down-regulated APOA1 expressions may responsible for the active phase of the disease. These proteins also seem to have a key role in anti-inflammation (Abe et al. , 2001; Kazemipour et al. , 2015). Our results on APOA1 expression levels agree with the previous studies and seem to confirm the active SLE disease state of the patients used in this study. A great deal of evidence has demonstrated that extreme oxidative stress leads to severe inflammation. Moreover, SLE is known to cause severe persistent inflammation in many major organs of the body. If we examine earlier SLE proteomic studies, some of the identified protein expressions by this study are consistent with previous reports, examples being ORM1/A1AG, TF, and CP, all of which have been detected in urine and renal biopsy samples obtained from SLE samples and were reported to act as biomarkers for class IV LN (Brunner et al. , 2012; Alaiya et al. , 2015; Suzuki et al. , 2007). Our study identified the similar changes in expression of these proteins in our plasma SLE samples. In addition to these, it has been shown that increased expression of 3/A1ACT and A1AT/1 seems to play an important role in moderating inflammatory responses, and reducing the production of inflammatory mediators and the blockage of inflammatory cells. Aggarwal et al. recently reported the increased expressions of 3/A1ACT in LN patients and demonstrated A1ACT as the best marker to differentiate active renal lupus patients from active non-renal patients (Aggarwal et al. , 2017). Thus, the identified differentially regulated antiprotease class of proteins may be relevant to renal dysregulation and inflammation in active lupus patients. HP is also involved in immune system regulation, homeostasis, and tissue repair. [SEP] Justify:

Output: The text corroborates the claim by discussing various proteins studied in relation to autoimmune diseases like SLE and RA. It emphasizes the involvement of proteins such as APOA1, APOA2, and others identified in proteomic studies, thereby supporting the assertion that proteomics examines the expression of proteins within biological contexts.