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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2018

Effects of age on the green autofluorescence of the skin and fingernails of healthy persons

Our recent studies have suggested that altered Pattern of Autofluorescence (AF) of skin and fingernails are novel biomarkers of multiple major diseases. The age of all of the subjects in these studies ranges from 50 to 80 years of old. For future studies on the potential diagnostic value of green AF for age-independent diseases, it is required to answer the following question: Are there differences in the green AF of healthy persons of various age populations? In our current study, we determined the green AF of the skin and fingernails of healthy persons in several age populations, showing significant age dependence of the AF: First, the green AF intensity of the age group between 15 to 20 years of old is significantly higher than that of the age group between 50 to 80 years of old at both right and left Centremetacarpus, right Dorsal Centremetacarpus, and right Dorsal Index Finger. Second, for the green AF intensity of the age groups of 15 to 20 years of old, 60 to 70 years of old, 70 to 80 years of old, and 81 to 85 years of old, the green AF intensity is negatively correlated with the age at both right and left Centremetacarpus and right Dorsal Centremetacarpus. Collectively, our study has provided first evidence indicating the age dependence of the AF intensity of humans skin, which has established essential basis for the studies that determine the diagnostic value of the green AF for the age-independent diseases.

physiology↗

bioRxiv2018

Striking reduction in neurons and glial cells in anterior thalamic nuclei of older patients with Down’s syndrome

The anterior thalamic nuclei are important for spatial and episodic memory; however, there is surprisingly little information about how these nuclei are affected in many conditions that present with memory impairments, including Downs syndrome. To assess the status of the anterior thalamic nuclei in Downs syndrome we quantified neurons and glial cells in the brains from four older patients with this condition. There was a striking reduction in the volume of the anterior thalamic nuclei and this appeared to reflect the loss of approximately 70% of neurons. The number of glial cells was also reduced but to a lesser degree than neurons. The anterior thalamic nuclei appear to be particularly sensitive to effects of aging in Downs syndrome and the pathology in this region likely contributes to the memory impairments observed. These findings re-affirm the importance of assessing the status of the anterior thalamic nuclei in conditions where memory impairments have been principally assigned to pathology in the medial temporal lobe.

neuroscience↗

bioRxiv2018

Nonlinear and Nonlocal Elasticity in Coarse-Grained Differential-Tension Models of Epithelia

The shapes of epithelial tissues result from a complex interplay of contractile forces in the cytoskeleta of the cells in the tissue, and adhesion forces between them. A host of discrete, cell-based models describe these forces by assigning different surface tensions to the apical, basal, and lateral sides of the cells. These differential-tension models have been used to describe the deformations of epithelia in different living systems, but the underlying continuum mechanics at the scale of the epithelium are still unclear. Here, we derive a continuum theory for a simple differential-tension model of a two-dimensional epithelium and study the buckling of this epithelium under imposed compression. The analysis reveals howthe cell-level properties encoded in the differential-tension model lead to linear, nonlinear as well as nonlocal elastic behavior at the continuum level.

biophysics↗

bioRxiv2018

Why would parthenogenetic females systematically produce males who never transmit their genes to females?

SummaryIn pseudogamous species, females use the sperm of males from another species to activate their oocytes and produce females, without using the sperm DNA. Here we report a novel reproductive strategy found in the pseudogamous nematode Mesorhabditis belari, which produces its own males at low frequency. We find that the 8% of M. belari males are necessary to fertilize all oocytes but pass on their genes only to males, and never to females. Thus, the production of males has no impact on the genetic diversity of females. Using game theory, we show that the production of males at low frequency constitutes an efficient strategy only if sons are more likely to mate with their sisters. We validate this prediction experimentally by revealing a mating preference between siblings. We uncover the remarkable reproductive strategy of parthenogenetic females that pay the cost of producing males while males do not spread their genes.

evolutionary biology↗

bioRxiv2018

Investigating the cytotoxic effects of the venom proteome of two species of the Viperidae family (Cerastes cerastes and Cryptelytrops purpureomaculatus) from various habitats

Animal secretions are of great interest in terms of drug development due to their complex protein and peptide composition. Especially, in the field of therapeutic medications such as anti-cancer drugs snake venoms receive attention. In this study we report of two Viperidae species from various habitats with a particular focus on the cytotoxic potential along with the decomplexation of the venom proteome: the horned desert viper (Cerastes cerastes), native to desert regions of North Africa and the mangrove pit viper (Cryptelytrops purpureomaculatus), found in coastal forests of Southeast Asia. Initial cytotoxic screenings of the crude venoms revealed diverse activity, with the highest effect against SHSY5Y human glioblastoma carcinoma cells compared to other cancerous and non-cancerous cell lines. In-depth cytotoxicity studies of SHSY5Y cells with purified venom fractions revealed dimeric disintegrins from C. cerastes venom which exerted a high cytotoxic activity with IC50 values from 0.11 to 0.58{micro}M and the disintegrins-like effect on SHSY5Y morphology was observed due to cell detachment. Furthermore, two polyproline BPP-related peptides, one PLA2 and a peptide-rich fraction were determined for C. purpureomaculatus with moderate IC50 values between 3-51{micro}M. Additionally, the decryption of the venom proteomes by snake venomic mass spectrometry and comparison of same species from different habitats revealed slight differences in the composition.

biochemistry↗

bioRxiv2018

Sensitivity and Specificity of Information Criteria

Information criteria (ICs) based on penalized likelihood, such as Akaikes Information Criterion (AIC), the Bayesian Information Criterion (BIC), and sample-size-adjusted versions of them, are widely used for model selection in health and biological research. However, different criteria sometimes support different models, leading to discussions about which is the most trustworthy. Some researchers and fields of study habitually use one or the other, often without a clearly stated justification. They may not realize that the criteria may disagree. Others try to compare models using multiple criteria but encounter ambiguity when different criteria lead to substantively different answers, leading to questions about which criterion is best. In this paper we present an alternative perspective on these criteria that can help in interpreting their practical implications. Specifically, in some cases the comparison of two models using ICs can be viewed as equivalent to a likelihood ratio test, with the different criteria representing different alpha levels and BIC being a more conservative test than AIC. This perspective may lead to insights about how to interpret the ICs in more complex situations. For example, AIC or BIC could be preferable, depending on the relative importance one assigns to sensitivity versus specificity. Understanding the differences and similarities among the ICs can make it easier to compare their results and to use them to make informed decisions.

bioinformatics↗

bioRxiv2018

Probing the circuits of conscious perception with magnetophosphenes

BackgroundConscious perception is thought to involve the large-scale, coordinated activation of distant brain regions, a process termed ignition in the Global Workspace Theory and integration in Integrated Information Theory, which are two of the major theories of consciousness.\n\nMethodsHere, we provide evidence for this process in humans by combining a magnetically-induced phosphene perception task with electroencephalography. Functional cortical networks were identified and characterized using graph theory to quantify the impact of conscious perception on local (segregation) and distant (integration) processing.\n\nResultsConscious phosphene perception activated frequency-specific networks, each associated with a specific spatial scale of information processing. Integration increased within an alpha-band functional network, while segregation occurred in the beta band.\n\nConclusionsThese results bring novel evidence for the functional role of distinct brain oscillations and confirm the key role of integration processes for conscious perception in humans.

neuroscience↗

bioRxiv2018

Direct and transgenerational effects of an experimental heat wave on early life stages in a freshwater snail

Global climate change imposes a serious threat to natural populations of many species. Estimates of the effects of climate change-mediated environmental stresses are, however, often based only on their direct effects on organisms, and neglect the potential transgenerational effects. We investigated whether high temperature (i.e. an experimental heat wave) that is known to reduce performance of adult Lymnaea stagnalis snails affects their offspring through maternal effects. Specifically, we tested whether eggs and hatched juveniles are affected by maternal thermal environment, and how strong these effects are compared with direct effects of temperature on offspring. We examined the effect of maternal thermal environment (15{degrees}C versus 25{degrees}C) on per offspring investment (egg size), and the role of both maternal and offspring thermal environments (15{degrees}C versus 25{degrees}C) on hatching success and developmental time of eggs, offspring survival after hatching, and hatchling size at the age of five weeks. Exposure of mothers to high temperature increased hatching success of eggs, and also made the onset of hatching earlier. However, high maternal temperature reduced the survival and the final size of hatched juveniles. Direct effects of high temperature on offspring survival were negative (both eggs and hatchlings), but increased the developmental rate and growth of those eggs and hatchlings that survived. Interestingly, the magnitude of transgenerational effects of high temperature on hatching success of eggs and hatchling survival were similar to its direct effects. This indicates that heat waves can affect natural populations through transgenerational effects, and that the magnitude of such effects can be equally strong to the direct effects of temperature, although this depends on the trait considered. Our results highlight the importance of considering transgenerational effects of climate warming when estimating its effects in the wild.

ecology↗

bioRxiv2018

Modeling cellular response in large-scale radiogenomic databases to advance precision radiotherapy

Radiotherapy is integral to the care of a majority of cancer patients. Despite differences in tumor responses to radiation (radioresponse), dose prescriptions are not currently tailored to individual patients. Recent large-scale cancer cell line databases hold the promise of unravelling the complex molecular arrangements underlying cellular response to radiation, which is critical to novel predictive biomarker discovery. Here, we present RadioGx, a computational platform for integrative analyses of radioresponse using radiogenomic databases. We first used RadioGx to investigate the robustness of radioresponse assays and indicators. We then combined radioresponse and genome-wide molecular data with established radiobiological models to predict molecular pathways that are relevant for individual tissue types and conditions. We also applied RadioGx to pharmacogenomic data to identify several classes of drugs whose effects correlate with radioresponse. RadioGx provides a unique computational toolbox to advance preclinical research for radiation oncology and precision medicine.

bioinformatics↗

bioRxiv2018

Calculating the Effects of Autism Risk Gene Variants on Dysfunction of Biological Processes Identifies Clinically-Useful Information

Autism spectrum disorders (ASD) are neurodevelopmental conditions that are influenced by genetic factors and encompass a wide-range and severity of symptoms. The details of how genetic variation contributes to variable symptomatology are unclear, creating a major challenge for translating vast amounts of data into clinically-useful information. To determine if variation in ASD risk genes correlates with symptomatology differences among individuals with ASD, thus informing treatment, we developed an approach to calculate the likelihood of genetic dysfunction in Gene Ontology-defined biological processes that have significant overrepresentation of known risk genes. Using whole-exome sequence data from 2,381 individuals with ASD included in the Simons Simplex Collection, we identified likely damaging variants and conducted a clustering analysis to define subgroups based on scores reflecting genetic dysfunction in each process of interest to ASD etiology. Dysfunction in cognition-related genes distinguished a distinct subset of individuals with increased social deficits, lower IQs, and reduced adaptive behaviors when compared to individuals with no evidence of cognition-related gene dysfunction. In particular, a stop-gain variant in the pharmacogene encoding cycloxygenase-2 was associated with having an IQ<70 (i.e. intellectual disability), a key comorbidity in ASD. We expect that screening genes involved in cognition for deleterious variants in ASD cases may be useful for identifying clinically-informative factors that should be prioritized for functional follow-up. This has implications in designing more comprehensive genetic testing panels and may help provide the basis for more informed treatment in ASD.

genetics↗

bioRxiv2018

The impact of bilingualism on executive functions and working memory in young adults.

A bilingual advantage in a form of a better performance of bilinguals in tasks tapping into executive function abilities has been reported repeatedly in the literature. However, recent research defends that this advantage does not stem from bilingualism, but from uncontrolled factors or imperfectly matched samples. In this study we explored the potential impact of bilingualism on executive functioning abilities by testing large groups of young adult bilinguals and monolinguals in the tasks that were most extensively used when the advantages were reported. Importantly, the recently identified factors that could be disrupting the between groups comparisons were controlled for, and both groups were matched. We found no differences between groups in their performance. Additional bootstrapping analyses indicated that, when the bilingual advantage appeared, it very often co-occurred with unmatched socio-demographic factors. The evidence presented here indicates that the bilingual advantage might indeed be caused by spurious uncontrolled factors rather than bilingualism per se. Secondly, bilingualism has been argued to potentially affect working memory also. Therefore, we tested the same participants in both a forward and a backward version of a visual and an auditory working memory task. We found no differences between groups in either of the forward versions of the tasks, but bilinguals systematically outperformed monolinguals in the backward conditions. The results are analyzed and interpreted taking into consideration different perspectives in the domain-specificity of the executive functions and working memory.

neuroscience↗

bioRxiv2018

Wakeful rest benefits memory when materials can be rehearsed

Wakeful rest is a brief (e.g., 10 minutes), quiet period of minimal stimulation, which has been shown to facilitate memory performance, compared to a distractor task. Researchers have argued that this benefit is driven by automatic consolidation during the wakeful rest period. However, prior studies have not fully ruled out a controlled rehearsal mechanism, which might also occur during wakeful rest. In the current study, we attempted to replicate the wakeful rest effect under conditions that more strictly limit the possibility of rehearsal. Across six experiments, we manipulated parameters of a standard wakeful rest paradigm, including the type of target materials (word lists or abstract shapes), intentionality of encoding (incidental or intentional), and final retrieval delay (immediate or delayed). Additionally, we tested both younger and older adults to test whether these effects are consistent across the adult lifespan. Importantly, we observed the expected wakeful rest memory benefit in recall for verbal targets, which are easily rehearseable, but not for abstract shapes, which cannot be readily rehearsed. This pattern occurred in both younger and older adults. These results place constraints on the generalizability of wakeful rest memory benefits and suggest that the effect may be at least partly driven by rehearsal processes, rather than an automatic consolidation process.

animal behavior and cognition↗

bioRxiv2018

Chemotactic motility and biofilm formation in Campylobacter jejuni are coordinated by the CheAYWVX system

Flagellar motility plays a central role in the bacterial foodborne pathogen Campylobacter jejuni, as flagellar motility is required for reaching the intestinal epithelium and subsequent colonisation or disease. Flagellar proteins also contribute strongly to biofilm formation during transmission. Chemotaxis is the process directing flagellar motility in response to attractant and repellent stimuli, but its role in biofilm formation of C. jejuni is not well understood. Here we show that inactivation of the core chemotaxis genes cheVAWY in C. jejuni strain NCTC 11168 affects both chemotactic motility and biofilm formation. Inactivation of any of the core chemotaxis genes (cheA, cheY, cheV or cheW) impaired chemotactic motility but did not affect flagellar assembly or growth. The {Delta}cheY mutant swam in clockwise loops, while complementation restored normal motility. Inactivation of the core chemotaxis genes interfered with the ability to form a discrete biofilm at the air-media interface, and the {Delta}cheY mutant displayed reduced dispersal/shedding of bacteria into the planktonic fraction. This suggests that while the chemotaxis system is not required for biofilm formation per se, it is necessary for organized biofilm formation. Hence interference with the Campylobacter chemotaxis system at any level disrupts optimal chemotactic motility and transmission modes such as biofilm formation.

microbiology↗

bioRxiv2018

Molecular epidemiology of Colombian Histoplasma capsulatum isolates shows their polyphyletic behavior and point out raw chicken manure as one of the infections sources

The thermally dimorphic fungus Histoplasma capsulatum is the causative agent of histoplasmosis, which is the most prevalent endemic mycosis in America. The replacement of organic matter in agro-ecosystems is necessary in the tropics, and the use of organic fertilizers has increased. Cases and outbreaks due to the presence of the fungus in these components have been reported. In Colombia, chicken manure is the most common raw material in the organic fertilizers production. In this work, we reached the isolation of the fungus from a chicken manure. Then, we were able to compare genetically 3 environmental isolates with 42 Colombian human clinical isolates. The genetic comparison showed the environmental isolates grouping together with the clinical isolates. This result suggests chicken manure as one of the infection source with H. capsulatum. Also, the phylogenetic analysis using another H. capsulatum isolates from databases showed that the Colombian isolates widely distributed in the relation tree. This result pointed out the great genetic diversity among H. capsulatum Colombian population.

microbiology↗

bioRxiv2018

Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions

Genome-wide association studies have reported that, amongst other microglial genes, variants in TREM2 can profoundly increase the incidence of developing Alzheimers disease (AD). We have investigated the role of TREM2 in primary microglial cultures from wild type mice by using siRNA to decrease Trem2 expression, and in parallel from knock-in mice heterozygous or homozygous for the Trem2 R47H AD risk variant. The prevailing phenotype of Trem2 R47H knock-in mice was decreased expression levels of Trem2 in microglia, which resulted in decreased density of microglia in the hippocampus. Overall, primary microglia with reduced Trem2 expression, either by siRNA or from the R47H knock-in mice, displayed a similar phenotype. Comparison of the effects of decreased Trem2 expression under conditions of LPS pro-inflammatory or IL-4 anti-inflammatory stimulation revealed the importance of Trem2 in driving a number of the genes up-regulated in the anti-inflammatory phenotype. RNA-seq analysis showed that IL-4 induced the expression of a programme of genes including Arg1 and Ap1b1 in microglia, which showed an attenuated response to IL-4 when Trem2 expression was decreased. Genes showing a similar expression profile to Arg1 were enriched for STAT6 transcription factor recognition elements in their promoter, and Trem2 knockdown decreased levels of the transcription factor STAT6. LPS-induced pro-inflammatory stimulation suppressed Trem2 expression, thus preventing TREM2s anti-inflammatory drive. Given that anti-inflammatory signaling is associated with tissue repair, understanding the signaling mechanisms downstream of Trem2 in coordinating the pro- and anti-inflammatory balance of microglia, particularly mediating effects of the IL-4-regulated anti-inflammatory pathway, has important implications for fighting neurodegenerative disease. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=189 HEIGHT=200 SRC="FIGDIR/small/449884v2_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1393670org.highwire.dtl.DTLVardef@1251691org.highwire.dtl.DTLVardef@1eca1c5org.highwire.dtl.DTLVardef@70a30a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2018

Growth substrate may influence biofilm susceptibility to antibiotics

The CDC biofilm reactor is a robust culture system with high reproducibility in which biofilms can be grown for a wide variety of analyses. Multiple material types are available as growth substrates, yet data from biofilms grown on biologically relevant materials is scarce, particularly for antibiotic efficacy against differentially supported biofilms. In this study, CDC reactor holders were modified to allow growth of biofilms on collagen, a biologically relevant substrate. Susceptibility to multiple antibiotics was compared between biofilms of varying species grown on collagen versus standard polycarbonate coupons. Data indicated that in 13/18 instances, biofilms on polycarbonate were more susceptible to antibiotics than those on collagen, suggesting that when grown on a complex substrate, biofilms may be more tolerant to antibiotics. These outcomes may influence the translatability of antibiotic susceptibility profiles that have been collected for biofilms on hard plastic materials. Data may also help to advance information on antibiotic susceptibility testing of biofilms grown on biologically relevant materials for future in vitro and in vivo applications.

microbiology↗

bioRxiv2018

Genetic population variation and phylogeny of Sinomenium acutum (Menispermaceae) in subtropical China through chloroplast marker

Sinomenium acutum (Menispermaceae) is a traditional Chinese medicine. In recent years, extensive harvesting for medicinal purposes has resulted in a sharp decline in its population. Genetic information is crucial for the proper exploitation and conservation of Sinomenium acutum, but little is known about it at present. In this study, we analyzed 77 samples from 4 populations using four non-coding regions (atpI-atpH, trnQ-5rps16, trnH-psbA, and trnL-trnF) of chloroplast DNA and 14 haplotypes (from C1 to C14) were identified. C1 and C3 were common haplotypes, which were shared by all populations, and C3 was an ancestral haplotype, the rest were rare haplotypes. Obvious phylogeographic structure was not existed inferred by GST / NST test. Mismatch distribution, Tajimas D and Fus FS tests failed to support a rapid demographic expansion in Sinomenium acutum. AMOVA highlighted that the high level of genetic differentiation within population. Low genetic variation among populations illustrated gene flow was not restricted. Genetic diversity analyses demonstrated that the populations of Xuefeng, Dalou, and Daba Mountains were possible refugia localities of Sinomenium acutum. Based on this study, we proposed a preliminary protection strategy for it that C1, C3, C11 and C12 must be collected. These results offer an valuable and useful information for this species of population genetic study as well as further conservation.

molecular biology↗

bioRxiv2018

Catch me if you can: Species interactions and moon illumination effect on mammals of tropical semi-evergreen forest of Manas National Park, Assam, India

Species interaction plays a vital role in structuring communities by stimulating behavioral responses in temporal niche affecting the sympatric associations and prey-predator relationships. We studied relative abundance indices (RAI) and activity patterns of each species, temporal overlap between sympatric species, and effects of moon cycle on predator-prey relationships, through camera-trapping in tropical semi-evergreen forests of Manas National Park. A total of 35 species were photo-captured with 16214 independent records over 7337 trap nights. Overall, relatively high number of photographs was obtained for large herbivores (11 species, n=13669), and low number of photographs were recorded for large carnivores (five species, n=657). Activity periods were classified into four categories: diurnal (day-time), nocturnal (night-time), crepuscular (twilight), and cathemeral (day and night time) of which 52% records were found in diurnal period followed by 37% in nocturnal phase whereas only 11% photographs during twilight. Small carnivores were strictly nocturnal (leopard cat and civets) or diurnal (yellow-throated marten and mongooses); whereas large carnivores were cathemeral (tiger, leopard, clouded leopard and Asiatic black bear). Analysis of activity patterns throughout the 24-h cycle revealed a high degree of temporal overlap (>60%) among most of the sympatric species; however, differences in the activity peaks were found between most of the species pairs. Moon phase was classified according to the percentage of visible moon surface as new (0-25%), waxing (25-50%), waning (50-75%) and full moon (75-100%). Moon phase did not have any correlation with activity of large carnivore and large prey. The large carnivore followed the feed and starve pattern of cyclic activity. The activity of small carnivore was influenced negatively by moonlight (partial correlation r = -0.221, p<0.01). The result suggests that large carnivores were active non-differentially across moon phases; however, small carnivores showed significantly high activity in darker nights. These patterns indicate that small predators may differ their activity temporally as an anti-predator strategy or otherwise to increase their foraging efficiency.

animal behavior and cognition↗