bluuebunny/crossref_metadata_2025_split huggingface dataset:
FOXO mediates organismal hypoxia tolerance by regulating NF-κB inDrosophila
Authors: Barretto Elizabeth C , Polan Danielle M , Beever-Potts Amy N , Lee Byoungchun , Grewal Savraj S 
Published: June 2019

ABSTRACTExposure of tissues and organs to low oxygen (hypoxia) occurs in both physiological and pathological conditions in animals. Under these conditions, organisms have to adapt their physiology to ensure proper functioning and survival. Here we define a role for the transcription factor FOXO as a mediator of hypoxia tolerance inDrosophila. We find that upon hypoxia exposure, FOXO transcriptional activity is rapidly induced in both larvae and adults. Moreover, we see thatfoxomutant animals show misregulated glucose metabolism in low oxygen and subsequently exhibit reduced hypoxia survival. We identify the innate immune transcription factor, NF-KappaB/Relish, as a key FOXO target in the control of hypoxia tolerance. We find that expression of Relish and its target genes are increase in a FOXO-dependent manner in hypoxia, and thatrelishmutant animals show reduced survival in hypoxia. Together, these data indicate that FOXO is a hypoxia inducible factor that mediates tolerance to low oxygen by inducing immune-like responses.
Multi-session visual cortex transcranial random noise stimulation in adults with amblyopia
Authors: Donkor Richard , Silva Andrew E. , Teske Caroline , Wallis-Duffy Margaret , Johnson Aaron , Thompson Benjamin 
Published: June 2019

PurposeWe tested the hypothesis that five daily sessions of visual cortex transcranial random noise stimulation would improve contrast sensitivity, crowded and uncrowded visual acuity in adults with amblyopia.MethodsNineteen adults with amblyopia (44.2 ± 14.9yrs, 10 female) were randomly allocated to active or sham tRNS of the visual cortex (active, n = 9; sham, n = 10). tRNS was delivered for 25 minutes across five consecutive days. Monocular contrast sensitivity, uncrowded and crowded visual acuity were measured before, during, 5 minutes and 30 minutes post stimulation on each day.ResultsActive tRNS significantly improved contrast sensitivity and uncrowded visual acuity for both amblyopic and fellow eyes whereas sham stimulation had no effect. An analysis of the day by day effects revealed large within session improvements on day 1 for the active group that waned across subsequent days. No long-lasting (multi-day) improvements were observed for contrast sensitivity, however a long-lasting improvement in amblyopic eye uncrowded visual acuity was observed for the active group. This improvement remained at 28 day follow up. However, between-group differences in baseline uncrowded visual acuity complicate the interpretation of this effect. No effect of tRNS was observed for amblyopic eye crowded visual acuity.ConclusionsIn agreement with previous non-invasive brain stimulation studies using different techniques, tRNS induced short-term contrast sensitivity improvements in adult amblyopic eyes, however, multiple sessions of tRNS did not lead to enhanced or long-lasting effects for the majority of outcome measures.
Sustained Co-evolution in a Stochastic Model of the Cancer-Immune Interaction
Authors: George Jason T. , Levine Herbert 
Published: June 2019

SummaryThe dynamical interaction between a growing cancer population and the adaptive immune system generates diverse evolutionary trajectories which ultimately result in tumor clearance or immune escape. Here, we create a simple mathematical model coupling T-cell recognition with an evolving cancer population which may randomly produce evasive subclones, imparting transient protection against the effector T-cells. We demonstrate that T-cell turnover declines and evasion rates together explain differential probabilities in early incidence data for almost all cancer types. Fitting the model to TRACERx evolutionary data argues in favor of substantial and sustained immune pressure exerted on a developing tumor, suggesting that measured incidence is a small proportion of all cancer initiation events. Most generally, dynamical models promise to increase our quantitative understanding of many immune escape contexts, with applications to cancer and intracellular pathogenic infections.
Comparison of marker selection methods for high throughput scRNA-seq data
Authors: Gilbert Anna C. , Vargo Alexander 
Published: June 2019

AbstractHere, we evaluate the performance of a variety of marker selection methods on scRNA-seq UMI counts data. We test on an assortment of experimental and synthetic data sets that range in size from several thousand to one million cells. In addition, we propose several performance measures for evaluating the quality of a set of markers when there is no known ground truth. According to these metrics, most existing marker selection methods show similar performance on experimental scRNA-seq data; thus, the speed of the algorithm is the most important consid-eration for large data sets. With this in mind, we introduce RANKCORR, a fast marker selection method with strong mathematical underpinnings that takes a step towards sensible multi-class marker selection.
Effector prediction and characterization in the oomycete pathogen Bremia lactucae reveal host-recognized WY domain proteins that lack the canonical RXLR motif
Authors: Wood Kelsey , Nur Munir , Gil Juliana , Fletcher Kyle , Lakeman Kim , Gothberg Ayumi , Khuu Tina , Kopetzky Jennifer , Pandya Archana , Pel Mathieu , Michelmore Richard 
Published: June 2019

AbstractPathogens infecting plants and animals use a diverse arsenal of effector proteins to suppress the host immune system and promote infection. Identification of effectors in pathogen genomes is foundational to understanding mechanisms of pathogenesis, for monitoring field pathogen populations, and for breeding disease resistance. We identified candidate effectors from the lettuce downy mildew pathogen, Bremia lactucae, using comparative genomics and bioinformatics to search for the WY domain. This conserved structural element is found in Phytophthora effectors and some other oomycete pathogens; it has been implicated in the immune-suppressing function of these effectors as well as their recognition by host resistance proteins. We predicted 54 WY domain containing proteins in isolate SF5 of B. lactucae that have substantial variation in both sequence and domain architecture. These candidate effectors exhibit several characteristics of pathogen effectors, including an N-terminal signal peptide, lineage specificity, and expression during infection. Unexpectedly, only a minority of B. lactucae WY effectors contain the canonical N-terminal RXLR motif, which is a conserved feature in the majority of cytoplasmic effectors reported in Phytophthora spp. Functional analysis effectors containing WY domains revealed eleven out of 21 that triggered necrosis, which is characteristic of the immune response on wild accessions and domesticated lettuce lines containing resistance genes. Only two of the eleven recognized effectors contained a canonical RXLR motif, suggesting that there has been an evolutionary divergence in sequence motifs between genera; this has major consequences for robust effector prediction in oomycete pathogens.Author SummaryThere is a microscopic battle that takes place at the molecular level during infection of plants and animals by pathogens. Some of the weapons that pathogens battle with are known as “effectors,” which are secreted proteins that enter host cells to alter physiology and suppress the immune system. Effectors can also be a liability for plant pathogens because plants have evolved ways to recognize these effectors, triggering a defense response leading to localized cell death, which prevents the spread of the pathogen. Here we used computer models to predict effectors from the genome of Bremia lactucae, the causal agent of lettuce downy mildew. Three effectors were demonstrated to suppress the basal immune system of lettuce. Eleven effectors were recognized by one or more resistant lines of lettuce. In addition to contributing to our understanding of the mechanisms of pathogenesis, this study of effectors is useful for breeding disease resistant lettuce, decreasing agricultural reliance on fungicides.
A receptor for herbivore-associated molecular patterns mediates plant immunity
Authors: Steinbrenner Adam D. , Muñoz-Amatriaín Maria , Aguilar Venegas Jessica Montserrat , Lo Sassoum , Shi Da , Holton Nicholas , Zipfel Cyril , Abagyan Ruben , Huffaker Alisa , Close Timothy J. , Schmelz Eric A. 
Published: June 2019

AbstractPlant-herbivore interactions are ubiquitous across nature and drive major agricultural losses. Inducible defense responses triggered through immune recognition aid in host plant protection; however, specific ligand-receptor pairs mediating the initial perception of herbivory remain unknown. Plants in the subtribe Phaseolinae detect herbivore-associated peptides in caterpillar oral secretions and the defined ligands are proteolytic fragments of chloroplastic ATP synthase termed inceptins. Using forward genetic mapping of inceptin-induced responses, we identify a cowpea (Vigna unguiculata) leucine-rich repeat receptor-like protein as an inceptin receptor (INR) sufficient for elicitor-induced responses and enhanced defense against armyworms (Spodoptera exigua). INR defines a receptor by which plants perceive herbivore-associated molecular patterns (HAMPs) and expands the paradigm of surface immune recognition to attack with mandibles.One Sentence SummaryA plant cell surface receptor directly perceives peptides associated with caterpillar herbivory.
Tumor fitness, immune exhaustion and clinical outcomes: impact of immune checkpoint inhibitors
Authors: Bubie Adrian , Gonzalez-Kozlova Edgar , Akers Nicholas , Villanueva Augusto , Losic Bojan 
Published: June 2019

AbstractRecently proposed tumor fitness measures, based on profiling neoepitopes for reactive viral epitope similarity, have been proposed to predict response to immune checkpoint inhibitors in melanoma and small-cell lung cancer. Here we apply these checkpoint based fitness measures measures to the matched checkpoint treatment naive TCGA samples where cytolytic activity imparts a known survival benefit. We observed no significant survival predictive power beyond that of overall patient tumor mutation burden, and furthermore, found no association between checkpoint based fitness and tumor T-cell infiltration, cytolytic activity (CYT), and abundance (TIL burden). In addition, we investigated the key assumption of viral epitope similarity driving immune response in the hepatitis B virally infected liver cancer TCGA cohort, and uncover suggestive evidence that tumor neoepitopes actually dominate viral epitopes in putative immunogenicity and plausibly drive immune response and recruitment.
Elizabethkingia anophelisresponse to iron stress: physiologic, genomic, and transcriptomic analyses
Authors: Chen Shicheng , Johnson Benjamin K. , Yu Ting , Nelson Brooke N. , Walker Edward D. 
Published: June 2019

AbstractElizabethkingia anophelisbacteria encounter fluxes of iron in the midgut of mosquitoes, where they live as symbionts. They also establish bacteremia with severe clinical manifestations in humans, and live in water service lines in hospitals. In this study, we investigated the global gene expression responses ofE. anophelisto iron fluxes in the midgut of femaleAnopheles stephensimosquitoes fed sucrose or blood, and in iron-poor or iron-rich culture conditions. Of 3,686 transcripts revealed by RNAseq technology, 218 were upregulated while 112 were down-regulated under iron-poor conditions. Most of these differentially expressed genes (DEGs) were enriched in functional groups assigned within “biological process,” “cell component” and “molecular function” categories.E. anophelispossessed 4 iron/heme acquisition systems. Hemolysin gene expression was significantly repressed when cells were grown under iron-rich or high temperature (37°C) conditions. Furthermore, hemolysin gene expression was down-regulated after a blood meal, indicating thatE. anopheliscells responded to excess iron and its associated physiological stress by limiting iron loading. By contrast, genes encoding respiratory chain proteins were up-regulated under iron-rich conditions, allowing these iron-containing proteins to chelate intracellular free iron.In vivostudies showed that growth ofE. anopheliscells increased 3-fold in blood-fed mosquitoes over those in sucrose-fed ones. Deletion of aerobactin synthesis genes led to impaired cell growth in both iron-rich and iron-poor media. Mutants showed more susceptibility to H2O2toxicity and less biofilm formation than did wild-type cells. Mosquitoes withE. anophelisexperimentally colonized in their guts produced more eggs than did those treated with erythromycin or left unmanipulated, as controls. Results reveal thatE. anophelisbacteria respond to varying iron concentration in the mosquito gut, harvest iron while fending off iron-associated stress, contribute to lysis of red blood cells, and positively influence mosquito host fecundity.
Computational and experimental performance of CRISPR homing gene drive strategies with multiplexed gRNAs
Authors: Champer Samuel E. , Oh Suh Yeon , Liu Chen , Wen Zhaoxin , Clark Andrew G. , Messer Philipp W. , Champer Jackson 
Published: June 2019

ABSTRACTCRISPR homing gene drives potentially have the capacity for large-scale population modification or suppression. However, resistance alleles formed by the drives can prevent them from successfully spreading. Such alleles have been found to form at high rates in most studies, including those in both insects and mammals. One possible solution to this issue is the use of multiple guide RNAs (gRNAs), thus allowing cleavage by the drive even if resistance sequences are present at some of the gRNA target sequences. Here, we develop a high-fidelity model incorporating several factors affecting the performance of drives with multiple gRNAs, including timing of cleavage, reduction in homology-directed repair efficiency due to imperfect homology around the cleavage site, Cas9 activity saturation, variance in the activity level of individual gRNAs, and formation of resistance alleles due to incomplete homology-directed repair. We parameterize the model using data from homing drive experiments designed to investigate these factors and then use it to analyze several types of homing gene drives. We find that each type of drive has an optimal number of gRNAs, usually between two and eight, dependent on drive type and performance parameters. Our model indicates that utilization of multiple gRNAs is insufficient for construction of successful gene drives, but that it provides a critical boost to drive efficiency when combined with other strategies for population modification or suppression.
Fitness and productivity increase with ecotypic diversity amongE. colievolved in a simple, constant environment
Authors: Yang Dong-Dong , Alexander Ashley , Kinnersley Margie , Cook Emily , Caudy Amy , Rosebrock Adam , Rosenzweig Frank 
Published: June 2019

ABSTRACTCommunity productivity often correlates with diversity. In the microbial world this phenomenon can sometimes be explained by highly-specific metabolic interactions that include cross-feeding and syntrophy. Such interactions help account for the astonishing variety of microbial life, and drive many of the biogeochemical cycles without which life as we know it could not exist. While it is difficult to recapitulate experimentally how these interactions evolved among multiple taxa, we can explore in the laboratory how they arise within one. These experiments provide insight into how different bacterial ecotypes evolve and from these, possibly new ‘species.’ We have previously shown that in a simple, constant environment a single clone ofE. colican give rise to a consortium of genetically-and physiologically-differentiated strains, in effect, a set of ecotypes, that coexist by cross-feeding. We marked these different ecotypes and their shared ancestor by integrating fluorescent protein into their genomes. We then used flow cytometry to show that each strain by itself is more fit than the shared ancestor, that pairs of evolved strains are fitter still, and that the entire consortium is fittest of all. We further demonstrate that the rank order of fitness values agrees with estimates of yield, indicating that an experimentally evolved consortium more efficiently converts resources to offspring than its ancestor or any member acting in isolation.ImportanceIn the microbial world, diversity and productivity of communities and consortia often correlate positively. However, it is challenging to tease apart a consortium whose members have co-evolved, and connect estimates of their fitness and the fitness of their ancestor(s) with estimates of productivity. Such analyses are prerequisite to understanding the evolutionary origins of all biological communities. Here we dissect anE. coliconsortium that evolved in the laboratory and show that cooperative interactions are favored under continuous glucose limitation because a partnership of ecotypes is better able to scavenge all available resources and more efficiently convert those resources to offspring than any single individual. Such interactions may be a prelude to a special form of syntrophy, and are likely to be key determinants of microbial community structure in nature, including those having clinical significance, such as chronic infections.
Shotgun Metagenomics of 361 elderly women reveals gut microbiome change in bone mass loss
Authors: Wang Qi , Sun Qiang , Li Xiaoping , Wang Zhefeng , Zheng Haotian , Ju Yanmei , Guo Ruijin , Peng Songlin , Jia Huijue 
Published: June 2019

AbstractBone mass loss contributes to the risk of bone fracture in the elderly. Many factors including age, obesity, estrogen and diet, are associated with bone mass loss. Mice studies suggest that the intestinal microbiome might influence the bone mass by regulating the immune system, however there has been little evidence from human studies.We have recruited 361 Chinese elderly women to collect data for a metagenomic-wide association study (MWAS) to investigate the influence of the gut microbiome on bone health. Gut microbiome data were produced using BGISEQ500 sequencing, BMD was calculated using Hologic dual energy X-ray machine, BMI (Body Mass Index) and age were also provided. This therefore data allows exploration of gut microbiome diversity and links to bone mass loss, as well as microbial species and modules as markers for bone mineral density. Making these data potentially useful in studying the role the gut microbiota might play in bone mass loss and offering exploration into the bone mass loss process.
On the mechanistic roots of an ecological law: parasite aggregation
Authors: Rabajante Jomar F. , Anzia Elizabeth L. , Gokhale Chaitanya S. 
Published: June 2019

AbstractParasite aggregation, a recurring pattern in macroparasite infections, is considered one of the “laws” of parasite ecology. Few hosts have a large number of parasites while most hosts have a low number of parasites. Phenomenological models of host-parasite systems thus use the negative-binomial distribution. However, to infer the mechanisms of aggregation, a mechanistic model that does not make any a priori assumptions is essential. Here we formulate a mechanistic model of parasite aggregation in hosts without assuming a negative-binomial distribution. Our results show that a simple model of parasite accumulation still results in an aggregated pattern, as shown by the derived mean and variance of the parasite distribution. By incorporating the derived statistics in host-parasite interactions, we can predict how aggregation affects the population dynamics of the hosts and parasites through time. Thus, our results can directly be applied to observed data as well as can inform the designing of statistical sampling procedures. Overall, we have shown how a plausible mechanistic process can result in the often observed phenomenon of parasite aggregation occurring in numerous ecological scenarios, thus providing a basis for a “law” of ecology.
Integrated analysis of different non-coding features across the Sox2 locus implicates a diencephalic enhancer in adult brain expression
Authors: Carter D.A. 
Published: June 2019

ABSTRACTSOX2 is a prominent member of the SOX family of transcription factors that has many different functional roles. This pleiotropy is made possible by multiple regulatory mechanisms that direct appropriate spatial and temporal patterns of expression, and therefore action. The current study concerns the mechanisms that determine Sox2 gene expression in the adult mammalian brain, where SOX2 protein is absent in general, but is selectively and abundantly expressed in a majority of neurons within a ventral diencephalic brain structure, the suprachiasmatic nucleus (SCN). In this study, a comparative bioinformatic and biochemical analysis of different adult rat brain regions was conducted in order to identify SCN-selective (immaturity-related) regulatory mechanisms. The approach incorporated an integrated analysis of Sox2 enhancers, CTCF binding sites, and also expression of the Sox2-overlapping, long non-coding (lnc)RNA, Sox2ot. Initial experiments revealed brain region-specific Sox2ot expression (including region-specific novel transcripts), indicating a significant diversity of Sox2ot expression across the adult brain. However, the pattern and abundance of Sox2ot expression in the SCN, relative to selected control areas of the brain, did not indicate an overt relationship to Sox2 gene expression. Furthermore, although multiple individual Sox2ot exon sequences were shown to overlap annotated Sox2 gene enhancers at different sites across the Sox2 locus, again there was no indication of a SCN-specific functional correlation. Further integration with an analysis of selectively-active CTCF sites within the Sox2 locus directed attention to one site with both a prominent peak of activity in immature brain, and proximity to a functionally-characterized, ventral diencephalic, Sox2 enhancer termed U6 (upstream enhancer 6). Ex vivo analysis of the U6-associated CTCF site revealed SCN-selective CTCF binding, and these sequences were both localized within a known (brain region-selective) super-enhancer. Bioinformatic analysis of the U6 enhancer sequence revealed an abundance of consensus sites for the SCN-selective transcription factor LHX1, and over-expression of this factor enhanced the activity of cloned U6 sequence in transfected cells. However, despite this compelling evidence for a molecular mechanism that underlies adult brain expression of SOX2, further analysis of LHX1-SOX2 co-expression in the SCN confounded this view, indicating the presence of other concurrent mechanisms in the different cell populations of the SCN.
Polyhyrdoxybutyrate production by Bacillus marcorestinctum using a Cheaper substrate and its electrospinned blends with polymer
Authors: Narayankumar Swetha , Shaji Neethu K. , Krishnaswamy Veena gayathri 
Published: June 2019

ABSTRACTPoly(hydroxybutyric acid) (PHB) and other biodegradable polyesters are promising candidates for the development of environment-friendly and completely biodegradable plastics. One of the major drawbacks in the production of PHB is production costs, since it requires large amount of carbon source. This calls for cheaper substrates that can be used as an alternative carbon source such as agro-industrial residues. In this study, cane molasses was used as an additional carbon source at 2% concentration along with glucose for large scale production of PHB. Ammonium nitrate was used as the nitrogen source and the C:N ratio was maintained at 1:15. The maximum production of PHB was obtained at 24hours of growth which was found to be 0.5g/L and had a dry cell weight of 3.7g/ L.The PHB produced was further analysed by GC-MS Analysis and Transmission Electron Microscopy (TEM).The obtained PHB from scale-up studies were further electrospinned using different blends of polymers.