bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Proteome-scale Analysis of Vertebrate Protein Amino Acid Occurrence: Thermoadaptation shows a Correlation with Protein Solvation but less so with Dynamics
Authors: Li Z.L. , Buck M 
Published: August 2020

AbstractDespite differences in behaviors and living conditions, vertebrate organisms share the great majority of proteins, often with subtle differences in amino acid sequence. Here, we present a simple way to analyze the difference in amino acid occurrence by comparing highly homologous proteins on a sub-proteome level between several vertebrate model organisms. Specifically, we use this method to identify a pattern of amino acid conservation as well as a shift in amino acid occurrence between homeotherms (warm-blooded species) and poikilotherms (cold-blooded species). Importantly, this general analysis and a specific example further establish a correlation, if not likely connection between the thermoadaptation of protein sequences and two of their physical features: a possible change in their protein dynamics and, even more strongly, in their solvation. For poikilotherms, such as frog and fish, the lower body temperature is expected to increase the association of proteins due to a decrease in protein internal dynamics. In order to prevent overly-sticky protein association at low temperatures, the use of amino acids suggests that poikilotherms enhance the solvation of their proteins by favoring polar groups on their protein’s surface. This feature appears to dominate over possible changes in dynamics. The results suggest that a general trend for amino acid choice is part of the mechanism for thermoadaptation of vertebrate organisms at the molecular level.
Location, location, location: Feeding site affects aphid performance by altering access and quality of nutrients
Authors: Nalam Vamsi J. , Han Jinlong , Pitt William Jacob , Acharya Shailesh Raj , Nachappa Punya 
Published: August 2020

AbstractFeeding location on a plant can affect aphid reproduction and survival, however little is known about factors that influence aphid performance on specific plant parts. We determined performance and feeding behavior of soybean aphid (Aphis glycines) on stem, adaxial (upper) and abaxial (lower) leaf surfaces during early vegetative growth of soybean plants and analyzed the associated phloem sap composition. Stems harbored greater aphid populations and aphids had shorter development time on stems compared to adaxial and abaxial leaf surfaces. While aphids feeding on the stem took the longest time to begin probing, potentially due to higher density and length of trichomes, this did not impact aphid population growth. Once aphids began probing, the sieve elements were more conducive to feeding as evidenced by less salivation from the stem as compared to either leaf surface. Moreover, vascular sap-enriched exudates from stems had higher sugars and amino acids, which supported higher aphid populations in artificial diet feeding assays. The high quality of stems as a food source may in part explain the shorter development time and overall greater population of aphids observed on stems. In summary, our findings suggest that the choice of feeding location and performance of aphids on a specific plant is driven largely by accessibility to and the quality of nutrients rather than morphological factors.
Meta-matching: a simple framework to translate phenotypic predictive models from big to small data
Authors: He Tong , An Lijun , Feng Jiashi , Bzdok Danilo , Holmes Avram J , Eickhoff Simon B. , Yeo B.T. Thomas 
Published: August 2020

AbstractThere is significant interest in using brain imaging data to predict non-brain-imaging phenotypes in individual participants. However, most prediction studies are underpowered, relying on less than a few hundred participants, leading to low reliability and inflated prediction performance. Yet, small sample sizes are unavoidable when studying clinical populations or addressing focused neuroscience questions. Here, we propose a simple framework – “meta-matching” – to translate predictive models from large-scale datasets tonew unseennon-brain-imaging phenotypes in boutique studies. The key observation is that many large-scale datasets collect a wide range inter-correlated phenotypic measures. Therefore, a unique phenotype from a boutique study likely correlates with (but is not the same as) some phenotypes in some large-scale datasets. Meta-matching exploits these correlations to boost prediction in the boutique study. We applied meta-matching to the problem of predicting non-brain-imaging phenotypes using resting-state functional connectivity (RSFC). Using the UK Biobank (N = 36,848), we demonstrated that meta-matching can boost the prediction of new phenotypes in small independent datasets by 100% to 400% in many scenarios. When considering relative prediction performance, meta-matching significantly improved phenotypic prediction even in samples with 10 participants. When considering absolute prediction performance, meta-matching significantly improved phenotypic prediction when there were least 50 participants. With a growing number of large-scale population-level datasets collecting an increasing number of phenotypic measures, our results represent a lower bound on the potential of meta-matching to elevate small-scale boutique studies.
Reelin deficiency contributes to long-term behavioral abnormalities induced by chronic adolescent exposure to Δ9-tetrahydrocannabinol in mice
Authors: Iemolo Attilio , Nur Aisha , Montilla-Perez Patricia , Risbrough Victoria B , Telese Francesca 
Published: August 2020

AbstractHeavy and frequent use of cannabis during adolescence increases the risk of developing psychiatric disorders. However, the neurobiological mechanisms underlying this vulnerability remain largely unknown. Here, we explore whether adolescent vulnerability to long-term behavioral effects of cannabis is modulated byReelin, a gene implicated in the development of the brain and of psychiatric disorders. To this aim, heterozygous Reeler (HR) mice, that express reduced level ofReelin, were chronically exposed during adolescence to high doses (10mg/kg) of Δ9-tetrahydrocannabinol (THC), a major psychoactive component of cannabis. Mice were tested in early adulthood with multiple behavioral assays, including working memory, social interaction, locomotor activity, anxiety-like responses, stress reactivity, and pre-pulse inhibition. Compared to wild-type (WT), HR mice treated with THC showed impaired social behaviors, elevated disinhibitory phenotypes and increased responsiveness to aversive situations, in a sex-specific manner. Independent of THC exposure, HR mice also spent more time exploring unfamiliar objects, indicating that Reelin modulates novelty seeking behavior. To identify the neuronal ensemble underlying this elevated novelty seeking in HR mice, we mapped the regional brain expression of the immediate early gene,Fos, in mice exposed to novel objects. HR mice exhibited reduced neuronal activation in the lateral septum, a subcortical brain structure implicated in emotions, cognition and reward processes. Overall, these findings show that (1)Reelindeficiency influences behavioral abnormalities caused by heavy consumption of THC during adolescence, and (2) that Reelin plays a role in the neurobiological mechanisms underlying disinhibitory behaviors, such as novelty seeking.Significant StatementThe link between cannabis abuse and the development psychiatric disorders, especially in adolescents, makes understanding the neurobiological mechanisms underlying cannabis effects on the brain a significant biomedical problem. Reelin is a key signaling molecule in the development of the adolescent brain and of psychiatric disorders, but its role in modulating the behavioral changes induced by cannabis remain unknown. Here, we report an interaction betweenReelindeficiency and chronic adolescent exposure to THC, a major psychoactive component of cannabis. This interaction led to cognitive deficits, disinhibitory behaviors and altered emotional reactivity in mice, in a sex-specific manner. These experiments are the first to establish a link between Reelin signaling and the endocannabinoid system targeted by THC.
Redefining De Novo Gammaherpesvirus Infection Through High-Dimensional, Single-Cell Analysis of Virus and Host
Authors: Berger Jennifer N. , Sanford Bridget , Kimball Abigail K. , Oko Lauren M. , Kaspar Rachael E. , Niemeyer Brian F. , Jones Kenneth L. , Clambey Eric T. , van Dyk Linda F. 
Published: August 2020

SUMMARYVirus infection is frequently characterized using bulk cell populations. How these findings correspond to infection in individual cells remains unclear. Here, we integrate high-dimensional single-cell approaches to quantify viral and host RNA and protein expression signatures using de novo infection with a well-characterized model gammaherpesvirus. While infected cells demonstrated genome-wide transcription, individual cells revealed pronounced variation in gene expression, with only 9 of 80 annotated viral open reading frames uniformly expressed in all cells, and a 1000-fold variation in viral RNA expression between cells. Single-cell analysis further revealed positive and negative gene correlations, many uniquely present in a subset of cells. Beyond variation in viral gene expression, individual cells demonstrated a pronounced, dichotomous signature in host gene expression, revealed by measuring host RNA abundance and post-translational protein modifications. These studies provide a resource for the high-dimensional analysis of virus infection, and a conceptual framework to define virus infection as the sum of virus and host responses at the single-cell level.HIGHLIGHTSCyTOF and scRNA-seq identify wide variation in gene expression between infected cells.Host RNA expression and post-translational modifications stratify virus infection.Single cell RNA analysis reveals new relationships in viral gene expression.Simultaneous measurement of virus and host defines distinct infection states.
Swarming bacteria undergo localized dynamic phase transition to form stress-induced biofilms
Authors: Grobas Iago , Polin Marco , Asally Munehiro 
Published: August 2020

SummarySelf-organized multi-cellular behaviors enable cells to adapt and tolerate stressors to a greater degree than isolated cells. However, whether and how cellular communities alter their collective behaviors adaptively upon exposure to stress is largely unclear. Here we address this question usingBacillus subtilis, a model system for bacterial multicellularity. We discover that, upon exposure to a spatial gradient of kanamycin, swarming bacteria activate matrix genes and transit to biofilms. The initial stage of this transition is underpinned by a stress-induced multi-layer formation, emerging from a biophysical mechanism reminiscent to motility-induced phase separation (MIPS). The physical nature of the process suggests that stressors which suppress the expansion of swarms would induce biofilm formation. Indeed, a simple physical barrier also induces a swarm-to-biofilm transition. Based on the gained insight, we propose a promising strategy of antibiotic treatment to effectively inhibit the transition from swarms to biofilms by targeting the localized phase transition.
The luteinizing hormone receptor knock-out mouse as a tool to probe thein vivoactions of gonadotropic hormones/receptors in females
Authors: Jonas Kim Carol , Rivero Müller Adolfo , Oduwole Olayiwola , Peltoketo Hellevi , Huhtaniemi Ilpo 
Published: August 2020

ABSTRACTMouse models with altered gonadotropin functions have provided invaluable insight into the functions of these hormones/receptors. Here we describe the repurposing of the infertile and hypogonadal LHR knockout mouse model (LuRKO), to address outstanding questions in reproductive physiology. Using crossbreeding strategies and physiological and histological analyses, we first addressed the physiological relevance of forced LHR homomerization in female mice using BAC expression of two mutant LHR, that have previously shown to undergo functional complementation and rescue the hypogonadal phenotype of male LuRKO mice. In female LuRKO mice, co-expression of signal and binding deficient LHR mutants failed to rescue the hypogonadal and anovulatory phenotype. This was apparently due to the low-level expression of the two mutant LHR and potential lack of LH/LHR-dependent pleiotropic signaling that has previously been shown to be essential for ovulation. Next, we utilized a mouse model overexpressing human chorionic gonadotropin (hCG) with increased circulating ‘LH/hCG’-like bioactivity to ~40 fold higher than WT females, to determine if high circulating hCG could reveal putative LHR-independent actions. No effects were found, thus, suggesting that LH/hCG mediate their gonadal and non-gonadal effects solely via LHR. Finally, targeted expression of a constitutively active FSHR progressed antral follicles to pre-ovulatory follicles and displayed phenotypic markers of enhanced estrogenic activity but failed to induce ovulation in LuRKO mice. This study highlights the critical importance and precise control of LHR and FSHR for mediating ovarian functions and of the potential re-purposing existing genetically modified mouse models in answering outstanding physiological questions.
Anti-pausing activity of region 4 of the RNA polymerase σ subunit and its regulation by σ-remodeling factors
Authors: Brodolin Konstantin , Morichaud Zakia 
Published: August 2020

ABSTRACTThe basal transcription factors of cellular RNA polymerases (RNAPs) stimulate the initial RNA synthesis via poorly understood mechanisms. Here, we explored the mechanism employed by the bacterial factor σ in promoter-independent initial transcription. We found that the RNAP holoenzyme lacking the promoter-binding domain σ4 is ineffective inde novotranscription initiation and displays high propensity to pausing upon extension of RNAs 3 to 7 nucleotides in length. The σ4 domain stabilizes short RNA:DNA hybrids and suppresses pausing by stimulating RNAP active-center translocation. The anti-pausing activity of σ4 is modulated by its interaction with the β subunit flap domain and by the σ remodeling factors AsiA and RbpA. Our results suggest that the presence of σ4 within the RNA exit channel compensates for the intrinsic instability of short RNA:DNA hybrids by increasing RNAP processivity, thus favoring productive transcription initiation. This “RNAP boosting” activity of the initiation factor is shaped by the the thermodynamics of RNA:DNA interactions and thus, should be relevant for any factor-dependent RNAP.
Shiga toxin remodels the intestinal epithelial transcriptional response to Enterohemorrhagic Escherichia coli
Authors: Warr Alyson R. , Kuehl Carole J. , Waldor Matthew K. 
Published: August 2020

AbstractEnterohemorrhagicEscherichia coli(EHEC) is a food-borne pathogen that causes diarrheal disease and the potentially lethal hemolytic uremic syndrome. We used an infant rabbit model of EHEC infection that recapitulates many aspects of human intestinal disease to comprehensively assess colonic transcriptional responses to this pathogen. Cellular compartment-specific RNA-sequencing of intestinal tissue from animals infected with EHEC strains containing or lacking Shiga toxins (Stx) revealed that EHEC infection elicits a robust response that is dramatically shaped by Stx, particularly in epithelial cells. Many of the differences in the transcriptional responses elicited by these strains were in genes involved in immune signaling pathways, such asIL23A,and coagulation, includingF3, the gene encoding Tissue Factor. RNA FISH confirmed that these elevated transcripts were found almost exclusively in epithelial cells. Collectively, these findings suggest that within the intestine, Stx primarily targets epithelial cells, and that the potent Stx-mediated modulation of innate immune signaling skews the host response to EHEC towards type 3 immunity.Significance StatementEnterohemorrhagicEscherichia coli(EHEC) is a potentially lethal foodborne pathogen. During infection, EHEC releases a potent toxin, Shiga toxin (Stx), into the intestine, but there is limited knowledge of how this toxin shapes the host response to infection. We used an infant rabbit model of infection that closely mimics human disease to profile intestinal transcriptomic responses to EHEC infection. Comparisons of the transcriptional responses to infection by strains containing or lacking Stx revealed that this toxin markedly remodels how the epithelial cell compartment responds to infection. Our findings suggest that Stx biases the intestinal innate immune response to EHEC and provide insight into the complex host-pathogen dialogue that underlies disease.
Production of common carp donor-derived offspring from goldfish surrogate broodstock
Authors: Franěk Roman , Kašpar Vojtěch , Gela David , Pšenička Martin 
Published: August 2020

AbstractBackgroundCommon carp is the fourth most-produced species in worldwide aquaculture. Significant efforts are invested in breeding and preservation of genetic integrity of this important species. However, maintaining carp gene bankin situcan be considered as demanding due to its big body size. Recent progress in reproductive biotechnologies in fish allows improving some unfavourable characteristics of a target species using surrogate reproduction. Germ stem cells (gamete precursors) from one species are transplanted into different surrogate species with small body size. After maturation, surrogates are producing donor-derived progeny. Efficient protocols for cryopreservation of carp male and female germ stem cells have been developed lately. Thus, the next logical goal was to assess the potential of goldfish surrogate to produce donor-derived gametes of common carp after intraperitoneal transplantation of testicular cells.ResultsHigh transplantation success was achieved when 44% of the surviving goldfish produced pure donor-derived gametes of common carp. More importantly, both viable eggs and sperm giving rise to pure common carp progeny were produced, witnessing sustainability of the presented method. Donor-derived identity of the offspring was confirmed by genotyping and typical phenotype corresponding to the donor species. Reproductive performance of chimeras was similar to goldfish controls. Assessment of gamete characteristics showed that the size of donor-derived eggs is between control carp and goldfish eggs. Interestingly, flagellum length in donor-derived spermatozoa was comparable to common carp flagellum and significantly shorter than goldfish flagellum.ConclusionsIn this study, we succeeded in the production of pure common carp progeny from surrogate goldfish recipients transplanted intraperitoneally by testicular germ cells. Here we reported production of viable eggs between most distant species up to date. Good reproductive performance of goldfish germline chimeras gives a promising prospect for further analysis about the long-term reproductive performance of surrogates, recovery of cryopreserved germ cells or production of monosex stocks. Presented technology is ready to ease needs for carp breeds preservation and their recovery using many times smaller goldfish surrogates.
Carbamazepine and GABA have distinct effects on seizure onset dynamics in mouse brain slices
Authors: Crisp Dakota N. , Parent Rachel , Nakatani Mitsuyoshi , Murphy Geoffrey G. , Stacey William C. 
Published: August 2020

AbstractOptimizing antiepileptic drug therapy is very challenging due to the absence of a reliable method to assess how brain activity changes between seizures. This work uses the Taxonomy of Seizure Dynamics (Saggioet al., 2020) to investigate how anticonvulsants influence seizure onset dynamotypes. The no Mg2+/high K+mouse brain-slice seizure model (N = 92) was used to generate consistent epileptiform onsets. We compared the onset bifurcations of controls with slices treated with either GABA or carbamazepine. Each anticonvulsant uniquely changed the types of bifurcations in the slices. This experiment provides proof-of-concept evidence that brain states exist on a “map” of seizure dynamics, and that antiepileptic drugs with different mechanisms can change the positioning of the brain states on the map.Impact statementAntiepileptic drugs modify underlying brain states and influence the pathway into seizure onset in brain slices.
Evaluation of Fecal Immunoassays for CanineEchinococcusInfection in China
Authors: Wang Liying , Wang Qian , Cai Huixia , Wang Hu , Huang Yan , Feng Yu , Bai Xuefei , Qin Min , Manguin Sylvie , Gavotte Laurent , Wu Weiping , Frutos Roger 
Published: August 2020

AbstractHuman echinococcosis is present worldwide but it is in China that prevalence is the highest. Western China and in particular the Tibetan plateau is the region where the burden of echinococcosis is the most important. Dogs are a major carrier of echinococcosis and monitoring the presence ofEchinococcusworms in dogs is therefore essential for efficiently controlling the disease. Detection kits based on three different technologies, i.e. sandwich ELISA, ELISA and gold immunodiffusion are currently marketed and used in China. The objective of this work was to assess the efficacy of these kits, in particular with respect to sensitivity and specificity. Four fecal antigen detection kits for canine echinococcosis covering the three technologies were obtained from companies and tested in parallel on 220 fecal samples. The results indicate that the performance is lower than expected, in particular in terms of sensitivity. The best results were obtained with the sandwich ELISA technology. The gold immunofiltration yielded the poorest results. In all cases, further development is needed to improve the performance of these kits, which represent a key element for the control of echinococcosis.Author summaryAlthough present worldwide, human echinococcosis is at its highest prevalence in Western China and particularly on the Tibetan plateau. Controlling echinococcosis is a national priority and routine monitoring must be established. Dogs are the main carriers of echinococcosis and surveyingEchinococcusworms in dogs is therefore a key issue. Commercial detection kits are currently in use in China for monitoring the presence of Echinococcosis in dogs. These kits are based on three different technologies, i.e. sandwich ELISA with two monoclonal antibodies, ELISA, and gold immunodiffusion. National survey programs are essential for the control of echinococcosis and it is thus very important to assess the efficacy of these kits, planned to be used for the national survey programs. The work was thus undertaken to assess this efficacy, in particular with respect to sensitivity and specificity. Four fecal antigen detection kits for canine echinococcosis covering the three technologies were obtained from companies and tested in parallel on 220 fecal samples. The performance was lower than expected, in particular for their sensitivity, which ranged from 51.5% to 83.9% with only two samples displaying a worm burden lower than 100. Three out of four kits showed non-specific cross-reactions with other parasites. The best results were obtained with the sandwich ELISA technology, whereas gold immunofiltration yielded the poorest results. However, in all cases, further development is strongly needed to improve the performance of these kits, which represent a key element for the control of echinococcosis.