bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genomic architecture of adaptation to larval malnutrition points to a trade-off with adult starvation resistance inDrosophila
Authors: Kawecki Tadeusz J. , Erkosar Berra , Dupuis Cindy , Hollis Brian , Stillwell R. Craig , Kapun Martin 
Published: December 2020

AbstractPeriods of nutrient shortage impose strong selection on animal populations. Experimental studies of genetic adaptation to nutrient shortage largely focus on resistance to acute starvation at adult stage; it is not clear how conclusions drawn from these studies extrapolate to other forms of nutritional stress. We studied the genomic signature of adaptation to chronic juvenile malnutrition in six populationsof Drosophila melanogasterevolved for 150 generations on an extremely nutrient-poor larval diet. Comparison with control populations evolved on standard food revealed repeatable genomic differentiation between the two set of population, involving >3,000 candidate SNPs forming >100 independently evolving clusters. The candidate genomic regions were enriched in genes implicated in hormone, carbohydrate, and lipid metabolism, including some with known effects on fitness-related life-history traits. Rather than being close to fixation, a substantial fraction of candidate SNPs segregated at intermediate allele frequencies in all malnutrition-adapted populations. This, together with patterns of among-population variation in allele frequencies and estimates of Tajima’sD, suggests that the poor diet results in balancing selection on some genomic regions. Our candidate genes for tolerance to larval malnutrition showed a high overlap with genes previously implicated in acute starvation resistance. However, adaptation to larval malnutrition in our study was associated with reduced tolerance to acute adult starvation. Thus, rather than reflecting synergy, the shared genomic architecture appears to mediate an evolutionary trade-off between tolerances to these two forms of nutritional stress.
Competition between parallel sensorimotor learning systems
Authors: Albert Scott T. , Jang Jihoon , Haith Adrian M. , Lerner Gonzalo , Della-Maggiore Valeria , Krakauer John W. , Shadmehr Reza 
Published: December 2020

AbstractSensorimotor adaptation benefits from learning in two parallel systems: one that has access to explicit knowledge, and another that relies on implicit, unconscious correction. However, it is unclear how these systems interact: does enhancing one system’s contributions, for example through instruction, impair the other, or do they learn independently? Here we illustrate that certain contexts can lead to competition between implicit and explicit learning. In some cases, each system is responsive to a task-related visual error. This shared error appears to create competition between these systems, such that when the explicit system increases its response, errors are siphoned away from the implicit system, thus reducing its learning. This model suggests that explicit strategy can mask changes in implicit error sensitivity related to savings and interference. Other contexts suggest that the implicit system can respond to multiple error sources. When these error sources conflict, a second type of competition occurs. Thus, the data show that during sensorimotor adaptation, behavior is shaped by competition between parallel learning systems.
Single Cell and Spatial Transcriptomics Defines the Cellular Architecture of the Antimicrobial Response Network in Human Leprosy Granulomas
Authors: Ma Feiyang , Hughes Travis K. , Teles Rosane M.B. , Andrade Priscila R. , de Andrade Silva Bruno J. , Plazyo Olesya , Tsoi Lam C. , Do Tran , Wadsworth Marc H , Oulee Aislyn , Ochoa Maria Teresa , Sarno Euzenir N. , Iruela-Arispe M. Luisa , Bryson Bryan , Shalek Alex K. , Bloom Barry R. , Gudjonsson Johann E. , Pellegrini Matteo , Modlin Robert L. 
Published: December 2020

AbstractGranulomas are complex cellular structures comprised predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated single cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RR), a dynamic process in which some patients with disseminated lepromatous leprosy (L-lep) transition towards self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions, and regulated by IFN-γ and IL-1β. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts contribute to the antimicrobial response.
Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues
Authors: Yang Fan , Nielsen Sandra C. A. , Hoh Ramona A. , Lee Ji-Yeun , Pham Tho D. , Jackson Katherine J. L. , Roskin Krishna M. , Liu Yi , Ohgami Robert S. , Osborne Eleanor M. , Niemann Claus U. , Parsonnet Julie , Boyd Scott D. 
Published: December 2020

AbstractVaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells encoding humoral immune memory. We evaluated convergent antigen-specific antibody genes of similar sequences shared between individuals in pediatric and adult blood, and deceased organ donor tissues. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults’ convergent clones often express mutated IgM or IgD in blood and are class-switched in lymphoid tissues; in contrast, children have abundant class-switched convergent clones in blood. Consistent with serological reports, pre-pandemic children had class-switched convergent clones to SARS-CoV-2, enriched in cross-reactive clones for seasonal coronaviruses, while adults showed few such clones in blood or lymphoid tissues. These results extend age-related and anatomical mapping of human humoral pathogen-specific immunity.One Sentence SummaryChildren have elevated frequencies of pathogen-specific class-switched memory B cells, including SARS-CoV-2-binding clones.
Genetic and pharmacological evidence for kinetic competition between alternative poly(A) sites in yeast
Authors: Turner Rachael E. , Harrison Paul F. , Swaminathan Angavai , Kraupner-Taylor Calvin A. , Curtis Melissa J. , Goldie Belinda J. , See Michael M. , Peterson Amanda L. , Schittenhelm Ralf B. , Powell David R. , Creek Darren J. , Dichtl Bernhard , Beilharz Traude H. 
Published: December 2020

ABSTRACTMost eukaryotic mRNAs accommodate alternative sites of poly(A) addition in the 3’ untranslated region in order to regulate mRNA function. Here we present a systematic analysis of 3’ end formation factors, which revealed 3’UTR lengthening in response to a loss of the core machinery, whereas a loss of the Sen1 helicase resulted in shorter 3’UTRs. We show that the anti-cancer drug cordycepin, 3’ deoxyadenosine, caused nucleotide accumulation and the usage of distal poly(A) sites. Mycophenolic acid, a drug which reduces GTP levels and impairs RNA polymerase II (RNAP II) transcription elongation, promoted the usage of proximal sites and reversed the effects of cordycepin on alternative polyadenylation. Moreover, cordycepin mediated usage of distal sites was associated with a permissive chromatin template and was suppressed in the presence of anrpb1mutation, which slows RNAP II elongation rate. We propose that alternative polyadenylation is governed by temporal coordination of RNAP II transcription and 3’ end processing and controlled by the availability of 3’ end factors, nucleotide levels and chromatin landscape.
Decision value signals in the ventromedial prefrontal cortex and motivational and hedonic symptoms across mood and psychotic disorders
Authors: Kang Min Su , Wolf Daniel H. , Kazinka Rebecca , Lee Sangil , Ruparel Kosha , Elliott Mark A. , Xu Anna , Cieslak Matthew , Prettyman Greer , Satterthwaite Theodore D. , Kable Joseph W. 
Published: December 2020

AbstractDeficits in motivation and pleasure are common across many psychiatric disorders, and manifest as symptoms of amotivation and anhedonia, which are prominent features of both mood and psychotic disorders. Here we provide evidence for a shared transdiagnostic mechanism underlying impairments in motivation and pleasure across major depression, bipolar disorder, and schizophrenia. We found that value signals in the ventromedial prefrontal cortex (vmPFC) during decision-making were dampened in individuals with greater motivational and hedonic deficits, regardless of the primary diagnosis. This relationship remained significant while controlling for diagnosis-specific symptoms of mood and psychosis, such as depression as well as positive and negative symptoms. Our results demonstrate that dysfunction in the vmPFC during value-based decision-making is specifically linked to motivational and hedonic impairments across various psychiatric conditions. These findings provide a quantitative neural target for the potential development of novel treatments for amotivation and anhedonia.
Hamster PIWI proteins bind to piRNAs with stage-specific size variations during oocyte maturation
Authors: Ishino Kyoko , Hasuwa Hidetoshi , Yoshimura Jun , Iwasaki Yuka W. , Nishihara Hidenori , Seki Naomi M. , Hirano Takamasa , Tsuchiya Marie , Ishizaki Hinako , Masuda Harumi , Kuramoto Tae , Saito Kuniaki , Sakakibara Yasubumi , Toyoda Atsushi , Itoh Takehiko , Siomi Mikiko C. , Morishita Shinichi , Siomi Haruhiko 
Published: December 2020

AbstractIn animal gonads, transposable elements (TEs) are actively repressed to preserve genome integrity through the Piwi-interacting RNA (piRNA) pathway. In mice, piRNAs are most abundantly expressed in male germ cells, and form effector complexes with three distinct PIWI proteins. The depletion of individualPiwigenes causes male-specific sterility owing to severe defects in spermatogenesis with no discernible phenotype in female mice. Unlike mice, most other mammals have four PIWI genes, some of which are expressed in the ovary. Here, purification of PIWI complexes from oocytes of the golden hamster revealed that the size of the piRNAs loaded onto PIWIL1 changed during oocyte maturation. In contrast, PIWIL3, an ovary-specific PIWI in most mammals, associates with short piRNAs only in metaphase II oocytes, which coincides with intense phosphorylation of the protein. An improved high-quality genome assembly and annotation revealed that PIWIL1- and PIWIL3-associated piRNAs appear to share the 5′- ends of common piRNA precursors and are mostly derived from unannotated sequences with a diminished contribution from TE-derived sequences, most of which correspond to endogenous retroviruses (ERVs). Although binding sites for the transcription factor A-Myb are identified in the transcription start site regions of the testis piRNA clusters, the piRNA clusters in the ovary show no well-defined binding motifs in their upstream regions. These results show that hamster piRNA clusters are transcribed by different transcriptional factors in the ovary and testis, resulting in the generation of sex-specific piRNAs. Our findings show the complex and dynamic nature of biogenesis of piRNAs in hamster oocytes, and together with the new genome sequence generated, serve as the foundation for developing useful models to study the piRNA pathway in mammalian oocytes.Highlights-The size of PIWIL1-associated piRNAs changes during oocyte maturation-Phosphorylation of PIWIL3 in MII oocytes coincides with its association with small 19-nt piRNAs-Improved high-quality genome assembly and annotation identifies young endogenous retroviruses as major targets of piRNAs in hamster oocytes-PIWIL1- and PIWIL3-associated piRNAs share the 5′-ends of the common piRNA precursors in oocytes
Binding Profile Mapping of the S100 Protein Family Using a High-throughput Local Surface Mimetic Holdup Assay
Authors: Simon Márton A. , Bartus Éva , Mag Beáta , Boros Eszter , Roszjár Lea , Gógl Gergő , Travé Gilles , Martinek Tamás A. , Nyitray László 
Published: December 2020

AbstractS100 proteins are small, typically homodimeric, vertebrate-specific EF-hand proteins that establish Ca2+-dependent protein-protein interactions in the intra- and extracellular environment and are overexpressed in various pathologies. There are about 20 distinct human S100 proteins with numerous potential partner proteins. Here, we used a quantitative holdup assay to measure affinity profiles of most members of the S100 protein family against a library of chemically synthetized foldamers. The profiles allowed us to quantitatively map the binding promiscuity of each member towards the foldamer library. Since the library was designed to systematically contain most binary natural amino acid side chain combinations, the data also provide insight into the promiscuity of each S100 protein towards all potential naturally-occurring S100 partners in the human proteome. Such information will be precious for future drug design of modulators of S100 pathological activities.
Ageing disrupts reinforcement learning whilst learning to help others is preserved
Authors: Cutler Jo , Wittmann Marco , Abdurahman Ayat , Hargitai Luca , Drew Daniel , Husain Masud , Lockwood Patricia 
Published: December 2020

AbstractReinforcement learning is a fundamental mechanism displayed by many species. However, adaptive behaviour depends not only on learning about actions and outcomes that affect ourselves, but also those that affect others. Here, using computational reinforcement learning models, we tested whether young (age 18-36) and older (age 60-80, total n=152) adults can learn to gain rewards for themselves, another person (prosocial), or neither individual (control). Detailed model comparison showed that a model with separate learning rates for each recipient best explained behaviour. Young adults were faster to learn when their actions benefitted themselves, compared to helping others. Strikingly, compared to younger adults, older adults showed preserved prosocial learning rates but reduced self-relevant learning rates. Moreover, psychopathic traits were lower in older adults and negatively correlated with prosocial learning. These findings suggest learning how to benefit others is preserved across the lifespan with implications for reinforcement learning and theories of healthy ageing.
One hundred million years history of bornavirus infections hidden in vertebrate genomes
Authors: Kawasaki Junna , Kojima Shohei , Mukai Yahiro , Tomonaga Keizo , Horie Masayuki 
Published: December 2020

AbstractAlthough viruses have threatened our ancestors for millions of years, prehistoric epidemics of viruses are largely unknown. Endogenous bornavirus-like elements (EBLs) are ancient viral sequences that have been integrated into animal genomes. These elements can be used as molecular fossil records to trace past bornaviral infections. In this study, we systematically identified EBLs in vertebrate genomes and revealed the history of bornavirus infections over nearly 100 million years. We found that ancient bornaviral infections have occurred in diverse vertebrate lineages, especially in primate ancestors. Phylogenetic analyses indicated that primate ancestors had been infected with various bornaviral lineages during evolution. Moreover, EBLs in primate genomes formed clades according to their integration ages, suggesting that epidemic lineages of bornaviruses had changed chronologically. However, we found that some bornaviral lineages coexisted with primate ancestors and underwent repeated endogenizations for tens of millions of years. Furthermore, this viral lineage that coexisted with primate ancestors was also endogenized in some ancestral bats. Notably, the geographic distributions of these bat ancestors have been reported to overlap with the migration route of primate ancestors, suggesting that long-term virus-host coexistence could have expanded the geographic distributions of the viral lineage and might have spread their infections to new hosts. Thus, our findings describe hidden virus-host co-evolutionary history over geological timescales, including chronological change in epidemic bornaviral lineages, long-term virus-host coexistence, and expansion of viral infections.
Optimization of antifungal edible pregelatinized potato starch-based coating formulations by response surface methodology to extend postharvest life of ‘Orri’ mandarins
Authors: Soto-Muñoz Lourdes , Palou Lluís , Argente-Sanchis Maricruz , Ramos-López Miguel Angel , Pérez-Gago María B. 
Published: December 2020

AbstractAntifungal composite edible coatings (ECs) formulated with pregelatinized potato starch (PPS, 1.0-2.0 % w/w) as biopolymer, glyceryl monostearate (GMS, 0.5-1.5 %, w/w) as hydrophobe, glycerol (Gly, 0.5-1.5 %, w/w) as plasticizer, and sodium benzoate (SB, 2 % w/w) as antifungal agent were optimized using the Box–Behnken response surface methodology to extend the postharvest life of Orri’ mandarins. The second order polynomial models satisfactorily fitted the experimental data, with high values of the coefficient of determination for the different variables (R2>0.91). The individual linear effect of GMS concentration was significant in all the responses evaluated, whereas PPS only affected emulsion viscosity, fruit tacking, and weight loss of coated mandarins. Gly only affected acetaldehyde content in the juice of coated mandarins when interacted with PPS and in the quadratic effect. The optimum concentrations of PPS, GMS, and Gly for the starch-based EC based on maximum fruit quality and required emulsion properties were predicted to be 2.0, 0.5 and 1.0 % (w/w), respectively. The optimal EC reduced weight loss of mandarins and created a modified atmosphere within the fruit without negatively affecting the overall acceptability of the fruit. On the other hand, the optimized antifungal EC containing SB significantly reduced postharvest green and blue molds and sour rot on mandarins artificially inoculated with the pathogensPenicillium digitatum, Penicillium italicumandGeotrichum citri-aurantii,respectively. Therefore, the optimized antifungal EC showed potential to control the main postharvest diseases and maintain the overall quality of ‘Orri’ mandarins and could be a suitable alternative to commercial citrus waxes formulated with conventional chemical fungicides.
Nuku, a family of primate retrogenes derived fromKU70
Authors: Rowley Paul A. , Ellahi Aisha , Han Kyudong , Patel Jagdish Suresh , Sawyer Sara L. 
Published: December 2020

AbstractThe ubiquitous DNA repair protein, Ku70p, has undergone extensive copy number expansion during primate evolution. Gene duplications ofKU70have the hallmark of long interspersed element-1 (LINE-1) mediated retrotransposition with evidence of target-site duplications, the poly-A tails, and the absence of introns. Evolutionary analysis of this expanded family ofKU70-derived “NUKU” retrogenes reveals that these genes are both ancient and also actively being created in extant primate species.NUKUretrogenes show evidence of functional divergence away fromKU70, as evinced by their altered pattern of tissue expression and possible translation in the human testes. Molecular modeling predicted that mutations in Nuku2p at the interaction interface with Ku80p would prevent the assembly of the Ku heterodimer. The lack of Nuku2p-Ku80p interaction was confirmed by yeast two-hybrid assay, which contrasts the robust interaction of Ku70p-Ku80p. While severalNUKUretrogenes appear to have been degraded by mutation,NUKU2shows evidence of positive natural selection, suggesting that this retrogene is undergoing neofunctionalization. Although Nuku proteins do not appear to antagonize retroviruses in cell culture, the observed expansion and rapid evolution ofNUKUscould be being driven by alternative selective pressures related to infectious disease or an undefined role in primate physiology.
Evaluating Coarse-Grained MARTINI Force-Fields for Capturing the Ripple Phase of Lipid Membranes
Authors: Sharma Pradyumn , Desikan Rajat , Ayappa K. Ganapathy 
Published: December 2020

AbstractPhospholipids, which are an integral component of cell membranes, exhibit a rich variety of lamellar phases modulated by temperature and composition. Molecular dynamics (MD) simulations have greatly enhanced our understanding of phospholipid membranes by capturing experimentally observed phases and phase transitions at molecular resolution. However, the ripple (Pβ′) membrane phase, observed as an intermediate phase below the main gel-to-liquid crystalline transition with some lipids, has been challenging to capture with MD simulations, both at all-atom and coarse-grained (CG) resolution. Here, with an aggregate ~2.5 μs all-atom and ~122 μs CG MD simulations, we systematically assess the ability of six CG MARTINI 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid and water force-field (FF) variants, parametrized to capture the DPPC gel and fluid phases, for their ability to capture thePβ′phase, and compared observations with those from an all-atom FF. Upon cooling from the fluid phase to below the phase transition temperature with smaller (380-lipid) and larger (> 2200-lipid) MARTINI and all-atom (CHARMM36 FF) DPPC lipid bilayers, we observed that smaller bilayers with both all-atom and MARTINI FFs sampled interdigitatedPβ′and ripple-like states, respectively. However, while all-atom simulations of the larger DPPC membranes exhibited the formation of thePβ′phase, similar to previous studies, MARTINI membranes did not sample interdigitated ripple-like states at larger system sizes. We then demonstrated that the ripple-like states in smaller MARTINI membranes were kinetically-trapped structures caused by finite size effects rather than being representative of truePβ′phases. We showed that even a MARTINI FF variant that could capture the tiltedLβ′gel phase, a prerequisite for stabilizing thePβ′phase, could not capture the rippled phase upon cooling. Our study reveals that the current MARTINI FFs (including MARTINI3) may require specific re-parametrization of the interaction potentials to stabilize lipid interdigitation, a characteristic of the ripple phase.TOC Graphic
Primary cilia sensitize insulin receptor-mediated negative feedback in pancreatic β cells
Authors: Li Yuezhe , Shrestha Prem. K. , Wu Yi I. 
Published: December 2020

AbstractInsulin receptors (IR) can localize to the primary cilia of pancreatic β cells. Because primary cilia are known to sensitize or bias the signaling of cell surface receptors, we investigate how ciliary insulin receptors influence glucose-stimulated insulin secretion (GSIS) in β cells by gauging how cytosolic calcium concentration changes in a mouse insulinoma cell line (MIN6). Purified recombinant insulin suppresses calcium elevation in response to glucose in these cells. Interestingly, ciliated cells show attenuated cytosolic calcium elevation compared to cilium-free cells after glucose stimulation even in the absence of exogenous insulin. We observe that ciliary IR is highly phosphorylated, and the phospho-IR density decreases when cells are either treated with an insulin receptor (IR) inhibitor, BMS536924, or ciliary function is disrupted through either IFT88 or BBS1 knockdown. Consistently, the attenuation of calcium elevation in ciliated cells is abrogated when cells are either treated with IR inhibitor or when primary cilia are impaired. We further demonstrate that ciliary IR signaling hyperpolarizes the plasma membrane but has no apparent impact on glucose-induced ATP production. Thus, our results argue that primary cilia sensitize insulin receptor signaling and mediate negative feedback in GSIS in pancreatic β cells.