bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel and specific regulator of neuronal V-ATPase inDrosophila
Authors: Dulac Amina , Issa Abdul-Raouf , Sun Jun , Matassi Giorgio , Chérif-Zahar Baya , Cattaert Daniel , Birman Serge 
Published: February 2021

AbstractThe V-ATPase is a highly conserved enzymatic complex that ensures appropriate levels of organelle acidification in virtually all eukaryotic cells. While the general mechanisms of this proton pump have been well studied, little is known about the specific regulations of neuronal V-ATPase. Here, we studied CG31030, a previously uncharacterizedDrosophilaprotein predicted from its sequence homology to be part of the V-ATPase family. We found that this protein is essential and apparently specifically expressed in neurons, where it is addressed to synaptic terminals. We observed that CG31030 co-immunoprecipitated with V-ATPase subunits, in particular with ATP6AP2, and that synaptic vesicles of larval motoneurons were not properly acidified inCG31030knockdown context. This defect was associated with a decrease in quantal size at the neuromuscular junction, severe locomotor impairments and shortened lifespan. Overall, our data provide evidence that CG31030 is a specific regulator of neuronal V-ATPase that is required for synaptic vesicle acidification and neurotransmitter release.
Adoptive transfer of allogeneic gamma delta T cells promotes HIV replication in a humanized mouse model
Authors: Biradar Shivkumar , Agarwal Yash , Lotze Michael T. , Rinaldo Charles R. , Bility Moses T. , Mailliard Robbie B. 
Published: February 2021

AbstractGamma-delta (γδ) T cells recognize antigens in an MHC-independent manner, with demonstrable cytotoxicity against cancer and virally infected cells. Human immunodeficiency virus (HIV) infection severely depletes the Vγ9Vδ2 (Vδ2) subset of these T cells in most infected individuals, with the exception of elite controllers. The capacity of Vδ2 cells to kill HIV-infected targets has been demonstratedin vitro, but this has not been verifiedin vivo. Here, we examined the immunotherapeutic potential of Vδ2 cells in controlling HIV replicationin vivoand provide the first characterization of reconstituted γδ T cell subsets in the peripheral blood and lymphoid tissue in a humanized mouse model. We demonstrate the depletion of Vδ2 cells and increase in Vδ1 cells in the blood following HIV infection, similar to that observed in HIV-infected humans. The functionality of human Vδ2 cells isolated from humanized mice was confirmed viaex vivoexpansion in response to zoledronate and IL-2 treatment. The adoptive transfer of activated Vδ2 cells failed to control HIV infectionin vivobut instead exacerbated viremia by serving as early targets for HIV infection. Our findings suggest that Vδ2 cells play a critical and unappreciated role as early HIV targets of infection to promote viral dissemination.
A refinement to gene editing in Atlantic salmon using asymmetrical oligonucleotide donors
Authors: Straume Anne Hege , Kjærner-Semb Erik , Skaftnesmo Kai Ove , Güralp Hilal , Lillico Simon , Wargelius Anna , Edvardsen Rolf Brudvik 
Published: February 2021

AbstractSelective breeding programs in aquaculture are limited by the heritability of the trait and long generation time in most fish species. New breeding technology (NBT) using CRISPR/Cas9-induced homology directed repair (HDR) have the potential to expedite genetic improvement in aquaculture, but the method requires optimization. Here we show that asymmetrical oligonucleotide (ODN) donors induce highly efficient and precise edits in individual Atlantic salmon founder animals. We performed single nucleotide replacement (SNR) indndwith up to 59.2% efficiency, and inserted FLAG elements intoslc45a2anddnd, with up to 36.7 % and 32.7% efficiency, respectively. We found HDR efficiency to be dependent on template concentration, but a trade-off with respect to toxicity was observed. Using this NBT in salmon we demonstrate that precise modification of the genome can be achieved in a single generation, allowing efficient introgression of favorable alleles and bypassing challenges associated with traditional selective breeding.
Body size dependent dispersal influences stability in heterogeneous metacommunities
Authors: Anderson Kurt E. , Fahimipour Ashkaan K. 
Published: February 2021

AbstractBody size affects key biological processes across the tree of life, with particular importance for food web dynamics and stability. Traits influencing movement capabilities depend strongly on body size, yet the effects of allometrically-structured dispersal on food web stability are less well understood than other demographic processes. Here we study the stability properties of spatially-arranged model food webs in which larger bodied species occupy higher trophic positions, while species’ body sizes also determine the rates at which they traverse spatial networks of heterogeneous habitat patches. Our analysis shows an apparent stabilizing effect of positive dispersal rate scaling with body size compared to negative scaling relationships or uniform dispersal. However, as the global coupling strength among patches increases, the benefits of positive body size-dispersal scaling disappear. A permutational analysis shows that breaking allometric dispersal hierarchies while preserving dispersal rate distributions rarely alters qualitative aspects of metacommunity stability. Taken together, these results suggest that the oft-predicted stabilizing effects of large mobile predators may, for some dimensions of ecological stability, be attributed to increased patch couplingper se, and not necessarily coupling by top trophic levels in particular.
Diet High in Soybean Oil Increases Susceptibility to Colitis in Mice
Authors: Deol Poonamjot , Ruegger Paul , Logan Geoffrey D. , Shawki Ali , Li Jiang , Mitchell Jonathan D. , Yu Jacqueline , Piamthai Varadh , Radi Sarah H. , Borkowski Kamil , Newman John W. , McCole Declan F. , Nair Meera G. , Hsiao Ansel , Borneman James , Sladek Frances M. 
Published: February 2021

SUMMARYThe current American diet is high in soybean oil (SO), which consists of unsaturated fatty acids, most notably linoleic acid (LA, C18:2 omega-6). While LA is an essential fatty acid that must be obtained from the diet, high LA consumption has been linked to the development of inflammatory bowel disease (IBD) in humans. Here, we show that a high fat diet (HFD) based on soybean oil increases susceptibility to colitis in wild-type and IL10 knockout mice. It causes immune dysfunction, decreases colon and crypt length and increases intestinal epithelial barrier permeability; these effects were not observed in low LA HFDs. The SO diet also disrupts the balance of isoforms encoded by the IBD susceptibility gene Hepatocyte Nuclear Factor 4α (HNF4α). Both the SO diet and an LA gavage cause gut dysbiosis: the SO diet increases the abundance of an adherent, invasiveEscherichia coli(AIEC), which can use LA as a carbon source, and the LA gavage decreases the beneficial bacteriaLactobacillus murinus. Metabolomic analysis of both host-associated and cultured bacteria shows that SO increases levels of LA and oxylipins while decreasing eicosapentaenoic acid (EPA, C20:5 omega-3) and endocannabinoids. Our results suggest that excess LA, obtained from a diet high in soybean oil, increases susceptibility to colitis by alterations in intestinal HNF4α, gut microbiota and bioactive metabolites.
Feedforward and feedback interactions between visual cortical areas use different population activity patterns
Authors: Semedo João D. , Jasper Anna I. , Zandvakili Amin , Aschner Amir , Machens Christian K. , Kohn Adam , Yu Byron M. 
Published: February 2021

AbstractBrain function relies on the coordination of activity across multiple, recurrently connected, brain areas. For instance, sensory information encoded in early sensory areas is relayed to, and further processed by, higher cortical areas and then fed back. However, the way in which feedforward and feedback signaling interact with one another is incompletely understood. Here we investigate this question by leveraging simultaneous neuronal population recordings in early and midlevel visual areas (V1-V2 and V1-V4). Using a dimensionality reduction approach, we find that population interactions are feedforward-dominated shortly after stimulus onset and feedback-dominated during spontaneous activity. The population activity patterns most correlated across areas were distinct during feedforward- and feedback-dominated periods. These results suggest that feedforward and feedback signaling rely on separate “channels”, such that feedback signaling does not directly affect activity that is fed forward.
Mechanistic underpinning of nonuniform collective motions in swarming bacteria
Authors: Bera Palash , Wasim Abdul , Mondal Jagannath , Ghosh Pushpita 
Published: February 2021

AbstractSelf-propelled bacteria can exhibit a large variety of non-equilibrium self-organized phenomena. Swarming is one such fascinating dynamical scenario where a number of motile individuals grouped into clusters and move in synchronized flows and vortices. While precedent investigations in rod-like particles confirm that increased aspect-ratio promotes alignment and order, recent experimental studies in bacteriaBacillus subtilisshow a non-monotonic dependence of cell-aspect ratio on their swarming motion. Here, by computer simulations of an agent-based model of selfpropelled, mechanically interacting, rod-shaped bacteria in overdamped condition, we explore the collective dynamics of bacterial swarm subjected to a variation of cell-aspect ratio. When modeled with an identical self-propulsion speed across a diverse range of cell aspect ratio, simulations demonstrate that both shorter and longer bacteria exhibit slow dynamics whereas the fastest speed is obtained at an intermediate aspect ratio. Our investigation highlights that the origin of this observed non-monotonic trend of bacterial speed and vorticity with cell-aspect ratio is rooted in the cell-size dependence of motility force. The swarming features remain robust for a wide range of surface density of the cells, whereas asymmetry in friction attributes a distinct effect. Our analysis identifies that at an intermediate aspect ratio, an optimum cell size and motility force promote alignment, which reinforces the mechanical interactions among neighboring cells leading to the overall fastest motion. Mechanistic underpinning of the collective motions reveals that it is a joint venture of the short-range repulsive and the size-dependent motility forces, which determines the characteristics of swarming.
Atomic structure of human sapovirus capsid by single particle cryo-electron microscopy
Authors: Miyazaki Naoyuki , Murakami Kosuke , Oka Tomoichiro , Miki Motohiro , Iwasaki Kenji , Katayama Kazuhiko , Murata Kazuyoshi 
Published: February 2021

SummarySapovirus is a cause of acute gastroenteritis in humans and animals. Infants and younger children have the greatest disease burden. Although it shares many similarities with norovirus, the lack of detailed structural information has hampered the development of vaccines and therapeutics. Here, we investigated the human sapovirus VLP by single particle cryo-electron microscopy and are the first to report the atomic structure of the capsid at 2.9 Å resolution. The atomic model revealed the domain interactions of the capsid protein and functionally important amino acid residues. The extended loop from the P1 subdomain was involved in interactions in the P2 domain, forming unique arch-like dimeric protrusions of capsid proteins. All hypervariable regions that are important candidates for immune response or receptor binding, formed a large cluster at the top of the P domain. These results pave the way for developing vaccines, antiviral drugs, and diagnostic systems for this infectious disease.
Ongoing production of low-fitness hybrids limits range overlap between divergent cryptic species
Authors: Mikkelsen Else K. , Irwin Darren 
Published: February 2021

AbstractContact zones between recently-diverged taxa provide opportunities to examine the causes of reproductive isolation and to examine the processes that determine whether two species can coexist over a broad region. The Pacific Wren (Troglodytes pacificus) and the Winter Wren(Troglodytes hiemalis) are two morphologically similar songbird species that started diverging about 4 million years ago, older than most sister species pairs. The ranges of these species come into narrow contact in western Canada, where the two species remain distinct in sympatry. To assess evidence for differentiation, hybridization, and introgression in this system, we examined variation in over 250,000 single nucleotide polymorphism markers distributed across the genomes of the two species. The two species formed highly divergent genetic clusters, consistent with long-term differentiation. In a set of 75 individuals from allopatry and sympatry, two first-generation hybrids (i.e., F1’s) were detected, indicating only moderate levels of assortative mating between these taxa. We found no recent backcrosses or F2’s or other evidence of recent breeding success of F1 hybrids, indicating very low or zero fitness of F1 hybrids. Examination of genomic variation shows evidence for only a single backcrossing event in the distant past. The sizeable rate of hybridization combined with very low fitness of F1 hybrids is expected to result in a population sink in the contact zone, largely explaining the narrow overlap of the two species. If such dynamics are common in nature, they could explain the narrow range overlap often observed between pairs of closely related species. Additionally, we present evidence for a rare duplication of a large chromosomal segment from an autosome to the W chromosome, the female-specific sex chromosome in birds.
Single-cell ATAC and RNA sequencing reveal pre-existing and persistent subpopulations of cells associated with relapse of prostate cancer
Authors: Taavitsainen S , Engedal N , Cao S , Handle F , Erickson A , Prekovic S , Wetterskog D , Tolonen T , Vuorinen EM , Kiviaho A , Nätkin R , Häkkinen T , Devlies W , Henttinen S , Kaarijärvi R , Lahnalampi M , Kaljunen H , Nowakowska K , Syvälä H , Bläuer M , Cremaschi P , Claessens F , Visakorpi T , Tammela TLJ , Murtola T , Granberg KJ , Lamb AD , Ketola K , Mills IG , Attard G , Wang W , Nykter M , Urbanucci A 
Published: February 2021

AbstractProstate cancer is profoundly heterogeneous and patients would benefit from methods that stratify clinically indolent from more aggressive forms of the disease. We employed single-cell assay for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identified pre-existing and treatment-persistent cell subpopulations that possess transcriptional stem-like features and regenerative potential when subjected to treatment. We found distinct chromatin landscapes associated with enzalutamide treatment and resistance that are linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent stem-like cells were able to stratify the treatment response of patients. Ultimately, we show that defining changes in chromatin and gene expression in single-cell populations from pre-clinical models can reveal hitherto unrecognized molecular predictors of treatment response. This suggests that high analytical resolution of pre-clinical models may powerfully inform clinical decision-making.
Linking Labs: Interconnecting Experimental Environments
Authors: Schultz Tanja , Putze Felix , Fehr Thorsten , Meier Moritz , Mason Celeste , Ahrens Florian , Herrmann Manfred 
Published: February 2021

AbstractWe introduce the concept ofLabLinking: a technology-based interconnection of experimental laboratories across institutions, disciplines, cultures, languages, and time zones - in other wordsexperiments without borders. In particular, we introduce LabLinking levels (LLL), which define the degree of tightness of empirical interconnection between labs. We describe the technological infrastructure in terms of hard- and software required for the respective LLLs and present examples of linked laboratories along with insights about the challenges and benefits. In sum, we argue that linked labs provide a unique platform for a continuous exchange between scientists and experimenters, thereby enabling a time synchronous execution of experiments performed with and by decentralized user and researchers, improving outreach and ease of subject recruitment, allowing to establish new experimental designs and to incorporate a panoply of complementary biosensors, devices, hard- and software solutions.
Transcriptome signature of cell viability predicts drug response and drug interaction for Tuberculosis
Authors: Srinivas Vivek , Ruiz Rene A. , Pan Min , Christinal Immanuel Selva Rupa , Peterson Eliza J.R. , Baliga Nitin S. 
Published: February 2021

AbstractThe treatment of tuberculosis (TB), which kills 1.8 million each year, remains difficult, especially with the emergence of multidrug resistant strains ofMycobacterium tuberculosis(Mtb). While there is an urgent need for new drug regimens to treat TB, the process of drug evaluation is slow and inefficient owing to the slow growth rate of the pathogen, the complexity of performing bacteriologic assays in a high-containment facility, and the context-dependent variability in drug sensitivity of the pathogen. Here, we report the development of “DRonA” and “MLSynergy”, algorithms to perform rapid drug response assays and predict response of Mtb to novel drug combinations. Using a novel transcriptome signature for cell viability, DRonA accurately detects bacterial killing by diverse mechanisms in broth culture, macrophage infection and patient sputum, providing an efficient, and more sensitive alternative to time- and resource-intensive bacteriologic assays. Further, MLSynergy builds on DRonA to predict novel synergistic and antagonistic multi-drug combinations using transcriptomes of Mtb treated with single drugs. Together DRonA and MLSynergy represent a generalizable framework for rapid monitoring of drug effects in host-relevant contexts and accelerate the discovery of efficacious high-order drug combinations.
Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5
Authors: Harris Andrzej , Wagner Manuel , Du Dijun , Raschka Stefanie , Gohlke Holger , Smits Sander H. J. , Luisi Ben F. , Schmitt Lutz 
Published: February 2021

AbstractPdr5, a member of the extensive ABC transporter superfamily, is representative of a clinically relevant subgroup involved in pleiotropic drug resistance. Through the coupling of nucleotide hydrolysis with drug efflux, Pdr5 homologues enable pathogenic species to survive in the presence of chemically diverse antifungal agents. Our structural and functional results reveal details of an ATP-driven conformational cycle, which mechanically drives drug translocation through an amphipathic channel, and a clamping switch within a conserved linker loop that acts as a nucleotide sensor. One half of the transporter remains nearly invariant throughout the cycle, while its partner undergoes changes that are transmitted across interdomain interfaces to support a peristaltic motion of the pumped molecule. The efflux model proposed here rationalises the pleiotropic impact of Pdr5 and opens avenues for the development of effective antifungal compounds.
Interspecies activation correlations reveal functional correspondences between marmoset and human brain areas
Authors: Hori Yuki , Cléry Justine C. , Schaeffer David J. , Menon Ravi S. , Everling Stefan 
Published: February 2021

AbstractThe common marmoset has enormous promise as a nonhuman primate model of human brain functions. While resting-state functional magnetic resonance imaging (fMRI) has provided evidence for a similar organization of marmoset and human cortices, the technique cannot be used to map the functional correspondences of brain regions between species. This limitation can be overcome by movie-driven fMRI (md-fMRI), which has become a popular tool for non-invasively mapping the neural patterns generated by rich and naturalistic stimulation. Here, we used md-fMRI in marmosets and humans to identify whole-brain functional correspondences between the two primate species. In particular, we describe functional correlates for the well-known human face, body, and scene patches in marmosets. We find that these networks have a similar organization in both species, suggesting a largely conserved organization of higher-order visual areas between New World marmoset monkeys and humans. However, while face patches in humans and marmosets were activated by marmoset faces, only human face patches responded to the faces of other animals. Together, the results demonstrate that md-fMRI is a powerful tool for interspecies functional mapping and characterization of higher-order visual functions.
Differential bioactivity of four BMP-family members as function of biomaterial stiffness
Authors: Sales Adrià , Khodr Valia , Machillot Paul , Fourel Laure , Guevara-Garcia Amaris , Migliorini Elisa , Albigès-Rizo Corinne , Picart Catherine 
Published: February 2021

ABSTRACTWhereas soft biomaterial is not able to induce cell spreading, BMP-2 presented by a soft film has been described to be sufficient to trigger cell spreading, migration and downstream BMP-2 signaling. Based on thin polyelectrolyte films of controlled stiffness, we investigated whether the presentation of four BMP members (2, 4, 7, 9) in a matrix-bound manner may differentially impact cell adhesion and bone differentiation of skeletal progenitors. We performed high content and automated screening of cellular responses, including cell number, cell spreading area, SMAD phosphorylation and alkaline phosphatase activity. The basolateral presentation of the different BMPs allowed us to discriminate the specificity of cellular response and the role of BMP receptors type I, type II, as well as three β integrins, in a BMP type and stiffness-dependent manner.
Prenatal environmental conditions underlie alternative reproductive tactics that drive the formation of a mixed-kin cooperative society
Authors: Shah Shailee S. , Rubenstein Dustin R. 
Published: February 2021

AbstractAlthough animal societies often evolve due to limited natal dispersal that results in kin clustering and facilitates cooperation among relatives, many species form cooperative groups with low and variable kin structure. Groups in such mixed-kin societies often comprise residents and immigrants of the same sex that compete for breeding opportunities. To understand how such mixed-kin societies form despite their potential for social conflict, we investigated the environmental causes and subsequent fitness consequences of dispersal decisions in male cooperatively breeding superb starlings (Lamprotornis superbus) that live in a climatically unpredictable environment. We show that the two alternative reproductive tactics—natal dispersal or philopatry—exhibit reproductive tradeoffs resulting in equal lifetime inclusive fitness. The tactic an individual adopts is governed by the environment its parents experience prior to laying rather than the environment it experiences during its juvenile stage. When individuals adopt the tactic not predicted by early life environmental conditions, their fitness is reduced. Ultimately, climate-driven oscillating selection may help stabilize mixed-kin animal societies, despite their reduced kin structure and potential for social conflict.