bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanism of high affinity sugar transport in plants unveiled by structures of glucose/H+symporter STP10
Authors: Bavnhøj Laust , Paulsen Peter Aasted , Flores-Canales Jose C. , Schiøtt Birgit , Pedersen Bjørn Panyella 
Published: November 2020

ABSTRACTSugars are essential sources of energy and carbon, and also function as key signaling molecules in plants. Sugar Transport Proteins (STP) are proton-coupled symporters, solely responsible for uptake of glucose from the apoplastic compartment into cells in all plant tissues. They are integral to organ development in symplastically isolated tissues such as seeds, pollen and fruit. Additionally, STPs play a significant role in plant responses to both environmental stressors such as dehydration, and prevalent fungal infections like rust and mildew. Here, we present two high-resolution crystal structures of the outward-occluded and inward-open conformations ofArabidopsis thalianaSTP10 with glucose and protons bound. The two structures describe key states in the STP transport cycle. Together within vivobiochemical analysis and Molecular Dynamics simulations they pinpoint structural elements that explain how STPs exhibit high affinity for sugar binding on the extracellular side and how it is considerably lowered on the intracellular side to facilitate substrate release. These structural elements, conserved in all STPs across plant species, clarify the basis of proton-to-glucose coupling, essential for symport. The results advance our understanding of a key molecular mechanism behind plant organ development, and sets the stage for novel bioengineering strategies in crops that could target seeds, fruits and plant resistance to fungal infections.
Immunocompetent Mouse Model for Crimean-Congo Hemorrhagic Fever Virus
Authors: Hawman David W. , Meade-White Kimberly , Leventhal Shanna , Feldmann Friederike , Okumura Atsushi , Smith Brian , Scott Dana , Feldmann Heinz 
Published: November 2020

AbstractCrimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. CCHF is caused by infection with the Crimean-Congo hemorrhagic fever virus (CCHFV) and case fatality rates can be as high as 30%. Despite causing severe disease in humans, our understanding of the host and viral determinants of CCHFV pathogenesis are limited. A major limitation in the investigation of CCHF has been the lack of suitable small animal models. Wild-type mice are resistant to clinical isolates of CCHFV and consequently, mice must be deficient in type I interferon responses to study the more severe aspects of CCHFV. We report here a mouse-adapted variant of CCHFV that recapitulates in adult, immunocompetent mice the severe CCHF observed in humans. This mouse-adapted variant of CCHFV significantly improves our ability to study host and viral determinants of CCHFV-induced disease in a highly tractable mouse model.
Innate fear responses are reflected in the blood epigenome of rhesus macaques
Authors: Bravo-Rivera Hector , Lardenoije Roy , Merced Dimaris , Mas-Rivera Adaris , Ayala James E. , Gonçalves Joana P. , Seligowski Antonia V. , Jovanovic Tanja , Ressler Kerry J. , Klengel Torsten , Quirk Gregory J. 
Published: November 2020

AbstractFear and anxiety are complex physiological states aimed at promoting adaptive behaviors. They are also core symptoms of many neuropsychiatric disorders; yet, our knowledge of the underlying biological correlates remains fragmented. Non-human primate models are critical for our understanding of mechanisms associated with complex higher-order behavioral phenotypes. Here we investigated individual variations in innate fear responses to a snake stimulus in free-ranging rhesus macaques and discovered an unusual bimodal distribution of fearful and fearless behavior, likely as a result of an environmental insult by a hurricane. In a translational approach, we discovered a DNA methylation profile associated with fear behavior in these monkeys. We also found evidence that this epigenetic signature is associated with innate fear responses in humans in the form of acoustic startle. Our data highlight the importance and translational utility of non-human primate models for neuropsychiatric research and provide a potential epigenetic signature of innate fear.
Warmer temperatures result in maladaptive learning of sexual preferences
Authors: Holveck Marie-Jeanne , Muller Doriane , Visser Bertanne , Timmermans Arthur , Colonval Lidwine , Jan Fabrice , Crucifix Michel , Nieberding Caroline M. 
Published: November 2020

AbstractThe impact of learning ability and sexual selection on the climate and biodiversity crisis are currently unclear.Using the African butterfly Bicyclus anynana, which shows strong phenotypic plasticity (i.e., polyphenism) in response to temperature, we tested whether learning affects mate preferences under climate warming.We first modelled climate warming scenarios and then showed experimentally that as temperature becomes an unreliable cue to the onset of the dry season, adult butterflies displayed the wet season rather than the dry season form.Experienced females that were exposed to different male seasonal phenotypes during sexual maturation changed sexual preferences.Female fertilization success was reversed for naive compared to experienced females, likely reducing female fitness following climate warming.Our results emphasize the importance of sexual selection, learning, and their fitness consequences for understanding (mal)adaptation of natural populations to climate warming.
Synergy and allostery in ligand binding by HIV-1 Nef
Authors: Aldehaiman Abdullah , Momin Afaque A. , Restouin Audrey , Wang Luyao , Shi Xiaoli , Aljedani Safia , Opi Sandrine , Lugari Adrien , Hameed Umar F. Shahul , Ponchon Luc , Morelli Xavier , Huang Mingdong , Dumas Christian , Collette Yves , Arold Stefan T. 
Published: November 2020

AbstractThe Nef protein of human and simian immunodeficiency viruses (HIV and SIV, respectively) boosts viral pathogenicity through its interactions with host cell proteins. Nef has a folded core domain and large flexible regions, each carrying several protein interaction sites. By combining the polyvalency intrinsic to unstructured regions with the binding selectivity and strength of a 3D folded domain, Nef can bind to many different host cell proteins, perturbing their cellular functions. For example, the combination of a linear proline-rich motif and a hydrophobic core domain surface allows Nef to increase affinity and selectivity for particular Src family SH3 domains. Here we investigated whether the interplay between Nef’s flexible regions and its core domain can allosterically influence ligand selection. We found that the flexible regions can bind back to the core domain in different ways, producing distinct conformational states that alter the SH3 domain selectivity and availability of Nef’s functional motifs. The resulting cross-talk might help synergising certain subsets of ligands while excluding others, promoting functionally coherent Nef-bound protein ensembles. Further, we combined proteomic and bioinformatic analyses to identify human proteins that select SH3 domains in the same way as does Nef. We found that only 2–3% of clones from a whole human fetal library displayed a Nef-like SH3 selectivity. However, in most cases this selectivity appears to be achieved by a canonical linear interaction rather than a Nef-like ‘tertiary’ interaction. This analysis suggests that Nef’s SH3 recognition surface has no (or marginally few) cellular counterparts, validating the Nef tertiary binding surface as a promising unique drug target.
High-resolution electrochemistry of the extracellular electron transfer ofEscherichia coli
Authors: Xiao Yong , Zheng Zhiyong , Gang Haiyin , Ulstrup Jens , Zhao Feng , Zhang Jingdong 
Published: November 2020

AbstractEscherichia coliis one of the most important model bacteria in microorganism research and is broadly encountered in nature. In the present study, a wild-typeE. colistrain K-12 was used for electrochemical investigations. Differential pulse voltammetry showed five pairs of redox peaks both for K-12 cells and the supernatant with potentials (anodic/cathodic) at −0.450/−0.378, −0.125/−0.105, −0.075/−0.055, +0.192/+0.264, and +0.300/+0.414 V (vs. Ag/AgCl), respectively. Chronoamperometry indicates that K-12 cells can produce immediate current by addition of glucose. The current production from K-12 can be 8-fold enhanced by 10.0 μM exogenetic vitamin K3, but addition of 10.0 μM riboflavin did not enhance the current production. Medium replacement experiments show that 50 % of the K-12 biofilm current was produced via direct extracellular electron transfer pathways. The study provides new insight in the voltammetry of strain K-12 and confirms thatE. coliis an electrochemically active bacterium.E. colihas the potential to serve as a model bacterium for studying microbial extracellular electron transfer mechanisms.
“CandidatusDechloromonas phosphatis” and “CandidatusDechloromonas phosphovora”, two novel polyphosphate accumulating organisms abundant in wastewater treatment systems
Authors: Petriglieri Francesca , Singleton Caitlin , Peces Miriam , Petersen Jette F. , Nierychlo Marta , Nielsen Per H. 
Published: November 2020

AbstractMembers of the genusDechloromonasare often abundant in enhanced biological phosphorus removal (EBPR) systems and are recognized putative polyphosphate accumulating organisms (PAOs), but their role in phosphate (P) removal is still unclear. Here, we used 16S rRNA gene sequencing and fluorescencein situhybridization (FISH) to investigate the abundance and distribution ofDechloromonasspp. in Danish wastewater treatment plants. Two species were abundant, novel, and uncultured, and could be targeted by existing FISH probes. Raman microspectroscopy of probe-defined organisms (FISH-Raman) revealed the levels and dynamics of important intracellular storage polymers in abundantDechloromonasspp. in the activated sludge from four full-scale EBPR plants and from a lab-scale sequencing batch reactor fed with different carbon sources (acetate, glucose, glycine, and glutamate). Moreover, 7 distinctDechloromonasspecies were determined from a set of 10 high-quality metagenome-assembled genomes (MAGs) from Danish EBPR plants, each encoding the potential for poly-P, glycogen, and polyhydroxyalkanoates (PHA) accumulation. The two most abundant species exhibited anin situphenotype in complete accordance with the metabolic information retrieved by the MAGs, with dynamic levels of poly-P, glycogen, and PHA during feast-famine anaerobic-aerobic cycling, legitimately placing these microorganisms among the important PAOs. As no isolates are available for the two species, we propose the namesCandidatusDechloromonas phosphatis andCandidatusDechloromonas phosphovora.
The human ApoE4 variant reduces functional recovery and neuronal sprouting after incomplete spinal cord injury in male mice
Authors: Toro Carlos A. , Hansen Jens , Siddiq Mustafa M. , Johnson Kaitlin , Zhao Wei , Azulai Daniella , Das Dibash K. , Bauman William , Sebra Robert , Cai Dongming , Iyengar Ravi , Cardozo Christopher P. 
Published: November 2020

AbstractSpinal cord injury (SCI) is a devastating form of neurotrauma. Patients who carry one or two ApoE4 alleles show worse functional outcomes and longer hospital stays after SCI but the cellular and molecular underpinnings for this genetic link remain poorly understood. Thus, there is a great need to generate animal models to accurately replicate the genetic determinants of outcomes after SCI to spur development of treatments that improve physical function. Here, we examined outcomes after a moderate contusion SCI of transgenic mice expressing human ApoE3 or ApoE4. ApoE4 mice have worse locomotor function and coordination after SCI. Histological examination revealed greater glial staining in ApoE4 mice after SCI associated with reduced levels of neuronal sprouting markers. Bulk RNA sequencing revealed that subcellular processes (SCPs), such as extracellular matrix organization and inflammatory responses, were highly-ranked among upregulated genes at 7 days after SCI in ApoE4 variants. Conversely, SCPs related to neuronal action potential and neuron projection development were increased in ApoE3 mice at 21 days. In summary, our results reveal a clinically relevant SCI mouse model that recapitulates the influence of ApoE genotypes on post-SCI function in individuals who carry these alleles and suggest that the mechanisms underlying worse recovery for ApoE4 animals involve glial activation and loss of sprouting and synaptic activity.
BCL11b interacts with RNA and proteins involved in RNA processing and developmental diseases
Authors: Sobhy Haitham , Rovere Marco De , Ait-Ammar Amina , Kashif Muhammad , Wallet Clementine , Daouad Fadoua , Loustau Thomas , Lint Carine Van , Schwartz Christian , Rohr Olivier 
Published: November 2020

ABSTRACTBCL11b (B-cell lymphoma/leukemia 11B, CTIP2) is a C2H2 zinc-finger transcription regulator and tumor suppressor. BCL11b is involved in lymphomagenesis and in fetal, central nervous system (CNS) and immune system developments. Therefore, it may contribute in congenital disorders and cancers (e.g. leukemia). BCL11b favors persistence of HIV latency in microglia, CNS macrophages. BCL11b contributes to control cell cycle, differentiation and apoptosis in multiple organisms and cell models; however exact mechanisms are unknown. Although BCL11b recruits non-coding RNA and epigenetic enzymes to regulate gene expression, BCL11b-associated ribonucleoprotein complexes are unknown. Here, using immunoprecipitation of BCL11b-binding RNA and proteins (CLIP-seq and quantitative LC-MS/MS mass spectrometry) complemented with systems biology validations, we show that BCL11b interacts with RNA splicing and nonsense-mediated decay proteins, including FUS, SMN1, UPF1 and Drosha, which may contribute in isoform selection of protein-coding RNA isoforms from noncoding-RNAs isoforms (retained introns or nonsense mediated RNA). Interestingly, BCL11b binds to RNA transcripts and proteins encoded by the same genes (FUS, ESWR1, CHD and Tubulin). Our study highlights that BCL11b targets RNA processing and splicing proteins, and RNAs that implicate cell cycle, development, neurodegenerative, and cancer pathways. These findings will help future mechanistic understanding of developmental disorders.IMPORTANCEFirst genome-wide BCL11b-protein and RNA interactome BCL11b interacts with RNA processing and splicing proteins BCL11b interacts with neurodegenerative genes and sarcoma genes BCL11b targets during cell proliferation and disease pathways
AMPK Modulates Associative Learning via Neuronal Mitochondrial Fusion inC. elegans
Authors: Escoubas Caroline C. , Laversenne Vanessa , Tabakovic Emina , Weir Heather J. , Clark Nicole , Mair William B. 
Published: November 2020

ABSTRACTLoss of metabolic homeostasis is one of the hallmarks of the aging process that might contribute to pathogenesis by creating a permissive landscape over which neurodegenerative diseases can take hold. AMPK, a conserved energy sensor, extends lifespan and is protective in some neurodegenerative models. AMPK regulates mitochondrial homeostasis and morphology, however, whether mitochondrial regulation causally links AMPK to protection against loss of neuronal function with aging and diseases remains unclear. Here we use an associative learning protocol inC. elegansas a readout of neuronal function and show that AMPK activation enhances associative learning and prevents age-related loss of learning capacity. AMPK promotes neuronal mitochondrial fusion and mitochondrial fragmentation viafzo-1deletion blocks AMPK’s effects on associative learning. Restoring mitochondrial fusion capacity specifically in the neurons rescued learning capacity downstream of AMPK. Finally, AMPK activation rescues neuronal Aβ1-42induced loss of associative learning. Overall, our results suggest that targeting neuronal metabolic flexibility may be a viable therapeutic option to restore neuronal function in the context of aging and neurodegenerative diseases.
Boreal forests will be more severely affected by projected anthropogenic climate forcing than mixedwood and northern hardwood forests in eastern Canada
Authors: Boulanger Yan , Puigdevall Jesus Pascual 
Published: November 2020

AbstractContextIncreased anthropogenic climate forcing is projected to have tremendous impacts on global forest ecosystems, with northern biomes being more at risk.ObjectivesTo model the impacts of harvest and increased anthropogenic climate forcing on eastern Canada’s forest landscapes and to assess the strong spatial heterogeneity in the severity, the nature and direction of the impacts expected within northern forest regions.MethodsWe used LANDIS-II to project species-specific aboveground biomass (AGB) between 2020 and 2150 under three climate (baseline, RCP 4.5 and RCP 8.5) and two harvest (baseline harvest, no harvest) scenarios within four forest regions (boreal west, boreal east, mixedwood and northern hardwood).ResultsClimate change impacts within the boreal forest regions would mainly result from increases in wildfires activity which will strongly alter total AGB. In the mixedwood and northern hardwood, changes will be less important and will result from climate-induced growth constraints that will alter species composition towards more thermophilous species. Climate-induced impacts were much more important and swifter under RCP 8.5 after 2080 suggesting that eastern Canada’s forests might cross important tipping points under strong anthropogenic climate forcing.ConclusionsBoreal forest regions will be much less resilient than mixedwood or northern hardwoods to the projected changes in climate regimes. Current harvest strategies will interact with anthropogenic climate forcing to further modify forest landscapes, notably by accelerating thermophilous species AGB gain in southernmost regions. Major changes to harvest practices are strongly needed to preserve the long-term sustainability of wood supply in eastern Canada. Adaptation strategies should be region-specific.
Soil bacterial community diversity and composition vary more with elevation than seasons in alpine habitats of western Himalaya
Authors: Bhattacharya Pamela , Mondol Samrat , Talukdar Gautam , Rawat Gopal Singh 
Published: November 2020

AbstractSoil heterotrophic respiration-driven CO2emissions, its impact on global warming and the mechanistic roles of soil bacterial communities in this process have been an area of active research. However, our knowledge regarding the effects of environmental changes on soil bacterial communities is limited. To this end, the climate-sensitive high-altitude alpine ecosystems offer ideal opportunities to investigate relationship between climate change and bacterial communities. While data from several high-altitude mountain regions suggest that local environment factors and geological patterns govern bacterial communities, no information is available from the Himalaya. Here we provide baseline information on seasonal soil bacterial community diversity and composition along a 3200-4000 m elevation gradient covering four alpine habitats (subalpine forest, alpine scrub, alpine meadow and moraine) in Gangotri National Park, western Himalaya. Bacterial metabarcoding data from 36 field-collected samples showed no elevation trend in the bacterial richness and a non-monotonous decrease in their diversity. Further, their community diversity and composition varied significantly among habitats along elevation but were stable seasonally within each habitat. The richness was primarily influenced by soil inorganic carbon (SOC) and total nitrogen (TN), whereas temperature, SOC and TN affected diversity and composition patterns. Given the importance of the Himalaya in the context of global carbon cycle this information will help in accurate modeling of climate adaptation scenarios of bacterial niches and their downstream impacts towards climate warming.
SARS-CoV-2 Assembly and Egress Pathway Revealed by Correlative Multi-modal Multi-scale Cryo-imaging
Authors: Mendonça Luiza , Howe Andrew , Gilchrist James B. , Sun Dapeng , Knight Michael L. , Zanetti-Domingues Laura C. , Bateman Benji , Krebs Anna-Sophia , Chen Long , Radecke Julika , Sheng Yuewen , Li Vivian D. , Ni Tao , Kounatidis Ilias , Koronfel Mohamed A. , Szynkiewicz Marta , Harkiolaki Maria , Martin-Fernandez Marisa L. , James William , Zhang Peijun 
Published: November 2020

SummarySince the outbreak of the SARS-CoV-2 pandemic, there have been intense structural studies on purified recombinant viral components and inactivated viruses. However, investigation of the SARS-CoV-2 infection in the native cellular context is scarce, and there is a lack of comprehensive knowledge on SARS-CoV-2 replicative cycle. Understanding the genome replication, assembly and egress of SARS-CoV-2, a multistage process that involves different cellular compartments and the activity of many viral and cellular proteins, is critically important as it bears the means of medical intervention to stop infection. Here, we investigated SARS-CoV-2 replication in Vero cells under the near-native frozen-hydrated condition using a unique correlative multi-modal, multi-scale cryo-imaging approach combining soft X-ray cryo-tomography and serial cryoFIB/SEM volume imaging of the entire SARS-CoV-2 infected cell with cryo-electron tomography (cryoET) of cellular lamellae and cell periphery, as well as structure determination of viral components by subtomogram averaging. Our results reveal at the whole cell level profound cytopathic effects of SARS-CoV-2 infection, exemplified by a large amount of heterogeneous vesicles in the cytoplasm for RNA synthesis and virus assembly, formation of membrane tunnels through which viruses exit, and drastic cytoplasm invasion into nucleus. Furthermore, cryoET of cell lamellae reveals how viral RNAs are transported from double-membrane vesicles where they are synthesized to viral assembly sites; how viral spikes and RNPs assist in virus assembly and budding; and how fully assembled virus particles exit the cell, thus stablishing a model of SARS-CoV-2 genome replication, virus assembly and egress pathways.