bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do l’Hoest’s monkeys show sensitivity to conspecifics’ informational state?
Authors: Rivoal Lola , Dezecache Guillaume , Berthet Mélissa , Maille Audrey 
Published: May 2020

AbstractA series of field studies in chimpanzees have shown that the examination of communicative behaviour (e.g. alarm calling) could be particularly fruitful to help uncover mind-reading abilities in non-human animals. In this study, we sought to extend communication-based protocols to one species of Cercopithecids. Specifically, we looked at whether social gazing behaviour of L’Hoest’s monkeys (Allochrocebus lhoesti) is sensitive to the informational state of conspecifics using an original experimental design, thereby focusing on their ability to represent conspecifics’ rather than human experimenters’ mental states. We presented a group of 11 zoo-housed monkeys with a box that contained either an appetitive (mealworms), aversive (raptor stuffed toy) or neutral stimulus (wood bark chips). The discoverer (the first individual that inspected the content of the box) emitted more social gazes in the aversive condition than in the neutral and appetitive conditions. Besides, social gazing was related to the informational state of the conspecifics in the appetitive and neutral conditions, with more social gazes directed towards informed individuals (who had inspected the box) rather than uninformed ones (who had not inspected the box yet). Additional examination of the behaviour of the discoverers revealed that they were likely addressing social gazes to individuals who were in close proximity to them, suggesting that they preferentially gaze at informed conspecifics because the latter remained in proximity. Our study calls for a more widespread assessment of mind-reading capacities in primates, to further reveal the evolutionary history of traits that were thought to be uniquely human until fairly recently.
An engineered 4-1BBL fusion protein with “activity-on-demand”
Authors: Mock Jacqueline , Stringhini Marco , Villa Alessandra , Neri Dario 
Published: May 2020

ABSTRACTEngineered cytokines are gaining importance for cancer therapy but those products are often limited by toxicity, especially at early time points after intravenous administration. 4-1BB is a member of the tumor necrosis factor receptor superfamily, which has been considered as a target for therapeutic strategies with agonistic antibodies or using its cognate cytokine ligand, 4-1BBL. Here we describe the engineering of an antibody fusion protein (termed F8-4-1BBL), which does not exhibit cytokine activity in solution but regains biological activity upon antigen binding. F8-4-1BBL bound specifically to its cognate antigen, the alternatively-spliced EDA domain of fibronectin, and selectively localized to tumorsin vivo, as evidenced by quantitative biodistribution experiments. The product promoted a potent anti-tumor activity in various mouse models of cancer, without apparent toxicity at the doses used. F8-4-1BBL represents a prototype for antibody-cytokine fusion proteins, which conditionally display “activity-on-demand” properties at the site of disease upon antigen binding and reduce toxicity to normal tissues.
Phylogeny and Biogeography of South American Marsh Pitcher Plant GenusHeliamphora(Sarraceniaceae) Endemic to the Guiana Highlands
Authors: Liu Sukuan , Smith Stacey D. 
Published: May 2020

AbstractHeliamphorais a genus of carnivorous pitcher plants endemic to the Guiana Highlands with fragmented distributions. We presented a well resolved, time-calibrated, and nearly comprehensiveHeliamphoraphylogeny estimated using Bayesian inference and maximum likelihood based on nuclear genes (26S, ITS, andPHYC) and secondary calibration. We used stochastic mapping to infer ancestral states of morphological characters and ecological traits. Our ancestral state estimations revealed that the pitcher drainage structures characteristic of the genus transformed from a hole to a slit in single clade, while other features (scape pubescence and hammock-like growth) have been gained and lost multiple times. Habitat was similarly labile inHeliamphora, with multiple transitions from the ancestral highland habitats into the lowlands. Using Mantel test, we found closely related species tend to be geographically closely distributed. Placing our phylogeny in a historical context, major clades likely emerged through both vicariance and dispersal during Miocene with more recent diversification driven by vertical displacement during the Pleistocene glacial-interglacial thermal oscillations. Despite the dynamic climatic history experienced byHeliamphora, the temperature changes brought by global warming pose a significant threat, particularly for those species at the highest elevations.
Structural and functional analysis of pyocin S8 fromPseudomonas aeruginosa: requirement of a glutamate in the H-N-H motif for the DNase activity
Authors: Turano Helena G. , Gomes Fernando , Domingos Renato M. , Degenhardt Maximilia F. S. , Oliveira Cristiano L. P. , Garratt Richard C. , Lincopan Nilton , Netto Luis E. S. 
Published: May 2020

AbstractMulti-drug resistance (MDR) is a serious threat to global public health, making the development of new antimicrobials an urgent necessity. Pyocins are protein antibiotics produced byPseudomonas aeruginosastrains to kill closely related cells during intraspecific competition. Here, we report an in depth biochemical, microbicidal and structural characterization of a new S-type pyocin, named S8. Initially, we described the domain organization and secondary structure of S8. Subsequently, we observed that a recombinant S8 composed of the killing subunit in complex with the immunity (Im) protein killed the strain PAO1. Furthermore, mutation of a highly conserved glutamic acid to alanine (Glu100Ala) completely inhibited this antimicrobial activity. Probably the integrity of the H-N-H motif is essential in the killing activity of S8, as Glu100 is a highly conserved component of this structure. Next, we observed that S8 is a metal-dependent endonuclease, as EDTA treatment abolished its ability to cleave supercoiled pUC18 plasmid. Supplementation of apo S8 with Ni2+strongly induced this DNase activity, whereas Mn2+and Mg2+exhibited moderate effects and Zn2+was inhibitory. Additionally, S8 bound Zn2+with a higher affinity than Ni2+and the Glu100Ala mutation decreased the affinity of S8 for these metals as shown by isothermal titration calorimetry (ITC). Finally, we describe the crystal structure of the Glu100Ala pyocin-S8DNase-Im complex at 1.38 Å, which gave us new insights into the endonuclease activity of S8. Our results reinforce the possible use of S8 as an alternative antibiotic for MDRPseudomonas aeruginosastrains, while leaving commensal human microbiota intact.
Dopamine neurons promotes wakefulness via the DopR receptor in the Drosophila mushroom body
Authors: Driscoll Margaret , Buchert Steven , Coleman Victoria , McLaughlin Morgan , Nguyen Amanda , Sitaraman Divya 
Published: May 2020

AbstractNeural circuits involved in regulation of sleep play a critical role in sleep-wake transition and ability of an organism to engage in other behaviors critical for survival. The fruit fly, Drosophila melanogaster is a powerful system for the study of sleep and circuit mechanisms underlying sleep and co-regulation of sleep with other behaviors. InDrosophila, two neuropils in the central brain, mushroom body (MB) and central complex (CX) have been shown to influence sleep homeostasis and receive neuromodulator input critical to sleep-wake switch.Dopamine neurons (DANs) are the primary neuromodulator inputs to the MB but the mechanisms by which they regulate sleep- and wake-promoting neurons within MB are unknown. Here we investigate the role of subsets of DANs that signal wakefulness and project to wake-promoting compartments of the MB. We find that inhibition of specific subsets of PAM and PPL1 DANs projecting to the MB increase sleep in the presence of strong wake-inducing stimuli that reduces GABA transmission, although activity of these neurons is not directly modulated by GABA signaling. Of these subsets we find that DANs innervating the γ5 and β’2 MB compartments require both DopR1 and DopR2 receptors located in downstream Kenyon cells and mushroom body output neurons (MBONs). Further, we report that unlike the activity of wake-promoting MBONs and KCs, whose activity is modulated by sleep-need and PAM-DAN activity is independent of sleep-need. We have characterized a dopamine mediated sleep-circuit providing an inroad into understanding how common circuits within MB regulate sleep, wakefulness and behavioral arousal.
α-Synuclein facilitates clathrin assembly in synaptic vesicle endocytosis
Authors: Vargas Karina J. , Colosi P. L. , Girardi Eric , Park Jae-Min , Chandra Sreeganga S. 
Published: May 2020

Abstractα-Synuclein and family members β-, and γ-synuclein, are presynaptic proteins that sense and generate membrane curvature, properties important for synaptic vesicle (SV) cycling. αβγ-synuclein triple knockout (KO) neurons exhibit SV endocytosis (SVE) deficits. Here, we investigate how SVE is regulated by α-synuclein. Immuno-electron microscopy (EM) of synaptosomes reveals that α-synuclein relocalizes from SVs to the synaptic membrane upon stimulation, allowing α-synuclein to function on presynaptic membranes during or after stimulation. On cell membranes, we observe that α-synuclein is colocalized with clathrin and its adaptor AP180. Clathrin patches that contain both α-synuclein and AP180 were significantly larger than clathrin patches containing either protein alone. We also find that recruitment of clathrin and AP180 recruitment to membranes are altered in the absence of synucleins. Visualizing clathrin assembly on membranes using anin vitroendocytosis reconstitution system reveals that α-synuclein increases clathrin patch size and enhances clathrin lattice curvature, facilitating normal clathrin coated pit maturation. Thus, α-synuclein is an endocytic accessory protein that acts at early stages of SVE to controls the size and curvature of clathrin structures on the membrane.
Mesophyll conductance in two cultivars of wheat (Triticum aestivum) grown in glacial to super-elevated [CO2]
Authors: Jahan Eisrat , Thomson Peter C. , Tissue David T. 
Published: May 2020

AbstractMesophyll conductance (gm) is an important factor limiting photosynthesis. However,gmresponse to long-term growth in variable [CO2] is not well understood, particularly in crop plants. Here, we grew two cultivars of wheat (Halberd and Cranbrook), known to differ ingmunder current environmental conditions, in four [CO2] treatments: glacial (180 μmol mol−1), pre-industrial (280 μmol mol−1), current ambient (450 μmol mol−1) and super-elevated (1000 μmol mol−1) in well-watered and moderate water limitation conditions, to develop an evolutionary and future climate perspective ongmcontrol of photosynthesis and water use efficiency (WUE). In the two wheat genotypes,gmincreased with rising [CO2] from glacial to ambient [CO2], but declined at super-elevated [CO2]; however, the specific mechanism ofgmresponse to [CO2] remains unclear. Althoughgmandgm/gsc(mesophyll conductance/stomatal conductance) were strongly associated with the variability ofAand WUE, we found that plants with highergmmay increaseAwithout increasinggsc, which increased WUE. These results may be useful to inform plant breeding programs and cultivar selection for Australian wheat under future environmental conditions.HighlightMesophyll conductance increased with increasing [CO2] from glacial to ambient CO2levels, then declined at super-elevated CO2for both well-watered and water-limited treatments. These responses of mesophyll conductance with varying [CO2] have a physiological basis.
AKI during COVID-19 infection: low incidence, high risk of death
Authors: Mou Zhixiang , Zhang Xu 
Published: May 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) has spread rapidly worldwide and seriously threatens human health since December 2019. However, information about acute kidney injury (AKI) during COVID-19 infection is limited. Some studies thought that presence of AKI is very common and cannot be ignored, while some studies pointed that AKI only is a rare incident during COVID-19 infection. This meta-analysis aimed to find out the truth of COVID-19 related AKI and to provide stronger evidence.MethodsTwo authors independently performed a literature search using PubMed, Web of Science, Embase, and Cochrane Library fulfilled the pre-specified criteria until April 25, 2020 to include studies reported the necessary clinic characteristics, then the incidence of AKI, incidence of required RRT, the mortality with AKI and the death risk with AKI during COVID-19 infection were pooled for statistical analysis by Open Meta-Analyst software to get conclusions.FindingsIt was found that the incidence of AKI in hospitalized patients with COVID-19 infection is low, only about 3.8%; the in-hospital mortality with AKI in COVID-19 infected patients is reach up to 32.6%; the death risk with AKI in COVID-19 infected patients is about 16.1 times higher than those without AKI.ConclusionsThis meta-analysis indicated AKI during COVID-19 infection should be pay more attention, it maybe a strong red flag to death risk. It is still need additional studies to support the conclusions and to explore the AKI mechanism during COVID-19 infection.
Genome-wide mutagenesis identifies factors involved inEnterococcus faecalisvaginal adherence and persistence
Authors: Alhajjar Norhan , Chatterjee Anushila , Spencer Brady L. , Burcham Lindsey R. , Willett Julia L. E. , Dunny Gary M. , Duerkop Breck A. , Doran Kelly S. 
Published: May 2020

ABSTRACTEnterococcus faecalisis a Gram-positive commensal bacterium native to the gastrointestinal tract and an opportunistic pathogen of increasing clinical concern.E. faecalisalso colonizes the female reproductive tract and reports suggest vaginal colonization increases following antibiotic treatment or in patients with aerobic vaginitis. Currently, little is known about specific factors that promoteE. faecalisvaginal colonization and subsequent infection. We modified an established mouse vaginal colonization model to exploreE. faecalisvaginal carriage and demonstrate that both vancomycin resistant and sensitive strains colonize the murine vaginal tract. Following vaginal colonization, we observedE. faecalisin vaginal, cervical and uterine tissue. A mutant lacking endocarditis- and biofilm-associated pili (Ebp) exhibited a decreased ability to associate with human vaginal and cervical cellsin vitro, but did not contribute to colonizationin vivo. Thus, we screened a low-complexity transposon (Tn) mutant library to identify novel genes important forE. faecaliscolonization and persistence in the vaginal tract. This screen revealed 383 mutants that were underrepresented during vaginal colonization at 1, 5 and 8 days post-inoculation compared to growth in culture medium. We confirmed that mutants deficient in ethanolamine catabolism or in the type VII secretion system were attenuated in persisting during vaginal colonization. These results reveal the complex nature of vaginal colonization and suggest that multiple factors contribute toE. faecalispersistence in the reproductive tract.IMPORTANCEDespite increasing prevalence and association ofE. faecaliswith aerobic vaginitis, essentially nothing is known about the bacterial factors that influenceE. faecalisvaginal colonization. We have adapted an animal model of vaginal colonization that supports colonization of multipleE. faecalisstrains. Additionally, we determined that ethanolamine utilization and type VII secretion system genes contribute to vaginal colonization and persistence. Identification of factors important for vaginal colonization and persistence provides potential targets for the development of therapeutics. This study is the first to identify key determinants that promote vaginal colonization byE. faecalis, which may represent an important reservoir for antibiotic resistant enterococci.
Structural basis of norepinephrine recognition and transport inhibition in neurotransmitter transporters
Authors: Pidathala Shabareesh , Mallela Aditya Kumar , Joseph Deepthi , Penmatsa Aravind 
Published: May 2020

AbstractNorepinephrine is a biogenic amine neurotransmitter that has widespread effects on cardiovascular tone, alertness and sensation of pain. As a consequence, blockers of norepinephrine uptake have served as vital tools to treat depression and chronic pain. Here, we employ a modifiedDrosophila melanogasterdopamine transporter as a surrogate for the human norepinephrine transporter and determine the X-ray structures of the transporter in its substrate-free and norepinephrine-bound forms. We also report structures of the transporter in complex with inhibitors of chronic pain including duloxetine, milnacipran and a synthetic opioid, tramadol. When compared to dopamine, we observe that norepinephrine binds in a different pose, in the vicinity of subsite C within the primary binding site. Our experiments reveal that this region is the binding site for chronic pain inhibitors and a determinant for norepinephrine-specific reuptake inhibition, thereby providing a paradigm for the design of specific inhibitors for catecholamine neurotransmitter transporters.HighlightsX-ray structures of theDrosophiladopamine transporter in substrate-free and norepinephrine bound forms.Norepinephrine and dopamine bind in distinct conformations within the binding pocket.Chronic pain inhibitors S-duloxetine, milnacipran and tramadol bind in the primary binding site and overlap with the norepinephrine-binding pose.Selective norepinephrine reuptake inhibition occurs through specific interactions at the subsite C in the primary binding pocket.
Spatial Regulation of MCAK Promotes Cell Polarization and Focal Adhesion Turnover to Drive Robust Cell Migration
Authors: Zong Hailing , Hazelbaker Mark , Moe Christina , Ems-McClung Stephanie C. , Hu Ke , Walczak Claire E. 
Published: May 2020

AbstractThe asymmetric distribution of microtubule (MT) dynamics in migrating cells is important for cell polarization, yet the underlying regulatory mechanisms remain underexplored. Here, we addressed this question by studying the role of the MT depolymerase, MCAK, in the highly persistent migration of RPE-1 cells. MCAK knockdown leads to slowed migration and poor directional movement. Fixed and live cell imaging revealed that MCAK knockdown results in excessive membrane ruffling as well as defects in cell polarization and the maintenance of a major protrusive front. Additionally, loss of MCAK increases the lifetime of focal adhesions by decreasing their disassembly rate. These defects are due in part to the loss of the spatial distribution of MCAK activity, wherein activity is higher in the trailing edge of cells compared to the leading edge. Overexpression of Rac1 has a dominant effect over MCAK activity, placing it downstream or in a parallel pathway to MCAK function in migration. Together, our data support a model that places MCAK at a key nexus of a feedback loop, in which polarized distribution of MCAK activity and subsequent differential regulation of MT dynamics contributes to cell polarity and directional migration.
Origin of imported SARS-CoV-2 strains in The Gambia identified from Whole Genome Sequences
Authors: Kanteh Abdoulie , Manneh Jarra , Jabang Sona , Kujabi Mariama A. , Sanyang Bakary , Oboh Mary A. , Bojang Abdoulie , Jallow Haruna S. , Nwakanma Davis , Secka Ousman , Roca Anna , Amambua-Ngwa Alfred , Antonio Martin , Baldeh Ignatius , Forrest Karen , Samateh Ahmadou Lamin , D’Alessandro Umberto , Sesay Abdul Karim 
Published: May 2020

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a positive-sense single stranded RNA virus with high human transmissibility. This study generated Whole Genome data to determine the origin and pattern of transmission of SARS-CoV-2 from the first six cases tested in The Gambia. Total RNA from SARS-CoV-2 was extracted from inactivated nasopharyngeal-oropharyngeal swabs of six cases and converted to cDNA following the ARTIC COVID-19 sequencing protocol. Libraries were constructed with the NEBNext ultra II DNA library prep kit for Illumina and Oxford Nanopore Ligation sequencing kit and sequenced on Illumina MiSeq and Nanopore GridION, respectively. Sequencing reads were mapped to the Wuhan reference genome and compared to eleven other SARS-CoV-2 strains of Asian, European and American origins. A phylogenetic tree was constructed with the consensus genomes for local and non-African strains. Three of the Gambian strains had a European origin (UK and Spain), two strains were of Asian origin (Japan). In The Gambia, Nanopore and Illumina sequencers were successfully used to identify the sources of SARS-CoV-2 infection in COVID-19 cases.
Insurgence and worldwide diffusion of genomic variants in SARS-CoV-2 genomes
Authors: Comandatore Francesco , Chiodi Alice , Gabrieli Paolo , Biffignandi Gherard Batisti , Perini Matteo , Ricagno Stefano , Mascolo Elia , Petazzoni Greta , Ramazzotti Matteo , Rimoldi Sara Giordana , Gismondo Maria Rita , Micheli Valeria , Sassera Davide , Gaiarsa Stefano , Bandi Claudio , Brilli Matteo 
Published: May 2020

AbstractThe SARS-CoV-2 pandemic that we are currently experiencing is exerting a massive toll both in human lives and economic impact. One of the challenges we must face is to try to understand if and how different variants of the virus emerge and change their frequency in time. Such information can be extremely valuable as it may indicate shifts in aggressiveness, and it could provide useful information to trace the spread of the virus in the population. In this work we identified and traced over time 7 amino acid variants that are present with high frequency in Italy and Europe, but that were absent or present at very low frequencies during the first stages of the epidemic in China and the initial reports in Europe. The analysis of these variants helps defining 6 phylogenetic clades that are currently spreading throughout the world with changes in frequency that are sometimes very fast and dramatic. In the absence of conclusive data at the time of writing, we discuss whether the spread of the variants may be due to a prominent founder effect or if it indicates an adaptive advantage.