bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM
Authors: Liu Chuang , Yang Yang , Gao Yuanzhu , Shen Chenguang , Ju Bin , Liu Congcong , Tang Xian , Wei Jinli , Ma Xiaomin , Liu Weilong , Xu Shuman , Liu Yingxia , Yuan Jing , Wu Jing , Liu Zheng , Zhang Zheng , Wang Peiyi , Liu Lei 
Published: March 2020

AbstractSince December 2019, the outbreak of Coronavirus Disease 2019 (COVID-19) spread from Wuhan, China to the world, it has caused more than 87,000 diagnosed cases and more than 3,000 deaths globally. To fight against COVID-19, we carried out research for the near native SARS-CoV-2 and report here our preliminary results obtained. The pathogen of the COVID-19, the native SARS-CoV-2, was isolated, amplified and purified in a BSL-3 laboratory. The whole viral architecture of SARS-CoV-2 was examined by transmission electron microscopy (both negative staining and cryo-EM). We observed that the virion particles are roughly spherical or moderately pleiomorphic. Spikes have nail-like shape towards outside with a long body embedded in the envelope. The morphology of virion observed in our result indicates that the S protein of SARS-CoV-2 is in post-fusion state, with S1 disassociated. This state revealed by cryo-EM first time could provide an important information for the identification and relevant clinical research of this new coronavirus.
Deletion of Autophagy geneATG1and F-box motif encoding geneYDR131Ctogether leads to Synthetic Growth Defects and Flocculation behaviour inSaccharomyces cerevisiae
Authors: Shoket Heena , Parvez Sadia , Sharma Meenu , Pandita Monika , Sharma Vishali , Kumar Prabhat , Bairwa Narendra K 
Published: March 2020

AbstractF-box motif encodingYDR131Cis functionally uncharacterized gene which forms the complex with the SCF-E3 ligase. The F-box motif containing proteins are involved in substrate recruitment for the ubiquitination and subsequent degradation through 26S proteasome. Autophagy gene,ATG1 (ULK1in human) is a well conserved serine-threonine kinase, required for vesicle formation and cytoplasm to vacuole targeting pathway. Atg1p forms the complex with Atg13p and Atg17p during autophagy. The understanding of crosstalk between ubiquitin and autophagy pathways is crucial for synthetic lethality screen and drug targeting. Here we have conducted the study for genetic interaction between uncharacterizedYDR131CandATG1 gene representing both specific and non-specific protein degradation pathways. The single and double gene knockout strains ofYDR131CandATG1genes were constructed in the BY4741 genetic background and analysed for growth fitness. The strains were also evaluated for cellular growth response in presence of hydroxyurea (HU), methyl methane sulfonate (MMS), and hydrogen peroxide (H2O2) stress causing agents by spot assay. Theydr131cΔatg1Δshowed the synthetic growth defect phenotype with floc formation in rich medium which showed floc disruption in presence of EDTA. Theydr131cΔatg1Δcells showed the sensitivity to stress agents HU, MMS, and H2O2when compared withydr131cΔ, atg1Δ, and WT cells.. Based on the observations, we report thatYDR131CandATG1functions in parallel pathways for growth fitness and cellular growth response to stress agents. Interestingly this study also revealed the crosstalk between ubiquitination and autophagy pathways. The defects in both the pathways could lead to synthetic growth defects which may have implication for the precision medicine initiatives.
FastField: An Open-Source Toolbox for Efficient Approximation of Deep Brain Stimulation Electric Fields
Authors: Baniasadi Mehri , Proverbio Daniele , Gonçalves Jorge , Hertel Frank , Husch Andreas 
Published: March 2020

AbstractDeep brain stimulation (DBS) is a surgical therapy to alleviate symptoms of certain brain disorders by electrically modulating neural tissues. Computational models predicting electric fields and volumes of tissue activated are key for efficient parameter tuning and network analysis. Currently, we lack efficient and flexible software implementations supporting complex electrode geometries and stimulation settings. Available tools are either too slow (e.g. finite element method–FEM), or too simple, with limited applicability to basic use-cases. This paper introduces FastField, an efficient open-source toolbox for DBS electric field and VTA approximations. It computes scalable e-field approximations based on the principle of superposition, and VTA activation models from pulse width and axon diameter. In benchmarks and case studies, FastField is solved in about 0.2s, ~ 1000 times faster than using FEM. Moreover, it is almost as accurate as using FEM: average Dice overlap of 92%, which is around typical noise levels found in clinical data. Hence, FastField has the potential to foster efficient optimization studies and to support clinical applications.
Quantifying flight aptitude variation in wildA. gambiaes.l. in order to identify long-distance migrants
Authors: Faiman Roy , Yaro Alpha S. , Diallo Moussa , Dao Adama , Djibril Samake , Sanogo Zana L. , Sullivan Margery , Krishna Asha , Krajacich Benjamin J. , Lehmann Tovi 
Published: March 2020

AbstractBackgroundIn the West African Sahel, during the 5-7 month-long dry season mosquito reproduction is halted due to the absence of surface waters required for larval development. Recent studies have suggested that bothAnopheles gambiaes.s andA. arabiensispersist in this region by migration from distant locations where larval sites are perennial, andA. coluzziiengages in long-distance migration, presumably within the Sahel, following shifting resources due to the ever-changing patterns of Sahelian rainfall. Understanding mosquito migration is key to malaria control, a disease that still kills >400,000 people, mostly children in Africa.MethodsWe used a new tethered-flight assay to characterize flight in the three primary malaria vectors mentioned above and evaluated seasonal differences in their flight activity. The flight of tethered wild mosquitoes was audio-recorded from 21:00h to 05:00h in the following morning and three flight aptitude indices were examined: total flight duration, longest flight bout, and the number of flight bouts during the assay. Based on recent studies, we predicted that(i)the distribution of the flight aptitude indices would exhibit bi-modality and/or marked skewness, indicating a subpopulation of high flight activity (HFA) associated with long-distance migrants, in contrast to low flight activity (LFA) in appetitive flyers. Additionally, flight aptitude would(ii)increase in the wet season, (iii) increase in gravid females, and(iv)vary among the vector species.ResultsThe distributions of all flight indices departed sharply from a normal curve, and were strongly skewed to the right, consistent with the division of the population into a majority of LFAs and a minority of HFAs, e.g., the median total flight was 586 seconds, and its maximum value was 16,110 seconds (~4.5 h). As predicted, flight aptitude peaked in the wet season and was higher in gravid females than in non-bloodfed females. Flight aptitude was higher inA. coluzziithan inA. arabiensis, butA. gambiaes.s. was not statistically different from either. We evaluated differences in wing size and shape between LFAs and HFAs. During the wet season, wing size of HFAA. coluzziiwas larger than that of LFAs; it was wider than predicted by its length, indicating a shape change. However, no statistically significant differences were found in wings ofA. gambiaes.s. orA. arabiensis.ConclusionsThe partial agreement between the assay results and predictions suggest a degree of discrimination between appetitive flyers and long-distance migrants. Wing size and shape seems to indicate higher flight activity inA. coluzziiduring the wet season.
Speech-evoked brain activity is more robust to competing speech when it is spoken by someone familiar
Authors: Holmes Emma , Johnsrude Ingrid S. 
Published: March 2020

AbstractPeople are much better at understanding speech when it is spoken by a familiar talker—such as a friend or partner—than when the interlocutor is unfamiliar. This provides an opportunity to examine the substrates of intelligibility and familiarity, independent of acoustics. Is the familiarity effect evident as early as primary auditory cortex, or only at later processing stages? Here, we presented sentences spoken by naturally familiar talkers (the participant’s friend or partner) and unfamiliar talkers (the friends or partners of other participants). We compared multivariate activity in speech-sensitive regions of cortex between conditions in which target sentences were presented alone and conditions in which the same target sentences were presented at the same time as a competing sentence. Using representational similarity analysis (RSA), we demonstrate that the pattern of activity evoked by a spoken sentence is less degraded by the presence of a competing sentence when it is spoken by a friend or partner than by someone unfamiliar; the results cannot be explained by acoustic differences since familiar and unfamiliar talkers were nearly identical across the group. This familiar-voice advantage is most prominent in nonprimary auditory cortical areas, along the posterior superior and middle temporal gyri. Across participants, the magnitude of the familiar-unfamiliar RSA difference correlates with the familiar-voice benefit to intelligibility. Overall, our results demonstrate that experience-driven improvements in intelligibility are associated with enhanced patterns of neural activity in nonprimary auditory cortical areas.Significance statementSpeech is a complex signal, and we do not yet fully understand how the content of a spoken sentence is encoded in cortex. Here, we used a novel approach based on analysing multivariate activity: we compared activity evoked by highly intelligible sentences presented alone and by the same sentences presented with a competing masker. The distributed pattern of activity in speech-sensitive regions of the brain was more similar between the alone and masker conditions when the target sentence was spoken by someone familiar—the participant’s friend or partner—than someone unfamiliar. This metric correlated with the intelligibility of the familiar voice. These results imply that the spatial pattern of activity in speech-sensitive regions reflects the intelligibility of a spoken sentence.
Significance of hydrophobic and charged sequence similarities in sodium-bile acid cotransporter and vitamin D-binding protein macrophage activating factor
Authors: Zunaid Ibne Raihan , Pacini Stefania , Ruggiero Marco 
Published: March 2020

AbstractSodium-bile acid cotransporter, also denominated sodium-taurocholate cotransporting polypeptide (NTCP) is an integral membrane protein with multiple hydrophobic transmembrane domains. The third extracellular domain of NTCP presents a stretch of nine aminoacids (KGIVISLVL) that is characterized by pronounced hydrophobicity and serves as receptor for a protein, preS1, showing the hydrophobic epta-peptide sequence NPLGFFP. Vitamin D-binding protein macrophage activating factor (DBP-MAF) is a multifunctional protein that is characterized by two hydrophobic regions able to bind fatty acids and vitamin D, respectively. Here we demonstrate that NTCP and DBP-MAF show significant sequence similarities as far as hydrophobic stretches of aminoacids are concerned. Alignment of the sequence of seven aminoacids preceding the 157-KGIVISLVL-165 stretch of NTCP shows four aminoacids that are identical to those of the corresponding sequence of DBP-MAF, and two that are conserved substitutions. In addition, in the sequence of DBP-MAF that is aligned with the sequence YKGIVISLVL of NTCP, there are two contiguous negatively charged aminoacids (ED) and, in the preceding epta-peptide sequence, there are three negatively charged aminoacids (D-ED), whereas in the corresponding sequence of NTCP there are only two (D--D) that are not contiguous. This concentration of negatively charged aminoacids may be involved in binding of protein inserts characterized by high density of positively charges residues. The alternating hydrophobic and electrostatic interactions described in this paper may help elucidating the biological roles of these proteins as far as protein-protein interactions are concerned.
Early maturational emergence of adult-like emotional reactivity and anxiety after brief exposure to an obesogenic diet
Authors: Vega-Torres Julio D. , Azadian Matine , Rios-Orsini Raul , Reyes-Rivera Arsenio L. , Ontiveros-Angel Perla , Figueroa Johnny D. 
Published: March 2020

ABSTRACTBackgroundEmerging evidence demonstrates that diet-induced obesity disrupts corticolimbic circuits underlying emotional regulation. Studies directed at understanding how obesity alters brain and behavior are easily confounded by a myriad of complications related to obesity. This study investigated the early neurobiological stress response triggered by an obesogenic diet. Furthermore, this study directly determined the combined impact of a short-term obesogenic diet and adolescence on critical behavioral and molecular substrates implicated in emotion regulation and stress.MethodsAdolescent (postnatal day 31) or adult (postnatal day 81) Lewis rats were fed for one week with an experimental Western-like high-saturated fat diet (WD, 41% kcal from fat) or a matched control diet (CD, 13% kcal from fat). We used the acoustic fear-potentiated startle (FPS) paradigm to determine the effects of the WD on cued fear conditioning and fear extinction. We used c-Fos mapping to determine the functional influence of the diet and stress on corticolimbic circuits.ResultsWe report that one-week WD consumption was sufficient to induce fear extinction deficits in adolescent rats, but not in adult rats. We identify fear-induced alterations in corticolimbic neuronal activation and demonstrate increased prefrontal cortex CRHR1 mRNA levels in the rats that consumed the WD.ConclusionsOur findings demonstrate that short-term consumption of an obesogenic diet during adolescence heightens behavioral and molecular vulnerabilities associated with risk for anxiety and stress-related disorders. Given that fear extinction promotes resilience, and that fear extinction principles are the foundation of psychological treatments for PTSD, understanding how obesogenic environments interact with the adolescent period to affect the acquisition and expression of fear extinction memories is of tremendous clinical relevance.HIGHLIGHTSShort-term WD consumption during adolescence impairs cued fear extinction memory retention in a fear-potentiated startle paradigm.Short-term WD consumption during adolescence attenuates neuronal activation to electric footshock stress in the basomedial nuclei of the amygdala.Short-term WD consumption increases CRHR1 mRNA levels in the medial prefrontal cortex.Adult LEW rats exhibit increased basal HPA axis tone and heightened emotional reactivity to footshock stress relative to adolescent rats.
Serological detection of 2019-nCoV respond to the epidemic: A useful complement to nucleic acid testing
Authors: Zhang Jin , Liu Jianhua , Li Na , Liu Yong , Ye Rui , Qin Xiaosong , Zheng Rui 
Published: March 2020

AbstractBackgroundPneumonia caused by 2019 novel coronavirus (2019-nCoV) was first reported in Wuhan, Hubei Province, China in December 2019. Then it has been reported in more than 20 countries and regions overseas rapidly. More than eighty thousand cases have been infected, resulting in more than three thousand deaths. Due to the limitation of nucleic acid detection, many clinical suspected cases cannot be diagnosed in time.MethodsWe used automated chemiluminescent immunoassay to detect serum IgM and IgG antibodies to 2019-nCoV of 736 subjects including confirmed Corona Virus Disease 2019 (COVID-19) patients, non-COVID-19 fever patients, other disease patients and medical staff as well as healthy people. The dynamic process of antibody production in COVID-19 disease progression were analyzed, and the value of antibody detection in the laboratory diagnosis of COVID-19 were evaluated.ResultsCOVID-19 patients were becoming reactive(positive) for specific anti-2019-nCoV IgM antibodies from 7-12 days after the onset of morbidity, followed closely by the IgG. The levels of specific IgM and IgG antibodies increased with the progression of the disease. The trend of IgM and IgG changes in different cases is not exactly the same. The levels of IgM and IgG and their distributions in different groups were different with that of healthy people. The areas under the ROC curves for IgM and IgG to diagnose COVID-19 were 0.988 and 1.000, respectively.ConclusionsSpecific IgM or IgG antibody detection had good sensitivity and specificity for the diagnosis of suspected fever cases. Detection of specific antibodies in patients with fever can be a good distinction between COVID-19 and other diseases in low epidemic area.
Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection
Authors: Diao Bo , Wang Chenhui , Wang Rongshuai , Feng Zeqing , Tan Yingjun , Wang Huiming , Wang Changsong , Liu Liang , Liu Ying , Liu Yueping , Wang Gang , Yuan Zilin , Ren Liang , Wu Yuzhang , Chen Yongwen 
Published: March 2020

SummaryBACKGROUNDThe outbreak of a novel coronavirus (SARS-CoV-2, previously provisionally named 2019 novel coronavirus or 2019-nCoV) since December 2019 in Wuhan, China, has become an emergency of major international concern. Apart from the respiratory system, it is unclear whether SARS-CoV-2 can also directly infect other tissues such as the kidney or induce acute renal failure.METHODSWe conducted a retrospective analysis of estimated glomerular filtration rate (eGFR) along with other clinical parameters from 85 patients with laboratory-confirmed COVID-19 admitted to a hospital in Wuhan from January 17, 2020 to March 3, 2020. Kidney tissues from six patients with postmortem examinations were analyzed by Hematoxylin and Eosin (H&E) andin situexpression of viral nucleocaspid protein (NP) antigen, immune cell markers (CD8, CD68 and CD56) and the complement C5b-9 was detected by immunohistochemistry. Moreover, the viral particles in kidneys were also investigated by transmission electronic microscope (EM).RESULTS27.06% (23/85) patients exhibited acute renal failure (ARF). The eldery patients and cases with comorbidities such as hypertension and heart failure more easily developed ARF (65.22%vs24.19%,p< 0.001; 69.57% vs 11.29%,p< 0.001, respectively). H&E staining demonstrated kidney tissues from postmortems have severe acute tubular necrosis and lymphocyte infiltration. Immunohistochemistry showed that SARS-CoV-2 NP antigen was accumulated in kidney tubules. EM observation also demonstrated that viruses-like particles are visible in the kidneys. Viral infection not only induces CD68+macrophages infiltrated into tubulointerstitium, but also enhances complement C5b-9 deposition on tubules.CONCLUSIONSSARS-CoV-2 induces ARF in COVID-19 patients. Viruses directly infect human kidney tubules to induce acute tubular damage. The viruses not only have direct cytotoxicity, but also initiate CD68+macrophage together with complement C5b-9 deposition to mediate tubular pathogenesis.
Differential virulence contributions of the efflux transporter MexAB-OprM inPseudomonas syringaeinfecting a variety of host plants
Authors: Helmann Tyler C. , King Dana M. , Lindow Steven E. 
Published: March 2020

AbstractEfflux transporters such as MexAB-OprM contribute to bacterial resistance to diverse antimicrobial compounds. Here, we show that MexB contributes to epiphytic and apoplastic growth ofPseudomonas syringaestrain B728a, as well as lesion formation in common bean (Phaseolus vulgaris). While amexBdeletion mutant formed fewer lesions after topical application to common bean, these lesions contain the same number of cells (105to 107cells) as those caused by the wild-type strain. The internalized population size of both the WT and the MexB mutant within small segments of surface-sterilized asymptomatic portions of the leaves varied from undetectably low to as high as 105cells/cm2. Localized populations of bacteria within the leaf must apparently exceed a threshold size of about 105cells/cm2in order for a visible lesion to form. Strain B728a was capable of moderate to extensive apoplastic growth in diverse host plants including lima bean (P. lunatus), fava bean (Vicia faba), pepper (Capsicum annuum),Nicotiana benthamiana, sunflower (Helianthus annuus), and tomato (Solanum lycopersicum). MexB was not required for growth in a subset of these plant species, and in which the duration of growth after inoculation was longer, indicating apparent variation in onset time or magnitude of plant chemical defenses among those hosts. The use of a hyper-susceptible efflux pump mutant strain is an informative strategy to explore the diversity of host chemical immune responses.
Computing and Optimizing Over All Fixed-Points of Discrete Systems on Large Networks
Authors: Riehl James R. , Zimmerman Maxwell I. , Singh Matthew F. , Bowman Gregory R. , Ching ShiNung 
Published: March 2020

AbstractEquilibria, or fixed points, play an important role in dynamical systems across various domains, yet finding them can be computationally challenging. Here, we show how to efficiently compute all equilibrium points of discrete-valued, discrete-time systems on sparse networks. Using graph partitioning, we recursively decompose the original problem into a set of smaller, simpler problems that are easy to compute, and whose solutions combine to yield the full equilibrium set. This makes it possible to find the fixed points of systems on arbitrarily large networks meeting certain criteria. This approach can also be used without computing the full equilibrium set, which may grow very large in some cases. For example, one can use this method to check the existence and total number of equilibria, or to find equilibria that are optimal with respect to a given cost function. We demonstrate the potential capabilities of this approach with examples in two scientific domains: computing the number of fixed points in brain networks and finding the minimal energy conformations of lattice-based protein folding models.