bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small molecules exploiting structural differences within microRNA-200 precursors family members reverse a type 2 diabetes phenotype
Authors: Haniff Hafeez S. , Liu Xiaohui , Knerr Laurent , Lemurell Malin , Abegg Daniel , Adibekian Alexander , Disney Matthew D. 
Published: June 2020

AbstractMicroRNA families are pervasive in the human transcriptome, but specific targeting of individual members is a challenge because of sequence homology. Many of the secondary structures of the precursors to these miRs (pre-miRs), however, are quite different. Here, we demonstrate bothin vitroandin cellulisthat design of structure-specific small molecules can inhibit specific miR family members to modulate a disease pathway. In particular, the miR-200 family consists five miRs, miR-200a, −200b, −200c, −141, and - 429, and is associated with Type II Diabetes (T2D). We designed a small molecule that potently and selectively targets pre-miR-200c’s structure. The compound reverses a pro-apoptotic effect in a pancreatic β-cell model. In contrast, oligonucleotides targeting the RNA’s sequence inhibit all family members. Global proteomics analysis further demonstrates selectivity for miR-200c. Collectively, these studies establish that miR-200c plays an important role in T2D and that small molecules targeting RNA structure can be an important complement to oligonucleotides targeting sequence.Significance StatementThe most common way to develop medicines targeting RNA is by using oligonucleotides that target its sequence by using base pairing. Some RNAs, however, have similar sequences and thus are impossible to target selectively by using oligonucleotides. Here, we show that a class of RNAs that have similar sequences emerge from precursors that have very different structures. Exploiting these structural differences afforded a selective compound. In particular, the selective small molecule targets a member of the microRNA (miR)-200 family, the overexpression of which is linked to diabetes and pancreatic cell death. Selective inhibition of family member miR-200c alleviates pancreatic cell death, and thus the small molecule provides a path to the treatment of diabetes.
Cryo-EM Structures of Respiratorybc1-cbb3type CIII2CIV Supercomplex and Electronic Communication Between the Complexes
Authors: Steimle Stefan , VanEeuwen Trevor , Ozturk Yavuz , Kim Hee Jong , Braitbard Merav , Selamoglu Nur , Garcia Benjamin A. , Schneidman-Duhovny Dina , Murakami Kenji , Daldal Fevzi 
Published: June 2020

AbstractThe respiratory electron transport complexes convey electrons from nutrients to oxygen and generate a proton-motive force used for energy (ATP) production in cells. These enzymes are conserved among organisms, and organized as individual complexes or combined forming large super-complexes (SC). Bacterial electron transport pathways are more branched than those of mitochondria and contain multiple variants of such complexes depending on their growth modes. The Gram-negative species deploy a mitochondrial-like cytochromebc1(Complex III, CIII2), and may have bacteria-specificcbb3-type cytochromecoxidases (Complex IV, CIV) in addition to, or instead of, the canonicalaa3-type CIV. Electron transfer between these complexes is mediated by two different carriers: the soluble cytochromec2which is similar to mitochondrial cytochromecand the membrane-anchored cytochromecywhich is unique to bacteria. Here, we report the first cryo-EM structure of a respiratorybc1-cbb3type SC (CIII2CIV, 5.2Å resolution) and several conformers of native CIII2(3.3Å resolution) from the Gram-negative bacteriumRhodobacter capsulatus. The SC contains all catalytic subunits and cofactors of CIII2and CIV, as well as two extra transmembrane helices attributed to cytochromecyand the assembly factor CcoH. Remarkably, some of the native CIII2are structural heterodimers with different conformations of their [2Fe-2S] cluster-bearing domains. The unresolved cytochromecdomain ofcysuggests that it is mobile, and it interacts with CIII2CIV differently than cytochromec2. Distance requirements for electron transfer suggest that cytochromecyand cytochromec2donate electrons to hemecp1and hemecp2of CIV, respectively. For the first time, the CIII2CIV architecture and its electronic connections establish the structural features of two separate respiratory electron transport pathways (membrane-confined and membrane-external) between its partners in Gram-negative bacteria.
Modeling the Coronavirus Disease 2019 Incubation Period: Impact on Quarantine Policy
Authors: Pak Daewoo , Langohr Klaus , Ning Jing , Martínez Jordi Cortés , Melis Guadalupe Gómez , Shen Yu 
Published: June 2020

AbstractThe incubation period of coronavirus disease 2019 (COVID-19) is not always observed exactly due to uncertain onset times of infection and disease symptom. In this paper, we demonstrate how to estimate the distribution of incubation and its association with patient demographic factors when the exact dates of infection and symptoms onset may not be observed. The findings from analysis on the confirmed COVID-19 cases indicate that age could be associated with the incubation period, and an age-specific quarantine policy might be more efficient than a unified one in confining COVID-19.
SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice
Authors: Tian Jing-Hui , Patel Nita , Haupt Robert , Zhou Haixia , Weston Stuart , Hammond Holly , Lague James , Portnoff Alyse D. , Norton James , Guebre-Xabier Mimi , Zhou Bin , Jacobson Kelsey , Maciejewski Sonia , Khatoon Rafia , Wisniewska Malgorzata , Moffitt Will , Kluepfel-Stahl Stefanie , Ekechukwu Betty , Papin James , Boddapati Sarathi , Wong C. Jason , Piedra Pedro A. , Frieman Matthew B. , Massare Michael J. , Fries Louis , Lövgren Bengtsson Karin , Stertman Linda , Ellingsworth Larry , Glenn Gregory , Smith Gale 
Published: July 2020

AbstractThe COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).
Emergence of Zika virus: Direct reversion of mutations and fitness restoration prior to spread to the Americas
Authors: Liu Jianying , Liu Yang , Shan Chao , Nunes Bruno T.D. , Yun Ruimei , Haller Sherry L. , Rafael Grace H. , Azar Sasha R. , Andersen Clark R. , Plante Kenneth , Vasilakis Nikos , Shi Pei-Yong , Weaver Scott C. 
Published: July 2020

Summary ParagraphMosquito-borne viruses have recently spread globally, with major impacts on human health. Zika virus (ZIKV) emerged from obscurity in 2013 to spread from Asia to the South Pacific and the Americas, where millions of people were infected. For the first time, severe clinical manifestations, including Guillain Barré syndrome and defects to the fetuses of pregnant women, were detected. Phylogenetic studies have shown that ZIKV evolved in Africa and later spread to Asia, and that the Asian lineage is responsible for the recent epidemics. However, the reasons for the sudden emergence of ZIKV remain incompletely understood. Accumulating evidence on other arboviruses like chikungunya and West Nile suggest the likelihood that viral mutations could be determinants of change in ZIKV transmission efficiency responsible for efficient spread. Using evolutionary analyses, we determined that four mutations, which occurred just before ZIKV introduction to the Americas, represent direct reversions of previous mutations that accompanied spread many decades ago from ZIKV’s native Africa to Asia and early circulation there. Experimental infections of mosquitoes, human cells, and mice using ZIKV strains with and without these mutations demonstrated that the original mutations reduced fitness for urban transmission, while the reversions restored fitness, increasing epidemic risk. Overall, our findings include the three newly identified, transmission-adaptive ZIKV mutations, and demonstration that these and one identified previously restored fitness for epidemic transmission soon before introduction into the America. The initial mutations may have followed founder effects and/or drift when the virus was introduced into Asia, or could be related to changes on host or vector utilization within Asia.
Validation and Comparison of a Modified CDC Assay with two Commercially Available Assays for the Detection of SARS-CoV-2 in Respiratory Specimen
Authors: Lima Amorce , Healer Vicki , Vendrone Elaine , Silbert Suzane 
Published: July 2020

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has spread rapidly around the globe since it was first identified in December of 2019 in Wuhan, China. In a race to contain the infection, researchers and healthcare officials have developed several assays to help diagnose individuals with COVID-19. To help laboratories in deciding what assay to bring into testing lines, factors such as assay availability, cost, throughput, and TAT should be considered. Here we validated a modified version of the CDC assay and used it as a reference to evaluate the performance of the NeuMoDx™ SARS-CoV-2 and DiaSorin Simplexa™ Covid-19 Direct assays.In silicoanalysis and clinical sample testing showed that the primesr/probes designed by the CDC were specific to the SARS-CoV-2 as they accurately detected all reactive samples with an assay LoD of 200 copies/ml. The performance of the three assays were analyzed using 161 nasopharyngeal swabs specimen tested within 24 hours or 5 days from routine testing. A 100% agreement was observed between the commercial assays and the modified CDC SARS-CoV-2 assay. A deeper look at the Ct values showed no significant difference between NeuMoDx and the modified CDC SARS-CoV-2 assay, whereas DiaSorin had lower overall Ct values than the modified CDC SARS-CoV-2 assay. NeuMoDx and DiaSorin workflows were much easier to perform. NeuMoDx has the highest throughput and shortest TAT, whereas although the modified CDC SARS-CoV-2 assay has comparable throughput to DiaSorin, it has the longest hands-on time, and highest TAT.
Asymmetric neurogenic commitment of retinal progenitors is regulated via the Notch endocytic pathway
Authors: Nerli Elisa , Rocha-Martins Mauricio , Norden Caren 
Published: July 2020

AbstractDuring brain development, progenitor cells need to balance proliferation and differentiation in order to generate different neurons in the correct numbers and proportions. Currently, the patterns of multipotent progenitors’ division that lead to neurogenic entry and the factors that regulate them are not fully understood. We here use the zebrafish retina to address this gap, exploiting the possibilities for quantitative live-imaging. We show that early neurogenic progenitors arise from asymmetric divisions. Notch regulates this asymmetry as when inhibited, symmetric divisions producing two neurogenic progenitors occur. Surprisingly, Notch does not act through an apicobasal activity gradient as previously suggested but through asymmetric inheritance of Sara-positive endosomes. Further, the resulting neurogenic progenitors show cell biological features different from multipotent progenitors, raising the possibility that an intermediate state of progenitors exists in the retina. Our study thus opens new insights into the regulation of proliferative and differentiative events during central nervous system development.
Impact of COVID-19 related lockdown on cognition and emotion: A pilot study
Authors: Lahiri Durjoy , Dubey Souvik , Ardila Alfredo 
Published: July 2020

AbstractCOVID-19 pandemic has posed an unprecedented challenge in front of the world contributed mostly by social distancing and lockdown. Among several other effects this pandemic has wreaked havoc on the psychology and cognition of people across the globe. In this paper we attempted to find out the impact of lockdown and social isolation on the cognition and emotion of young healthy adults with high education (n=43) by means of a questionnaire sent through email. We found that more than 50% of the participants had some kind of emotional or cognitive (dysexecutive) symptoms, as calculated through emotional symptom index (ESI) and cognitive symptom index (CSI). The correlation between cognitive and emotional symptoms was also found to be moderately strong (0.59). Although it is a pilot study and larger samples are required to draw firm conclusion, the results argue in favor of a negative impact on the cognition and emotion of healthy educated young people caused by the COVID-19 related lockdown. It can be conjectured that, if taking an older sample with a lower education, emotional and cognitive changes would be more evident.
Developing and Validating a New Web-Based Tapping Test for Measuring Distal Bradykinesia in Parkinson’s Disease
Authors: Akram Noreen , Li Haoxuan , Ben-Joseph Aaron , Budu Caroline , Gallagher David , Bestwick Jonathan P , Noyce Alastair J , Simonet Cristina 
Published: July 2020

ABSTRACTBackgroundDisability in Parkinson’s disease (PD) is measured by standardised scales including the MDS-UPDRS, which are subject to high inter and intra-rater variability and fail to capture subtle motor impairment. The BRadykinesia Akinesia INcoordination (BRAIN) test is a previously validated keyboard tapping test, evaluating proximal upper-limb motor impairment. Here, a new Distal Bradykinesia Tapping (DBT) test was developed to assess distal upper-limb function. Kinetic parameters of the test include kinesia score (KS20, key taps over 20 seconds), akinesia time (AT20, mean dwell-time on each key) and incoordination score (IS20, variance of travelling time between key taps).ObjectiveTo develop and validate a new keyboard-tapping test to assess distal motor function in PD patients.MethodsThe DBT test was validated in 45 PD patients and 24 controls, alongside the BRAIN test. Test scores were compared between groups and correlated with MDS-UPDRS-III scores. 10 additional PD patients were recruited to assess the DBT test in monitoring motor fluctuations.ResultsAll three parameters discriminated between patients and controls, with KS20 performing best, yielding 75% sensitivity for 85% specificity; area under the receiver operating characteristic curve (AUC) = 0.87. Combination of both the DBT and BRAIN tests improved discrimination (AUC=0.91). KS20 and AT20 correlated with MDS-UPDRS-III (Pearson’s r=-0.49, p<0.001 and r=0.54, p<0.001, respectively). The DBT test detected subtle changes in motor fluctuation states, which were not reflected clearly by MDS-UPDRS-III sub-scores.ConclusionThe DBT test is a user-friendly method of assessing distal motor dysfunction in PD, possibly permitting longitudinal monitoring of PD motor complications.
BDNF overexpression in the ventral hippocampus promotes antidepressant- and anxiolytic-like activity in serotonin transporter knockout rats
Authors: Diniz Danielle M. , Calabrese Francesca , Brivio Paola , Riva Marco A. , Grandjean Joanes , Homberg Judith R. 
Published: July 2020

AbstractBrain-derived neurotrophic factor is one of the most studied proteins playing a pivotal role in neuroplasticity events and vulnerability and resilience to stress-related disorders. Most importantly, BDNF is decreased in depressive patients, and increased after antidepressant treatment. Additionally, BDNF was found to be reduced in a genetic subset of depression susceptible patients carrying the human polymorphism in the serotonin transporter promoter region (5-HTTLPR). The serotonin knockout rat (SERT-/-) is one of the animal models used to investigate the underlying molecular mechanisms behind the genetic susceptibility to depression in humans. SERT-/-rats present decreased BDNF levels, especially BDNF exon IV, in the prefrontal cortex (PFC) and ventral hippocampus (vHIP), and display anxiety- and depression-like behavior. To investigate whether upregulating BDNF in the vHIP would meliorate the phenotype of SERT-/-rats, we overexpressed BDNF locally into the rat brain by means of stereotaxic surgery and submitted the animals to behavioral challenges, including the sucrose consumption, the open field, and forced swim tests. Additionally, we measured hypothalamus-pituitary-adrenal (HPA)-axis reactivity. The results showed that lentivirus-induced BDNF IV overexpression in the vHIP of SERT-/-rats promoted higher sucrose preference and sucrose intake, on the first day of the sucrose consumption test, indicative for decreased anhedonia-like behavior. Moreover, it decreased immobility time in the forced swim test, suggesting adaptive passive coping. Additionally, BDNF upregulation increased the time spent in the center of a novel environment, implying decreased novel-induced anxiety-like behavior. Finally, it promoted a stronger decrease in plasma corticosterone levels 60 minutes after restraint stress. In conclusion, modulation of BDNF IV levels in the vHIP of SERT-/-rats led to a positive behavioral outcome placing BDNF upregulation in the vHIP as a potential candidate for the development new therapeutic approaches targeting the improvement of depressive symptoms.
An analytical method for spiral-wound heat exchanger: design and cost estimation considering temperature-dependent fluid properties
Authors: Hosseinian Seyed Mohsen , Mostafazade Abolmaali Ali , Afshin Hossein 
Published: July 2020

Purpose
Spiral-wound heat exchangers (SWHEs) are widely used in different industries. In special applications, such as cryogenic (HEs), fluid properties may significantly depend on fluid temperature. This paper aims to present an analytical method for design and rating of SWHEs considering variable fluid properties with consistent shell geometry and single-phase fluid.

Design/methodology/approach
To consider variations of fluid properties, the HE is divided into identical segments, and the fluid properties are assumed to be constant in each segment. Validation of the analytical method is accomplished by using three-dimensional numerical simulation with shear stress transport k-ω model, and the numerical model is verified by using the experimental data. Moreover, the HE cost is selected as the main criterion in obtaining the proper design, and the most affordable geometry is selected as the proper design.

Findings
The accuracy of different heat transfer and pressure drop correlations is investigated by comparing the analytical and numerical results. The average errors in the calculation of effectiveness, shell-side pressure drop and tube-side pressure drop using the analytical method are 2.1%, 13.9% and 13.3%, respectively. Moreover, the effect of five main geometrical parameters on the SWHE cost is investigated. The results indicate that the effect of longitudinal pitch ratio on the SWHE cost can be neglected, whereas other geometrical parameters have a significant impact on the total cost of the SWHE.

Originality/value
This work contains a versatile and low-cost analytical method to design and rating the SWHEs considering the variable fluid property with consistent shell geometry. The previous studies have introduced complex methods and have not considered the consistency of shell geometry.
Use of social media for information discovery and delivery among information professionals in Pakistan
Authors: Hussain Ashfaq , Taimoor-Ul-Hassan  , Shabir Ghulam 
Published: July 2020

Purpose
This study aims to examine how information professionals select a social media channel for information discovery and delivery. This analysis was focused to provide usage based ranking of social media channels for information discovery and delivery. This study has also measured the preference of social media as compared with other information and communication channels such as radio, TV, newspapers, etc., for information discovery and delivery. This study compared the global social media rank with the study rank to record the variances in the light of uses and gratification theory.

Design/methodology/approach
For this quantitative research study a self-administered survey questionnaire was used to collect data from the participants of the study. Sample of this study was 700 information professionals necessarily user of social media.

Findings
Findings of this reveals that social media is the most preferred channel for information discovery and delivery among information professionals and study validates the assumption of uses and gratification theory with a view that information professionals are independent and active users of social media and global rank of social media is significantly different from the rank developed in this study.

Research limitations/implications
The present study is limited to information professionals only and considers social media (only top 20 sites) as an information and communication channel among information professionals.

Practical implications
This study has determined the preference of social media as an information and communication channel as compared with other information and communication channels and present a ranking based on usage among information professional, which is significantly different from the existing global user based ranking.

Social implications
Social media provides versatility of information in different forms and large numbers of information professionals are the users of social media around globe. This study shall help information professional to select appropriate channels for information discovery and delivery. Usage based ranking provided in this study shall stream line the social media practices at large.

Originality/value
This study has developed a usage based rank of top social media. This study elaborated the preference of social media as an information and communication channel.
Why customers make mobile payments? Applying a means-end chain approach
Authors: Sankaran Raja , Chakraborty Shibashish 
Published: July 2020

PurposeThis study aims to explore the motivational factors (or value components) using a consumer-centric view to enable consumer make mobile payments (mPayments).Design/methodology/approachMeans-end chain (MEC) theory, an exploratory approach was employed to understand personally relevant reasons for consumer use mPayments in India. In addition, the MEC phenomenon was investigated by examining the relationships among the three layers Attribute-Consequence-Value (A-C-V).FindingsThe study revealed the most important attribute to be handling money, followed by ease of use (consequence) and convenience as value. There was a wider recognition and penetration for acceptance of mPayments in smaller amounts or micro-payments with vendors, specifically in urban cities.Originality/valueThis research is the first of its kind wherein the concept of MEC has been utilized to evaluate why consumers make mPayments and demonstrate a novel approach to explore consumer insight into this domain.