bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donor Leukocyte Trafficking and Damage-associated Molecular Pattern Expression During Ex Vivo Lung Perfusion
Authors: Davis Robert P. , Yerxa John , Gao Qimeng , Gloria Jared , Scheuermann Uwe , Song Mingqing , Zhang Min , Parker William , Lee Jaewoo , Hartwig Matthew G. , Barbas Andrew S. 
Published: February 2020

Background.
While ex vivo lung perfusion (EVLP) has become established in lung transplantation, the cellular processes occurring during this period are not yet fully understood. Prior studies demonstrated that donor leukocytes (DLs) migrate from the graft into the perfusate during EVLP, but the distribution of DLs in graft and perfusate compartments has not been characterized. Moreover, cell death of DLs has been implicated in mediating graft injury during EVLP, but the underlying mechanisms have not been elucidated. We hypothesized the following: (1) there is a nonspecific migration of DLs from the graft into perfusate and (2) cell death of DLs releases damage-associated molecular patterns (DAMPs) that contribute to the inflammatory milieu during EVLP.

Methods.
EVLP was performed on rat lungs for 3 hours (N = 6). At the end of EVLP, flow cytometry was used to quantify the distribution of different DL cell types in both the graft and perfusate compartments. During EVLP, the perfusate was also sampled hourly to measure levels of DAMPs and downstream inflammatory cytokines generated during EVLP.

Results.
At the conclusion of EVLP, there was a significantly higher proportion of T and B cells present in the perfusate compartment compared with the graft compartment. There was a time-dependent increase in extracellular DNA and tumor necrosis factor α in the perfusate during EVLP.

Conclusions.
T cells and B cells are enriched in the perfusate compartment during EVLP. Cell death of DLs contributes to an accumulation of DAMPs during EVLP.
Survival in Living Kidney Donors: An Australian and New Zealand Cohort Study Using Data Linkage
Authors: De La Mata Nicole L. , Clayton Philip A. , Kelly Patrick J. , McDonald Stephen , Chadban Steven , Polkinghorne Kevan R. , Webster Angela C. 
Published: February 2020

Background.
Living kidney donors are a highly selected healthy population expected to have high survival postdonation, but mortality studies are limited. Our study aimed to compare mortality in living kidney donors with the general population in Australia and New Zealand, hypothesizing that donor survival would exceed average survival.

Methods.
All living kidney donors in Australia, 2004–2013, and New Zealand, 2004–2012, from the Australian and New Zealand Living Kidney Donor Registry were included. We ascertained primary cause of death from data linkage with national death registers. Standardized mortality ratios and relative survival were estimated, matching on age, sex, calendar year, and country.

Results.
Among 3253 living kidney donors, there were 32 deaths over 20 331 person-years, with median follow-up 6.2 years [interquartile range: 3.9–8.4]. Only 25 donors had diabetes-fasting blood sugar level predonation, of which 3 had impaired glucose tolerance. At discharge, the median creatinine was 108 µmol/L and estimated glomerular filtration rate was 58 mL/min/1.72 m2. Four deaths occurred in the first year: 2 from immediate complications of donation, and 2 from unrelated accidental causes. The leading cause of death was cancer (n = 16). The crude mortality rate was 157 (95% confidence interval [CI], 111-222)/100 000 person-y, and the standardized mortality ratio was 0.33 (95% CI, 0.24-0.47). The 5-year cumulative relative survival was 1.019 (95% CI, 1.014-1.021), confirming that the survival probability in living kidney donors was 2% higher relative to the general population.

Conclusions.
As expected, mortality in living kidney donors was substantially lower than the general population and is reassuring for potential donor counseling. The Living Donor Registry only captured a third of the deaths, highlighting the benefit of data linkage to national death registries in the long-term follow-up of living kidney donors.
Aestuariirhabdus litorea gen. nov., sp. nov., isolated from a sea tidal flat and proposal of Aestuariirhabdaceae fam. nov.
Authors: Khan Shehzad Abid , Jung Hye Su , Kim Hyung Min , Oh Jeill , Lee Sang-Suk , Jeon Che Ok 
Published: February 2020

A Gram-negative, moderately halophilic and facultatively aerobic bacterium, designated strain GTF13T, was isolated from a sea tidal flat. Cells were curved rods and motile by a single polar flagellum showing catalase and oxidase activities. Growth was observed at 20–37 °C, pH 5.0–8.5 and 1.0–6.0 % (w/v) NaCl. Strain GTF13T contained C16:0, summed feature 3 (comprising C16 : 1
ω6c/C16 : 1
ω7c), summed feature 8 (comprising C18 : 1
ω6c/C18 : 1
ω7c) and C12 : 0 3-OH as major fatty acids and ubiquinone-9 and ubiquinone-8 as major quinones. Phosphatidylethanolamine and two unidentified phospholipids were detected as major polar lipids. The G+C content of the genomic DNA was 59.8 mol%. Strain GTF13T was most closely related to

Simiduia agarivorans

SA1T,

Endozoicomonas montiporae

CL-33T and

Pseudomonas segetis

FR1439T, belonging to different families or orders of the class

Gammaproteobacteria

, with less than 92.0 % 16S rRNA gene sequence similarities. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain GTF13T formed a phylogenetic lineage with the family

Litoricolaceae

, but the genome-based phylogenomic tree showed that strain GTF13T formed a distinct phylogenetic lineage within the order

Oceanospirillales

. The very low 16S rRNA gene sequence similarities and distinct phylogenetic relationships, together with distinct phenotypic and chemotaxonomic properties, served to differentiate strain GTF13T from phylogenetically closely related families. Here, strain GTF13T is proposed as a novel genus and species, for which the name Aestuariirhabdus litorea gen. nov., sp. nov. is proposed, within a new family Aestuariirhabdaceae fam. nov. of the order

Oceanospirillales

. The type strain is GTF13T (=KACC 19788T=JCM 32043T).
Endogenous SIRT3 activity is dispensable for normal hearing recovery after noise exposure in young adult mice
Authors: Patel Sally , Shah Lisa , Dang Natalie , Tan Xiaodong , Almudevar Anthony , White Patricia M. 
Published: February 2020

ABSTRACTOccupational noise-induced hearing loss (NIHL) affects millions of people worldwide and presents a large social and personal burden. Some genetic variants in the mitochondrial oxidative stress response correlate strongly with susceptibility to NIHL in both humans and mice. Here we test the hypothesis that SIRT3, a regulator of the mitochondrial oxidative stress response, is required in mice for endogenous recovery of auditory thresholds after a sub-traumatic noise exposure. We expose homozygousSirt3-KOmice and their wild-type littermates to a noise dose that confers a temporary threshold shift, but is not sufficient to permanently reduce cochlear function, compromise cell survival, or damage synaptic structures. We find no difference in hearing function after recovery from noise exposure between the two genotypes, when measured by either auditory brainstem response (ABR) or distortion product otoacoustic emissions (DPOAE). We show that SIRT3-specific immunoreactivity is present in outer hair cells, around the post-synaptic regions of inner hair cells, and faintly within inner hair cells. Nonetheless, outer hair cells and auditory synapses show no increase in loss after noise exposure in the homozygousSirt3-KOmouse. These data show that SIRT3-dependent processes are not necessary for endogenous hearing recovery after a single, sub-traumatic noise exposure. They demonstrate the existence of cellular mechanisms of cochlear homeostasis in addition to the mitochondrial oxidative stress response. We also present a novel statistical analysis for identifying differences between peak 1 amplitude progressions in ABR waveforms.
Tracking the spread of novel coronavirus (2019-nCoV) based on big data
Authors: Zhao Xumao , Liu Xiang , Li Xinhai 
Published: February 2020

AbstractThe novel coronavirus (2019-nCoV) appeared in Wuhan in late 2019 have infected 34,598 people, and killed 723 among them until 8th February 2020. The new virus has spread to at least 316 cities (until 1st February 2020) in China. We used the traffic flow data from Baidu Map, and number of air passengers who left Wuhan from 1st January to 26th January, to quantify the potential infectious people. We developed multiple linear models with local population and air passengers as predicted variables to explain the variance of confirmed cases in every city across China. We found the contribution of air passengers from Wuhan was decreasing gradually, but the effect of local population was increasing, indicating the trend of local transmission. However, the increase of local transmission is slow during the early stage of novel coronavirus, due to the super strict control measures carried out by government agents and communities.
The Ph.D. Panic: Examining the relationships among teaching anxiety, teaching self-efficacy, and coping in Biology graduate teaching assistants (GTAs)
Authors: Chen Musgrove Miranda M. , Schussler Elisabeth E. 
Published: February 2020

ABSTRACTAnxiety among graduate students in the United States has increased over the last several decades, affecting not only their overall mental health but also reducing retention in graduate programs. Teachers with high teaching anxiety can negatively impact student learning, yet the impacts of teaching anxiety on graduate teaching assistants (GTAs) is not well studied. Biology GTAs teach most introductory Biology labs and discussions nationally, thus broadly influencing the quality of undergraduate education. In Fall 2016, we investigated Biology GTA teaching anxiety at a large research-intensive southeastern university by (1) measuring teaching anxiety of Biology GTAs, and (2) exploring the relationships among teaching anxiety, self-efficacy, and coping. Using multiple linear regressions, we found that greater teaching self-efficacy is related to lower teaching anxiety in Biology GTAs (R2adi=0.65,p<0.001). Coping strategies and frequencies did not significantly contribute to teaching anxiety in our models. We found similar levels of teaching anxiety across genders, ethnicities, student citizenship status (domestic vs. international) and teaching experience level. However, there were significant differences among student subgroups in teaching self-efficacy and coping strategies. Effective coping may contribute to the lack of anxiety differences among some of the student subgroups. These results can inform teaching professional development for GTAs, and encourage greater awareness and dialogue about the impacts of mental health issues in academia.
Potential G-quadruplex forming sequences andN6-methyladenosine colocalize at human pre-mRNA intron splice sites
Authors: Jara-Espejo Manuel , Fleming Aaron M. , Burrows Cynthia J. 
Published: February 2020

ABSTRACTUsing bioinformatic analysis of published data, we identify in human mRNA that potential G-quadruplex forming sequences (PQSs) colocalize with the epitranscriptomic modificationsN6-methyladenosine (m6A), pseudouridine (Ψ), and inosine (I). A deeper analysis of the colocalized m6A and PQSs found them intronic in pre-mRNA near 5′ and 3′ splice sites. The loop lengths and sequence context of the m6A-bearing PQSs found short loops most commonly comprised of A nucleotides. This observation is consistent with literature reports of intronic m6A found in SAG (S = C or G) consensus motifs that are also recognized by splicing factors. The localization of m6A and PQSs in pre-mRNA at intron splice junctions suggests that these features could be involved in alternative mRNA splicing. A similar analysis for PQSs around sites of Ψ installation or A-to-I editing in mRNA also found a colocalization; however, the frequency was less than that observed with m6A.TOC Graphic
Exploring the coronavirus epidemic using the new WashU Virus Genome Browser
Authors: Flynn Jennifer A. , Purushotham Deepak , Choudhary Mayank NK , Zhuo Xiaoyu , Fan Changxu , Matt Gavriel , Li Daofeng , Wang Ting 
Published: February 2020

AbstractSince its debut in mid-December, 2019, the novel coronavirus (2019-nCoV) has rapidly spread from its origin in Wuhan, China, to several countries across the globe, leading to a global health crisis. As of February 7, 2020, 44 strains of the virus have been sequenced and uploaded to NCBI’s GenBank [1], providing insight into the virus’s evolutionary history and pathogenesis. Here, we present the WashU Virus Genome Browser, a web-based portal for viewing virus genomic data. The browser is home to 16 complete 2019-nCoV genome sequences, together with hundreds of related viral sequences including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus. In addition, the browser features unique customizability, supporting user-provided upload of novel viral sequences in various formats. Sequences can be viewed in both a track-based representation as well as a phylogenetic tree-based view, allowing the user to easily compare sequence features across multiple strains. The WashU Virus Genome Browser inherited many features and track types from the WashU Epigenome Browser, and additionally incorporated a new type of SNV track to address the specific needs of viral research. Our Virus Browser portal can be accessed athttps://virusgateway.wustl.edu, and documentation is available athttps://virusgateway.readthedocs.io/.
The architecture of protein synthesis in the developing neocortex at near-atomic resolution reveals Ebp1-mediated neuronal proteostasis at the 60S tunnel exit
Authors: Kraushar Matthew L. , Krupp Ferdinand , Turko Paul , Ambrozkiewicz Mateusz C. , Sprink Thiemo , Imami Koshi , Vieira-Vieira Carlos H. , Schaub Theres , Harnett Dermot , Münster-Wandowski Agnieszka , Bürger Jörg , Zinnall Ulrike , Borisova Ekaterina , Yamamoto Hiroshi , Rasin Mladen-Roko , Beule Dieter , Landthaler Markus , Mielke Thorsten , Tarabykin Victor , Vida Imre , Selbach Matthias , Spahn Christian M.T. 
Published: February 2020

SUMMARYProtein synthesis must be finely tuned in the nervous system, as it represents an essential feature of neurodevelopmental gene expression, and dominant pathology in neurological disease. However, the architecture of ribosomal complexes in the developing mammalian brain has not been analyzed at high resolution. This study investigates the architecture of ribosomesex vivofrom the embryonic and perinatal mouse neocortex, revealing Ebp1 as a 60S peptide tunnel exit binding factor at near-atomic resolution by multiparticle cryo-electron microscopy. The impact of Ebp1 on the neuronal proteome was analyzed by pSILAC and BONCAT coupled mass spectrometry, implicating Ebp1 in neurite outgrowth proteostasis, within vivoembryonic Ebp1 knockdown resulting in dysregulation of neurite outgrowth. Our findings reveal Ebp1 as a central component of neocortical protein synthesis, and the 60S peptide tunnel exit as a focal point of gene expression control in the molecular specification of neuronal morphology.Graphical abstract
Administration of fusion cytokines induces tumor regression and systemic antitumor immunity
Authors: Zhang Jinyu , Zhao Xuan 
Published: February 2020

AbstractThe curative effects of cancer immunotherapy are hard to be improved in solid tumors. Cytokines, as powerful immune regulators, show potential in awaking host antitumor immunity. We have previously found that administration of certain cytokine combinations induced complete tumor clearance. Here we constructed the cognate fusion cytokines and evaluated their antitumor effects in various mouse tumor models.In situinduced expression of the fusion cytokine IL12IL2GMCSF led to tumor eradication, even those in high advanced stage. An immune memory against other irrelated syngeneic tumors was elicited. Flow cytometry analysis revealed that tumor infiltrating CD3+ cells greatly increased, accompanied with an elevation of CD8+/CD4+ ratio. The fusion protein exhibited superior immune activating capability to cytokine mixtures in vitro, and induced tumor regression in various immune competent tumor models by intratumoral injection. To improve translational potential, an immunocytokine IL12IL2DiaNFGMCSF for systemic administration was constructed by inserting tumor targeting diabody. The protein also displayed good activities in vitro. Intravenous infusion of IL12IL2DiaNFGMCSF induced a tumor infiltrating immune cell alteration like IL12IL2GMCSF, with moderate serum IFNγ increment. Therapeutic effects were observed in various tumor models after systemic administration of IL12IL2DiaNFGMCSF, with slight toxicity. These results provide the feasibility of developing a versatile cancer immunotherapy remedy.
A cryptic pocket in Ebola VP35 allosterically controls RNA binding
Authors: Cruz Matthew A. , Frederick Thomas E. , Mallimadugula Upasana , Singh Sukrit , Vithani Neha , Zimmerman Maxwell I. , Porter Justin R. , Moeder Katelyn E. , Amarasinghe Gaya K. , Bowman Gregory R. 
Published: February 2020

AbstractProtein-protein and protein-nucleic acid interactions are often considered difficult drug targets because the surfaces involved lack obvious druggable pockets. Cryptic pockets could present opportunities for targeting these interactions, but identifying and exploiting these pockets remains challenging. Here, we apply a general pipeline for identifying cryptic pockets to the interferon inhibitory domain (IID) of Ebola viral protein 35 (VP35). VP35 plays multiple essential roles in Ebola’s replication cycle but lacks pockets that present obvious utility for drug design. Using adaptive sampling simulations and machine learning algorithms, we predict VP35 harbors a cryptic pocket that is allosterically coupled to a key dsRNA-binding interface. Thiol labeling experiments corroborate the predicted pocket and mutating the predicted allosteric network supports our model of allostery. Finally, covalent modifications that mimic drug binding allosterically disrupt dsRNA binding that is essential for immune evasion. Based on these successes, we expect our pipeline is equally applicable to other proteins.
Real-time suppression and amplification of frequency-specific neural activity using stimulation evoked oscillations
Authors: Sanabria David Escobar , Johnson Luke A. , Yu Ying , Busby Zachary , Nebeck Shane , Zhang Jianyu , Harel Noam , Johnson Matthew D. , Molnar Gregory F. , Vitek Jerrold L. 
Published: February 2020

AbstractBackgroundApproaches to predictably control neural oscillations are needed to understand their causal role in brain function in healthy or diseased states and to advance the development of neuromodulation therapies. In this study, we present a closed-loop neural control and optimization framework to actively suppress or amplify low-frequency neural oscillations observed in local field potentials in real-time by using electrical stimulation.Objective/HypothesisThe rationale behind this control approach and our working hypothesis is that neural oscillatory activity evoked by electrical pulses can suppress or amplify spontaneous oscillations via destructive or constructive interference when stimulation pulses are continuously delivered with appropriate amplitudes and at precise phases of these oscillations in a closed-loop scheme.MethodsWe tested our hypothesis in two nonhuman primates that exhibited a robust increase in low-frequency (8-30 Hz) oscillatory power in the subthalamic nucleus (STN) following administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To test our neural control approach, we targeted 8-17 Hz oscillations and used electrode arrays and electrical stimulation waveforms similar to those used in humans chronically implanted with brain stimulation systems. Stimulation parameters that maximize the suppression or amplification of neural oscillations were predicted using mathematical models of the stimulation evoked oscillations.ResultsOur neural control and optimization approach was capable of actively and robustly suppressing or amplifying oscillations in the targeted frequency band (8-17 Hz) in real-time in the studied subjects.ConclusionsThe results from this study support our hypothesis and suggest that the proposed neural control framework allows one to characterize in controlled experiments the functional role of frequency-specific neural oscillations by using electrodes and stimulation waveforms currently being employed in humans.
Stochastic synchronization of dynamics on the human connectome
Authors: Pang James C. , Gollo Leonardo L. , Roberts James A. 
Published: February 2020

AbstractSynchronization is a collective mechanism by which oscillatory networks achieve their functions. Factors driving synchronization include the network’s topological and dynamical properties. However, how these factors drive the emergence of synchronization in the presence of potentially disruptive external inputs like stochastic perturbations is not well understood, particularly for real-world systems such as the human brain. Here, we aim to systematically address this problem using a large-scale model of the human brain network (i.e., the human connectome). The results show that the model can produce complex synchronization patterns transitioning between incoherent and coherent states. When nodes in the network are coupled at some critical strength, a counterintuitive phenomenon emerges where the addition of noise increases the synchronization of global and local dynamics, with structural hub nodes benefiting the most. This stochastic synchronization effect is found to be driven by the intrinsic hierarchy of neural timescales of the brain and the heterogeneous complex topology of the connectome. Moreover, the effect coincides with clustering of node phases and node frequencies and strengthening of the functional connectivity of some of the connectome’s subnetworks. Overall, the work provides broad theoretical insights into the emergence and mechanisms of stochastic synchronization, highlighting its putative contribution in achieving network integration underpinning brain function.