bluuebunny/crossref_metadata_2025 huggingface dataset:
The assessment of Computer Vision Algorithms for the Diagnosis of Prostatic Adenocarcinoma in Surgical Specimens
Authors: Bukhari Syed Usama Khalid , Mehtab Ubeer , Hussain Syed Shahzad , Syed Asmara , Armaghan Syed Umar , Shah Syed Sajid Hussain
Published: July 2020

Introduction

Prostatic malignancy is a major cause of morbidity and fatality among men around the globe. More than a million new cases of prostatic cancer are diagnoses annually. The incidence of prostatic malignancy is rising and it is expected that more than two million new cases of prostatic carcinoma will be diagnosed in 2040. The application of machine learning to assist the histopathologists could be a very valuable adjunct tool for the histological diagnosis of prostatic malignant tumors.

Aim & Objectives

To evaluate the effectiveness of artificial intelligence for the histopathological diagnosis of prostatic carcinoma by analyzing the digitized pathology slides.

Materials & Methods

Eight hundred and two (802) images in total, were obtained from the anonymised slides stained with hematoxylin and eosin which included anonymised 337 images of prostatic adenocarcinoma and 465 anonymised images of nodular hyperplasia of prostate. Eighty percent (80%) of the total digital images were used for training and 20% for testing. Three ResNet architectures ResNet-18, ResNet-34, and ResNet-50 were employed for the analysis of these images.

Results

The evaluation of digital images by ResNet-18, ResNet-34, and ResNet-50 revealed the diagnostic accuracy of 97.1%, 98 % and 99.5 % respectively.

Discussion

The application of artificial intelligence is being considered as a very useful tool which may improve the patient care by improving the diagnostic accuracy and reducing the cost. In radiology, the application of deep learning to interpret radiological images has revealed excellent results. In the present study, the analysis of pathology images by convolutional neural network architecture revealed the diagnostic accuracy of 97.1%, 98 % and 99.5 % with by ResNet-18, ResNet-34, and ResNet-50 respectively. The findings of the present study are in accordance with the other published series, which were carried out to determine the accuracy of machine learning for the diagnosis of cancers of lung, breast and prostate. The application of deep learning for the histological diagnosis of malignant tumors could be quite helpful in improving the patient care.

Conclusion

The findings of the present study suggest that intelligent vision system possibly a worthwhile tool for the histopathological evaluation of prostatic tissue to differentiate between the benign and malignant disorders.
Genome-wide association study of resistance to Mycobacterium tuberculosis infection identifies a locus at 10q26.2 in three distinct populations
Authors: Quistrebert Jocelyn , Orlova Marianna , Kerner Gaspard , Ton Le Thi , Luong Nguyễn Trong , Danh Nguyễn Thanh , Jabot-Hanin Fabienne , Seeleuthner Yoann , Bustamante Jacinta , Boisson-Dupuis Stéphanie , Huong Nguyen Thu , Ba Nguyen Ngoc , Casanova Jean-Laurent , Delacourt Christophe , Hoal Eileen G. , Alcaïs Alexandre , Thai Vu Hong , Thành Lai The , Abel Laurent , Schurr Erwin , Cobat Aurélie
Published: July 2020

The natural history of tuberculosis (TB) is characterized by a large inter-individual outcome variability after exposure to Mycobacterium tuberculosis. Specifically, some highly exposed individuals remain resistant to M. tuberculosis infection, as inferred by tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). We performed a genome-wide association study of resistance to M. tuberculosis infection in an endemic region of Southern Vietnam. We enrolled household contacts (HHC) of pulmonary TB cases and compared subjects who were negative for both TST and IGRA (n=185) with infected individuals (n=353) who were either positive for both TST and IGRA or had a diagnosis of TB. We found a genome-wide significant locus on chromosome 10q26.2 with a cluster of variants associated with strong protection against M. tuberculosis infection (OR=0.42, 95%CI 0.35-0.49, P = 3.71×10−8, for the genotyped variant rs17155120). The locus was replicated in a French multi-ethnic HHC cohort and a familial admixed cohort from a hyper-endemic area of South Africa, with an overall OR for rs17155120 estimated at 0.50 (95%CI 0.45-0.55, P = 1.26×10−9). The variants are located in intronic regions and upstream of C10orf90, a tumor suppressor gene which encodes an ubiquitin ligase activating the transcription factor p53. In silico analysis showed that the protective alleles were associated with a decreased expression in monocytes of the nearby gene ADAM12 which could lead to an enhanced response of Th17 lymphocytes. Our results reveal a novel locus controlling resistance to M. tuberculosis infection across different populations.
SARS-CoV-2 Viral Load is Associated with Increased Disease Severity and Mortality
Authors: Fajnzylber Jesse , Regan James , Coxen Kendyll , Corry Heather , Wong Colline , Rosenthal Alexandra , Worrall Daniel , Giguel Francoise , Piechocka-Trocha Alicja , Atyeo Caroline , Fischinger Stephanie , Chan Andrew , Flaherty Keith T. , Hall Kathryn , Dougan Michael , Ryan Edward T. , Gillespie Elizabeth , Chishti Rida , Li Yijia , Jilg Nikolaus , Hanidziar Dusan , Baron Rebecca M. , Baden Lindsey , Tsibris Athe M. , Armstrong Katrina A. , Kuritzkes Daniel R. , Alter Galit , Walker Bruce D. , Yu Xu , Li Jonathan Z. ,   for the Massachusetts Consortium for Pathogen Readiness
Published: July 2020

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). We quantified SARS-CoV-2 viral load from participants with a diverse range of COVID-19 severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. SARS-CoV-2 plasma RNA was detected in 27% of hospitalized participants and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, higher prevalence of detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, were associated with increased risk of mortality. SARS-CoV-2 viral load may aid in the risk stratification of patients with COVID-19 and its role in disease pathogenesis should be further explored.
Chronotropic Incompetence Limits Aerobic Exercise Capacity in Patients Taking Beta-Blockers
Authors: Tysarowski Maciej , Smarz Krzysztof , Zaborska Beata , Pilichowska-Paszkiet Ewa , Sikora-Frac Malgorzata , Budaj Andrzej , Jaxa-Chamiec Tomasz
Published: July 2020

Background

Chronotropic incompetence in patients taking beta-blockers is associated with poor prognosis; however, its impact on exercise capacity (EC) remains unclear.

Methods

We retrospectively analyzed data from consecutive patients taking beta-blockers referred for cardiopulmonary exercise testing. EC was expressed as peak oxygen uptake (peak VO2; mL/kg/min). Chronotropic incompetence was defined as chronotropic index (CI) ≤ 62%. CI was calculated as [(HR at peak–HR at rest) / (maximum predicted HR–HR at rest)] × 100%.

Results

Among 140 patients all taking beta-blockers (age 61 ± 9.7 years; 73% males), there were 113 (80.7%) patients with chronotropic incompetence. EC was lower in the group with chronotropic incompetence than the group without it, peak VO2 18.3 ± 5.7 vs. 24.0 ± 5.3 mL/kg/min, p < 0.001. In multivariate analysis EC correlated positively with CI (β = 0.14, p < 0.001) and male gender (β = 5.12, p < 0.001), and negatively with age (β = −0.17, p < 0.001) and presence of heart failure (β = −3.35, p < 0.001). Beta-blocker dose was not associated with EC. Partial correlation attributable to CI accounted for more than one-third of the variance in EC explained by the model.

Conclusions

In patients taking beta-blockers, presence of chronotropic incompetence was associated with lower EC, regardless of the beta-blocker dose. CI accounted for more than one-third of EC variance explained by our model.

HIGHLIGHTS

Patients on beta blockers with chronotropic incompetence have lower exercise capacity

Beta-blocker dose is not associated with exercise capacity

We recommend incorporating chronotropic index into exercise stress testing
Sensitive alignment using paralogous sequence variants improves long read mapping and variant calling in segmental duplications
Authors: Prodanov Timofey , Bansal Vikas
Published: July 2020

The ability to characterize repetitive regions of the human genome is limited by the read lengths of short-read sequencing technologies. Although long-read sequencing technologies such as Pacific Biosciences and Oxford Nanopore can potentially overcome this limitation, long segmental duplications with high sequence identity pose challenges for long-read mapping. We describe a probabilistic method, DuploMap, designed to improve the accuracy of long read mapping in segmental duplications. It analyzes reads mapped to segmental duplications using existing long-read aligners and leverages paralogous sequence variants (PSVs) – sequence differences between paralogous sequences – to distinguish between multiple alignment locations. On simulated datasets, Duplomap increased the percentage of correctly mapped reads with high confidence for multiple long-read aligners including Minimap2 (74.3% to 90.6%) and BLASR (82.9% to 90.7%) while maintaining high precision. Across multiple whole-genome long-read datasets, DuploMap aligned an additional 8-21% of the reads in segmental duplications with high confidence relative to Minimap2. Using Duplomap aligned PacBio CCS reads, an additional 8.9 Mbp of DNA sequence was mappable, variant calling achieved a higher F1-score and 14,713 additional variants supported by linked-read data were identified. Finally, we demonstrate that a significant fraction of PSVs in segmental duplications overlap with variants and adversely impact short-read variant calling.
Bystander CD4+T cells infiltrate human tumors and are phenotypically distinct
Authors: Simoni Yannick , Li Shamin , Zhuang Summer , Heit Antja , Koo Si-Lin , Chow I-Ting , Kwok William W. , Tan Iain Beehuat , Tan Daniel S.W. , Newell Evan W.
Published: July 2020

Tumor-specific T cells likely underpin effective immune checkpoint-blockade therapies. Yet, most studies focus on Treg cells and CD8+tumor-infiltrating lymphocytes (TILs). Here we study CD4+TILs in human lung and colorectal cancers and observe that non-Treg CD4+TILs average more than 70% of total CD4+TILs in both cancer types. Leveraging high dimensional analyses including mass cytometry and single-cell sequencing, we reveal that CD4+TILs are heterogeneous at both gene and protein levels, within each tumor and across patients. Consistently, we find different subsets of CD4+TILs showing characteristics of effectors, tissue resident memory (Trm) or exhausted cells (expressing PD-1, CTLA-4 and CD39). In both cancer types, the frequencies of CD39−non-Treg CD4+TILs strongly correlate with frequencies of CD39−CD8+TILs, which we and others have previously shown to be enriched for cells specific for cancer-unrelated antigens (bystanders).Ex-vivo, we demonstrate that CD39−CD4+TILs can be specific for cancer unrelated antigens, such as HCMV epitopes. Overall, our findings highlight that CD4+TILs cells are not necessarily tumor-specific and suggest measuring CD39 expression as a straightforward way to quantify or isolate bystander CD4+T cells.

Graphical abstract
Varying perivascular astroglial endfoot dimensions along the vascular tree maintain perivascular-interstitial flux through the cortical mantle
Authors: Wang Marie Xun , Ray Lori , Tanaka Kenji F. , Iliff Jeffrey J. , Heys Jeffrey
Published: July 2020

The glymphatic system is a recently defined brain-wide network of perivascular spaces along which cerebrospinal fluid (CSF) and interstitial solutes exchange. Astrocyte endfeet encircling the perivascular space form a physical barrier in between these two compartments, and fluid and solutes that are not taken up by astrocytes move out of the perivascular space through the junctions in between astrocyte endfeet. However, little is known about the anatomical structure and the physiological roles of the astrocyte endfeet in regulating the local perivascular exchange. Here, visualizing astrocyte endfoot-endfoot junctions with immunofluorescent labeling against the protein megalencephalic leukoencephalopathy with subcortical cysts-1 (MLC1), we characterized endfoot dimensions along the mouse cerebrovascular tree. We observed marked heterogeneity in endfoot dimensions along vessels of different sizes, and of different types. Specifically, endfoot size was positively correlated with the vessel diameters, with large vessel segments surrounded by large endfeet and small vessel segments surrounded by small endfeet. This association was most pronounced along arterial, rather than venous segments. Computational modeling simulating vascular trees with uniform or varying endfeet dimensions demonstrates that varying endfoot dimensions maintain near constant perivascular-interstitial flux despite correspondingly declining perivascular pressures along the cerebrovascular tree through the cortical depth. These results describe a novel anatomical feature of perivascular astroglial endfeet and suggest that endfoot heterogeneity may be an evolutionary adaptation to maintain perivascular CSF-interstitial fluid exchange through deep brain structures.
Simultaneous Epigenetic Perturbation and Genome Imaging Reveal Distinct Roles of H3K9me3 in Chromatin Architecture and Transcription
Authors: Feng Ying , Wang Yao , Wang Xiangnan , He Xiaohui , Yang Chen , Naseri Ardalan , Pederson Thoru , Zheng Jing , Zhang Shaojie , Xiao Xiao , Xie Wei , Ma Hanhui
Published: July 2020

Despite the long-observed correlation between H3K9me3, chromatin architecture and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Here we develop EpiGo (EpigeneticperturbationinducedGenomeorganization)-KRAB to introduce H3K9me3 at hundreds of loci spanning megabases on human chromosome 19 and simultaneously track genome organization. EpiGo-KRAB is sufficient to inducede novoheterochromatin-like domain formation, which requires SETDB1, a methyltransferase of H3K9me3. Unexpectedly, EpiGo-KRAB induced heterochromatin-like domain does not result in widespread gene repression except a small set of genes with concurrent loss of H3K4me3 and H3K27ac. Ectopic H3K9me3 appears to spread in inactive regions but is largely restricted to transcriptional initiation sites in active regions. Finally, Hi-C analysis showed that EpiGo-KRAB induced to reshape existing compartments. These results reveal the role of H3K9me3 in genome organization could be partially separated from its function in gene repression.
A Kmer-based paired-end read (KPR)de novoassembler and genotyper to genotype major histocompatibility complex class I (MHC-I) alleles for the dog
Authors: Feng Yuan , Hildebrand William H. , Tompkins Stephen M. , Zhao Shaying
Published: July 2020

The major histocompatibility complex class I (MHC-I) genes are highly polymorphic among individuals. MHC-I genotyping is required for determining the antigen-binding specificity of each MHC-I molecule in an individual. Numerous tools have been developed for human MHC-I genotyping using deep sequencing data such as RNA-seq; however they do not work for the dog, due to very limited information for canine alleles. To address this issue, we developed a Kmer-based paired-end read (KPR)de novoassembler and genotyper, which first assemble paired-end RNA-seq reads mapped to the MHC-I regions into contigsde novoand then genotype each contig. Our KPR tools are validated by Sanger sequencing, simulation and published genotype data. Applying our KPR tools on the published RNA-seq data of 158 tumor and 64 normal samples from 158 dogs, we have achieved a genotyping success rate of 86%, which includes 133 tumor and 57 normal samples from 142 dogs. We have identified 39 known alleles and 83 new alleles of high confidence in these dogs, yielding a more comprehensive MHC-I allele diversity landscape for the dog.
Segregation of brain and organizer precursors is differentially regulated by Nodal signaling at blastula stage
Authors: Castro Colabianchi Aitana M. , Tavella María B. , Boyadjián López Laura E. , Rubinstein Marcelo , Franchini Lucía F. , López Silvia L.
Published: July 2020

The Blastula Chordin- and Noggin Expressing Center (BCNE) comprises animal-dorsal and marginal-dorsal cells of the amphibian blastula and contains the precursors of the brain and of the gastrula organizer. Previous findings suggested that the BCNE behaves as a homogeneous cell population that depends only on nuclear β-catenin activity but does not require Nodal and segregates into its descendants later, during gastrulation. In this work, we analyzed if the BCNE is already compartmentalized at the blastula stage. In contrast to previous findings, we show that the BCNE does not behave as a homogeneous cell population in response to Nodal antagonists. In fact, we found that thechordin.1expression in a marginal subpopulation of notochordal precursors indeed requires Nodal input. We also establish that an animal BCNE subpopulation of cells that express both,chordin.1andsox2(a marker of pluripotent neuroectodermal cells), and gives rise to most of the brain, persisted at blastula stage after blocking Nodal. Moreover, RT-qPCR analysis showed thatchordin.1andsox2expression increased at blastula stage after blocking Nodal. Therefore, Nodal signaling is required to define a population ofchordin.1+cells and to restrict the recruitment of brain precursors within the BCNE as early as at blastula stage.
Metronomic doses and drug schematic combination response tested within microfluidic models for the treatment of breast cancer cells (JIMT-1)
Authors: Rosero Gustavo , Pattarone Gisela , Peñaherera Ana , Pilz Julia Felicitas , Bödecker Joschka , Lerner B , Mertelsmann Roland , Perez M.S , Follo Marie
Published: July 2020

Low-dose metronomic (LDM) chemotherapy is an alternative to conventional chemotherapy and is the most common use of low-dose levels of traditional chemotherapeutics in patients. The selection of patients, drug dosages and dosing intervals in LDM is empirical. In this study we systematically examined the schedule-dependent interaction of drugs on a breast cancer cell line (BCC) cultured in Lab on a Chip (LOC) microdevices. The LDM studies were combined with cell staining in order to better characterize different cell stages and modes of cell death, including caspase-dependent apoptosis, caspase-independent cell death and autophagy-dependent cell death. Microscope images were examined using the Fiji plugin Trainable Weka Segmentation to analyze cell area in 7500 images showing different types of cell death modes. Paclitaxel combined with LDM chemotherapy demonstrated a reduction in the area covered by live cells. In contrast, there was an induction of high levels of cell death due to caspase-dependent apoptosis. Furthermore, the microdevice used in this study is also an attractive alternative for staining cells in order to characterize and study BCC growth and development in situ.
Saliva TwoStep for rapid detection of asymptomatic SARS-CoV-2 carriers
Authors: Yang Qing , Meyerson Nicholas R. , Clark Stephen K. , Paige Camille L. , Fattor Will T. , Gilchrist Alison R. , Barbachano-Guerrero Arturo , Healy Benjamin G. , Worden-Sapper Emma R. , Wu Sharon S. , Muhlrad Denise , Decker Carolyn J. , Saldi Tassa K. , Lasda Erika , Gonzales Patrick K. , Fink Morgan R. , Tat Kimngan L. , Hager Cole R. , Davis Jack C. , Ozeroff Christopher D. , Brisson Gloria R. , McQueen Matthew B. , Leinwand Leslie , Parker Roy , Sawyer Sara L.
Published: July 2020

Here, we develop a simple molecular test for SARS-CoV-2 in saliva based on reverse transcription loop-mediated isothermal amplification (RT-LAMP). The test has two steps: 1) heat saliva with a stabilization solution, and 2) detect virus by incubating with a primer/enzyme mix. After incubation, saliva samples containing the SARS-CoV-2 genome turn bright yellow. Because this test is pH dependent, it can react falsely to some naturally acidic saliva samples. We report unique saliva stabilization protocols that rendered 295 healthy saliva samples compatible with the test, producing zero false positives. We also evaluated the test on 278 saliva samples from individuals who were infected with SARS-CoV-2 but had no symptoms at the time of saliva collection, and from 54 matched pairs of saliva and anterior nasal samples from infected individuals. The Saliva TwoStep test described herein identified infections with 94% sensitivity and >99% specificity in individuals with sub-clinical (asymptomatic or pre-symptomatic) infections.
IgG antibody seroconversion and the clinical progression of COVID-19 pneumonia: A retrospective, cohort study
Authors: Kurashima Kazuyoshi , Kagiyama Naho , Ishiguro Takashi , Takaku Yotaro , Nakajima Hiromi , Shibata Shun , Matsui Yuma , Takano Kenji , Isono Taisuke , Nishida Takashi , Kawate Eriko , Hosoda Chiaki , Kobayashi Yoichi , Takayanagi Noboru , Yanagisawa Tsutomu
Published: July 2020

Background

Coronavirus Disease 2019 (COVID-19) causes severe acute respiratory failure. Antibody-dependent enhancement (ADE) is known as the mechanism for severe forms of other coronavirus diseases. The clinical progression of COVID-19 before and after IgG antibody seroconversion was investigated.

Methods

Fifty-three patients with reverse transcriptase PCR (RT-PCT)-confirmed COVID-19 viral pneumonia with or without respiratory failure were retrospectively investigated. The timing of the first IgG antibody against SARS-CoV-2-positive date, as well as changes of C-reactive protein (CRP) as an inflammatory marker and blood lymphocyte numbers, was assessed using serial preserved blood samples.

Findings

Ten patients recovered without oxygen therapy (mild/moderate group), 32 patients had hypoxemia and recovered with antiviral drugs (severe/non-ICU group), and 11 patients had severe respiratory failure and were treated in the ICU (6 of them died; critical/ICU group). The first IgG-positive date (day 0) was observed from 5 to 18 days from the onset of disease. At day 0, a CRP peak was observed in the severe and critical groups, whereas there was no synchronized CRP peak on day 0 in the mild/moderate group. In the severe/non-ICU group, the blood lymphocyte number increased (P=0.0007) and CRP decreased (P=0.0007) after day 0, whereas CRP did not decrease and the blood lymphocyte number further decreased (P=0.0370) in the critical/ICU group.

Interpretation

The respiratory failure due to COVID-19 viral pneumonia observed in week 2 may be related to an antibody-related mechanism rather than uncontrolled viral replication. In the critical form of COVID-19, inflammation was sustained after IgG seroconversion.

Funding

none
The heart of an endurance athlete: impact of and recovery after an ultra-endurance event
Authors: Swart Anton , Constantinou Demitri
Published: July 2020

Aims

Acute bouts of ultra-endurance exercise may cause an acute reduction in cardiac function, causing a physiological cascade which releases cardiac biomarkers. This study set out to determine the cardiac stress and recovery of participation in a three-day ultra-endurance mountain biking event of athletes using heart rate variability (HRV) as an outcome measure.

Methods

Sixteen healthy participants (male and female) participating in a three-day ultra-endurance mountain biking event underwent a five-minute resting ECG recording in a supine position. Heart rate variability measurements were recorded two days before the race (baseline testing), after each race day, and at 24-hour post-event (recovery).

Results

Time-domain and frequency domain measures showed significant (p≤0.05) changes from baseline in HRV parameters after each race day. The significant changes in HRV parameters reflected an increase in sympathetic activity after each day of the event. Our data revealed that the mean HR and RR variability variables did not return to baseline value after 24-hours of recovery, reflecting autonomic nervous system dysfunction, and that changes persisted for at least 24-hours post-event.

Conclusion

Our study shows that competing in an ultra-endurance mountain bike event led to diminished vagal activity and a decrease in HRV throughout the event and persisted for at least 24-hours post-event. The body was under continuous sympathetic dominance during rest as well as during each day of racing, implying each race day can be considered a physiological stress. This may, in turn, cause a disturbance in homeostasis and an increase in autonomic nervous system dysfunction. This has implications for further research, including dysrhythmia risk, and monitoring of athletes in advising a return to strenuous activity.
Temporal patterns of vampire bat rabies and host connectivity in Belize
Authors: Becker Daniel J. , Broos Alice , Bergner Laura M. , Meza Diana K. , Simmons Nancy B. , Fenton M. Brock , Altizer Sonia , Streicker Daniel G.
Published: July 2020

In the Neotropics, vampire bats (Desmodus rotundus) are the main reservoir host for rabies, a highly fatal encephalitis caused by viruses in the genusLyssavirus. Although patterns of rabies virus exposure and infection have been well-studied for vampire bats in South America and Mexico, exploring the ecology of vampire bat rabies in other regions is crucial for predicting risks to livestock and humans. In Belize, rabies outbreaks in livestock have increased in recent years, underscoring the need for systematic data on viral dynamics in vampire bats. In this study, we examine the first three years of a longitudinal study on the ecology of vampire bat rabies in northern Belize. Rabies seroprevalence in bats was high across years (29–80%), suggesting active and endemic virus circulation. Across two locations, the seroprevalence time series per site were inversely related and out of phase by at least a year. Microsatellite data demonstrated historic panmixia of vampire bats, and mark–recapture detected rare but contemporary inter-site dispersal. This degree of movement could facilitate spatial spread of rabies virus but is likely insufficient to synchronize infection dynamics, which offers one explanation for the observed phase lag in seroprevalence. More broadly, our analyses suggest frequent transmission of rabies virus within and among vampire bat roosts in northern Belize and highlight the need for future spatiotemporal, phylogenetic, and ecological studies of vampire bat rabies in Central America.
A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection
Authors: Hassan Ahmed O. , Kafai Natasha M. , Dmitriev Igor P. , Fox Julie M. , Smith Brittany , Harvey Ian B. , Chen Rita E. , Winkler Emma S. , Wessel Alex W. , Case James Brett , Kashentseva Elena , McCune Broc T. , Bailey Adam L. , Zhao Haiyan , VanBlargan Laura A. , Dai Yanan , Ma Meisheng , Adams Lucas J. , Shrihari Swathi , Gralinski Lisa E. , Hou Yixuan J. , Schaefer Alexandra , Kim Arthur S. , Keeler Shamus P. , Weiskopf Daniela , Baric Ralph , Holtzman Michael J. , Fremont Daved H. , Curiel David T. , Diamond Michael S.
Published: July 2020

The Coronavirus Disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of systemic and mucosal IgA and T cell responses, completely prevents SARS-CoV-2 infection in the upper and lower respiratory tracts, and likely confers sterilizing immunity in most animals. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission, and curtailing pandemic spread.
Auditory experience prevents loss of the innate song preference as a selective cue inDrosophila
Authors: Li Xiaodong , Kruszelnicki James , Chiba Yukina , Ishimoto Hiroshi , Ishikawa Yuki , Kamikouchi Azusa
Published: July 2020

Auditory learning is a prerequisite step for acoustic communication learning, which was previously assumed to be restricted to animals with high levels of cognition, such as humans, cetaceans, and birds. How animals that rely on auditory learning for acoustic communication form sound preferences is not known. Fruit flies are a recently proposed novel animal model for studying experience-dependent auditory perceptual plasticity because of their ability to acquire song preferences via song exposure. Whether fruit flies have innate courtship song preferences, however, is unclear. Here we report that, similar to songbirds, fruit flies exhibit an innate preference for conspecific courtship songs. Maintenance of innate song preference requires song input, reminiscent of the song learning process in songbirds. Our findings also indicate that the response to conspecific and heterospecific songs manifests temporal and experience-dependent differentiation, which may underlie innate song preference and its plasticity. In addition, we find that flies have a robust ability to reacquire song preference during aging. Fruit flies thus offer a novel and simple approach for studying sound preference formation and its underlying mechanisms.
Elucidating essential genes in plant-associatedPseudomonas protegensPf-5 using transposon insertion sequencing
Authors: Fabian Belinda K , Foster Christie , Asher Amy J , Elbourne Liam DH , Cain Amy K , Hassan Karl A , Tetu Sasha G , Paulsen Ian T
Published: July 2020

Gene essentiality studies have been performed on numerous bacterial pathogens, but essential gene sets have been determined for only a few plant-associated bacteria.Pseudomonas protegensPf-5 is a plant-commensal, biocontrol bacteria that can control disease-causing pathogens on a wide range of crops. Work on Pf-5 has mostly focused on secondary metabolism and biocontrol genes, but genome-wide approaches such as high-throughput transposon mutagenesis have not yet been used in this species. Here we generated a denseP. protegensPf-5 transposon mutant library and used transposon-directed insertion site sequencing (TraDIS) to identify 446 genes essential for growth on rich media. Genes required for fundamental cellular machinery were enriched in the essential gene set, while genes related to nutrient biosynthesis, stress responses and transport were under-represented. Comparison of the essential gene sets of Pf-5 andP. aeruginosaPA14, an opportunistic human pathogen, provides insight into the biological processes important for their different lifestyles. Key differences include cytochromecbiogenesis, formation of periplasmic disulfide bonds, lipid biosynthesis, ribonuclease activity, lipopolysaccharides and cell surface structures. Comparison of the Pf-5in silicopredicted andin vitrodetermined essential gene sets highlighted the essential cellular functions that are over- and underestimated by each method. Expanding essentiality studies into bacteria with a range of lifestyles can improve our understanding of the biological processes important for survival and growth in different environmental niches.

Importance

Essential genes are those crucial for survival or normal growth rates in an organism. Essential gene sets have been identified in numerous bacterial pathogens, but only a few plant-associated bacteria. Employing genome-wide approaches, such as transposon insertion sequencing, allows for the concurrent analysis of all genes of a bacterial species and rapid determination of essential gene sets. We have used transposon insertion sequencing to systematically analyze thousands ofPseudomonas protegensPf-5 genes and gain insights into gene functions and interactions that are not readily available using traditional methods. Comparing Pf-5 essential genes with those ofP. aeruginosaPA14, an opportunistic human pathogen, provides insight into differences in gene essentiality which may be linked to their different lifestyles.
Npac Is a Co-factor of Histone H3K36me3 and Regulates Transcriptional Elongation in Mouse ES Cells
Authors: Yu Sue , Li Jia , Ji Guanxu , Ng Zhen Long , Siew Jiamin , Lo Wan Ning , Ye Ying , Chew Yuan Yuan , Long Yun Chau , Zhang Wensheng , Guccione Ernesto , Loh Yuin Han , Jiang Zhi-Hong , Yang Henry , Wu Qiang
Published: July 2020

Chromatin modification contributes to pluripotency maintenance in embryonic stem cells (ESCs). However, the related mechanisms remain obscure. Here, we show that Npac, a “reader” of histone H3 lysine 36 trimethylation (H3K36me3), is required to maintain mouse ESC pluripotency since knockdown ofNpaccauses mouse ESC differentiation. Depletion of Npac in mouse embryonic fibroblasts (MEFs) inhibits reprogramming efficiency. Furthermore, our Npac ChIP-seq results reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs. Interestingly, we find that Npac interacts with p-TEFb, RNA Pol II Ser2 and Ser5. Depletion of Npac disrupts transcriptional elongation of pluripotency genesNanogandRif1. Taken together, we propose that Npac is essential for transcriptional elongation of pluripotency genes by recruiting of p-TEFb and interacting with RNA Pol II Ser2 and Ser5.
Masitinib mediates TGF-Beta1 and Nitric Oxide Secretion and Ameliorates MPTP/Microglia-Induced Degeneration of Differentiated SH-SY5Y Cells
Authors: Göksu Erol Azize Yasemin , Akıncı Ersin , Koçancı Fatma Gonca , Akçakale Fatma , Dora Devrim Demir , Uysal Hilmi
Published: July 2020

Introduction

Microglia secretome includes not only growth factors and cytokines which support neuronal survival, it includes neurotoxic cytokines/enzymes, as well. MPTP is a neurotoxin which has degenerative effects on SH-SY5Y neuroblastoma cells. Masitinib mesylate is a tyrosine kinase inhibitor which has been shown to have beneficial effects in neurodegenerative diseases.

Aim

We first aimed to determine the most efficient microglial cell conditioned medium in terms of neurodegenerative effect. Next, we investigated the possible protective/therapeutic effects of masitinib against MPTP/microglia-induced degeneration of differentiated (d)-SH-SY5Y cells, and the role of transforming growth factor (TGF)-β1 and nitric oxide (NO) in these events.

Material-Methods

Non-stimulated/LPS-stimulated microglia cells were treated with masitinib or its solvent, DMSO. With or without MPTP-d-SH-SY5Y cell cultures were exposed to the conditioned media (CM) from microglia cell cultures, followed by cell survival analysis. Immunofluorescence staining of microglia andd-SH-SY5Y cells were performed with anti-CD-11b and anti-PGP9.5 antibody, respectively. TGF-β1/NO concentrations in CM of microglia/d-SH-SY5Y cell culture were measured.

Results

The initial 24 hrs CM of non-stimulated microglia cell culture was found to be the most detrimental microglial medium with lowest survival rates of treatedd-SH-SY5Y cells. The toxicity of 48 and 72 hrs’ CM ond-SH-SY5Y cells were both lower than that of 24 hrs’ CM. Masitinib (0.5 µM), significantly prevented MPTP-related cell degeneration ofd-SH-SY5Y cells. It also decreased the degenerative effects of both non-induced/LPS-induced microglia CM on with or without MPTP-d-SH-SY5Y cells. Although NO levels in microglia CM showed a negative correlation with survival rates of treatedd-SH-SY5Y cells, a positive correlation was seen between TGF-β1 concentrations in microglial CM and rates of treatedd-SH-SY5Y cell survival.

Conclusion

Masitinib ameliorates viability of with/without MPTP-d-SH-SY5Y cells. It does not only reverse the degenerative effects of its solvent, DMSO, but also prevents the degenerative effects of microglial secretions and MPTP. We suggest that masitinib begins to act as a neuroprotective agent via mediating TGF-β1 and NO secretion, as neurons are exposed to over-activated microglia or neurotoxins.
Genetic diversity and population structure ofLuffa acutangulaaccessions in a Thailand collection using SNP markers
Authors: Perez Grimar Abdiel , Tongyoo Pumipat , Chunwongse Julapark , de Jong Hans , Chuenwarin Paweena
Published: July 2020

This study explored a germplasm consisting of 112Luffa acutangula(ridge gourd) accessions mainly from Thailand, and some accessions from Vietnam, China, Philippines, Indonesia, USA, Bangladesh and Laos for an analysis of the population structure and underlying genetic diversity using 2,834 SNPs. STRUCTURE analysis (ΔKatK=6) allowed us to group the accessions into six subpopulations that corresponded well with the unrooted phylogenetic tree and principal coordinate analyses. The phylogenetic tree showed the diversity ofL. acutangulain Thailand, and accessions from other countries apart from Thailand were grouped together in the same branches. In STRUCTURE, subpopulation 2 contained only accessions from Thailand while other subpopulations contained a combination of accessions from Thailand and from other countries. When plotted, the STRUCTURE bars to the area of collection, it revealed the geneflow from the surrounding places nearby as indicated by the admixed genetic in the STRUCTURE bars. AMOVA based on STRUCTURE clustering showed the variation between populations (12.83%) and confirmed the absence of population structure in subpopulations (−10.59%). There was a distinguishing characteristic fruit shape and length in each subpopulation. The ample genetic diversity found in theL. acutangulagermplasm can be utilized in ridge gourd breeding programs to help meet the demands and needs of both consumers and farmers.
Prevalence of Hepatitis B Virus (HBV) Basal Core Promoter/Precore region molecular variants among HIV/HBV co-infected and HBV mono-infected patients in Ile-Ife, Nigeria
Authors: Osasona Oluwadamilola Gideon , Boudarene Lydia , Adewale-Fasoro Opeoluwa , George Uwem , Oguzie Judith , Ariyo Olumuyiwa Elijah , Olumade Testimony J. , Adeniyi Awe , Adewumi Moses Olubusuyi , Adeniji Adekunle Johnson
Published: July 2020

Introduction

Evolution of phenotypic diversity among viruses occurs as an escape mechanism against host immune pressure or drug selective pressure. Among HIV/HBV co-infected individuals, various HBV basal core promoter (BCP)/precore (PC) region molecular mutants had been reported with associated phenotypic defect in HBeAg production. The emergence of HBeAg negative variants of HBV in HIV co-infected individuals have profound implication on the diagnosis, management and prognosis of this subset of individuals. This includes delayed clearance of HBV, early development of adverse hepatic events such as liver cirrhosis and hepatocellular carcinoma. Currently, little is known about HBV BCP/PC region genomic heterogeneity in HIV/HBV co-infected patients in Nigeria. Therefore, this study was focussed on investigating evidence of precore/core region genomic variability among HIV/HBV co-infected patients in Nigeria.

Materials and methods

A total of 40 patients (20 HIV/HBV co-infected and 20 HBV mono-infected samples) were enrolled into the study and subsequently tested for HBsAg, HBeAg and HBeAb using specific Enzyme-Linked Immunosorbent Assay (ELISA). The BCP/PC genome regions (nucleotides 1653-1959) were amplified using a nested PCR assay and then subjected to BCP/PC mutational analysis in genome sites affecting HBeAg expression especially at the BCP transcriptional and PC Translational stop codon sites.

Results

Overall, 5(83.3%) of the six exploitable sequences after analysis showed various BCP/PC mutations. Only 1(16.6%) sequence from an HIV/HBV co-infected patient had the BCP transcriptional (double mutation; A1762T/G1764A) mutant. Analysis of the PC translational stop codon showed 4 (66.6%) having the G1896A mutants while 33.3% (2) had G1899A mutants.

Conclusion

This study has broadened the available evidence of BCP/PC region molecular mutants among HIV/HBV co-infected patients in Nigeria and assessed the difference of mutation prevalence in comparison with HBV mono-infected cohort. We therefore recommend that HIV/HBV co-infected patients be routinely screened for hepatitis B virus precore region mutants to improve their patient outcome.
The left dorsal stream causally mediates the tone labeling in absolute pitch
Authors: Rogenmoser Lars , Arnicane Andra , Jäncke Lutz , Elmer Stefan
Published: July 2020

Background

Absolute pitch (AP) refers to the ability of effortlessly identifying given pitches without the reliance on any reference pitch. Correlative evidence suggests that the left posterior dorsolateral prefrontal cortex (DLPFC) is responsible for the process underlying pitch labeling in AP.

Objective

Here, we aimed at investigating the causal relationship between the DLPFC and the pitch-labeling process underlying AP.

Methods

To address this, we measured sight-reading performance of right-handed AP possessors and matched control musicians (N=18 per sample) under cathodal and sham transcranial direct current stimulation of the left DLPFC. The participants were instructed to report visually presenting notations as accurately and fast as possible by playing with their right hand on a piano. The notations were simultaneously presented with distracting auditory stimuli that either matched or mismatched them in different semitone degrees.

Results

Unlike the control participants, the AP possessors revealed an interference effect in that they responded slower in mismatching conditions than in the matching one. Under cathodal stimulation, half of the time discrepancies between matching and mismatching conditions vanished; specifically, the ones with small up to moderate deviations.

Conclusions

These findings confirm that the pitch-labeling process underlying AP occurs automatically and is largely non-suppressible when triggered by tone exposure. The improvement of the AP possessors’ sight-reading performance in response to the suppression of the left DLPFC using cathodal stimulation confirms a causal relationship between this brain structure and pitch labeling.
Gut Microbiota Mediates High-Fiber Diet Alleviation of Maternal Obesity-Induced Cognitive and Social Deficits in Offspring
Authors: Liu Xiaoning , Li Xiang , Xia Bing , Jin Xin , Zeng Zhenhua , Yan Shikai , Li Ling , Yuan Shufen , Zhao Shancen , Dai Xiaoshuang , Yin Fei , Cadenas Enrique , Liu Rui Hai , Zhao Beita , Hou Min , Liu Zhigang , Liu Xuebo
Published: July 2020

Maternal obesity has been reported to be related to the neurodevelopmental disorders in offspring. However, the underlying mechanisms and effective interventions remain unclear. Here, a cross-sectional study on 778 children aged 7-14 years in two cities of China indicates that the maternal obesity is highly associated with the poorer cognition and sociality of their children. Moreover, we also find that the maternal obesity in mice disrupts the behavior and the gut microbiome in the offspring, which are alleviated by a high-fiber diet in either dams or offspring. Co-housing and feces microbiota transplantation experiments reveal a causal relationship between the reshaped microbiota and the behavioral changes. Moreover, treatment of the microbiota-derived short-chain fatty acids exhibits a similar beneficial effect on alleviating the behavioral deficits in offspring. Together, our study purports the microbiota-metabolites-brain axis as a mechanism, and high-dietary fiber intake is a promising intervention against maternal obesity-induced cognitive and social dysfunctions.
PartSeg, a Tool for Quantitative Feature Extraction From 3D Microscopy Images for Dummies
Authors: Bokota Grzegorz , Sroka Jacek , Basu Subhadip , Das Nirmal , Trzaskoma Paweł , Yushkevich Yana , Grabowska Agnieszka , Magalska Adriana , Plewczyński Dariusz
Published: July 2020

Background

Bioimaging techniques offer a robust tool for studying molecular pathways and morphological phenotypes of cell populations subjected to various conditions. As modern high resolution 3D microscopy provides access to an ever-increasing amount of high quality images, there arises a need for their analysis in an automated, unbiased and simple way.

Segmentation of structures within cell nucleus, which is the focus of this paper, presents a new layer of complexity in the form of dense packing and significant signal overlap.

At the same time the available segmentation tools provide a steep learning curve for new users with limited technical background. This is especially apparent in bulk processing of image sets, which requires the use of some form of programming notation.

Results

In this paper, we present PartSeg, a tool for segmentation and reconstruction of 3D microscopy images, optimised for the study of cell nucleus. PartSeg integrates refined versions of several state-of-the-art algorithms, including a new multi-scale approach for segmentation and quantitative analysis of 3D microscopy images.

The features and user-friendly interface of PartSeg were carefully planned with biologists in mind, based on analysis of multiple use cases and difficulties encountered with other tools, to offer ergonomic interface with a minimal entry barrier. Bulk processing in an ad-hoc manner is possible without the need for programmer support. As the size of datasets of interest grows, such bulk processing solutions become essential for proper statistical analysis of results.

Advanced users can use PartSeg components as a library within Python data processing and visualisation pipelines, for example within Jupyter notebooks. The tool is extensible so that new functionality and algorithms can be added by the use of plugins.

For biologists the utility of PartSeg is presented in several scenarios, showing the quantitative analysis of nuclear structures.

Conclusions

In this paper, we have presented PartSeg which is a tool for precise and verifiable segmentation and reconstruction of 3D microscopy images. PartSeg is optimised for cell nucleus analysis and offers multiscale segmentation algorithms best-suited for this task. PartSeg can also be used for bulk processing of multiple images and its components can be reused in other systems or computational experiments.

Contactg.bokota@cent.uw.edu.pl,a.magalska@nencki.edu.pl,d.plewczynski@cent.uw.edu.pl