bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Serum Prolactin and Metabolic Disorders: a Systematic Review
Authors: Yang Zaibo , She Junsen , Zhou Congcong , Liangshan Mu
Published: August 2020

Background

Serum prolactin levels are associated with metabolic disorders. However, the conclusions were inconsistent among published studies.

Methods

PubMed, EMBASE, and the Cochrane Library were used to search for studies investigating the association between serum prolactin levels and metabolic disorders. Studies were included and reviewed if they reported the association between serum prolactin and metabolic components (including waist circumference, body weight indexes, blood pressure, blood glucose, blood lipids, insulin resistance, and type 2 diabetes).

Results

A total of 14 studies were included in this systematic review. Evidence for certain associations between serum prolactin levels and body weight, blood lipids, blood glucose was insufficient, while some evidence showed a positive association between serum prolactin and blood pressure. High serum prolactin levels were found to be associated with lower risk of type 2 diabetes in women but not in men, but evidence for an exact correlation between serum prolactin and type 2 diabetes was insufficient.

Conclusion

Evidence for associations between serum prolactin and metabolic profiles were insufficient. Higher serum prolactin levels might be associated with lower risk of type 2 diabetes in women. Further high-quality prospective studies are required.
The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya
Authors: Mburu CN , Ojal J , Chebet R , Akech D , Karia B , Tuju J , Sigilai A , Abbas K , Jit M , Funk S , Smits G , van Gageldonk PGM , van der Klis FRM , Tabu C , Nokes DJ ,   LSHTM CMMID COVID-19 Working Group, Scott JAG , Flasche S , Adetifa IMO
Published: August 2020

Background

The COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region.

Methods

Combining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020.

Findings

In February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 22% (0-46). As the COVID-19 restrictions to physical contact are lifted, from December 2020, the probability of a large measles outbreak increased to 31% (8-51), 35% (16-52) and 43% (31-56) assuming a 15%, 50% and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 37% (17-54), 44% (29-57) and 57% (48-65) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of restrictions on contact can be overcome by conducting an SIA with ≥ 95% coverage in under-fives.

Interpretation

While contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once physical distancing is relaxed. Implementing delayed SIAs will be critical for prevention of measles outbreaks once contact restrictions are fully lifted in Kenya.

Funding

The United Kingdom’s Medical Research Council and the Department for International Development
Causes of false-negative rapid diagnostic tests for symptomatic malaria in the DRC
Authors: Parr Jonathan B. , Kieto Eddy , Phanzu Fernandine , Mansiangi Paul , Mwandagalirwa Kashamuka , Mvuama Nono , Landela Ange , Atibu Joseph , Efundu Solange Umesumbu , Olenga Jean W. , Thwai Kyaw Lay , Morgan Camille E. , Denton Madeline , Poffley Alison , Juliano Jonathan J. , Mungala Pomie , Likwela Joris L. , Sompwe Eric M. , Tshefu Antoinette K. , N’Siala Adrien , Kalonji Albert
Published: August 2020

Background

The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern about existing malaria diagnostic strategies. We previously identified pfhrp2-negative parasites among asymptomatic children in the Democratic Republic of the Congo (DRC), but their impact on diagnosis of symptomatic malaria is unknown.

Methods

We performed a cross-sectional study of false-negative RDTs in symptomatic subjects in 2017. Parasites were characterized by microscopy; RDT; pfhrp2/3 genotyping and species-specific PCR assays; a multiplex bead-based immunoassay; and/or whole-genome sequencing.

Results

Among 3,627 symptomatic subjects, we identified 427 (11.8%) RDT-/microscopy+ cases. Parasites from eight (0.2%) samples were initially classified as putative pfhrp2/3 deletions by PCR, but antigen testing and whole-genome sequencing confirmed the presence of intact genes. Malaria prevalence was high (57%) and non-falciparum co-infection common (15%). HRP2-based RDT performance was satisfactory and superior to microscopy.

Conclusions

Symptomatic malaria due to pfhrp2/3-deleted P. falciparum was not observed in the DRC.

Ongoing HRP2-based RDT use is appropriate for the detection of falciparum malaria in the DRC.
PRELIMINARY ASSESSMENT OF STRUCTURE AND COLLECTIVE DOSE FROM CT EXAMINATIONS RELATED TO COVID-19 DIAGNOSTICS IN THE RUSSIAN FEDERATION IN MARCH - JUNE 2020
Authors: Vodovatov A.V. , Romanovich I.K. , Istorik O.A. , Eremina L.A. , Morozov S.P. , Ryzhov S.A. , Berkovich G.V. , Kamyshanskaya I.G. , Trufanov G.E. , Chipiga L.A. , Druzhinina P. S. , Biblin A.M. , Akhmatdinov R.R. , Basek I.V. , Karatetskiy A.A. , Merkulov D. V. , Ispravnikova Yu.S. , Pritz V.V. , Polishchuk N.S. , Mukhortova A.N , Pyzyrev V.G.
Published: August 2020

The use of computed tomography (CT) for the diagnostics of COVID-19 in the Russian Federation led to significant changes in the structure of X-ray diagnostics and levels of medical exposure of the patients. This study was aimed at the preliminary operative assessment of changes in the structure and collective dose from CT examinations in several representative hospitals, regions and on the level of the Russian Federation. The results of the study indicate that during the transformation of hospitals from general medical practice into dedicated COVID-19 facilities, the number of CT examinations increased up to 30%; the collective dose from CT exams increased up to a factor of 1.5. During a partial transformation of a medical facility into the hospital with separate COVID-19 departments, the increase in the number of CT examinations in the facility was more significant (up to a factor of 2 or more). These numbers correspond to 1.5 - 2.5 chest CT examinations (from 1 to 6) per patient admitted to hospital with COVID-19 diagnosis; and 1.2 chest CT examinations per patient in outpatient facilities, including a mandatory CT scan for the staging of COVID-19. The collective dose from CT examinations in the Russian Federation for March-June period of 2020 increased by the factor of 2 (from 16k man-Sv to 32k man-Sv); the collective dose of COVID-19 patients was about 12k man-Sv. For a more detailed and reliable assessment of the dynamics of changes in the structure of diagnostic radiology and levels of radiation exposure of patients in the Russian Federation, data collection in the regions of the Russian Federation and individual medical facilities will continue.
COVID-19 hospitalisation rates rise exponentially with age, inversely proportional to thymic T-cell production
Authors: Palmer Sam , Cunniffe Nik , Donnelly Ruairí
Published: August 2020

Here we report that COVID-19 hospitalisation rates follow an exponential relationship with age, doubling for every 16 years of age or equivalently increasing by 4.5% per year of life (R2=0.98). This mirrors the well studied exponential decline of both thymus volume and T-cell production, which halve every 16 years. COVID-19 can therefore be added to the list of other diseases with this property, including those caused by MRSA, MERS-CoV, West Nile virus, Streptococcus Pneumonia and certain cancers, such as chronic myeloid leukemia and brain cancers. In addition, incidence of severe disease and mortality due to COVID-19 are both higher in men, consistent with the degree to which thymic involution (and the decrease in T-cell production with age) is more severe in men compared to women. Since these properties are shared with some non-contagious diseases, we hypothesised that the age-dependence does not come from social-mixing patterns, i.e. that the probability of hospitalisation given infection rises exponentially, doubling every 16 years. A Bayesian analysis of daily hospitalisations, incorporating contact matrices, found that this relationship holds for every age group except for the under 20s. While older adults have less contacts than young adults, our analysis suggests that there is an approximate cancellation between the effects of less contacts for the elderly and higher infectiousness due to a higher probability of developing severe disease. Our model fitting suggests under 20s have 49-75% additional immune protection beyond that predicted by strong thymus function alone, consistent with increased juvenile cross-immunity from other viruses. We found no evidence for differences between age groups in susceptibility to infection or infectiousness to others (given disease state), i.e. the only important factor in the age-dependence of hospitalisation rates is the probability of hospitalisation given infection. These findings suggest the existence of a T-cell exhaustion threshold, proportional to thymic output, and that clonal expansion of peripheral T-cells does not affect disease risk. The strikingly simple inverse relationship between risk and thymic T-cell output adds to the evidence that thymic involution is an important factor in the decline of the immune system with age and may also be an important clue in understanding disease progression, not just for COVID-19 but other diseases as well.
Stratification of Systemic Lupus Erythematosus Patients with Gene Expression Data Reveals Expression of Distinct Immune Pathways
Authors: Deokar Aditi
Published: August 2020

Systemic lupus erythematosus (SLE) is the tenth leading cause of death in females 15-24 years old in the US. The diversity of symptoms and immune pathways expressed in SLE patients causes difficulties in treating SLE as well as in new clinical trials. This study used unsupervised learning on gene expression data from adult SLE patients to separate patients into clusters. The dimensionality of the gene expression data was reduced by three separate methods (PCA, UMAP, and a simple linear autoencoder) and the results from each of these methods were used to separate patients into six clusters with k-means clustering. The clusters revealed three separate immune pathways in the SLE patients that caused SLE. These pathways were: (1) high interferon levels, (2) high autoantibody levels, and (3) dysregulation of the mitochondrial apoptosis pathway. Mitochondrial apoptosis has not been investigated before to our knowledge as a standalone cause of SLE, independent of autoantibody production, and mitochondrial proteins could be investigated as a therapeutic target for SLE in the future.
Recommendations for Primary Prevention of Skin Melanoma
Authors: Tasa Tõnis , Puustusmaa Mikk , Tõnisson Neeme , Kolk Berit , Padrik Peeter
Published: August 2020

Melanoma (MEL) is an aggressive form of skin cancer, causing over 60,000 deaths every year and it is considered one of the fastest-growing cancer forms. Genome-wide association studies have identified numerous genetic variants (SNPs) independently associated with MEL. The effects of such SNPs can be combined into a single polygenic risk score (PRS). Stratification of individuals according to PRS could be introduced to the primary prevention of melanoma. Our aim was to combine PRS with health behavior recommendations to develop a personalized recommendation for primary prevention of melanoma.

Previously published PRS models for predicting the risk of melanoma were collected from the literature. Models were validated on the UK Biobank dataset consisting of a total of 487,410 quality-controlled genotypes with 3791 prevalent and 2345 incident cases. The best performing sex-specific models were selected based on the AUC in prevalent data and independently validated on an independent UKBB incident dataset for females and males separately. The best performing model included 28 SNPs. The C-index of the best performing model in the dataset was 0.59 (0.009) and hazard ratio (HR) per unit of PRS was 1.38 (standard error of log (HR) = 0.03) for both males and females.

We performed absolute risk simulations on the Estonian population and developed individual risk-based clinical follow-up recommendations. Both models were able to identify individuals with more than a 2-fold risk increase. The observed 10-year risks of developing melanoma for individuals in the 99th percentile exceeded the risk of individuals in the 1st percentile more than 4.5-fold.

We have developed a PRS-based recommendations pipeline for individual health behavior suggestions to support melanoma prevention.
COVID-19 Cases and Testing in 53 Prison Systems
Authors: Lemasters Katherine , McCauley Erin , Nowotny Kathryn , Brinkley-Rubinstein Lauren
Published: August 2020

Background

COVID-19 has entered United States prison systems at alarming rates. Disparities in social and structural determinants of health disproportionately affect those experiencing incarceration, making them more vulnerable to COVID-19. Additionally, prisons are sites of congregate living, making it impossible to practice social distancing, and most prisons have relied only on incremental measures to reduce risk and spread of COVID-19. To more fully understand the impact that COVID-19 is having on incarcerated populations, it is critical to have systematic data on testing, test positivity, cases, and case fatality. Using data from the COVID Prison Project, we present data on 53 prison systems COVID-19 testing, test positivity, case, and case fatality by state and compare these data with each state’s general population.

Results

Many states are not reporting full information on COVID testing with some also not reporting on case fatality. Among those reporting data, there is a wide variation between testing, test positivity, and case rates within prison systems and as compared to the general population. However, when more tests are deployed more cases are identified with the majority of state prisons having higher case rates than their general population.

Conclusions

These findings underscore the need for the implementation and study of COVID-19 mitigation and surveillance strategies to flatten the COVID-19 curve in prisons across the country. We call for future research to build on this data from the COVID Prison Project to protect the health of our nations’ often forgotten residents.
Spontaneous Cervical Artery Dissection: A Case Series
Authors: Basgaran Amedra , Hsu Catherine Hsiao-wei , Sivagnanaratnam Aravinth
Published: August 2020

Cervical artery dissection refers to dissection of the vertebral or carotid arteries, and accounts for up to 20% of strokes in those under 45. Antithrombotic therapy is therefore essential to limit thrombosis at the site of injury and distal neuronal damage. However, the exact choice of drugs, timing and duration of therapy remain a challenging decision.

A review of data was conducted on three cases of unprovoked cervical dissection at our stroke center between 2017 and 2020. They include bilateral internal carotid artery dissection, right vertebral artery dissection, and left internal carotid artery dissection.

Three key outcomes were identified: narrowing, occlusion and pseudoaneurysm; such outcomes dictated our management approach. Two patients were given antiplatelet therapy for at least one year. The patient with bilateral dissection was perceived to have higher thromboembolic risk, due to the presence of a free-floating thrombus. Thus, he was anticoagulated for a year, and thereafter given antiplatelet therapy.

The evidence behind long-term management of carotid artery dissection remains equivocal. There is no strong evidence favouring anticoagulation over antiplatelets or vice versa. Anticoagulation tends to be preferred in cases of severe stenosis, occlusion or pseudoaneurysm, to reduce the risk of thromboembolic phenomena. Anti-platelets are preferred where there is a high risk of haemorrhagic transformation or contraindication to anticoagulation. The duration of secondary prevention is similarly unclear. Advances in radiology and increased follow-up have resulted in uncertainty on the management of incomplete healing at the six-month point. Varying clinical practice has been identified and there is a lack of a clear guideline. We propose continuing antithrombotic therapy in cases of incomplete healing, as in our case series. Nevertheless, we require more data on the subject and thus suggest an initial nation-wide survey to compare the different management strategies followed by large-scale retrospective analyses comparing long-term outcomes.
The urgent need for phased university reopenings to mitigate the spread of COVID-19 and conserve institutional resources: A modeling study
Authors: Rennert Lior , Kalbaugh Corey A. , McMahan Christopher , Shi Lu , Colenda Christopher C.
Published: August 2020

Introduction

Recent outbreaks of COVID-19 in universities across the United States highlight the difficulties in containing the spread of COVID-19 on college campuses. While research has shown that mitigation strategies such as frequent student testing, contact tracing, and isolation of confirmed and suspected cases can detect early outbreaks, such mitigation strategies may have limited effectiveness if large outbreaks occur. A phased reopening is a practical intervention to limit early outbreaks, conserve institutional resources, and ensure proper safety protocols are in place before the return of additional students to campus.

Methods

We develop dynamic compartmental transmission models of SARS-CoV-2 to assess the impact of a phased reopening and pre-arrival testing on minimizing outbreaks (measured by daily infections) and conserving university resources (measured by isolation bed capacity). We assume that one-third of the student population returns to campus each month as part of the phased reopening, and that pre-arrival testing removes 90% of infections at the semester start. We assume an on-campus population of N = 7500, an active COVID-19 prevalence of 2% at baseline, and that 60% of infected students require isolation for an average period of 11 days. We vary the reproductive number (Rt) between 1.25 and 4 to represent the effectiveness of alternative mitigation strategies throughout the semester, where Rt is constant or improving throughout the semester (ranging from 4 to 1.25).

Results

Compared to pre-arrival testing only or neither intervention, phased reopening with pre-arrival testing reduced peak daily infections by 6% and 18% (Rt=1.25), 44% and 48% (Rt=2.5), 63% and 64% (Rt=4), and 72% and 74% (improving Rt), respectively, and reduced the proportion of on-campus beds needed for isolation from 10%-25% to 5%-9% across different values of Rt.

Conclusion

Phased reopening with pre-arrival testing substantially reduces the peak number of daily infections throughout the semester and conserves university resources compared to strategies involving the simultaneous return of all students to campus. Phased reopenings allow institutions to improve safety protocols, adjust for factors that drive outbreaks, and if needed, preemptively move online before the return of additional students to campus, thus preventing unnecessary harm to students, institutional faculty and staff, and local communities.
DNA Methylation Architecture of the ACE2 gene in Nasal Cells
Authors: Cardenas Andres , Rifas-Shiman Sheryl L. , Sordillo Joanne E. , DeMeo Dawn L. , Baccarelli Andrea A , Hivert Marie-France , Gold Diane R , Oken Emily
Published: August 2020

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 enters cells via angiotensin-Converting Enzyme 2 (ACE2) receptors, highly expressed in nasal epithelium with parallel high infectivity.1,2 The nasal epigenome is in direct contact with the environment and could explain COVID-19 disparities by reflecting social and environmental influences on ACE2 regulation. We collected nasal swabs from anterior nares of 547 children, measured DNA methylation (DNAm), and tested differences at 15 ACE2 CpGs by sex, age, race/ethnicity and epigenetic age. ACE2 CpGs were differentially methylated by sex with 12 sites having lower DNAm (mean=12.71%) and 3 sites greater DNAm (mean=1.45%) among females relative to males. We observed differential DNAm at 5 CpGs for Hispanic females (mean absolute difference=3.22%) and lower DNAm at 8 CpGs for Black males (mean absolute difference=1.33%), relative to white participants. Longer DNAm telomere length was associated with greater ACE2 DNAm at 11 and 13 CpGs among males (mean absolute difference=7.86%) and females (mean absolute difference=8.21%), respectively. Nasal ACE2 DNAm differences could contribute to our understanding COVID-19 severity and disparities reflecting upstream environmental and social influences.
An exploratory analysis of the association between moral injury and mental healthcare-seeking attitudes and behaviors in returning veterans of the Iraq and Afghanistan wars
Authors: Lewis Chad
Published: August 2020

Objectives

This study examines the degree to which veterans who have experienced more “moral injury” are less likely to seek the mental healthcare services they may urgently need.

Methods

The sampling frame for this study included American veterans of the Iraq and/or Afghanistan wars aged 25-44. Participants were recruited into the study by posting a call for participants to social media platforms such as Facebook and LinkedIn. A web link was provided to direct them to an anonymous online survey. We then collected data assessing veterans’ combat experiences, healthcare-seeking attitudes and behaviors, and various sociodemographic data. No identifying information was collected, and an Institutional Review Board exemption was granted under DHHS Regulatory Category II by the George Washington University’s Office of Human Research Study.

Results

The results from the Inventory of Attitudes toward Seeking Mental Health Services (IASMHS) clearly showed that moral injury was associated with more negative mental health services-seeking attitudes in all measurable areas. Those respondents scoring higher on the Moral Injury Events Scale (MIES) were presumably less likely to acknowledge their psychological problems, more likely to have fear of anticipated stigma from loved ones if they were to seek mental health treatment, and less willing and able to seek out mental health treatment when needed.

Conclusions

It is probable that we will not be able to reach a significant number of veterans suffering from moral injury unless we dedicate further research in the area of developing effective techniques to recruit veterans suffering from moral injury into mental health treatment programs by taking their specific symptoms (independent of PTSD) into consideration.
Transfer learning to detect COVID-19 automatically from X-ray images, using convolutional neural networks
Authors: Taresh Mundher , Zhu Ningbo , Ali Talal Ahmed Ali
Published: August 2020

Novel coronavirus pneumonia (COVID-19) is a contagious disease that has already caused thousands of deaths and infected millions of people worldwide. Thus, all technological gadgets that allow the fast detection of COVID-19 infection with high accuracy can offer help to healthcare professionals. This study is purposed to explore the effectiveness of artificial intelligence (AI) in the rapid and reliable detection of COVID-19 based on chest X-ray imaging. In this study, reliable pre-trained deep learning algorithms were applied to achieve the automatic detection of COVID-19-induced pneumonia from digital chest X-ray images.

Moreover, the study aims to evaluate the performance of advanced neural architectures proposed for the classification of medical images over recent years. The data set used in the experiments involves 274 COVID-19 cases, 380 viral pneumonia, and 380 healthy cases, which was derived from several open sources of X-Rays, and the data available online. The confusion matrix provided a basis for testing the post-classification model. Furthermore, an open-source library PYCM was used to support the statistical parameters. The study revealed the superiority of Model vgg16 over other models applied to conduct this research where the model performed best in terms of overall scores and based-class scores. According to the research results, deep Learning with X-ray imaging is useful in the collection of critical biological markers associated with COVID-19 infection. The technique is conducive for the physicians to make a diagnosis of COVID-19 infection. Meanwhile, the high accuracy of this computer-aided diagnostic tool can significantly improve the speed and accuracy of COVID-19 diagnosis.
Noc corrals migration of FtsZ protofilaments during cytokinesis inBacillus subtilis
Authors: Yu Yuanchen , Zhou Jinsheng , Gueiros-Filho Fredy , Kearns Daniel B. , Jacobson Stephen C.
Published: August 2020

Bacteria that divide by binary fission form FtsZ rings at the geometric midpoint of the cell between the bulk of the replicated nucleoids. InB. subtilis, the DNA- and membrane-binding Noc protein is thought to mediate nucleoid occlusion to prevent FtsZ rings from forming over the chromosome. To explore the role of Noc, we used time-lapse fluorescence microscopy to monitor FtsZ and the nucleoid of cells growing in microfluidic channels. Our data show that Noc does not prevent FtsZ formation over the chromosome or control cell division site selection. Instead, Noc inhibits migration of FtsZ protofilaments from one FtsZ structure to the next. Moreover, we show that FtsZ protofilaments travel due to a local reduction in ZapA association, and the Noc mutant phenotype can be suppressed by ZapA overexpression. Thus, Noc maintains a high local concentration of FtsZ to stabilize FtsZ rings during cytokinesis.

IMPORTANCE

In bacteria, a condensed structure of FtsZ (Z-ring) recruits cell division machinery, and Z-ring formation is inhibited over the chromosome by a poorly understood phenomenon called nucleoid occlusion. InB. subtilis, nucleoid occlusion has been reported to be mediated by the DNA-membrane bridging protein, Noc. Using time-lapse fluorescence microscopy of cells growing in microchannels, we show that Noc neither protects the chromosome from proximal Z-ring formation nor determines the future site of cell division. Rather, Noc plays a corralling role by preventing protofilaments from leaving a Z-ring undergoing cytokinesis and traveling over the nucleoid.
dagLogo: an R/Bioconductor Package for Identifying and Visualizing Differential Amino Acid Group Usage in Proteomics data
Authors: Ou Jianhong , Liu Haibo , Nirala Niraj K. , Stukalov Alexey , Acharya Usha , Green Michael R. , Zhu Lihua Julie
Published: August 2020

Sequence logos have been widely used as graphical representations of conserved nucleic acid and protein motifs. Due to the complexity of the amino acid (AA) alphabet, rich post-translational modification, and diverse subcellular localization of proteins, few versatile tools are available for effective identification and visualization of protein motifs. In addition, various reduced AA alphabets based on physicochemical, structural, or functional properties have been valuable in the study of protein alignment, folding, structure prediction, and evolution. However, there is lack of tools for applying reduced AA alphabets to the identification and visualization of statistically significant motifs. To fill this gap, we developed an R/Bioconductor package dagLogo, which has several advantages over existing tools. First, dagLogo allows various formats for input sets and provides comprehensive options to build optimal background models. It implements different reduced AA alphabets to group AAs of similar properties. Furthermore, dagLogo provides statistical and visual solutions for differential AA (or AA group) usage analysis of both large and small data sets. Case studies showed that dagLogo can better identify and visualize conserved protein sequence patterns from different types of inputs and can potentially reveal the biological patterns that could be missed by other logo generators.
Preconditioning ofCaenorhabditis elegansto Anoxic Insult by Inactivation of Cholinergic, GABAergic, and Muscle Activity
Authors: Bennett Heather L. , McClanahan Patrick D. , Fang-Yen Christopher , Kalb Robert G.
Published: August 2020

For most metazoans, oxygen deprivation leads to cell dysfunction and if severe, death. Sublethal stress prior to a hypoxic or anoxic insult (“preconditioning”) can protect cells from subsequent oxygen deprivation. The molecular mechanisms by which sublethal stress can buffer against a subsequent toxic insult and the role of the nervous system in the response are not well understood. We studied the role of neuronal activity preconditioning to oxygen deprivation inC. elegans. Animals expressing the histamine gated chloride channels (HisCl1) in select cell populations were used to temporally and spatially inactivate the nervous system or tissue prior to an anoxic insult. We find that inactivation of the nervous system for 3 hours prior to the insult confers resistance to a 48-hour anoxic insult in 4th-stage larval animals. Experiments show that this resistance can be attributed to loss of activity in cholinergic and GABAergic neurons as well as in body wall muscles. These observations indicate that the nervous system activity can mediate the organism’s response to anoxia.
Performance Evaluation and Selection of ImprovedTef(Eragrostis tefL)varieties at Main Campus Site Hadiya Zone, Southern Ethiopia
Authors: Dutamo Dargicho , Assefa Ermias , Menamo Muluneh
Published: August 2020

Tef [Eragrostis tef (Zucc.) Trotter] is a cereal crop resilient to adverse climatic and soil conditions, and possessing desirable storage properties. It is, a tetraploid with 40 chromosomes (2n = 4x = 40), belongs to the family Poaceae and, together with finger millet (Eleusine coracana Gareth.), to the subfamily Chloridoideae. It was originated and domesticated in Ethiopia. The experiment was conducted to identify, select and recommend adaptable, high yielding, Insect pest and disease resistant twelve released and one local variety at Main Campus Site Hadiya zone of SNNPR. Twelve tef varieties were evaluated in RCBD with three replications on station of Main Campus Site during main cropping season of 2019/2020. Analysis of variance revealed that there were significant differences among tef varieties, Culm length, panicle length, plant height, days to heading, days to maturity, grain filling period, primary panicle brunch, grain yield, biomass yield and harvest index at Main Campus site. Based on the obtained result, the improved tef varieties namely; DZ-Cr-438 DZ-Cr-974 (Dukem), DZ-01-899 (Gimbechu) and DZ-01-196 (Magna) at Main Campus site. Therefore, these varieties showed better performance for most of the studied characters including grain yield. Therefore, these varieties were selected and recommended for the study area and similar ecologies of Hadiya Zone. This finding, being the result of one year with single location, it is recommended that the experiment should be repeated at multi locations for several years to confirm the obtained results.
Cold Exposure Protects from Neuroinflammation Through Immunologic Reprogramming
Authors: Spiljar Martina , Steinbach Karin , Rigo Dorothée , Suárez-Zamorano Nicolas , Wagner Ingrid , Hadadi Noushin , Vincenti Ilena , Page Nicolas , Klimek Bogna , Rochat Mary-Aude , Kreutzfeldt Mario , Chevalier Claire , Stojanović Ozren , Mack Matthias , Cansever Dilay , Greter Melanie , Merkler Doron , Trajkovski Mirko
Published: August 2020

Autoimmunity is energetically costly, but the impact of a metabolically active state on immunity and immune-mediated diseases is unclear. Ly6Chimonocytes are key effectors in CNS autoimmunity with elusive role in priming naïve autoreactive T cells. Here we provide unbiased analysis of the immune changes in various compartments during cold exposure, and show that this energetically costly stimulus markedly ameliorates active experimental autoimmune encephalomyelitis (EAE). Cold exposure decreases MHCII on monocytes at steady-state and in various inflammatory mouse models, and suppresses T cell priming and pathogenicity through the modulation of monocytes. Genetic, or antibody-mediated monocyte depletion, or adoptive transfer of Th1- or Th17-polarized cells for EAE abolish the cold-induced effects on T cells or EAE, respectively. These findings provide a mechanistic link between environmental temperature and neuroinflammation, and suggest competition between cold-induced metabolic adaptations and autoimmunity as energetic trade-off beneficial for the immune-mediated diseases.
Cellxgene VIP unleashes full power of interactive visualization and integrative analysis of scRNA-seq, spatial transcriptomics, and multiome data
Authors: Li Kejie , Ouyang Zhengyu , Chen Yirui , Gagnon Jacob , Lin Dongdong , Mingueneau Michael , Chen Will , Sexton David , Zhang Baohong
Published: August 2020

To meet the growing demands from scientists to effectively extract deep insights from single cell RNA sequencing, spatial transcriptomics, and emerging multiome datasets, we developed cellxgene VIP (Visualization In Plugin), a frontend interactive visualization plugin of cellxgene framework, which greatly expanded capabilities of the base tool in the following aspects. First, it generates a comprehensive set of over eighteen commonly used quality control and analytical plots in high resolution with highly customizable settings in real time. Second, it provides more advanced analytical functions to gain insights on cellular compositions and deep biology, such as marker gene identification, differential gene expression analysis, and gene set enrichment analysis. Third, it empowers advanced users to perform analysis in a Jupyter Notebook like environment, dubbed Command Line Interface (CLI) by programming in Python and/or R directly without limiting themselves to functional modules available via graphical user interface (GUI). Finally, it pioneers methods to visualize multi-modal data, such as spatial transcriptomics embedding aligned with histological image on one slice or multiple slices in a grid format, and the latest 10x Genomic Multiome dataset where both DNA accessibility and gene expression in the same cells are measured, under the same framework in an integrative way to fully leverage the functionalities mentioned above. Taken together, the open-source tool makes large scale single cell data visualization and analysis more accessible to biologists in a user-friendly manner and fosters computational reproducibility by simplifying data and code reuse through the CLI. Going forward, it has the potential to become a crowdsourcing ecosystem for the scientific community to contribute even more modules to the Swiss Army knife of single cell data exploration tools.
Insect threats and conservation through the lens of global experts
Authors: Miličić Marija , Popov Snežana , Branco Vasco Veiga , Cardoso Pedro
Published: August 2020

While many recent studies have focused on global insect population trends, all are limited either in space or taxonomic scope. Since global monitoring programs for insects are not implemented, biased data are therefore the norm. However, expert opinion is both valuable and widely available, and should be fully exploited when hard data are not available. Our aim is to use global expert opinion to provide insights on the root causes of potential insect declines worldwide, as well as on effective conservation strategies that could mitigate insect biodiversity loss. We obtained 753 responses from 413 respondents with a wide variety of expertise. The most relevant threats identified through the survey were agriculture and climate change, followed by pollution, while land management and land protection were recognized as the most significant conservation measures. Nevertheless, there were differences across regions and insect groups, reflecting the variability within the most diverse class of living organisms on our planet. Lack of answers for certain biogeographic regions or taxa also reflects the need for research, particularly in less investigated settings. Our results provide a first step towards understanding global threats and conservation measures for insects.
Spontaneous neurotransmission at evocable synapses predicts their responsiveness to action potentials
Authors: Grasskamp Andreas T. , Jusyte Meida , McCarthy Anthony W. , Götz Torsten W.B. , Ditlevsen Susanne , Walter Alexander M.
Published: August 2020

Synaptic transmission relies on presynaptic neurotransmitter (NT) release from synaptic vesicles (SVs) and on NT detection by postsynaptic receptors. Transmission exists in two principal modes: action-potential (AP) evoked and AP-independent, “spontaneous” transmission. AP-evoked neurotransmission is considered the primary mode of inter-neural communication, whereas spontaneous transmission is required for neuronal development, homeostasis, and plasticity. While some synapses appear dedicated to spontaneous transmission only, all AP-responsive synapses also engage spontaneously, but whether this encodes functional information regarding their excitability is unknown. Here we report on functional interdependence of both transmission modes at individual synaptic contacts ofDrosophilalarval neuromuscular junctions (NMJs) which were identified by the presynaptic scaffolding protein Bruchpilot (BRP). Consistent with its role in organizing the AP-dependent release machinery (voltage-dependent Ca2+channels and SV fusion machinery), most active BRP-positive synapses (>85%) responded to APs. At these synapses, the level of spontaneous activity was a precise predictor for their responsiveness to AP-stimulation. Both transmission modes engaged an overlapping pool of SVs and NT-receptors, and both were affected by the non-specific Ca2+channel blocker cadmium. Thus, by using overlapping machinery, spontaneous transmission is a continuous, stimulus independent predictor for the AP-responsiveness of individual synapses.
A Micro-engineered Human Colon Intestine-Chip Platform to Study Leaky Barrier
Authors: Apostolou Athanasia , Panchakshari Rohit A. , Banerjee Antara , Manatakis Dimitris V. , Paraskevopoulou Maria D. , Luc Raymond , AbuAli Galeb , Dimitriou Alexandra , Lucchesi Carolina , Kulkarni Gauri , Maulana Tengku Ibrahim , Bleck Bertram , Manolakos Elias S. , Hamilton Geraldine A. , Giallourakis Cosmas , Karalis Katia
Published: August 2020

The intestinal epithelial barrier supports the symbiotic relationship between the microbiota colonizing the intestinal epithelium and the host immune system to maintain homeostasis. Leaky barrier is increasingly recognized as part of the pathogenesis of a number of chronic conditions in addition to inflammatory and infectious diseases. As our understanding on the regulation of the barrier remains limited, effective therapeutic targeting for the compromised barrier is still an unmet need. Here we combined advancements on the organoids and Organ-on-Chip technologies to establish a micro-engineered Colon Intestine-Chip for studying development and regulation of the human intestinal barrier. Our data demonstrate the significance of the endothelium in co-culture with the epithelial cells within a tissue-relevant microenvironment for the establishment of a tight epithelial barrier of polarized cells. Pathway analysis of the RNA sequencing (RNA-Seq), revealed significant upregulation of mechanisms relevant to the maturation of the intestinal epithelium in organoid-derived epithelial cells in co-culture with endothelium as compared to organoids maintained in suspension. We provide evidence that the Colon Intestine-Chip platform responds to interferon gamma (IFNγ), a prototype cytokine utilized to model inflammation-induced barrier disruption, by induction of apoptosis and reorganization of the apical junctional complexes as shown with other systems. We also describe the mechanism of action of interleukin 22 (IL-22) on mature, organoid-derived intestinal epithelial cells that is consistent with barrier disruption. Overall we propose the Colon Intestine-Chip as a promising human organoid-derived platform to decipher mechanisms driving the development of leaky gut in patients and enable their translation for this unmet medical need.
A simple and dynamic thermal gradient device for measuring thermal performance in small ectotherms
Authors: Ritchie Marshall W. , Dawson Jeff W. , MacMillan Heath A.
Published: August 2020

The body temperature of ectothermic animals is heavily dependent on environmental temperature, impacting fitness. Laboratory exposure to favorable and unfavorable temperatures is used to understand these effects, as well as the physiological, biochemical, and molecular underpinnings of variation in thermal performance. Although small ectotherms, like insects, can often be easily reared in large numbers, it can be challenging and expensive to simultaneously create and manipulate several thermal environments in a laboratory setting. Here, we describe the creation and use of a thermal gradient device that can produce a wide range of constant or varying temperatures concurrently. This device is composed of a solid aluminum plate and copper piping, combined with a pair of programmable refrigerated circulators. As a simple proof-of-concept, we completed single experimental runs to produce a low-temperature survival curve for flies (Drosophila melanogaster) and explore the effects of daily thermal cycles of varying amplitude on growth rates of crickets (Gryllodes sigillatus). This approach avoids the use of multiple heating/cooling water or glycol baths or incubators for large-scale assessments of organismal thermal performance. It makes static or dynamic thermal experiments (e.g., creating a thermal performance or survival curves, quantifying responses to fluctuating thermal environments, or monitoring animal behaviour across a range of temperatures) easier, faster, and less costly.
The life-history fitness of F1hybrids of the microcrustaceanDaphnia pulexandD. pulicaria(Crustacea, Anomopoda)
Authors: Moy Irene , Green Makayla , Pham Thinh Phu , Luu Dustin , Xu Sen
Published: August 2020

Negative interaction between alleles that arise independently in diverging populations (i.e., Dobzhansky-Muller incompatibilities) can cause reduction of fitness in their hybrids. However, heterosis in hybrids can emerge if hybridization breaks down detrimental epistatic interaction within parental lineages. In this study, we examined the life-history fitness of the inter-specific F1hybrids of two recently diverged microcrustacean speciesDaphnia pulexandD. pulicariaas well as intra-specific F1hybrids ofD. pulex. We identified heterosis in four out of five life-history traits in the inter-specific F1 hybrids. The observation of heterosis in these life-history traits suggests that there are no major genetic incompatibilities between these two species affecting these traits. This also suggests thatD. pulexandD. pulicariaare at the early stage of speciation where heterosis can still occur.
Single extracellular vesicles protein profiling classifies renal fibrosis stages in mice model
Authors: Cai Yanling , Cao Rong , Liu Yuefei , Xiang Jinsheng , Li Zesong , Wan Qijun , Wu Di
Published: August 2020

Renal fibrosis is a common consequence of various chronic kidney diseases (CKD), leading to the loss of renal function and even end-stage renal failure. Extracellular vesicles (EVs) were shown to be involved in development of CKD and renal fibrosis. In this study, we induced renal fibrosis in mice model through unilateral ureteral obstruction (UUO) and extracted EVs from the kidney with induced fibrosis. Proximity barcoding assay (PBA) was performed to detect the expression of 112 proteins at individual EVs level for renal fibrosis of Grade I to IV and sham control group as well. The single EVs are classified into subpopulations according to the surface proteomic characteristics. We discovered several EV subpopulations, with presence of ITGAM, ITGA6, CD73, CD13 and ALDH1, increase significantly with development of renal fibrosis. These findings indicate that besides protein expression, proteomic fingerprints of single EVs can be potential biomarkers for surveillance of CKD and renal fibrosis.
gEAR: gene Expression Analysis Resource portal for community-driven, multi-omic data exploration
Authors: Orvis Joshua , Gottfried Brian , Kancherla Jayaram , Adkins Ricky S. , Song Yang , Dror Amiel A. , Olley Dustin , Rose Kevin , Chrysostomou Elena , Kelly Michael C. , Milon Beatrice , Matern Maggie S. , Azaiez Hela , Herb Brian , Colantuoni Carlo , Carter Robert L. , Ament Seth A. , Kelley Matthew W. , White Owen , Bravo Hector Corrada , Mahurkar Anup , Hertzano Ronna
Published: August 2020

The gEAR portal (gene Expression Analysis Resource, umgear.org) is an open access community-driven tool for multi-omic and multi-species data visualization, analysis and sharing. The gEAR supports visualization of multiple RNA-seq data types (bulk, sorted, single cell/nucleus) and epigenomics data, from multiple species, time points and tissues in a single-page, user-friendly browsable format. An integrated scRNA-seq workbench provides access to raw data of scRNA-seq datasets forde novoanalysis, as well as marker-gene and cluster comparisons of pre-assigned clusters. Users can upload, view, analyze and privately share their own data in the context of previously published datasets. Short, permanent URLs can be generated for dissemination of individual or collections of datasets in published manuscripts. While the gEAR is currently curated for auditory research with over 90 high-value datasets organized in thematic profiles, the gEAR also supports the BRAIN initiative (via nemoanalytics.org) and is easily adaptable for other research domains.
Integrated transcriptome, DNA methylome and chromatin state accessibility landscapes reveal regulators of Atlantic salmon maturation
Authors: Mohamed Amin R. , Naval-Sanchez Marina , Menzies Moira , Evans Bradley , King Harry , Reverter Antonio , Kijas James W.
Published: August 2020

Despite sexual development being ubiquitous to vertebrates, the epigenetic mechanisms controlling this fundamental transition remain largely undocumented in many organisms. Through whole-methylome, whole-transcriptome and chromatin landscape sequencing, we discovered global control mechanisms as well as specific regulators of sexual maturation in Atlantic salmon. This large integrated study was based on an experimental time course that successfully sampled the period when Atlantic salmon commence their trajectory towards sexual maturation. Co-analysis of DNA methylome and gene expression changes revealed chromatin remodelling genesarid1bandsmarca2were both significantly hypermethylated and upregulated in the ovary during the onset of maturation. We also observed changes in chromatin state landscape occurred early in the transition and were strongly correlated with fundamental remodelling of gene expression. Finally, we integrated our multiomics datasets to identifytrim25andznf423as key regulators in the pituitary that underwent 60 fold change in connectivity during the transition to sexual maturation. The study provides a comprehensive view of the spatiotemporal changes involved in a complex trait and opens the door to future efforts aiming to manipulate puberty in an economically important aquaculture species.