bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Ethanol-Assisted Aqueous Oil Extraction from aCicadidae Sp
Authors: Mahmoudi-Kordi Farzaneh , Balvardi Mohammad , Akhavan Hamid-Reza
Published: January 2021

Edible insects have been considering as a rich resource of high-quality protein and lipid content and at the same time a low-cost nutritious resource acquiring the least expenditure during farming, breeding, rearing and harvesting. On the other hand, organic solvent consumptions in industrial areas need to be limited; being flammable by environmental hazards. That is why seeking for alternative non-toxic solvents is highly substantial. In this study ethanol-aqueous extraction method applied at three different levels to find the optimum yield of edible oil extracted of Homoptera Cicadidae Magicicada, a seasonal insect residing underground, which is consuming locally as a whole meal. These levels set using Design of expert software to variables as pH, ethanol-concentration and solvent/sample ratio and the maximum yield extracted respectively at 6, 50 and 5, by the yield of 19.5%, that is comparable to oil extracted by conventional hexane oil extraction method at 27%. Fatty acids profile of recent method and hexane extraction method analyzed using GC-MS method and the physicochemical properties of either alternative method investigated. The results were on the standard ranges. Fatty acid profile of HCM was for the most part consisted of oleic acid, following by palmitic and linoleic acid 66.5, 19.2 and 7.8 respectively in hexane extraction method and 66.3, 17.7 and 9.5 in ethanol aqueous extraction method. The Iodine Value of HCM oil was noticeably high which introduces a medicinal applicatory besides the rich amount of MUFAs and PUFAs essential oils that are well-known for their incredible health benefits.
Ecological consequences of urbanization on a legume-rhizobia mutualism
Authors: Murray-Stoker David , Johnson Marc T. J.
Published: January 2021

Mutualisms are key determinants of community assembly and composition, but urbanization can alter the dynamics of these interactions and associated effects on ecosystem functions. Legume-rhizobia mutualisms are a model interaction to evaluate the ecological and ecosystem-level effects of urbanization, particularly urban-driven eutrophication and nitrogen (N) deposition. Here, we evaluated how urbanization affected the ecology of the mutualism between white clover (Trifolium repens) and its rhizobial symbiont (Rhizobium leguminosarumsymbiovartrifolii) along an urbanization gradient. We found that the abundance of rhizobium nodules on white clover decreased with urbanization. White clover acquired N from mixed sources of N fixation and uptake from the soil for the majority of the urbanization gradient, but white clover primarily acquired N from the soil rather than N fixation by rhizobia at the urban and rural limits of the gradient. Importantly, we identified soil N as a critical nexus for urban-driven changes in the white clover-rhizobium mutualism. Taken together, our results demonstrate that urbanization alters the ecological consequences of a legume-rhizobium mutualism, with direct and indirect effects of the urban landscape on an ecologically-important mutualistic interaction.
P4HA2-induced prolyl hydroxylation suppresses YAP1-mediated prostate cancer cell migration, invasion, and metastasis
Authors: Zhu Ming , Peng Ruiqing , Liang Xin , Lan Zhengdao , Tang Ming , Hou Pingping , Song Jian H. , Mak Celia Sze Ling , Park Jiwon , Zheng Shui-er , Huang Ailing , Ma Xingdi , Chen Ruidong , Chang Qing , Logothetis Christopher J. , Jain Abhinav K. , Lin Sue-Hwa , Katayama Hiroyuki , Hanash Samir M. , Wang Guocan
Published: January 2021

Yes-associated protein 1 (YAP1), a key player in the Hippo pathway, has been shown to play a critical role in tumor progression. However, the role of YAP1 in prostate cancer cell invasion, migration, and metastasis is not well defined. Through functional, transcriptomic, epigenomic, and proteomic analyses, we showed that prolyl hydroxylation of YAP1 plays a critical role in the suppression of cell migration, invasion, and metastasis in prostate cancer. Knockdown (KD) or knockout (KO) ofYAP1led to an increase in cell migration, invasion, and metastasis in prostate cancer cells. Microarray analysis showed that the EMT pathway was activated inYap1-KD cells. ChIP-seq analysis showed that YAP1 target genes are enriched in pathways regulating cell migration. Mass spectrometry analysis identified P4H prolyl hydroxylase in the YAP1 complex and YAP1 was hydroxylated at multiple proline residues. Proline-to-alanine mutations of YAP1 isoform 3 identified proline 174 as a critical residue, and its hydroxylation suppressed cell migration, invasion, and metastasis. KO ofP4ha2led to an increase in cell migration and invasion, which was reversed uponYap1KD. Our study identified a novel regulatory mechanism of YAP1 by which P4HA2-dependent prolyl hydroxylation of YAP1 determines its transcriptional activities and its function in prostate cancer metastasis.
rtcisE2F drives liver TIC self-renewal and metastasis via m6A-modulated mRNA stability ofE2F6andE2F3
Authors: Chen Zhenzhen , Liu Benyu , Huang Lan , Zhong Xiang , Yan Zhongyi , Zhu Pingping
Published: January 2021

Background

Liver tumor initiating cells (TICs) harbor self-renewal and differentiation capacities, and well contribute to liver tumorigenesis, metastasis and heterogeneity. However, the molecular mechanisms of liver TIC self-renewal are unclear. N6-methyladenosine is the most abundant modification of RNA molecules, and is involved in RNA stability and translation, but the molecular mechanisms of m6A regulation remain largely unknown.

Methods

circRNA expression was detected byin situhybridization, fluorescencein situhybridization, quantitative real-time PCR and Northern blot. Target gene expression was examined by microarray analyses, quantitative real-time PCR and Western blot. CRISPR, CRISPR interference (CRISPRi) and short-hairpin RNA (shRNA) were used for circRNA/target gene knockout and knockdown. Liver TICs were enriched through sphere formation and FACS using CD133 as a marker, and liver TIC activity was assessed by tumor propagation, sphere formation, tumor-initiating, and transwell assays. Quantitative real-time PCR and Northern blot were used to determine mRNA stability. RNA–protein interactions were examined by RNA pulldown, RNA immunoprecipitation, Tagged RNA affinity purification (TRAP) and electrophoretic mobility shift assays (EMSA).

Results

Here, we identified a functional rt-circRNA, termed rtcisE2F, that is highly expressed in liver cancer and liver TICs. rtcisE2F plays essential roles in the self-renewal and activities of liver TICs. rtcisE2F targetsE2F6andE2F3mRNAs, attenuates mRNA turnover, and increases E2F6/E2F3 expression. Mechanistically, rtcisE2F functions as a scaffold of m6A reader IGF2BP2 andE2F6/E2F3mRNA, promotes the association ofE2F6/E2F3mRNAs with IGF2BP2, and then inhibits their association with another m6A reader, YTHDF2. IGF2BP2 inhibitsE2F6/E2F3mRNA decay, whereas YTHDF2 promotesE2F6/E2F3mRNA decay. By switching m6A readers, rtcisE2F enhancesE2F6/E2F3mRNA stability. E2F6 and E2F3 are both required for liver TIC self-renewal and Wnt/β-catenin activation, and inhibition of these pathways is a potential strategy for preventing liver tumorigenesis and metastasis.

Conclusion

This work identified rtcisE2F as a key modulator in liver cancer and liver TICs, providing evidence for the biological function of rt-circRNA and unveiling a new regulatory layer for liver TIC self-renewal. rtcisE2F is involved in E2F6/E2F3 stability by switching their binding to the m6A readers IGF2BP2 and YTHDF2, providing a competitive mechanism between RNA molecules and m6A readers. Both E2F6 and E2F3 are required for liver TIC self-renewal and serve as therapeutic targets for liver TIC elimination.
Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis
Authors: Vastrad Basavaraj , Tengli Anandkumar , Vastrad Chanabasayya
Published: January 2021

Heart failure (HF) is a heterogeneous clinical syndrome and affects millions of people all over the world. HF occurs when the cardiac overload and injury, which is a worldwide complaint. The aim of this study was to screen and verify hub genes involved in developmental HF as well as to explore active drug molecules. The expression profiling by high throughput sequencing of GSE141910 dataset was downloaded from the Gene Expression Omnibus (GEO) database, which contained 366 samples, including 200 heart failure samples and 166 non heart failure samples. The raw data was integrated to find differentially expressed genes (DEGs) and were further analyzed with bioinformatics analysis. Gene ontology (GO) and REACTOME enrichment analyses were performed via ToppGene; protein-protein interaction (PPI) networks of the DEGs was constructed based on data from the HiPPIE interactome database; modules analysis was performed; target gene - miRNA regulatory network and target gene - TF regulatory network were constructed and analyzed; hub genes were validated; molecular docking studies was performed. A total of 881 DEGs, including 442 up regulated genes and 439 down regulated genes were observed. Most of the DEGs were significantly enriched in biological adhesion, extracellular matrix, signaling receptor binding, secretion, intrinsic component of plasma membrane, signaling receptor activity, extracellular matrix organization and neutrophil degranulation. The top hub genes ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 were identified from the PPI network. Module analysis revealed that HF was associated with adaptive immune system and neutrophil degranulation. The target genes, miRNAs and TFs were identified from the target gene - miRNA regulatory network and target gene - TF regulatory network. Furthermore, receiver operating characteristic (ROC) curve analysis and RT-PCR analysis revealed that ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 might serve as prognostic, diagnostic biomarkers and therapeutic target for HF. The predicted targets of these active molecules were then confirmed. The current investigation identified a series of key genes and pathways that might be involved in the progression of HF, providing a new understanding of the underlying molecular mechanisms of HF.
Impulse dispersion of aerosols during playing wind instruments
Authors: Gantner Sophia , Echternach Matthias , Veltrup Reinhard , Westphalen Caroline , Köberlein Marie Christine , Kuranova Liudmila , Peters Gregor , Jakubaß Bernhard , Benthaus Tobias , Döllinger Michael , Kniesburges Stefan
Published: January 2021

Musical activities especially singing and playing wind instruments have been singled out as potentially high-risk activities for transmission of SARS CoV-2, because of a higher rate of aerosol production and emission. Playing wind instruments can produce condensation water, droplets of saliva, and aerosol particles, which hover and convectional spread in the environmental air and can be potentially infectious.

The aim of this study is to investigate the primary impulse dispersion of aerosols during playing different wind instruments in comparison to breathing and speaking. Nine professional musicians (3 trumpeters, 3 cross flutists and 3 clarinetists) of the Bavarian Symphony Orchestra performed the main theme of Ludwig van Beethoven‘s 9th symphony, 4th movement in different pitches and loudness. Thereby, the inhaled air volume was marked with small aerosol particles produced with a commercial e-cigarette. The expelled aerosol cloud was recorded by cameras from different perspectives. Afterwards, the dimensions and dynamics of the aerosol cloud was measured by segmenting the video footage at every time point.

Overall, the cross flutes produced the largest dispersion at the end of task of up to maximum distances of 1.88 m in front direction. Thereby it was observed an expulsion of aerosol in different directions: upwards and downwards at the mouthpiece, at the end of the instrument and along the cross flute at the key plane. In comparison, the maximum impulse dispersion generated by the trumpets and clarinets were lower in frontal and lateral direction (1.2 m and 1.0 m in front-direction). The expulsion to the sides was also lower. Consequently, a distance of 3 m to the front and to the sides of 2 m for the cross flutes in an orchestral formation is proposed, for trumpets and clarinets a safety distance of 2 m to the front and 1.5 m between instrumentalists are recommendable.
Phenotype Risk Scores: moving beyond ‘cases’ and ‘controls’ to classify psychiatric disease in hospital-based biobanks
Authors: Lebovitch Dannielle S. , Johnson Jessica S. , Dueñas Hillary R. , Huckins Laura M.
Published: January 2021

Current phenotype classifiers for large biobanks with coupled electronic health records EHR and multi-omic data rely on ICD-10 codes for definition. However, ICD-10 codes are primarily designed for billing purposes, and may be insufficient for research. Nuanced phenotypes composed of a patients’ experience in the EHR will allow us to create precision psychiatry to predict disease risk, severity, and trajectories in EHR and clinical populations. Here, we create a phenotype risk score (PheRS) for major depressive disorder (MDD) using 2,086 cases and 31,000 individuals from Mount Sinai’s biobank BioMe ™. Rather than classifying individuals as ‘cases’ and ‘controls’, PheRS provide a whole-phenome estimate of each individual’s likelihood of having a given complex trait. These quantitative scores substantially increase power in EHR analyses and may identify individuals with likely ‘missing’ diagnoses (for example, those with large numbers of comorbid diagnoses and risk factors, but who lack explicit MDD diagnoses).

Our approach applied ten-fold cross validation and elastic net regression to select comorbid ICD-10 codes for inclusion in our PheRS. We identified 158 ICD-10 codes significantly associated with Moderate MDD (F33.1). Phenotype Risk Score were significantly higher among individuals with ICD-10 MDD diagnoses compared to the rest of the population (Kolgorov-Smirnov p<2.2e-16), and were significantly correlated with MDD polygenic risk scores (R2>0.182). Accurate classifiers are imperative for identification of genetic associations with psychiatric disease; therefore, moving forward research should focus on algorithms that can better encompass a patient’s phenome.
Home-based management of COVID-19 by identification of low-risk features
Authors: Cabanillas Fernando , Morales Javier , Conde José G. , Bertrán-Pasarell Jorge , Fernández Ricardo , Hernandez-Silva Yaimara , Liboy Idalia
Published: January 2021

Background

Covid-19 is a triphasic disorder characterized by a viral phase lasting 7-10 days from first onset of symptoms. In approximately 20% it is followed by a second stage heralded by elevation of pro-inflammatory markers such as ferritin, IL-6, CRP, LDH and D-dimers. We hypothesized that those with few abnormalities would have a low risk for progression to respiratory insufficiency and could be monitored at home without treatment.

Methods

Inclusion criteria included age >21, O2 saturation >90%. To be observed without treatment patients could not have >1 of the following: CRP > 10 mg/dL, high LDH, ferritin > 500 ng/ml, D-dimer > 1 mg/L, IL-6 > 10 pg/ml, absolute lymphocyte count <1,000, O2 sat <94%, or CT chest evidence of pneumonia. Primary endpoint: progression to respiratory failure. Secondary endpoint: 28-day survival.

Results

Of 208 entered, 132 were monitored without therapy. None progressed to respiratory failure or died.

Conclusions

We have shown that our approach can identify cases who can safely be observed without treatment, thus avoiding expensive, potentially toxic therapies, and circumventing unnecessary, costly hospitalizations. These results support our hypothesis that after applying our criteria, 64% of Covid-19 cases can be monitored as outpatients without therapy.
ARE GEOGRAPHIC FACTORS ASSOCIATED WITH POORER OUTCOMES IN PATIENTS DIAGNOSED WITH COVID-19?
Authors: Magallón-Botaya Rosa , Oliván-Blázquez Bárbara , Ramirez-Cervantes Karen Lizzette , Mendez-Lopez de la Mazanara Fatima , Casajuana-Closas Marc , Esteban-Andrés Eva
Published: January 2021

Background

The prognosis of patients with COVID-19, with older age and comorbidities, is associated with a more severe course and higher fatality rates but no analysis has yet included factors related to the geographical area/municipality in which the affected patients live. So the objective of this study is to analyse the prognosis of patients with COVID-19 in terms of sex, age, comorbidities, and geographic variables.

Methods

A retrospective cohort of 6286 patients diagnosed with COVID-19 was analysed, considering demographic data, previous comorbidities and geographic variables. The main study variables were hospital admission, Intensive Care Unit (ICU) admission and death due to worsening symptoms; and the secondary variables were sex, age, comorbidities and geographic variables (size of the area of residence, distance to the hospital and the driving time to the hospital). A comparison analysis and a multivariate Cox model were performed.

Results

The multivariate Cox model showed that women had a better prognosis in any type of analysed prognosis. Most of the comorbidities studied were related to a poorer prognosis except for dementia, which is related to lower admissions and higher mortality. Suburban areas were associated with greater mortality and with less hospital or ICU admission. Distance to the hospital was also associated with hospital admission.

Conclusions

Factors such as type of municipality and distance to hospital act as social health determinants. This fact must be taken account in order to stablish specifics prevention measures and treatment protocols.
Implementation of predictive risk stratification to reduce emergency admissions to hospital: experiences of general practitioners and practice managers
Authors: Evans Bridie Angela , Davies Jan , Dale Jeremy , Hutchings Hayley , Kingston Mark , Porter Alison , Russell Ian , Williams Victoria , Snooks Helen
Published: January 2021

Aim

In a trial evaluating the introduction of a predictive risk stratification model (PRISM) into primary care, we reported statistically significant increases in emergency hospital admissions and use of other NHS services without evidence of benefits to patients or the NHS. The aim of this study was to explore the views and experiences of general practitioners (GPs) and practice managers on incorporating PRISM into routine practice.

Methods

We interviewed 22 GPs and practice managers in 18 participating practices at two timepoints: 3-6 months after PRISM was available in their practice; and at study end, up to 18 months later. We recorded and transcribed interviews and analysed data thematically using Normalisation Process Theory.

Results

Respondents reported that the decision to use PRISM was based mainly on fulfilling reporting requirements for Quality and Outcome Framework (QOF) incentives. Most applied it to a very small number of patients for a short period. Using PRISM entailed technical tasks, information sharing within practice meetings and changes to patient care. These were diverse and generally small scale. Use was inhibited by PRISM not being integrated with practice systems. Respondents’ evaluation of PRISM was mixed: most doubted it had any large scale impact, but many cited examples of impact on individual patient care. They reported increased awareness of patients in high risk groups.

Conclusions

Qualitative results suggest mixed views of predictive risk stratification in primary care and raised awareness of highest-risk patient groups, potentially affecting unplanned hospital attendance and admissions. To inform future policy, decision-makers need more information about implementation and effects of emergency admissions risk stratification tools in primary and community settings.

Trial registration

Controlled Clinical Trials no. ISRCTN55538212.
Molecular epidemiology of SARS-CoV-2 - a regional to global perspective
Authors: Brandt Christian , Spott Riccardo , Hölzer Martin , Kühnert Denise , Fuchs Stephan , Lohde Mara , Marquet Mike , Viehweger Adrian , Rimek Dagmar , Pletz Mathias W.
Published: January 2021

Background

After a year of the global SARS-CoV-2 pandemic, a highly dynamic genetic diversity is surfacing. Among nearly 1000 reported virus lineages, dominant lineages such as B.1.1.7 or B.1.351 attract media attention with questions regarding vaccine efficiency and transmission potential. In response to the pandemic, the Jena University Hospital began sequencing SARS-CoV-2 samples in Thuringia in early 2020.

Methods

Viral RNA was sequenced in tiled amplicons using Nanopore sequencing. Subsequently, bioinformatic workflows were used to process the generated data. As a genomic background, 9,642 representative SARS-CoV-2 genomes (1,917 of German origin) were extracted from more than 300.000 genomes.

Results

In a comprehensive bioinformatics analysis, we have set Thuringian isolates in the German, European and global context. In Thuringia, a largely rural German region without an international airport and a population density below the German average, we discovered many of the common “EU lineages”. German samples are scattered across eight major clades, and Thuringian samples occupy four of them.

Conclusion

The rapid emergence and spread of novel variants are of great concern as these lineages could transmit more efficiently, evade current vaccine efforts or undermine diagnostic test accuracy. To anticipate and mitigate these threats, a continuous molecular surveillance is essential.

Key messages

Bioinformatics analysis of 1,917, 4,251, and 3,474 SARS-CoV-2 genomes from Germany, the EU (except Germany), and non-EU, respectively, subsampled from more than 300,000 public genomes and placed in the context of Thuringian sequences

Constant antigenic drift for SARS-CoV-2 and no clear pattern or clustering is visible in Thuringia based on the current number of samples

Currently over 100 described lineages are identified in Germany and only a subset (9) are detected in Thuringia so far, most likely due to genetic undersampling

From a national perspective, it is likely that high-frequency lineages, which are currently spreading throughout Europe, will eventually also reach Thuringia

Systematic and dense molecular surveillance via whole-genome sequencing is needed to detect concerning new lineages early, limit spread and adjust vaccines if necessary
REM: An Integrative Rule Extraction Methodology for Explainable Data Analysis in Healthcare
Authors: Shams Zohreh , Dimanov Botty , Kola Sumaiyah , Simidjievski Nikola , Terre Helena Andres , Scherer Paul , Matjašec Urška , Abraham Jean , Jamnik Mateja , Liò Pietro
Published: January 2021

Deep learning models are receiving increasing attention in clinical decision-making, however the lack of explainability impedes their deployment in day-to-day clinical practice. We propose REM, an explainable methodology for extracting rules from deep neural networks and combining them with rules from non-deep learning models. This allows integrating machine learning and reasoning for investigating basic and applied biological research questions. We evaluate the utility of REM in two case studies for the predictive tasks of classifying histological and immunohistochemical breast cancer subtypes from genotype and phenotype data. We demonstrate that REM efficiently extracts accurate, comprehensible rulesets from deep neural networks that can be readily integrated with rulesets obtained from tree-based approaches. REM provides explanation facilities for predictions and enables the clinicians to validate and calibrate the extracted rulesets with their domain knowledge. With these functionalities, REM caters for a novel and direct human-in-the-loop approach in clinical decision-making.
AngioNet: A Convolutional Neural Network for Vessel Segmentation in X-ray Angiography
Authors: Iyer Kritika , Najarian Cyrus P. , Fattah Aya A. , Arthurs Christopher J. , Soroushmehr S.M. Reza , Subban Vijayakumar , Sankardas Mullasari A. , Nadakuditi Raj R. , Nallamothu Brahmajee K. , Figueroa C. Alberto
Published: January 2021

Abstract

Coronary Artery Disease (CAD) is commonly diagnosed using X-ray angiography, in which images are taken as radio-opaque dye is flushed through the coronary vessels to visualize stenosis severity. Cardiologists typically use visual estimation to approximate the percent diameter reduction of the stenosis, and this directs therapies like stent placement. A fully automatic method to segment the vessels would eliminate potential subjectivity and provide a quantitative and systematic measurement of diameter reduction. Here, we have designed a convolutional neural network, AngioNet, for vessel segmentation in X-ray angiography images. The main innovation in this network is the introduction of an Angiographic Processing Network which significantly improves segmentation performance on multiple network backbones, with the best performance using Deeplabv3+ (Dice score 0.864, sensitivity 0.918, specificity 0.987). We have also demonstrated the interchangeability of our network in measuring vessel diameter with Quantitative Coronary Angiography. Our results indicate that AngioNet is a powerful tool for automatic angiographic vessel segmentation that could facilitate systematic anatomical assessment of coronary stenosis in the clinical workflow.
Community structured model for vaccine strategies to control COVID19 spread: a mathematical study
Authors: Aruffo Elena , Yuan Pei , Tan Yi , Gatov Evgenia , Gournis Effie , Collier Sarah , Ogden Nick , Bélair Jacques , Zhu Huaiping
Published: January 2021

Efforts to mitigate the COVID-19 pandemic have relied heavily on non-pharmaceutical interventions (NPIs), including physical distancing, hand hygiene, and mask-wearing. However, an effective vaccine is essential to containing the spread of the virus. The first doses were distributed at the end of 2020, but the efficacy, period of immunity it will provide, and percentage of coverage still remain unclear. We developed a compartment model to examine different vaccine strategies for controlling the spread of COVID-19. Our framework accounts for testing rates, test-turnaround times, and vaccination waning immunity. Using reported case data from the city of Toronto, Canada between Mar-Dec, 2020 we defined epidemic phases of infection using contact rates, which depend on individuals’ duration of time spent within the household, workplace/school, or community settings, as well as the probability of transmission upon contact. We investigated the impact of vaccine distribution by comparing different permutations of waning immunity, vaccine coverage and efficacy throughout various stages of NPI’s relaxation in terms of cases, deaths, and household transmission, as measured using the basic reproduction number (R0). We observed that widespread vaccine coverage substantially reduced the number of cases and deaths. In order for NPIs to be relaxed 8 months after vaccine distribution, infection spread can be kept under control with either 60% vaccine coverage, no waning immunity, and 70% efficacy, or with 60% coverage with a 12-month waning immunity and 90% vaccine efficacy. Widespread virus resurgence can result when the immunity wanes under 3 months and/or when NPI’s are relaxed in concomitance with vaccine distribution. In addition to vaccination, our analysis of R0 showed that the basic reproduction number is reduced by decreasing the tests turnaround time and transmission in the household. While we found that household transmission can decrease following the introduction of a vaccine, public health efforts to reduce test turnaround times remain important for virus containment. Our findings suggest that vaccinating two-thirds of the population with a vaccine that is at least 70% effective may be sufficient for controlling COVID-19 spread, as long as NPI’s are not immediately relaxed.
Logistic advantage of two-step screening strategy for SARS-CoV-2 at airport quarantine
Authors: Yokota Isao , Shane Peter Y , Teshima Takanori
Published: January 2021

Background

Airport quarantine is required to reduce the risk of entry of travelers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is challenging for both high accuracy and rapid turn-around time to coexist in testing; polymerase chain reaction (PCR) is time-consuming with high accuracy, while antigen testing is rapid with less accuracy.

Methods

88,924 (93.2%) of 95,457 arrivals at three international airports in Japan were tested for SARS-CoV-2 using self-collected saliva by a screening strategy with initial chemiluminescent enzyme immunoassay (CLEIA) followed by confirmatory nucleic acid amplification tests (NAAT) only for intermediate range antigen concentrations.

Results

254 (0.27%) persons were found to be SARS-CoV-2 antigen positive (≥ 4.0 pg/mL) by CLEIA. NAAT was required for confirmatory testing in 513 (0.54%) persons with intermediate antigen concentrations (0.67-4.0 pg/mL) whereby the virus was detected in 34 (6.6%) persons. This two-step strategy dramatically reduced the utilization of NAAT to approximately one out of every 200 test subjects.

Estimated performance of this strategy did not show significant increase in false negatives as compared to performing NAAT in all subjects. Further reduction in imported cases may be achieved by post-screening quarantine.

Conclusions

Point of care testing by quantitative CLEIA using self-collected saliva is less labor-intensive and yields results rapidly, thus suitable as an initial screening test. Reserving NAAT for CLEIA indeterminate cases may prevent compromising accuracy while significantly improving the logistics of administering mass-screening at large venues.
A Catalog of the Diversity and Ubiquity of Metabolic Organelles in Bacteria
Authors: Sutter Markus , Melnicki Matthew R. , Schulz Frederik , Woyke Tanja , Kerfeld Cheryl A.
Published: January 2021

Bacterial microcompartments (BMCs) are organelles that segregate segments of metabolic pathways, which are incompatible with surrounding metabolism. In contrast to their eukaryotic counterparts, the selectively permeable membrane of BMCs, the shell, is composed of protein. While the sequestered enzymes vary among functionally distinct BMCs, the proteins that form diverse BMC shells are structurally homologous; this enables the bioinformatic identification of the organelles by locating genes encoding shell proteins, which are typically proximal to those for the encapsulated enzymes. With recent advances in genome‐resolved metagenomics and the emphasis on “microbial dark matter”, many new genome sequences from diverse and obscure bacterial clades have become available. We find the number of identifiable BMC loci has increased twenty‐fold since the last comprehensive census of 2014. Moreover, the addition of new types we uncovered doubles the number of distinct BMC types known. These expand the range of catalysis encapsulated in BMCs, underscoring that there is dark biochemistry that is compartmentalized in bacterial organelles yet to be discovered through genome sequencing. Our comprehensive catalog of BMCs provides a framework for their identification, correlation with bacterial niche adaptation, and experimental characterization, and broadens the foundation for the development of BMC‐based nanoarchitectures for biomedical and bioengineering applications.
Implication of synaptotagmins 4 and 7 in activity-dependent somatodendritic dopamine release
Authors: Delignat-Lavaud Benoît , Ducrot Charles , Kouwenhoven Willemieke , Feller Nina , Trudeau Louis-Éric
Published: January 2021

Dopamine (DA) neurons can release DA not just from axon terminals, but also from their somatodendritic (STD) compartment thought a mechanism that is still incompletely understood. Using voltammetry in mouse mesencephalic brain slices, we find that STD DA release has low capacity, is stable in response to electrical but not optogenetic train pulses and shows a calcium sensitivity that is comparable to that of axonal release. It is also strikingly more resilient compared to axonal release in a 6‐ hydroxydopamine model of Parkinson’s disease plasticity. We find that the molecular mechanism of STD DA release differs from axonal release with regards to the implication of synaptotagmin (Syt) calcium sensors. While individual constitutive knock-out Syt4 and Syt7 is not sufficient to reduce STD DA release, removal of both isoforms reduces this release by ~50%, leaving axonal release unimpaired. Our works unveils clear differences in the mechanisms of STD and axonal DA release.
Integrating Sample Similarities into Latent Class Analysis: A Tree-Structured Shrinkage Approach
Authors: Li Mengbing , Park Daniel E. , Aziz Maliha , Liu Cindy M. , Price Lance B. , Wu Zhenke
Published: January 2021

Summary

This paper is concerned with using multivariate binary observations to estimate the probabilities of unobserved classes with scientific meanings. We focus on the setting where additional information about sample similarities is available and represented by a rooted weighted tree. Every leaf in the given tree contains multiple samples. Shorter distances over the tree between the leaves indicatea priorihigher similarity in class probability vectors. We propose a novel data integrative extension to classical latent class models (LCMs) with tree-structured shrinkage. The proposed approach enables 1) borrowing of information across leaves, 2) estimating data-driven leaf groups with distinct vectors of class probabilities, and 3) individual-level probabilistic class assignment given the observed multivariate binary measurements. We derive and implement a scalable posterior inference algorithm in a variational Bayes framework. Extensive simulations show more accurate estimation of class probabilities than alternatives that suboptimally use the additional sample similarity information. A zoonotic infectious disease application is used to illustrate the proposed approach. The paper concludes by a brief discussion on model limitations and extensions.
LeafGo: Leaf to Genome, a quick workflow to produce high-qualityDe novogenomes with Third Generation Sequencing technology
Authors: Driguez Patrick , Bougouffa Salim , Carty Karen , Putra Alexander , Jabbari Kamel , Reddy Muppala , Soppe Richard , Cheung Nicole , Fukasawa Yoshinori , Ermini Luca
Published: January 2021

Recent years have witnessed a rapid development of sequencing technologies. Fundamental differences and limitations among various platforms impact the time, the cost and the accuracy for sequencing whole genomes. Here we designed a completede novoplant genome generation workflow that starts from plant tissue samples and produces high-quality draft genomes with relatively modest laboratory and bioinformatic resources within seven days. To optimize our workflow we selected different species of plants which were used to extract high molecular weight DNA, to make PacBio and ONT libraries for sequencing with the Sequel I, Sequel II and GridION platforms. We assembled high-quality draft genomes of two differentEucalyptusspeciesE. rudis, andE. camaldulensisto chromosome level without using additional scaffolding technologies. For the rapid production ofde novogenome assembly of plant species we showed that our DNA extraction protocol followed by PacBio high fidelity sequencing, and assembly with new generation assemblers such as hifiasm produce excellent results. Our findings will be a valuable benchmark for groups planning wet- and dry-lab plant genomics research and for high throughput plant genomics initiatives.
TRPM7 is critical for short-term synaptic depression by regulating synaptic vesicle endocytosis
Authors: Jiang Zhong-Jiao , Li Wenping , Yao Li-Hua , Grewe Brian S. , McGinley Andrea , Varga Kelly , Alford Simon , Gong Liang-Wei
Published: January 2021

TRPM7 contributes to a variety of physiological and pathological processes in many tissues and cells. With a widespread distribution in the nervous system, TRPM7 is involved in animal behaviors and neuronal death induced by ischemia. However, the physiological role of TRPM7 in CNS neuron remains unclear. Here, we identify endocytic defects in neuroendocrine cells and neurons from TRPM7 knockout (KO) mice, indicating a role of TRPM7 in synaptic vesicle endocytosis. Our experiments further pinpoint the importance of TRPM7 as an ion channel in synaptic vesicle endocytosis. Ca2+imaging detects a defect in presynaptic Ca2+dynamics in TRPM7 KO neuron, suggesting an importance of Ca2+influx via TRPM7 in synaptic vesicle endocytosis. Moreover, the short-term depression is enhanced in both excitatory and inhibitory synaptic transmission from TRPM7 KO mice. Taking together, our data suggests that Ca2+influx via TRPM7 may be critical for short-term plasticity of synaptic strength by regulating synaptic vesicle endocytosis in neurons.
Diet composition, body condition and sexual size dimorphism of the common African toad(Amietophrynus regularis)in urban and agricultural landscape
Authors: Ofori Benjamin Yeboah , Mensah John Bosu , Anderson Roger Sigismund , Attuquayefio Daniel Korley
Published: January 2021

Land use and land cover change (LULCC) are major drivers of global biodiversity loss. The conversion of natural habitats into human-modified landscapes poses novel and multifaceted environmental stressors to organisms, influencing their ecology, physiology, life history and fitness. Although the effects of LULCC have been studied extensively at the community level, there is scant information about its effect on population and individual characteristics. We assessed the diet composition, body condition, and sexual size dimorphism of the common African toad(Amietophrynus regularis)in urban and agricultural landscape. Diet composition was evaluated using gut content analysis, while body condition was measured using residual mass index. Overall, 935 prey items comprising six classes, at least 18 orders and 31 families were obtained from toads. This broad dietary niche suggested thatAmietophrynus regularisis a generalist predator. The family Formicidae was the most consumed prey item, with a frequency of occurrence above 80% at both sites. We found no sex- or habitat-biased dietary partitioning in the toads. A statistically significant positive correlation existed between snout-vent-length (SVL) and diversity of prey items (Pearson’s correlation r = 0.999, p ≤ 0.0001) for toads from farmland, which also had better body conditions. The toads showed female-biased sexual size dimorphism, but males had longer tibio-fibula, radio-ulna, foot, and distal fore limbs. This study is probably the first to assess the diet composition, body condition and sexual size dimorphism ofAmietophrynus regularissimultaneously. The ecological, evolutionary and conservation implications of our findings are discussed.
Identification of developmentally important genes inSilene latifoliathrough chemical genetics and transcriptome profiling
Authors: Bačovský Václav , Čegan Radim , Tihlaříková Eva , Neděla Vilém , Hudzieczek Vojtěch , Smrža Lubomír , Beneš Vladimír , Hobza Roman
Published: January 2021

Dioecious plants possess diverse sex determination systems and unique mechanisms of reproductive organ development; however, little is known about how sex-linked genes shape the expression of regulatory cascades that lead to developmental differences between sexes. InSilene latifolia, a dioecious plant with stable dimorphism in floral traits, early experiments suggested that female-regulator genes act on the factors that determine the boundaries of the flower whorls. To identify these regulators, we sequenced the transcriptome of male flowers with fully developed gynoecia induced by rapid demethylation in the parental generation. As the hermaphrodite flower trait is holandric (transmitted only from male to male, inherited on the Y chromosome), we screened for genes that are differentially expressed between male, female, and hermaphrodite flowers. Dozens of candidate genes that are upregulated in hermaphrodite flowers compared to male and female flowers were detected and found to have putative roles in floral organization, affecting the expression of floral MADS-box and other genes. Amongst these genes, eight candidates were found to promote gynoecium formation in female and hermaphrodite flowers, affecting organ size, whorl boundary, and the expression of mainly B class flower genes. To complement our transcriptome analysis, we closely examined the floral organs in their native state using a field emission environmental scanning electron microscope. Our results reveal the principal regulatory pathways involved in sex-specific flower development in the classical model of dioecy,S. latifolia.
Elucidation of an anaerobic pathway for metabolism of L-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria
Authors: Rajakovich Lauren J. , Fu Beverly , Bollenbach Maud , Balskus Emily P.
Published: January 2021

Trimethylamine (TMA) is an important gut microbial metabolite strongly associated with human disease. There are prominent gaps in our understanding of how TMA is produced from the essential dietary nutrient L-carnitine, particularly in the anoxic environment of the human gut where oxygen-dependent L-carnitine-metabolizing enzymes are likely inactive. Here, we elucidate the chemical and genetic basis for anaerobic TMA generation from the L-carnitine-derived metabolite γ-butyrobetaine (γbb) by the human gut bacteriumEmergencia timonensis. We identify a set of genes upregulated by γbb and demonstrate that the enzymes encoded by the induced γbb utilization (bbu) gene cluster convert γbb to TMA. The key TMA-generating step is catalyzed by a previously unknown type of TMA-lyase enzyme that utilizes a flavin cofactor to catalyze a redox neutral transformation. We identify additional cultured and uncultured host-associated bacteria that possess thebbugene cluster, providing insights into the distribution of anaerobic γbb metabolism. Lastly, we present genetic, transcriptional, and metabolomic evidence that confirms the relevance of this metabolic pathway in the human gut microbiota. These analyses indicate that the anaerobic pathway is a more substantial contributor to TMA generation from L-carnitine in the human gut than the previously proposed aerobic pathway. The discovery and characterization of thebbupathway provides the critical missing link in anaerobic metabolism of L-carnitine to TMA, enabling investigation into the connection between this microbial function and human disease.

SIGNIFICANCE

Trimethylamine (TMA) is a disease-associated metabolite produced in the human body exclusively by microbes. Gut microbes generate TMA from essential nutrients consumed in the human diet, including L-carnitine. However, our understanding of the biochemical mechanisms involved in these transformations is incomplete. In this work, we define the biochemical pathway and genetic components in gut bacteria required for anaerobic production of TMA from γ-butyrobetaine, a metabolite derived from L-carnitine. This discovery identifies a new type of TMA-producing enzyme and fills a critical gap in our knowledge of L-carnitine metabolism to TMA in the anaerobic environment of the human gut. This knowledge will enable evaluation of the link between L-carnitine metabolism and human disease, and the design of potential therapeutics.
mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge
Authors: Meyer Michelle , Wang Yuan , Edwards Darin , Smith Gregory R. , Rubenstein Aliza B. , Ramanathan Palaniappan , Mire Chad E. , Pietzsch Colette , Chen Xi , Ge Yongchao , Cheng Wan Sze , Henry Carole , Woods Angela , Ma LingZhi , Stewart-Jones Guillaume B. E. , Bock Kevin W. , Minai Mahnaz , Nagata Bianca M. , Periasamy Sivakumar , Shi Pei-Yong , Graham Barney S. , Moore Ian N. , Ramos Irene , Troyanskaya Olga G. , Zaslavsky Elena , Carfi Andrea , Sealfon Stuart C. , Bukreyev Alexander
Published: January 2021

The mRNA-1273 vaccine was recently determined to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from interim Phase 3 results. Human studies, however, cannot provide the controlled response to infection and complex immunological insight that are only possible with preclinical studies. Hamsters are the only model that reliably exhibit more severe SARS-CoV-2 disease similar to hospitalized patients, making them pertinent for vaccine evaluation. We demonstrate that prime or prime-boost administration of mRNA-1273 in hamsters elicited robust neutralizing antibodies, ameliorated weight loss, suppressed SARS-CoV-2 replication in the airways, and better protected against disease at the highest prime-boost dose. Unlike in mice and non-human primates, mRNA-1273- mediated immunity was non-sterilizing and coincided with an anamnestic response. Single-cell RNA sequencing of lung tissue permitted high resolution analysis which is not possible in vaccinated humans. mRNA-1273 prevented inflammatory cell infiltration and the reduction of lymphocyte proportions, but enabled antiviral responses conducive to lung homeostasis. Surprisingly, infection triggered transcriptome programs in some types of immune cells from vaccinated hamsters that were shared, albeit attenuated, with mock-vaccinated hamsters. Our results support the use of mRNA-1273 in a two-dose schedule and provides insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.
Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7
Authors: Wang Pengfei , Nair Manoj S. , Liu Lihong , Iketani Sho , Luo Yang , Guo Yicheng , Wang Maple , Yu Jian , Zhang Baoshan , Kwong Peter D. , Graham Barney S. , Mascola John R. , Chang Jennifer Y. , Yin Michael T. , Sobieszczyk Magdalena , Kyratsous Christos A. , Shapiro Lawrence , Sheng Zizhang , Huang Yaoxing , Ho David D.
Published: January 2021

The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody (mAb) therapeutics have received emergency use authorization1–3, with more in the pipeline4–7. Furthermore, multiple vaccine constructs have shown promise8, including two with ~95% protective efficacy against COVID-199,10. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK11and B.1.351 in South Africa12is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants13,14with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.