bluuebunny/crossref_metadata_2025 huggingface dataset:
bla
OXA-48-like genome architecture among carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in the Netherlands
Authors: Hendrickx Antoni P. A. , Landman Fabian , de Haan Angela , Witteveen Sandra , van Santen-Verheuvel Marga G. , Schouls Leo M. ,   the Dutch CPE surveillance Study Group
Published: May 2021

Carbapenem-hydrolysing enzymes belonging to the OXA-48-like group are encoded by bla
OXA-48-like alleles and are abundant among

Enterobacterales

in the Netherlands. Therefore, the objective here was to investigate the characteristics, gene content and diversity of the bla
OXA-48-like carrying plasmids and chromosomes of

Escherichia coli

and

Klebsiella pneumoniae

collected in the Dutch national surveillance from 2014 to 2019 in comparison with genome sequences from 29 countries. A combination of short-read genome sequencing with long-read sequencing enabled the reconstruction of 47 and 132 complete bla
OXA-48-like plasmids for

E. coli

and

K. pneumoniae

, respectively. Seven distinct plasmid groups designated as pOXA-48-1 to pOXA-48-5, pOXA-181 and pOXA-232 were identified in the Netherlands which were similar to internationally reported plasmids obtained from countries from North and South America, Europe, Asia and Oceania. The seven plasmid groups varied in size, G+C content, presence of antibiotic resistance genes, replicon family and gene content. The pOXA-48-1 to pOXA-48-5 plasmids were variable, and the pOXA-181 and pOXA-232 plasmids were conserved. The pOXA-48-1, pOXA-48-2, pOXA-48-3 and pOXA-48-5 groups contained a putative conjugation system, but this was absent in the pOXA-48-4, pOXA-181 and pOXA-232 plasmid groups. pOXA-48 plasmids contained the PemI antitoxin, while the pOXA-181 and pOXA-232 plasmids did not. Furthermore, the pOXA-181 plasmids carried a virB2-virB3-virB9-virB10-virB11 type IV secretion system, while the pOXA-48 plasmids and pOXA-232 lacked this system. A group of non-related pOXA-48 plasmids from the Netherlands contained different resistance genes, non-IncL-type replicons or no replicons. Whole genome multilocus sequence typing revealed that the bla
OXA-48-like plasmids were found in a wide variety of genetic backgrounds in contrast to chromosomally encoded bla
OXA-48-like alleles. Chromosomally localized bla
OXA-48 and bla
OXA-244 alleles were located on genetic elements of variable sizes and comprised regions of pOXA-48 plasmids. The bla
OXA-48-like genetic element was flanked by a direct repeat upstream of IS1R, and was found at multiple locations in the chromosomes of

E. coli

. Lastly,

K. pneumoniae

isolates carrying bla
OXA-48 or bla
OXA-232 were mostly resistant for meropenem, whereas E. coli bla
OXA-48, bla
OXA-181 and chromosomal bla
OXA-48 or bla
OXA-244 isolates were mostly sensitive. In conclusion, the overall bla
OXA-48-like plasmid population in the Netherlands is conserved and similar to that reported for other countries, confirming global dissemination of bla
OXA-48-like plasmids. Variations in size, presence of antibiotic resistance genes and gene content impacted pOXA-48, pOXA-181 and pOXA-232 plasmid architecture.
Network alignment and similarity reveal atlas-based topological differences in structural connectomes
Authors: Frigo Matteo , Cruciani Emilio , Coudert David , Deriche Rachid , Natale Emanuele , Deslauriers-Gauthier Samuel
Published: May 2021

The interactions between different brain regions can be modeled as a graph, called connectome, whose nodes correspond to parcels from a predefined brain atlas. The edges of the graph encode the strength of the axonal connectivity between regions of the atlas which can be estimated via diffusion Magnetic Resonance Imaging (MRI) tractography. Herein, we aim at providing a novel perspective on the problem of choosing a suitable atlas for structural connectivity studies by assessing how robustly an atlas captures the network topology across different subjects in a homogeneous cohort. We measure this robustness by assessing the alignability of the connectomes, namely the possibility to retrieve graph matchings that provide highly similar graphs. We introduce two novel concepts. First, the graph Jaccard index (GJI), a graph similarity measure based on the well-established Jaccard index between sets; the GJI exhibits natural mathematical properties that are not satisfied by previous approaches. Second, we devise WL-align, a new technique for aligning connectomes obtained by adapting the Weisfeiler-Lehman (WL) graph-isomorphism test. We validated the GJI and WL-align on data from the Human Connectome Project database, inferring a strategy for choosing a suitable parcellation for structural connectivity studies. Code and data are publicly available.

AUTHOR SUMMARY

An important part of our current understanding of the structure of the human brain relies on the concept of brain network, which is obtained by looking at how different brain regions are connected with each other. In this paper we present a strategy for choosing a suitable parcellation of the brain for structural connectivity studies by making use of the concepts of network alignment and similarity. To do so, we design a novel similarity measure between weighted networks called graph Jaccard index, and a new network alignment technique called WL-align. By assessing the possibility to retrieve graph matchings that provide highly similar graphs, we show that morphology- and structure-based atlases define brain networks which are more topologically robust across a wide range of resolutions.
Phylodynamic insights on the early spread of the COVID-19 pandemic and the efficacy of intervention measures
Authors: Gao Jiansi , May Michael R. , Rannala Bruce , Moore Brian R.
Published: May 2021

We performed phylodynamic analyses of all available SARS-CoV-2 genomes from the early phase of the COVID-19 pandemic—combined with a novel dataset on contemporary global air-travel volume—to assess the efficacy of public-health measures on viral geographic spread. Globally, viral dispersal rates are significantly correlated with air-travel volume, and widespread international air-travel bans imposed against China by early February coincide with a significant reduction in geographic viral spread. In North America, the efficacy of this travel ban was temporary, possibly due to the lack of both containment measures against other infected regions and domestic mitigation measures. By contrast, in China, domestic mitigation measures were correlated with a long-term reduction in viral spread, despite repeated international introductions. Our study supports a role for both targeted international containment and domestic mitigation measures as critical components of a more comprehensive public-health strategy to mitigate future outbreaks caused by the emergence of novel SARS-CoV-2 variants.

One sentence summary

Phylodynamic analyses reveal that variation in rates of early geographic spread of COVID-19 are correlated with intervention measures.
Persistent malaria transmission from asymptomatic children despite highly effective malaria control in eastern Uganda
Authors: Andolina Chiara , Rek John , Briggs Jessica , Okoth Joseph , Musiime Alex , Ramjith Jordache , Teyssier Noam , Conrad Melissa , Nankabirwa Joaniter I. , Lanke Kjerstin , Rodriguez-Barraquer Isabel , Meerstein-Kessel Lisette , Arinaitwe Emmanuel , Olwoch Peter , Rosenthal Philip J. , Kamya Moses R. , Dorsey Grant , Greenhouse Bryan , Drakeley Chris , Staedke Sarah G. , Bousema Teun
Published: May 2021

Background

Persistent asymptomaticPlasmodium falciparuminfections are common in malaria-endemic settings, but their contribution to transmission is poorly understood.

Methods

A cohort of children and adults from Tororo, Uganda was closely followed for 24 months by continuous passive surveillance and routine assessments.P. falciparumparasite density, gametocyte density and genetic composition were determined molecularly; mosquito membrane feeding assays were performed on samples from participants with symptomatic and asymptomatic infections.

Findings

From October 2017 to October 2019, we followed all 531 residents from 80 households. Parasite prevalence was 5·8% by microscopy and 17·3% by PCR at enrolment and declined thereafter. We conducted 538 mosquito feeding experiments on samples from 107 individuals. Mosquito infection rates were strongly associated with gametocyte densities of participants. Considering both transmissibility of infections and their relative frequency, the estimated human infectious reservoir was primarily asymptomatic microscopy-detected infections (83·8%), followed by asymptomatic submicroscopic (15·6%) and symptomatic (0·6%) infections. Over half of the infectious reservoir was children aged 5-15 years (56·8%); individuals <5 years (27·5%) and>16 years (15·7%) contributed less. Four children were responsible for 62·6% (279/446) of infected mosquitos and were infectious at multiple timepoints.

Interpretation

Individuals with asymptomatic infections were important drivers of malaria transmission. School-aged children were responsible for over half of all mosquito infections, with a small minority of asymptomatic children highly infectious. Demographically targeted interventions, aimed at school-aged children, could further reduce transmission in areas under effective vector control.

Funding

National institute of Health, Bill & Melinda Gates Foundation, European Research Council.
Small nucleolar RNAs in plasma and their discriminatory power as diagnostic biomarkers of Alzheimer’s disease
Authors: Fitz Nicholas F. , Nam Kyong Nyon , Wang Jiebiao , Kamboh M. Ilyas , Koldamova Radosveta , Lefterov Iliya
Published: May 2021

Abstract

The clinical diagnosis of Alzheimer’s disease, at its early stage, remains a difficult task. Advanced imaging technologies and laboratory assays to detect Aβ peptides Aβ42 and Aβ40, total and phosphorylated tau in CSF provide a set of biomarkers of developing AD brain pathology and facilitate the diagnostic process. The search for biofluid biomarkers, other than in CSF, and the development of biomarker assays have accelerated significantly and now represent the fastest-growing field in AD research. The goal of this study was to determine the differential enrichment of noncoding RNAs (ncRNAs) in plasma-derived extracellular vesicles (EV) of AD patients and Cognitively Normal controls (NC). Using RNA-seq, we profiled four significant classes of ncRNAs: miRNAs, snoRNAs, tRNAs, and piRNAs. We report a significant enrichment of SNORDs – a group of snoRNAs, in AD samples compared to NC. To verify the differential enrichment of two clusters of SNORDs – SNORD115 and SNORD116, localized on human chromosome 15q11-q13, we used plasma samples of an independent group of AD patients and NC. We applied ddPCR technique and identified SNORD115 and SNORD116 with a high discriminatory power to differentiate AD samples from NC. The results of our study present evidence that AD is associated with changes in the enrichment of SNORDs, transcribed from imprinted genomic loci, in plasma EV and provide a rationale to further explore the validity of those SNORDs as plasma biomarkers of AD.
Prognostic value of the level of gut microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: a meta-analysis and systematic review
Authors: Li-na Miao , Jian-peng Du , Ming Guo , Zhu-hong Chen , Hua Qu , Da-zhuo Shi
Published: May 2021

Aims

Intestinal microbial metabolite trimethylamine N-oxide (TMAO) is considered to be a key mediator between intestinal microbiota changes and heart failure (HF). Clinical evidences showed that patients with HF had relatively high level of plasma TMAO than those without. However, the relationship between plasma TMAO and the prognostics of patients with HF has not been investigated. This study aims to evaluate the relationship between plasma TMAO and the outcomes of patients with HF.

Methods and results

PubMed, EMBASE, Cochrane Library databases were included for systematic literature search. The included studies were used for the extraction of overall hazard ratios of adverse events data (myocardial infarction, cardiovascular hospitalization, cardiovascular mortality, revascularization and stroke) as well as all‐cause mortality data. Cochran’s Q test and I2 statistical methods were applied to assess heterogeneity. Selection of random effects model or fixed effects model were according to heterogeneity. Sensitivity analysis and subgroup analysis were used to find the source of heterogeneity. Among the 7 included studies, all studies published all‐cause mortality data and 6 provided adverse events. And the results demonstrated that higher level of plasma TMAO (defined according to original studies)was an indicator of risk of all‐cause mortality (HR =0.26, 95% CI: 0.20-0.32, I2 = 96.1%,) and risk of adverse events (HR =1.79, 95% CI: 1.37-2.22, I2 = 78.6%). There was no significant publication bias among the included studies (Egger’s,P = 0.130;Begg’s tests P = 0.452). Further subgroup analysis did not show that study location, follow-up time, or year of publication had any effect on the results. The results of sensitivity analysis do not indicate that any of the included affected the robustness of the results.

Conclusion

Heart failure patients with higher baseline plasma TMAO is a risk factor for all-cause mortality and adverse events.
Effects of recreational sports and combined training on blood pressure and glycosylated hemoglobin in middle-aged and older adults: a systematic review and meta-analysis
Authors: Schneider Vinícius Mallmann , Frank Paula , Fuchs Sandra C. , Ferrari Rodrigo
Published: May 2021

Background

Combined resistance and aerobic training (CT) is the most suitable form of exercise training to simultaneously improve cardiometabolic profile and functional capacity in middle-aged and older adults. Recreational sports (RS) emerge as an alternative to traditional exercises to improve these outcomes that could be used as a retention and continuity strategy, promoting health benefits associated with pleasure and satisfaction during the physical activity.

Objectives

The aim was to conduct a meta-analysis on the effects of RS and CT on systolic blood pressure (SBP), diastolic blood pressure (DBP) and glycosylated hemoglobin (HbA1c) in middle-aged and older adults and to compare these exercise interventions to a non-exercising control group (CON).

Data Sources

A literature search was conducted using the databases at PubMed, COCHRANE and SciELO between July and August 2020.

Study Eligibility Criteria

Studies that included men and women aged ≥45 years, healthy or with values of baseline for SBP ≥130mmHg or DBP ≥80 mmHg or with type II diabetes, in which the participants performed RS or CT versus CON, and evaluated SBP, DBP and HbA1c.

Study Appraisal and Synthesis Methods

Two independent reviewers screened search results, performed data extraction, and assessed of methodological quality of studies. Random effects modeling was used to compare pre-to post-intervention changes in BP and HbA1c from RS and CT versus CON, and the effect size were calculated through the weighted mean difference (MD) with a 95% confidence interval (CI).

Results

From 6017 records, 27 studies were included (9 RS and 18 CT interventions). The analysis included 1411 participants with 55 ± 8 years (range, 45–73 years). Overall, RS was associated reduction in SBP (MD: -7.20 mmHg; CI: -13.7 to -0.7) and DBP (MD: -3.6 mmHg; 95%CI: -6.6 to -0.5) versus CON. CT reduction SBP (MD: -3.6 mmHg; 95%CI: -5.2 to -2.0) and DBP (MD: -3.10 mmHg; 95%CI: -3.75 to -2.44) versus CON. RS not reduced HbA1c (MD: -0.24 %; CI: -0.53 to 0.06) versus CON. However, CT reduced HbA1c (MD: -0.47%; 95%CI: -0.67 to -0.27) versus CON.

Conclusions

RS and CT are effective exercise interventions to improve blood pressure in middle-aged and older adults. Additionally, CT seems to be an excellent strategy to reduce HbA1c, and future studies are necessary to confirm the effectiveness of recreational sports to improve HbA1c.

Systematic Review Registration Number

CRD42020207250

Key Points

Recreational sports promote similar or even greater blood pressure reduction when compared to traditional exercises.

Combined training promotes improvements in blood pressure and HbA1c in aging adults.

As alternative to traditional exercises, recreational sports emerge as an effective strategy to improve the cardiometabolic profile in middle-aged and older adults.
Extracorporeal membrane oxygenation in COVID-19 patients and in-hospital mortality: results from the Brazilian Registry using a propensity score matched analysis
Authors: Ponce Daniela , Marcolino Milena Soriano , Pires Magda Carvalho , de Carvalho Rafael Lima Rodrigues , Vianna Heloisa Reniers , Alves Nogueira Matheus Carvalho , Botoni Fernando Antonio , Graça Aranha Fernando , de Moura Costa André Soares , Vietta Giovanna Grunewald , Martins Graça Aranha Felipe Ferraz , Barbosa Lima Maria Clara Pontello , da Silva Etges Ana Paula Beck , de Sá Antonio Tolentino Nogueira , Oliveira Luana Martins , Polanczyk Carisi Anne
Published: May 2021

Around 5% of coronavirus disease 2019 (COVID-19) patients develop critical disease, with severe pneumonia and acute respiratory distress syndrome (ARDS). In these cases, extracorporeal membrane oxygenation (ECMO) may be considered when conventional therapy fails. This study aimed to assess the clinical characteristics and in-hospital outcomes of COVID-19 patients with ARDS refractory to standard lung-protective ventilation and pronation treated with ECMO support and to compare them to patients who did not receive ECMO. Patients were selected from the Brazilian COVID-19 Registry. At the moment of the analysis, 7,646 patients were introduced in the registry, eight of those received ECMO support (0.1%). The convenience sample of patients submitted to ECMO was compared to control patients selected by genetic matching for gender, age, comorbidities, pronation, ARDS and hospital, in a 5:1 ratio. From the 48 patients included in the study, eight received ECMO and 40 were matched controls. There were no significant differences in demographic, clinical and laboratory characteristics. Mortality was higher in the ECMO group (n = 7; 87.5%) when compared with controls (n = 17; 42.5%), (p=0.048). In conclusion, COVID 19 patients with ARDS refractory to conventional therapy who received ECMO support had worse outcomes to patients who did not receive ECMO. Our findings are not different from previous studies including a small number of patients, however there is a huge difference from Extracorporeal Life Support Organization results, which encourages us to keep looking for our best excellence.
Evaluation of the Weightage on Pain Management in Pharmacology Curricula of the Undergraduate Medical Program (MBBS) of Bangladesh
Authors: Ferdoush Jannatul , Johora Fatema , Jeenia Fatiha Tasmin , Momtaz Tashfia , Towfiq Hossain Sharif Mohammad , Sadia Halima , Abbasy Asma Akter , Rahman Md. Sayedur
Published: May 2021

Background

Prioritizing problem-oriented undergraduate medical education is paramount to adequate management of pain in real life scenarios. The present research was conducted with an attempt to explore the important baseline information for pain medicine education and evaluation within undergraduate pharmacology curricula in Bangladesh.

Materials and methods

This descriptive cross-sectional study evaluates the curriculum (pharmacology portion of undergraduate medical curriculum), and written question (SAQ) of MBBS Examination of last ten years extending from January 2010 to November,2019 of all 7 universities offering MBBS degree. The evaluation was conducted through searching certain key phrases.

Result

In Pharmacology & Therapeutics portion of the curriculum, only 4 hours and 2 hours are allocated to discuss pain management in lecture and tutorial respectively. In the study period, average marks allocated in pharmacology written question papers was 4.4 (SD = 2.7) and the difference among studied universities was not significant (p value 0.7).

Conclusion

Allocated time in the curriculato teach pain management is very low and weightage received in assessment is also inadequate. Education on pain medication as well as management should receive more emphasis.
Unified real-time environmental-epidemiological data for multiscale modeling of the COVID-19 pandemic
Authors: Badr Hamada S. , Zaitchik Benjamin F. , Kerr Gaige H. , Nguyen Nhat-Lan H. , Chen Yen-Ting , Hinson Patrick , Colston Josh M. , Kosek Margaret N. , Dong Ensheng , Du Hongru , Marshall Maximilian , Nixon Kristen , Mohegh Arash , Goldberg Daniel L. , Anenberg Susan C. , Gardner Lauren M.
Published: May 2021

An impressive number of COVID-19 data catalogs exist. None, however, are optimized for data science applications, e.g., inconsistent naming and data conventions, uneven quality control, and lack of alignment between disease data and potential predictors pose barriers to robust modeling and analysis. To address this gap, we generated a unified dataset that integrates and implements quality checks of the data from numerous leading sources of COVID-19 epidemiological and environmental data. We use a globally consistent hierarchy of administrative units to facilitate analysis within and across countries. The dataset applies this unified hierarchy to align COVID-19 case data with a number of other data types relevant to understanding and predicting COVID-19 risk, including hydrometeorological data, air quality, information on COVID-19 control policies, and key demographic characteristics.
SARS CoV-2 variant B.1.617.1 is highly pathogenic in hamsters than B.1 variant
Authors: Yadav Pragya D. , Mohandas Sreelekshmy , Shete Anita M , Nyayanit Dimpal A , Gupta Nivedita , Patil Deepak Y. , Sapkal Gajanan N. , Potdar Varsha , Kadam Manoj , Kumar Abhimanyu , Kumar Sanjay , Suryavanshi Deepak , Mote Chandrashekhar S. , Abraham Priya , Panda Samiran , Bhargava Balram
Published: May 2021

Background

The recent emergence of new SARS-CoV-2 lineage B.1.617 in India has been associated with a surge in the number of daily infections. This variant has combination of specific mutations L452R, E484Q and P681R reported to possibly enhance the transmissibility with likelihood of escaping the immunity. We investigated the viral load and pathogenic potential of B.1.617.1 in Syrian golden hamsters.

Methods

Two groups of Syrian golden hamsters (9 each) were inoculated intranasally with SARS CoV-2 isolates, B.1 (D614G) and B.1.617.1 respectively. The animals were monitored daily for the clinical signs and body weight. The necropsy of three hamsters each was performed on 3, 5- and 7-days post-infection (DPI). Throat swab (TS), nasal wash (NW) and organ samples (lungs, nasal turbinate, trachea) were collected and screened using SARS-CoV-2 specific Real-time RT-PCR.

Results

The hamsters infected with B.1.617.1 demonstrated increased body weight loss compared to B.1 variant. The highest viral load was observed in nasal turbinate and lung specimens of animals infected with B.1.167.1 on 3 DPI. Neutralizing antibody (NAb) and IgG response in hamsters of both the groups were observed from 5 and 7 DPI respectively. However, higher neutralizing antibody titers were observed against B.1.167.1. Gross pathology showed pronounced lung lesions and hemorrhage with B.1.671 compared to B.1.

Conclusions

B.1617.1 and B.1 variant varied greatly in their infectiousness, pathogenesis in hamster model. This study demonstrates higher pathogenicity in hamsters evident with reduced body weight, higher viral load in lungs and pronounced lung lesions as compared to B.1 variant.

B.1.617.1 is the new SARS-CoV-2 lineage that emerged in India. Maximal body weight loss and higher viral load in hamsters infected with B.1.617.1. It caused pronounced lung lesions in hamsters compared to B.1 variant which demonstrates the pathogenic potential of B.1.617.1.
Manipulation of carotenoid metabolism stimulates biomass and stress tolerance in tomato
Authors: Vallarino Jose G. , Mi Jianing , Petřík Ivan , Novák Ondřej , Correa Sandra M. , Kosmacz Monika , Havaux Michel , Rodriguez-Concepcion Manuel , Al-Babili Salim , Fernie Alisdair R. , Skirycz Aleksandra , Moreno Juan C.
Published: May 2021

Improving yield, nutritional value and tolerance to abiotic stress are major targets of current breeding and biotechnological approaches that aim at increasing crop production and ensuring food security. Metabolic engineering of carotenoids, the precursor of Vitamin-A and plant hormones that regulate plant growth and response to adverse growth conditions, has been mainly focusing on provitamin A biofortification or the production of high-value carotenoids. Here, we show that the introduction of a single gene of the carotenoid biosynthetic pathway in different tomato cultivars simultaneously improved photosynthetic capacity and tolerance to various abiotic stresses (e.g., high light, salt, and drought), caused an up to 77% fruit yield increase and enhanced fruit’s provitamin A content and shelf life. Our findings pave the way for developing a new generation of crops that combine high productivity and increased nutritional value with the capability to cope with climate change-related environmental challenges.
Optimized Quantification of Intrahost Viral Diversity in SARS-CoV-2 and Influenza Virus Sequence Data
Authors: Roder AE , Johnson KEE , Knoll M , Khalfan M , Wang B , Schultz-Cherry S , Banakis S , Kreitman A , Mederos C , Youn J-H , Mercado R , Wang W , Ruchnewitz D , Samanovic MI , Mulligan MJ , Lassig M , Łuksza M , Das S , Gresham D , Ghedin E
Published: May 2021

High error rates of viral RNA-dependent RNA polymerases lead to diverse intra-host viral populations during infection. Errors made during replication that are not strongly deleterious to the virus can lead to the generation of minority variants. However, accurate detection of minority variants in viral sequence data is complicated by errors introduced during sample preparation and data analysis. We used synthetic RNA controls and simulated data to test seven variant calling tools across a range of allele frequencies and simulated coverages. We show that choice of variant caller, and use of replicate sequencing have the most significant impact on single nucleotide variant (SNV) discovery and demonstrate how both allele frequency and coverage thresholds impact both false discovery and false negative rates. We use these parameters to find minority variants in sequencing data from SARS-CoV-2 clinical specimens and provide guidance for studies of intrahost viral diversity using either single replicate data or data from technical replicates. Our study provides a framework for rigorous assessment of technical factors that impact SNV identification in viral samples and establishes heuristics that will inform and improve future studies of intrahost variation, viral diversity, and viral evolution.

IMPORTANCE

When viruses replicate inside a host, the virus replication machinery makes mistakes. Over time, these mistakes create mutations that result in a diverse population of viruses inside the host. Mutations that are neither lethal to the virus, nor strongly beneficial, can lead to minority variants that are minor members of the virus population. However, preparing samples for sequencing can also introduce errors that resemble minority variants, resulting in inclusion of false positive data if not filtered correctly. In this study, we aimed to determine the best methods for identification and quantification of these minority variants by testing the performance of seven commonly used variant calling tools. We used simulated and synthetic data to test their performance against a true set of variants, and then used these studies to inform variant identification in data from clinical SARS-CoV-2 clinical specimens. Together, analyses of our data provide extensive guidance for future studies of viral diversity and evolution.
The division defect of aBacillus subtilis minD nocdouble mutant can be suppressed by Spx-dependent and Spx-independent mechanisms
Authors: Yu Yuanchen , Dempwolff Felix , Oshiro Reid T. , Gueiros-Filho Frederico J. , Jacobson Stephen C. , Kearns Daniel B.
Published: May 2021

During growth, bacteria increase in size and divide. Division is initiated by the formation of the Z-ring, an intense ring-like cytoskeletal structure formed by treadmilling protofilaments of the tubulin homolog FtsZ. FtsZ localization is thought to be controlled by the Min and Noc systems, and here, we explore why cell division fails at high temperature when the Min and Noc systems are simultaneously mutated. Microfluidic analysis of aminD nocdouble mutant indicated that FtsZ formed proto-Z-rings at periodic inter-chromosome locations but that the rings failed to mature and become functional. Extragenic suppressor analysis indicated that a variety of mutations restored high temperature growth to theminD nocdouble mutant, and while many were likely pleiotropic, others implicated the proteolysis of the transcription factor Spx. Further analysis indicated that a Spx-dependent pathway activated the expression of ZapA, a protein that primarily compensates for the absence of Noc. Additionally, an Spx-independent pathway increased the activity of the divisome to reduce the length of the cytokinetic period. Finally, we provide evidence of an as-yet-unidentified protein that is activated by Spx and governs the frequency of polar division and minicell formation.

IMPORTANCE

Bacteria must properly position the location of the cell division machinery in order to grow, divide, and ensure each daughter cell receives one copy of the chromosome. InB. subtilis, cell division site selection is thought to depend on two systems called Min and Noc, and while neither is individually essential, cells fail to grow at high temperature when both are mutated. Here, we show that cell division fails in the absence of Min and Noc, not due to a defect in FtsZ localization, but rather a failure in the maturation of the cell division machinery. To understand what happens when the division machinery fails to mature, suppressor mutations that bypass the need for Min, Noc, or both were selected. Some of the mutants activated the Spx stress response pathway while others appeared to directly enhance divisome activity.
Insights into the L3 to L4 developmental program through proteomics
Authors: Bennuru Sasisekhar , Meng Zhaojing , McKerrow James , Lustigman Sara , Nutman Thomas B
Published: May 2021

The establishment of infection with the lymphatic dwelling filarial parasites is dependent on the infectivity and subsequent development of the infective larvae (L3) within the human host to later stages (L4, adults) that require several developmental molts. The molecular mechanisms underlying the developmental processes in parasitic nematodes are not clearly defined. We report the proteomic profiles throughout the entire L3 to L4 molt using an establishedin vitromolting process for the human pathogenB. malayi. A total of 3466 proteins ofB. malayiand 54 fromWolbachiawere detected at one or more time points. Based on the proteomic profiling, the L3 to L4 molting proteome can be broadly divided into an early, middle and late phase. Enrichment of proteins, protein families and functional categories between each time point or between phases primarily relate to energy metabolism, immune evasion through secreted proteins, protein modification, and extracellular matrix-related processes involved in the development of new cuticle. Comparative analyses with somatic proteomes and transcriptomes highlighted the differential usage of cysteine proteinases (CPLs), BmCPL-1, -4 and -5 in the L3-L4 molt compared to the adults and microfilariae. Inhibition of the CPLs effectively blocked thein-vitroL3 to L4 molt. Overall, only 4Wolbachiaproteins (Wbm0495, Wbm0793, Wbm0635, and Wbm0786) were detected across all time points and suggest that they play an inconsequential role in the early developmental process.

Importance

The neglected tropical diseases of lymphatic filariasis, onchocerciasis (or river blindness), and loiasis are the three major filarial infections of humans that cause long-term disability, impaired childhood growth, reduced reproductive capacity. Global efforts to control and/or eliminate these infections as a public health concern are based on strategies and tools to strengthen the diagnostics, therapeutic and prophylactic measures. A deeper understanding of the genes, proteins and pathways critical for the development of the parasite is needed to help further investigate the mechanisms of parasite establishment and disease progression, because not all the transmitted infective larvae get to develop successfully and establish infections. The significance of this study is in identifying the proteins and the pathways that are needed by the parasite for successful developmental molts, that in turn will allow for investigating targets of therapeutic and prophylactic potential.
Protistan plankton communities in the Galápagos Archipelago respond to changes in deep water masses resulting from the 2015/16 El Niño
Authors: Neave Erika F. , Seim Harvey , Gifford Scott , Torano Olivia , Johnson Zackary I. , Páez-Rosas Diego , Marchetti Adrian
Published: May 2021

The Galápagos Archipelago lies within the eastern equatorial Pacific Ocean at the convergence of major ocean currents that are subject to changes in circulation. The nutrient-rich Equatorial Undercurrent upwells from the west onto the Galápagos platform, stimulating primary production, but this source of deep water weakens during El Niño events. From measurements collected on repeat cruises, the 2015/16 El Niño was associated with declines in phytoplankton biomass at most sites throughout the archipelago and reduced utilization of nitrate, particularly in large-sized phytoplankton in the western region. Protistan assemblages were identified by sequencing the V4 region of the 18S rRNA gene. Dinoflagellates, chlorophytes, and diatoms dominated most sites. Shifts in dinoflagellate communities were most apparent between the years; parasitic dinoflagellates,Syndiniales, were highly detected during the El Niño (2015) while the dinoflagellate genus,Gyrodiniumdominated many sites during the neutral period (2016). Variations in protistan communities were most strongly correlated with changes in subthermocline water density. These findings indicate that marine protistan communities in this region are regimented by deep water mass sources and thus could be profoundly affected by altered ocean circulation.
CommensalStreptococcus mitisproduces two different lipoteichoic acids of type I and type IV
Authors: Gisch Nicolas , Peters Katharina , Thomsen Simone , Vollmer Waldemar , Schwudke Dominik , Denapaite Dalia
Published: May 2021

The opportunistic pathogenStreptococcus mitispossesses, like other members of the Mitis group of viridans streptococci, phosphorylcholine (P-Cho)-containing teichoic acids (TAs) in its cell wall. Bioinformatic analyses predicted the presence of TAs that are almost identical with those identified in the pathogenS. pneumoniae, but a detailed analysis ofS. mitislipoteichoic acid (LTA) was not performed to date. Here we determined the structures of LTA from twoS. mitisstrains, the high-level beta-lactam and multiple antibiotic resistant strain B6 and the penicillin-sensitive strain NCTC10712. In agreement with bioinformatic predictions we found that the structure of one LTA (type IV) was like pneumococcal LTA, except the exchange of a glucose moiety with a galactose within the repeating units. Further genome comparisons suggested that the majority ofS. mitisstrains should contain the same type IV LTA asS. pneumoniae, providing a more complete understanding of the biosynthesis of theseP-Cho-containing TAs in members of the Mitis group of streptococci. Remarkably, we observed besides type IV LTA an additional polymer belonging to LTA type I in both investigatedS. mitisstrains. This LTA consists of β-galactofuranosyl-(1,3)-diacylglycerol as glycolipid anchor and a poly-glycerol-phosphate chain at theO-6 position of the furanosidic galactose. Hence, these bacteria are capable of synthesizing two different LTA polymers, most likely produced by distinct biosynthesis pathways. Our bioinformatics analysis revealed the prevalence of the LTA synthase LtaS, most probably responsible for the second LTA version (type I), amongstS. mitisandS. pseudopneumoniaestrains.
Direct comparison of contralateral bias and face/scene selectivity in human occipitotemporal cortex
Authors: Silson Edward H , Groen Iris I A , Baker Chris I
Published: May 2021

Human visual cortex is organised broadly according to two major principles: retinotopy (the spatial mapping of the retina in cortex) and category-selectivity (preferential responses to specific categories of stimuli). Historically, these principles were considered anatomically separate, with retinotopy restricted to the occipital cortex and category-selectivity emerging in the lateral-occipital and ventral-temporal cortex. However, recent studies show that category-selective regions exhibit systematic retinotopic biases, for example exhibiting stronger activation for stimuli presented in the contra- compared to the ipsilateral visual field. It is unclear, however, whether responseswithincategory-selective regions are more strongly driven by retinotopic location or by category preference, and if there are systematic differencesbetweencategory-selective regions in the relative strengths of these preferences. Here, we directly compare contralateral and category preferences by measuring fMRI responses to scene and face stimuli presented in the left or right visual field and computing two bias indices: a contralateral bias (response to the contralateral minus ipsilateral visual field) and a face/scene bias (preferred response to scenes compared to faces, or vice versa). We compare these biases within and between scene- and face-selective regions and across the lateral and ventral surfaces of visual cortex more broadly. We find an interaction between surface and bias: lateral surface regions show a stronger contralateral than face/scene bias, whilst ventral surface regions show the opposite. These effects are robust across and within subjects, and appear to reflect large-scale, smoothly varying gradients. Together, these findings support distinct functional roles for lateral and ventral visual cortex in terms of the relative importance of the spatial location of stimuli during visual information processing.
Host adaptation through hybridization: Genome analysis of triticale powdery mildew reveals unique combination of lineage-specific effectors
Authors: Müller Marion C. , Kunz Lukas , Graf Johannes , Schudel Seraina , Keller Beat
Published: May 2021

The emergence of new fungal pathogens through hybridization represents a serious challenge for agriculture. Hybridization between the wheat mildew (Blumeria graminis f.sp. tritici) and rye mildew (B.g. f.sp. secalis) pathogens have led to the emergence of a new mildew form (B.g. f.sp. triticale) growing on triticale, a man-made amphiploid crop derived from crossing rye and wheat which was originally resistant to the powdery mildew disease. The identification of the genetic basis of host-adaptation in triticale mildew has been hampered by the lack of a reference genome. Here we report the 141.4 Mb reference assembly ofB.g. triticaleisolate THUN-12 derived from long-read sequencing and genetic map-based scaffolding. All elevenB.g. triticalechromosomes were assembled from telomere-to-telomere and revealed that 19.7% of the hybrid genome was inherited from the rye mildew parental lineage. We identified lineage-specific regions in the hybrid, inherited from the rye or wheat mildew parental lineages, that harbour numerous bona fide candidate effectors. We propose that the combination of lineage-specific effectors in the hybrid genome is crucial for host-adaptation, allowing the fungus to simultaneously circumvent the immune systems contributed by wheat and rye in the triticale crop. In line with this we demonstrate the functional transfer of theSvrPm3effector from wheat to triticale mildew, a virulence effector that specifically suppresses resistance of the wheatPm3allelic series. This transfer is the likely underlying cause for the observed poor effectiveness of severalPm3alleles against triticale mildew and exemplifies the negative implications of pathogen hybridizations on resistance breeding.
The influence of the respiratory cycle on reaction times in sensory-cognitive paradigms
Authors: Johannknecht Michelle , Kayser Christoph
Published: May 2021

Behavioural and electrophysiological studies point to widespread influence of the state of respiration on brain activity and cognitive performance. Still, the prevalence and relevance of such respiratory-behavioural relations in typical sensory-cognitive tasks remain unclear. We here used a battery of six tasks probing sensory detection, discrimination and short-term memory to address the questions of whether and by how much behaviour covaries with the respiratory cycle. Our results show that participants tended to align their respiratory cycle to the experimental paradigm. Furthermore, their reaction times, but not so much their response accuracy, consistently and significantly covaried with the respiratory cycle, and this effect was strongest when analyzed contingent on the respiratory state at participants’ responses. The respective effect sizes where comparable to those seen in many typical neurocognitive experimental manipulations. These results support a prominent relation between respiration and sensory-cognitive function and suggest that sensation is intricately linked to rhythmic bodily or interoceptive functions.
Squeegee: de-novo identification of reagent and laboratory induced microbial contaminants in low biomass microbiomes
Authors: Liu Yunxi , Elworth R. A. Leo , Jochum Michael D. , Aagaard Kjersti M. , Treangen Todd J.
Published: May 2021

Computational analysis of host-associated microbiomes has opened the door to numerous discoveries relevant to human health and disease. However, contaminant sequences in metagenomic samples can potentially impact the interpretation of findings reported in microbiome studies, especially in low biomass environments. Our hypothesis is that contamination from DNA extraction kits or sampling lab environments will leave taxonomic “bread crumbs” across multiple distinct sample types, allowing for the detection of microbial contaminants when negative controls are unavailable. To test this hypothesis we implemented Squeegee, ade novocontamination detection tool. We tested Squeegee on simulated and real low biomass metagenomic datasets. On the low biomass samples, we compared Squeegee predictions to experimental negative control data and show that Squeegee accurately recovers known contaminants. We also analyzed 749 metagenomic datasets from the Human Microbiome Project and identified likely previously unreported kit contamination. Collectively, our results highlight that Squeegee can identify microbial contaminants with high precision. Squeegee is open-source and available at:https://gitlab.com/treangenlab/squeegee
Limacus flavusyellow slug: bioactive molecules in the mucus
Authors: Hayashida Patricia Yumi , da Silva Júnior Pedro Ismael
Published: May 2021

Background

Snails and slugs were used as a treatment for many health problems therefore ancient times. Since the antimicrobial resistance became a major global thread, antimicrobial peptides have been considered as a potential source for development of new drugs, especially for drug-resistant bacteria. Nowadays reports confirm that the mucous secretions have antimicrobial, antiviral and antifungal properties.

Methods

The present study has the objective to characterize and evaluate antimicrobial peptides ofLimacus flavusmucus. The mucus was obtained by thermal shock and submitted to RP-HPLC. Fractions were used to perform the antimicrobial activity and hemolytic assays, electrophoresis (SDS-Page Gel) and submitted to mass spectrometry (LC-MS / MS). Identification and characterization was performed by PeaksX+ software. The physicochemical parameters were evaluated with bioinformatics tools, which predicted water solubility, iso-electric point, charge net and its primary structure.

Results

Three fractions were isolated from the mucus ofL. flavusand presented antifungal and antibacterial activity. The mucus showed greater inhibition for filamentous fungi (Aspergillus niger), yeast (Cryptococcus neoformans), Gram positive bacteria (Bacillus subtilis, Micrococcus luteus) and Gram negative bacteria (Enterobacter cloacae). These fractions also did not show hemolytic activity for human blood cells (erythrocytes). Fraction’s sequences were identified and presents Mw <3kDa, WLGH, DLQW, YLRW, respectively.

Conclusion

This study revealed three antimicrobial peptides ofL. flavusmucus with a wide range of antimicrobial activity and its physic-chemical characterization.
From theory to experiment and back again — Challenges in quantifying a trait-based theory of predator-prey dynamics
Authors: Wootton K. L. , Curtsdotter Alva , Jonsson Tomas , Banks H.T. , Bommarco Riccardo , Roslin Tomas , Laubmeier A. N.
Published: May 2021

Food webs map feeding interactions among species, providing a valuable tool for understanding and predicting community dynamics. Trait-based approaches to food webs are increasingly popular, using e.g. species’ body sizes to parameterize dynamic models. Although partly successful, models based on body size often cannot fully recover observed dynamics, suggesting that size alone is not enough. For example, differences in species’ use of microhabitat or non-consumptive effects of other predators may affect dynamics in ways not captured by body size.

Here, we report on the results of a pre-registered study (Laubmeier et al., 2018) where we developed a dynamic food-web model incorporating body size, microhabitat use, and non-consumptive predator effects and used simulations to optimize the experimental design. Now, after performing the mesocosm experiment to generate empirical time-series of insect herbivore and predator abundance dynamics, we use the inverse method to determine parameter values of the dynamic model. We compare four alternative models with and without microhabitat use and non-consumptive predator effects. The four models achieve similar fits to observed data on herbivore population dynamics, but build on different estimates for the same parameters. Thus, each model predicts substantially different effects of each predator on hypothetical new prey species. These findings highlight the imperative of understanding the mechanisms behind species interactions, and the relationships mediating the effects of traits on trophic interactions. In particular, we believe that increased understanding of the estimates of optimal predator-prey body-size ratios and maximum feeding rates will improve future predictions. In conclusion, our study demonstrates how iterative cycling between theory, data and experiment may be needed to hone current insights into how traits affect food-web dynamics.