bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct age-specific SARS-CoV-2 IgG decay kinetics following natural infection
Authors: Sjaarda Calvin P , Moslinger Emily , Tozer Kyla , Colautti Robert I. , Kheitan Samira , Meurant Robyn , Cleaf Stefanie Van , Ardakani Ali , Bosnjak Oliver , Ghaffari Abdi , Sheth Prameet M
Published: August 2021

Background

Antibody responses to SARS-CoV-2 can be observed as early as 14 days post-infection, but little is known about the stability of antibody levels over time. Here we evaluate the long-term stability of anti-SARS-CoV-2 IgG antibodies following infection with SARS-CoV-2 in 402 adult donors.

Methods

We performed a multi-center study carried out at Plasma Donor Centers in the city of Heidelberg (Plasmazentrum Heidelberg, Germany) and Munich (Plasmazentrum München, Germany). We present anti-S/N and anti-N IgG antibody levels in prospective serum samples collected up to 403 days post recovery from SARS-CoV-2 infected individuals.

Results

The cohort includes 402 adult donors (185 female, 217 male; 17 - 68 years of age) where anti-SARS-CoV-2 IgG levels were measured in plasma samples collected between 18- and 403-days post SARS-CoV-2 infection. A linear mixed effects model demonstrated IgG decay rates that decrease over time (χ2=176.8, p<0.00001) and an interaction of time*age χ (χ2=10.0, p<0.005)), with those over 60+ years showing the highest baseline IgG levels and the fastest rate of IgG decay. Baseline viral neutralization assays demonstrated that serum IgG levels correlated within vitroneutralization capacity in 91% of our cohort.

Conclusion

Long-term antibody levels and age-specific antibody decay rates suggest the potential need for age-specific vaccine booster guidelines to ensure long term vaccine protection against SARS-CoV-2 infection.
Recording of “COVID-19 vaccine declined” among vaccination priority groups: a cohort study on 57.9 million NHS patients’ primary care records in situ using OpenSAFELY
Authors: Curtis Helen J , Inglesby Peter , MacKenna Brian , Croker Richard , Hulme William , Rentsch Christopher T , Bhaskaran Krishnan , Walker Alex J , Morton Caroline E , Evans David , Mehrkar Amir , Bacon Seb , Bates Chris , Hickman George , Ward Tom , Morley Jessica , Cockburn Jonathan , Davy Simon , Schultze Anna , Williamson Elizabeth , McDonald Helen I , Tomlinson Laurie , Mathur Rohini , Eggo Rosalind M , Wing Kevin , Wong Angel YS , Forbes Harriet , Tazare John , Parry John , Hester Frank , Harper Sam , O’Hanlon Shaun , Eavis Alex , Jarvis Richard , Avramov Dima , Griffiths Paul , Fowles Aaron , Parkes Nasreen , Evans Stephen JW , Douglas Ian J , Smeeth Liam , Goldacre Ben
Published: August 2021

Background

All patients in England within vaccine priority groups were offered a COVID-19 vaccine by mid-April 2021. Clinical record systems contain codes to denote when such an offer has been declined by a patient (although these can in some cases be entered for a variety of other reasons including vaccination delay, or other administrative issues). We set out to describe the patterns of usage of codes for COVID-19 vaccines being declined.

Methods

With the approval of NHS England and using the full pseudonymised primary care records for 57.9 million NHS patients, we identified all patients in key vaccine priority groups: aged over 50, or over 16 and at increased risk from COVID-19 (Clinically Extremely Vulnerable [CEV] or otherwise “at risk”). We describe the proportion of patients recorded as declining a COVID-19 vaccination for each priority group, and by other clinical and demographic factors; whether patients recorded as “declined” subsequently went on to receive a vaccination; and the distribution of code usage across GP practices.

Results

Of 24.5 million patients in priority groups as of May 25th 2021, 89.2% had received a vaccine, 8.8% had neither a vaccination nor a decline recorded, and 663,033 (2.7%) had a decline code recorded. Of patients with a recorded decline, 125,587 (18.9%) were subsequently vaccinated. Subsequent vaccination was slightly more common in the South Asian population than other ethnicities (e.g. 32.3% vs 22.8%, over 65s). The proportion of declining-unvaccinated patients varied strongly with ethnicity (Black 15.3%, South Asian 5.6%, White 1.5% in over 80s); and was higher in patients from more deprived areas. COVID-19 vaccine decline codes were present in almost all practices (98.8%), but with wide variation between practices in rates of usage. Among all priority groups, declining-unvaccinated status was most common in CEV (3.3%).

Conclusions

Clinical codes indicative of COVID-19 vaccinations being declined are widely used in English general practice. They are substantially more common among Black and South Asian patients, and patients from more deprived areas. There is a need for more detailed survey and/or qualitative research with patients and clinicians to determine the most common reasons for these recorded declines.
Megakaryocytes are a Novel SARS-CoV-2 Infection Target and Risk Factor for Mortality and Multi-Organ Failure
Authors: Fortmann Seth D. , Patton Michael J. , Frey Blake F. , Vieira Cristiano P. , Reddy Sivani B. , Huls Forest , Crouse Andrew , Floyd Jason , Prasad Ram , Hanumanthu Vidya Sagar , Sterrett Sarah , Zucker Jeremy D. , Li Peng , Erdmann Nathan , Goepfert Paul A. , Gaggar Amit , Grant Maria B. , Might Matthew
Published: August 2021

Discovery of a biomarker for patients at high risk of progression to severe Coronavirus Disease 2019 (COVID-19) is critical for clinical management, particularly in areas of the world where widespread vaccine distribution and herd immunity have yet to be achieved. Herein, we characterize peripheral blood from 218 COVID-19 patients with flow cytometry and provide evidence that megakaryocytes are a target for infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We demonstrate a positive correlation between infected megakaryocytes expressing the protein calprotectin (also called S100A8/A9), a known marker of COVID-19 severity. Additionally, we show that infected, calprotectin expressing megakaryocytes are correlated with COVID-19 severity and are a prognostic indicator of 30-day clinical outcomes including respiratory failure, thrombotic events, acute kidney injury (AKI), ICU admission, and mechanical ventilation. These findings represent a novel SARS-CoV-2 infection target with significant clinical implications as a biomarker for clinical outcomes associated with severe COVID-19.
Estimation of Total Immunity to SARS-CoV-2 in Texas
Authors: Desantis Stacia M. , León-Novelo Luis G. , Swartz Michael D. , Yaseen Ashraf S. , Valerio Melissa A. , Brito Frances A. , Ross Jessica A. , Kohl Harold W. , Messiah Sarah E. , Kelder Steve H. , Wu Leqing , Zhang Shiming , Aguillard Kimberly A. , Gonzalez Michael O. , Omega-Njemnob Onyinye S. , Breaux Camille J. , Lakey David L , Shuford Jennifer A. , Pont Stephen , Boerwinkle Eric D
Published: August 2021

Given the underestimate of seroprevalence in the US due to insufficient testing, accurate estimates of population immunity to SARS-CoV-2 or vaccinations do not exist. Although model-based estimates have been proposed, they require inputting unknown parameters such as viral reproduction number, longevity of immune response, and other dynamic factors. In contrast to a model-based approach for estimating population immunity, or simplistic summing of natural- and vaccine-induced immunity, the current study presents a data-driven statistical procedure for estimating the total immunity rate in a region using prospectively collected serological data along with state-level vaccination data. We present a detailed procedure so that efforts can be replicated regionally to inform policy-making decisions relevant to SARS-CoV-2. Specifically, we conducted a prospective longitudinal statewide cohort serological survey with 10,482 participants and more than 14,000 blood samples beginning on September 30, 2020. Along with Department of State Health Services vaccination data, as of July 4, 2021, the estimated percentage of those with naturally occurring antibodies to SARS-CoV-2 in Texas is 35.3% (95% CI = (33.7%, 36.9%) and total estimated immunity is 69.1%. We conclude the seroprevalence of SARS-CoV-2 is 4 times higher than the state-confirmed COVID-19 cases (8.8%). This methodology is integral to pandemic preparedness.
Three-dimensional cephalometric landmarking and Frankfort horizontal plane construction: reproducibility of conventional and novel landmarks
Authors: Dot Gauthier , Rafflenbeul Frédéric , Kerbrat Adeline , Rouch Philippe , Gajny Laurent , Schouman Thomas
Published: August 2021

In some dentofacial deformity patients, especially patients undergoing surgical ortho-dontic treatments, Computed Tomography (CT) scans are useful to assess complex asymmetry or to plan orthognathic surgery. This assessment would be made easier for orthodontists and sur-geons with a three-dimensional (3D) cephalometric analysis, which would require the localiza-tion of landmarks and the construction of reference planes. The objectives of this study were to assess manual landmarking repeatability and reproducibility (R&R) of a set of 3D landmarks and to evaluate R&R of vertical cephalometric measurements using two Frankfort Horizontal (FH) planes as references for horizontal 3D imaging reorientation. Thirty-three landmarks, di-vided into “conventional”, “foraminal” and “dental”, were manually located twice by 3 experi-enced operators on 20 randomly-selected CT scans of orthognathic surgery patients. R&R confi-dence intervals (CI) of each landmark in the -x, -y and -z directions were computed according to the ISO 5725 standard. These landmarks were then used to construct 2 FH planes: a conventional FH plane (orbitale left, porion right and left) and a newly proposed FH plane (midinternal acous-tic foramen, orbitale right and left). R&R of vertical cephalometric measurements were computed using these 2 FH planes as horizontal references for CT reorientation. Landmarks showing a 95% CI of repeatability and/or reproducibility > 2mm were found exclusively in the “conventional” landmarks group. Vertical measurements showed excellent R&R (95% CI < 1mm) with either FH plane as horizontal reference. However, the 2 FH planes were not found to be parallel (absolute angular difference of 2.41°, SD 1.27°). Overall, “dental” and “foraminal” landmarks were more reliable than the “conventional” landmarks. Despite the poor reliability of the landmarks orbitale and porion, the construction of the conventional FH plane provided a reliable horizontal reference for 3D craniofacial CT scan reorientation.
Systematic review protocol exploring the impact of the COVID-19 pandemic on the wellbeing of general practitioners
Authors: Jefferson L. , Golder S. , Dale V. , Essex H. , McHugh E. , Bloor K.
Published: August 2021

Background

Over recent years chronic stress and burnout have been reported by doctors working in general practice in the UK NHS and internationally. The COVID-19 pandemic has changed general practitioners’ working lives – adding potential pressures from avoiding infection and addressing pent-up demand for care, but also changing processes such as rapidly taking up remote consultations. To date, there has been a focus on exploring the impact of the pandemic on the wellbeing of hospital clinicians. No registered systematic reviews currently focus on exploring the impact of the pandemic on the mental health and wellbeing of general practitioners.

Aims and objectives

To synthesise the current international evidence base exploring the impact of COVID-19 on the mental health and wellbeing of general practitioners, and which factors are associated with their reported mental health and wellbeing during the pandemic.

Methods

In this paper we report a systematic review protocol, following PRISMA guidance. In our search strategy we will identify primary research studies or systematic reviews exploring the mental health and wellbeing of general practitioners during the COVID-19 pandemic in four databases (MEDLINE, Embase, PsychInfo and Medrxiv) and Google Scholar. We will hand-search reference lists and grey literature.

Two reviewers will undertake all stages including study selection, data extraction and quality assessment, with arbitration by a third reviewer where necessary. We will use standardised quality assessment tools to ensure transparency and reduce bias in quality assessment. Depending on the quality of included studies, we may undertake a sensitivity analysis by excluding studies from narrative synthesis that are rated as low quality using the checklists.

We will describe the findings across studies using narrative thematic data synthesis, and if sufficiently homogenous data are identified, we will pool quantitative findings through meta-analysis.
COVID-19 vaccination coverage and hesitancy among Australians with disability and long-term health conditions
Authors: Aitken Zoe , Emerson Eric , Kavanagh Anne
Published: August 2021

Background

COVID-19 vaccination is the cornerstone of managing Australia’s COVID-19 pandemic and the success of the vaccination program depends on high vaccination coverage. This paper examined differences in COVID-19 vaccination coverage and vaccine hesitancy for people with disability, long-term health conditions, and carers – subgroups that were prioritised in the vaccination program.

Methods

Using data from 2,400 Australians who participated in two waves of the Taking the Pulse of the Nation survey in April and May 2021, we described vaccination coverage and hesitancy among people with disability, severe mental health conditions, severe long-term health conditions, frequent need for assistance with everyday activities, and carers, disaggregated by age group and gender.

Findings

Vaccination coverage was estimated to be 8.2% in the sample overall and was similar for people with disability, those with frequent need for assistance, and carers. It was higher for people with severe long-term health conditions (13.4%) and lower for people with severe mental health conditions (4.3%). Vaccine hesitancy was high overall (35.6%) and was similarly high across the priority groups.

Interpretation

This study highlights the lack of a difference in vaccination coverage and vaccine hesitancy for people with disability, long-term health conditions, and carers compared to the general population. Sub-optimal vaccination coverage for people in the priority population groups leaves many people at significant risk of serious disease or death if exposed to COVID-19, particularly in light of the easing of disease-control restrictions across Australia and the emergence of new COVID-19 variants.

Funding

National Health and Medical Research Council
The unique evolutionary dynamics of the SARS-CoV-2 Delta variant
Authors: Stern Adi , Fleishon Shay , Kustin Talia , Dotan Edo , Mandelboim Michal , Erster Oran ,   Israel Consortium of SARS-CoV-2 sequencing, Mendelson Ella , Mor Orna , Zuckerman Neta S.
Published: August 2021

The SARS-Coronavirus-2 (SARS-CoV-2) driven pandemic was first recognized in late 2019, and the first few months of its evolution were relatively clock-like, dominated mostly by neutral substitutions. In contrast, the second year of the pandemic was punctuated by the emergence of several variants that bore evidence of dramatic evolution. Here, we compare and contrast evolutionary patterns of various variants, with a focus on the recent Delta variant. Most variants are characterized by long branches leading to their emergence, with an excess of non-synonymous substitutions occurring particularly in the Spike and Nucleocapsid proteins. In contrast, the Delta variant that is now becoming globally dominant, lacks the signature long branch, and is characterized by a step-wise evolutionary process that is ongoing. Contrary to the “star-like” topologies of other variants, we note the formation of several distinct clades within Delta that we denote as clades A-E. We find that sequences from the Delta D clade are dramatically increasing in frequency across different regions of the globe. Delta D is characterized by an excess of non-synonymous mutations, mostly occurring in ORF1a/b, some of which occurred in parallel in other notable variants. We conclude that the Delta surge these days is composed almost exclusively of Delta D, and discuss whether selection or random genetic drift has driven the emergence of Delta D.
Does Robotic-Assisted Surgery improve outcomes of total hip arthroplasty compared to manual technique? A protocol for systematic review and meta-analysis
Authors: Kumar Vishal , Patel Sandeep , Baburaj Vishnu , Rajnish Rajesh Kumar , Aggarwal Sameer
Published: August 2021

Background

Robot-assisted total hip arthroplasty (THA) is an emerging technology that claims to position THA components with a very high degree of accuracy. It is unclear if this increase in accuracy leads to improved long-term functional outcomes of the patient.

Objectives

This systematic review aims to compare robot-assisted THA to those done using conventional manual techniques, in terms of both short-term radiographic outcomes, as well as long-term clinical outcomes.

Methods

This systematic review will be conducted according to the PRISMA guidelines. A literature search will be conducted on the electronic databases of PubMed, Embase, Scopus, and Ovid with a pre-determined search strategy. A manual bibliography search of included studies will also be done. Original articles in English that directly compare robot-assisted THA to manual THA will be included. Data on outcomes will be extracted from included studies and analysis carried out with the help of appropriate software.
COVID-19 & Mental Health: Impact on Working people and Students
Authors: Moghe Kshipra V. , Kotecha Disha , Patil Manjusha
Published: August 2021

A total of N=618 responses (16-60 years) were recorded to gauge the impact of COVID-19 socially, personally, and psychologically. Comparative results based on employment status, gender, and background were evaluated to identify the impact. While all the groups maintain having information about the pandemic and necessary safety protocols, there is an observable difference in the apprehension levels of financial and mental stability. Due to job security, employed people are less tense and better connected to their family, while unemployed people and students are more concerned with their productivity and quality of work. Students also display higher feelings of uncertainty and helplessness. A considerable number of people feel lonely and deserted during the pandemic. Such thoughts may leave a lasting effect if not tackled at the earliest. While an increase in awareness about mental health is observable, rural and unemployed people are less inclined to approach a professional. The significant difference COVID 19 has created between working people and students and based on gender and background, suggests that the preventive measures to avoid its lasting effects must be devised separately.
Prevalence and correlates of SARS-CoV-2 seropositivity among people who inject drugs in the San Diego-Tijuana border region
Authors: Strathdee Steffanie A. , Abramovitz Daniela , Harvey-Vera Alicia , Vera Carlos , Rangel Gudelia , Artamonova Irina , Chaillon Antoine , Ignacio Caroline , Calderon Alheli , Martin Natasha K. , Patterson Thomas L.
Published: August 2021

Background

People who inject drugs may be at elevated SARS-CoV-2 risk due to their living conditions and/or exposures when seeking or using drugs. No study to date has reported upon risk factors for SARS-CoV-2 infection among people who inject drugs or sex workers.

Methods and Findings

Between October, 2020 and June, 2021, participants aged ≥18 years from San Diego, California, USA and Tijuana, Baja California, Mexico who injected drugs within the last month underwent interviews and testing for SARS-CoV-2 RNA and antibodies. Binomial regressions identified correlates of SARS-CoV-2 seropositivity. Of 386 participants, SARS-CoV-2 seroprevalence was 36.3% (95% CI: 31.5%-41.1%); 92.1% had detectable IgM antibodies. Only 37.5% had previously been tested. Seroprevalence did not differ by country of residence. None tested RNA-positive. Most (89.5%) reported engaging in ≥1 protective behavior [e.g., facemasks (73.5%), social distancing (46.5%), or increasing handwashing/sanitizers (22.8%)]. In a multivariate model controlling for sex, older age, and Hispanic/Latinx/Mexican ethnicity were independently associated with SARS-CoV-2 seropositivity, as was engaging in sex work (AdjRR: 1.63; 95% CI: 1.18-2.27) and having been incarcerated in the past six months (AdjRR: 1.49; 95% CI: 0.97-2.27). Presence of comorbidities and substance using behaviors were not associated with SARS-CoV-2 seropositivity.

Conclusions

This is the first study to show that sex work and incarceration were independently associated with SARS-CoV-2 infection. Despite engaging in protective measures, over one-third had evidence of infection, reinforcing the need for a coordinated binational response. Risk mitigation and vaccination is especially needed among older and Hispanic people who inject drugs and those with less agency to protect themselves, such as those who are sex workers or incarcerated.
Sex differences in the risk of cataract associated with type 2 diabetes: a Mendelian randomization study
Authors: Zhang Haoyang , Xiu Xuehao , Yang Yuedong , Yang Yuanhao , Zhao Huiying
Published: August 2021

Type 2 diabetes (T2D) is a recognized risk factor for developing cataract. However, it is unclear if the shared genetic variance and potential genetic causal relationship between T2D and cataract are different for males and females. We evaluated sex-specific genetic correlation (rg) and putative genetic causality between the two diseases by using linkage disequilibrium score regression (LDSC) and six Mendelian randomization (MR) approaches after leveraging large-scale population-based genome-wide association studies (GWAS) summary of T2D and cataract. Application of LDSC found a significant genetic correlation between T2D and cataract in East Asian males (rg=0.68, 95% confident interval [CI]=0.17 to 1, p-value=8.60×10−3) but a non-significant genetic correlation in East Asian females (rg=0.25, CI= -0.02 to 0.52, p-value=8.38×10−2). MR analyses indicated a consistently stronger (paired t-test |t|=5.87, p-value=2.04×10−3) causal effect of T2D on cataract in East Asian males (liability OR=1.20 to 1.41, p-value=5.86×10−27 to 6.60×10−6) than in females (liability OR=1.12 to 1.21, p-value=2.02×10−14 to 1.82×10−2). In Europeans, the LDSC analysis suggested a close significant genetic correlation between the two diseases in males (rg=0.20, 95% confident interval [CI]=0.08 to 0.32, p-value=7.00×10−4) and females (rg=0.17, CI= 0.05 to 0.29, p-value=4.90×10−3); but the MR analyses provided weak evidences on a causal relationship between the two diseases in both sexes. These results presented the first evidence on sex difference of the casual relationship between cataract and T2D in East Asians, and supported a potential genetic heterogeneity of the shared genetics underlying T2D and cataract between East Asians and Europeans in both sexes.
Analysis of Gene Expression Profiles to study Malaria Vaccine Dose Efficacy & Immune Response Modulation
Authors: Dey Supantha , Kaur Harpreet , Mazumder Mohit , Brodsky Elia
Published: August 2021

Malaria is a life-threatening disease, and the Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of the different vaccination doses on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on 275 and 583 samples collected from the GEO datasets. At first, exploratory data analysis based Principal component analysis (PCA) shown the distinct pattern of different doses. Subsequently, differential gene expression analysis using edgeR revealed the significantly (FDR <0.005) 158 down-regulated and 61 upregulated genes between control vs. Controlled Human Malaria Infection (CHMI) samples. Further, enrichment analysis of significant genes using Annotation and GAGE tools delineate the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc.,genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight to the dual role of cytokine responses in malaria pathogenesis and variations in their expression patterns after various doses of vaccination involved in protection.
On the edge: Evolution of polarity protein BASL and the capacity for stomatal lineage asymmetric divisions
Authors: Nir Ido , Amador Gabriel O. , Gong Yan , Smoot Nicole K. , Cai Le , Shohat Hagai , Bergmann Dominique C.
Published: August 2021

Asymmetric and oriented stem cell divisions enable the continued production of patterned tissues. The molecules that guide these divisions include several “polarity proteins” that are localized to discrete plasma membrane domains, are differentially inherited during asymmetric divisions, and whose scaffolding activities can guide division plane orientation and subsequent cell fates. In the stomatal lineages on the surfaces of plant leaves, asymmetric and oriented divisions create distinct cell types in physiologically optimized patterns. The polarity protein BASL is a major regulator of stomatal lineage division and cell fate asymmetries in Arabidopsis, but its role in the stomatal lineages of other plants is unclear. Here, using phylogenetic and functional assays, we demonstrate that BASL is a eudicot-specific polarity protein. Among dicots, divergence in BASL’s roles may reflect some intrinsic protein differences, but more likely reflects previously unappreciated differences in how asymmetric cell divisions are employed for pattern formation in different species. This multi-species analysis therefore provides insight into the evolution of a unique polarity regulator and into the developmental choices available to cells as they build and pattern tissues.

HIGHLIGHTS

BASL is a eudicot-specific regulator of stomatal lineage asymmetric cell divisions

BASL protein evolution includes stepwise addition of polarity domains to an ancestral MAPK-binding chassis

Cellular quiescence and BASL-guided polarity generate proper stomatal spacing in tomato

Cell size and fate asymmetries are uncoupled in the tomato stomatal lineage
DBpred: A deep learning method for the prediction of DNA interacting residues in protein sequences
Authors: Patiyal Sumeet , Dhall Anjali , Raghava Gajendra P. S.
Published: August 2021

DNA-protein interaction is one of the most crucial interactions in the biological system, which decide the fate of many processes such as transcription, regulation of gene expression, splicing, and many more. Though many computational approaches exist that can predict the DNA interacting residues from the protein sequences, there is still a significant opportunity for improvement in terms of performance and accessibility. In this study, we have downloaded the benchmark dataset from method hybridNAP and recently published method ProNA2020, for training and validation purposes, that comprise 864 and 308 proteins, respectively. We have implemented CD-HIT software to handle the redundancy with 30% identity, and left with 646 proteins for training and 46 proteins for validation purposes, in which the validation dataset do not share more than 30% of sequence identity with the training dataset. We have generated amino acid binary profiles, physicochemical-properties based binary profiles, PSSM profiles, and a combination of all profiles described as hybrid feature. 1D-CNN based model performed best as compared to other models for each set of features. The model developed using amino acid binary profile achieved AUROC of 0.83 and 0.74 for training and validation dataset. Using physicochemical properties based binary profile, model attained AUROC of 0.86 and 0.73 for training and validation dataset. Model generated using PSSM profile resulted in the better performance with AUROC 0.91 and 0.74 for training and validation dataset. And, model developed using hybrid of all features performed best with AUROC of 0.91, and 0.79 for training and validation dataset, respectively. We have compared our method’s performance with the current approach and shown improvements. We have included the best-performing models in the standalone and web server accessible athttps://webs.iiitd.edu.in/raghava/dbpred. DBPred is an effective approach to predict the DNA interacting residues in the protein using its primary structure.
Adaptation of the autosomal part of the genome on the presence of dioecy
Authors: Žlůvová Jitka , Hobza Roman , Janoušek Bohuslav
Published: August 2021

We have attempted to answer the question of whether the presence of sex chromosomes in the genome can affect the evolution of the autosomal part of the genome. As a model, we used dioecious plants from the section Otites of the genus Silene. We have observed a rise in adaptive evolution in the autosomal and pseudoautosomal parts of the genome, which are associated with the evolution of dioecy. This rise is caused neither by the accumulation of sexually antagonistic genes in the pseudoautosomal region nor by the co-evolution of genes acting in mitochondria (in spite of the fact that the dioecy evolved in this case most likely from cytoplasmic male sterility). Thus, this rise in the amount of positively selected codons is most likely caused by the adaptive evolution of genes involved in the specialization of the autosomal part of the genome on the dioecy as described in sex-allocation theory.
Interleukin-33 coordinates a microglial phagocytic response and limits corticothalamic excitability and seizure susceptibility
Authors: Han Rafael T. , Vainchtein Ilia D. , Schlachetzki Johannes C. M. , Cho Frances S. , Dorman Leah C. , Johung Tessa , Ahn Eunji , Barron Jerika T. , Nakao-Inoue Hiromi , Joshi Akshaj , Molofsky Ari. B , Glass Christopher K. , Paz Jeanne T. , Molofsky Anna V.
Published: August 2021

Microglia are key remodelers of neuronal synapses during brain development, but the mechanisms that regulate this process and its ultimate impact on neural circuit function are not well defined. We previously identified the IL-1 family cytokine Interleukin-33 (IL-33) as a novel mediator of microglial synapse remodeling. Here we define the phagocytic program induced in microglia in response to IL-33. We find that IL-33 markedly alters the microglial enhancer landscape and exposes AP-1 transcription factor sites that promote target gene expression. We identify the scavenger receptor MARCO and the pattern recognition receptor TLR2 as downstream mediators of IL-33 dependent synapse engulfment. Conditional deletion of IL-33 in the CNS or its receptor on microglia results in increased numbers of excitatory synapses in the corticothalamic circuit and spontaneous epileptiform activity as well as increased seizure susceptibility by early adulthood. These findings define novel mechanisms through which IL-33 coordinates experience-dependent synaptic refinement to restrict hyperexcitability in the developing brain.
Presenting the Compendium Isotoporum Medii Aevi (CIMA) and Bayesian Case Studies
Authors: Cocozza Carlo , Cirelli Enrico , Groß Marcus , Teegen Wolf-Rüdiger , Fernandes Ricardo
Published: August 2021

Abstract

The Compendium Isotoporum Medii Aevi (CIMA) gathers more than 50 000 isotopic measurements for bioarchaeological samples located within Europe and its margins dating between AD 500–1500. This volume of isotopic data, together with collected supporting information, offers multiple research opportunities. This is illustrated here using novel Bayesian modelling methods on selected case studies to reconstruct medieval human lifeways (i.e. human subsistence, spatial mobility), animal management practices, and paleo-environmental conditions. We also discuss how the integration of isotopic data with other types of archaeological and historical data can improve our knowledge of historical developments throughout medieval Europe.
Voltage imaging in Drosophila using a hybrid chemical-genetic rhodamine voltage reporter
Authors: Kirk Molly J. , Benlian Brittany R. , Han Yifu , Gold Arya , Ravi Ashvin , Deal Parker E. , Molina Rosana S. , Drobizhev Mikhail , Dickman Dion , Scott Kristin , Miller Evan W.
Published: August 2021

We combine a chemically-synthesized, voltage-sensitive fluorophore with a genetically encoded, self-labeling enzyme to enable voltage imaging in Drosophila melanogaster. Previously, we showed that a rhodamine voltage reporter (RhoVR) combined with the HaloTag self-labeling enzyme could be used to monitor membrane potential changes from mammalian neurons in culture and brain slice. Here, we apply this hybrid RhoVR-Halo approach in vivo to achieve selective neuron labeling in intact fly brains. We generate a Drosophila UAS-HaloTag reporter line in which the HaloTag enzyme is expressed on the surface of cells. We validate the voltage sensitivity of this new construct in cell culture before driving expression of HaloTag in specific brain neurons in flies. We show that selective labeling of synapses, cells, and brain regions can be achieved with RhoVR-Halo in either larval neuromuscular junction (NMJ) or in whole adult brains. Finally, we validate the voltage sensitivity of RhoVR-Halo in fly tissue via dual-electrode/imaging at the NMJ, show the efficacy of this approach for measuring synaptic excitatory post-synaptic potentials (EPSPs) in muscle cells, and perform voltage imaging of carbachol-evoked depolarization and osmolarity-evoked hyperpolarization in projection neurons and in interoceptive subesophageal zone neurons in fly brain explants following in vivo labeling. We envision the turn-on response to depolarizations, fast response kinetics, and two-photon compatibility of chemical indicators, coupled with the cellular and synaptic specificity of genetically-encoded enzymes, will make RhoVR-Halo a powerful complement to neurobiological imaging in Drosophila.

Significance Statement

Voltage imaging is a powerful method for interrogating neurobiology. Chemical indicators possess fast response kinetics, turn-on responses to membrane depolarization, and can be compatible with two-photon excitation. However, selective cell labeling in intact tissues and in vivo remains a challenge for completely synthetic fluorophores. Here, we show that a chemical – genetic hybrid approach in Drosophila enables cell-specific staining in vivo and voltage imaging in whole-brain explants and at neuromuscular junction synapses.
A population of descending neurons that regulate the flight motor of Drosophila
Authors: Namiki Shigehiro , Ros Ivo G. , Morrow Carmen , Rowell William J. , Card Gwyneth M. , Korff Wyatt , Dickinson Michael H.
Published: August 2021

Like many insect species, Drosophila melanogaster are capable of maintaining a stable flight trajectory for periods lasting up to several hours(1, 2). Because aerodynamic torque is roughly proportional to the fifth power of wing length(3), even small asymmetries in wing size require the maintenance of subtle bilateral differences in flapping motion to maintain a stable path. Flies can even fly straight after losing half of a wing, a feat they accomplish via very large, sustained kinematic changes to the both damaged and intact wings(4). Thus, the neural network responsible for stable flight must be capable of sustaining fine-scaled control over wing motion across a large dynamic range. In this paper, we describe an unusual type of descending neurons (DNg02) that project directly from visual output regions of the brain to the dorsal flight neuropil of the ventral nerve cord. Unlike most descending neurons, which exist as single bilateral pairs with unique morphology, there is a population of at least 15 DNg02 cell pairs with nearly identical shape. By optogenetically activating different numbers of DNg02 cells, we demonstrate that these neurons regulate wingbeat amplitude over a wide dynamic range via a population code. Using 2-photon functional imaging, we show that DNg02 cells are responsive to visual motion during flight in a manner that would make them well suited to continuously regulate bilateral changes in wing kinematics. Collectively, we have identified a critical set of DNs that provide the sensitivity and dynamic range required for flight control.
Vinculin recruitment to α-catenin halts the differentiation and maturation of enterocyte progenitors to maintain homeostasis of the Drosophila intestine
Authors: Bohère Jérôme , Eldridge-Thomas Buffy L. , Kolahgar Golnar
Published: August 2021

Mechanisms communicating changes in tissue stiffness and size are particularly relevant in the intestine, because it is subject to constant mechanical stresses caused by peristalsis of its variable content. Using the Drosophila intestinal epithelium, we investigate the role of vinculin, one of the best characterised mechanoeffectors, which functions in both cadherin and integrin adhesion complexes. We discovered that vinculin regulates cell fate decisions, by preventing precocious activation and differentiation of intestinal progenitors into absorptive cells. It achieves this in concert with α-catenin at sites of cadherin adhesion, rather than as part of integrin function. Following asymmetric division of the stem cell into a stem cell and an enteroblast, the two cells initially remain connected by adherens junctions, where vinculin is required, only on the enteroblast side, to maintain the enteroblast in a quiescent state and inhibit further divisions of the stem cell. Removing vinculin increases enteroblast differentiation and numbers, resulting in an enlarged gut with improved ability to recover after starvation. Thus, mechanical regulation at the contact between stem cells and their progeny is used to control tissue cell number.
Impaired dynamics of brain precapillary sphincters and pericytes at first order capillaries explains reduced neurovascular functions in aging
Authors: Cai Changsi , Zambach Stefan Andreas , Grubb Søren , Thomsen Kirsten Joan , Lind Barbara Lykke , Hald Bjørn Olav , Lønstrup Micael , Nielsen Reena Murmu , Lauritzen Martin Johannes
Published: August 2021

The microvascular inflow tract (MIT), comprising the penetrating arterioles, precapillary sphincters, and first order capillaries, is the bottleneck for brain blood flow and energy supply. However, the exact structural and functional alterations of the MIT during aging remain elusive. In vivo 4-dimensional two-photon imaging showed an age-dependent decrease in vaso-responsivity, with reduced sensitivity of the MIT to pinacidil and papaverine, vasoconstrictor endothelin-1, and nitric oxide synthase inhibitor L-NAME. This was accompanied by an age-dependent decrease in capillary density close to the arterioles and loss of pericyte processes, though the number of pericyte somas and pericyte αSMA density were preserved. The age-related reduction in vascular reactivity was most pronounced at precapillary sphincters, highlighting their crucial role in capillary blood flow regulation. Mathematical modeling revealed dysregulated but preserved pressure and flow in aged mice during vasoconstriction. Preventing reduced responsivity of the MIT may ameliorate the blood flow decrease associated with aging-related brain frailty.
Transitions in the proteome and phospho-proteome duringXenopus laevisdevelopment
Authors: Van Itallie Elizabeth , Sonnett Matthew , Kalocsay Marian , Wühr Martin , Peshkin Leonid , Kirschner Marc W.
Published: August 2021

Vertebrate development from an egg to a complex multi-cell organism is accompanied by multiple phases of genome-scale changes in the repertoire of proteins and their post-translational modifications. While much has been learned at the RNA level, we know less about changes at the protein level. In this paper, we present a deep analysis of changes of ∼15,000 proteins and ∼11,500 phospho-sites at 11 developmental time points inXenopus laevisembryos ranging from the stage VI oocyte to juvenile tadpole. We find that the most dramatic changes to the proteome occur during the transition to functional organ systems, which occurs as the embryo becomes a tadpole. At that time, the absolute amount of non-yolk protein increases two-fold, and there is a shift in the balance of expression from proteins regulating gene expression to receptors, ligands, and proteins involved in cell-cell and cell-environment interactions. Between the early and late tadpole, the median increase for membrane and secreted proteins is substantially higher than that of nuclear proteins. To begin to appreciate changes at the post-translational level, we have measured quantitative phospho-proteomic data across the same developmental stages. In contrast to the significant protein changes that are concentrated at the end of the time series, the most significant phosphorylation changes are concentrated in the very early stages of development. A clear exception are phosphorylations of proteins involved in gene expression: these increase just after fertilization, with patterns that are highly correlated with the underlying protein changes. To facilitate the interpretation of this unique phospho-protoeme data set, we created a pipeline for identifying homologous human phosphorylations from the measured Xenopus phospho-proteome. Overall, we detected many profound temporal transitions, that suggest concerted changes in developmental strategies in the embryo, which are particularly pronounced once early patterning and specification are complete.
A general deep learning model for bird detection in high resolution airborne imagery
Authors: Weinstein Ben G. , Garner Lindsey , Saccomanno Vienna R. , Steinkraus Ashley , Ortega Andrew , Brush Kristen , Yenni Glenda , McKellar Ann E. , Converse Rowan , Lippitt Christopher D. , Wegmann Alex , Holmes Nick D. , Edney Alice J. , Hart Tom , Jessopp Mark J. , Clarke Rohan H , Marchowski Dominik , Senyondo Henry , Dotson Ryan , White Ethan P. , Frederick Peter , Ernest S.K. Morgan
Published: August 2021

Advances in artificial intelligence for computer vision hold great promise for increasing the scales at which ecological systems can be studied. The distribution and behavior of individuals is central to ecology, and computer vision using deep neural networks can learn to detect individual objects in imagery. However, developing supervised models for ecological monitoring is challenging because it needs large amounts of human-labeled training data, requires advanced technical expertise and computational infrastructure, and is prone to overfitting. This limits application across space and time. One solution is developing generalized models that can be applied across species and ecosystems. Using over 250,000 annotations from 13 projects from around the world, we develop a general bird detection model that achieves over 65% recall and 50% precision on novel aerial data without any local training despite differences in species, habitat, and imaging methodology. Fine-tuning this model with only 1000 local annotations increase these values to an average of 84% recall and 69% precision by building on the general features learned from other data sources. Retraining from the general model improves local predictions even when moderately large annotation sets are available and makes model training faster and more stable. Our results demonstrate that general models for detecting broad classes of organisms using airborne imagery are achievable. These models can reduce the effort, expertise, and computational resources necessary for automating the detection of individual organisms across large scales, helping to transform the scale of data collection in ecology and the questions that can be addressed.
Peptidergic modulation of fear responses by the Edinger-Westphal nucleus
Authors: Priest Michael F. , Freda Sara N. , Badong Deanna , Dumrongprechachan Vasin , Kozorovitskiy Yevgenia
Published: August 2021

Many neuronal populations that release fast-acting excitatory and inhibitory neurotransmitters in the brain also contain slower acting neuropeptides. These facultative peptidergic cell types are common, but it remains uncertain whether obligate peptidergic neurons exist. Our fluorescence in situ hybridization, genetically-targeted electron microscopy, and electrophysiological characterization data strongly suggest that neurons of the non-cholinergic, centrally-projecting Edinger-Westphal nucleus in mice are fundamentally obligately peptidergic. We further show, using fiber photometry, monosynaptic retrograde tracing, anterograde projection mapping, and a battery of behavioral assays, that this peptidergic population both promotes fear responses and analgesia and activates in response to loss of motor control and pain. Together, these findings elucidate an integrative, ethologically relevant function for the Edinger-Westphal nucleus and functionally align the nucleus with the periaqueductal gray, where it resides. This work advances our understanding of the peptidergic modulation of fear and provides a framework for future investigations of putative obligate peptidergic systems.