bluuebunny/crossref_metadata_2025 huggingface dataset:
An empirical analysis of what people learned about COVID-19 through web search and the impacts on misinformation and attitude towards public health safety guidelines
Authors: Akpan Ikpe Justice , Aguolu Obianuju Genevieve , Akpan Asuama
Published: February 2021

Several people flocked to the Internet to learn about the SARS-CoV-2 and COVID-19 after the outbreak in Wuhan, China, in December 2019. As the novel coronavirus spread rapidly worldwide and was declared a global pandemic, the public rushed to Internet platforms to learn about the outbreak through Google search, online news outlets, and social media platforms. This paper evaluates the public’s web search to learn about the pandemic and the possible impacts on attitude to the public health guidelines. The results highlight four outcomes: First, a significant global population learned about the ongoing pandemic through a web search. Second, there is a direct correlation between learning SARS-CoV-2, COVID-19, and SARS-CoV and searching information on public health measures (wearing a facial mask and social distancing). Third, learning conspiracy theories or misinformation correspond with a lack of interest in gaining knowledge about public health safety guidelines. Also, the initial high interest in learning about Influenza declined as people gained information about SARS-CoV-2 and COVID-19. The results highlight the critical need to promptly sensitize the public about global health concerns using both the Internet platforms and traditional sources, adopt effective health communication strategies, and build trust.
Sequence-function Relationships in Phage-encoded Bacterial Cell Wall Lytic Enzymes and their Implications for Phage-derived Products Design
Authors: Vázquez Roberto , García Ernesto , García Pedro
Published: February 2021

Phage (endo)lysins are thought to be a viable alternative to usual antibiotic chemotherapy to fight resistant bacterial infections. However, a landscape view of lysins’ structure and properties regarding their function, with an applied focus, is somewhat lacking. Current literature suggests that specific features typical of lysins from phages infecting Gram-negative bacteria (G−) (higher net charge, amphipathic helices) are responsible for an improved interaction with G− envelope. Such antimicrobial peptide (AMP)-like elements are also of interest for antimicrobial molecules design. Thus, this study aims to provide an updated view on the primary structural landscape of phage lysins to clarify the evolutionary importance of several sequence-predicted properties, particularly for the interaction with the G− surface. A database of 2,182 lysin sequences was compiled, containing relevant information such as domain architectures, data on the phages’ host bacteria and sequence-predicted physicochemical properties. Based on such classifiers, an investigation on the differential appearance of certain features was conducted. Such analyses revealed different lysin architectural variants that are preferably found in phages infecting certain bacterial hosts. Particularly, some physicochemical properties (higher net charge, hydrophobicity, hydrophobic moment and aliphatic index) were associated to G− phage lysins, appearing specifically at their C-terminal end. Evidences on the remarkable genetic specialization of lysins regarding the features of the bacterial hosts have been provided, specifically supporting the nowadays common hypothesis that lysins from G− usually contain AMP-like regions.

IMPORTANCE

Phage-encoded lytic enzymes, also called lysins, are one of the most promising alternatives to common antibiotics. The lysins potential as novel antimicrobials to tackle antibiotic-resistant bacteria not only arises from features such as a lower chance to provoke resistance, but also from their versatility as synthetic biology parts. Functional modules derived from lysins are currently being used for the design of novel antimicrobials with desired properties. This study provides a view of the lysins diversity landscape by examining a set of phage lysin genes. This way, we have uncovered the fundamental differences between the lysins from phages that infect bacteria with different superficial architectures, and, thus, also the reach of their specialization regarding cell wall structures. These results provide clarity and evidences to sustain some of the common hypothesis in current literature, as well as make available an updated and characterized database of lysins sequences for further developments.
Sensing and decoding the neural drive to paralyzed muscles during attempted movements of a person with tetraplegia using a sleeve array
Authors: Ting Jordyn E. , Vecchio Alessandro Del , Sarma Devapratim , Colachis Samuel C. , Annetta Nicholas V. , Collinger Jennifer L. , Farina Dario , Weber Douglas J.
Published: February 2021

Motor neurons in the brain and spinal cord convey information about motor intent that can be extracted and interpreted to control assistive devices, such as computers, wheelchairs, and robotic manipulators. However, most methods for measuring the firing activity of single neurons rely on implanted microelectrodes. Although intracortical brain-computer interfaces (BCIs) have been shown to be safe and effective, the requirement for surgery poses a barrier to widespread use. Here, we demonstrate that a wearable sensor array can detect residual motor unit activity in paralyzed muscles after severe cervical spinal cord injury (SCI). Despite generating no observable hand movement, volitional recruitment of motor neurons below the level of injury was observed across attempted movements of individual fingers and overt wrist and elbow movements. Subgroups of motor units were coactive during flexion or extension phases of the task. Single digit movement intentions were classified offline from the EMG power (RMS) or motor unit firing rates with median classification accuracies >75% in both cases. Simulated online control of a virtual hand was performed with a binary classifier to test feasibility of real time extraction and decoding of motor units. The online decomposition algorithm extracted motor units in 1.2 ms, and the firing rates predicted the correct digit motion 88 ± 24% of the time. This study provides the first demonstration of a wearable interface for recording and decoding firing rates of motor neurons below the level of injury in a person with tetraplegia after motor complete SCI.

Significance Statement

A wearable electrode array and machine learning methods were used to record and decode myoelectric signals and motor unit firing in paralyzed muscles of a person with motor complete tetraplegia. Motor unit action potentials were extracted from myoelectric signals during attempted movements of the fingers and voluntary movements of the wrist and elbow. The patterns of EMG and motor unit firing rates were highly task-specific, even in the absence of visible motion in the limb, enabling accurate classification of attempted movements of single digits. These results demonstrate the potential to create a wearable sensor for determining movement intentions from spared motor neurons, which may enable people with severe tetraplegia to control assistive devices such as computers, wheelchairs, and robotic manipulators.
Discovery of SARS-CoV-2 strain of P.1 lineage harboring K417T/ E484K / N501Y by whole genome sequencing in the city, Japan
Authors: Hirotsu Yosuke , Omata Masao
Published: February 2021

On the February 2020, the very first case was an American female from Diamond Princess cruise ship. Since, we have confirmed 136 patients infected with coronavirus disease 2019 (COVID-19) until February 2021. Here, we conducted the whole genome sequencing analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on samples from 70 of 136 patients (51.5%). These patients were infected in Diamond Princess cruise ship (n=1), Africa (n=2), Japan (n=66) and Brazil (n=1). The viral genome sequence of a patient on the Diamond Princess cruise ship in February 2020 was similar to that of original strain found in Wuhan, China (19A clade). Four patients, including two returnees from Africa and two lived in Japan, confirmed at the end of March 2020 had sequences similar to those of lineage with D614G mutation, which was endemic in Europe (20A [n=3] and 20B [n=1] clade). The 64 Japanese patients confirmed from September 2020 to January 2021 had sequences similar to those of the currently prevalent lineage (20B [n=58] and 20C clade [n=6]). Subsequent analysis revealed three mutations (K417T/ E484K / N501Y) in the receptor binding domain of the spike protein in a man in his 40s. The sequence was identical to the P.1 lineage (also known as 20J/501Y.V3) reported in Brazil. This is the first report of SARS-CoV-2 P.1 lineage identified in the city, Japan.
Evaluation of a surrogate virus neutralization test for high-throughput serosurveillance of SARS-CoV-2
Authors: Mariën Joachim , Michiels Johan , Heyndrickx Leo , Nkuba-Ndaye Antoine , Ceulemans Ann , Bartholomeeusen Koen , Madinga Joule , Mbala-Kingebeni Placide , Vanlerberghe Veerle , Ahuka-Mundeke Steve , Wang Lin-Fa , Ariën Kevin K.
Published: February 2021

High-throughput serological tests that can detect neutralizing antibodies against SARS-CoV-2 are desirable for serosurveillance and vaccine efficacy evaluation. Although the conventional neutralization test (cVNT) remains the gold standard to confirm the presence of neutralizing antibodies in sera, the test is too labour-intensive for massive screening programs and less reproducible as live virus and cell culture is involved. Here, we performed an independent evaluation of a commercially available surrogate virus neutralization test (sVNT, GenScript cPass™) that can be done without biosafety level 3 containment in less than 2 hours. When using the cVNT and a Luminex multiplex immunoassay (MIA) as reference, the sVNT obtained a sensitivity of 94% (CI 90-96%) on a panel of 317 immune sera that were obtained from hospitalized and mild COVID-19 cases from Belgium and a sensitivity of 89% (CI 81-93%) on a panel of 184 healthcare workers from the Democratic Republic of Congo. We also found strong antibody titer correlations (rs>0.8) among the different techniques used. In conclusion, our evaluation suggests that the sVNT could be a powerful tool to monitor/detect neutralising antibodies in cohort and population studies. The technique could be especially useful for vaccine evaluation studies in sub-Saharan Africa where the basic infrastructure to perform cVNTs is lacking.
COVIDReady2 Study Protocol: Cross-sectional Survey of Medical Student Volunteering and Education During the COVID-19 Pandemic in the United Kingdom
Authors: Byrne Matthew H V , Ashcroft James , Alexander Laith , Wan Jonathan C M , Arora Anmol , Brown Megan E L , Harvey Anna , Clelland Andrew , Schindler Nicholas , Brassett Cecilia , Allan Rachel
Published: February 2021

Background and objectives

Covid-19 has led to global disruption of healthcare. Many students volunteered to provide clinical support. Volunteering to work in a clinical capacity was a unique medical education opportunity; however, it is unknown whether this was a positive learning experience or which volunteering roles were of most benefit to students.

Methods and Design

The COVIDReady2 study is a national cross-sectional study of all medical students at UK medical schools. The primary outcome is to explore the experiences of medical students who volunteered during the pandemic in comparison to those who did not. We will compare responses to determine the educational benefit and issues they faced. In addition to quantitative analysis, thematic analysis will be used to identify themes in qualitative responses.

Discussion

There is a growing body of evidence to suggest that service roles have potential to enhance medical education; yet, there is a shortage of studies able to offer practical advice for how these roles may be incorporated in future medical education. We anticipate that this study will help to identify volunteer structures that have been beneficial for students, so that similar infrastructures can be used in the future, and help inform medical education in a non-pandemic setting.
Risk factors for increased COVID-19 case-fatality in the United States: A county-level analysis during the first wave
Authors: Millar Jess A. , Dao Hanh Dung N. , Stefopulos Marianne E. , Estevam Camila G. , Fagan-Garcia Katharine , Taft Diana H. , Park Christopher , Alruwaily Amaal , Desai Angel N. , Majumder Maimuna S.
Published: February 2021

The ongoing COVID-19 pandemic is causing significant morbidity and mortality across the US. In this ecological study, we identified county-level variables associated with the COVID-19 case-fatality rate (CFR) using publicly available datasets and a negative binomial generalized linear model. Variables associated with decreased CFR included a greater number of hospitals per 10,000 people, banning religious gatherings, a higher percentage of people living in mobile homes, and a higher percentage of uninsured people. Variables associated with increased CFR included a higher percentage of the population over age 65, a higher percentage of Black or African Americans, a higher asthma prevalence, and a greater number of hospitals in a county. By identifying factors that are associated with COVID-19 CFR in US counties, we hope to help officials target public health interventions and healthcare resources to locations that are at increased risk of COVID-19 fatalities.
Virtual handover of patients in the pediatric intensive care unit during COVID-19 crisis
Authors: Temsah Mohamad-Hani , Abouammoh Noura , Ashry Ahmad , Al-Eyadhy Ayman , Alhaboob Ali , Alsohime Fahad , Almazyad Mohammed , Alabdulhafid Majed , Temsah Reem , AlJamaan Fadi , Jamal Amr , Halwani Rabih , Alhasan Khalid , Al-Tawfiq Jaffar A. , Barry Mazin
Published: February 2021

Objectives

A key measure to mitigate coronavirus disease 2019 (COVID-19) has been social distancing. Incorporating video-conferencing applications in the patient handover process between healthcare workers can enhance social distancing while maintaining handover elements. This study describes pediatric intensive care unit (PICU) physicians’ experience of using an online video-conferencing application for handover during the COVID-19 pandemic. Design: qualitative content analysis

Setting

PICU at a university hospital in Riyadh, Saudi Arabia Subjects: PICU Physicians

Interventions

Due to the pandemic, the hospital’s PICU used Zoom® as a remote conferencing application, instead of a face-to-face handover. Following institutional review board approval, data were collected over two weeks (July 1, 2020 to July 14, 2020). Measurements: Demographic data and narrative descriptions of the perceived efficacy of remote handover were collected using open-ended questions through a created online link. The analysis process included open coding, creating categories, and abstraction.

Main Results

All 37 PICU physicians who participated in the handover completed the survey. The participants comprised six attendings, nine specialists, and 22 residents. They had variable previous teleconferencing experiences. Most physicians (78.4%) were comfortable conducting a remote endorsement. Most found that Situation–Background– Assessment–Recommendation handover elements were properly achieved through this remote handover process. The perceived advantages of online handover included fewer interruptions, time efficiency, and facilitation of social distancing. The perceived disadvantages were the paucity of nonverbal communication and teaching during virtual meetings.

Conclusions

Video-conferencing applications used for online handovers could supplement traditional face-to-face intensive care unit patient endorsement during outbreaks of infectious diseases. The use of video streaming and more emphasis on teaching should be encouraged to optimize the users’ experience.
A national mixed-mode seroprevalence random population-based cohort on SARS-CoV-2 epidemic in France: the socio-epidemiological EpiCov study
Authors: Warszawski Josiane , Bajos Nathalie , Barlet Muriel , de Lamballerie Xavier , Rahib Delphine , Lydié Nathalie , Durrleman S , Slama Rémy , Seng Rémonie , Raynaud Philippe , Leduc Aude , Bagein Guillaume , Paliod Nicolas , Legleye Stéphane , Favre-Martinoz Cyril , Castell Laura , Sillard Patrick , Meyer Laurence , Beck François ,   The EPICOV study group
Published: February 2021

Background

the EpiCov study, initiated at the end of the first national lockdown in France, aimed to provide national and regional estimates of the seroprevalence of SARS-CoV-2 infection, and to analyze relations between living conditions and the dynamics of the epidemic. We present and discuss here the survey methodology, and describe the first-round fieldwork.

Method

371,000 individuals aged 15 years or more were randomly selected from the national tax register, stratified by departments, including three overseas departments, and by poverty level with over-representation of people living below the poverty line. Health, socio-economics, migration history, and living conditions were collected through self-computed-assisted web interviews or via computer-assisted telephone interviews. The first-round survey was conducted in May. A random subsample was eligible to receive material for home blood self-sample on dried blood spot (DBS), in order to detect IgG antibodies against the spike protein (Euroimmun ELISA-S), and neutralizing antibodies for non-negative ELISA-S. For the second-round conducted in November, all respondents were eligible for the antibodies detection from home DBS sample, as well as the other household members aged 6 years or more for 20% of them.

Participation and adjustment for nonresponse

134,391 respondents completed the first-round questionnaire from May 2 to June 1, 2020, including 16,970 (12.6%) respondents under the poverty line. Multimodal web/tel interviews was randomly assigned to 20% of the sample. The other were assigned to exclusive CAWI. Overall 17,441 respondents were eligible for home blood sample, among them 12,114 returned the DBS (interquartile date: May 25-June 5). The response probability was first estimated from logit models adjusted on a wide range of auxiliary demographic and socio-economic variables available from the sampling frame, and final weights calibrated to the margins of the population census permitted to correct for a large part of the non-response bias.

Conclusion

The Epicov study is one of the largest national random population-based seroprevalence cohort, with both an epidemiological and sociological approaches to evaluate the spread of the COVID-19 epidemic, and the impact on health and living conditions. One of the major interests of this study is the broad coverage of the socio-economic and territorial diversity of the population.
MRI Intensity Standardization Evaluation Design for Head and Neck Quantitative Imaging Applications
Authors: Wahid Kareem A. , He Renjie , McDonald Brigid A. , Anderson Brian M. , Salzillo Travis , Mulder Sam , Wang Jarey , Sharafi Christina Setareh , McCoy Lance A. , Naser Mohamed A. , Ahmed Sara , Sanders Keith L. , Mohamed Abdallah S.R. , Ding Yao , Wang Jihong , Hutcheson Kate , Lai Stephen Y. , Fuller Clifton D. , van Dijk Lisanne V.
Published: February 2021

Background

Conventional MRI poses unique challenges in quantitative analysis due to a lack of specific physical meaning for voxel intensity values. In recent years, intensity standardization methods to optimize MRI signal consistency have been developed to address this problem. However, the effects of standardization methods on the head and neck region have not been previously investigated.

Purpose

This study proposes a workflow based on healthy tissue region of interest (ROI) analysis to determine intensity consistency within a patient cohort. Through this workflow, we systematically evaluate different intensity standardization methods for T2-weighted MRI of the head and neck region.

Methods

Two image cohorts of five head and neck cancer patients, one with heterogeneous acquisition parameters (median age 59 years [range, 53-61]), and another with homogeneous acquisition parameters from a clinical trial (NCT04265430) (median age 61 years [range, 54-77]) were retrospectively analyzed. The standard deviation of cohort-level normalized mean intensity (SD NMIc), a metric of intensity consistency, was calculated across ROIs to determine the effect of five intensity standardization methods on T2-weighted images. For each cohort, the Friedman test with a subsequent post-hoc Bonferroni-corrected Wilcoxon signed-rank test was conducted to compare SD NMIc among methods.

Results

Consistency (SD NMIc across ROIs) between T2-weighted images is substantially more impaired in the cohort with heterogeneous acquisition parameters (0.28 ± 0.04) than in the cohort with homogeneous acquisition parameters (0.15 ± 0.05). Consequently, intensity standardization methods more significantly improve consistency in the cohort with heterogeneous acquisition parameters (corrected p < 0.005 for all methods compared to no standardization) than in the cohort with homogeneous acquisition parameters (corrected p > 0.5 for all methods compared to no standardization).

Conclusions

Our findings stress the importance of image acquisition parameter standardization, together with the need for testing intensity consistency before performing quantitative analysis of MRI.
The neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives
Authors: Rogers Jonathan P , Watson Cameron , Badenoch James , Cross Benjamin , Butler Matthew , Song Jia , Hafeez Danish , Morrin Hamilton , Rengasamy Emma Rachel , Thomas Lucretia , Ralovska Silviya , Smakowski Abigail , Sundaram Ritika Dilip , Hunt Camille Kaitlyn , Lim Mao Fong , Aniwattanapong Daruj , Singh Vanshika , Hussain Zain , Chakraborty Stuti , Burchill Ella , Jansen Katrin , Holling Heinz , Walton Dean , Pollak Thomas A , Ellul Mark , Koychev Ivan , Solomon Tom , Michael Benedict Daniel , Nicholson Timothy R , Rooney Alasdair G
Published: February 2021

Objectives

There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations.

Methods

We searched MEDLINE, Embase, PsycInfo and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence.

Results

13,292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% [35.2—51.3], n=15,975, 63 studies), weakness (40.0% [27.9—53.5], n=221, 3 studies), fatigue (37.8% [31.6—44.4], n=21,101, 67 studies), dysgeusia (37.2% [30.0—45.3], n=13,686, 52 studies), myalgia (25.1% [19.8—31.3], n=66.268, 76 studies), depression (23.0 % [11.8—40.2], n=43,128, 10 studies), headache (20.7% [95% CI 16.1—26.1], n=64,613, 84 studies), anxiety (15.9% [5.6—37.7], n=42,566, 9 studies) and altered mental status (8.2% [4.4—14.8], n=49,326, 19 studies). Heterogeneity for most clinical manifestations was high.

Conclusions

Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic’s early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.
Longitudinal protection following natural SARS-CoV-2 infection and early vaccine responses: insights from a cohort of community based dental health care professionals
Authors: Shields Adrian M. , Faustini Sian E. , Kristunas Caroline A. , Cook Alex M. , Backhouse Claire , Dunbar Lynsey , Ebanks Daniel , Emmanuel Beena , Crouch Eddie , Kroeger Annika , Hirschfeld Josefine , Sharma Praveen , Jaffery Razza , Nowak Sylwia , Gee Samantha , Drayson Mark T. , Richter Alex G. , Dietrich Thomas , Chapple Iain C.
Published: February 2021

Background

The threshold of protection for anti-SARS-CoV-2 spike glycoprotein antibodies and their longevity are not known. Interpretation of serological results in with respect to international reference material can inform this essential question.

Methods

1,507 West Midlands dental care professionals were recruited into this study in June 2020. Baseline seroprevalence of antibodies directed against the SARS-CoV-2 spike glycoprotein was determined and the cohort was followed longitudinally for 6 months until January/February 2021 through the second wave of the COVID-19 pandemic in the United Kingdom, and commencement of vaccination.

Results

Baseline seroprevalence was 16.3% in this cohort, compared to estimates in the general population of between 6-7%. Seropositivity was retained in over 70% of participants at 3 and 6-month follow up and conferred a 74% reduced risk of infection. During follow-up, no PCR-proven infections occurred in individuals with a baseline anti-SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. Post-vaccination, antibody responses were more rapid and of higher magnitude in individuals with who were seropositive at baseline.

Conclusion

Natural infection leads to a serological response that remains detectable in over 70% of individuals 6 months after initial sampling and 9 months from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech vaccine is associated with an antibody response indicative of immunological memory.

Funding

The Association of Clinical Biochemistry and Laboratory Medicine and The Institute for Global Innovation (IGI) of the University of Birmingham.
Symptoms associated with a COVID-19 infection in the general population of Vienna
Authors: Munsch Nicolas , Gruarin Stefanie , Nateqi Jama , Lutz Thomas , Binder Michael , Aberle Judith H. , Martin Alistair , Knapp Bernhard
Published: February 2021

Background

Most clinical studies report the symptoms experienced by those infected with Coronavirus disease 2019 (COVID-19) via patients already hospitalised. Here we analyse the symptoms experienced by the general population in Vienna.

Methods

The Vienna Social Fund (FSW, Vienna, Austria), the Public Health Services of the City of Vienna (MA15) and the private company Symptoma collaborated to implement Vienna’s official online COVID-19 symptom checker. Users answered 12 yes/no questions about symptoms to assess their risk for COVID-19. They could also specify their age and sex, and whether they had contact with someone who tested positive for COVID-19. Depending on the assessed risk of COVID-19 positivity, a SARS-CoV-2 nucleic acid amplification test (NAAT) was performed. In this publication, we analysed which factors (symptoms, sex or age) are associated with COVID-19 positivity. We also trained a classifier to correctly predict COVID-19 positivity from the collected data.

Results

Between the 2nd of November 2020 and the 18th of November 2021, 9133 people experiencing COVID-19-like symptoms were assessed as high risk by the chatbot and were subsequently tested by a NAAT. Symptoms significantly associated with a positive COVID-19 test were malaise, fatigue, headache, cough, fever, dysgeusia and hyposmia. Our classifier could successfully predict COVID-19 positivity with an Area Under the Curve (AUC) of 0.74.

Conclusion

This study provides reliable COVID-19 symptom statistics based on the general population verified by NAATs.
Isolation and structure of the fibril protein, a major component of the internal ribbon forSpiroplasmaswimming
Authors: Sasajima Yuya , Kato Takayuki , Miyata Tomoko , Kawamoto Akihiro , Namba Keiichi , Miyata Makoto
Published: February 2021

Spiroplasma, which are known pathogens and commensals of arthropods and plants, are helical-shaped bacteria that lack a peptidoglycan layer.Spiroplasmaswim by alternating between left- and right-handed helicity. Of note, this system is not related to flagellar motility, which is widespread in bacteria. A helical ribbon running along the inner side of the helical cell should be responsible for cell helicity and comprises the bacterial actin homolog, MreB, and a protein specific toSpiroplasma, fibril. Here, we isolated the ribbon and its major component, fibril filament, for electron microscopy (EM) analysis. Single-particle analysis of the fibril filaments using the negative-staining EM revealed a three-dimensional chain structure composed of rings with a size of 11 nm wide and 6 nm long, connected by a backbone cylinder with an 8.7 nm interval with a twist along the filament axis. This structure was verified through EM tomography of quick-freeze deep-etch replica sample, with a focus on its handedness. The handedness and pitch of the helix for the isolated ribbon and fibril filament agreed with those of the cell in the resting state. Structures corresponding to the alternative state were not identified. These results suggest that the helical cell structure is supported by fibril filaments; however, the helical switch is caused by the force generated by the MreB proteins. The isolation and structural outline of the fibril filaments provide crucial information for an in-depth clarification of the unique swimming mechanism ofSpiroplasma.
Odor Blocking Of Stress
Authors: Lee Eun Jeong , Saraiva Luis R. , Hanchate Naresh K. , Ye Xiaolan , Asher Gregory , Ho Jonathan , Buck Linda B.
Published: February 2021

Scents have been employed for millennia to allay fear and stress, but whether they do so is poorly understood. In response to fear and stress, hypothalamic corticotropin releasing hormone neurons (CRHNs) induce increases in blood stress hormones. Here, we find that certain structurally and perceptually dissimilar odorants can block mouse stress hormone responses to three potent stressors: physical restraint, predator odor, and male-male social confrontation. Both odorants activate GABAergic inhibitory neurons presynaptic to CRHNs in the hypothalamic ventromedial nucleus (VMH). Stimulation of those neurons inhibits restraint-induced activation of CRHNs and stress hormone increase, mimicking a blocking odorant. Conversely, their silencing prevents odorant blocking of both responses. Notably, we also observed odor blocking of stressor activation in neurons presynaptic to CRHNs in the bed nucleus of the stria terminalis (BNST). Together, these findings indicate that selected odorants can indeed block stress responses, and that odor blocking can occur via two routes: a direct route in which blocking odor signals directly inhibit CRHNs and an indirect route in which they inhibit stressor activation of neurons presynaptic to CRHNs and prevent them from transmitting stress signals to CRHNs.
Self-reported Memory Problems Eight Months after Non-Hospitalized COVID-19 in a Large Cohort
Authors: Søraas Arne , Bø Ragnhild , Kalleberg Karl Trygve , Ellingjord-Dale Merete , Landrø Nils Inge
Published: February 2021

Background

Neurological manifestations of COVID-19 range from ageusia and anosmia, experienced by most patients, to altered consciousness and rare and severe encephalopathy. A direct affection of the central nervous system (CNS) in the disease has been supported by animal models and MRI findings in patients with mild and severe symptoms. Here we report eight-month data on memory problems for non-hospitalized COVID-19 patients compared to SARS-CoV-2 negative patients and untested volunteers.

Objective

To explore the association between non-hospitalized COVID-19 eight months previously and self-reported memory problems.

Methods

We followed a cohort of 13156 participants that was invited after (1) being tested for SARS-CoV-2 with a combined oropharyngeal- and nasopharyngeal swab or (2) randomly selected from the Norwegian population (untested). Participants completed online baseline- and follow-up questionnaires detailing underlying medical conditions, demographics, symptoms, and items from the RAND-36 questionnaire on health-related quality of life and known confounders for memory problems.

Results

After repeated invitations, the participation rate was 40% (N=794) of SARS-CoV-2 positive, 26% (N=7993) of negative, and 22% (N=4369) of untested randomly selected invitees. All participants completed the baseline questionnaire as a part of inclusion.

The follow-up period was 248 days (SD=18) from baseline, and the follow-up questionnaire was completed by 75% of SARS-CoV-2 positive participants, 65% of negative participants, and 73% of untested randomly selected participants.

At follow-up, 49 (11.5%) of the SARS-CoV-2 positive participants reported memory problems in contrast to 173 (4.1%) of the SARS-CoV-2 negative participants and 65 (2.4%) of the untested randomly selected participants.

In a multivariate model, SARS-CoV-2 positivity remained strongly associated with reporting memory problems at eight months follow-up compared to the SARS-CoV-2 negative group (odds ratio (OR) 4.0, 95% confidence interval (CI) 2.8-5.2) and the untested group (OR 4.9, 95% CI 3.4-7.2).

Compared to the other groups, SARS-CoV-2 positive participants also reported more concentration problems and a significant worsening of health compared to one year ago at follow-up. Feeling depressed, less energy, or pain were reported relatively equally by the different groups.

We find that 11.5% of COVID-19 patients experience memory problems eight months after the disease. SARS-CoV-2 is a new virus, and the long-term consequences of infections are therefore unknown. Our results show that a relatively high proportion of non-hospitalized COVID-19 patients report memory problems eight months after the disease.
The plant immune receptors NRG1.1 and ADR1 are calcium influx channels
Authors: Jacob Pierre , Kim Nak Hyun , Wu Feihua , El-Kasmi Farid , Walton William G. , Furzer Oliver J. , Lietzan Adam D. , Sunil Sruthi , Kempthorn Korina , Redinbo Matthew R. , Pei Zhen-Ming , Wan Li , Dangl Jeffery L.
Published: February 2021

Plant nucleotide-binding leucine-rich repeat receptors (NLRs) regulate immunity and cell death. RPW8 domain-containing “helper” NLRs (RNLs) are required by many “sensor” NLRs. Our crystal structure of the RNL N REQUIREMENT GENE 1.1 (NRG1.1) N-terminal signaling domain resembled that of the resting state plant resistosome-forming HOPZ-ACTIVATED RESISTANCE 1 (ZAR1) and the animal MIXED-LINEAGE KINASE-LIKE (MLKL) cation channel. Active NRG1.1 oligomerized, was enriched in plasma membrane puncta and conferred cytoplasmic Ca2+influx in plant and human HeLa cells. NRG1.1-dependent Ca2+influx and cell death were sensitive to Ca2+channel blockers. Ca2+influx and cell death mediated by NRG1.1 and ACTIVATED DISEASE RESISTANCE 1 (ADR1), another RNL, required conserved negatively charged N-terminal residues. Thus, RNLs apparently form influx channels to directly regulate cytoplasmic [Ca2+] and consequent cell death.

One Sentence Summary

A specific class of plant immune receptors function as calcium-permeable channels upon activation to induce cell death.
Chronos: a CRISPR cell population dynamics model
Authors: Dempster Joshua M. , Boyle Isabella , Vazquez Francisca , Root David , Boehm Jesse S. , Hahn William C. , Tsherniak Aviad , McFarland James M.
Published: February 2021

CRISPR loss of function screens are a powerful tool to interrogate cancer biology but are known to exhibit a number of biases and artifacts that can confound the results, such as DNA cutting toxicity, incomplete phenotype penetrance and screen quality bias. Computational methods that more faithfully model the CRISPR biological experiment could more effectively extract the biology of interest than typical current methods. Here we introduce Chronos, an algorithm for inferring gene knockout fitness effects based on an explicit model of the dynamics of cell proliferation after CRISPR gene knockout. Chronos is able to exploit longitudinal CRISPR data for improved inference. Additionally, it accounts for multiple sources of bias and can effectively share information across screens when jointly analyzing large datasets such as Project Achilles and Score. We show that Chronos outperforms competing methods across a range of performance metrics in multiple types of experiments.
Structural and molecular characterization of theRpv3locus towards the development of KASP markers for downy mildew resistance in grapevine (Vitisspp.)
Authors: Wairich Andriele , Malabarba Jaiana , Buffon Vanessa , Porto Diogo Denardi , Togawa Roberto , Revers Luís F.
Published: February 2021

Plasmopara viticolais the oomycete that causes downy mildew in grapevine. Varying levels of resistance toP. viticolaacross grape cultivars allowed quantitative trait loci to be identified. TheRpv3locus is located at chromosome 18, in a region enriched in TIR-NBS-LRR genes, and the phenotype associated is a high hypersensitive response. In this work, we aimed to identify candidate genes associated with resistance to downy mildew on theRpv3locus and to evaluate their transcriptional profiles in a susceptible and a resistant grapevine cultivar after challenging withP. viticola. Candidate genes were identified by representational differential analysis and also by functional enrichment tests. Many predicted genes associated with resistance to diseases were found at theRpv3locus. In total, seventeen genes were evaluated by RT-qPCR. Differences in the steady-state expression of these genes were observed between the two cultivars. Four genes were found to be expressed only in Villard Blanc, suggesting their association to the hypersensitivity reaction. Concerning marker assisted-selection for downy mildew resistance, we show the efficient use of a haplotype of SSR markers. Furthermore, based onRpv3-located SNPs between grapevine cultivars contrasting in downy mildew resistance, we developed and tested forty-one new markers for assisted selection. After genotypic and phenotypic evaluations on segregant populations, two markers, Rpv3_15 and Rpv3_33, were considered efficient for downy mildew resistance identification. This study constitutes an in-depth genomic characterization of theRpv3locus, confirms its involvement in resistance againstP. viticolainfection and presents promising biotechnological tools for the selection of young resistant individuals.
Impaired activation of Transposable Elements in SARS-CoV-2 infection
Authors: Sorek Matan , Meshorer Eran , Schlesinger Sharon
Published: February 2021

Transposable element (TE) transcription is induced in response to viral infections. TE induction triggers a robust and durable interferon (IFN) response, providing a host defense mechanism. Still, the connection between SARS-CoV-2 IFN response and TEs remains largely unknown. Here, we analyzed TE expression changes in response to SARS-CoV-2 infection in different human cellular models. We find that compared to other viruses, which cause global upregulation of TEs, SARS-CoV-2 infection results in a significantly milder TE response in both primary lung epithelial cells and in iPSC-derived lung alveolar type 2 cells. TE activation precedes, and correlates with, the induction of IFN-related genes, suggesting that the limited activation of TEs following SARS-CoV-2 infection may be the reason for the weak IFN response. Diminished TE activation was not observed in lung cancer cell lines with very high viral load. Moreover, we identify two variables which explain most of the observed diverseness in immune responses: basal expression levels of TEs in the pre-infected cells, and the viral load. Finally, analyzing the SARS-CoV-2 interactome, as well as the epigenetic landscape around the TEs that are activated following infection, we identify SARS-CoV-2 interacting proteins, which may regulate chromatin structure and TE transcription in response to a high viral load. This work provides a functional explanation for SARS-CoV-2’s success in its fight against the host immune system, and suggests that TEs could be used as sensors and serve as potential drug targets for COVID-19.

Key points

Unlike other viruses, SARS-CoV-2 invokes a weak and inefficient transposable element (TE) response

TE induction precedes and predicts IFN response

Basal TE expression and viral load explain immune responses

Distinct chromatin and enhancer binding factors occupancy on TEs induced by SARS-CoV-2
Tissue-resident, extravascular CD64-Ly6C-population forms a critical barrier for inflammation in the synovium
Authors: Montgomery Anna B. , Chen Shang Yang , Gadhvi Gaurav , Mayr Maximilian G. , Cuda Carla M , Dominguez Salina , Makinde Hadijat-Kubura Moradeke , Misharin Alexander , Gurra Miranda G. , Akbarpour Mahzad , Bharat Ankit , Budinger G. R. Scott , Winter Deborah R. , Perlman Harris
Published: February 2021

Monocytes are one of the most abundant immune cells infiltrating the inflamed organs. However, the majority of studies on monocytes focus on circulating cells, rather than those in the tissue. Here, we identify and characterize an intravascular (i.v.) and extravascular (e.v.) synovial population (Syn Ly6C-cells) which lack cell surface markers of classical monocytes (Ly6C and CD62) or tissue macrophages (CD64 and Tim4), are transcriptionally distinct and conserved in RA patients. e.v. Syn Ly6C-cells are independent of NR4A1 and CCR2, long-lived and embryonically derived while the i.v. Syn Ly6C-cells are dependent on NR4A1, short lived and derived from circulating NCM. e.v. Syn Ly6C-cells undergo increased proliferation and reverse diapedesis dependent on LFA1 in response to arthrogenic stimuli and are required for the development of RA-like disease. These findings uncover a new facet of mononuclear cell biology and are imperative to understanding tissue-resident myeloid cell function in RA.
Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2
Authors: Penner Robert
Published: February 2021

Abstract

New tools developed by Moderna, BioNTech/Pfizer, and Oxford/Astrazeneca, among others, provide universal solutions to previously problematic aspects of drug or vaccine delivery, uptake and toxicity, portending new tools across the medical sciences. A novel method is presented based on estimating protein backbone free energy via geometry to predict effective antiviral targets, antigens and vaccine cargos that are resistant to viral mutation. This method, partly described in earlier work of the author, is reviewed and reformulated here in light of the recent proliferation of structural data on the SARS-CoV-2 spike glycoprotein and its latest mutations in the variants of concern and several further variants of interest including all international lineages. Particular attention to structures computed with Cryo Electron Microscopy allows the novel approach of probing the pH dependence of free energy in order to infer function. Key findings include: collections of recurring mutagenic residues occur across strains, presumably through cooperative convergent evolution; the preponderance of mutagenic residues do not participate in backbone hydrogen bonds; metastability of the spike glycoprotein limits the change of free energy from before to after mutation and thereby constrains selective pressure; and there are mRNA or virus-vector cargos which target low free energy peptides proximal to conserved high free energy peptides providing specific recipes for vaccines with greater specificity than the current full-spike approach. These results serve to limit peptides in the spike glycoprotein with high mutagenic potential and thereby provide a priori constraints on viral and attendant vaccine evolution. Scientific and regulatory challenges to nucleic acid therapeutic and vaccine development and deployment are finally discussed.
A precise and general FRET-based method for monitoring structural transitions in protein self-organization
Authors: Wan Qi , Mouton Sara N. , Veenhoff Liesbeth M. , Boersma Arnold J.
Published: February 2021

Proteins assemble into a tremendous variety of dynamic and functional structures. Sensitive measurements directly in cells with a high spatiotemporal resolution are needed to distinguish these different assemblies. Here, we demonstrate precise and continuous monitoring of cytoplasmic protein self-assemblies and their structural transitions. Intermolecular FRET with both the donor and acceptor protein at the same target protein provides high sensitivity while retaining the advantage of straightforward ratiometric imaging. We measure different assembly structures, transient intermediate states’ kinetics, and assembly formation resolved in space and time. Specifically, the method recapitulates that i) the mutant Huntingtin exon1 (mHttex1) protein first forms low-FRET and presumably less ordered assemblies in yeast and human cells, which develop into high-FRET aggregates, ii) the chaperone DNAJB6b prevents low-FRET mHttex1 assemblies, yet coassembles with mHttex1 aggregates, and iii) FUS’ condensates have mutation-dependent nanoscopic structures. FACS measurements allow assembly measurement in a high-throughput manner crucial for screening efforts, while fluorescence microscopy provides spatiotemporally-resolved measurements on the single-condensate level during a cell’s lifetime to assess the biological consequences. Implementation in other native or non-native proteins could provide insight into many studies involving protein condensation or aggregation.
Low-input ATAC&mRNA-Seq: a simple and robust method for simultaneous dual-omics profiling with low cell number
Authors: Li Ruifang , Grimm Sara A , Wade Paul A
Published: February 2021

Deciphering epigenetic regulation of gene expression requires measuring the epigenome and transcriptome jointly. Single-cell multi-omics technologies have been developed for concurrent profiling of chromatin accessibility and gene expression. However, multi-omics profiling of low-input bulk samples remains challenging. Therefore, we developed low-input ATAC&mRNA-seq, a simple and robust method for studying the role of chromatin structure in gene regulation in a single experiment with thousands of cells, to maximize insights from limited input material by obtaining ATAC-seq and mRNA-seq data simultaneously from the same cells with data quality comparable to conventional mono-omics assays. Integrative data analysis revealed similar strong association between promoter accessibility and gene expression using the data of low-input ATAC&mRNA-seq as using single-assay data, underscoring the accuracy and reliability of our dual-omics assay to generate both data types simultaneously with just thousands of cells. We envision our method to be widely applied in many biological disciplines with limited materials.