bluuebunny/crossref_metadata_2025 huggingface dataset:
Separate to operate: the centriole-free inner core of the centrosome regulates the assembly of the intranuclear spindle in Toxoplasma gondii
Authors: Tomasina Ramiro , Martins-Duarte Érica S. , Bastin Philippe , Gissot Mathieu , Francia María E.
Published: January 2022

Centrosomes are the main microtubule-organizing center of the cell. They are normally formed by two centrioles, embedded in a cloud of proteins known as pericentriolar material (PCM). The PCM ascribes centrioles with their microtubule nucleation capacity. Toxoplasma gondii, the causative agent of toxoplasmosis, divides by endodyogeny. Successful cell division is critical for pathogenesis. The centrosome, one of the microtubule organizing centers of the cell, plays central roles in orchestrating the temporal and physical coordination of major organelle segregation and daughter cell formation. The Toxoplasma centrosome is constituted by two domains; an outer core, distal from the nucleus, and an inner core, proximal to the nucleus. This dual organization has been proposed to underlie T. gondii’s cell division plasticity. Homeostasis of the outer core has been shown to be critical for the proper assembly of the daughter cells. However, the role of the inner core remains undeciphered. Here, we focus on understanding the function of the inner core by studying the dynamics and role of its only known molecular marker; TgCEP250L1. We show that upon conditional degradation of TgCEP250L1, parasites are unable to survive. Mutants exhibit nuclear segregation defects, whilst normally forming daughter cells. In addition, the rest of the centrosome, defined by the position of the centrioles, disconnects from the nucleus. We explore the structural defects underlying these phenotypes by high resolution microscopy. We show that TgCEP250L1’s location is dynamic and encompasses the formation of the mitotic spindle. Moreover, we show that in the absence of TgCEP250L1, the microtubule binding protein TgEB1, fails to translocate from the nucleus to the mitotic spindle, while polyploid nuclei accumulate. Overall, our data supports a model in which the inner core of the T. gondii centrosome critically participates in cell division by directly impacting the formation or stability of the mitotic spindle.
Molecular surveillance reveals widespread colonisation by carbapenemase and extended spectrum beta-lactamase producing organisms in neonatal units in Kenya and Nigeria
Authors: Edwards Thomas , Williams Christopher T , Olwala Macrine , Andang’o Pauline , Otieno Walter , Nalwa Grace N , Akindolire Abimbola , Cubas-Atienzar Ana I , Ross Toby , Tongo Kemi , Adams Emily R , Nabwera Helen , Allen Stephen
Published: January 2022

Objectives

Neonatal sepsis, a major cause of death amongst infants in sub-Saharan Africa, is often gut derived. Impairments in immunity and the gut barrier in sick neonates allow colonisation by opportunistic pathogens such as Enterobacteriaceae to progress to blood stream infection. Colonisation by Enterobacteriaceae producing extended spectrum beta-lactamase (ESBL) or carbapenemase enzymes is particularly problematic and can lead to antimicrobial-resistant (AMR) or untreatable infections. We sought to explore the rates of colonisation by ESBL or carbapenemase producers and their genotypes in two neonatal units (NNUs) in West and East Africa.

Methods

Stool and rectal swab samples were taken at multiple timepoints from newborns admitted to the NNUs at the University College Hospital, Ibadan, Nigeria and the Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu, western Kenya. Samples were tested for ESBL and carbapenemase genes using a previously validated qPCR assay with high resolution melt analysis. Kaplan-Meier survival analysis was used to examine colonisation rates at both sites.

Results

A total of 119 stool and rectal swab samples were taken from 42 infants admitted to the two NNUs. Six (14.3%) infants were extremely preterm (gestation <28 weeks), 19 (45.2%) were born by Caesarean section and 3 (8.6%) mothers were HIV positive. Median (IQR) duration of admission was 12.5 (5-26) days and 12 (28.6%) infants died. Overall, colonisation with ESBL (37 infants, 89%) was more common than with carbapenemase producers (26, 62.4%; P = 0.093). Median survival time before colonisation with ESBL organisms was 7 days and with carbapenemase producers 16 days (P=0.035). The majority of ESBL genes detected belonged to the CTX-M-1 (36/38; 95%), and CTX-M-9 (2/36; 5%) groups. The most prevalent carbapenemase was blaNDM (27/29, 93%). Single blaVIM (1/32, 3%) and blaOXA-48 genes (1/32, 3%) were also detected.

Conclusions

Gut colonisation of neonates by AMR organisms was common and occurred rapidly in NNUs in Kenya and Nigeria. Active surveillance of colonisation will improve the understanding of AMR in these settings and guide infection control and antibiotic prescribing practice to improve clinical outcomes.

Highlights

Colonisation with extended spectrum beta-lactamase (ESBL) or carbapenemase producing bacteria was common in two neonatal units in Kenya and Nigeria

ESBL colonisation occurred in 89% of neonates, with a median colonisation time of 7 days

Colonisation with carbapenemase producers occurred in 62% of neonates, with a median time to colonisation of 16 days

The most common ESBL genes detected were of the CTX-M-1 family, whilst the most common carbapenemase detected was blaNDM
Barley stripe mosaic virusγb protein targets thioredoxin h-type 1 to dampen SA-mediated antiviral defenses
Authors: Jiang Zhihao , Jin Xuejiao , Yang Meng , Pi Qinglin , Cao Qing , Li Zhenggang , Zhang Yongliang , Wang Xian-Bing , Han Chenggui , Yu Jialin , Li Dawei
Published: January 2022

Salicylic acid (SA) acts as a signaling molecule to perceive and defend against pathogen infections. Accordingly, pathogens evolve versatile strategies to disrupt the SA-mediated signal transduction. However, it is necessary to further characterize how plant viruses manipulate the SA-dependent defense responses. Here, we show thatBarley stripe mosaic virus(BSMV) infection activates SA-mediated defense signaling pathway and upregulates the expression ofNicotiana benthamianathioredoxin h-type 1 (NbTRXh1). The γb protein interacts directly with NbTRXh1in vivoandin vitro. Overexpression of NbTRXh1, but not a reductase-defective mutant, impedes BSMV infection, whereas lowNbTRXh1expression level results in increased viral accumulation. Similar with its orthologues inArabidopsis, NbTRXh1 also plays an essential role in SA signaling transduction inN. benthamiana. To counteract NbTRXh1-mediated defenses, the BSMV γb protein targets NbTRXh1 to dampen its reductase activity and thereby impairing downstream SA defense genes expression to optimize viral cell-to-cell movement. We also found that NbTRXh1-mediated resistance defends againstLychnis ringspot virus,Beet black scorch virus, andBeet necrotic yellow vein virus. Taken together, our results reveal a novel role for the multifunctional γb protein in counteracting plant defense responses, and broadens the broad-spectrum antibiotic role of SA signaling pathway.

One sentence summary

BSMV γb protein impairs NbTRXh1 reductase activity and dampen downstream SA-related genes expression to facilitate viral cell-to-cell movement.
Functional oscillation of a multienzyme glucosome assembly during cell cycle progression
Authors: Jeon Miji , Schmitt Danielle L. , Kyoung Minjoung , An Songon
Published: January 2022

Glucose metabolism has been studied extensively to understand functional interplays between metabolism and a cell cycle. However, our understanding of cell cycle-dependent metabolic adaptation particularly in human cells remains largely elusive. Meanwhile, human enzymes in glucose metabolism are shown to functionally organize into three different sizes of a multienzyme metabolic assembly, the glucosome, to regulate glucose flux in a size-dependent manner. Here, using fluorescence single-cell imaging techniques, we discover that glucosomes spatiotemporally oscillate during a cell cycle in an assembly size-dependent manner. Importantly, their oscillation at single-cell levels is in accordance with functional contributions of glucose metabolism to cell cycle progression at a population level. Collectively, we demonstrate functional oscillation of glucosomes during cell cycle progression and thus their biological significance to human cell biology.
COVID-19-related school disruptions and well-being of children and adolescents in Geneva
Authors: Richard Viviane , Dumont Roxane , Lorthe Elsa , Baysson Hélène , Zaballa María-Eugenia , Barbe Rémy P. , Posfay-Barbe Klara M. , Guessous Idris , Stringhini Silvia
Published: January 2022

Background

Various studies showed the negative impact of COVID-19-related lockdowns and school closures on the well-being of children and adolescents. However, the prevalence and consequences of occasional short-term school disruptions due to COVID-19-related quarantine or isolation remain unknown. This study evaluated their impact on the well-being and stress level of children and adolescents.

Methods

In June/July 2021, we conducted a survey selecting a representative sample of children and adolescents of a Swiss canton population. Parents of school-aged children reported information about them missing school because of COVID-19, from August 2020 to June 2021, as well as about their health-related quality of life (HRQoL) measured with the KINDL® scale and their stress level.

Results

Among the 538 participants, 216/538 (40.1%) pupils missed school at least once for COVID-19-related causes, with a total of 272 absences. We observed no relationship between the frequency of COVID-19-related absences and the HRQoL or stress level, even when stratifying by the type of absence or socio-demographic factors.

Discussion

Overall, these findings are reassuring in that quarantines and related school disruptions, which we know are a common and effective way of controlling SARS-CoV-2 transmission, did not seem to meaningfully impact children and adolescent’s wellbeing and stress. Finding the right balance between SARS-CoV-2 control and young populations’ well-being is challenging, and the current results provide additional information for decision makers.
Reconstructing transmission chains of SARS-CoV-2 amid multiple outbreaks in a geriatric acute-care hospital
Authors: Abbas Mohamed , Cori Anne , Cordey Samuel , Laubscher Florian , Robalo Nunes Tomás , Myall Ashleigh , Salamun Julien , Huber Philippe , Zekry Dina , Prendki Virginie , Iten Anne , Vieux Laure , Sauvan Valérie , Graf Christophe E. , Harbarth Stephan
Published: January 2022

Background

There is ongoing uncertainty regarding transmission chains and the respective roles of healthcare workers (HCWs) and elderly patients in nosocomial outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in geriatric settings.

Methods

We performed a retrospective cohort study including patients with nosocomial coronavirus disease 2019 (COVID-19) in four outbreak-affected wards, and all SARS-CoV-2 RT-PCR positive HCWs from a Swiss university-affiliated geriatric acute-care hospital that admitted both Covid-19 and non-Covid-19 patients during the first pandemic wave in Spring 2020. We combined epidemiological and genetic sequencing data using a Bayesian modelling framework, and reconstructed transmission dynamics of SARS-CoV-2 involving patients and HCWs, in order to determine who infected whom. We evaluated general transmission patterns according to type of case (HCWs working in dedicated Covid-19 cohorting wards: HCWcovid; HCWs working in non-Covid-19 wards where outbreaks occurred: HCWoutbreak; patients with nosocomial Covid-19: patientnoso) by deriving the proportion of infections attributed to each type of case across all posterior trees and comparing them to random expectations.

Results

During the study period (March 1 to May 7, 2020) we included 180 SARS-CoV-2 positive cases: 127 HCWs (91 HCWcovid, 36 HCWoutbreak) and 53 patients. The attack rates ranged from 10-19% for patients, and 21% for HCWs. We estimated that there were 16 importation events (3 patients, 13 HCWs) that jointly led to 16 secondary cases. Most patient-to-patient transmission events involved patients having shared a ward (97.6%, 95% credible interval [CrI] 90.4-100%), in contrast to those having shared a room (44.4%, 95%CrI 27.8-62.5%). Transmission events tended to cluster by type of case: patientnosowere almost twice as likely to be infected by other patientnosothan expected (observed:expected ratio 1.91, 95%CrI 1.08 – 4.00,p= 0.02); similarly, HCWoutbreakwere more than twice as likely to be infected by other HCWoutbreakthan expected (2.25, 95%CrI 1.00-8.00,p= 0.04). The proportion of infectors of HCWcovidwere as expected as random. The proportions of high transmitters (≥2 secondary cases) were significantly higher among HCWoutbreakthan patientnosoin the late phases (26.2% vs. 13.4%, p<2.2e-16) of the outbreak.

Conclusions

Most importation events were linked to HCW. Unexpectedly, transmission between HCWcovidwas more limited than transmission between patients and HCWoutbreak. This highlights gaps in infection control and suggests possible areas of improvements to limit the extent of nosocomial transmission.
Amyloid-associated increases in soluble tau is a key driver in accumulation of tau aggregates and cognitive decline in early Alzheimer
Authors: Binette Alexa Pichet , Franzmeier Nicolai , Spotorno Nicola , Ewers Michael , Brendel Matthias , Biel Davina ,   ADNI, Strandberg Olof , Janelidze Shorena , Palmqvist Sebastian , Mattsson-Carlgren Niklas , Smith Ruben , Stomrud Erik , Ossenkoppele Rik , Hansson Oskar
Published: January 2022

For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, it is important to understand how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with PET and subsequent cognitive decline across the Alzheimer’s disease (AD) continuum. In early stages of AD, increased concentration of soluble CSF p-tau was the main driver of accumulation of insoluble tau aggregates across the brain, and mediated the effect of Aβ on tau aggregation. Further, higher soluble p-tau concentrations were mainly related to faster accumulation of tau aggregates in the regions with strong functional connectivity to individual tau epicenters. In this early stage, higher soluble p-tau concentrations were associated with cognitive decline, which was mediated by faster increase of tau aggregates. In AD dementia, when Aβ fibrils and soluble p-tau levels have plateaued, cognitive decline was driven by the accumulation rate of insoluble tau aggregates. Our data suggest that therapeutic approaches reducing soluble p-tau levels might be most favorable in early AD.
Two schizophrenia imaging signatures and their associations with cognition, psychopathology, and genetics in the general population
Authors: Chand Ganesh B. , Singhal Pankhuri , Dwyer Dominic B. , Wen Junhao , Erus Guray , Doshi Jimit , Srinivasan Dhivya , Mamourian Elizabeth , Varol Erdem , Sotiras Aristeidis , Hwang Gyujoon , Dazzan Paola , Kahn Rene S. , Schnack Hugo G. , Zanetti Marcus V. , Meisenzahl Eva , Busatto Geraldo F. , Crespo-Facorro Benedicto , Pantelis Christos , Wood Stephen J. , Zhuo Chuanjun , Shinohara Russell T. , Shou Haochang , Fan Yong , Koutsouleris Nikolaos , Kaczkurkin Antonia N. , Moore Tyler M. , Verma Anurag , Calkins Monica E. , Gur Raquel E. , Gur Ruben C. , Ritchie Marylyn D. , Satterthwaite Theodore D. , Wolf Daniel H. , Davatzikos Christos
Published: January 2022

The prevalence and significance of schizophrenia-related phenotypes at the population-level are debated in the literature. Here we assess whether two recently reported neuroanatomical signatures of schizophrenia, signature 1 with widespread reduction of gray matter volume, and signature 2 with increased striatal volume, could be replicated in an independent schizophrenia sample, and investigate whether expression of these signatures can be detected at the population-level and how they relate to cognition, psychosis spectrum symptoms, and schizophrenia genetic risk. This cross-sectional study used an independent schizophrenia-control sample (n=347; age 16-57 years) for replication of imaging signatures, and then examined two independent population-level datasets: Philadelphia Neurodevelopmental Cohort [PNC; n=359 typically developing (TD) and psychosis-spectrum symptoms (PS) youth] and UK Biobank (UKBB; n=836; age 44-50 years) adults. We quantified signature expression using support-vector machine learning, and compared cognition, psychopathology, and polygenic risk between signatures. Two neuroanatomical signatures of schizophrenia were replicated. Signature 1 but not signature 2 was significantly more common in youth with PS than TD youth, whereas signature 2 frequency was similar. In both youth and adults, signature 1 had worse cognitive performance than signature 2. Compared to adults with neither signature, adults expressing signature 1 had elevated schizophrenia polygenic risk scores, but this was not seen for signature 2. We successfully replicate two neuroanatomical signatures of schizophrenia, and describe their prevalence in population-based samples of youth and adults. We further demonstrate distinct relationships of these signatures with psychosis symptoms, cognition, and genetic risk, potentially reflecting underlying neurobiological vulnerability.
Clinical Performance of the cobas Liat SARS-CoV-2 & Influenza AB for the Detection of SARS-CoV-2 in Nasal Samples
Authors: Akashi Yusaku , Horie Michiko , Kiyotaki Junichi , Takeuchi Yuto , Togashi Kenichi , Adachi Yuki , Ueda Atsuo , Notake Shigeyuki , Nakamura Koji , Terada Norihiko , Kurihara Yoko , Kiyasu Yoshihiko , Suzuki Hiromichi
Published: January 2022

Background and Objective

Point-of-care type molecular diagnostic tests have been used for detecting SARS-CoV-2, although their clinical utility with nasal samples has yet to be established. This study evaluated the clinical performance of the cobas Liat SARS-CoV-2 & Influenza AB (Liat) in nasal samples.

Methods

Nasal and nasopharyngeal samples were collected and were tested using the Liat, the cobas 6800 system and the cobas SARS-CoV-2 & Influenza AB (cobas), and a method developed by National Institute of Infectious Diseases, Japan (NIID).

Results

A total of 814 nasal samples were collected. The Liat assay was positive for SARS-CoV-2 in 113 (13.9%). The total, positive, and negative concordance rate between the Liat and cobas/NIID assays were 99.3%/98.4%, 99.1%/100%, and 99.3%/98.2%, respectively. Five samples were positive only using the Liat assay. Their Ct values ranged from 31.9 to 37.2. The Ct values of the Liat assay were significantly lower (p < 0.001) but were correlated (p < 0.001) with those of other molecular assays. In the participants who tested positive for SARS-CoV-2 on the Liat assay using nasopharyngeal samples, 88.2% of their nasal samples also tested positive using the Liat assay.

Conclusion

The Liat assay showed high concordance with other molecular assays in nasal samples. Some discordance occurred in samples with Ct values > 30 on the Liat assay.

Key Points

The cobas Liat SARS-CoV-2 & Influenza AB assay showed high concordance with other molecular assays in nasal and nasopharyngeal samples, providing results within 20 minutes.

Some discordance occurred in samples with Ct values > 30 on the Liat assay.

The Liat assay may be suitable for use in a variety of clinical situations, primarily where accurate detection of SARS-CoV-2 is necessary.
Safety and immunogenicity of the BBIBP-CorV vaccine in adolescents aged 12-17 years in Thai population, prospective cohort study
Authors: Tawinprai Kriangkrai , Siripongboonsitti Taweegrit , Porntharukchareon Thachanun , Vanichsetakul Preeda , Thonginnetra Saraiorn , Niemsorn Krongkwan , Promsena Pathariya , Tandhansakul Manunya , Kasemlawan Naruporn , Ruangkijpaisal Natthanan , Banomyong Narin , Phattraprayoon Nanthida , Ungtrakul Teerapat , Wittayasak Kasiruck , Thonwirak Nawarat , Soonklang Kamonwan , Sornsamdang Gaidganok , Mahanonda Nithi
Published: January 2022

Introduction

COVID-19 pandemic affects all populations worldwide, including adolescents. Adolescents can develop a severe form of COVID-19, especially with comorbidity underlying. The prior studies of the mRNA COVID-19 vaccine showed excellent effectiveness in adolescents. Therefore, this study aimed to evaluate the safety and effectiveness of the BBIBP-CorV vaccine with the immunobridging approach in Thai adolescents.

Methods

This single-center, prospective cohort study compared the immunogenicity after 2 doses of the BBIBO-CorV vaccine with 21 days interval of participants aged 12-17 years with 18-30 years at Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand. The key eligible criteria were healthy or had stable pre-existing comorbidity participants, aged 12-17 years. The primary endpoint was the anti-receptor binding domain antibody concentration at 4 weeks after dose 2 of the vaccine. In addition, safety profiles were solicited adverse events within 7 days after each dose of vaccine and any adverse events through 1 month after dose 2 of the vaccine.

Results

Four weeks after the second vaccination, the GMC of anti-RBD antibody in the adolescent cohort was 102.9 BAU/mL (95%CI; 91.0-116.4) and 36.9 BAU/mL (95%CI; 30.9-44.0) in the adult cohort. The GMR of the adolescent cohort was 2.79 (95%CI; 2.25-3.46, p-value; <0.0001) compared with the adult cohort which met non-inferiority criteria. The reactogenicity was slightly less reported in the adolescent cohort compared with the adult cohort. No serious adverse events were reported in both cohorts.

Conclusion

Vaccination with the BBIBP-CorV vaccine in the adolescent participants was safe and effective.
Mobile Phone Virtual Reality Game for Pediatric Home Burn Dressing Pain Management, a Randomized Clinical Trial
Authors: Armstrong Megan , Lun Jonathan , Groner Jonathan I. , Thakkar Rajan K. , Fabia Renata , Noffsinger Dana , Xiang Henry
Published: January 2022

Importance

Virtual Reality (VR) gaming is considered a safe and effective alternative to standard pain alleviation in the hospital, we advocate for its use during repeated redressing at home.

Objective

This study will address the effectiveness and feasibility of the Virtual Reality Pain Alleviation Tool (VR-PAT) that was developed by the research team at the Nationwide Children’s Hospital for repeated at-home burn dressing changes.

Design, Setting and Participants

Randomized clinical trial among patients recruited at the Nationwide Children’s Hospital (NCH) outpatient burn clinic between September 2019 and June 2021. We included English-speaking burn patients 5-17 years old requiring daily dressing changes for at least one week after first outpatient dressing change.

Interventions

One group played an interactive VR-PAT game during dressing changes, while the other utilized standard distraction techniques available in the home for a week. Both child and caretaker were later asked to assess perceived pain. Those in the intervention group were asked to evaluate convenience and enjoyment of the VR-PAT game.

Outcomes

Patients were asked to rate perceived pain on a scale of 1-10, and caregivers were asked to rate observed pain on a scale of 1-10. For the VR-PAT group, patients were also asked to rate various aspects of the VR game on a scale of 1-10 and caregivers were asked questions assessing ease of use.

Conclusions

Subjects found the VR-PAT to be a useful distraction during home dressing changes and reported it be easy to implement. In the VR-PAT group, child and caregiver reported pain decreased as the week of dressing changes progressed and was lower than those in the control group after the fourth dressing change. Children playing the VR-PAT reported consistent happiness and fun as the week went on and increased realism and engagement, which means our results weren’t just due to the novel experience of VR-PAT.

Trial Registration

ClinicalTrials.gov Identifier: NCT04548635
Identifying SARS-CoV-2 regional introductions and transmission clusters in real time
Authors: McBroome Jakob , Martin Jennifer , de Bernardi Schneider Adriano , Turakhia Yatish , Corbett-Detig Russell
Published: January 2022

The unprecedented SARS-CoV-2 global sequencing effort has suffered from an analytical bottleneck. Many existing methods for phylogenetic analysis are designed for sparse, static datasets and are too computationally expensive to apply to densely sampled, rapidly expanding datasets when results are needed immediately to inform public health action. For example, public health is often concerned with identifying clusters of closely related samples, but the sheer scale of the data prevents manual inspection and the current computational models are often too expensive in time and resources. Even when results are available, intuitive data exploration tools are of critical importance to effective public health interpretation and action. To help address this need, we present a phylogenetic summary statistic which quickly and efficiently identifies newly introduced strains in a region, resulting clusters of infected individuals, and their putative geographic origins. We show that this approach performs well on simulated data and is congruent with a more sophisticated analysis performed during the pandemic. We also introduce Cluster Tracker (https://clustertracker.gi.ucsc.edu/), a novel interactive web-based tool to facilitate effective and intuitive SARS-CoV-2 geographic data exploration and visualization. Cluster-Tracker is updated daily and automatically identifies and highlights groups of closely related SARS-CoV-2 infections resulting from inter-regional transmission across the United States, streamlining public health tracking of local viral diversity and emerging infection clusters. The combination of these open-source tools will empower detailed investigations of the geographic origins and spread of SARS-CoV-2 and other densely-sampled pathogens.
Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants
Authors: Tseng Hung Fu , Ackerson Bradley K. , Luo Yi , Sy Lina S. , Talarico Carla A. , Tian Yun , Bruxvoort Katia J. , Tubert Julia E. , Florea Ana , Ku Jennifer H. , Lee Gina S. , Choi Soon Kyu , Takhar Harpreet S. , Aragones Michael , Qian Lei
Published: January 2022

SARS-CoV-2 omicron (B.1.1.529) variant is highly transmissible with potential immune escape. We conducted a test-negative case-control study to evaluate mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with omicron or delta. The large, diverse study population included 26,683 SARS-CoV-2 test-positive cases with variant determined by spike gene status (16% delta, 84% omicron). The 2-dose VE against omicron infection at 14-90 days was 44.0% (95% CI, 35.1–51.6%) but declined quickly. The 3-dose VE was 93.7% (92.2–94.9%) and 86.0% (78.1–91.1%) against delta infection and 71.6% (69.7–73.4%) and 47.4% (40.5–53.5%) against omicron infection at 14-60 days and >60 days, respectively. The 3-dose VE was 29.4% (0.3–50.0%) against omicron infection in immunocompromised individuals. The 3-dose VE against hospitalization with delta or omicron was >99%. Our findings demonstrate high, durable 3-dose VE against delta infection but lower effectiveness against omicron infection, particularly among immunocompromised people. However, 3-dose VE was high against hospitalization with delta or omicron.
Frequency Effects on Spelling Error Recognition: An ERP Study
Authors: Larionova Ekaterina V. , Martynova Olga V.
Published: January 2022

Spelling errors are ubiquitous in all writing systems. Most studies exploring spelling errors focused on the phonological plausibility of errors. However, unlike typical pseudohomophones, spelling errors occur in naturally produced written language with variable frequencies. We investigated the time course of recognition of the most frequent orthographic errors in Russian (error in an unstressed vowel at the root) and the effect of word frequency on this process. During ERP recording, 26 native Russian speakers silently read high-frequency correctly spelled words, low-frequency correctly spelled words, high-frequency words with errors, and low-frequency words with errors. The amplitude of P200 was more positive for correctly spelled words than for misspelled words and did not depend on the frequency of the words. Word frequency affected spelling recognition in the later stages of word processing (350–700 ms): high-frequency misspelled words elicited a greater P300 than high-frequency correctly spelled words, and low-frequency misspelled words elicited a greater N400 than low-frequency correctly spelled words. We observe spelling effects in the same time window for both the P300 and N400, which may reflect temporal overlap between mainly categorization processes based on orthographic properties for high-frequency words and phonological processes for low-frequency words. We concluded that two independent pathways can be active simultaneously during spelling recognition: one reflects mainly orthographic processing of high-frequency words and the other is the phonological processing of low-frequency words. Our findings suggest that these pathways are associated with different ERP components. Therefore, our results complement existing reading models and demonstrate that the neuronal underpinnings of spelling error recognition during reading depend on word frequency.
Ecological speciation promoted by divergent regulation of functional genes within African cichlid fishes
Authors: Carruthers Madeleine , Edgley Duncan E. , Saxon Andrew D. , Gabagambi Nestory P. , Shechonge Asilatu , Miska Eric A. , Durbin Richard , Bridle Jon R. , Turner George F. , Genner Martin J.
Published: January 2022

Rapid ecological speciation along depth gradients has taken place independently and repeatedly in freshwater fishes. While the extent of genomic divergence between ecomorphs is often well understood, the molecular mechanisms facilitating such rapid diversification are typically unclear. In Lake Masoko, an East African crater lake, the cichlidAstatotilapia callipterahas diverged into shallow littoral and deep benthic ecomorphs with strikingly different jaw structures within the last 1,000 years. Using genome-wide transcriptome data from jaw tissue, we explore two major regulatory transcriptional mechanisms, expression and splicing QTL variants and examine their contribution to differential gene expression underpinning functional phenotypes. We identified 7,550 genes with significant differential expression between ecomorphs, of which 4.2% were regulated bycis-regulatory expression QTLs, and 6.4% were regulated bycis-regulatory splicing QTLs. There were also strong signals of divergent selection of differentially expressed genes that showed divergent regulation from expression, splicing or both QTL variants, including genes associated with major jaw plasticity and adaptation networks, adaptive immune system response, and oxidoreductase processes. These results suggest that transcriptome plasticity and modification have important roles during early-stage ecological speciation and demonstrate the role of regulatory-variants as important targets of selection driving ecologically-relevant divergence in gene expression that is associated with adaptive diversification.
Ecology, more than antibiotics consumption, is the major predictor for the global distribution of aminoglycoside-modifying enzymes
Authors: Pradier Léa , Bedhomme Stéphanie
Published: January 2022

Antibiotics consumption and its abuses have been historically and repeatedly pointed out as the major driver of antibiotic resistance emergence and propagation. However, several examples show that resistance may persist despite substantial reductions in antibiotic use, and that other factors are at stake. Here we study the temporal, spatial, and ecological distribution patterns of aminoglycoside resistance, by screening more than 160,000 publicly available genomes for 27 clusters of genes encoding aminoglycoside-modifying enzymes (AMEGs). We find that AMEGs are ubiquitous: about 25% of sequenced bacteria carry AMEGs. These bacteria were sequenced from all the continents and terrestrial biomes, and belong to a wide number of phyla. By focusing on several European countries between 1997 and 2018, we show that aminoglycoside consumption has little impact on the prevalence of AMEG-carrying bacteria, whereas most variation in prevalence is observed among biomes. We further analyze the resemblance of resistome compositions across biomes: soil, wildlife, and human samples appear to be central to understand the exchanges of AMEGs between different ecological contexts. Moreover, the genomic distribution of AMEGs suggests a selection for widening resistance spectra, mostly driven by mobile genetic elements. Together, these results support the idea that interventional strategies based on reducing antibiotic use should be complemented by a stronger control of exchanges, especially between ecosystems.
Transcription shapes 3D chromatin organization by interacting with loop extrusion
Authors: Banigan Edward J. , Tang Wen , van den Berg Aafke A. , Stocsits Roman R. , Wutz Gordana , Brandão Hugo B. , Busslinger Georg A. , Peters Jan-Michael , Mirny Leonid A.
Published: January 2022

Cohesin folds mammalian interphase chromosomes by extruding the chromatin fiber into numerous loops. “Loop extrusion” can be impeded by chromatin-bound factors, such as CTCF, which generates characteristic and functional chromatin organization patterns. It has been proposed that transcription relocalizes or interferes with cohesin, and that active promoters are cohesin loading sites. However, the effects of transcription on cohesin have not been reconciled with observations of active extrusion by cohesin. To determine how transcription modulates extrusion, we studied mouse cells in which we could alter cohesin abundance, dynamics, and localization by genetic ‘knockouts’ of the cohesin regulators CTCF and Wapl. Through Hi-C experiments, we discovered intricate, cohesin-dependent contact patterns near active genes. Chromatin organization around active genes exhibited hallmarks of interactions between transcribing RNA polymerases (RNAPs) and extruding cohesins. These observations could be reproduced by polymer simulations in which RNAPs were “moving barriers” to extrusion that obstructed, slowed, and pushed cohesins. The simulations predicted that preferential loading of cohesin at promoters is inconsistent with our experimental data. Additional ChIP-seq experiments showed that the putative cohesin loader Nipbl is not predominantly enriched at promoters. Therefore, we propose that cohesin is not preferentially loaded at promoters and that the barrier function of RNAP accounts for cohesin accumulation at active promoters. Altogether, we find that RNAP is a new type of extrusion barrier that is not stationary, but rather, translocates and relocalizes cohesin. Loop extrusion and transcription might interact to dynamically generate and maintain gene interactions with regulatory elements and shape functional genomic organization.

Significance Statement

Loop extrusion by cohesin is critical to folding the mammalian genome into loops. Extrusion can be halted by CTCF proteins bound at specific genomic loci, which generates chromosomal domains and can regulate gene expression. However, the process of transcription itself can modulate cohesin, thus refolding chromosomes near active genes. Through experiments and simulations, we show that transcribing RNA polymerases (RNAPs) act as “moving barriers” to loop-extruding cohesins. Unlike stationary CTCF barriers, RNAPs actively relocalize cohesins, which generates characteristic patterns of spatial organization around active genes. Our model predicts that the barrier function of RNAP can explain why cohesin accumulates at active promoters and provides a mechanism for clustering active promoters. Through transcription-extrusion interactions, cells might dynamically regulate functional genomic contacts.
Wnt11 family dependent morphogenesis during frog gastrulation is marked by the cleavage furrow protein anillin
Authors: Van Itallie Elizabeth S. , Field Christine M. , Mitchison Timothy J. , Kirschner Marc W.
Published: January 2022

Wnt11 family proteins are ligands that activate a type of Dishevelled-mediated, non-canonical Wnt signaling pathway. Loss of function causes defects in gastrulation and/or anterior-posterior axis extension in all vertebrates. Non-mammalian vertebrate genomes encode two Wnt11 family proteins whose distinct functions have been unclear. We knocked down zygotic Wnt11b and Wnt11, separately and together, in Xenopus laevis. Single morphants exhibited very similar phenotypes of delayed blastopore closure, but they had different phenotypes at the tailbud stage. In response to their very similar gastrulation phenotypes, we chose to characterize dual morphants. Using dark field illuminated time-lapse imaging and kymograph analysis, we identified a failure of dorsal blastopore lip maturation that correlated with slower blastopore closure and failure to internalize the endoderm at the dorsal blastopore lip. We connected these externally visible phenotypes to cellular events in the internal tissues – including the archenteron – by imaging intact embryos stained for anillin and microtubules. The cleavage furrow protein anillin provided an exceptional cytological marker for blastopore lip and archenteron morphogenesis and the consequent disruption through loss of Wnt 11 signaling. These cytological changes suggest a novel role for the regulation of contractility and stiffness of the epithelial cells that result in dramatic shape changes and are important in gastrulation.
Toxin-producing endosymbionts shield pathogenic fungus against micropredators
Authors: Richter Ingrid , Radosa Silvia , Cseresnyés Zoltán , Ferling Iuliia , Büttner Hannah , Niehs Sarah P. , Gerst Ruman , Figge Marc Thilo , Hillmann Falk , Hertweck Christian
Published: January 2022

The phytopathogenic fungus Rhizopus microsporus harbours a bacterial endosymbiont (Mycetohabitans rhizoxinica) for the production of the toxin rhizoxin, the causative agent of rice seedling blight. This toxinogenic bacterial-fungal alliance is, however, not restricted to the plant disease, but has been detected in numerous environmental isolates from geographically distinct sites covering all five continents. Yet, the ecological role of rhizoxin beyond rice seedling blight has been unknown.

Here we show that rhizoxin serves the fungal host in fending off protozoan and metazoan predators. Fluorescence microscopy and co-culture experiments with the fungivorous amoeba Protostelium aurantium revealed that ingestion of R. microsporus spores is toxic to P. aurantium. This amoebicidal effect is caused by the bacterial rhizoxin congener rhizoxin S2, which is also lethal towards the model nematode Caenorhabditis elegans. By combining stereomicroscopy, automated image analyses, and quantification of nematode movement we show that the fungivorous nematode Aphelenchus avenae actively feeds on R. microsporus that is lacking endosymbionts, while worms co-incubated with symbiotic R. microsporus are significantly less lively.

This work uncovers an unexpected ecological role of rhizoxin as shield against micropredators. This finding suggests that predators may function an evolutionary driving force to maintain toxin-producing endosymbionts in non-pathogenic fungi.
Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome
Authors: Yatskevich Stanislau , Muir Kyle W. , Bellini Dom , Zhang Ziguo , Yang Jing , Tischer Thomas , Predin Masa , Dendooven Tom , McLaughlin Stephen H. , Barford David
Published: January 2022

Accurate chromosome segregation, controlled by kinetochore-mediated chromatid attachments to the mitotic spindle, ensures the faithful inheritance of genetic information. Kinetochores assemble onto specialized CENP-A nucleosomes (CENP-ANuc) of centromeric chromatin. In humans, this is mostly organized as thousands of copies of an ∼171 bpα-satellite repeat. Here, we describe the cryo-EM structure of the human inner kinetochore CCAN (Constitutive Centromere Associated Network) complex bound to CENP-ANucreconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-ANuc, while a linker DNA segment of the α-satellite repeat emerges from the fully-wrapped end of the nucleosome to thread through the central CENP-LN channel which tightly grips the DNA. The CENP-TWSX histone-fold module, together with CENP-HIKHead, further augments DNA binding and partially wraps the linker DNA in a manner reminiscent of canonical nucleosomes. Our study suggests that the topological entrapment of theα-satellite repeat linker DNA by CCAN provides a robust mechanism by which the kinetochore withstands the pushing and pulling of centromeres associated with chromosome congression and segregation forces.

One-Sentence Summary

The human inner kinetochore CCAN complex tightly grips the linker DNA of the α-satellite CENP-A nucleosome.
The scaffolding protein Flot2 regulates cytoneme-based transport of Wnt3 in gastric cancer
Authors: Routledge Daniel , Rogers Sally , Ashktorab Hassan , Phesse Toby J , Scholpp Steffen
Published: January 2022

The Wnt/β-catenin signalling pathway regulates multiple cellular processes during development and many diseases, including cell proliferation, migration, and differentiation. Despite their hydrophobic nature, Wnt proteins exert their function over long distances to induce paracrine signalling. Recent studies have identified several factors involved in Wnt secretion, however, our understanding of how Wnt ligands are transported between cells to interact with their cognate receptors is still debated. Here, we demonstrate that gastric cancer cells utilise cytonemes to transport Wnt3 intercellularly to promote proliferation. Furthermore, we identify the membrane-bound scaffolding protein Flotillin-2 (Flot2), frequently overexpressed in gastric cancer, as a regulator of these cytonemes. Together with the Wnt co-receptor and cytoneme initiator Ror2, Flot2 determines the number and length of Wnt3 cytonemes in gastric cancer. Finally, we show that Flot2 is necessary for Wnt8a cytonemes during zebrafish embryogenesis, suggesting a conserved mechanism for Flot2-mediated Wnt transport on cytonemes in development and disease.
Adaptation and validation of a scale to evaluate the quality of virtual courses developed for medical students in Peru during the COVID-19 pandemic
Authors: Intimayta-Escalante Claudio , Plasencia-Dueñas Rubí , Flores-Lovon Kevin , Nuñez-Lupaca Janeth N. , Chavez-Hermosilla Mario , Castillo-Blanco Ronald
Published: January 2022

Background

During the COVID-19 pandemic, medical education migrated to digital environments, without clear guidelines for virtual courses or evaluations of how these courses have been developed.

Objective

To adapt and validate a scale to evaluate the quality of virtual courses developed for human medicine students in Peru.

Methods

Cross-sectional study that adapted a scale to assess the quality of virtual courses to the context of Peruvian medical students during the COVID-19 pandemic, using the Delphi methodology and pilot tests for a rigorous evaluation of the items, resulting in a scale of 30 items that were described with summary statistics. In addition to the exploratory factor analysis (EFA) with Oblimin rotation, together with the adequacy and sample fit with Bartlett test and Kaiser-Meyer-Olkin (KMO), while the internal consistency was estimated with the alpha coefficient.

Results

A total of 297 medical students in Peru were surveyed. The descriptive statistics for the items showed a normal distribution, while the Bartlett test showed no inadequacy (X2=6134.34, p<0.01) and with the KMO test an overall value greater than 0.92 was found, therefore an AFE was performed where five factors were identified (General Quality and Didactic Methodology, Design and Navigation of the Virtual Platform, Multimedia Resources, Academic Materials) with 30 items. In the internal consistency, an alpha coefficient greater than 0.85 was estimated for the factors evaluated.

Conclusions

The adapted scale of 30 items grouped into five factors or domains, show adequate evidence of validity and reliability to be used in the evaluation of the quality of virtual courses developed for Peruvian human medicine students during the context of the COVID-19 pandemic.
The Challenges for Screening and Diagnosing Gestational Diabetes Mellitus in Brazil: a cross-sectional study in a low-risk obstetric hospital
Authors: Paes Maria Bruna Marcolino , Fernandes Vivaldo Debora Giovanna , Izidoro Thais Sales , De Freitas Ana Paula Costa , Takano Luiz , Caldeirao Talita Domingues , Sartorao Filho Carlos Izaias
Published: January 2022

Background

Gestational Diabetes Mellitus (GDM) is a very prevalent disease and can cause several morbidities for women and their offspring. The literature demonstrates the necessity for a better approach during prenatal assistance to detect and treat the disease. We aimed to evaluate the model and efficacy of GDM screening and diagnosis in a referenced low-risk obstetrical center of the municipality of Assis, Sao Paulo state, Brazil. Moreover, the specific objective was to evaluate the prevalence of GDM.

Methods

We conducted a retrospective cross-sectional study of pregnant women, in which 257 prenatal cards and the clinical approaches used for GDM diagnosis and their results. We observed the consecutive patients admitted to the low-risk referenced obstetrical service of the “Santa Casa de Assis-SP” for childbirth from January to August 2021.

Results

There were 257 pregnant women, 227 prenatal cards obtained. Of these, 24.6% of the cards were considered incomplete, 25 (9.72%) did not contain the initial fasting plasma glucose information, and 93 (36.18%) did not describe this information in the second to the third trimester. The prevalence of GDM in the population was 14.78%.

Conclusion

We observed many pregnant women not screened according to the recommended guidelines and many prenatal cards with incomplete information. According to the screening and diagnosis guidelines, GDM prevalence was underestimated. The lack of prenatal card information and inadequacy of screening and diagnoses were observed in this population.