bluuebunny/crossref_metadata_2025 huggingface dataset:
The Evolution of euAPETALA2 Genes in Vascular Plants: From Plesiomorphic Roles in Sporangia to Acquired Functions in Ovules and Fruits
Authors: Zumajo-Cardona Cecilia , Pabón-Mora Natalia , Ambrose Barbara A
Published: January 2021

The field of evolutionary developmental biology can help address how morphological novelties evolve, a key question in evolutionary biology. In Arabidopsis thaliana, APETALA2 (AP2) plays a role in the development of key plant innovations including seeds, flowers, and fruits. AP2 belongs to the AP2/ETHYLENE RESPONSIVE ELEMENT BINDING FACTOR family which has members in all viridiplantae, making it one of the oldest and most diverse gene lineages. One key subclade, present across vascular plants is the euAPETALA2 (euAP2) clade, whose founding member is AP2. We reconstructed the evolution of the euAP2 gene lineage in vascular plants to better understand its impact on the morphological evolution of plants, identifying seven major duplication events. We also performed spatiotemporal expression analyses of euAP2/TOE3 genes focusing on less explored vascular plant lineages, including ferns, gymnosperms, early diverging angiosperms and early diverging eudicots. Altogether, our data suggest that euAP2 genes originally contributed to spore and sporangium development, and were subsequently recruited to ovule, fruit and floral organ development. Finally, euAP2 protein sequences are highly conserved; therefore, changes in the role of euAP2 homologs during development are most likely due to changes in regulatory regions.
RNA polymerase clamp conformational dynamics: long-lived states and modulation by crowding, cations, and nonspecific DNA binding
Authors: Mazumder Abhishek , Wang Anna , Uhm Heesoo , Ebright Richard H , Kapanidis Achillefs N
Published: January 2021

The RNA polymerase (RNAP) clamp, a mobile structural element conserved in RNAP from all domains of life, has been proposed to play critical roles at different stages of transcription. In previous work, we demonstrated using single-molecule Förster resonance energy transfer (smFRET) that RNAP clamp interconvert between three short-lived conformational states (lifetimes ∼ 0.3–0.6 s), that the clamp can be locked into any one of these states by small molecules, and that the clamp stays closed during initial transcription and elongation. Here, we extend these studies to obtain a comprehensive understanding of clamp dynamics under conditions RNAP may encounter in living cells. We find that the RNAP clamp can populate long-lived conformational states (lifetimes > 1.0 s) and can switch between these long-lived states and the previously observed short-lived states. In addition, we find that clamp motions are increased in the presence of molecular crowding, are unchanged in the presence of elevated monovalent-cation concentrations, and are reduced in the presence of elevated divalent-cation concentrations. Finally, we find that RNAP bound to non-specific DNA predominantly exhibits a closed clamp conformation. Our results raise the possibility of additional regulatory checkpoints that could affect clamp dynamics and consequently could affect transcription and transcriptional regulation.
The role and uses of antibodies in COVID-19 infections: a living review
Authors: Scourfield D Oliver , Reed Sophie G , Quastel Max , Alderson Jennifer , Bart Valentina M T , Teijeira Crespo Alicia , Jones Ruth , Pring Ellie , Richter Felix Clemens ,   The Oxford-Cardiff COVID-19 Literature Consortium, Ahern David J , Almuttaqi Hannah , Alonzi Dominic S , Alrubayyi Aljawharah , Alsaleh Ghada , Bart Valentina M T , Batchelor Vicky , Bayliss Rebecca , Berthold Dorothée L , Bezbradica Jelena S , Bharuchq Tehmina , Borrmann Helene , Borsa Mariana , Borst Rowie , Brun Juliane , Burnell Stephanie E A , Capitani Lorenzo , Cavounidis Athena , Chapman Lucy , Chauveau Anne , Cifuentes Liliana , Codd Amy Susan , Compeer Ewoud Bernardus , Coveney Clarissa , Cross Amy , Danielli Sara , Davies Luke C , Dendrou Calliope A , Dimonte Sandra , Peter Durairaj Ruban Rex , Dustin Lynn B , Dyer Arthur , Fielding Ceri , Fischer Fabian , Gallimore Awen , Galloway Sarah , Gammage Anís , Gea-Mallorquí Ester , Godkin Andrew , Hanna Stephanie Jean , Heuberger Cornelia , Hulin-Curtis Sarah , Issa Fadi , Jones Emma , Jones Ruth , Ladell Kristin , Lauder Sarah N , Liddiard Kate , Ligoxygakis Petros , Lu Fangfang , MacLachlan Bruce , Maleki-Toyserkani Shayda , Mann Elizabeth H , Marzeda Anna M , James Matthews Reginald , Mazet Julie M , Milicic Anita , Mitchell Emma , Moon Owen , Nguyen Van Dien , O'Hanlon Miriam , Eléonore Pavillet Clara , Peppa Dimitra , Pires Ana , Pring Eleanor , Quastel Max , Reed Sophie , Rehwinkel Jan , Richmond Niamh , Richter Felix Clemens , Robinson Alice J B , Rodrigues Patrícia R S , Sabberwal Pragati , Sami Arvind , Peres Raphael Sanches , Sattentau Quentin , Schonfeldova Barbora , Scourfield David Oliver , Selvakumar Tharini A , Shepherd Freya R , Shorten Cariad , Simon Anna Katharina , Smith Adrian L , Crespo Alicia Teijeira , Tellier Michael , Thornton Emily , Uhl Lion F K , van Grinsven Erinke , Wann Angus K T , Williams Richard , Wilson Joseph D , Zhou Dingxi , Zhu Zihan , Burnell Stephanie E A
Published: January 2021

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity.
A recombineering pipeline to clone large and complex genes in Chlamydomonas
Authors: Emrich-Mills Tom Z , Yates Gary , Barrett James , Girr Philipp , Grouneva Irina , Lau Chun Sing , Walker Charlotte E , Kwok Tsz Kam , Davey John W , Johnson Matthew P , Mackinder Luke C M
Published: January 2021

The ability to clone genes has greatly advanced cell and molecular biology research, enabling researchers to generate fluorescent protein fusions for localization and confirm genetic causation by mutant complementation. Most gene cloning is polymerase chain reaction (PCR)�or DNA synthesis-dependent, which can become costly and technically challenging as genes increase in size, particularly if they contain complex regions. This has been a long-standing challenge for the Chlamydomonas reinhardtii research community, as this alga has a high percentage of genes containing complex sequence structures. Here we overcame these challenges by developing a recombineering pipeline for the rapid parallel cloning of genes from a Chlamydomonas bacterial artificial chromosome collection. To generate fluorescent protein fusions for localization, we applied the pipeline at both batch and high-throughput scales to 203 genes related to the Chlamydomonas CO2 concentrating mechanism (CCM), with an overall cloning success rate of 77%. Cloning success was independent of gene size and complexity, with cloned genes as large as 23 kb. Localization of a subset of CCM targets confirmed previous mass spectrometry data, identified new pyrenoid components, and enabled complementation of mutants. We provide vectors and detailed protocols to facilitate easy adoption of this technology, which we envision will open up new possibilities in algal and plant research.
Comparative genomics of Chlamydomonas
Authors: Craig Rory J , Hasan Ahmed R , Ness Rob W , Keightley Peter D
Published: January 2021

Despite its role as a reference organism in the plant sciences, the green alga Chlamydomonas reinhardtii entirely lacks genomic resources from closely related species. We present highly contiguous and well-annotated genome assemblies for three unicellular C. reinhardtii relatives: Chlamydomonas incerta, Chlamydomonas schloesseri, and the more distantly related Edaphochlamys debaryana. The three Chlamydomonas genomes are highly syntenous with similar gene contents, although the 129.2 Mb C. incerta and 130.2 Mb C. schloesseri assemblies are more repeat-rich than the 111.1 Mb C. reinhardtii genome. We identify the major centromeric repeat in C. reinhardtii as a LINE transposable element homologous to Zepp (the centromeric repeat in Coccomyxa subellipsoidea) and infer that centromere locations and structure are likely conserved in C. incerta and C. schloesseri. We report extensive rearrangements, but limited gene turnover, between the minus mating type loci of these Chlamydomonas species. We produce an eight-species core-Reinhardtinia whole-genome alignment, which we use to identify several hundred false positive and missing genes in the C. reinhardtii annotation and >260,000 evolutionarily conserved elements in the C. reinhardtii genome. In summary, these resources will enable comparative genomics analyses for C. reinhardtii, significantly extending the analytical toolkit for this emerging model system.
Genomic imbalance determines positive and negative modulation of gene expression in diploid maize
Authors: Shi Xiaowen , Yang Hua , Chen Chen , Hou Jie , Hanson Katherine M , Albert Patrice S , Ji Tieming , Cheng Jianlin , Birchler James A
Published: January 2021

Genomic imbalance caused by changing the dosage of individual chromosomes (aneuploidy) has a more detrimental effect than varying the dosage of complete sets of chromosomes (ploidy). We examined the impact of both increased and decreased dosage of 15 distal and 1 interstitial chromosomal regions via RNA-seq of maize (Zea mays) mature leaf tissue to reveal new aspects of genomic imbalance. The results indicate that significant changes in gene expression in aneuploids occur both on the varied chromosome (cis) and the remainder of the genome (trans), with a wider spread of modulation compared with the whole-ploidy series of haploid to tetraploid. In general, cis genes in aneuploids range from a gene-dosage effect to dosage compensation, whereas for trans genes the most common effect is an inverse correlation in that expression is modulated toward the opposite direction of the varied chromosomal dosage, although positive modulations also occur. Furthermore, this analysis revealed the existence of increased and decreased effects in which the expression of many genes under genome imbalance are modulated toward the same direction regardless of increased or decreased chromosomal dosage, which is predicted from kinetic considerations of multicomponent molecular interactions. The findings provide novel insights into understanding mechanistic aspects of gene regulation.
Polycomb Repressive Complex 2 and KRYPTONITE regulate pathogen-induced programmed cell death in Arabidopsis
Authors: Dvořák Tomaštíková Eva , Hafrén Anders , Trejo-Arellano Minerva S , Rasmussen Sheena Ricafranca , Sato Hikaru , Santos-González Juan , Köhler Claudia , Hennig Lars , Hofius Daniel
Published: January 2021

The Polycomb Repressive Complex 2 (PRC2) is well-known for its role in controlling developmental transitions by suppressing the premature expression of key developmental regulators. Previous work revealed that PRC2 also controls the onset of senescence, a form of developmental programmed cell death (PCD) in plants. Whether the induction of PCD in response to stress is similarly suppressed by the PRC2 remained largely unknown. In this study, we explored whether PCD triggered in response to immunity- and disease-promoting pathogen effectors is associated with changes in the distribution of the PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) modification in Arabidopsis thaliana. We furthermore tested the distribution of the heterochromatic histone mark H3K9me2, which is established, to a large extent, by the H3K9 methyltransferase KRYPTONITE, and occupies chromatin regions generally not targeted by PRC2. We report that effector-induced PCD caused major changes in the distribution of both repressive epigenetic modifications and that both modifications have a regulatory role and impact on the onset of PCD during pathogen infection. Our work highlights that the transition to pathogen-induced PCD is epigenetically controlled, revealing striking similarities to developmental PCD.
Recognizing humanity: dehumanization predicts neural mirroring and empathic accuracy in face-to-face interactions
Authors: Simon Jeremy C , Gutsell Jennifer N
Published: January 2021

Dehumanization is the failure to recognize the cognitive and emotional complexities of the people around us. While its presence has been well documented in horrific acts of violence, it is also theorized to play a role in everyday life. We measured its presence and effects in face-to-face dyadic interactions between strangers and found that not only was there variance in the extent to which they perceived one another as human, but this variance predicted neural processing and behavior. Specifically, participants showed stronger neural mirroring, indexed by electroencephalography (EEG) mu-suppression, in response to partners they evaluated as more human, suggesting their brains neurally simulated those targets’ actions more. Participants were also marginally more empathically accurate about the emotions of partners deemed more human and performed better with them on a cooperative task. These results suggest that there are indeed differences in our recognition of the humanity of people we meet—demonstrated for the first time in a real, face-to-face interaction—and that this mundane variation affects our ability to neurally simulate, cooperate and empathize.
Brain Activation during Thoughts of One’s Own Death and Its Linear and Curvilinear Correlations with Fear of Death in Elderly Individuals: An fMRI Study
Authors: Hirano Kanan , Oba Kentaro , Saito Toshiki , Yamazaki Shohei , Kawashima Ryuta , Sugiura Motoaki
Published: January 2021

Facing one’s own death and managing the fear of death are important existential issues, particularly in older populations. Although recent functional magnetic resonance imaging (fMRI) studies have investigated brain responses to death-related stimuli, none has examined whether this brain activation was specific to one’s own death or how it was related to dispositional fear of death. In this study, during fMRI, 34 elderly participants (aged, 60–72 years) were presented with either death-related or death-unrelated negative words and asked to evaluate the relevance of these words to the “self” or the “other.” The results showed that only the left supplementary motor area (SMA) was selectively activated during self-relevant judgments of death-related words. Regression analyses of the effect of fear of death on brain activation during death-related thoughts identified a significant negative linear correlation in the right supramarginal gyrus (SMG) and an inverted-U-shaped correlation in the posterior cingulate cortex (PCC) only during self-relevant judgments. Our results suggest potential involvement of the SMA in the existential aspect of thoughts of death. The distinct fear-of-death-dependent responses in the SMG and PCC may reflect fear-associated distancing of the physical self and the processing of death-related thoughts as a self-relevant future agenda, respectively.
FutureTox IV Workshop Summary: Predictive Toxicology for Healthy Children
Authors: Knudsen Thomas B , Fitzpatrick Suzanne Compton , De Abrew K Nadira , Birnbaum Linda S , Chappelle Anne , Daston George P , Dolinoy Dana C , Elder Alison , Euling Susan , Faustman Elaine M , Fedinick Kristi Pullen , Franzosa Jill A , Haggard Derik E , Haws Laurie , Kleinstreuer Nicole C , Buck Louis Germaine M , Mendrick Donna L , Rudel Ruthann , Saili Katerine S , Schug Thaddeus T , Tanguay Robyn L , Turley Alexandra E , Wetmore Barbara A , White Kimberly W , Zurlinden Todd J
Published: January 2021

FutureTox IV, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in November 2018. Building upon FutureTox I, II, and III, this conference focused on the latest science and technology for in vitro profiling and in silico modeling as it relates to predictive developmental and reproductive toxicity (DART). Publicly available high-throughput screening data sets are now available for broad in vitro profiling of bioactivities across large inventories of chemicals. Coupling this vast amount of mechanistic data with a deeper understanding of molecular embryology and post-natal development lays the groundwork for using new approach methodologies (NAMs) to evaluate chemical toxicity, drug efficacy, and safety assessment for embryo-fetal development. NAM is a term recently adopted in reference to any technology, methodology, approach, or combination thereof that can be used to provide information on chemical hazard and risk assessment to avoid the use of intact animals (U.S. Environmental Protection Agency [EPA], Strategic plan to promote the development and implementation of alternative test methods within the tsca program, 2018, https://www.epa.gov/sites/production/files/2018-06/documents/epa_alt_strat_plan_6-20-18_clean_final.pdf). There are challenges to implementing NAMs to evaluate chemicals for developmental toxicity compared with adult toxicity. This forum article reviews the 2018 workshop activities, highlighting challenges and opportunities for applying NAMs for adverse pregnancy outcomes (eg, preterm labor, malformations, low birth weight) as well as disorders manifesting postnatally (eg, neurodevelopmental impairment, breast cancer, cardiovascular disease, fertility). DART is an important concern for different regulatory statutes and test guidelines. Leveraging advancements in such approaches and the accompanying efficiencies to detecting potential hazards to human development are the unifying concepts toward implementing NAMs in DART testing. Although use of NAMs for higher level regulatory decision making is still on the horizon, the conference highlighted novel testing platforms and computational models that cover multiple levels of biological organization, with the unique temporal dynamics of embryonic development, and novel approaches for estimating toxicokinetic parameters essential in supporting in vitro to in vivo extrapolation.
Addressing Quality of Care in Pediatric Units using a Digital Tool: Implementation Experience from 18 SNCU of India
Authors: Saboth MD Prasant Kumar , Sarin PhD Enisha , Alwadhi MD Varun , Jaiswal MPH Avinash , Mohanty MD Jaya Swarup , Choudhary DCH Nidhi , Bisht MBBS Nitin , Gupta MBBS Anil , Kumar BSc Arvind , Gupta MD Sachin , Kumar MD Harish
Published: January 2021

Lack of quality care is associated with newborn mortality and stillbirth. India launched the Special newborn care unit (SNCU) Quality of Care Index (SQCI) for measuring quality indicators in SNCU. The USAID Vriddhi project provided support to the use of SQCI in 19 SNCU across aspirational districts of Jharkhand, Uttarakhand, Himachal Pradesh, Punjab and Haryana. The objective was to provide holistic support to quality care processes by generating analyzed quarterly reports for action with the goal toward sustainability by capacitating SNCU personnel and program officers to use SQCI, over a 1period from April 2019 to June 2020. The composite index has seven indicators and converts them into indices, each having a range from 0.1 to 1, to measure performance of SNCU.7 of the 18 SNCU improved their composite scores from the first to the last quarter. Rational use of antibiotics showed improvement in 12 SNCU. Survival in newborns >2500 g and <2500, low birth weight admission and optimal bed utilization had the most variations between and within facilities. Based on quarterly data analysis, all facilities introduced KMC, 10 facilities improved equipment and drug supply, 9 facilities launched in-house capacity building to improve asphyxia management. The SQCI implementation helped to show a process of using SQCI data for identifying bottlenecks and addressing quality concerns. The project has transitioned to complete responsibility of SQCI usage by the district and facility teams. Use of an existing mechanism of quality monitoring without any major external support makes the SQCI usable and doable.
The Cotton Lignin Biosynthetic Gene Gh4CL30 Regulates Lignification and Phenolic Content and Contributes to Verticillium Wilt Resistance
Authors: Xiong Xian-Peng , Sun Shi-Chao , Zhu Qian-Hao , Zhang Xin-Yu , Li Yan-Jun , Liu Feng , Xue Fei , Sun Jie
Published: January 2021

Verticillium wilt is a vascular disease causing tremendous damage to cotton production worldwide. However, our knowledge of the mechanisms of cotton resistance or susceptibility to this disease is very limited. In this study, we compared the defense transcriptomes of cotton (Gossypium hirsutum) cultivars Shidalukang 1 (Verticillium dahliae resistant, HR) and Junmian 1 (V. dahliae susceptible, HS) before and after V. dahliae infection, identified hub genes of the network associated with responses to V. dahliae infection, and functionally characterized one of the hub genes involved in biosynthesis of lignin and phenolics. We identified 6,831 differentially expressed genes (DEGs) between the basal transcriptomes of HR and HS; 3,685 and 3,239 of these DEGs were induced in HR and HS, respectively, at different time points after V. dahliae infection. KEGG pathway analysis indicated that DEGs were enriched for genes involved in lignin biosynthesis. In all, 23 hub genes were identified based on a weighted gene coexpression network analysis of the 6,831 DEGs and their expression profiles at different time points after V. dahliae infection. Knockdown of Gh4CL30, one of the hub genes related to the lignin biosynthesis pathway, by virus-induced gene silencing, led to a decreased content of flavonoids, lignin, and S monomer but an increased content of G monomer, G/S lignin monomer, caffeic acid, and ferulic acid, and enhanced cotton resistance to V. dahliae. These results suggest that Gh4CL30 is a key gene modulating the outputs of different branches of the lignin biosynthesis pathway, and provide new insights into cotton resistance to V. dahliae.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Evolving Plant Diagnostics During a Pandemic
Authors: Smart Alicyn , Byrne Jan , Hammerschmidt Ray , Snover-Clift Karen L. , Stack James P. , Brenes-Arguedas Tania , Jones Jeffrey B. , Harmon Carrie L.
Published: January 2021

The National Plant Diagnostic Network (NPDN), comprising diagnostic professionals from more than 70 pathology, entomology, and nematology laboratories, safeguards U.S. plant systems through accurate diagnosis and effective communications with clients, partners, and stakeholders. As a USDA-NIFA extension program built on the land-grant university system, the network has dual responsibilities to extension clientele such as farmers and the green industry, as well as state and federal regulatory agencies. Following strategic planning in 2019, the network emerged with a concise plan and strong committees of network participants to enhance and sustain service to NPDN clientele and partners, even through significant disruptions like the 2020 coronavirus pandemic. The commitment to building diagnostic capacity and expertise across the country allows these plant clinics to assist during a response to detections of high-consequence plant pathogens by clearing healthy plants for commerce while identifying potential positives for regulators to quarantine and/or eradicate, similar to the test and trace efforts for human diseases such as COVID-19. In this review, we describe the network’s recent activities to protect U.S. plant agriculture and natural ecosystems and its plans to improve and expand capacity for national plant biosecurity.
First Report of Branched Broomrape (Orobanche ramosa) on Turnip (Brassica rapa) in Morocco
Authors: Chedadi Toufik , Idrissi Omar , Elkhabli Anas , Khachtib Youssef , Haddioui Abdelmajid , El Hansali Mohammed
Published: January 2021

In September 2020, during a field survey in the province of Berrechid (central Morocco), located in the region of Casablanca-Settat (33°18′35.3″N, 7°22′30.4″W), we found several Orobanche ramosa plants in Brassica rapa L. fields. After morphological identification, this will be added to the list of enemies of the turnip crop in the Chaouia-Ouardigha region (north-central Morocco). To our knowledge, this is the first time that O. ramosa has been reported on turnip in Morocco.
What’s in a Name? A Mixed Method Study on How Young Women Who Sell Sex Characterize Male Partners and Their Use of Condoms
Authors: Busza Joanna , Hensen Bernadette , Birdthistle Isolde , Chabata Sungai T. , Hargreaves James R. , Floyd Sian , Chiyaka Tarisai , Mushati Phillis , Cowan Frances M.
Published: January 2021

Introduction:

Young women who sell sex (YWSS) are at disproportionate risk of HIV. Reducing YWSS' vulnerability requires engaging their male sexual partners. To achieve this, we need to understand the characteristics and dynamics of their sexual partnerships to inform effective interventions.

Methods:

We conducted a mixed-methods study to compare YWSS' qualitative descriptions of male partners with categories reported in a behavioral survey. Data were drawn from enrollment into an evaluation of the DREAMS initiative in Zimbabwe in 2017. As part of a respondent-driven sampling survey, we recruited 40 seed participants from 2 intervention and 4 comparison sites. We conducted semistructured interviews with 19 “seeds,” followed by a behavioral survey with 2387 YWSS. We interpreted quantitative and qualitative data together to understand how YWSS perceived male sexual partners, assess how well survey variables related to narrative descriptions, and describe patterns of risk behavior within partnerships.

Results:

Qualitative data suggest survey categories “husband” and “client” reflect YWSS' perceptions but “regular partner/boyfriend” and “casual partner” do not. In interviews, use of the term “boyfriend” was common, describing diverse relationships with mixed emotional and financial benefits. More than 85% of male partners provided money to YWSS, but women were less likely to report condomless sex with clients than regular partners (11% vs 37%) and more likely to report condomless sex with partners who ever forced them to have sex (37% vs 21%).

Conclusions:

Reducing HIV risk among YWSS requires prevention messages and tools that recognize diverse and changing vulnerability within and between sexual relationships with different male partners.
The magnitude of extended-spectrum beta-lactamase- producing Enterobacteriaceae from clinical samples in Ethiopia: a systematic review and meta-analysis
Authors: Diriba Kuma , Awulachew Ephrem , Gemede Aschelew , Anja Asrat
Published: January 2021

Background. The rapid spread of resistance among extended-spectrum β-lactamase (ESBL)-producing

Enterobacteriaceae

is a serious problem around the world. It results in serious clinical complications in humans and has become a global threat. Therefore, this systematic review and meta-analysis was aimed to estimate the pooled prevalence of ESBL-producing

Enterobacteriaceae

in different clinical samples in Ethiopia.

Methods. A systematic search was conducted on PubMed, Web of Science, Embase, Google Scholar and the Cochrane Library. All identified observational studies reporting the prevalence of ESBL-producing

Enterobacteriaceae

from clinical samples in Ethiopia were included. Four authors independently extracted data and analysed using R software version 3.6.1 and STATA statistical software version 13. A random-effects model was computed to estimate the pooled prevalence of ESBL-producing

Enterobacteriaceae

in Ethiopia.

Results. Of 142 articles reviewed, 14 studies that fulfilled the inclusion criteria were included in the meta-analysis. The pooled prevalence of ESBL-producing

Enterobacteriaceae

in the different clinical specimens in Ethiopia was 49 % (95 % CI: 39, 60).

Klebsiella pneumoniae

was the leading ESBL-producing

Enterobacteriaceae

followed by

Escherichia coli

and

Acinetobacter baumannii

with a prevalence of 74, 67 and 60 %, respectively. ESBL-producing isolates showed a high rate of resistance to cefotaxime, ceftriaxone, ceftazidime, Amoxicillin clavulanic acid (AMC), ampicillin and aztreonam. The better options for the treatment of ESBL-producing

Enterobacteriaceae

are amikacin and Imipenem.

Conclusion. The magnitude of ESBL-producing

Enterobacteriaceae

in different clinical samples in Ethiopia is alarmingly high and represents a threat to human health. Hence, a coordinated effort needs to be implemented for the prevention and control of these

Enterobacteriaceae

.
Zebrafish as an animal model for the antiviral RNA interference pathway
Authors: Ren Yanxin , Li Xueyu , Tian Zhonghui , Xu Yan , Zhang Ruilin , Li Yang
Published: January 2021

The zebrafish (Danio rerio) possesses evolutionarily conserved innate and adaptive immunity as a mammal and has recently become a popular vertebrate model to exploit infection and immunity. Antiviral RNA interference (RNAi) has been illuminated in various model organisms, including Arabidopsis thaliana, Drosophila melanogaster, Caenorhabditis elegans and mice. However, to date, there is no report on the antiviral RNAi pathway of zebrafish. Here, we have evaluated the possible use of zebrafish to study antiviral RNAi with Sindbis virus (SINV), vesicular stomatitis virus (VSV) and Nodamura virus (NoV). We find that SINVs and NoVs induce the production of virus-derived small interfering RNAs (vsiRNAs), the hallmark of antiviral RNAi, with a preference for a length of 22 nucleotides, after infection of larval zebrafish. Meanwhile, the suppressor of RNAi (VSR) protein, NoV B2, may affect the accumulation of the NoV in zebrafish. Furthermore, taking advantage of the fact that zebrafish argonaute-2 (Ago2) protein is naturally deficient in cleavage compared with that of mammals, we provide evidence that the slicing activity of human Ago2 can virtually inhibit the accumulation of RNA virus after being ectopically expressed in larval zebrafish. Thus, zebrafish may be a unique model organism to study the antiviral RNAi pathway.
Targeting novel structural and functional features of coronavirus protease nsp5 (3CLpro, Mpro) in the age of COVID-19
Authors: Roe Molly K. , Junod Nathan A. , Young Audrey R. , Beachboard Dia C. , Stobart Christopher C.
Published: January 2021

Coronavirus protease nsp5 (M
pro
, 3CL
pro
) remains a primary target for coronavirus therapeutics due to its indispensable and conserved role in the proteolytic processing of the viral replicase polyproteins. In this review, we discuss the diversity of known coronaviruses, the role of nsp5 in coronavirus biology, and the structure and function of this protease across the diversity of known coronaviruses, and evaluate past and present efforts to develop inhibitors to the nsp5 protease with a particular emphasis on new and mostly unexplored potential targets of inhibition. With the recent emergence of pandemic SARS-CoV-2, this review provides novel and potentially innovative strategies and directions to develop effective therapeutics against the coronavirus protease nsp5.
The first UK report of a rare Cryptosporidium hominis genetic variant isolated during a complex Scottish swimming pool outbreak
Authors: Polubotho Padmaja , Denvir Lucy , Connelly Lisa , Anderson Eleanor , Alexander Claire L.
Published: January 2021

Cryptosporidium species are responsible for causing the majority of parasite-related gastrointestinal infections in the UK. This report describes an outbreak of 12 laboratory-confirmed cryptosporidiosis cases identified as part of a Scottish swimming pool investigation, with 9 primary and 3 secondary cases occurring over an 8-week period. Molecular speciation was successful for 11/12 cases, which revealed 10 Cryptosporidium hominis cases and 1 Cryptosporidium parvum case. Of the 10 C. hominis cases, further typing identified 7 as being an unusual sub-type, IbA6G3, which is the first description in the UK of this rare variant. The remaining three C. hominis cases were identified as the common IbA10G2 subtype. Following implementation of control measures on two occasions, no further cases were reported. This report highlights the importance of molecular typing to identify and characterize outbreaks, and emphasizes the need to adhere to swimming pool guidance. It also raises awareness of the potential for outbreaks to involve multiple species/sub-types, and emphasizes the importance of strong public health leadership to ensure effective multi-agency investigations and management of outbreaks.
A novel adhesive complex at the base of intestinal microvilli
Authors: Hartmann Christian , Thüring Eva-Maria , Michels Birgitta E. , Pajonczyk Denise , Leußink Sophia , Greune Lilo , Brinkmann Frauke , Glaesner-Ebnet Mark , Wardelmann Eva , Zobel Thomas , Schmidt M. Alexander , Gerke Volker , Ebnet Klaus
Published: January 2021

Intestinal epithelial cells form dense arrays of microvilli at the apical membrane to enhance their functional capacity. Microvilli contain a protocadherin-based intermicrovillar adhesion complex localized at their tips which regulates microvillar length and packaging. Here, we identify a second adhesive complex in microvilli of intestinal epithelial cells. This complex is localized at the basal region of microvilli and consists of the adhesion molecule TMIGD1, the phosphoprotein EBP50 and the F-actin – plasma membrane cross-linking protein ezrin. Ternary complex formation requires unmasking of the EBP50 PDZ domains by ezrin binding and is strongly enhanced upon mutating Ser162 located in PDZ domain 2 of EBP50. Dephosphorylation of EBP50 at S162 is mediated by PP1α, a serine/threonine phosphatase localized at the microvillar base and involved in ezrin phosphocycling. Importantly, the binding of EBP50 to TMIGD1 enhances the dynamic turnover of EBP50 at microvilli in a Ser162 phosphorylation-dependent manner. We identify an adhesive complex at the microvillar base and propose a potential mechanism that regulates microvillar dynamics in enterocytes.
Genetic analysis of mitochondrial DNA copy number and associated traits identifies loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation, and reveals a causal association of mitochondrial function with mortality
Authors: Longchamps RJ , Yang SY , Castellani CA , Shi W , Lane J , Grove ML , Bartz TM , Sarnowski C , Burrows K , Guyatt AL , Gaunt TR , Kacprowski T , Yang J , De Jager PL , Yu L ,   CHARGE Aging and Longevity Group, Bergman A , Xia R , Fornage M , Feitosa MF , Wojczynski MK , Kraja AT , Province MA , Amin N , Rivadeneira F , Tiemeier H , Uitterlinden AG , Broer L , Van Meurs JBJ , Van Duijn CM , Raffield LM , Lange L , Rich SS , Lemaitre RN , Goodarzi MO , Sitlani CM , Mak ACY , Bennett DA , Rodriguez S , Murabito JM , Lunetta KL , Sotoodehnia N , Atzmon G , Kenny Y , Barzilai N , Brody JA , Psaty BM , Taylor KD , Rotter JI , Boerwinkle E , Pankratz N , Arking DE
Published: January 2021

Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses were used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p= 3.09 x 10−15) and the gene ontology (GO) terms for mtDNA metabolism (p= 1.43 x 10−8) and mtDNA replication (p= 1.2 x 10−7). A clustering approach leveraged pleiotropy between mtDNA-CN associated SNPs and 41 mtDNA-CN associated phenotypes to identify functional domains, revealing three distinct groups, including platelet activation, megakaryocyte proliferation, and mtDNA metabolism. Finally, using mitochondrial SNPs, we establish causal relationships between mitochondrial function and a variety of blood cell related traits, kidney function, liver function and overall (p= 0.044) and non-cancer mortality (p= 6.56 x 10−4).
Elevation-related climate trends dominate fungal co-occurrence patterns on Mt. Norikura, Japan
Authors: Yang Ying , Shi Yu , Kerfahi Dorsaf , Ogwu Matthew C , Wang Jianjun , Dong Ke , Takahashi Koichi , Moroenyane Itumeleng , Adams Jonathan M.
Published: January 2021

Although many studies have explored patterns of fungal community diversity and composition along various environmental gradients, the trends of co-occurrence networks across similar gradients remain elusive. Here, we constructed co-occurrence networks for fungal community along a 2300 m elevation gradient on Mt Norikura, Japan, hypothesizing a progressive decline in network connectivity with elevation due to reduced niche differentiation caused by declining temperature and ecosystem productivity. Results agreed broadly with predictions, with an overall decline in network connectivity with elevation for all fungi and the high abundance phyla. However, trends were not uniform with elevation, most decline in connectivity occurred between 700 m and 1500 m elevation, remaining relatively stable above this. Temperature and precipitation dominated variation in network properties, with lower mean annual temperature (MAT) and higher mean annual precipitation (MAP) at higher elevations giving less network connectivity, largely through indirect effects on soil properties. Among keystone taxa that played crucial roles in network structure, the variation in abundance along the elevation gradient was also controlled by climate and also pH. Our findings point to a major role of climate gradients in mid-latitude mountain areas in controlling network connectivity. Given the importance of the orographic precipitation effect, microbial community trends seen along elevation gradients might not be mirrored by those seen along latitudinal temperature gradients.

Importance

Although many studies have explored patterns of fungal community diversity and composition along various environmental gradients, it is unclear how the topological structure of co-occurrence networks shifts across environmental gradients. In this study, we found that the connectivity of the fungal community decreased with increasing elevation, and that climate was the dominant factor regulating co-occurrence patterns, apparently acting indirectly through soil characteristics. Assemblages of keystone taxa playing crucial roles in network structure varied along the elevation gradient and were also largely controlled by climate. Our results provide insight into the shift of soil fungal community co-occurrence structure along elevational gradients, and possible driving mechanisms behind this.

Graphic abstract
Detecting therapy-guiding RNA aberrations in platelets of non-small cell lung cancer patients
Authors: Meng Pei , Rybczynska Anna A. , Wei Jiacong , Terpstra Miente Martijn , Timens Wim , Schuuring Ed , Hiltermann T. Jeroen N. , Groen Harry J.M. , van der Wekken Anthonie J. , van den Berg Anke , Kok Klaas
Published: January 2021

Background

Nowadays, the detection of therapy-guiding aberrations such as EGFR mutations and ALK fusion genes in tumor tissue is common practice for lung cancer patients. The aim of this study is to explore the feasibility of detecting common therapy-guiding aberrations in RNA isolated from platelets.

Methods

We applied a single primed enrichment-based targeted next generation sequencing (NGS) approach on 10 platelet RNA samples isolated from patients with active disease. In parallel, we applied RNA-based ddPCR focusing on EGFR p.(T790M), p.(L858R) and E19del, on KRAS codon 12 and 13 and on ALK-EML4/KIF5B fusions on 22 platelet RNA samples from patients with tumors known to harbor one of these drivers. For 11 cases ddPCR analysis of circulating cell free (cf)DNA from the same blood sample was performed in parallel.

Results

Despite having good quality NGS data, none of the variants detected in the tumor biopsy were observed in platelet-derived RNA samples. Using the more sensitive ddPCR, we detected known aberrations in three of 22 platelet-derived RNA samples. EGFR mutant droplets were not observed in any of the seven platelet samples, while these mutations were detected in three of six cfDNA samples of which five were extracted from the same blood sample. KRAS mutant droplets were detected in three out of nine platelet RNA samples with fractional abundances of 0.07%, 0.11% and 0.55%. Analysis of five cfDNA samples from the same blood samples revealed KRAS-mutant droplets in four of them. Two of the four corresponding platelet RNA samples were also positive for mutant KRAS. No ALK fusion droplets were detected in seven platelet derived RNA samples.

Conclusions

The level of tumor-derived RNA transcripts in platelets of non-small cell lung cancer patients was too low to be measured reliably for clinically relevant alterations in EGFR, KRAS and ALK fusion gene transcripts.
Lack of Accuracy of the GRACE score to Predict Coronary Anatomy in Acute Coronary Syndromes
Authors: Viana Mateus dos Santos , Silva Thomaz Emanoel Azevedo , Bagano Gabriela Oliveira , de Sá Barreto Pontes Bruna , de Melo Milton Henrique Vitoria , Filgueiras Pedro Henrique Correia , Meireles Andre Costa , de Andrade Lopes Paula Oliveira , de Oliveira Junior Andre Luiz Freitas , de Oliveira Porto João Vitor Miranda , de Almeida Correia Vitor Calixto , Correia Luis Claudio Lemos
Published: January 2021

Introduction

Coronary anatomy is one of the strongest risk predictors in Acute Coronary Syndromes (ACS), which justifies early coronary angiography. Diagnostic scores for predicting outcomes are usually superior to clinical judgment. Despite being validated for prognosis, the GRACE score has been used to discriminate patients with high or low probability of anatomical severity.

Objective

To test the hypothesis that the GRACE score actually predicts anatomical severity.

Methods

The study was carried out by assessing consecutive patients with ACS who underwent invasive angiography. Severe anatomical disease was defined as obstructive involvement (≥ 70% in diameter) in (1) left main coronary artery or (2) double or triple vessel disease involving proximal left anterior descending artery or (3) subocclusion. The GRACE score was evaluated under numerical and dichotomous tests.

Results

A total of 733 patients were evaluated, aged 63 ± 14 years, 61% male and GRACE score of 119 ± 37. Obstructive coronary disease was observed in 81% of the patients, classified as one, two or three vessel disease, or left main coronary artery involvement in 28%, 23%, 26% and 4%, respectively. The area under the ROC curve of the GRACE score was 0.65 (95% CI = 0.61 - 0.69) for predicting severe disease. The cutoff point below which the first GRACE tertile is defined (109) was used to dichotomize low-risk (N = 318) and medium-high-risk (N = 415) samples. This standard definition of intermediate-high risk by the GRACE score (> 109) revealed sensitivity of 67% in detecting severe anatomy (95% CI = 61% - 72%) and specificity of 50% (95% CI = 46% - 55%), resulting in positive likelihood ratio of 1.3 (95% CI = 1.2 - 1.5) and negative likelihood ratio of 0.66 (95% CI = 0.55 - 0.80). There was a weak correlation between GRACE and anatomical scores such as SYNTAX (r = 0.36, P < 0.001) and Gensini (r = 0.36, P < 0.001).

Conclusion

Despite statistical association with extent of anatomical coronary disease, the GRACE Score is not accurate to predict severity of disease before coronary angiography.
Individual factors underlie temperature variation in sickness and in health: influence of age, BMI and genetic factors in a multi-cohort study
Authors: Penfold Rose S. , Zazzara Maria Beatrice , Osterdahl Marc F. ,   GSTT CovidCollaborative, Welch Carly , Lochlainn Mary Ni , Freidin Maxim B. , Bowyer Ruth C.E. , Thompson Ellen , Antonelli Michela , Tan Yu Xian Rachel , Sudre Carole H. , Modat Marc , Murray Benjamin , Wolf Jonathan , Ourselin Sebastien , Veenith Tonny , Lord Janet M. , Steves Claire J.
Published: January 2021

Introduction

Ageing affects immune function resulting in aberrant fever response to infection. We assess the effects of biological variables on basal temperature and temperature in COVID-19 infection, proposing an updated temperature threshold for older adults.

Methods

Participants:

Unaffected twin volunteers: 1089 adult TwinsUK participants.

London hospitalised COVID-19+: 520 adults with emergency admission.

Birmingham hospitalised COVID-19+: 757 adults with emergency admission.

Community-based COVID-19+: 3972 adults self-reporting a positive test using the COVID Symptom Study mobile application.

Analysis

Heritability assessed using saturated and univariate ACE models; Linear mixed-effect and multivariable linear regression analysing associations between temperature, age, sex and BMI; multivariable logistic regression analysing associations between fever (≥37.8°C) and age; receiver operating characteristic (ROC) analysis to identify temperature threshold for adults ≥ 65 years.

Results

Among unaffected volunteers, lower BMI (p=0.001), and older age (p<0.001) associated with lower basal temperature. Basal temperature showed a heritability of 47% (95% Confidence Interval 18-57%).

In COVID-19+ participants, increasing age associated with lower temperatures in cohorts (c) and (d) (p<0.001). For each additional year of age, participants were 1% less likely to demonstrate a fever (OR 0.99; p<0.001).

Combining healthy and COVID-19+ participants, a temperature of 37.4°C in adults ≥65 years had similar sensitivity and specificity to 37.8°C in adults <65 years for discriminating fever in COVID-19.

Conclusions

Ageing affects temperature in health and acute infection. Significant heritability indicates biological factors contribute to temperature regulation.

Our observations indicate a lower threshold (37.4°C) should be considered for assessing fever in older adults.

Key Points

Older adults, particularly those with lower BMI, have a lower basal temperature and a lower temperature in response to infection

Basal temperature is heritable, suggesting biological factors underlying temperature regulation

Our findings support a lower temperature threshold of 37.4°C for identifying possible COVID-19 infection in older adults

This has implications for case detection, surveillance and isolation and could be incorporated into observation assessment