bluuebunny/crossref_metadata_2025 huggingface dataset:
Convergent and distributed effects of the schizophrenia-associated 3q29 deletion on the human neural transcriptome
Authors: Sefik Esra , Purcell Ryan H. ,   The Emory 3q29 Project, Walker Elaine F. , Bassell Gary J. , Mulle Jennifer G.
Published: May 2020

The 3q29 deletion (3q29Del) confers >40-fold increased risk for schizophrenia. However, no single gene in this interval is definitively associated with disease, prompting the hypothesis that neuropsychiatric sequelae emerge upon loss of multiple functionally-connected genes. 3q29 genes are unevenly annotated and the impact of 3q29Del on the human neural transcriptome is unknown. To systematically formulate unbiased hypotheses about molecular mechanisms linking 3q29Del to neuropsychiatric illness, we conducted a systems-level network analysis of the non-pathological adult human cortical transcriptome and generated evidence-based predictions that relate 3q29 genes to novel functions and disease associations. The 21 protein-coding genes located in the interval segregated into seven clusters of highly co-expressed genes, demonstrating both convergent and distributed effects of 3q29Del across the interrogated transcriptomic landscape. Pathway analysis of these clusters indicated involvement in nervous-system functions, including synaptic signaling and organization, as well as core cellular functions, including transcriptional regulation, post-translational modifications, chromatin remodeling and mitochondrial metabolism. Top network-neighbors of 3q29 genes showed significant overlap with known schizophrenia, autism and intellectual disability-risk genes, suggesting that 3q29Del biology is relevant to idiopathic disease. Leveraging “guilt by association”, we propose nine 3q29 genes, including one hub gene, as prioritized drivers of neuropsychiatric risk. These results provide testable hypotheses for experimental analysis on causal drivers and mechanisms of the largest known genetic risk factor for schizophrenia and highlight the study of normal function in non-pathological post-mortem tissue to further our understanding of psychiatric genetics, especially for rare syndromes like 3q29Del, where access to neural tissue from carriers is unavailable or limited.
Far-red light enhances soluble sugar levels andBotrytis cinereadisease development in tomato leaves in a jasmonate-dependent manner
Authors: Courbier Sarah , Grevink Sanne , Sluijs Emma , Bonhomme Pierre-Olivier , Kajala Kaisa , Van Wees Saskia C.M. , Pierik Ronald
Published: May 2020

Plants lacking phytochrome photoreceptors display elevated soluble sugar levels in leaves. Although pathogens principally feed on sugars supplied by the plant, the link between increased plant sugar levels upon phytochrome inactivation and disease development has not been considered.

Tomato plants were exposed to control white LED (WL) or a combination of white and far-red LED (WL+FR) light, to inactivate phytochrome signaling and modulate soluble sugar levels. We also experimentally manipulated internal sugar levels by either supplementing glucose or inhibiting photosynthesis in tomato leaflets prior to performing soluble sugar quantifications or bioassays with pathogens.

Tomato plants exposed to WL+FR or lacking phytochrome B (phyB1phyB2double mutants) show enhanced levels of soluble sugars, especially glucose and fructose, in their leaves. The jasmonic acid biosynthesis mutantdef1also has elevated soluble sugar levels, which could be rescued by exogenous methyl-jasmonate application. This indicates an interplay between JA signaling and primary metabolism.

The increase in soluble sugar levels in tomato leaves upon phytochrome inactivation is regulated in a JA-dependent manner. Our data stress the importance of primary metabolism in the FR-induced susceptibility in tomato that could contribute to promote plant resistance when grown at high density.
Prediction of disordered regions in proteins with recurrent Neural Networks and protein dynamics
Authors: Orlando Gabriele , Raimondi Daniele , Codice Francesco , Tabaro Francesco , Vranken Wim
Published: May 2020

The role of intrinsically disordered protein regions (IDRs) in cellular processes has become increasingly evident over the last years. These IDRs continue to challenge structural biology experiments because they lack a well-defined conformation, and bioinformatics approaches that accurately delineate disordered protein regions remain essential for their identification and further investigation. Typically, these predictors use only the protein amino acid sequence, without taking into account likely emergent properties that are sequence context dependent, such as protein backbone dynamics.

The DisoMine method predicts protein disorder with recurrent neural networks not directly from the amino acid sequence, but instead from more generic predictions of key biophysical properties, here protein dynamics, secondary structure and early folding. The tool is fast and requires only a single sequence, making it applicable for large-scale screening, including poorly studied and orphan proteins. DisoMine compares well to 10 state of the art predictors, also if these use evolutionary information.

DisoMine is freely available through an interactive webserver athttp://bio2byte.com/disomine/
Human melanocyte development and melanoma dedifferentiation at single cell resolution
Authors: Belote Rachel L. , Le Daniel , Maynard Ashley , Lang Ursula E. , Sinclair Adriane , Planells-Palop Vicente , Baskin Laurence , Tward Aaron D. , Darmanis Spyros , Judson-Torres Robert L.
Published: May 2020

In humans, epidermal melanocytes are responsible for skin pigmentation, defense against ultraviolet radiation, and the deadliest common skin cancer, melanoma. While there is substantial overlap in melanocyte development pathways between different model organisms, species dependent differences are frequent and the conservation of these processes in human skin remains unresolved1–3. Thus, the biology of developing and adult human melanocytes remains largely uncharacterized. Here, we used a single-cell enrichment and RNA-sequencing pipeline to study human epidermal melanocytes derived directly from skin, capturing transcriptomes across different anatomic sites, developmental age, sexes, and multiple skin tones. Using donor-matched skin from distinct volar and non-volar anatomic locations, we uncovered subpopulations of melanocytes exhibiting site-specific enrichment that occurs during gestation and persists through adulthood. In addition, we identified human melanocyte differentiation transcriptional programs that are distinct from gene signatures generated from model systems. Finally, we use these programs to define patterns of dedifferentiation that are predictive of melanoma prognosis. Overall, the characterization of human melanocytes fresh from skin revealed new subpopulations, human-specific transcriptional programs, and valuable insights into melanoma dedifferentiation.
Development of microsatellite markers for a giant water bug,Appasus japonicus, distributed in East Asia
Authors: Suzuki Tomoya , Hirao Akira S. , Takenaka Masaki , Yano Koki , Tojo Koji
Published: May 2020

We developed microsatellite markers forAppasus japonicus(Hemiptera: Belostomatidae). This belostomatid bug is distributed in East Asia (Japanese Archipelago, Korean Peninsula, and Mainland China), and often listed as endangered species in the ‘Red List’ or the ‘Red Data Book’ at the national and local level in Japan. Here we describe twenty novel polymorphic microsatellite loci developed forA. japonicus, and marker suitability was evaluated on 56 individuals from fourA. japonicuspopulations (Nagano, Hiroshima, and Yamaguchi prefecture, Japan, and Chungcheongnam-do, Korea). The number of alleles per locus ranged 1–12 (mean = 2.5), and average observed and expected heterozygosity, and fixation index per locus were 0.270, 0.323, and 0.153, respectively. The 20 markers described here will be useful for investigating the genetic structure ofA. japonicuspopulations, which can contribute in population genetics studies of this species.
Viewing communities as coupled oscillators: elementary forms from Lotka and Volterra to Kuramoto
Authors: Hajian-Forooshani Zachary , Vandermeer John
Published: May 2020

Ecosystems and their embedded ecological communities are almost always by definition collections of oscillating populations. This is apparent given the qualitative reality that oscillations emerge from consumer-resource interactions, which are the simple building blocks for ecological communities. It is also likely always the case that oscillatory consumer-resource pairs will be connected to one another via trophic cross-feeding with shared resources or via competitive interactions among resources. Thus, one approach to understanding the dynamics of communities conceptualizes them as collections of oscillators coupled in various arrangements. Here we look to the pioneering work of Kuramoto on coupled oscillators and ask to what extent can his insights and approaches be translated to ecological systems. We explore all possible coupling arrangements of the simple case of three oscillator systems with both the Kuramoto model and with the classical Lotka-Volterra equations that are foundational to ecology. Our results show that the six-dimensional analogous Lotka-Volterra systems behave strikingly similarly to that of the corresponding Kuramoto systems across all possible coupling combinations. This qualitative similarity in the results between these two approaches suggests that a vast literature on coupled oscillators that has largely been ignored by ecologists may in fact be relevant in furthering our understanding of ecosystem and community organization.
Activation of the Anaphase Promoting Complex reverses multiple drug resistant cancer
Authors: Arnason T.G. , MacDonald-Dickinson V. , Davies J.F. , Lobanova L. , Gaunt C. , Trost B. , Waldner M. , Baldwin P. , Borrowman D. , Marwood H. , Gillespie Z.E. , Vizeacoumar F.S. , Vizeacoumar F.J. , Eskiw C.H. , Kusalik A. , Harkness T.A.A.
Published: May 2020

Like humans, canines spontaneously develop lymphomas that are treated by chemotherapy cocktails and frequently develop multiple drug resistance (MDR). Their shortened clinical timelines and tumor accessibility make them excellent models to study MDR mechanisms. We previously demonstrated that adjunct treatment ofin vitroMDR cell lines with insulin-sensitizers effectively restored MDR chemosensitivity and prevented MDR development. This study extends the use of an insulin-sensitizer to clinical and tumor responsesin vivoin volunteer canines with MDR lymphoma, including assessing changes in MDR protein biomarkers and global gene expression. Longitudinal tumor sampling and analysis of MDR cases throughout treatment allowed a correlation betweenin vivomolecular mechanisms and clinical responsiveness. We found reduced MDR biomarkers within all tumors, yet only one canine entered clinical remission. Analysis of tumor samples during remission and relapse allowed comparison of gene expression profiles. This revealed the Anaphase Promoting Complex (APC), a ubiquitin-E3 ligase regulating cell cycle progression, was impaired during chemoresistance/MDR and restored during remission. Validatingin vitrotests restored MDR chemosensitivity upon APC activation, supporting the idea that APC activity is an important underlying cellular mechanism associated with treatment resistance, and a novel potential therapeutic target.
Fear learning sculpts functional brain connectivity at rest beyond the traditional fear network in humans
Authors: Fraenz Christoph , Metzen Dorothea , Merz Christian J. , Selpien Helene , Friedrich Patrick , Ocklenburg Sebastian , Axmacher Nikolai , Genç Erhan
Published: May 2020

Neuroscientific research has identified specific brain networks involved in the acquisition of fear memories. Using fMRI to assess changes in resting-state functional connectivity (RSFC) induced by fear acquisition, single brain regions from these networks have also been linked to fear memory consolidation. However, previous studies only examined RSFC changes within restricted sets of brain regions or without a proper control group, leaving our knowledge about fear consolidation outside of traditional fear networks incomplete. Here, we tested a group of 84 healthy participants in a differential fear conditioning paradigm and quantified RSFC changes between 358 cortical and 16 subcortical brain areas. Subsequent to fear learning, 21 functional connections exhibited significant RSFC changes. Importantly, these connections were not restricted to the traditional fear networks but also comprised various frontal and visual areas. Our findings indicate that fear memory consolidation is a complex process that integrates relevant information across the entire brain.
Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time
Authors: Barnes Kayla G. , Lachenauer Anna E. , Nitido Adam , Siddiqui Sameed , Gross Robin , Beitzel Brett , Siddle Katherine J. , Freije Catherine A. , Dighero-Kemp Bonnie , Mehta Samar , Carter Amber , Uwanibe Jessica , Ajogbasile Fehintola , Olumade Testimony J. , Odia Ikponmwosa , Sandi John Demby , Momoh Mambu , Metsky Hayden C. , Boehm Chloe K. , Lin Aaron E. , Kemball Molly , Park Daniel J. , Grant Donald S. , Happi Christian T. , Branco Luis , Boisen Matt , Sullivan Brian M. , Amare Mihret , Tiamiyu Abdulwasiu , Parker Zahra , Iroezindu Michael , Modjarrad Kayvon , Myhrvold Cameron , Garry Robert F. , Palacios Gustavo , Hensley Lisa E. , Schaffner Stephen F. , Colubri Andres , Sabeti Pardis C.
Published: May 2020

Viral hemorrhagic fevers (VHFs) remain some of the most devastating human diseases, and recent outbreaks of Ebola virus disease (EVD)1,2and Lassa fever (LF)3,4highlight the urgent need for sensitive, field-deployable tests to diagnose them5,6. Here we develop CRISPR-Cas13a-based (SHERLOCK) diagnostics targeting Ebola virus (EBOV) and Lassa virus (LASV), with both fluorescent and lateral flow readouts. We demonstrate on laboratory and clinical samples the sensitivity of these assays and the capacity of the SHERLOCK platform to handle virus-specific diagnostic challenges. Our EBOV diagnostic detects both theLandNPgenes, thereby eliminating the potential for false positive results caused by the rVSVΔG-ZEBOV-GP live attenuated vaccine. Our two LASV diagnostics together capture 90% of known viral diversity and demonstrate that CRISPR-RNAs (crRNAs) can be effectively multiplexed to provide greater coverage of known viral diversity. We performed safety testing to demonstrate the efficacy of our HUDSON protocol in heat-inactivating and chemically treating VHF viruses before SHERLOCK testing, eliminating the need for an extraction. We developed a user-friendly field protocol and mobile application (HandLens) to report results, facilitating SHERLOCK’s use in endemic regions. Finally, we successfully deployed our tests in Sierra Leone and Nigeria in response to recent outbreaks.
Development and validation of IMMUNO-COV™: a high-throughput clinical assay for detecting antibodies that neutralize SARS-CoV-2
Authors: Vandergaast Rianna , Carey Timothy , Reiter Samantha , Lech Patrycja , Gnanadurai Clement , Tesfay Mulu , Buehler Jason , Suksanpaisan Lukkana , Naik Shruthi , Brunton Bethany , Recker Jordan , Haselton Michelle , Ziegler Christopher , Roesler Anne , Mills John R. , Theel Elitza , Weaver Scott C. , Rafael Grace , Roforth Matthew M. , Jerde Calvin , Tran Sheryl , Diaz Rosa Maria , Bexon Alice , Baum Alina , Kyratsous Christos A. , Peng Kah Whye , Russell Stephen J.
Published: May 2020

We here describe the development and validation of IMMUNO-COV™, a high-throughput clinical test to quantitatively measure SARS-CoV-2-neutralizing antibodies, the specific subset of anti-SARS-CoV-2 antibodies that block viral infection. The test measures the capacity of serum or purified antibodies to neutralize a recombinant Vesicular Stomatitis Virus (VSV) encoding the SARS-CoV-2 spike glycoprotein. This recombinant virus (VSV-SARS-CoV-2-S-Δ19CT) induces fusion in Vero cell monolayers, which is detected as luciferase signal using a dual split protein (DSP) reporter system. VSV-SARS-CoV-2-S-Δ19CT infection was blocked by monoclonal α-SARS-CoV-2-spike antibodies and by plasma or serum from SARS-CoV-2 convalescing individuals. The assay exhibited 100% specificity in validation tests, and across all tests zero false positives were detected. In blinded analyses of 230 serum samples, only two unexpected results were observed based on available clinical data. We observed a perfect correlation between results from our assay and 80 samples that were also assayed using a commercially available ELISA. To quantify the magnitude of the anti-viral response, we generated a calibration curve by adding stepped concentrations of α-SARS-CoV-2-spike monoclonal antibody to pooled SARS-CoV-2 seronegative serum. Using the calibration curve and a single optimal 1:100 serum test dilution, we reliably measured neutralizing antibody levels in each test sample. Virus neutralization units (VNUs) calculated from the assay correlated closely (p < 0.0001) with PRNTEC50 values determined by plaque reduction neutralization test against a clinical isolate of SARS-CoV-2. Taken together, these results demonstrate that the IMMUNO-COV™ assay accurately quantitates SARS-CoV-2 neutralizing antibodies in human sera and therefore is a potentially valuable addition to the currently available serological tests. The assay can provide vital information for comparing immune responses to the various SARS-CoV-2 vaccines that are currently in development, or for evaluating donor eligibility in convalescent plasma therapy studies.
Defining the familial fold of the vicilin-buried peptide family
Authors: Payne Colton D. , Vadlamani Grishma , Fisher Mark F. , Zhang Jingjing , Clark Richard J. , Mylne Joshua S. , Rosengren K. Johan
Published: May 2020

Plants and their seeds have been shown to be a rich source of cystine-stabilized peptides. Recently a new family of plant seed peptides whose sequences are buried within precursors for seed storage vicilins was identified. Members of this Vicilin Buried Peptide (VBP) family are found in distantly related plant species including the monocot date palm, as well as dicotyledonous species like pumpkin and sesame. Genetic evidence for their widespread occurrence indicates that they are of ancient origin. Limited structural studies have been conducted on VBP family members, but two members have been shown to adopt a helical hairpin fold. We here present an extensive characterization of VBPs using solution NMR spectroscopy, to better understand their structural features. Four peptides were produced by solid phase peptide synthesis and shown to adopt a helix-loop-helix hairpin fold, as a result of the I-IV/II-III ladder-like connectivity of their disulfide bonds. Inter-helix interactions, including hydrophobic contacts and salt bridges, are critical for the fold stability and control the angle at which the anti-parallel α-helices interface. Activities reported for VBPs include trypsin inhibitory activity and inhibition of ribosomal function, however their diverse structural features despite a common fold suggest additional bioactivities yet to be revealed are likely.
Isolation And Identification Of Major Pathogenic Bacteria From Clinical Mastitic Cows In Asella Town, Ethiopia
Authors: Tufa Gezehagn Kasa , Muluneh Betelhem Tegegne , Siyamregn Belege Tadesse
Published: May 2020

Mastitis is a multi-etiological and complex disease causing inflammation of parenchyma of mammary glands is a problem in many dairy herds. The objective of this study was isolation and identification of the pathogenic bacteria that cause bovine clinical mastitis. A cross sectional study was undertaken from November 2018 to April 2019 on small scale and government dairy farms in Asella town. Cows were examined directly at quarter and teat level for clinical manifestation. A total of 83 milk samples were collected from 46 cows that shows clinical sign of mastitis from a total of 12 farms. Isolation and identification of major bacterial species was carried out by culturing on different media and using primary and secondary biochemical tests. Out of the 83 samples collected and examined, all (100%) were positive for cultural isolation of bacterial species. The bacteria were identified to genus and species level. Among the 83 isolates 32 (38.6%) wereS. aureus, 24 (28.9%) wereStaphylococcus intermediusand 6 (7.2%) wereStaphyloco ccus hyicus, other bacteria likeEscherichia coli12(14.5%), Streptococcus species 2 (2.4%) were also isolated. Bacillus Species 2 (2.4%), Proteus species 2(2.4%) and 3 (3.6%) of them were mixed bacterial infections. The present study revealed that both contagious and environmental bacterial pathogens were responsible for the occurrence of clinical mastitis. Proper milking practices and farm husbandry practices as well as future detailed studies up to the species level and on antibiotic profiles of the pathogens are needed.
Vpr R36W and R77Q Mutations Alter HIV-1 Replication and Cytotoxicity in T Lymphocytes
Authors: Solis-Leal Antonio , Karlinsey Dalton C. , Lopez J. Brandon , Planelles Vicente , Poole Brian D. , Berges Bradford K.
Published: May 2020

Chronic immune inflammation (CII) is a characteristic symptom of HIV-1 infection that contributes to acquired immunodeficiency syndrome (AIDS) progression in infected patients. Distinct AIDS development rates have shown that there are Rapid Progressor (RP) and Long-Term Non-Progressor (LTNP) patients, but the circumstances governing these differences in disease progression are poorly understood. Mutations in the Viral Protein R (Vpr) have been suggested to have a direct impact on disease progression. Studies have shown that Vpr interacts with both host and viral factors; these interactions affect cellular activities such as cell cycle progression and enhancement of apoptosis. The Vpr mutants R36W and R77Q have been associated with RP and LTNP phenotypes, respectively; however, these findings are still controversial. This study sheds light on the effects that Vpr mutations have in the context of HIV-1 infection of the HUT78 T cell line, using replication-competent CXCR4-tropic virus strains. Our results show a replication enhancement of the R36W mutant (increased viral load and percentage of p24+ cells) accompanied by increased cytotoxicity. Interestingly, the R77Q mutant showed a unique enhancement of apoptosis (measured by Annexin V and TUNEL staining) and G2 cell cycle arrest; these effects were not seen with WT or R36W viruses. Since necrosis is associated with the release of pro-inflammatory factors, the R36 mutation could lead to more robust CII and the RP phenotype. Conversely, the R77Q mutation leads to apoptosis, potentially avoiding CII and leading to a LTNP phenotype. Thus, Vpr mutations may impact HIV-1 related progression to AIDS.

Importance

Thevprgene is thought to be an important virulence factor in Human Immunodeficiency Virus type 1 (HIV-1).vprpolymorphisms have been associated with different rates of acquired immunodeficiency syndrome (AIDS) progression. However, there is controversy about the cytopathic and virulence phenotypes of Vpr mutants, with contradictory conclusions about the same mutants. Here, we examine the replication capacity, apoptosis induction, and G2 cell cycle arrest phenotypes of threevprmutants compared to wild-type HIV-1. One mutant associated with rapid AIDS progression replicated more efficiently and killed cells more rapidly than wild-type HIV-1. Another mutant associated with slow AIDS progression triggered apoptosis more efficiently than wild-type HIV-1. These results shed additional light on the role ofvprpolymorphisms in T cell killing by HIV-1 and may help to explain the role of Vpr in different rates of AIDS progression.
Model Based Comparison of Covid-19 Cases in Two Counties in the Silicon Valley
Authors: Basu Santanu
Published: May 2020

A recently developed model to analyze Covid-19 case data has been applied to compare the Covid-19 cases and hospital bed usage in Santa Clara county and San Mateo county which are in the Silicon Valley region of California. The model gives prediction for number of cases and deaths and number of hospital beds six weeks in advance. The model is versatile and can be applied to other countries and regions as well.
The global explosion of eukaryotic algae: the potential role of phosphorus?
Authors: Eckford-Soper Lisa K , Canfield Donald E.
Published: May 2020

There arose one of the most important ecological transitions in Earth’s history approximately 750 million years ago during the middle Neoproterozoic Era (1000 to 541 million years ago, Ma). Biomarker evidence suggests that around this time there was a rapid shift from a predominantly bacterial-dominated world to more complex ecosystems governed by eukaryotic primary productivity. The resulting ‘Rise of the algae’ led to dramatically altered food webs that were much more efficient in terms of nutrient and energy transfer. Yet, what triggered this ecological shift? In this study we examined the theory that it was the alleviation of phosphorus (P) deficiency that gave eukaryotic alga the prime opportunity to flourish. We performed laboratory experiments on the cyanobacteriumSynochystis salinaand the eukaryotic algaeTetraselmis sueciaand examined their ability to compete for phosphorus. Both these organisms co-occur in modern European coastal waters and are not known to have any allelopathic capabilities. The strains were cultured in mono and mixed cultures in chemostats across a range of dissolved organic phosphorus (DIP) conditions to reflect modern and ancient oceanic conditions of 0.2 μM P and 2 μM P, respectively. Our results show that the cyanobacteria outcompete the algae at the low input (0.2 μM P) treatment, yet the eukaryotic algae were not completely excluded and remained a constant background component in the mixed-culture experiments. Also, despite it’s relatively large cell size, the algaeT. sueciahad a high affinity for DIP. With DIP input concentrations resembling modern-day levels (2 μM), the eukaryotic algae could effectively compete against the cyanobacteria in terms of total biomass production. These results suggest that the availability of phosphorus could have influenced the global expansion of eukaryotic algae. However, P limitation does not seem to explain the complete absence of eukaryotic algae in the biomarker record before ca. 750 Ma.
Functional reconstitution of a bacterial CO2concentrating mechanism inE. coli
Authors: Flamholz Avi I. , Dugan Eli , Blikstad Cecilia , Gleizer Shmuel , Ben-Nissan Roee , Amram Shira , Antonovsky Niv , Ravishankar Sumedha , Noor Elad , Bar-Even Arren , Milo Ron , Savage David F.
Published: May 2020

Many photosynthetic organisms employ a CO2concentrating mechanism (CCM) to increase the rate of CO2fixation via the Calvin cycle. CCMs catalyze ≈50% of global photosynthesis, yet it remains unclear which genes and proteins are required to produce this complex adaptation. We describe the construction of a functional CCM in a non-native host, achieved by expressing genes from an autotrophic bacterium in an engineeredE. colistrain. Expression of 20 CCM genes enabledE. colito grow by fixing CO2from ambient air into biomass, with growth depending on CCM components. Bacterial CCMs are therefore genetically compact and readily transplanted, rationalizing their presence in diverse bacteria. Reconstitution enabled genetic experiments refining our understanding of the CCM, thereby laying the groundwork for deeper study and engineering of the cell biology supporting CO2assimilation in diverse organisms.

One Sentence Summary

A bacterial CO2concentrating mechanism enablesE. colito fix CO2from ambient air.
Contribution of segment 3 to the acquisition of virulence in contemporary H9N2 avian influenza viruses
Authors: Clements Anabel L. , Sealy Joshua E. , Peacock Thomas P. , Sadeyen Jean-Remy , Hussain Saira , Lycett Samantha J. , Shelton Holly , Digard Paul , Iqbal Munir
Published: May 2020

H9N2 avian influenza viruses circulate in poultry throughout much of Asia, the Middle East and Africa. These viruses cause huge economic damage to poultry production systems and pose a zoonotic threat both in their own right as well as in the generation of novel zoonotic viruses, for example H7N9. In recent years it has been observed that H9N2 viruses have further adapted to poultry, becoming more highly transmissible and causing higher morbidity and mortality. Here, we investigate the molecular basis for this increased virulence, comparing a virus from the 1990s and a contemporary field strain. The modern virus replicated to higher titres in various systems and this difference mapped to a single amino acid polymorphism at position 26 of the endonuclease domain shared by the PA and PA-X proteins. This change was responsible for the virulent phenotype and extended tissue tropism seen in chickens. Although the PA K26E change correlated with increased host cell shutoff activity of the PA-X proteinin vitro, it could not be overridden by frameshift site mutations that block PA-X expression and therefore increased PA-X activity could not explain the differences in replication phenotype. Instead, this indicates these differences are due to subtle effects on PA function. This work gives insight into the ongoing evolution and poultry adaptation of H9N2 and other avian influenza viruses and helps us understand the soaring morbidity and mortality rates in the field, as well as rapidly expanding geographical range seen in these viruses.

Author Summary

Avian influenza viruses, such as H9N2, cause huge economic damage to poultry production worldwide and are additionally considered potential pandemic threats. Understanding how these viruses evolve in their natural hosts is key to effective control strategies. In the Middle East and South Asia an older H9N2 virus strain has been replaced by a new reassortant strain with greater fitness. Here we take representative viruses and investigate the genetic basis for this ‘fitness’. A single mutation in the virus was responsible for greater fitness, enabling high growth of the contemporary H9N2 virus in cells, as well as in chickens. The genetic mutation that modulates this change is within the viral PA protein, a part of the virus polymerase gene that contributes in viral replication as well as contribute in the virus accessory functions – however we find that the fitness effect is specifically due to changes in the protein polymerase activity.
Automated and partially-automated contact tracing: a rapid systematic review to inform the control of COVID-19
Authors: Braithwaite Isobel , Callender Tom , Bullock Miriam , Aldridge Robert W
Published: May 2020

Background

Automated or partially-automated contact tracing tools are being deployed by many countries to contain SARS-CoV-2; however, the evidence base for their use is not well-established.

Methods

We undertook a rapid systematic review of automated or partially-automated contact tracing, registered with PROSPERO (CRD42020179822). We searched PubMed, EMBASE, OVID Global Health, EBSCO COVID Portal, Cochrane Library, medRxiv, bioRxiv, arXiv and Google Advanced for articles relevant to COVID-19, SARS, MERS, influenza or Ebola from 1/1/200014/4/2020. Two authors reviewed all full-text manuscripts. One reviewer extracted data using a pre-piloted form; a second independently verified extracted data. Primary outcomes were the number or proportion of contacts (and/or subsequent cases) identified; secondary outcomes were indicators of outbreak control, app/tool uptake, resource use, cost-effectiveness and lessons learnt. The Effective Public Health Practice Project tool or CHEERS checklist were used in quality assessment.

Findings

4,033 citations were identified and 15 were included. No empirical evidence of automated contact tracing’s effectiveness (regarding contacts identified or transmission reduction) was identified. Four of seven included modelling studies suggested that controlling COVID-19 requires high population uptake of automated contact-tracing apps (estimates from 56% to 95%), typically alongside other control measures. Studies of partially-automated contact tracing generally reported more complete contact identification and follow-up, and greater intervention timeliness (0.5-5 hours faster), than previous systems. No meta-analyses were possible.

Interpretation

Automated contact tracing has potential to reduce transmission with sufficient population uptake and usage. However, there is an urgent need for well-designed prospective evaluations as no studies provided empirical evidence of its effectiveness.
Climate change education in school: knowledge, behavior and attitude
Authors: Tibola da Rocha Vanessa , Brandli Luciana Londero , Kalil Rosa Maria Locatelli
Published: May 2020

Purpose

The purpose of this paper is to present an experience of inclusion of the theme “climate change” in a Brazilian public school through training conducted with teachers.

Design/methodology/approach

The methodology was based on three specific phases: reflection, focusing on the application of a pretest with 45 questions directed to three domains (knowledge, attitude and behavior); climate change education (CCE) training; and application of a post-test and action, regarding the insertion in the school space.

Findings

The survey results highlight the difficulty teachers have in understanding and applying CCE in the classroom and it underscores the importance of this approach.

Research limitations/implications

The research approach is related to a specific case in a school located in south of Brazil. Although the school has its own context, the reported experience can be considered elsewhere.

Practical implications

This case study reinforces that CCE presents broad challenges for the scientific community. For the reason that the understanding of the topic (CCE) is complex, considering the global context and the divergent opinions on the subject.

Social implications

The paper reinforces that for today’s society, sustainable development is no longer a choice but a necessity, underpinned by global Agenda 2030 discussions. In this context, teachers are essential to the transformation toward a better future.

Originality/value

The difficulties and facilities encountered during the experience serve to enhance new actions at national or even global level, respecting each new context of study and insertion of research directed to the theme – CCE.
Organizing professionalism: integrating institutional logics in Brazilian law firms
Authors: Tureta César , Castelo Júnior Clóvis
Published: May 2020

Purpose

The purpose of this study is to analyse organizing professionalism and its consequences for the work of lawyers in large Brazilian corporate law firms.

Design/methodology/approach

The study used qualitative interviews with lawyers linked to six of the Brazilian’s leading law firms. The focus of the interviews was to explore the work organization form considering the changes to the legal profession in recent years.

Findings

The results indicate that the institutional changes had substantial consequences for lawyers: a need to organize work, to integrate professional and management logic and to develop typical managerial skills to be more connective when performing tasks in work teams.

Research limitations/implications

Socio-economic changes that gave rise to more flexible forms of work organization have imposed professional restructuring and leading law firms to adopt a business model of organizing. The study is based on qualitative interviews, meaning that the findings cannot be generalized.

Practical implications

Lawyers need to develop typical managerial skills to align their competencies with the management logic incorporated by law firms.

Originality/value

Despite the increase of studies on professions, the integration of professional and managerial logic and its consequences to lawyers has been underdeveloped. Furthermore, research has focussed mainly on macro-level changes and given less attention to how institutional changes impact individual level.
The Impact of The Covid-19 Pandemic on Italian Mobility
Authors: Finazzi Francesco , Fassò Alessandro
Published: May 2020

Francesco Finazzi and Alessandro Fassò use location data collected by an earthquake-monitoring app to gauge compliance with lockdown measures in Italy
High expression of KITLG is a new hallmark activating the MAPK pathway in type A and AB thymoma
Authors: Yang Zhaoyu , Liu Shinan , Wang Yuanguo , Chen Yuan , Zhang Peng , Liu Yimei , Zhang Hui , Zhang Peng , Tao Ziyou , Xiong Kai
Published: May 2020

Background

KIT proto‐oncogene ligand (KITLG) is a pleiotropic factor which is found in diverse cancers and is involved in cell proliferation, differentiation, and survival. However, the value of KITLG in thymoma remains unclear.

Methods

A total of 121 thymoma samples from The Cancer Genome Atlas Thymoma (TCGA‐THYM) dataset were used to analyze KITLG related genome‐wide expression profiles, and microRNA profiles and methylation alterations and a GEO dataset‐GSE29695, including 37 samples was used as verification. For cell‐based studies, specific small interfering RNA targeting KITLG or a KITLG overexpression vector were used to clarify the changes of the MAPK pathway in an AB thymoma cell line Thy0517.

Results

Both datasets showed that high expression of KITLG was significantly associated with type A and AB thymoma. Through multiomic analysis of the TCGA‐THYM, it was found that with the high expression of KITLG, there were 220 upregulated and 72 downregulated genes at the mRNA level, 79 positive and 78 negative miRNAs, 28 hypermethylation and 163 hypomethylation regions. In the thymoma cell line Thy0517, it was found that the expression of GRB2 and the phosphorylation levels of BRAF, MEK1/2, and ERK1/2 in the MAPK pathway were positively correlated with the change in KITLG.

Conclusions

High expression of KITLG is a new hallmark of WHO type A and AB thymomas in which it might play a critical role through the activation of the MAPK signaling pathway. Additionally, it is hoped that KITLG will become a potential target for the diagnosis of type A and AB thymoma through further research in the future.

Key points

Significant findings of the study

KIT proto‐oncogene ligand (KITLG) is a new hallmark of type A and AB thymomas which induce a series of aberrant alteration of mRNA, miRNA and DNA methylation. The expression of KITLG is significantly higher in type A and AB than other subtypes of thymoma.

What this study adds

KITLG activated the MAPK signaling pathway to promote type A and AB thymoma which might be a potential diagnostic biomarker or target.
Sepsis is underreported in Swedish intensive care units: A retrospective observational multicentre study
Authors: Lengquist Maria , Lundberg Oscar H. M. , Spångfors Martin , Annborn Martin , Levin Helena , Friberg Hans , Frigyesi Attila
Published: May 2020

Background

Sepsis is a common indication for admission to the intensive care unit (ICU). Since definitions vary across studies, comparisons of prevalence and outcomes have been challenging. We aimed to compare sepsis according to ICU discharge codes with sepsis according to Sepsis‐3 criteria and to investigate the epidemiology of sepsis in the ICU. We hypothesized that sepsis using discharge codes is underreported.

Methods

Adult ICU admissions to four ICUs in Sweden between 2015 and 2017 were screened for sepsis according to the Sepsis‐3 criteria. Medical records were reviewed and data extracted from the Swedish Intensive Care Registry.

Results

Of 5990 adult ICU patients, 28% fulfilled the Sepsis‐3 criteria on admission, but only 31% of them had sepsis as the registered main diagnosis at ICU discharge. Of the 1654 Sepsis‐3 patients, 38% met the septic shock criteria. The Sepsis‐3 in‐hospital mortality was 26% compared to 33% in patients with septic shock. The incidence rate for ICU‐treated sepsis was 81 cases per 100 000 person‐years. One in four had a positive blood culture, and 44% were culture negative.

Conclusion

This large Swedish multicentre study showed that 28% of adult ICU patients fulfilled the Sepsis‐3 criteria, but only one third of them had sepsis according to ICU discharge codes. We could confirm our hypothesis, that sepsis is severely underreported in Swedish ICUs, and we conclude that discharge codes should not be used for quality control or research purposes.
Smicridea (Smicridea) nigripennis species group (Trichoptera: Hydropsychidae) from Brazil: new species, new distributional records and an identification key
Authors: Desidério Gleison R , Rázuri‐Gonzales Ernesto , Pes Ana M , Hamada Neusa
Published: May 2020

Three new species in the Smicridea (Smicridea) nigripennis species group are described and illustrated based on specimens collected in Serra da Mocidade National Park and Serra do Tepequém in the northern mountain range of Brazilian Amazonia, Roraima State, and in Rio Formosinho located in Cerrado biome of midwestern Brazil, Mato Grosso do Sul State. Smicridea (Smicridea) mocidade Desidério & Rázuri‐Gonzales, sp. nov., Smicridea (Smicridea) santosi Desidério & Rázuri‐Gonzales, sp. nov. and Smicridea (Smicridea) tepequensis Desidério & Rázuri‐Gonzales, sp. nov. can be recognised mainly by the morphology of the phallic apparatus. New distributional records are provided for Smicridea (Smicridea) caatinga Alves et al., 2018, Smicridea (Smicridea) franciscana Rocha et al., 2016, Smicridea (Smicridea) mirnae Almeida & Flint, 2002 and Smicridea (Smicridea) palifera Flint, 1981. Smicridea (Smicridea) cornuta Flint, 1974 is recorded for the first time from Brazil. Additionally, a key to identify males of the 10 species in the Smicridea (Smicridea) nigripennis species group known from Brazil is provided.
Anaphylaxis in pregnancy: a population‐based multinational European study
Authors: McCall S. J. , Bonnet M.‐P. , Äyräs O. , Vandenberghe G. , Gissler M. , Zhang W.‐H. , Van Leeuw V. , Deneux‐Tharaux C. , Kurinczuk J. J. , Knight M. ,   the INOSS collaboration
Published: May 2020

Anaphylaxis in pregnancy is a rare but severe complication for both mother and infant. Population‐based data on anaphylaxis in pregnancy are lacking from mainland European countries. This multinational study presents the incidence, causative agents, management and maternal and infant outcomes of anaphylaxis in pregnancy. This descriptive multinational study used a combination of retrospective (Finnish medical registries) and prospective population‐based studies (UK, France, Belgium and the Netherlands) to identify cases of anaphylaxis. Sixty‐five cases were identified among 4,446,120 maternities (1.5 per 100,000 maternities; 95%CI 1.1–1.9). The incidence did not vary between countries. Approximately three‐quarters of reactions occurred at the time of delivery. The most common causes were antibiotics in 27 women (43%), and anaesthetic agents in 11 women (17%; including neuromuscular blocking drugs, 7), which varied between countries. Anaphylaxis had very poor outcomes for one in seven mothers and one in seven babies; the maternal case fatality rate was 3.2% (95%CI 0.4–11.0) and the neonatal encephalopathy rate was 14.3% (95%CI 4.8–30.3). Across Europe, anaphylaxis related to pregnancy is rare despite having a multitude of causative agents and different antibiotic prophylaxis protocols.
Age‐dependent changes in glutathione metabolism pathways in the lens: New insights into therapeutic strategies to prevent cataract formation—A review
Authors: Lim Julie C. , Grey Angus C. , Zahraei Ali , Donaldson Paul J.
Published: May 2020

Ocular tissues possess a robust antioxidant defence system to minimize oxidative stress and preserve tissue structure and function. Glutathione (GSH) is a powerful antioxidant and in the lens exists at unusually high concentrations. However, with advancing age, GSH levels deplete specifically in the lens centre initiating a chain of biochemical events that ultimately result in protein aggregation, light scattering and age‐related nuclear cataract. However, antioxidant supplementation has been shown to be ineffective in preventing or delaying cataract indicating that a better understanding of the delivery, uptake and metabolism of GSH in the different regions of the lens is required. This information is essential for the development of scientifically informed approaches that target the delivery of GSH to the lens nucleus, the region of the lens most affected by age‐related cataract.
“The Land of the Free and the Home of the Brave”: Lessons Learned in (Im)migrant Communities
Authors: Kim Jung Ha
Published: May 2020

Although situating itself at the core, the mainstream is not the center that embraces and draws the diverse nation together. Although attributing to itself a singleness of purpose and resolve, the mainstream is neither uniform nor powerful in its imperialism and hegemony. Although casting the periphery beyond the bounds of civility and religion, the mainstream derives its identity, its integrity, from its representation of the other. And despite its authorship of the central tenets of democracy, the mainstream has been silent on the publication of its creed. In fact, the margin has tested and ensured the guarantees of citizenship, and the margins have been the true defender of American democracy, equality, and liberty. From that vantage, we can see the margin as mainstream.
Adding a second skin prick test reading and modifying the cut‐off for beta‐lactam–specificIgEenhances the sensitivity in the routine diagnostic workup for immediate beta‐lactam hypersensitivity
Authors: Rosti Bernadette , Mahler Vera
Published: May 2020

Background

Beta‐lactam (BL)–antibiotics are the most frequent reason for drug‐induced hypersensitivity reactions. Because they are more efficient, less toxic, and less costly than other antibiotics, confirmation or exclusion of BL allergy is worthwhile. However, allergy tests for drug allergies are often false‐negative.

Objectives

To evaluate the components of a stepwise diagnostic algorithm for immediate BL hypersensitivity with regard to sensitivity (SENS).

Methods

Consecutive patients with suspected allergy to BL antibiotics were retrospectively analyzed with regard to increasing sensitivity (plausible history of immediate BL hypersensitivity serving as external criterion) of (i) skin prick test (SPT) by adding a second reading (n = 746), (ii) BL‐specific IgE‐determination in vitro at two cut‐offs (n = 539), and (iii) adding in vivo testing of minor and major BL determinants (n = 288).

Results

In the history‐based population indicative of immediate BL hypersensitivity (n = 457), SPT with a sole 20‐minute reading identified 99 (SENS: 0.21) and SPT with 20‐ and 40‐minute‐reading identified 133 cases (SENS: 0.29). in vitro specific IgE‐examination identified 31 positives at a cut‐off ≥0.35 kUA/L (5.8% of tested) and 99 at cut‐off ≥0.11 kUA/L (18.4% of tested). In 203 SPT‐negative individuals, immediate BL hypersensitivity was identified by additional tests: in 79 by specific IgE (cut‐off ≥0.11 kUA/L) (thereof 53 identified solely by this test) and in 150 by in vivo testing of BL determinants in combination with Penicillin and Ampicillin intradermally (thereof 124 solely by this test); in 26 individuals both additional tests were positive. The combination of the three outpatient‐based test modalities—(i) optimized SPT, (ii) specific IgE at optimized cut‐off, and (iii) in vivo testing of BL determinants/Penicillin/Ampicillin—identified altogether 336/457 individuals with immediate BL‐hypersensitivity (SENS: 0.73), whereas the combination of the two (i) + (ii) identified 212/457 (SENS: 0.46); (i) + (iii) 283/457 (SENS: 0.61).

Conclusions

To overcome the low sensitivity of allergological tests, optimized reading times of the SPT of BL, a lower cut‐off for in vitro detection of BL‐specific IgE, and intradermal testing of Penicillin, Ampicillin, and BL‐determinants contribute to overall sensitivity under real life conditions to diagnose immediate BL‐hypersensitivity.