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Kids' Happiness Doesn't Depend on 2 Natural Parents, Says Study

Title: Kids' Happiness Doesn't Depend on 2 Natural Parents, Says Study
Category: Health News
Created: 4/25/2014 2:35:00 PM
Last Editorial Review: 4/28/2014 12:00:00 AM




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Type 2 Diabetes May Shrink the Brain, Study Suggests

Title: Type 2 Diabetes May Shrink the Brain, Study Suggests
Category: Health News
Created: 4/29/2014 9:35:00 AM
Last Editorial Review: 4/29/2014 12:00:00 AM




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2nd U.S. Ice Cream Maker Pulls All Products After Listeria Threat

Title: 2nd U.S. Ice Cream Maker Pulls All Products After Listeria Threat
Category: Health News
Created: 4/24/2015 12:00:00 AM
Last Editorial Review: 4/27/2015 12:00:00 AM




2

Company to Destroy 265 Tons of Ice Cream Over Listeria Contamination

Title: Company to Destroy 265 Tons of Ice Cream Over Listeria Contamination
Category: Health News
Created: 4/28/2015 12:00:00 AM
Last Editorial Review: 4/29/2015 12:00:00 AM




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2-Minute Walk Every Hour May Help Offset Effects of Sitting

Title: 2-Minute Walk Every Hour May Help Offset Effects of Sitting
Category: Health News
Created: 4/30/2015 12:00:00 AM
Last Editorial Review: 5/1/2015 12:00:00 AM




2

Psoriasis Tied to Obesity, Type 2 Diabetes

Title: Psoriasis Tied to Obesity, Type 2 Diabetes
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM




2

Type 2 Diabetes May Damage Hearing, Study Finds

Title: Type 2 Diabetes May Damage Hearing, Study Finds
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM




2

California Handgun Sales Spiked After 2 Mass Shootings

Title: California Handgun Sales Spiked After 2 Mass Shootings
Category: Health News
Created: 5/1/2017 12:00:00 AM
Last Editorial Review: 5/2/2017 12:00:00 AM




2

Low-Dose Aspirin May Lower Risk for Common Breast Cancer by 20 Percent

Title: Low-Dose Aspirin May Lower Risk for Common Breast Cancer by 20 Percent
Category: Health News
Created: 5/1/2017 12:00:00 AM
Last Editorial Review: 5/2/2017 12:00:00 AM




2

Doctors Remove 132-Pound Tumor From Woman

Title: Doctors Remove 132-Pound Tumor From Woman
Category: Health News
Created: 5/4/2018 12:00:00 AM
Last Editorial Review: 5/4/2018 12:00:00 AM




2

Meal Swaps That Save 200 Calories

Title: Meal Swaps That Save 200 Calories
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM




2

Could You Be Short on Vitamin B12?

Title: Could You Be Short on Vitamin B12?
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM




2

MS Patients Now Pay 20 Times More for Drugs Than a Decade Ago

Title: MS Patients Now Pay 20 Times More for Drugs Than a Decade Ago
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM




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U.S. Jobless Rate at Nearly 15 Percent as Coronavirus Cases Top 1.2 Million

Title: U.S. Jobless Rate at Nearly 15 Percent as Coronavirus Cases Top 1.2 Million
Category: Health News
Created: 5/8/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM




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Trump Says Obamacare Must Go as U.S. Coronavirus Cases Climb Past 1.2 Million

Title: Trump Says Obamacare Must Go as U.S. Coronavirus Cases Climb Past 1.2 Million
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM




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Coronavirus Daily Digest: May 6, 2020

A roundup of the latest news about COVID-19




2

EuroPCR 2020 Canceled as SCAI, SCCT, TVT Go Virtual

In a sign of the times and things to come, in-person cardiovascular society meetings pivot to virtual events.




2

Coronavirus Daily Digest: May 7, 2020

A roundup of the latest news about COVID-19




2

European Society of Cardiology 2020 Congress Goes Virtual

COVID-19 has led the ESC to transition its annual congress to a virtual format; ESC 2020 Congress 'Challenging Times, Infinite Possibilities' will run online from August 29 to September 1.




2

SARS-CoV-2 in Semen of COVID-19 Patients?

Researchers report evidence of SARS-CoV-2, which causes COVID-19, in the semen of patients; the data raise the possibility of sexual transmission, but experts say there is no evidence of infectivity.




2

Coronavirus Daily Digest: May 8, 2020

A roundup of the latest news about COVID-19




2

PMC Canada to Start in Fall 2009

Canada is soon expected to join the international effort to provide access to health research through the PMC International network of digital archives. PMC Canada is the result of a three-way collaborative effort by the National Library of Medicine (NLM), the Canadian Institutes of Health Research (CIHR), and the National Research Council's Canada Institute for Scientific and Technical Information (NRC-CISTI). Similar to UK PubMed Central, PMC Canada will include most of the health and life sciences literature available through the U.S. PMC. PMC Canada will also include research resulting from funding through the Canadian Institutes of Health Research (CIHR). Components of the new repository will include a bilingual interface as well a manuscript submission system for CIHR researchers.




2

First-Ever Journal Article Tag Suite Conference (JATS-Con) to be Held in November 2010

PMC is pleased to announce the first of what we hope will be an annual series of conferences for users of the Journal Article Tag Suite, that is, for users of any of the “NLM DTDs”. The Journal Article Tag Suite Conference (JATS-Con) is a peer-reviewed conference that will feature a broad range of content on the Tag Suite—from the technical components to publishing theory—as well as the latest news on the Tag Suite. The conference will be hosted by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine on the NIH campus in Bethesda, Maryland on November 1 & 2, 2010.

For more information on the conference, see https://jats.nlm.nih.gov/jats-con.

Note: There is no charge for the conference; however, space is limited so preregistration is required.




2

JATS-Con Dates Announced for 2012!

The third annual Journal Article Tag Suite Conference (JATS-Con) will be held on October 16 and 17, 2012 on the NIH Campus in Bethesda, Maryland. JATS-Con is a conference for users of the NISO Z39.96 Journal Article Tag Suite: that is, users of any of the NLM DTDs. JATS-Con is a peer-reviewed conference with a broad range of content on the Tag Suite from the technical to publishing theory — and the latest news on the Tag Suite. For more information, see JATS-Con.




2

JATS-Con 2013 Program is Now Available

JATS-Con is a conference for users of the Journal Article Tag Suite, that is, users of any of the "NLM DTDs" or NISO Z39.96. JATS-Con will take place on the NIH campus in Bethesda, Maryland on October 22 and 23, 2013.

The full program is now available, as are proceedings from previous years.

There is no charge for the conference; however, space is limited so registration is required.

You may also sign up for a pre-conference tutorial on October 21, 2013. Details are on the Tutorial Registration page.




2

Open Access Week 2018 and PMC

Collaboration with publishers and funders to ensure the openness and preservation of the scientific record is one of PMC’s core principles. Open Access Week offers an opportunity to celebrate some of the recent outcomes of these collaborations:

  • In July 2018, the PMC corpus of publicly accessible articles hit 5 million articles.
  • In May 2018, the PMC Open Access Subset surpassed the 2 million article mark.
  • The Author Manuscript Collection now includes more than 500,000 papers for text mining.
  • The PMC and Research Funder Policy page underwent an update in September 2018 to increase transparency around funder support in PMC for publishers, authors, and the public.
  • Funder policy support in PMC has been extended to the US Department of Homeland Security, in addition to several new US private research funders via the Health Research Alliance.

In FY2018 more than 200 new journals committed to archiving their complete contents in PMC, to be made publicly accessible in 12 months or less.




2

Obesity Is Biggest Type 2 Diabetes Risk Factor

Title: Obesity Is Biggest Type 2 Diabetes Risk Factor
Category: Health News
Created: 4/16/2020 12:00:00 AM
Last Editorial Review: 4/17/2020 12:00:00 AM




2

After 2nd Patient Cured of HIV, Hope Revives for an End to AIDS

Title: After 2nd Patient Cured of HIV, Hope Revives for an End to AIDS
Category: Health News
Created: 3/10/2020 12:00:00 AM
Last Editorial Review: 3/11/2020 12:00:00 AM




2

24 Best Foods for Blood Circulation

Title: 24 Best Foods for Blood Circulation
Category: Health and Living
Created: 4/9/2020 12:00:00 AM
Last Editorial Review: 4/9/2020 12:00:00 AM




2

2 in 3 Women Unhappy With Their Breast Size. Could That Harm Their Health?

Title: 2 in 3 Women Unhappy With Their Breast Size. Could That Harm Their Health?
Category: Health News
Created: 2/6/2020 12:00:00 AM
Last Editorial Review: 2/6/2020 12:00:00 AM




2

Were You Born in an H1N1 Flu Year or an H3N2? It Matters

Title: Were You Born in an H1N1 Flu Year or an H3N2? It Matters
Category: Health News
Created: 2/11/2020 12:00:00 AM
Last Editorial Review: 2/12/2020 12:00:00 AM




2

Flu Season That's Sickened 26 Million May Be at Its Peak

Title: Flu Season That's Sickened 26 Million May Be at Its Peak
Category: Health News
Created: 2/21/2020 12:00:00 AM
Last Editorial Review: 2/21/2020 12:00:00 AM




2

High Heat, Humidity Could Affect More Than 1.2 Billion People by End of Century

Title: High Heat, Humidity Could Affect More Than 1.2 Billion People by End of Century
Category: Health News
Created: 3/24/2020 12:00:00 AM
Last Editorial Review: 3/25/2020 12:00:00 AM




2

Dangerously Hot Days for U.S. Farm Workers Could Double by 2050

Title: Dangerously Hot Days for U.S. Farm Workers Could Double by 2050
Category: Health News
Created: 5/5/2020 12:00:00 AM
Last Editorial Review: 5/6/2020 12:00:00 AM




2

Tukysa Approved for Unresectable, Metastatic HER2-Positive Breast Cancer

Title: Tukysa Approved for Unresectable, Metastatic HER2-Positive Breast Cancer
Category: Health News
Created: 4/20/2020 12:00:00 AM
Last Editorial Review: 4/21/2020 12:00:00 AM




2

Erratum for 'The Chalk Group (Upper Cretaceous) of the Northern Province, eastern England - a review, Proceedings of the Yorkshire Geological Society, 62, 153-177




2

Yorkshire Geological Society Registered Charity No. 220014 Society Proceedings 2018




2

Subject Index to Volume 83 (2019)




2

Author Index to Volume 83 (2019)




2

Top-Cited Articles from Dental Education Journals, 2009 to 2018: A Bibliometric Analysis

The number of citations an article receives is an important indicator to quantify its influence in its field. The aim of this study was to identify and analyze the characteristics of the 50 top-cited articles addressing dental education published in two journals dedicated to dental education (European Journal of Dental Education and Journal of Dental Education). The Web of Science database was searched to retrieve the 50 most-cited articles from the two journals in December 2018. The top-cited articles were analyzed for journal of publication, number of citations, institution and country of origin, year of publication, study type, keywords, theme and subtheme, and international collaborations. The results showed the 50 top-cited articles were cited between 24 and 146 times each. The majority of these top-cited articles (n=34) were published in the Journal of Dental Education. Half (n=25) of the articles were by authors in the U.S. The most common study types were surveys (n=26) and reviews (n=10). The main themes of these top-cited articles were curriculum and learner characteristics. This bibliometric analysis can serve as a reference for recognizing studies with the most impact in the scholarship of dental education.




2

The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay

ABSTRACT

The nonsense-mediated decay (NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3' untranslated regions (UTRs). The umbravirus Pea enation mosaic virus 2 (PEMV2) is a nonsegmented, positive-sense RNA virus with an unusually long 3' UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2 long-distance movement protein p26 was previously shown to both stabilize viral RNAs and bind them for transport through the plant’s vascular system. The current study demonstrated that p26 protects both viral and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclusively in the cytoplasm independently of long-distance movement. Using a transcriptome-wide approach in the model plant Nicotiana benthamiana, p26 protected a subset of cellular NMD target transcripts, particularly those containing long, structured, GC-rich 3' UTRs. Furthermore, transcriptome sequencing (RNA-seq) revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with 1,820 (48%) of NMD targets increasing in abundance. Widespread changes in the host transcriptome are common during plant RNA virus infections, and these results suggest that, in at least some instances, virus-mediated NMD inhibition may be a major contributing factor.

IMPORTANCE Nonsense-mediated decay (NMD) represents an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3' untranslated regions. NMD targets diverse families of RNA viruses, requiring that viruses counteract the NMD pathway for successful amplification in host cells. A protein required for long-distance movement of Pea enation mosaic virus 2 (PEMV2) is shown to also protect both viral and host mRNAs from NMD. RNA-seq analyses of the Nicotiana benthamiana transcriptome revealed that PEMV2 infection significantly impairs the host NMD pathway. RNA viruses routinely induce large-scale changes in host gene expression, and, like PEMV2, may use NMD inhibition to alter the host transcriptome in an effort to increase virus amplification.




2

Merkel Cell Polyomavirus DNA Replication Induces Senescence in Human Dermal Fibroblasts in a Kap1/Trim28-Dependent Manner

ABSTRACT

Merkel cell polyomavirus (MCPyV) is the only polyomavirus known to be associated with tumorigenesis in humans. Similarly to other polyomaviruses, MCPyV expresses a large tumor antigen (LT-Ag) that, together with a small tumor antigen (sT-Ag), contributes to cellular transformation and that is of critical importance for the initiation of the viral DNA replication. Understanding the cellular protein network regulated by MCPyV early proteins will significantly contribute to our understanding of the natural MCPyV life cycle as well as of the mechanisms by which the virus contributes to cellular transformation. We here describe KRAB-associated protein 1 (Kap1), a chromatin remodeling factor involved in cotranscriptional regulation, as a novel protein interaction partner of MCPyV T antigens sT and LT. Kap1 knockout results in a significant increase in the level of viral DNA replication that is highly suggestive of Kap1 being an important host restriction factor during MCPyV infection. Differently from other DNA viruses, MCPyV gene expression is unaffected in the absence of Kap1 and Kap1 does not associate with the viral genome. Instead, we show that in primary normal human dermal fibroblast (nHDF) cells, MCPyV DNA replication, but not T antigen expression alone, induces ataxia telangiectasia mutated (ATM) kinase-dependent Kap1 S824 phosphorylation, a mechanism that typically facilitates repair of double-strand breaks in heterochromatin by arresting the cells in G2. We show that MCPyV-induced inhibition of cell proliferation is mainly conferred by residues within the origin binding domain and thereby by viral DNA replication. Our data suggest that phosphorylation of Kap1 and subsequent Kap1-dependent G2 arrest/senescence represent host defense mechanisms against MCPyV replication in nHDF cells.

IMPORTANCE We here describe Kap1 as a restriction factor in MCPyV infection. We report a novel, indirect mechanism by which Kap1 affects MCPyV replication. In contrast with from other DNA viruses, Kap1 does not associate with the viral genome in MCPyV infection and has no impact on viral gene expression. In MCPyV-infected nHDF cells, Kap1 phosphorylation (pKap1 S824) accumulates because of genomic stress mainly induced by viral DNA replication. In contrast, ectopic expression of LT or LT MCPyV mutants, previously shown to be important for induction of genotoxic stress, does not result in a similar extent of pKap1 accumulation. We show that cells actively replicating MCPyV accumulate pKap1 (in a manner dependent on the presence of ATM) and display a senescence phenotype reflected by G2 arrest. These results are supported by transcriptome analyses showing that LT antigen, in a manner dependent on the presence of Kap1, induces expression of secreted factors, which is known as the senescence-associated secretory phenotype (SASP).




2

CO2/HCO3- Accelerates Iron Reduction through Phenolic Compounds

ABSTRACT

Iron is a vital mineral for almost all living organisms and has a pivotal role in central metabolism. Despite its great abundance on earth, the accessibility for microorganisms is often limited, because poorly soluble ferric iron (Fe3+) is the predominant oxidation state in an aerobic environment. Hence, the reduction of Fe3+ is of essential importance to meet the cellular demand of ferrous iron (Fe2+) but might become detrimental as excessive amounts of intracellular Fe2+ tend to undergo the cytotoxic Fenton reaction in the presence of hydrogen peroxide. We demonstrate that the complex formation rate of Fe3+ and phenolic compounds like protocatechuic acid was increased by 46% in the presence of HCO3 and thus accelerated the subsequent redox reaction, yielding reduced Fe2+. Consequently, elevated CO2/HCO3 levels increased the intracellular Fe2+ availability, which resulted in at least 50% higher biomass-specific fluorescence of a DtxR-based Corynebacterium glutamicum reporter strain, and stimulated growth. Since the increased Fe2+ availability was attributed to the interaction of HCO3 and chemical iron reduction, the abiotic effect postulated in this study is of general relevance in geochemical and biological environments.

IMPORTANCE In an oxygenic environment, poorly soluble Fe3+ must be reduced to meet the cellular Fe2+ demand. This study demonstrates that elevated CO2/HCO3 levels accelerate chemical Fe3+ reduction through phenolic compounds, thus increasing intracellular Fe2+ availability. A number of biological environments are characterized by the presence of phenolic compounds and elevated HCO3 levels and include soil habitats and the human body. Fe2+ availability is of particular interest in the latter, as it controls the infectiousness of pathogens. Since the effect postulated here is abiotic, it generally affects the Fe2+ distribution in nature.




2

Genetic Manipulation of Human Intestinal Enteroids Demonstrates the Necessity of a Functional Fucosyltransferase 2 Gene for Secretor-Dependent Human Norovirus Infection

ABSTRACT

Human noroviruses (HuNoVs) are the leading cause of nonbacterial gastroenteritis worldwide. Histo-blood group antigen (HBGA) expression is an important susceptibility factor for HuNoV infection based on controlled human infection models and epidemiologic studies that show an association of secretor status with infection caused by several genotypes. The fucosyltransferase 2 gene (FUT2) affects HBGA expression in intestinal epithelial cells; secretors express a functional FUT2 enzyme, while nonsecretors lack this enzyme and are highly resistant to infection and gastroenteritis caused by many HuNoV strains. These epidemiologic associations are confirmed by infections in stem cell-derived human intestinal enteroid (HIE) cultures. GII.4 HuNoV does not replicate in HIE cultures derived from nonsecretor individuals, while HIEs from secretors are permissive to infection. However, whether FUT2 expression alone is critical for infection remains unproven, since routinely used secretor-positive transformed cell lines are resistant to HuNoV replication. To evaluate the role of FUT2 in HuNoV replication, we used CRISPR or overexpression to genetically manipulate FUT2 gene function to produce isogenic HIE lines with or without FUT2 expression. We show that FUT2 expression alone affects both HuNoV binding to the HIE cell surface and susceptibility to HuNoV infection. These findings indicate that initial binding to a molecule(s) glycosylated by FUT2 is critical for HuNoV infection and that the HuNoV receptor is present in nonsecretor HIEs. In addition to HuNoV studies, these isogenic HIE lines will be useful tools to study other enteric microbes where infection and/or disease outcome is associated with secretor status.

IMPORTANCE Several studies have demonstrated that secretor status is associated with susceptibility to human norovirus (HuNoV) infection; however, previous reports found that FUT2 expression is not sufficient to allow infection with HuNoV in a variety of continuous laboratory cell lines. Which cellular factor(s) regulates susceptibility to HuNoV infection remains unknown. We used genetic manipulation of HIE cultures to show that secretor status determined by FUT2 gene expression is necessary and sufficient to support HuNoV replication based on analyses of isogenic lines that lack or express FUT2. Fucosylation of HBGAs is critical for initial binding and for modification of another putative receptor(s) in HIEs needed for virus uptake or uncoating and necessary for successful infection by GI.1 and several GII HuNoV strains.




2

Structural Basis of Ca2+-Dependent Self-Processing Activity of Repeat-in-Toxin Proteins

ABSTRACT

The posttranslational Ca2+-dependent "clip-and-link" activity of large repeat-in-toxin (RTX) proteins starts by Ca2+-dependent structural rearrangement of a highly conserved self-processing module (SPM). Subsequently, an internal aspartate-proline (Asp-Pro) peptide bond at the N-terminal end of SPM breaks, and the liberated C-terminal aspartyl residue can react with a free -amino group of an adjacent lysine residue to form a new isopeptide bond. Here, we report a solution structure of the calcium-loaded SPM (Ca-SPM) derived from the FrpC protein of Neisseria meningitidis. The Ca-SPM structure defines a unique protein architecture and provides structural insight into the autocatalytic cleavage of the Asp-Pro peptide bond through a "twisted-amide" activation. Furthermore, in-frame deletion of the SPM domain from the ApxIVA protein of Actinobacillus pleuropneumoniae attenuated the virulence of this porcine pathogen in a pig respiratory challenge model. We hypothesize that the Ca2+-dependent clip-and-link activity represents an unconventional strategy for Gram-negative pathogens to adhere to the host target cell surface.

IMPORTANCE The Ca2+-dependent clip-and-link activity of large repeat-in-toxin (RTX) proteins is an exceptional posttranslational process in which an internal domain called a self-processing module (SPM) mediates Ca2+-dependent processing of a highly specific aspartate-proline (Asp-Pro) peptide bond and covalent linkage of the released aspartyl to an adjacent lysine residue through an isopeptide bond. Here, we report the solution structures of the Ca2+-loaded SPM (Ca-SPM) defining the mechanism of the autocatalytic cleavage of the Asp414-Pro415 peptide bond of the Neisseria meningitidis FrpC exoprotein. Moreover, deletion of the SPM domain in the ApxIVA protein, the FrpC homolog of Actinobacillus pleuropneumoniae, resulted in attenuation of virulence of the bacterium in a pig infection model, indicating that the Ca2+-dependent clip-and-link activity plays a role in the virulence of Gram-negative pathogens.




2

Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS-CoV-2/COVID-19




2

Epistatic Interplay between Type IV Secretion Effectors Engages the Small GTPase Rab2 in the Brucella Intracellular Cycle

ABSTRACT

Intracellular bacterial pathogens remodel cellular functions during their infectious cycle via the coordinated actions of effector molecules delivered through dedicated secretion systems. While the function of many individual effectors is known, how they interact to promote pathogenesis is rarely understood. The zoonotic bacterium Brucella abortus, the causative agent of brucellosis, delivers effector proteins via its VirB type IV secretion system (T4SS) which mediate biogenesis of the endoplasmic reticulum (ER)-derived replicative Brucella-containing vacuole (rBCV). Here, we show that T4SS effectors BspB and RicA display epistatic interactions in Brucella replication. Defects in rBCV biogenesis and Brucella replication caused by deletion of bspB were dependent on the host GTPase Rab2a and suppressed by the deletion of ricA, indicating a role of Rab2-binding effector RicA in these phenotypic defects. Rab2a requirements for rBCV biogenesis and Brucella intracellular replication were abolished upon deletion of both bspB and ricA, demonstrating that the functional interaction of these effectors engages Rab2-dependent transport in the Brucella intracellular cycle. Expression of RicA impaired host secretion and caused Golgi fragmentation. While BspB-mediated changes in ER-to-Golgi transport were independent of RicA and Rab2a, BspB-driven alterations in Golgi vesicular traffic also involved RicA and Rab2a, defining BspB and RicA’s functional interplay at the Golgi interface. Altogether, these findings support a model where RicA modulation of Rab2a functions impairs Brucella replication but is compensated by BspB-mediated remodeling of Golgi apparatus-associated vesicular transport, revealing an epistatic interaction between these T4SS effectors.

IMPORTANCE Bacterial pathogens with an intracellular lifestyle modulate many host cellular processes to promote their infectious cycle. They do so by delivering effector proteins into host cells via dedicated secretion systems that target specific host functions. While the roles of many individual effectors are known, how their modes of action are coordinated is rarely understood. Here, we show that the zoonotic bacterium Brucella abortus delivers the BspB effector that mitigates the negative effect on bacterial replication that the RicA effector exerts via modulation of the host small GTPase Rab2. These findings provide an example of functional integration between bacterial effectors that promotes proliferation of pathogens.




2

Nonproteolytic K29-Linked Ubiquitination of the PB2 Replication Protein of Influenza A Viruses by Proviral Cullin 4-Based E3 Ligases

ABSTRACT

The multifunctional nature of viral proteins is essentially driven by posttranslational modifications (PTMs) and is key for the successful outcome of infection. For influenza A viruses (IAVs), a composite pattern of PTMs regulates the activity of viral proteins. However, almost none are known that target the PB2 replication protein, except for inducing its degradation. We show here that PB2 undergoes a nonproteolytic ubiquitination during infection. We identified E3 ubiquitin ligases catalyzing this ubiquitination as two multicomponent RING-E3 ligases based on cullin 4 (CRL4s), which are both contributing to the levels of ubiquitinated forms of PB2 in infected cells. The CRL4 E3 ligase activity is required for the normal progression of the viral cycle and for maximal virion production, indicating that the CRL4s mediate a ubiquitin signaling that promotes infection. The CRL4s are recruiting PB2 through an unconventional bimodal interaction with both the DDB1 adaptor and DCAF substrate receptors. While able to bind to PB2 when engaged in the viral polymerase complex, the CRL4 factors do not alter transcription and replication of the viral segments during infection. CRL4 ligases catalyze different patterns of lysine ubiquitination on PB2. Recombinant viruses mutated in the targeted lysines showed attenuated viral production, suggesting that CRL4-mediated ubiquitination of PB2 contributes to IAV infection. We identified K29-linked ubiquitin chains as main components of the nonproteolytic PB2 ubiquitination mediated by the CRL4s, providing the first example of the role of this atypical ubiquitin linkage in the regulation of a viral infection.

IMPORTANCE Successful infection by influenza A virus, a pathogen of major public health importance, involves fine regulation of the multiple functions of the viral proteins, which often relies on post-translational modifications (PTMs). The PB2 protein of influenza A viruses is essential for viral replication and a key determinant of host range. While PTMs of PB2 inducing its degradation have been identified, here we show that PB2 undergoes a regulating PTM signaling detected during infection, based on an atypical K29-linked ubiquitination and mediated by two multicomponent E3 ubiquitin ligases. Recombinant viruses impaired for CRL4-mediated ubiquitination are attenuated, indicating that ubiquitination of PB2 is necessary for an optimal influenza A virus infection. The CRL4 E3 ligases are required for normal viral cycle progression and for maximal virion production. Consequently, they represent potential candidate host factors for antiviral targets.




2

The Cellular Response to Lanthanum Is Substrate Specific and Reveals a Novel Route for Glycerol Metabolism in Pseudomonas putida KT2440

ABSTRACT

Ever since the discovery of the first rare earth element (REE)-dependent enzyme, the physiological role of lanthanides has become an emerging field of research due to the environmental implications and biotechnological opportunities. In Pseudomonas putida KT2440, the two pyrroloquinoline quinone-dependent alcohol dehydrogenases (PQQ-ADHs) PedE and PedH are inversely regulated in response to REE availability. This transcriptional switch is orchestrated by a complex regulatory network that includes the PedR2/PedS2 two-component system and is important for efficient growth on several alcoholic volatiles. To study whether cellular responses beyond the REE switch exist, the differential proteomic responses that occur during growth on various model carbon sources were analyzed. Apart from the Ca2+-dependent enzyme PedE, the differential abundances of most identified proteins were conditional. During growth on glycerol—and concomitant with the proteomic changes—lanthanum (La3+) availability affected different growth parameters, including the onset of logarithmic growth and final optical densities. Studies with mutant strains revealed a novel metabolic route for glycerol utilization, initiated by PedE and/or PedH activity. Upon oxidation to glycerate via glyceraldehyde, phosphorylation by the glycerate kinase GarK most likely yields glycerate-2-phosphate, which is eventually channeled into the central metabolism of the cell. This new route functions in parallel with the main degradation pathway encoded by the glpFKRD operon and provides a growth advantage to the cells by allowing an earlier onset of growth with glycerol as the sole source of carbon and energy.

IMPORTANCE The biological role of REEs has long been underestimated, and research has mainly focused on methanotrophic and methylotrophic bacteria. We have recently demonstrated that P. putida, a plant growth-promoting bacterium that thrives in the rhizosphere of various food crops, possesses a REE-dependent alcohol dehydrogenase (PedH), but knowledge about REE-specific effects on physiological traits in nonmethylotrophic bacteria is still scarce. This study demonstrates that the cellular response of P. putida to lanthanum (La3+) is mostly substrate specific and that La3+ availability highly affects the growth of cells on glycerol. Further, a novel route for glycerol metabolism is identified, which is initiated by PedE and/or PedH activity and provides a growth advantage to this biotechnologically relevant organism by allowing a faster onset of growth. Overall, these findings demonstrate that lanthanides can affect physiological traits in nonmethylotrophic bacteria and might influence their competitiveness in various environmental niches.




2

NPHW 2020 work moves online

Health advocates across the country used National Public Health Week in April to highlight the important role of public health, which became even more crucial in the wake of the COVID-19 outbreak.