eco

Secondhand Smoke Blocks Artery Repair

Title: Secondhand Smoke Blocks Artery Repair
Category: Health News
Created: 4/30/2008 2:00:00 AM
Last Editorial Review: 4/30/2008 12:00:00 AM




eco

Record Number of Americans Got Flu Shots, CDC Says

Title: Record Number of Americans Got Flu Shots, CDC Says
Category: Health News
Created: 4/29/2010 4:10:00 PM
Last Editorial Review: 4/30/2010 12:00:00 AM




eco

Secondhand Smoke Permeates Many Apartment Buildings: Study

Title: Secondhand Smoke Permeates Many Apartment Buildings: Study
Category: Health News
Created: 4/29/2012 10:05:00 AM
Last Editorial Review: 4/30/2012 12:00:00 AM




eco

Study Recommends Putting Your Left Face Forward

Title: Study Recommends Putting Your Left Face Forward
Category: Health News
Created: 4/27/2012 6:06:00 PM
Last Editorial Review: 4/30/2012 12:00:00 AM




eco

Many Asthmatic Kids Harmed by Secondhand Smoke: Study

Title: Many Asthmatic Kids Harmed by Secondhand Smoke: Study
Category: Health News
Created: 5/1/2012 10:05:00 AM
Last Editorial Review: 5/1/2012 12:00:00 AM




eco

Health Tip: Recognize Early Signs of Autism

Title: Health Tip: Recognize Early Signs of Autism
Category: Health News
Created: 5/3/2012 8:05:00 AM
Last Editorial Review: 5/3/2012 12:00:00 AM




eco

Second Man Arrested in Tainted Letter Case, Officials Report

Title: Second Man Arrested in Tainted Letter Case, Officials Report
Category: Health News
Created: 4/27/2013 6:35:00 PM
Last Editorial Review: 4/29/2013 12:00:00 AM




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Antidepressants May Hasten Bypass Recovery, Study Finds

Title: Antidepressants May Hasten Bypass Recovery, Study Finds
Category: Health News
Created: 5/1/2013 10:35:00 AM
Last Editorial Review: 5/1/2013 12:00:00 AM




eco

Secondhand Smoke Tied to Lower 'Good' Cholesterol in Teen Girls

Title: Secondhand Smoke Tied to Lower 'Good' Cholesterol in Teen Girls
Category: Health News
Created: 4/30/2013 2:35:00 PM
Last Editorial Review: 5/1/2013 12:00:00 AM




eco

Radiation May Equal Surgery, With Easier Recovery, for Cancerous Lymph Nodes

Title: Radiation May Equal Surgery, With Easier Recovery, for Cancerous Lymph Nodes
Category: Health News
Created: 4/30/2014 2:36:00 PM
Last Editorial Review: 5/1/2014 12:00:00 AM




eco

Alzheimer's Variation May Often Go Unrecognized: Study

Title: Alzheimer's Variation May Often Go Unrecognized: Study
Category: Health News
Created: 5/2/2014 9:35:00 AM
Last Editorial Review: 5/2/2014 12:00:00 AM




eco

Women's Brains May Have Tougher Time Recovering From Concussion

Title: Women's Brains May Have Tougher Time Recovering From Concussion
Category: Health News
Created: 4/28/2015 12:00:00 AM
Last Editorial Review: 4/28/2015 12:00:00 AM




eco

U.S. Lowers Recommended Fluoride Levels in Drinking Water

Title: U.S. Lowers Recommended Fluoride Levels in Drinking Water
Category: Health News
Created: 4/27/2015 12:00:00 AM
Last Editorial Review: 4/28/2015 12:00:00 AM




eco

Drop in Drunk Driving Crashes May Have Boosted U.S. Economy

Title: Drop in Drunk Driving Crashes May Have Boosted U.S. Economy
Category: Health News
Created: 4/30/2015 12:00:00 AM
Last Editorial Review: 4/30/2015 12:00:00 AM




eco

Breast Reconstruction Often Involves Multiple Operations

Title: Breast Reconstruction Often Involves Multiple Operations
Category: Health News
Created: 4/30/2015 12:00:00 AM
Last Editorial Review: 5/1/2015 12:00:00 AM




eco

Teen Birth Rate at Record Low in U.S.

Title: Teen Birth Rate at Record Low in U.S.
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/29/2016 12:00:00 AM




eco

Health Tip: Recognizing Lung Disease

Title: Health Tip: Recognizing Lung Disease
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM




eco

AHA News: A Stroke Slowed Olympic Legend Michael Johnson, But F.A.S.T. Response Sped His Recovery

Title: AHA News: A Stroke Slowed Olympic Legend Michael Johnson, But F.A.S.T. Response Sped His Recovery
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM




eco

Health Tip: What to Expect From a Gynecologist Visit

Title: Health Tip: What to Expect From a Gynecologist Visit
Category: Health News
Created: 5/3/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM




eco

He Recovered From COVID-19. Can His Blood Help Others?

Title: He Recovered From COVID-19. Can His Blood Help Others?
Category: Health News
Created: 4/27/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM




eco

Do C-Section Babies Become Heavier Adults?

Title: Do C-Section Babies Become Heavier Adults?
Category: Health News
Created: 4/14/2020 12:00:00 AM
Last Editorial Review: 4/15/2020 12:00:00 AM




eco

Necklace Spots A-Fib in Just Over 30 Seconds

Title: Necklace Spots A-Fib in Just Over 30 Seconds
Category: Health News
Created: 5/6/2020 12:00:00 AM
Last Editorial Review: 5/7/2020 12:00:00 AM




eco

Necklace Spots A-Fib in Just Over 30 Seconds

A necklace outfitted with a high-tech pendant may be able to screen for signs of an abnormal heart rhythm condition known as atrial fibrillation.




eco

JATS Becomes NISO Standard

The Journal Archiving Tag Suite(JATS), known formerly as the NLM DTD, has now been officially adopted as an American National Standards Institute (ANSI)/ National Information Standards Organization (NISO) standard. According to the press release from NISO, "JATS provides a common XML format in which publishers and archives can exchange journal content by preserving the intellectual content of journals independent of the form in which that content was originally delivered." For more information, see NISO Publishes Journal Article Tag Suite (JATS) Standard.




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Webinar Recording "An Updated PubMed is on its Way!"

"NCBI Minute: An Updated PubMed is on its Way!" recorded on August 14th, 2019, is now available on the NCBI YouTube channel.




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Webinar Recording "A New PubMed: Highlights for Information Professionals"

In this webinar for librarians and other information professionals you will preview the new, modern PubMed. The new PubMed, currently available at https://pubmed.gov/labs for testing, will be the default PubMed system in early 2020.







eco

What Is the Recovery Time for An Umbilical Hernia Surgery?

Title: What Is the Recovery Time for An Umbilical Hernia Surgery?
Category: Procedures and Tests
Created: 4/15/2020 12:00:00 AM
Last Editorial Review: 4/15/2020 12:00:00 AM




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How Long Does It Take to Recover from Laparoscopic Inguinal Hernia Surgery?

Title: How Long Does It Take to Recover from Laparoscopic Inguinal Hernia Surgery?
Category: Procedures and Tests
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM




eco

Blood Sugar Control May Aid Stroke Recovery in Diabetes Patients

Title: Blood Sugar Control May Aid Stroke Recovery in Diabetes Patients
Category: Health News
Created: 3/30/2020 12:00:00 AM
Last Editorial Review: 3/31/2020 12:00:00 AM




eco

Gynecomastia (Enlarged Male Breasts)

Title: Gynecomastia (Enlarged Male Breasts)
Category: Diseases and Conditions
Created: 10/7/2009 12:00:00 AM
Last Editorial Review: 11/14/2019 12:00:00 AM




eco

Second HIV Patient Reportedly 'Cured'

Title: Second HIV Patient Reportedly 'Cured'
Category: Health News
Created: 3/9/2020 12:00:00 AM
Last Editorial Review: 3/10/2020 12:00:00 AM




eco

Vitamin D Might Aid Seniors' Recovery From Hip Fracture: Study

Title: Vitamin D Might Aid Seniors' Recovery From Hip Fracture: Study
Category: Health News
Created: 4/2/2020 12:00:00 AM
Last Editorial Review: 4/3/2020 12:00:00 AM




eco

Recommended Diuretic Drug Tied to Harmful Side Effects

Title: Recommended Diuretic Drug Tied to Harmful Side Effects
Category: Health News
Created: 2/18/2020 12:00:00 AM
Last Editorial Review: 2/19/2020 12:00:00 AM




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Two previously unrecorded xiphosurid trace fossils, Selenichnites rossendalensis and Crescentichnus tesiltus, from the Middle Jurassic of Yorkshire, UK

The invertebrate trace fossils Selenichnites rossendalensis and Crescentichnus tesiltus are recorded and described from the Middle Jurassic Gristhorpe Member of the Cloughton Formation of the Cleveland Basin. This is the first record of these ichnospecies from the basin and now completes the occurrence of these and other traces assumed to have been made by limulids from all three non-marine formations of the Ravenscar Group.




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Species-Specific Recognition of Sulfolobales Mediated by UV-Inducible Pili and S-Layer Glycosylation Patterns

ABSTRACT

The UV-inducible pili system of Sulfolobales (Ups) mediates the formation of species-specific cellular aggregates. Within these aggregates, cells exchange DNA to repair DNA double-strand breaks via homologous recombination. Substitution of the Sulfolobus acidocaldarius pilin subunits UpsA and UpsB with their homologs from Sulfolobus tokodaii showed that these subunits facilitate species-specific aggregation. A region of low conservation within the UpsA homologs is primarily important for this specificity. Aggregation assays in the presence of different sugars showed the importance of N-glycosylation in the recognition process. In addition, the N-glycan decorating the S-layer of S. tokodaii is different from the one of S. acidocaldarius. Therefore, each Sulfolobus species seems to have developed a unique UpsA binding pocket and unique N-glycan composition to ensure aggregation and, consequently, also DNA exchange with cells from only the same species, which is essential for DNA repair by homologous recombination.

IMPORTANCE Type IV pili can be found on the cell surface of many archaea and bacteria where they play important roles in different processes. The UV-inducible pili system of Sulfolobales (Ups) pili from the crenarchaeal Sulfolobales species are essential in establishing species-specific mating partners, thereby assisting in genome stability. With this work, we show that different Sulfolobus species have specific regions in their Ups pili subunits, which allow them to interact only with cells from the same species. Additionally, different Sulfolobus species have unique surface-layer N-glycosylation patterns. We propose that the unique features of each species allow the recognition of specific mating partners. This knowledge for the first time gives insights into the molecular basis of archaeal self-recognition.




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Epstein-Barr Virus Epitope-Major Histocompatibility Complex Interaction Combined with Convergent Recombination Drives Selection of Diverse T Cell Receptor {alpha} and {beta} Repertoires

ABSTRACT

Recognition modes of individual T cell receptors (TCRs) are well studied, but factors driving the selection of TCR repertoires from primary through persistent human virus infections are less well understood. Using deep sequencing, we demonstrate a high degree of diversity of Epstein-Barr virus (EBV)-specific clonotypes in acute infectious mononucleosis (AIM). Only 9% of unique clonotypes detected in AIM persisted into convalescence; the majority (91%) of unique clonotypes detected in AIM were not detected in convalescence and were seeming replaced by equally diverse "de novo" clonotypes. The persistent clonotypes had a greater probability of being generated than nonpersistent clonotypes due to convergence recombination of multiple nucleotide sequences to encode the same amino acid sequence, as well as the use of shorter complementarity-determining regions 3 (CDR3s) with fewer nucleotide additions (i.e., sequences closer to germ line). Moreover, the two most immunodominant HLA-A2-restricted EBV epitopes, BRLF1109 and BMLF1280, show highly distinct antigen-specific public (i.e., shared between individuals) features. In fact, TCRα CDR3 motifs played a dominant role, while TCRβ played a minimal role, in the selection of TCR repertoire to an immunodominant EBV epitope, BRLF1. This contrasts with the majority of previously reported repertoires, which appear to be selected either on TCRβ CDR3 interactions with peptide/major histocompatibility complex (MHC) or in combination with TCRα CDR3. Understanding of how TCR-peptide-MHC complex interactions drive repertoire selection can be used to develop optimal strategies for vaccine design or generation of appropriate adoptive immunotherapies for viral infections in transplant settings or for cancer.

IMPORTANCE Several lines of evidence suggest that TCRα and TCRβ repertoires play a role in disease outcomes and treatment strategies during viral infections in transplant patients and in cancer and autoimmune disease therapy. Our data suggest that it is essential that we understand the basic principles of how to drive optimum repertoires for both TCR chains, α and β. We address this important issue by characterizing the CD8 TCR repertoire to a common persistent human viral infection (EBV), which is controlled by appropriate CD8 T cell responses. The ultimate goal would be to determine if the individuals who are infected asymptomatically develop a different TCR repertoire than those that develop the immunopathology of AIM. Here, we begin by doing an in-depth characterization of both CD8 T cell TCRα and TCRβ repertoires to two immunodominant EBV epitopes over the course of AIM, identifying potential factors that may be driving their selection.




eco

Metabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in Escherichia coli

ABSTRACT

Microbes adapt their metabolism to take advantage of nutrients in their environment. Such adaptations control specific metabolic pathways to match energetic demands with nutrient availability. Upon depletion of nutrients, rapid pathway recovery is key to release cellular resources required for survival under the new nutritional conditions. Yet, little is known about the regulatory strategies that microbes employ to accelerate pathway recovery in response to nutrient depletion. Using the fatty acid catabolic pathway in Escherichia coli, here, we show that fast recovery can be achieved by rapid release of a transcriptional regulator from a metabolite-sequestered complex. With a combination of mathematical modeling and experiments, we show that recovery dynamics depend critically on the rate of metabolite consumption and the exposure time to nutrients. We constructed strains with rewired transcriptional regulatory architectures that highlight the metabolic benefits of negative autoregulation over constitutive and positive autoregulation. Our results have wide-ranging implications for our understanding of metabolic adaptations, as well as for guiding the design of gene circuitry for synthetic biology and metabolic engineering.

IMPORTANCE Rapid metabolic recovery during nutrient shift is critical to microbial survival, cell fitness, and competition among microbiota, yet little is known about the regulatory mechanisms of rapid metabolic recovery. This work demonstrates a previously unknown mechanism where rapid release of a transcriptional regulator from a metabolite-sequestered complex enables fast recovery to nutrient depletion. The work identified key regulatory architectures and parameters that control the speed of recovery, with wide-ranging implications for the understanding of metabolic adaptations as well as synthetic biology and metabolic engineering.




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Nucleic Acid-Sensing Toll-Like Receptors Play a Dominant Role in Innate Immune Recognition of Pneumococci

ABSTRACT

Streptococcus pneumoniae (or pneumococcus) is a highly prevalent human pathogen. Toll-like receptors (TLRs) function as immune sensors that can trigger host defenses against this bacterium. Defects in TLR-activated signaling pathways, including deficiency in the adaptor protein myeloid differentiation factor 88 (MyD88), are associated with markedly increased susceptibility to infection. However, the individual MyD88-dependent TLRs predominantly involved in antipneumococcal defenses have not been identified yet. Here we find that triple knockout mice simultaneously lacking TLR7, TLR9, and TLR13, which sense the presence of bacterial DNA (TLR9) and RNA (TLR7 and TLR13) in the phagolysosomes of phagocytic cells, display a phenotype that largely resembles that of MyD88-deficient mice and rapidly succumb to pneumococcal pneumonitis due to defective neutrophil influx into the lung. Accordingly, TLR7/9/13 triple knockout resident alveolar macrophages were largely unable to respond to pneumococci with the production of neutrophil-attracting chemokines and cytokines. Mice with single deficiencies of TLR7, TLR9, or TLR13 showed unaltered ability to control lung infection but were moderately more susceptible to encephalitis, in association with a decreased ability of microglia to mount cytokine responses in vitro. Our data point to a dominant, tissue-specific role of nucleic acid-sensing pathways in innate immune recognition of S. pneumoniae and also show that endosomal TLRs are largely capable of compensating for the absence of each other, which seems crucial to prevent pneumococci from escaping immune recognition. These results may be useful to develop novel strategies to treat infections by antibiotic-resistant pneumococci based on stimulation of the innate immune system.

IMPORTANCE The pneumococcus is a bacterium that frequently causes infections in the lungs, ears, sinus cavities, and meninges. During these infections, body defenses are triggered by tissue-resident cells that use specialized receptors, such as Toll-like receptors (TLRs), to sense the presence of bacteria. We show here that pneumococci are predominantly detected by TLRs that are located inside intracellular vacuoles, including endosomes, where these receptors can sense the presence of nucleic acids released from ingested bacteria. Mice that simultaneously lacked three of these receptors (specifically, TLR7, TLR9, and TLR13) were extremely susceptible to lung infection and rapidly died after inhalation of pneumococci. Moreover, tissue-resident macrophages from these mice were impaired in their ability to respond to the presence of pneumococci by producing inflammatory mediators capable of recruiting polymorphonuclear leucocytes to infection sites. This information may be useful to develop drugs to treat pneumococcal infections, particularly those caused by antibiotic-resistant strains.




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Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.

IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.




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Complete Structure of the Enterococcal Polysaccharide Antigen (EPA) of Vancomycin-Resistant Enterococcus faecalis V583 Reveals that EPA Decorations Are Teichoic Acids Covalently Linked to a Rhamnopolysaccharide Backbone

ABSTRACT

All enterococci produce a complex polysaccharide called the enterococcal polysaccharide antigen (EPA). This polymer is required for normal cell growth and division and for resistance to cephalosporins and plays a critical role in host-pathogen interaction. The EPA contributes to host colonization and is essential for virulence, conferring resistance to phagocytosis during the infection. Recent studies revealed that the "decorations" of the EPA polymer, encoded by genetic loci that are variable between isolates, underpin the biological activity of this surface polysaccharide. In this work, we investigated the structure of the EPA polymer produced by the high-risk enterococcal clonal complex Enterococcus faecalis V583. We analyzed purified EPA from the wild-type strain and a mutant lacking decorations and elucidated the structure of the EPA backbone and decorations. We showed that the rhamnan backbone of EPA is composed of a hexasaccharide repeat unit of C2- and C3-linked rhamnan chains, partially substituted in the C3 position by α-glucose (α-Glc) and in the C2 position by β-N-acetylglucosamine (β-GlcNAc). The so-called "EPA decorations" consist of phosphopolysaccharide chains corresponding to teichoic acids covalently bound to the rhamnan backbone. The elucidation of the complete EPA structure allowed us to propose a biosynthetic pathway, a first essential step toward the design of antimicrobials targeting the synthesis of this virulence factor.

IMPORTANCE Enterococci are opportunistic pathogens responsible for hospital- and community-acquired infections. All enterococci produce a surface polysaccharide called EPA (enterococcal polysaccharide antigen) required for biofilm formation, antibiotic resistance, and pathogenesis. Despite the critical role of EPA in cell growth and division and as a major virulence factor, no information is available on its structure. Here, we report the complete structure of the EPA polymer produced by the model strain E. faecalis V583. We describe the structure of the EPA backbone, made of a rhamnan hexasaccharide substituted by Glc and GlcNAc residues, and show that teichoic acids are covalently bound to this rhamnan chain, forming the so-called "EPA decorations" essential for host colonization and pathogenesis. This report represents a key step in efforts to identify the structural properties of EPA that are essential for its biological activity and to identify novel targets to develop preventive and therapeutic approaches against enterococci.




eco

Rupture geometries in anisotropic amphibolite recorded by pseudotachylytes in the Gairloch Shear Zone, NW Scotland

Recent earthquakes involving complex multi-fault rupture have increased our appreciation of the variety of rupture geometries and fault interactions that occur within the short duration of coseismic slip. Geometrical complexities are intrinsically linked with spatially heterogeneous slip and stress drop distributions, and hence need incorporating into seismic hazard analysis. Studies of exhumed ancient fault zones facilitate investigation of rupture processes in the context of lithology and structure at seismogenic depths. In the Gairloch Shear Zone, NW Scotland, foliated amphibolites host pseudotachylytes that record rupture geometries of ancient low-magnitude (≤MW 3) seismicity. Pseudotachylyte faults are commonly foliation parallel, indicating exploitation of foliation planes as weak interfaces for seismic rupture. Discordance and complexity are introduced by fault segmentation, stepovers, branching and brecciated dilational volumes. Pseudotachylyte geometries indicate that slip nucleation initiated simultaneously across several parallel foliation planes with millimetre and centimetre separations, leading to progressive interaction and ultimately linkage of adjacent segments and branches within a single earthquake. Interacting with this structural control, a lithological influence of abundant low disequilibrium melting-point amphibole facilitated coseismic melting, with relatively high coseismic melt pressure encouraging transient dilational sites. These faults elucidate controls and processes that may upscale to large active fault zones hosting major earthquake activity.

Supplementary material: Supplementary Figures 1 and 2, unannotated versions of field photographs displayed in Figures 4a and 5 respectively, are available at https://doi.org/10.6084/m9.figshare.c.4573256

Thematic collection: This article is part of the SJG Collection on Early-Career Research available at: https://www.lyellcollection.org/cc/SJG-early-career-research




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EPSIN1 Contributes to Plant Immunity by Modulating the Abundance of Pattern Recognition Receptors at the Plasma Membrane




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Towards Innovative Design and Application of Recombinant Eimeria as a Vaccine Vector [Minireviews]

Efficient delivery of antigenic cargo to trigger protective immune responses is critical to the success of vaccination. Genetically engineered microorganisms, including virus, bacteria, and protozoa, can be modified to carry and deliver heterologous antigens to the host immune system. The biological vectors can induce a broad range of immune responses and enhance heterologous antigen-specific immunological outcomes. The protozoan genus Eimeria is widespread in domestic animals, causing serious coccidiosis. Eimeria parasites with strong immunogenicity are potent coccidiosis vaccine candidates and offer a valuable model of live vaccines against infectious diseases in animals. Eimeria parasites can also function as a vaccine vector. Herein, we review recent advances in design and application of recombinant Eimeria as a vaccine vector, which has been a topic of ongoing research in our laboratory. By recapitulating the establishment of an Eimeria transfection platform and its application, it will help lay the foundation for the future development of effective parasite-based vaccine delivery vectors and beyond.




eco

HIV-1-Specific Chimeric Antigen Receptor T Cells Fail To Recognize and Eliminate the Follicular Dendritic Cell HIV Reservoir In Vitro [Vaccines and Antiviral Agents]

The major obstacle to a cure for HIV infection is the persistence of replication-competent viral reservoirs during antiretroviral therapy. HIV-specific chimeric antigen receptor (CAR) T cells have been developed to target latently infected CD4+ T cells that express virus either spontaneously or after intentional latency reversal. Whether HIV-specific CAR-T cells can recognize and eliminate the follicular dendritic cell (FDC) reservoir of HIV-bound immune complexes (ICs) is unknown. We created HIV-specific CAR-T cells using human peripheral blood mononuclear cells (PBMCs) and a CAR construct that enables the expression of CD4 (domains 1 and 2) and the carbohydrate recognition domain of mannose binding lectin (MBL) to target native HIV Env (CD4-MBL CAR). We assessed CAR-T cell cytotoxicity using a carboxyfluorescein succinimidyl ester (CFSE) release assay and evaluated CAR-T cell activation through interferon gamma (IFN-) production and CD107a membrane accumulation by flow cytometry. CD4-MBL CAR-T cells displayed potent lytic and functional responses to Env-expressing cell lines and HIV-infected CD4+ T cells but were ineffective at targeting FDC bearing HIV-ICs. CD4-MBL CAR-T cells were unresponsive to cell-free HIV or concentrated, immobilized HIV-ICs in cell-free experiments. Blocking intercellular adhesion molecule-1 (ICAM-1) inhibited the cytolytic response of CD4-MBL CAR-T cells to Env-expressing cell lines and HIV-infected CD4+ T cells, suggesting that factors such as adhesion molecules are necessary for the stabilization of the CAR-Env interaction to elicit a cytotoxic response. Thus, CD4-MBL CAR-T cells are unable to eliminate the FDC-associated HIV reservoir, and alternative strategies to eradicate this reservoir must be sought.

IMPORTANCE Efforts to cure HIV infection have focused primarily on the elimination of latently infected CD4+ T cells. Few studies have addressed the unique reservoir of infectious HIV that exists on follicular dendritic cells (FDCs), persists in vivo during antiretroviral therapy, and likely contributes to viral rebound upon cessation of antiretroviral therapy. We assessed the efficacy of a novel HIV-specific chimeric antigen receptor (CAR) T cell to target both HIV-infected CD4+ T cells and the FDC reservoir in vitro. Although CAR-T cells eliminated CD4+ T cells that express HIV, they did not respond to or eliminate FDC bound to HIV. These findings reveal a fundamental limitation to CAR-T cell therapy to eradicate HIV.




eco

Extent of Fermi-surface reconstruction in the high-temperature superconductor HgBa2CuO4+{delta} [Physics]

High magnetic fields have revealed a surprisingly small Fermi surface in underdoped cuprates, possibly resulting from Fermi-surface reconstruction due to an order parameter that breaks translational symmetry of the crystal lattice. A crucial issue concerns the doping extent of such a state and its relationship to the principal pseudogap and...




eco

A viral toolkit for recording transcription factor-DNA interactions in live mouse tissues [Neuroscience]

Transcription factors (TFs) enact precise regulation of gene expression through site-specific, genome-wide binding. Common methods for TF-occupancy profiling, such as chromatin immunoprecipitation, are limited by requirement of TF-specific antibodies and provide only end-point snapshots of TF binding. Alternatively, TF-tagging techniques, in which a TF is fused to a DNA-modifying enzyme...




eco

Reconciling global priorities for conserving biodiversity habitat [Ecology]

Degradation and loss of natural habitat is the major driver of the current global biodiversity crisis. Most habitat conservation efforts to date have targeted small areas of highly threatened habitat, but emerging debate suggests that retaining large intact natural systems may be just as important. We reconcile these perspectives by...




eco

Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody [Biochemistry]

Recent epidemics demonstrate the global threat of Zika virus (ZIKV), a flavivirus transmitted by mosquitoes. Although infection is usually asymptomatic or mild, newborns of infected mothers can display severe symptoms, including neurodevelopmental abnormalities and microcephaly. Given the large-scale spread, symptom severity, and lack of treatment or prophylaxis, a safe and...




eco

The effect of ecological factors on eye morphology in the western rainbowfish, Melanotaenia australis [RESEARCH ARTICLE]

Thomas J. Lisney, Shaun P. Collin, and Jennifer L. Kelley

Ecological factors such as spatial habitat complexity and diet can explain variation in visual morphology, but few studies have sought to determine whether visual specialisation can occur among populations of the same species. We used a small Australian freshwater fish (the western rainbowfish, Melanotaenia australis) to determine whether populations showed variation in eye size and eye position, and whether this variation could be explained by environmental (light availability, turbidity) and ecological (predation risk, habitat complexity, invertebrate abundance) variables. We investigated three aspects of eye morphology, (1) eye size relative to body size, (2) pupil size relative to eye size, and (3) eye position in the head, for fish collected from 14 sites in a major river catchment in northwest Western Australia. We found significant variation among populations in all three measures of eye morphology, but no effect of sex on eye size or eye position. Variation in eye diameter and eye position was best explained by the level of habitat complexity. Specifically, fish occurring in habitats with low complexity (i.e. open water) tended to have smaller, more dorsally-located eyes, than those occurring in more complex habitats (i.e. vegetation present). The size of the pupil relative to the size of the eye was most influenced by the presence of surrounding rock formations; fish living in gorge habitats had significantly smaller pupils (relative to eye size) than those occupying semi-gorge sites or open habitats. Our findings reveal that different ecological and environmental factors contribute to habitat-specific visual specialisations within a species.




eco

Secondary osteon structural heterogeneity between the cranial and caudal cortices of the proximal humerus in white-tailed deer [RESEARCH ARTICLE]

Jack Nguyen and Meir M. Barak

Cortical bone remodeling is an ongoing process triggered by microdamage, where osteoclasts resorb existing bone and osteoblasts deposit new bone in the form of secondary osteons (Haversian systems). Previous studies revealed regional variance in Haversian systems structure and possibly material, between opposite cortices of the same bone. As bone mechanical properties depend on tissue structure and material, it is predicted that bone mechanical properties will vary in accordance with structural and material regional heterogeneity. To test this hypothesis, we analyzed the structure, mineral content and compressive stiffness of secondary bone from the cranial and caudal cortices of the white-tailed deer proximal humerus. We found significantly larger Haversian systems and canals in the cranial cortex but no significant difference in mineral content between the two cortices. Accordingly, we found no difference in compressive stiffness between the two cortices and thus our working hypothesis was rejected. Seeing that the deer humerus is curved and thus likely subjected to bending during habitual locomotion, we expect that similar to other curved long bones, the cranial cortex of the deer humerus is likely subjected primarily to tensile strains and the caudal cortex is likely subject primarily to compressive strains. Consequently, our results suggest that strain magnitude (larger in compression) and sign (compression vs. tension) affect differently the osteoclasts and osteoblasts in the BMU. Our results further suggest that osteoclasts are inhibited in regions of high compressive strains (creating smaller Haversian systems) while osteoblasts’ osteoid deposition and mineralization is not affected by strain magnitude and sign.