Development and characterization of a reverse genetics system for the lineage II Chicava strain of Machupo virus in a guinea pig model.

Background: Machupo virus (MACV) is a New World mammarenavirus (hereafter referred to as "arenavirus") and the etiologic agent of Bolivian hemorrhagic fever (BHF). No vaccine or antiviral therapy exists for BHF, which causes up to 35% mortality in humans. New World arenaviruses evolve separately in different locations.

Massively parallel barcode sequencing revealed the interchangeability of capsule transporters in .

Multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) family transporters are essential in glycan synthesis, flipping lipid-linked precursors across cell membranes. Yet, how they select their substrates remains enigmatic. Here, we investigate the substrate specificity of the MOP transporters in the capsular polysaccharide (CPS) synthesis pathway in .

Macromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.

The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.

Optimized genetic tools for neuroanatomical and functional mapping of the Aedes aegypti olfactory system.

The mosquito Aedes aegypti is an emerging model insect for invertebrate neurobiology. We detail the application of a dual transgenesis marker system that reports the nature of transgene integration with circular donor template for CRISPR-Cas9-mediated homology-directed repair at target mosquito chemoreceptor genes. Employing this approach, we demonstrate the establishment of cell-type-specific T2A-QF2 driver lines for the A.

Elegant and Innovative Recoding Strategies for Advancing Vaccine Development.

Recoding strategies have emerged as a promising approach for developing safer and more effective vaccines by altering the genetic structure of microorganisms, such as viruses, without changing their proteins. This method enhances vaccine safety and efficacy while minimizing the risk of reversion to virulence. Recoding enhances the frequency of CpG dinucleotides, which in turn activates immune responses and ensures a strong attenuation of the pathogens.

Peptide Antigen Modifications Influence the On-Target and Off-Target Antibody Response for an Influenza Subunit Vaccine.

Background/objectives: Peptide amphiphile micelles (PAMs) are an exciting nanotechnology currently being studied for a variety of biomedical applications, especially for drug delivery. Specifically, PAMs can enhance in vivo trafficking, cell-targeting, and cell interactions/internalization. However, modifying peptides, as is commonly performed to induce micellization, can influence their bioactivity.

Safety, Tolerability, and Immunogenicity of the Invaplex Vaccine Co-Administered with the dmLT Adjuvant in Dutch and Zambian Adults: Study Protocol for a Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase Ia/b Clinical Trial.

Background: Shigella infections remain endemic in places with poor sanitation and are a leading cause of diarrheal mortality globally, as well as a major contributor to gut enteropathy and stunting. There are currently no licensed vaccines for shigellosis but it has been estimated that an effective vaccine could avert 590,000 deaths over a 20-year period. A challenge to effective Shigella vaccine development has been the low immunogenicity and protective efficacy of candidate Shigella vaccines in infants and young children.

Role of tRNA-Derived Fragments in Protozoan Parasite Biology.

tRNA molecules are among the most fundamental and evolutionarily conserved RNA types, primarily facilitating the translation of genetic information from mRNA into proteins. Beyond their canonical role as adaptor molecules during protein synthesis, tRNAs have evolved to perform additional functions. One such non-canonical role for tRNAs is through the generation of tRNA-derived fragments via specific cleavage processes.

Targeted Inhibition of GATA-3 by Pyrrothiogatain: Implications for Adipocyte Biology and Inflammatory Response.

GATA-3 is a master regulator of preadipocyte differentiation and function. Pharmacological or genetic targeting of GATA-3 will allow us to understand the function of GATA-3 in regulating metabolism, insulin signaling, and inflammation. Pyrrothiogatain, a novel small molecule inhibitor of GATA family proteins, has emerged as a promising tool for modulating GATA-3 activity.

Regulation of interferon alpha production by the MAGUK-family protein CASK under H5N1 infection.

CASK, a MAGUK family scaffold protein, regulates gene expression as a transcription co-activator in neurons. However, the mechanism of CASK nucleus translocation and the regulatory function of CASK in myeloid cells remains unclear. Here, we investigated its role in H5N1-infected macrophages.

ESAT-6 protein suppresses allograft rejection by inducing CD4Foxp3 regulatory T cells through IκBα/cRel pathway.

Background: Maintenance immunosuppression is required for suppression of alloimmunity or allograft rejection. However, continuous use of immunosuppressants may lead to various side effects, necessitating the use of alternative immunosuppressive drugs. The early secreted antigenic target of 6 kDa (ESAT-6) is a virulence factor and immunoregulatory protein of mycobacterium tuberculosis (Mtb), which alters host immunity through dually regulating development or activation of various immune cells.

Risk Factors for Post Laryngectomy Pharyngocutaneous Fistula and Impact of Pharyngeal Suture Type on Fistula Characteristics.

Introduction: Pharyngocutaneous fistula (PCF) is the most common complication following total laryngectomy (TL). The factors contributing to its occurrence are still a matter of debate. The impact of suture type has been relatively underexplored.

Mixed lipopeptide-based mucosal vaccine candidate induces cross-variant immunity and protects against SARS-CoV-2 infection in hamsters.

The global dissemination of SARS-CoV-2 led to a worldwide pandemic in March 2020. Even after the official downgrading of the COVID-19 pandemic, infection with SARS-CoV-2 variants continues. The rapid development and deployment of SARS-CoV-2 vaccines helped to mitigate the pandemic to a great extent.

Novel relatives of Mecsek Mountains mammarenavirus (family Arenaviridae) in hedgehogs living in different sampling areas in Hungary.

Mammarenaviruses (genus Mammarenavirus, family Arenaviridae) are rodent-borne zoonotic viruses consisting of 52 viral species, including ten that are pathogenic to humans. Currently, only two endemic mammarenavirus species are known in Europe: the human pathogenic Mammarenavirus choriomeningitidis (LCMV) and the recently discovered hedgehog-origin Mammarenavirus mecsekense (MEMV). In this study, 59 faecal specimens from Northern white-breasted hedgehogs (Erinaceus roumanicus) from different geographic regions in Hungary were investigated for mammarenavirus presence and complete genome characterization using newly designed screening primers by RT-semi-nested PCR and sequencing methods.

Targeting murine metastatic cancers with cholera toxin A1-adjuvanted peptide vaccines.

The dissemination of tumor cells with ensuing metastasis is responsible for most cancer-related deaths. Cancer vaccines may, by inducing tumor-specific effector T cells, offer a strategy to eliminate metastasizing tumor cells. However, several obstacles remain in the development of effective cancer vaccines, including the identification of adjuvants that enhance the evolvement and efficacy of tumor-specific T cells.

Changes in the intestinal microbiota induced by the postnatal environment and their association with hypertension.

It has been established that cross-fostering impacts the development of hypertension in spontaneously hypertensive rats (SHR). However, the ability of the cross-fostering protocol to shape gut microbiota profile in SHR and impact hypertension is not known. In this sense, the current study explored the influence of normotensive and hypertensive postnatal environments on the intestinal microbiota structure, composition, and functional capacity of SHR and Wistar rats.

Receptor binding, structure, and tissue tropism of cattle-infecting H5N1 avian influenza virus hemagglutinin.

The ongoing circulation of highly pathogenic avian influenza (HPAI) A (H5N1) viruses, particularly clade 2.3.4.

A genome-wide association study identified PRKCB as a causal gene and therapeutic target for Mycobacterium avium complex disease.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic progressive lung disease that is increasing in incidence. Host genetic factors are associated with NTM-PD susceptibility. However, the heritability of NTM-PD is not well understood.

Ultraviolet radiation vs air filtration to mitigate virus laden aerosol in an occupied clinical room.

Mitigation measures against infectious aerosols are desperately needed. We aimed to: 1) compare germicidal ultraviolet radiation (GUV) at 254 nm (254-GUV) and 222 nm (222-GUV) with portable high efficiency particulate air (HEPA) filters to inactivate/remove airborne bacteriophage ϕX174, 2) measure the effect of air mixing on the effectiveness of 254-GUV, and 3) determine the relative susceptibility of ϕX174, SARS-CoV-2, and Influenza A(H3N2) to GUV (254 nm, 222 nm). A nebulizer generated ϕX174 laden aerosols in an occupied clinical room (sealed-low flow).

Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.

The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines.

Permanent defects in renal medullary structure and function after reversal of urinary obstruction.

Urinary obstruction causes injury to the renal medulla, impairing the ability to concentrate urine, and increasing the risk of progressive kidney disease. However, the regenerative capacity of the renal medulla after reversal of obstruction is poorly understood. To investigate this, we developed a mouse model of reversible urinary obstruction.

Surveillance for variants escaping detection with the Aptima Combo 2 assay in Canada from 2019 to 2021.

Unlabelled: Nucleic acid amplification tests (NAATs) are the method of choice for diagnosis, but these strategies are susceptible to target site mutations. variants escaping detection with the Aptima Combo 2 (AC2) assay on the Hologic Panther instrument from 23S rRNA mutations have been reported in Nordic countries, England, Japan, and the United States. Given the potential for false negative results, this study investigated whether strains of with AC2 target site mutations were present in Canada.

Antifungal susceptibility testing and determination of local epidemiological cut-off values for species isolated from women with vulvovaginal candidiasis.

The lack of clinical breakpoints and epidemiological cut-off values (ECOFFs) for antifungals prescribed for vulvovaginal candidiasis (VVC) make interpretation of antifungal susceptibility data difficult. This leads to empirical prescribing, poor clinical management and emergence of resistance. The susceptibilities of 152 , 105 , 31 and 8 VVC isolates against eight antifungals, were determined according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) E.

Dehydration-induced regulates midgut infection in mosquitoes.

Unlabelled: Climate change is predicted to increase the spread of mosquito-borne viruses, but genetic mechanisms underlying the influence of environmental variation on the ability of insect vectors to transmit human pathogens is unknown. In response to a changing climate, mosquitoes will experience longer periods of drought. An important physiological response to dry environments is the protection against dehydration, here defined as desiccation tolerance.

The interplay between ZigA and SltB promotes zinc homeostasis and cell envelope integrity.

is an opportunistic human pathogen that acquires nutrient metals from the vertebrate host amid infection. During zinc (Zn) scarcity, upregulates the expression of the predicted Zn metallochaperone, . Loss of compromises fitness during Zn deficiency, highlighting its role in this condition.