Autoantibodies in COVID-19: implications for disease severity and clinical outcomes.

Few pathogens have historically been subjected to as intense scientific and clinical scrutiny as SARS-CoV-2. The genetic, immunological, and environmental factors influencing disease severity and post-infection clinical outcomes, known as correlates of immunity, remain largely undefined. Clinical outcomes of SARS-CoV-2 infection vary widely, ranging from asymptomatic cases to those with life-threatening COVID-19 symptoms.

Uncovering cryptic species diversity of () associated with from Thailand.

This study advances our understanding of , an extensively studied entomopathogenic fungus within the , particularly in Thailand. We introduce seven novel species associated with - , , , , , , and . Remarkably, , , and exhibit ascomata on the subterminal region of the stromata, with the asexual form appearing at the apex of the stipe, reminiscent of .

Fungal Planet description sheets: 1697-1780.

Novel species of fungi described in this study include those from various countries as follows: , from accumulated snow sediment sample. , on leaf spots of . , on submerged decaying wood in sea water, on , as endophyte from healthy leaves of .

Bacterial and viral assemblages in ulcerative colitis patients following fecal microbiota and fecal filtrate transfer.

Fecal microbiota filtrate transfer is discussed as a safe alternative to fecal microbiota transfer (FMT) to treat ulcerative colitis. We investigated modulation of viral and bacterial composition during fecal microbiota filtrate transfer followed by FMT in six patients with active ulcerative colitis (where clinical activity improved in three patients after filtrate transfer) and combined 16S ribosomal RNA gene amplicon sequencing with a virome analysis pipeline including fast viral particle enrichment and metagenome mapping to detect frequencies of 45,033 reference bacteriophage genomes. We showed that after antibiotic treatment and during filtrate transfer, the bacterial community typically adopted a stable composition distinct to that before antibiotic treatment, with no change toward a donor community.

Computational frameworks transform antagonism to synergy in optimizing combination therapies.

While drug combinations are increasingly important in disease treatment, predicting their therapeutic interactions remains challenging. This review systematically analyzes computational methods for predicting drug combination effects through multi-omics data integration. We comprehensively assess key algorithms including DrugComboRanker and AuDNNsynergy, and evaluate integration approaches encompassing kernel regression and graph networks.

Reverse mutational scanning of SARS-CoV-2 spike BA.2.86 identifies epitopes contributing to immune escape from polyclonal sera.

The recently detected Omicron BA.2.86 lineage contains more than 30 amino acid mutations relative to BA.

Passage of the HIV capsid cracks the nuclear pore.

Upon infection, human immunodeficiency virus type 1 (HIV-1) releases its cone-shaped capsid into the cytoplasm of infected T cells and macrophages. The capsid enters the nuclear pore complex (NPC), driven by interactions with numerous phenylalanine-glycine (FG)-repeat nucleoporins (FG-Nups). Whether NPCs structurally adapt to capsid passage and whether capsids are modified during passage remains unknown, however.

Regulatory workshop on standardisation of clinical procedures, endpoints and data robustness of human challenge studies - A stakeholder meeting report.

Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), brings together academic institutions, SMEs, and pharmaceutical companies to accelerate and de-risk vaccine development. The project has made significant strides in the selection and production of challenge agents for influenza, respiratory syncytial virus (RSV), and toxigenic Clostridioides difficile for controlled human infection model studies (CHIMs). A regulatory workshop held on March 20, 2024, addressed the standardisation of clinical procedures, ethical considerations, endpoints, and data integrity, highlighting the ongoing initiatives related to these CHIMs.

Nutritional and Sensory Properties of Meat Analogues: A Current Overview and Future Considerations.

For centuries, meat has been a staple in the human diet, cherished for its rich protein content, vitamins, appealing texture, and umami flavor. The future supply is, however, tenuous as the global population continues to grow. Additional issues regarding animal welfare, adverse health effects, and the environmental impact of meat production have accelerated the development of meat analogues (MAs) over the last decades.

Beating Cardiac Cell Cultures From Different Developmental Stages of Rainbow Trout as a Novel Approach for Replication of Cardiac Fish Viruses.

Piscine orthoreovirus-1 and 3 (PRV-1, PRV-3) cause highly prevalent infection in cultured salmonids and can induce heart and skeletal muscle inflammation (HSMI) resulting in economic losses in aquaculture. However, to date, PRV-1 and PRV-3 have withstood replication in continuous cell lines. In this study, we used beating heart cell cultures obtained from different developmental stages of rainbow trout (Oncorhynchus mykiss) (RTC-L and RTC-A) and tested their ability to sustain replication of PRV-1 and PRV-3.

Impaired Hepatitis B and COVID-19 vaccination responses show strong concordance in hemodialysis patients with end stage renal disease.

Background: Patients with end stage renal disease (ESRD) undergoing hemodialysis are at increased risk for infection and impaired vaccination responses. We analyzed overlap and influencing factors of vaccination responses against severe acute respiratory syndrome corona virus disease 2 (SARS-CoV-2) and Hepatitis B virus (HBV).

Methods: SARS-CoV-2 and HBV vaccination response was assessed in a cohort of German ESRD hemodialysis patients.

Structure-Based Optimization of Pyridone α-Ketoamides as Inhibitors of the SARS-CoV-2 Main Protease.

The main protease M is a clinically validated target to treat infections by the coronavirus SARS-CoV-2. Among the first reported M inhibitors was the peptidomimetic α-ketoamide , whose cocrystal structure with M paved the way for multiple lead-finding studies. We established structure-activity relationships for the series by modifying residues at the P1', P3, and P4 sites.

The translational landscape of HIV-1 infected cells reveals key gene regulatory principles.

Human immunodeficiency virus-1 (HIV-1) uses a number of strategies to modulate viral and host gene expression during its life cycle. To characterize the transcriptional and translational landscape of HIV-1 infected cells, we used a combination of ribosome profiling, disome sequencing and RNA sequencing. We show that HIV-1 messenger RNAs are efficiently translated at all stages of infection, despite evidence for a substantial decrease in the translational efficiency of host genes that are implicated in host cell translation.

Design, Synthesis, and Unprecedented Interactions of Covalent Dipeptide-Based Inhibitors of SARS-CoV-2 Main Protease and Its Variants Displaying Potent Antiviral Activity.

The main protease (M) of SARS-CoV-2 is a key drug target for the development of antiviral therapeutics. Here, we designed and synthesized a series of small-molecule peptidomimetics with various cysteine-reactive electrophiles. Several compounds were identified as potent SARS-CoV-2 M inhibitors, including compounds (IC = 0.

Large-scale production of infective larvae from engorged .

Background: is transmitted by species and affects hundred millions of inhabitants in about 33 countries in sub-Saharan Africa. It is known that Mansonellosis due to do not result in a clear clinical picture, but down-regulates the immunity of patients predisposing them to other diseases like tuberculosis, HIV and malaria or damping vaccine efficacy. However, research about novel drugs against this filarial nematode is missing because of the lack of parasite material.

Impact of Fluconazole Resistance on the Outcomes of Patients With Candida parapsilosis Bloodstream Infections: A Retrospective Multicenter Study.

Background: This study assesses the impact of fluconazole resistance on 30-day all-cause mortality and 1-year recurrence in patients with Candida parapsilosis bloodstream infections (BSI).

Methods: A multicenter retrospective study was performed at 3 hospitals in Italy and Spain between 2018 and 2022. Adult patients with positive blood cultures for C.

A Multicellular In Vitro Model of the Human Intestine with Immunocompetent Features Highlights Host-Pathogen Interactions During Early Salmonella Typhimurium Infection.

Studying the molecular basis of intestinal infections caused by enteric pathogens at the tissue level is challenging, because most human intestinal infection models have limitations, and results obtained from animals may not reflect the human situation. Infections with Salmonella enterica serovar Typhimurium (STm) have different outcomes between organisms. 3D tissue modeling of primary human material provides alternatives to animal experimentation, but epithelial co-culture with immune cells remains difficult.

Macrophages co-loaded with drug-associated and superparamagnetic nanoparticles for triggered drug release by alternating magnetic fields.

Two features of macrophages make them attractive for targeted transport of drugs: they efficiently take up a broad spectrum of nanoparticles (NPs) and, by sensing cytokine gradients, they are attracted to the sites of infection and inflammation. To expand the potential of macrophages as drug carriers, we investigated whether macrophages could be simultaneously coloaded with different types of nanoparticles, thus equipping individual cells with different functionalities. We used superparamagnetic iron oxide NPs (SPIONs), which produce apoptosis-inducing hyperthermia when exposed to an alternating magnetic field (AMF), and co-loaded them on macrophages together with drug-containing NPs (inorganic-organic nanoparticles (IOH-NPs) or mesoporous silica NPs (MSNs)).

Uncovering the genetic basis of antiviral polyketide limocrocin biosynthesis through heterologous expression.

Background: Streptomyces roseochromogenes NRRL 3504 produces clorobiocin, an aminocoumarin antibiotic that inhibits DNA replication. No other natural products have been isolated from this bacterium so far, despite the presence of a rich repertoire of specialized metabolite biosynthesis gene clusters (smBGCs) within its genome. Heterologous expression of smBGCs in suitable chassis speeds up the discovery of the natural products hidden behind these sets of genes.

Heterologous Expression and Optimization of Fermentation Conditions for Recombinant Ikarugamycin Production.

Ikarugamycin is a member of the natural product family of the polycyclic tetramate macrolactams (PoTeMs). The compound exhibits a diverse range of biological activities, including antimicrobial, antiprotozoal, anti-leukemic, and anti-inflammatory properties. In addition, it interferes with several crucial cellular functions, such as oxidized low-density lipoprotein uptake in macrophages, Nef-induced CD4 cell surface downregulation, and mechanisms of endocytosis.

Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology.

The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential increased transmissibility and/or disease severity.

Genetic parameters and single-step genome-wide association analysis for trematode (Fasciola hepatica and Calicophoron/Paramphistomum spp.) infections in German dairy cows.

Infections with the liver fluke (Fasciola hepatica) cause economic losses in cattle production worldwide. Also, infections with rumen flukes (Calicophoron/Paramphistomum spp.) are gaining importance in grazing cattle in Europe.

A plug-and-play system for polycyclic tetramate macrolactam production and functionalization.

Background: The biosynthesis of the natural product family of the polycyclic tetramate macrolactams (PoTeMs) employs an uncommon iterative polyketide synthase/non-ribosomal peptide synthetase (iPKS/NRPS). This machinery produces a universal PoTeM biosynthetic precursor that contains a tetramic acid moiety connected to two unsaturated polyene side chains. The enormous structural and hence functional diversity of PoTeMs is enabled by pathway-specific tailoring enzymes, particularly cyclization-catalyzing oxidases that process the polyene chains to form distinct ring systems, and further modifying enzymes.

Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia.

Tracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli, tuft cell-dependent mechanisms underlying the recruitment and activation of immune cells are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse tuft cells, which release ATP via pannexin 1 channels.

Apo structure of Mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase DXPS: Dynamics and implications for inhibitor design.

The enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) catalyses the first step of the MEP pathway, a key process for isoprenoid biosynthesis in bacteria that is absent in humans, making it a promising drug target. We present the structure of Mycobacterium tuberculosis DXPS in its apo form, obtained through a soaking method that removes thiamine diphosphate (ThDP) and metals from pre-formed crystals. The apo structure had three regions with absence of electron density near the active site that are unique to the apo form of the enzyme.