Bacteriophage derived dsRNA induces polarized activation of alveolar macrophages from Balb/c and C57Bl/6 mice in vitro in sex- and age-dependent manner.

Bacteriophage-derived dsRNA (bp-dsRNA), also known as Larifan, is a poly-functional and wide-spectrum antiviral medication with potent interferonogenic activity. In the lungs of golden Syrian hamsters infected with SARS-CoV-2, Larifan substantially reduces viral load and decreases infection-induced pathological lesion severity. Alveolar macrophages (AM) are key sentinel cells in the lung, which play an important role in antiviral innate immune responses and, at the same time, can trigger infection-associated hyper-inflammatory response.

Elucidating Extracellular Vesicle Isolation Kinetics via an Integrated Off-Stoichiometry Thiol-Ene and Cyclic Olefin Copolymer Microfluidic Device.

Extracellular vesicles (EVs) are promising biomarkers for diagnosing complex diseases such as cancer and neurodegenerative disorders. Yet, their clinical application is hindered by challenges in isolating cancer-derived EVs efficiently due to their broad size distribution in biological samples. This study introduces a microfluidic device fabricated using off-stoichiometry thiol-ene and cyclic olefin copolymer, addressing the absorption limitations of polydimethylsiloxane (PDMS).

Sensitivity Analysis of to Quinone-Outside Inhibitor and 14α-Demethylase Inhibitor Fungicides in Latvia.

Tan spot caused by is a severe threat to wheat production in all major wheat-growing regions. Sustainable tan spot control can be achieved by an integrated approach, including responsible management of fungicide sprays. The data about the sensitivity of to various fungicides in the Baltic Sea region are rare.

Improved Genetic Characterization of Hypercholesterolemia in Latvian Patients with Familial Hypercholesterolemia: A Combined Monogenic and Polygenic Approach Using Whole-Genome Sequencing.

Despite the implementation of next-generation sequencing-based genetic testing on patients with clinical familial hypercholesterolemia (FH), most cases lack complete genetic characterization. We aim to investigate the utility of the polygenic risk score (PRS) in specifying the genetic background of patients from the Latvian Registry of FH (LRFH). We analyzed the whole-genome sequencing (WGS) data of the clinically diagnosed FH patients (n = 339) and controls selected from the Latvian reference population (n = 515).

Identification of Factors Determining Patterns of Serum C-Reactive Protein Level Reduction in Response to Treatment Initiation in Patients with Drug-Susceptible Pulmonary Tuberculosis.

Serum C-reactive protein (CRP) levels vary depending on radiological and bacteriological findings at the time of tuberculosis (TB) diagnosis. However, the utility of this biomarker in monitoring response to anti-TB treatment and identifying patients at risk of treatment failure is not well established. This study evaluated the impact of patients' baseline characteristics and anti-TB drug plasma exposure on the early reduction in serum CRP levels and its relationship with treatment response.

Targeted anticancer pre-vinylsulfone covalent inhibitors of carbonic anhydrase IX.

We designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: (1) primary sulfonamide group recognizing carbonic anhydrases (CA), (2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and (3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein followed by complete irreversible inactivation of the protein via covalent modification.

CspZ variant-specific interaction with Factor H incorporates a metal site to support Lyme borreliae complement evasion.

Polymorphic microbial immune evasion proteins dictate the pathogen species- or strain-specific virulence. Metals can impact how microbial proteins confer host-pathogen interactions, but whether this activity can be allelically variable is unclear. Here, we investigate the polymorphic CspZ protein of Lyme disease (LD) spirochete bacteria to assess the role of metals in protein-protein interaction.

Recombinant design of the enzymatically active domain of phage Enc34 endolysin to improve its activity against Gram-negative bacteria.

Endolysins are bacteriophage-encoded peptidoglycan-degrading enzymes with potential applications for treating multidrug-resistant bacterial infections. While exogenously applied endolysins are active against Gram-positive bacteria in their native form, Gram-negative bacteria are protected from such activity of most native endolysins by an outer membrane. However, it was shown that recombinant endolysins can be designed to efficiently lyse Gram-negative bacteria from without as well.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Populations of Latvia and Lithuania in the context of some Indo-European and non-Indo-European speaking populations of Europe and India: insights from genetic structure analysis.

The aim of this study was to investigate the relationship among Lithuanian, Latvian, Indian, and some other populations through a genome-wide data analysis of single nucleotide polymorphisms (SNPs). Limited data of Baltic populations were mostly compared with geographically closer modern and ancient populations in the past, but no previous investigation has explored their genetic relationships with distant populations, like the ones of India, in detail. To address this, we collected and merged genome-wide SNP data from diverse publicly available sources to create a comprehensive dataset with a substantial sample size especially from Lithuanians and Latvians.

Isolation and Characterization of a Novel Jumbo Phage HPP-Temi Infecting Pa9 and Increasing Host Sensitivity to Ciprofloxacin.

is a bacteria responsible for many hospital-acquired infections. Phages are promising alternatives for treating infections, which are often intrinsically resistant. The combination of phage and antibiotics in clearing bacterial infection holds promise due to increasing reports of enhanced effectiveness when both are used together.

Endogenous reactivation cases identified by whole genome sequencing of : Exploration of possible causes in Latvian tuberculosis patients.

Background: The recurrence of tuberculosis (TB) continues to place a significant burden on patients and TB programs worldwide. Repeated TB episodes can develop either due to endogenous reactivation of previously treated TB or exogenous reinfection with a distinct strain of (Mtb). Determining the precise cause of the recurrent TB episodes and identifying reasons for endogenous reactivation of previously successfully treated patients is crucial for introducing effective TB control measures.

Probing novel epitopes on the Plasmodium falciparum circumsporozoite protein for vaccine development.

RTS,S and R21 are the only vaccines recommended by the WHO to protect children from Plasmodium falciparum (Pf) clinical malaria. Both vaccines target the Pf sporozoite surface protein circumsporozoite protein (CSP). Recent studies showed that human antibodies neutralize Pf sporozoites most efficiently when simultaneously binding to the PfCSP NANP repeat and the NPDP junction domain.

Mechanistic insights into structure-based design of a Lyme disease subunit vaccine.

The quality of protective immunity plays a critical role in modulating vaccine efficacy, with native antigens often not able to trigger sufficiently strong immune responses for pathogen killing. This warrants creation of structure-based vaccine design, leveraging high-resolution antigen structures for mutagenesis to improve protein stability and efficient immunization strategies. Here, we investigated the mechanisms underlying structure-based vaccine design using CspZ-YA, a vaccine antigen from , the bacteria causing Lyme disease (LD), the most common vector-borne disease in the Northern Hemisphere.

The Effect of High-Intensity Interval Training on Quality of Life and Incidence of Chemotherapy Side Effects in Women With Breast Cancer.

Unlabelled: Women with breast cancer (BC) experience multiple symptoms related to neoadjuvant chemotherapy (NAC) treatment that impair their functioning and quality of life (QoL). This study aimed to explore the effect of high-intensity aerobic interval training (HIIT) on quality of life and NAC side effects in women with BC.

Methods: 56 patients (48.

The phenotypic spectrum of deficiency.

The gene product (protein PTCD3 or MRPS39) forms the entry channel of the mitochondrial small ribosomal subunit and binds to single-stranded mRNA. Here, we expand on the clinical manifestations of pathogenic variants by describing an early-onset patient with Leigh-like syndrome and two patients with milder form of disease, with combined oxidative phosphorylation deficiency. A 34-year-old male and his 33-year-old sister both have horizontal nystagmus, pronounced rough tremor, truncal ataxia, dysmetria, spasticity and hyperreflexia.

Structural basis of epitope recognition by anti-alpha-synuclein antibodies MJFR14-6-4-2.

Alpha-synuclein (α-syn) inclusions in the brain are hallmarks of so-called Lewy body diseases. Lewy bodies contain mainly aggregated α-syn together with some other proteins. Monomeric α-syn lacks a well-defined three-dimensional structure, but it can aggregate into oligomeric and fibrillar amyloid species, which can be detected using specific antibodies.

Correction: Rothen et al. Preclinical Evaluation of Novel Sterically Optimized VLP-Based Vaccines against All Four DENV Serotypes. 2024, , 874.

The authors would like to make the following corrections to this published paper [...

Meta-analysis of the Vmp-like sequences of Lyme disease : evidence for the evolution of an elaborate antigenic variation system.

VMP-like sequence () antigenic variation systems are present in every Lyme disease strain with complete genome sequences. The linear plasmid-encoded system consists of a single expression site () and contiguous array(s) of silent cassettes that have ~90% identity with the central cassette region of the cognate gene; antigenic variation occurs through random, segmental, and unidirectional recombination of silent cassette sequences into the expression site. Automated annotation programs do not accurately recognize silent cassette sequences, so these regions are not correctly annotated in most genomic sequences.

Copper Nanoparticle Loaded Electrospun Patches for Infected Wound Treatment: From Development to In-Vivo Application.

This study investigates the development and application of electrospun wound dressings based on polylactic acid (PLA) nanofibers, chitosan, and copper nanoparticles (CuNPs) for the treatment of purulent skin wounds. The materials were evaluated for their structural, antibacterial, and wound healing properties using an animal model. PLA/Ch-CuNPs demonstrated the most significant antibacterial activity against , , and , surpassing the other tested materials.

Preparation and Characterization of Photo-Cross-Linkable Methacrylated Silk Fibroin and Methacrylated Hyaluronic Acid Composite Hydrogels.

Composite biomaterials with excellent biocompatibility and biodegradability are crucial in tissue engineering. In this work, a composite protein and polysaccharide photo-cross-linkable hydrogel was prepared using silk fibroin methacrylate (SFMA) and hyaluronic acid methacrylate (HAMA). SFMA was obtained by the methacrylation of degummed SF with glycidyl methacrylate (GMA), while HA was methacrylated by 2-aminoethyl methacrylate hydrochloride (AEMA).