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.

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.

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.

Enhancement of clinical signs in C3H/HeJ mice vaccinated with a highly immunogenic Leptospira methyl-accepting chemotaxis protein following challenge.

Leptospirosis is the most widespread zoonosis and a life-threatening disease in humans and animals. Licensed killed whole-cell vaccines are available for animals; however, they do not offer heterologous protection, do not induce long-term protection, or prevent renal colonization. In this study, we characterized an immunogenic Leptospira methyl-accepting chemotaxis protein (MCP) identified through a reverse vaccinology approach, predicted its structure, and tested the protective efficacy of a recombinant MCP fragment in the C3H/HeJ mice model.

Bacteria and RNA virus inactivation with a high-irradiance UV-A source.

Disinfection with LED lamps is a promising ecological and economical substitute for mercury lamps. However, the optimal time/dose relationship needs to be established. Pathogen inactivation by UV-A primarily relies on induced reactive oxygen species (ROS) formation and subsequent oxidative damage.

Tumor and α-SMA-expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade.

Alpha-smooth muscle actin (α-SMA) expression in the stroma is linked to the presence of cancer-associated fibroblasts and is known to correlate with worse outcomes in various tumors. In this study, using a GeoMx digital spatial profiling approach, we characterized the gene expression of the tumor and α-SMA-expressing stromal cell compartments in pancreatic neuroendocrine tumors (PanNETs). The profiling was performed on tissues from eight retrospective cases (three grade 1, four grade 2, and one grade 3).

Pituitary Adenoma: rs2236750, rs34037914, and rs267606574 Genetic Variants, Serum Levels, and Ki-67 Labeling Index Associations.

This study explores the complex pathogenesis of pituitary adenomas (PAs), prevalent intracranial tumors in the pituitary gland. Despite their generally benign nature, PAs exhibit a diverse clinical spectrum involving hormone hypersecretion and varying invasiveness, hinting at multifaceted molecular mechanisms and abnormalities in tumorigenesis and gene regulation. The investigation focuses on the Ki-67 labeling index, rs2236750, rs34037914, and rs267606574 polymorphisms, alongside serum levels of SSTR2, SSTR5, and AIP, to discern their association with PAs.

From sweat to hope: The role of exercise-induced extracellular vesicles in cancer prevention and treatment.

The benefits of regular physical exercise on cancer prevention, as well as reducing fatigue, treatment side effects and recurrence, and improving quality of life and overall survival of cancer patients, are increasingly recognised. Initial studies showed that the concentration of extracellular vesicles (EVs) increases during physical activity and that EVs carry biologically active cargo. These EVs are released by blood cells, skeletal muscle and other organs involved in exercise, thus suggesting that EVs may mediate tissue crosstalk during exercise.

Discordance Between Phenotypic and WGS-Based Drug Susceptibility Testing Results for Some Anti-Tuberculosis Drugs: A Snapshot Study of Paired Isolates with Small Genetic Distance.

Background: Current tuberculosis treatment regimens primarily rely on phenotypic drug susceptibility testing and rapid molecular assays. Although whole-genome sequencing (WGS) offers a promising alternative, disagreements between phenotypic and molecular testing methods remain. In this retrospective study, we compared the phenotypic and WGS-predicted drug resistance profiles of paired isolates with small genetic distances (≤10 single nucleotide variants) obtained from patients with longitudinal single-episode or recurrent tuberculosis.

Self-organisation of early stress response in the biology of cancer.

The early stress response by AP-1 (FOS/JUN), supported by upregulation of c-Myc and involved in cell-fate changes and adaptation to hostile environments, is increased in cancer. The review shows the biphasic character of this response with negative feed-back typically lasting a few hours as a feature of the genome regulation by self-organising criticality. It involves  rapid splitting of the pericentromeric heterochromatin clusters, opening of the active chromatin, and a massive transcription acceleration wave.