Genomic diversity of the locally developed Latvian Darkheaded sheep breed.

The Latvian Darkheaded is the only locally developed sheep breed. The breed was formed at the beginning of the 20th century by crossing local coarse-wooled sheep with the British Shropshire and Oxfordshire breeds. The breed was later improved by adding Ile-de-France, Texel, German blackheads, and Finnsheep to achieve higher prolificacy and better meat quality.

Variations in the Relative Abundance of Gut Bacteria Correlate with Lipid Profiles in Healthy Adults.

The gut microbiome is a versatile system regulating numerous aspects of host metabolism. Among other traits, variations in the composition of gut microbial communities are related to blood lipid patterns and hyperlipidaemia, yet inconsistent association patterns exist. This study aims to assess the relationships between the composition of the gut microbiome and variations in lipid profiles among healthy adults.

Metformin targets intestinal immune system signaling pathways in a high-fat diet-induced mouse model of obesity and insulin resistance.

Introduction: Research findings of the past decade have highlighted the gut as the main site of action of the oral antihyperglycemic agent metformin despite its pharmacological role in the liver. Extensive evidence supports metformin's modulatory effect on the composition and function of gut microbiota, nevertheless, the underlying mechanisms of the host responses remain elusive. Our study aimed to evaluate metformin-induced alterations in the intestinal transcriptome profiles at different metabolic states.

Genomic Characterization and Initial Insight into Mastitis-Associated SNP Profiles of Local Latvian Breeds.

Latvia has two local breeds-Latvian Brown (LBG) and Latvian Blue (LZG)-characterized by a good adaptation to the local climate, longevity, and high fat and protein contents in milk. Since these are desired traits in the dairy industry, this study investigated the genetic background of the LBG and LZG breeds and identified the genetic factors associated with mastitis. Blood and semen samples were acquired, and whole genome sequencing was then performed to acquire a genomic sequence with at least 35× or 10× coverage.

Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes.

Antidiabetic drug metformin alters the gut microbiome composition in the context of type 2 diabetes and other diseases; however, its effects have been mainly studied using fecal samples, which offer limited information about the intestinal site-specific effects of this drug. Our study aimed to characterize the spatial variation of the gut microbiome in response to metformin treatment by using a high-fat diet-induced type 2 diabetes mouse model of both sexes. Four intestinal parts, each at the luminal and mucosal layer level, were analyzed in this study by performing 16S rRNA sequencing covering six variable regions (V1-V6) of the gene and thus allowing to obtain in-depth information about the microbiome composition.

Epiphytic and Endophytic Fungi Colonizing Seeds of Two Weed Species and spp. Seed Degradation Potential In Vitro.

Fungi colonizing the surface and endosphere of two widespread Poaceae weed species, Avena fatua and Echinochloa crus-galli, were isolated to compare the taxonomic composition between the plant species, location, and year of the seed collection. The seed-degrading potential of Fusarium isolated from the seeds was tested by inoculating seeds of E. crus-galli with spore suspension.

Detection of SARS-CoV-2 RNA in wastewater and importance of population size assessment in smaller cities: An exploratory case study from two municipalities in Latvia.

Wastewater-based epidemiology (WBE) has regained global importance during the COVID-19 pandemic. The mobility of people and other factors, such as precipitation and irregular inflow of industrial wastewater, are complicating the estimation of the disease prevalence through WBE, which is crucial for proper crisis management. These estimations are particularly challenging in urban areas with moderate or low numbers of inhabitants in situations where movement restrictions are not adopted (as in the case of Latvia) because residents of smaller municipalities tend to be more mobile and less strict in following the rules and measures of disease containment.

Metformin Strongly Affects Gut Microbiome Composition in High-Fat Diet-Induced Type 2 Diabetes Mouse Model of Both Sexes.

Effects of metformin, the first-line drug for type 2 diabetes therapy, on gut microbiome composition in type 2 diabetes have been described in various studies both in human subjects and animals. However, the details of the molecular mechanisms of metformin action have not been fully understood. Moreover, there is a significant lack of information on how metformin affects gut microbiome composition in female mouse models, depending on sex and metabolic status in well controlled experimental setting.

Baseline gut microbiome composition predicts metformin therapy short-term efficacy in newly diagnosed type 2 diabetes patients.

Background: The study was conducted to investigate the effects of metformin treatment on the human gut microbiome's taxonomic and functional profile in the Latvian population, and to evaluate the correlation of these changes with therapeutic efficacy and tolerance.

Methods: In this longitudinal observational study, stool samples for shotgun metagenomic sequencing-based analysis were collected in two cohorts. The first cohort included 35 healthy nondiabetic individuals (metformin dose 2x850mg/day) at three time-points during metformin administration.

Whole-blood transcriptome profiling reveals signatures of metformin and its therapeutic response.

Metformin, a biguanide agent, is the first-line treatment for type 2 diabetes mellitus due to its glucose-lowering effect. Despite its wide application in the treatment of multiple health conditions, the glycemic response to metformin is highly variable, emphasizing the need for reliable biomarkers. We chose the RNA-Seq-based comparative transcriptomics approach to evaluate the systemic effect of metformin and highlight potential predictive biomarkers of metformin response in drug-naïve volunteers with type 2 diabetes in vivo.

Association of metformin administration with gut microbiome dysbiosis in healthy volunteers.

Background: Metformin is a widely used first-line drug for treatment of type 2 diabetes. Despite its advantages, metformin has variable therapeutic effects, contraindications, and side effects. Here, for the very first time, we investigate the short-term effect of metformin on the composition of healthy human gut microbiota.

Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-term response to metformin monotherapy in type 2 diabetes mellitus patients.

Objectives: High variability in clinical response to metformin is often observed in type 2 diabetes (T2D) patients, and it highlights the need for identification of genetic components affecting the efficiency of metformin therapy. Aim of this observational study is to evaluate the role of tagSNPs (tagging single nucleotide polymorphisms) from genomic regions coding for six metformin transporter genes with respect to the short-term efficiency.

Design: 102 tagSNPs in 6 genes coding for metformin transporters were genotyped in the group of 102 T2D patients treated with metformin for 3 months.

Genome-wide analysis reveals DNA methylation markers that vary with both age and obesity.

The combination of the obesity epidemic and an aging population presents growing challenges for the healthcare system. Obesity and aging are major risk factors for a diverse number of diseases and it is of importance to understand their interaction and the underlying molecular mechanisms. Herein the authors examined the methylation levels of 27578 CpG sites in 46 samples from adult peripheral blood.

The role of common and rare MC4R variants and FTO polymorphisms in extreme form of obesity.

Melanocortin 4 receptor (MC4R) is an important regulator of food intake and number of studies report genetic variations influencing the risk of obesity. Here we explored the role of common genetic variation from MC4R locus comparing with SNPs from gene FTO locus, as well as the frequency and functionality of rare MC4R mutations in cohort of 380 severely obese individuals (BMI > 39 kg/m(2)) and 380 lean subjects from the Genome Database of Latvian Population (LGDB). We found correlation for two SNPs--rs11642015 and rs62048402 in the fat mass and obesity-associated protein (FTO) with obesity but no association was detected for rs17782313 located in the MC4R locus in these severely obese individuals.

Polymorphisms in FTO and near TMEM18 associate with type 2 diabetes and predispose to younger age at diagnosis of diabetes.

Variations in the FTO gene and near the TMEM18 gene are risk factors for common form of obesity, but have also been linked with type 2 diabetes (T2D). Our aim was to investigate the contribution of these variants to risk of T2D in a population in Latvia. Four single nucleotide polymorphisms (SNP) in the first and fourth intronic regions of FTO and one close to TMEM18 were genotyped in 987 patients with T2D and 1080 controls selected from the Latvian Genome Data Base (LGDB).

Association of genetic variation in the organic cation transporters OCT1, OCT2 and multidrug and toxin extrusion 1 transporter protein genes with the gastrointestinal side effects and lower BMI in metformin-treated type 2 diabetes patients.

Objective: Metformin is the most widely used oral antidiabetic drug for the treatment of type 2 diabetes (T2D). So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin. However, there is no information on the influence of genetic variations within these genes on the side effects of metformin.

Identification of domains responsible for specific membrane transport and ligand specificity of the ACTH receptor (MC2R).

The adrenocorticotropic hormone (ACTH) receptor has highly specific membrane expression that is limited to adrenal cells; in other cell types the polypeptide fails to be transported to the cell surface. Unlike other evolutionarily related members of the melanocortin receptor family (MC1R-MC5R) that recognize different melanocortin peptides, ACTHR (MC2R) binds only ACTH. We used a mutagenesis approach involving systematic construction of chimeric ACTHR/MC4R receptors to identify the domains determining the selectivity of ACTHR membrane transport and ACTH binding.

Association between a rare SNP in the second intron of human Agouti related protein gene and increased BMI.

Background: The agouti related protein (AGRP) is an endogenous antagonist of the melanocortin 4 receptor and is one of the most potent orexigenic factors. The aim of the present study was to assess the genetic variability of AGRP gene and investigate whether the previously reported SNP rs5030980 and the rs11575892, a SNP that so far has not been studied with respect to obesity is associated with increased body mass index (BMI).

Methods: We determined the complete sequence of the AGRP gene and upstream promoter region in 95 patients with severe obesity (BMI > 35 kg/m2).

The evolutionary history and tissue mapping of GPR123: specific CNS expression pattern predominantly in thalamic nuclei and regions containing large pyramidal cells.

The Adhesion family of G protein-coupled receptors (GPCRs) includes 33 receptors and is the second largest GPCR family. Most of these proteins are still orphans and fairly little is known of their tissue distribution and evolutionary context. We report the evolutionary history of the Adhesion family protein GPR123 as well as mapping of GPR123 mRNA expression in mouse and rat using in situ hybridization and real-time PCR, respectively.