Landmark native breed of the Orenburg goats: progress in its breeding and genetics and future prospects

This paper reviews information about a unique and iconic breed of the Orenburg Oblast, the homeland and the only place where the best herds of Orenburg down-hair goats in Russia are concentrated. Three types of these small ruminant animals are widespread on the territory of the region: Orenburg purebred gray goats, Orenburg purebred white goats, as well as crossbred white goats of F1 White Don White Orenburg. Currently, at the farms of the Orenburg region, animals are selected according to their phenotype, with selected traits being color, weight and length of down hair. In recent years, the Orenburg goat breed has become an object of genetic research using various marker systems including immunogenetic, microsatellite, mtDNA and SNP markers. Overall, these studies evidence about the uniqueness of the allele pool in the landmark native breed of the Orenburg goats, which is a complex dynamic genetic system, prioritizing its further in-depth genome research and breeding applications

Actinomycetes as Producers of Biologically Active Terpenoids: Current Trends and Patents

Terpenes and their derivatives (terpenoids and meroterpenoids, in particular) constitute the largest class of natural compounds, which have valuable biological activities and are promising therapeutic agents. The present review assesses the biosynthetic capabilities of actinomycetes to produce various terpene derivatives; reports the main methodological approaches to searching for new terpenes and their derivatives; identifies the most active terpene producers among actinomycetes; and describes the chemical diversity and biological properties of the obtained compounds. Among terpene derivatives isolated from actinomycetes, compounds with pronounced antifungal, antiviral, antitumor, anti-inflammatory, and other effects were determined. Actinomycete-produced terpenoids and meroterpenoids with high antimicrobial activity are of interest as a source of novel antibiotics effective against drug-resistant pathogenic bacteria. Most of the discovered terpene derivatives are produced by the genus Streptomyces; however, recent publications have reported terpene biosynthesis by members of the genera Actinomadura, Allokutzneria, Amycolatopsis, Kitasatosporia, Micromonospora, Nocardiopsis, Salinispora, Verrucosispora, etc. It should be noted that the use of genetically modified actinomycetes is an effective tool for studying and regulating terpenes, as well as increasing productivity of terpene biosynthesis in comparison with native producers. The review includes research articles on terpene biosynthesis by Actinomycetes between 2000 and 2022, and a patent analysis in this area shows current trends and actual research directions in this field

Quantitative Prediction of Human Immunodeficiency Virus Drug Resistance

Drug resistance of pathogens, including viruses, is one of the reasons for decreased efficacy of therapy. Considering the impact of HIV type 1 (HIV-1) on the development of progressive immune dysfunction and the rapid development of drug resistance, the analysis of HIV-1 resistance is of high significance. Currently, a substantial amount of data has been accumulated on HIV-1 drug resistance that can be used to build both qualitative and quantitative models of HIV-1 drug resistance. Quantitative models of drug resistance can enrich the information about the efficacy of a particular drug in the scheme of antiretroviral therapy. In our study, we investigated the possibility of developing models for quantitative prediction of HIV-1 resistance to eight protease inhibitors based on the analysis of amino acid sequences of HIV-1 protease for 900 virus variants. We developed random forest regression (RFR), support vector regression (SVR), and self-consistent regression (SCR) models using binary vectors containing values from 0 or 1, depending on the presence of a specific peptide fragment in each amino acid sequence as independent variables, while fold ratio, reflecting the level of resistance, was the predicted variable. The SVR and SCR models showed the highest predictive performances. The models built demonstrate reasonable performances for eight out of nine (R2 varied from 0.828 to 0.909) protease inhibitors, while R2 for predicting tipranavir fold ratio was lower (R2 was 0.642). We believe that the developed approach can be applied to evaluate drug resistance of molecular targets of other viruses where appropriate experimental data are available

Risk Factors for Acquisition of Drug Resistance during Multidrug-Resistant Tuberculosis Treatment, Arkhangelsk Oblast, Russia, 2005–2010

Acquired resistance to antituberculosis drugs decreases effective treatment options and the likelihood of treatment success. We identified risk factors for acquisition of drug resistance during treatment for multidrug-resistant tuberculosis (MDR TB) and evaluated the effect on treatment outcomes. Data were collected prospectively from adults from Arkhangelsk Oblast, Russia, who had pulmonary MDR TB during 2005–2008. Acquisition of resistance to capreomycin and of extensively drug-resistant TB were more likely among patients who received 3 effective drugs (9.4% vs. 0% and 8.6% vs. 0.8%, respectively). Poor outcomes were more likely among patients with acquired capreomycin resistance (100% vs. 25.9%), acquired ofloxacin resistance (83.6% vs. 22.7%), or acquired extensive drug resistance (100% vs. 24.4%). To prevent acquired drug resistance and poor outcomes, baseline susceptibility to first- and second-line drugs should be determined quickly, and treatment should be adjusted to contain >3 effective drugs

Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: final analysis of LUCY

PurposeThe interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib arm of the phase III OlympiAD trial (7.03 months). This prespecified analysis provides final overall survival (OS) and safety data.MethodsThe open-label, single-arm LUCY trial of olaparib (300 mg, twice daily) enrolled adults with gBRCAm or somatic BRCA-mutated (sBRCAm), HER2-negative mBC. Patients had previously received a taxane or anthracycline for neoadjuvant/adjuvant or metastatic disease and up to two lines of chemotherapy for mBC.ResultsOf 563 patients screened, 256 (gBRCAm, n = 253; sBRCAm, n = 3) were enrolled. In the gBRCAm cohort, median investigator-assessed PFS (primary endpoint) was 8.18 months and median OS was 24.94 months. Olaparib was clinically effective in all prespecified subgroups: hormone receptor status, previous chemotherapy for mBC, previous platinum-based chemotherapy (including by line of therapy), and previous cyclin-dependent kinase 4/6 inhibitor use. The most frequent treatment-emergent adverse events (TEAEs) were nausea (55.3%) and anemia (39.2%). Few patients (6.3%) discontinued olaparib owing to a TEAE. No deaths associated with AEs occurred during the study treatment or 30-day follow-up.ConclusionThe LUCY patient population reflects a real-world population in line with the licensed indication of olaparib in mBC. These findings support the clinical effectiveness and safety of olaparib in patients with gBRCAm, HER2-negative mBC.Clinical trial registrationClinical trials registration number: NCT0328684