Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli.

Natural resistance to Mycobacterium tuberculosis (Mtb) infection in some people with HIV (PWH) is unexplained. We performed single cell RNA-sequencing of bronchoalveolar lavage cells, unstimulated or ex vivo stimulated with Mtb, for 7 PWH who were TST & IGRA positive (called LTBI) and 6 who were persistently TST & IGRA negative (called resisters). Alveolar macrophages (AM) from resisters displayed a baseline M1 macrophage phenotype while AM from LTBI did not.

Conventional and Tropism-Modified High-Capacity Adenoviral Vectors Exhibit Similar Transduction Profiles in Human iPSC-Derived Retinal Organoids.

Viral vector delivery of gene therapy represents a promising approach for the treatment of numerous retinal diseases. Adeno-associated viral vectors (AAV) constitute the primary gene delivery platform; however, their limited cargo capacity restricts the delivery of several clinically relevant retinal genes. In this study, we explore the feasibility of employing high-capacity adenoviral vectors (HC-AdVs) as alternative delivery vehicles, which, with a capacity of up to 36 kb, can potentially accommodate all known retinal gene coding sequences.

Transcriptome immune-regulatory differences between leprosy patients and type 1 reaction patients, before onset of symptoms.

Leprosy is a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. A major public health and clinical problem are leprosy reactions, which are inflammatory episodes that often contribute to nerve damage and disability. Type I reversal reactions (T1R) can occur after microbiological cure of leprosy and affect up to 50% of leprosy patients.

Trace Elements in Medicinal Metallomics.

This analytical mini-review focuses on the effects of trace elements, which includes Cu, Mn, Zn, and Se, as well as some rarer microelements, on the regulation of oxidative stress in the body and of certain diseases associated with it. Synergism and competition between certain microelements have been considered a hot topic in the applied molecular pharmacology of these specific bio-effects. Some ideas for further possible directions of research are expressed.

Spectrum of pathogenic variants and high prevalence of pathogenic variants in Russian patients with Bardet-Biedl syndrome.

Introduction: Bardet-Biedl syndrome is a rare condition characterized by obesity, retinitis pigmentosa, polydactyly, development delay, and structural kidney anomalies. This syndrome has an autosomal recessive type of inheritance. For the first time, molecular genetic testing has been provided for a large cohort of Russian patients with Bardet-Biedl syndrome.

Dynamics of pulmonary mucosal cytotoxic CD8 T-cells in people living with HIV under suppressive antiretroviral therapy.

Background: Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) suffer from a high burden of pulmonary diseases, even after accounting for their smoking status. Cytotoxic CD8 T-cells are likely implicated in this phenomenon and may act as a double-edged sword. While being essential in viral infection control, their hyperactivation can also contribute to lung mucosal tissue damage.

New Case of Spinocerebellar Ataxia, Autosomal Recessive 4, Due to Variants.

Movement disorders such as bradykinesia, tremor, dystonia, chorea, and myoclonus most often arise in several neurodegenerative diseases with basal ganglia and white matter involvement. While the pathophysiology of these disorders remains incompletely understood, dysfunction of the basal ganglia and related brain regions is often implicated. The gene, part of the family, has emerged as a crucial player in neurological pathology, implicated in diverse phenotypes ranging from movement disorders to Leigh syndrome.

Detection and Recognition of Voice Commands by a Distributed Acoustic Sensor Based on Phase-Sensitive OTDR in the Smart Home Concept.

In recent years, attention to the realization of a distributed fiber-optic microphone for the detection and recognition of the human voice has increased, whereby the most popular schemes are based on φ-OTDR. Many issues related to the selection of optimal system parameters and the recognition of registered signals, however, are still unresolved. In this research, we conducted theoretical studies of these issues based on the φ-OTDR mathematical model and verified them with experiments.

Age-related changes in human skeletal muscle transcriptome and proteome are more affected by chronic inflammation and physical inactivity than primary aging.

Evaluation of the influence of primary and secondary aging on the manifestation of molecular and cellular hallmarks of aging is a challenging and currently unresolved issue. Our study represents the first demonstration of the distinct role of primary aging and chronic inflammation/physical inactivity - the most important drivers of secondary aging, in the regulation of transcriptomic and proteomic profiles in human skeletal muscle. To achieve this purpose, young healthy people (n = 15), young (n = 8) and older (n = 37) patients with knee/hip osteoarthritis, a model to study the effect of long-term inactivity and chronic inflammation on the vastus lateralis muscle, were included in the study.

Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli.

To understand natural resistance to ( ) infection, we studied people living with HIV (PLWH) in an area of high transmission. Given that alveolar leukocytes may contribute to this resistance, we performed single cell RNA-sequencing of bronchoalveolar lavage cells, unstimulated or stimulated with . We obtained high quality cells for 7 participants who were TST & IGRA positive (called LTBI) and 6 who were persistently TST & IGRA negative (called resisters).

Tick-Borne Encephalitis in the Russian Caucasus: Virus Was Detected for the First Time on the Border of Europe and Asia Minor.

The tick-borne encephalitis (TBE) virus has been confirmed by molecular analysis in the Caucasus region for the first time. The virus obtained from a tick ex Caspian green lizard belongs to the Zausaev strain of the Siberian subtype (not to a strain of the European subtype highly distributed in the territories adjacent to the Caucasus). This unusual record indicates the need to study the role of lizards in the circulation of natural focal infections.

Characterization and AAV-mediated gene augmentation in human-derived and retinal organoids.

The majority of patients with mutations in develop either early-onset retinitis pigmentosa as young children or Leber congenital amaurosis as newborns. The cause for the phenotypic variability in -associated retinopathies is unknown, but might be linked to differences in CRB1 and CRB2 protein levels in Müller glial cells and photoreceptor cells. Here, and differentiation day 210 retinal organoids showed a significant decrease in the number of photoreceptor nuclei in a row and a significant increase in the number of photoreceptor cell nuclei above the outer limiting membrane.

Generation of two iPSC lines from patient with Mucopolysaccharidosis IV B type and autosomal recessive non-syndromic hearing loss 12.

We generated two human induced pluripotency stem cell (hiPSC) lines, RCMGi011-A and 11-B, from skin fibroblast from patient with Mucopolysaccharidosis IV B type and autosomal recessive non-syndromic hearing loss 12 using non-integrating, viral CytoTune™-iPS 2.0 Sendai Reprogramming Kit. We verified variant c.

Neutrophil extracellular trap formation and gene programs distinguish TST/IGRA sensitization outcomes among Mycobacterium tuberculosis exposed persons living with HIV.

Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and show no evidence of immune sensitization to Mycobacterium tuberculosis (Mtb) as defined by persistently negative tuberculin skin tests (TST) and interferon gamma release assays (IGRA). This group has been identified and defined as HIV+ persistently TB, tuberculin and IGRA negative (HITTIN).

Evaluation of Pathogenicity and Causativity of Variants in the and Genes in a Family Case of Hereditary Peripheral Neuropathy.

The implementation of NGS methods into clinical practice allowed researchers effectively to establish the molecular cause of a disorder in cases of a genetically heterogeneous pathology. In cases of several potentially causative variants, we need additional analysis that can help in choosing a proper causative variant. In the current study, we described a family case of hereditary motor and sensory neuropathy (HMSN) type 1 (Charcot-Marie-Tooth disease).

Generation of induced pluripotent stem cell line (RCMGi009-A) from urine cells of patient with fibrodysplasia ossificans progressiva.

Urine cells obtained from a 14-year-old man with genetically proven (ACVR1: c.6176G > A) and clinically manifested fibrodysplasia ossificans progressiva were successfully transformed into induced pluripotent stem cells by using Sendai virus-based reprogramming vectors including the four Yamanaka factors such as OCT3/4, SOX2, KLF4, and c-MYC. These iPSCs expressed pluripotency markers, exhibited the potential to differentiate into three germ layers in spontaneous differentiation assay and had a normal karyotype.

Symptomatic Infection with spp. Decreases Diapause Survival in a Wild Bumble Bee Species ().

, a microsporidian parasite (previously classified as ), has been implicated in the decline of wild bumble bee species in North America. Previous studies examining its influence on colony performance have displayed variable results, from extremely detrimental effects to no observable influence, and little is known about the effects it has on individuals during the winter diapause, a bottleneck for survival in many annual pollinators. Here, we examined the effect of infection, body size, and mass on diapause survival in gynes.

A new species of Spinturnix (Acari: Spinturnicidae) from the Turkestani long-eared bat Otonycteris leucophaea (Chiroptera: Vespertilionidae) in Kazakhstan.

The female, male and protonymph of Spinturnix otonycterisi Dundarova & Orlova, sp. nov. (Acari: Spinturnicidae) are described from specimens collected on the enigmatic and rarely captured vespertilionid bat Otonycteris leucophaea (Severcov, 1873) in South Kazakhstan.

Human alveolar macrophage metabolism is compromised during infection.

Pulmonary macrophages have two distinct ontogenies: long-lived embryonically-seeded alveolar macrophages (AM) and bone marrow-derived macrophages (BMDM). Here, we show that after infection with a virulent strain of (H37Rv), primary murine AM exhibit a unique transcriptomic signature characterized by metabolic reprogramming distinct from conventional BMDM. In contrast to BMDM, AM failed to shift from oxidative phosphorylation (OXPHOS) to glycolysis and consequently were unable to control infection with an avirulent strain (H37Ra).

Generation of two induced pluripotent stem cell lines (RCMGi005-A/B) from human skin fibroblasts of a cystic fibrosis patient with homozygous F508del mutation in CFTR gene.

Induced pluripotent stem cells (iPSCs) was successfully generated from skin fibroblast obtained from patient with cystic fibrosis by using non-integrating, viral CytoTune™-iPS 2.0 Sendai Reprogramming Kit, which contain three vectors preparation: polycistronic Klf4-Oct3/4-Sox2, cMyc, and Klf4. Created iPSC lines showed a normal karyotype, expressed pluripotency markers and demonstrated the potential to differentiate into three germ layers in spontaneous differentiation assay.

Generation of induced pluripotent stem cell line (RCMGi008-A) from human skin fibroblasts of a cystic fibrosis patient with compound heterozygous F508del/CFTRdele2.3 mutations in CFTR gene.

Skin fibroblasts obtained from a 20-year-old woman with clinically manifested and genetically proven (F508del/CFTRdele2.3) cystic fibrosis were successfully transformed into induced pluripotent stem cells (iPSCs) by using Sendai virus-based reprogramming vectors including the four Yamanaka factors, OCT3/4, SOX2, KLF4, and c-MYC. The iPSCs showed a normal karyotype, expressed pluripotency markers and exhibited the potential to differentiate into three germ layers in spontaneous differentiation assay.