Mustela palerminea (Mustelidae, Carnivora) from the Early Pleistocene of Crimea.

The mandibles of two individuals of Mustela palerminea (Petenyi, 1864) are described  from the Lower Pleistocene deposits of the Taurida cave in Crimea (Late Villafranchian, 1.8-1.5 Ma). This extinct mustelid species was a typical representative of the Villafranchian faunas of Europe. It is the first record of M. palerminea in Russia.

Mustela strandi (Mustelidae, Carnivora) from the Early Pleistocene of Crimea.

The dentary of Mustela strandi Kormos, 1934 is described from the Lower Pleistocene deposits (Late Villafranchian, 1.8-1.5 Ma) of the Taurida cave in Crimea. It is the first finding of M. strandi in Russia. This extinct mustelid species is rarely found in the Lower and Middle Pleistocene of Central Europe.

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.808 T > G and insertion in GLB1 gene, as well as two mutations, c.6992 T > C and c.805C > T, in CDH23 gene which lead to autosomal recessive hearing loss type 12. We have demonstrated normal karyotype of hiPSCs and capacity for cell differentiation into three germ layers.

Recombinant Adeno-associated Viral Vectors Serotypes 6 and 9 are Able to Transduce Human Tracheal Epithelial Cells but Not Human Induced Pluripotent Stem Cells.

Recombinant adeno-associated viruses (rAAVs) may be useful for the development of gene therapy for hereditary diseases. Patient-specific human induced pluripotent stem cells (hiPSCs) can be differentiated into a variety of cells which are difficult or impossible to obtain by biopsy. To date, few research on the efficiency of rAAV transduction of hiPSCs has been published, but the obtained data are very contradictory and do not answer the actual question: how effective are rAAVs for the delivery of transgenes into hiPSCs. In this work, we used rAAV serotypes 5, 6, and 9 carrying the GFP transgene. The transduction efficiency of rAAV2/9-GFP and rAAV2/6-GFP for the immortalized tracheal epithelial cell line derived from a patient with cystic fibrosis (CFTE29o-) was relatively high. At the same time, the efficiency of transduction of iPSCs from a healthy donor and a cystic fibrosis (CF) donor was extremely low. Thus, our results show that the efficiency of hiPSC transduction by rAAV serotypes 5, 6, and 9 is not suitable for the delivery of transgenes.

Evidence of Toxocara Eggs in Pachycrocuta brevirostris (Gervais, 1850) Coprolites from the Pleistocene of Taurida Cave (Crimea).

Coprolites of the hyena Pachycrocuta brevirostris from the Lower Pleistocene (Upper Villafranchian) of Taurida Cave (Crimea) were studied. One of the three hyena coprolites contained helminth eggs. These eggs were assigned to Toxocara sp. based on their size and morphology. Toxocariasis was evidently a very common infestation among extinct hyena species. The find of toxocara in P. brevirostris coprolite from the Taurida Cave is the earliest evidence of roundworm infestation in P. brevirostris.

Chasmaporthetes lunensis (Hyaenidae, Carnivora) from the Early Pleistocene of Crimea.

A maxillary fragment of the extinct hyena Chasmaporthetes lunensis (Del Campana, 1914) is described from the Early Pleistocene locality of the Taurida cave (Crimea, Late Villafranchian, 1.8-1.5 Ma). The species was a typical representative of the Villafranchian faunas of Eurasia. This is the first record of the genus Chasmaporthetes in the Pleistocene of Crimea.

Early Pleistocene Lynx issiodorensis (Felidae, Carnivora) from the Taurida Cave, Crimea.

The cranial and mandibular remains of two adult individuals of Lynx issiodorensis (Croizet et Jobert, 1828) are described from the Early Pleistocene locality of the Taurida cave (Crimea, Late Villafranchian, 1.8-1.5 Ma). This lynx species was a typical representative of the Villafranchian fauna of the Eastern Mediterranean. A high craniological variability of L. issiodorensis is noted.

Pleistocene foxes (Vulpes, Canidae, Carnivora) from the Taurida Cave, Crimea.

A mandible fragment and four isolated teeth of the fossil foxes, Vulpes alopecoides (Del Campana, 1913), Vulpes cf. vulpes (Linnaeus, 1758) and Vulpes sp., are described from the Early Pleistocene locality of Taurida cave (Crimea, Late Villafranchian, 1.8-1.5 Ma). Based on the size and morphological features, a mandible fragment and two M1 are attributed to V. alopecoides. The structure of m1 of Vulpes cf. vulpes is similar to that of V. vulpes and V. alopecoides, but the size greatly exceeds the size limits for the latter species. Although m1 of Vulpes sp. fits the size of the lower carnassials of V. alopecoides, its morphology is definitely unique among the Early Pleistocene representatives of the genus Vulpes.

Animal models for researching approaches to therapy of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a relatively widespread genetic disease which develops as a result of a mutation in the gene DMD encoding dystrophin. In this review, animal models of DMD are described. These models are used in preclinical studies to elucidate the pathogenesis of the disease or to develop effective treatments; each animal model has its own advantages and disadvantages. For instance, Caenorhabditis elegans, Drosophila melanogaster, and zebrafish (sapje) are suitable for large-scale chemical screening of large numbers of small molecules, but their disease phenotype differs from that of mammals. The use of larger animals is important for understanding of the potential efficacy of various treatments for DMD. While mdx mice have their advantages, they exhibit a milder disease phenotype compared to humans or dogs, making it difficult to evaluate the efficacy of new treatment for DMD. The disease in dogs and pigs is more severe and progresses faster than in mice, but it is more difficult to breed and obtain sufficient numbers of specimens in order to achieve statistically significant results. Moreover, working with large animals is also more labor-intensive. Therefore, when choosing the optimal animal model for research, it is worth considering all the goals and objectives.

Giant Hyena Pachycrocuta brevirostris (Hyaenidae, Carnivora) from the Lower Pleistocene of Taurida Cave, Crimea.

The dental remains of a giant hyena Pachycrocuta brevirostris (Gervais, 1850) from the Early Pleistocene locality of the Taurida cave (Crimea, Late Villafranchian, 1.8-1.5 Ma) are described. This species was a typical representative of the Villafranchian fauna of the Eastern Mediterranean. The Taurida cave was occasionally used by hyenas and other carnivorans as a den and retreat.

First Finding of Etruscan Bear (Ursus etruscus, Ursidae, Carnivora) in the Crimea (Taurida Cave, Early Pleistocene).

A fragment of a bear skull with partially preserved dentition is descibed from the Lower Pleistocene deposits of the Taurida cave (Crimea). The presence of P1-P3, the structure of P4, and sizes of the cheek teeth enable the identification of the specimen as Ursus etruscus Cuvier, 1823. The new find is the first in Crimea and the entire Russia and is of great interest due to rarity of this species in the Pleistocene of Eastern Europe.

TIRR: a potential front runner in HDR race-hypotheses and perspectives.

The majority of CRISPR-Cas9 methods for mutations correction are oriented on gene editing through homologous recombination that is normally restrained by non-homologous end joining (NHEJ). A recently identified protein TIRR can bind a 53BP1 protein, a key effector of NHEJ, and inhibit its recruitment to double-strand break loci. Several studies elucidated the molecular mechanisms of TIRR-53BP1 binding and established bidirectional role of TIRR in 53BP1 functions and stability. It was proved that overexpression of TIRR promotes the double-strand break repair through homologous recombination. All findings, which were described in the review, allow assuming TIRR as a suitable target for enhancing efficacy of genome editing through homology directed repair.

Saber-Toothed Cats (Carnivora, Felidae, Machairodoninae) from the Lower Pleistocene of the Taurida Cave, Crimea.

This paper describes the maxillaries of adult specimens of saber-toothed cats Homotherium crenatidens (Fabrini, 1890) and Megantereon sp. from the Taurida Cave (Crimea, Late Villafranchian; age, 1.8-1.5 Ma). We discuss the morphometric variability in the morphology of the upper carnassials and the length of the С1-Р3 diastema.

[The Importance of the Type of Heart Circulation for the Prognosis of Pulmonary Embolism].

AIM: To study the distribution of the type of heart circulation (left- dominant, right- dominant, and mixed (balanced) in patients with pulmonary thromboembolism of fatal and non-fatal outcome. MATERIALS AND METHODS: More than 36,000 case histories, protocols and findings of post-mortem examinations of patients hospitalized in 2003-2012 were subjected to analysis. (ten year period). Statistical processing of the actual material was carried out using the SAS 9 and SPSS 21 software packages. The critical level of significance p for all used procedures of statistical analysis was assumed to be 0.05. Results of the study. The study included 893 cases of pulmonary embolism registered in the data of the case histories and materials of the pathoanatomical studies. Data on the type of heart circulation and a detailed description of the coronary artery atherosclerosis were present in 264 cases: in 171 patients with pulmonary embolism and fatal outcome, and in 93 patients with pulmonary embolism and non-fatal outcome. A clear predominance was found in the group with pulmonary embolism and non-fatal outcome of patients with the right type of heart circulation - 78.5% versus 7% in the group of people who died with pulmonary embolism (p<0.0001). Accordingly, persons with "non-right type of heart circulation" (left and balanced) predominantly prevailed among patients with pulmonary embolism and fatal outcome. At the same time, the dead with the right type of heart circulation in all cases had a stenosis of the right coronary artery (RCA) more than 60%. RCA dominance in the heart circulation with absence its significant stenosis creates more favorable hemodynamic conditions for survival in patients with pulmonary embolism. Owners of other types of organization of coronary blood flow ("non-right type of heart circulation") have a worse prognosis both in the absence of coronary atherosclerosis and, moreover, in its presence, especially in the case of significant atherosclerotic lesion of the RCA pool. At the same time, in patients with the right type of heart circulation and hemodynamically significant atherosclerosis RCA in conditions of pulmonary embolism the prognosis is also unfavorable. In view of the above, in patients with coronary atherosclerosis, timely restoration of blood flow in RCA (coronary artery stenting) is great importance in relation to the prognosis associated not only with coronary heart disease, but also with PE.

Occurrence of the Giant Deer of the Genus Arvernoceros in Taurida Cave, Crimea.

The giant deer Arvernocerosverestchagini David, 1992, authochtonous species of the Early Pleistocene biota of North Black Sea coastal area, is discovered in Crimea. The giant deer was a member of fossil fauna of vertebrates from the Pleistocene deposits of Taurida karst cave. According to biochronological data, this fauna is dated to 1.8-1.5 Ma.

The Taurida Cave, a New Locality of Early Pleistocene Vertebrates in Crimea.

We describe a vertebrate assemblage from the Pleistocene deposits of the Taurida karst cave discovered in 2018 in central Crimea (Zuya village, Belogorsk raion). The assemblage is correlated with Late Villafranchian faunas of the Eastern Mediterranean and has an approximate age of 1.8-1.5 Ma.

Zoon vulvitis - a rare form of chronic inflammation of the vulva.

OBJECTIVE: Description of finding out rare disease Zoon vullvitis. Desing: Case report and differential diagnosis. SETTING: Department of Obstetric and Gynecology, University Hospital Ostrava. CASE REPORT: Zoon vulvitis or plasma cell vulvitis (PCV) belongs to extremely rare and often misdiagnosed inflammatory disease of the vulva. Lesions may look like shiny, sharply bordered , erythematosus patches or macular lesions. Less than 50 cases have been reported. This article is devoted to clinical findings, differential diagnosis and treatment of PCV. We present one clinical case with typical clinical and histopathological manifestations. Risk of dysplasia exists and long-term follow-up is desirable.

First Finding of a Representative of Giant Mustelids of the Genus Eomellivora (Carnivora, Mustelidae) in Russia (Tuva, Upper Miocene).

In the late Miocene deposits in the Taralik-Cher locality (Tuva Republic), fossil remains of a giant mustelid of the genus Eomellivora Zdansky, 1924 have been found. This finding is the first reliable evidence of the Eomellivora inhabiting the modern Russia. Teeth of the Eomelliovra from Taralik-Cher are similar in size to those of E. wimani and E. piveteaui from the late Miocene in Eurasia. The morphology of teeth of the material from Tuva is most similar to that of E. ursogulo; therefore, it is considered a small form of Eomellivora ursogulo. The described finding expands the understanding of diversity, variability, and distribution of representatives of the genus Eomellivora in Asia during the late Miocene.