New Case of Spinocerebellar Ataxia, Autosomal Recessive 4, Due to VPS13D 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 VPS13D gene, part of the VPS13 family, has emerged as a crucial player in neurological pathology, implicated in diverse phenotypes ranging from movement disorders to Leigh syndrome. We present a clinical case of VPS13D-associated disease with two variants in the VPS13D gene in an adult female. This case contributes to our evolving understanding of VPS13D-related diseases and underscores the importance of genetic screening in diagnosing and managing such conditions.

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. We designed an algorithm for fiber sensor signal processing, applied a testing kit, and designed a method for the quantitative evaluation of our obtained results. We also proposed a new setup model for lab tests of φ-OTDR single coordinate sensors, which allows for the quick variation of their parameters. As a result, it was possible to define requirements for the best quality of speech recognition; estimation using the percentage of recognized words yielded a value of 96.3%, and estimation with Levenshtein distance provided a value of 15.

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 Ixodes ricinus 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.

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. The iPSC line may provide a model for development of a personalized treatment including genome editing and drug screening, may be used for disease modelling, cell differentiation and pharmacological investigations. .

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. This iPSC line may be used for development of a personalized treatment including genome editing, disease modelling, cell differentiation and organoid formation, pharmacological investigations and drug screening.

New geographical and host records of bat fleas (Siphonaptera: Ischnopsyllidae) in Russia.

To better understand the distribution and host-parasite relationships, we explored 12 large regions of Russia and recorded new bat fleas (Insecta: Siphonaptera: Ischnopsyllidae) for Dagestan, Bashkiria, Mordovia, Khakassia and Buryatia Republics. Also we curate previously known data and registered new host-parasite associations for species belonging to genus Ischnopsyllus (Ischnopsyllus octactenus and I. variabilis ex Pipistrellus pygmaeus, I. intermedius ex Hypsugo savii, I. variabilis ex Myotis dasycneme, I. hexactenus ex Murina hilgendorfi) and species Myodopsylla trisellis. One of the associations we recorded in Altai republic is particularly interesting (Myodopsylla trisellis ­ Myotis blythii). Further investigation is required to study vector role of bat fleas and the effects of flea parasitism on their natural hosts.

A review of mites and ticks parasitizing rock lizards (Lacertidae: Darevskia).

Rock lizards of the genus Darevskia are interesting research models due to their asexual reproduction. Ectoparasitic mites and ticks of these lizards are poorly known, despite some of these chelicerates being vector pathogens of humans and wildlife. Here we document and curate previously known data on ectoparasitic Acari of rock lizards and, based on our extensive survey, provide an annotated list of these ectoparasitic arthropods (six tick species, one macronyssid species, and seven chigger species). We also provide new host records (Ixodes ricinus on Darevskia caucasica, D. dryada, D. mixta, and D. szczerbaki; Haemaphysalis sulcata on D. rudis; Odontacarus saxicolis on D. brauneri); and new geographical records (O. saxicolis in Russia and Georgia).

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. A key for the identification of the species of Spinturnix von Heyden, 1826 found in Kazakhstan is provided.

New findings of spinturnicid mites (Mesostigmata: Gamasina: Spinturnicidae) from the Caucasus.

The Caucasus is a large region in Eurasia consisting of four countries: Russia, Georgia, Azerbaijan, and Armenia. Although it is one of the biodiversity hotspots in the world, the bat ectoparasite fauna has been poorly studied. To promotionally fill in the gaps regarding bat ectoparasites, we conducted five field surveys on bats and their ectoparasites at nine localities within the region between April 2016 and March 2021. Eight species and subspecies of spinturnicid mites were recorded over the surveys: Eyndhovenia euryalis oudemansi, Spinturnix acuminata acuminata, S. emarginata, S. myoti, S. nobleti, S. plecotina, S. psi, and S. punctata. Among them, three species, Spinturnix emarginata, S. nobleti and S. punctate, are newly recorded from the Caucasus region, and one each of subspecies and species, Eyndhovenia euryalis oudemansi and S. plecotina, are newly recorded from Georgia. In addition, Myotis tschuliensis was recorded as a new host species of S. myoti.

New records of bat flies (Diptera: Nycteribiidae), with an updated checklist of the nycteribiids of Russia.

We assembled a checklist by documenting and curating previously published data as well as previously unpublished records of bat flies from the Russian Federation. A total of 20 bat fly species are listed, belonging to 4 genera. Basilia mongolensis nudior Hurka, 1972 and Basilia nattereri (Kolenati, 1857) are recorded from Russia for the first time. The following new host associations are reported: Basilia mongolensis nudior ex Myotis nattereri (Kuhl), Basilia nattereri ex Eptesicus nilssonii (Keyserling Blasius), Basilia rybini Hurka, 1969 ex Myotis dasycneme (Boie) and Eptesicus nilssonii, and Nycteribia quasiocellata Theodor, 1966 ex Vespertilio murinus Linnaeus. We provide data on nine major Russian regions for which nycteribiid records were previously lacking.

First record of Eyndhovenia (Mesostigmata: Gamasina: Spinturnicidae) from Vietnam.

Eyndhovenia is one of the twelve genera of Spinturnicidae which are highly specialised parasites of bats. Previously known hosts of this genus comprised 17 species of Old World bats: Eptesicus serotinus, Hipposideros larvatus, Miniopterus schreibersi, Myotis blythi, M. emarginatus, Pipistrellus pipistrellus, P. gaisleri, Rhinolophus axillaris, R. blasii, R. clivosus, R. cornutus, R. euryale, R. ferrumequinum, R. hipposideros, R. megachyllus, R. mehelyi, R. rouxi. Within Asia, Eyndhovenia was only recorded from two countries, China and Thailand. Between 2018 and 2020, we conducted a series of bats surveys and recorded of this genus from intermediate horseshoe bat, Rhinolophus affinis, in Vietnam. The present study exhibits the new record in both parasitological and geographical aspects.

The first finding of parasitic mite, Parasteatonyssus nyctinomi (Mesostigmata: Gamasina: Macronyssidae), in Namibia.

Sixty-four individuals of a macronyssid mite, Parasteatonyssus nyctinomi (Zumpt, Patterson 1951), were identified from Egyptian free-tailed bats Tadarida aegyptiaca (É. Geoffroy 1818) (Chiroptera: Molossidae) captured in the Kunene region of Namibia (southern Africa). This is the first report on P. nyctinomi in the country.

Conservation genetics of the pond bat (Myotis dasycneme) with special focus on the populations in northwestern Germany and in Jutland, Denmark.

Conservation genetics is important in the management of endangered species, helping to understand their connectivity and long-term viability, thus identifying populations of importance for conservation. The pond bat (Myotis dasycneme) is a rare species classified as "Near Threatened" with a wide but patchy Palearctic distribution. A total of 277 samples representing populations in Denmark, Germany, Latvia, Hungary, and Russia were used in the genetic analyses; 224 samples representing Denmark, Germany, and Russia were analyzed at 10 microsatellite loci; 241 samples representing all areas were analyzed using mitochondrial D-loop and cytochrome B sequences. A Bayesian clustering approach revealed two poorly resolved clusters, one representing the Danish and German groups and the other the Russian group. However, significantly different pairwise F ST and D EST estimates were observed between the Danish and German groups and between the Danish and Russian groups suggesting a recent population structure. These conflicting results might be attributed to the effect of migration or low resolution due to the number of microsatellite markers used. After concatenating the two mitochondrial sequences, analysis detected significant genetic differentiation between all populations, probably due to genetic drift combined with a founder event. The phylogenetic tree suggested a closer relationship between the Russian and Northern European populations compared to the Hungarian population, implying that the latter belongs to an older ancestral population. This was supported by the observed haplotype network and higher nucleotide diversity in this population. The genetic structuring observed in the Danish/German pond bat stresses the need for a cross-border management between the two countries. Further, the pronounced mtDNA structuring, together with the indicated migration between nearby populations suggest philopatric female behavior but male migration, emphasizes the importance of protecting suitable habitat mosaics to maintain a continuum of patches with dense pond bat populations across the species' distribution range.

Severe toxicity in adult patients with lung cancer under treatment with pemetrexed: a prospective cohort study.

Pemetrexed is an antimetabolite approved for treatment of non-small cell lung cancer. Harbouring interindividual variability in both the pharmacokinetic and pharmacogenetic profiles may lead to life-threatening toxicities. A prospective cohort study of adult patients initiating treatment with pemetrexed in combination with platinum between 2013 and 2015 were follow up. Primary exposure were the methylenetetrahydrofolate reductase (MTHFR) single base polymorphisms in exon 4 and 7 and 5'-UTR- thymidylate synthase (TYMS) VNTR genotypes, in addition to baseline clinical and demographic variables. We used a Cox regression model to evaluate patient's survival and toxicity experience and its association with both baseline characteristics, and a-priori determined genetic polymorphisms. Seventy two patients were included, 52.7% developed severe hematologic toxicity during follow-up. None of the tested genotypes were significantly associated with the main outcome on multivariate analysis, nor other basal clinical variables. Overall survival between patients experiencing the outcome was not different from those without it, but hospital admissions were more frequent. MTHFR and 5'-UTR-TYMS genotypes were not useful for predicting high grade toxicity events in patients under treatment with pemetrexed.

Genomics and Biochemistry of Metabolic Pathways for the C1 Compounds Utilization in Colorless Sulfur Bacterium Beggiatoa leptomitoformis D-402.

The metabolic pathways of one-carbon compounds utilized by colorless sulfur bacterium Beggiatoa leptomitoformis D-402 were revealed based on comprehensive analysis of its genomic organization, together with physiological, biochemical and molecular biological approaches. Strain D-402 was capable of aerobic methylotrophic growth with methanol as a sole source of carbon and energy and was not capable of methanotrophic growth because of the absence of genes of methane monooxygenases. It was established that methanol can be oxidized to CO2 in three consecutive stages. On the first stage methanol was oxidized to formaldehyde by the two PQQ (pyrroloquinolinequinone)-dependent methanol dehydrogenases (MDH): XoxF and Mdh2. Formaldehyde was further oxidized to formate via the tetrahydromethanopterin (H4MPT) pathway. And on the third stage formate was converted to CO2 by NAD+-dependent formate dehydrogenase Fdh2. Finally, it was established that endogenous CO2, formed as a result of methanol oxidation, was subsequently assimilated for anabolism through the Calvin-Benson-Bassham cycle. The similar way of one-carbon compounds utilization also exists in representatives of another freshwater Beggiatoa species-B. alba.

[Timely diagnosis of disseminated paracoccidioidomycosis in an immunocompetent adult]. / Diagnóstico oportuno de paracoccidioidomicosis diseminada en un adulto inmunocompetente.

Paracoccidioidomycosis is endemic in subtropical rainforests of Latin America. Acute/subacute presentations involve an aggressive dissemination throughout the lymphatic system, while chronic forms (more frequent) arise as differential diagnosis for other conditions involving lung, oropharynx, skin, and eventually the brain. We present the case of a man referred for evaluation and treatment of a possible lung tumor with brain metastasis. The finding of multibudded yeasts and the microbiological isolation of a dimorphic fungus identified as Paracoccidioides sp. from a brain biopsy prompted a cardinal change in prognosis and treatment. This case alerts on the importance of considering systemic fungal diseases as differential diagnosis of compatible clinical presentations in patients who had lived in, or visited, endemic areas.

Clinical and genetic factors influencing acenocoumarol dosing: a cross-sectional study.

: Coumadin oral anticoagulants are widely used in multiple clinical scenarios. Their narrow therapeutic range and a dosing strategy based on 'a posteriori' algorithms, pose them as an interesting group for prediction modelling research. Extensive literature explaining the association between clinical and genetic variables with the dose of warfarin have been published. Limited information exists regarding these factors and acenocoumarol dosing. The aim of the study is to explain through clinical/genetic variables, the weekly dose of acenocoumarol necessary for achieving stable anticoagulation status. We performed a cross-sectional study enrolling adults under treatment with acenocoumarol with at least three consecutive INRs between 2 and 3. To explain the association between demographic, clinical and genotype data (VKORC1, CYP2C9 and CYP4F2) and the mean weekly dose of acenocoumarol, we performed a multiple linear regression model. In our cohort, a higher age, the presence of atrial fibrillation, chronic renal failure and VKORC1 haplotype A were associated with a lower mean weekly dose of acenocoumarol. On the other side, a higher weight was associated with a higher weekly dose. Amongst anticoagulated adult patients, VKORC1 genotype and baseline clinical factors can explain acenocoumarol dosing, and therefore, help clinicians while deciding the initial anticoagulant dose.

Complete Genome Sequence of the Freshwater Bacterium Beggiatoa leptomitoformis Strain D-401.

Here, we report the complete closed genome sequence and methylome analysis of Beggiatoa leptomitoformis strain D-401 (DSM 14945, UNIQEMU 779), which is quite different from the previously described Beggiatoa leptomitoformis neotype strain D-402T (DSM 14946, UNIQEM U 779) with regard to morphology and lithotrophic growth in the presence of thiosulfate.