Ethnicity-specific BRCA1, BRCA2, PALB2, and ATM pathogenic alleles in breast and ovarian cancer patients from the North Caucasus.

BACKGROUND: Mountain areas of the North Caucasus host several large ethnic communities that have preserved their national identity over the centuries. METHODS: This study involved high-grade serous ovarian cancer (HGSOC) and breast cancer (BC) patients from Dagestan (HGSOC: 37; BC: 198), Kabardino-Balkaria (HGSOC: 68; BC: 155), North Ossetia (HGSOC: 51; BC: 104), Chechnya (HGSOC: 68; BC: 79), Ingushetia (HGSOC: 19; BC: 103), Karachay-Cherkessia (HGSOC: 13; BC: 47), and several Armenian settlements (HGSOC: 16; BC: 101). The group of BC patients was enriched by young-onset and/or family history-positive and/or bilateral and/or receptor triple-negative cases. The entire coding region of BRCA1, BRCA2, PALB2, and ATM genes was analyzed by next-generation sequencing. RESULTS: A significant contribution of BRCA1/2 pathogenic variants (PVs) to HGSOC and BC development was observed across all North Caucasus regions (HGSOC: 19-39%; BC: 6-13%). Founder alleles were identified in all ethnic groups studied, e.g., BRCA1 c.3629_3630delAG in Chechens, BRCA2 c.6341delC in North Ossetians, BRCA2 c.5351dupA in Ingush, and BRCA1 c.2907_2910delTAAA in Karachays. Some BRCA1/2 alleles, particularly BRCA2 c.9895C > T, were shared by several nationalities. ATM PVs were detected in 14 patients, with c.1673delG and c.8876_8879delACTG alleles occurring twice each. PALB2 heterozygosity was observed in 5 subjects, with one variant seen in 2 unrelated women. CONCLUSION: This study adds to the evidence for the global-wide contribution of BRCA1/2 genes to HGSOC and BC morbidity, although the spectrum of their PVs is a subject of ethnicity-specific variations. The data on founder BRCA1/2 alleles may be considered when adjusting the BRCA1/2 testing procedure to the ethnic origin of patients.

Forest genomics in the Caucasus through the lens of its dominant tree species - Fagus orientalis.

The last glacial period is known to have greatly influenced the demographic history of temperate forest trees, with important range contractions and post-glacial expansions that led to the formation of multiple genetic lineages and secondary contact zones in the Northern Hemisphere. These dynamics have been extensively studied for European and North American species but are still poorly understood in other temperate regions of rich biodiversity such as the Caucasus. Our study helps filling that gap by deciphering the genomic landscapes of F. orientalis across the South Caucasus. The use of genome-wide data confirmed a past demographic history strongly influenced by the Last Glacial Maximum, revealing two disjunct glacial refugia in the Colchis and Hyrcanian regions. The resulting patterns of genetic diversity, load and differentiation are not always concordant across the region, with genetic load pinpointing the location of the glacial refugia more efficiently than genetic diversity alone. The Hyrcanian forests show depleted genetic diversity and substantial isolation, even if long-distance gene flow is still present with the main centre of diversity in the Greater Caucasus. Finally, we characterize a strong heterogeneity of genetic diversity and differentiation along the species chromosomes, with noticeably a first chromosome showing low diversity and weak differentiation.

Active spread of ß-thalassemia beyond the thalassemia belt: A study on a Russian population.

ß-Thalassemia is a disease traditionally associated with thalassemia belt countries. Nonetheless, as global migration intensifies, ß-thalassemia-causing variants spread far from their origin. We investigated this process to detect some patterns underlying its course. We analyzed ß-thalassemia-causing variants and the origin of 676 unrelated participants in Moscow, the largest city of Russia, far away from the thalassemia belt. Our analyses revealed that modern Russia has one of the broadest spectra of thalassemia-causing variants: 46 different variants, including two novel ß0 variants. Only a small proportion of the reported pathogenic variants likely originated in the resident subpopulation. Almost half of the variants that supposedly had emerged outside the Russian borders have already been assimilated by (were found in) the resident subpopulation. The primary modern source of immigration transferring thalassemia to a nonthalassemic part of Russia is the Caucasus region. We also found traces of ancient migration flows from non-Caucasus countries. Our data indicate that ß-thalassemia-causing variants are actively spilling over into resident populations of countries outside thalassemia belt regions. Therefore, viewing thalassemia as a disease exclusive to specific ethnic groups creates a mind trap that can complicate the diagnosis.

Grey Zone Healers and the COVID-19 Pandemic in Chechnya, Russia.

The Chechen authorities' focus upon population health is enacted both through the principles of Islamic medicine and approved biomedical practices. Any healing practices beyond these domains are met with deep suspicion. Practitioners of unofficial complementary and alternative medicine healers may abruptly find themselves regarded as enemies of the state. In light of this precarious circumstance, it becomes pertinent to inquire: How do these healers employ their daily tactics to negotiate the intricate power dynamics between the formidable state apparatus and the established biomedical order? Drawing from our meticulous fieldwork conducted in the year 2021, we investigated the intricate tactics employed by unofficial healers in the Chechen medical landscape during COVID-19. Our research centred on discerning the nuanced tactics aimed at mitigating potential risks. We conclude that healers, having embodied tactics to creatively manoeuvre within the confines of the authoritarian state, perceived the challenges posed by COVID-19 as merely another, often inconsequential, obstacle in their enduring struggle.

Whole-genome analyses disentangle reticulate evolution of primroses in a biodiversity hotspot.

Biodiversity hotspots, such as the Caucasus mountains, provide unprecedented opportunities for understanding the evolutionary processes that shape species diversity and richness. Therefore, we investigated the evolution of Primula sect. Primula, a clade with a high degree of endemism in the Caucasus. We performed phylogenetic and network analyses of whole-genome resequencing data from the entire nuclear genome, the entire chloroplast genome, and the entire heterostyly supergene. The different characteristics of the genomic partitions and the resulting phylogenetic incongruences enabled us to disentangle evolutionary histories resulting from tokogenetic vs cladogenetic processes. We provide the first phylogeny inferred from the heterostyly supergene that includes all species of Primula sect. Primula. Our results identified recurrent admixture at deep nodes between lineages in the Caucasus as the cause of non-monophyly in Primula. Biogeographic analyses support the 'out-of-the-Caucasus' hypothesis, emphasizing the importance of this hotspot as a cradle for biodiversity. Our findings provide novel insights into causal processes of phylogenetic discordance, demonstrating that genome-wide analyses from partitions with contrasting genetic characteristics and broad geographic sampling are crucial for disentangling the diversification of species-rich clades in biodiversity hotspots.

Evolution of hygrophytic plant species in the Anatolia-Caucasus region: insights from phylogenomic analyses of Cardamine perennials.

BACKGROUND AND AIMS: Southwestern Asia is a significant centre of biodiversity and a cradle of diversification for many plant groups, especially xerophytic elements. In contrast, little is known about the evolution and diversification of its hygrophytic flora. To fill this gap, we focus on Cardamine (Brassicaceae) species that grow in wetlands over a wide altitudinal range. We aimed to elucidate their evolution, assess the extent of presumed historical gene flow between species, and draw inferences about intraspecific structure. METHODS: We applied the phylogenomic Hyb-Seq approach, ecological niche analyses and multivariate morphometrics to a total of 85 Cardamine populations from the target region of Anatolia-Caucasus, usually treated as four to six species, and supplemented them with close relatives from Europe. KEY RESULTS: Five diploids are recognized in the focus area, three of which occur in regions adjacent to the Black and/or Caspian Sea (C. penzesii, C. tenera, C. lazica), one species widely distributed from the Caucasus to Lebanon and Iran (C. uliginosa), and one western Anatolian entity (provisionally C. cf. uliginosa). Phylogenomic data suggest recent speciation during the Pleistocene, likely driven by both geographic separation (allopatry) and ecological divergence. With the exception of a single hybrid (allotetraploid) speciation event proven for C. wiedemanniana, an endemic of southern Turkey, no significant traces of past or present interspecific gene flow were observed. Genetic variation within the studied species is spatially structured, suggesting reduced gene flow due to geographic and ecological barriers, but also glacial survival in different refugia. CONCLUSIONS: This study highlights the importance of the refugial regions of the Black and Caspian Seas for both harbouring and generating hygrophytic species diversity in Southwestern Asia. It also supports the significance of evolutionary links between Anatolia and the Balkan Peninsula. Reticulation and polyploidization played a minor evolutionary role here in contrast to the European relatives.

Mining thermophiles for biotechnologically relevant enzymes: evaluating the potential of European and Caucasian hot springs.

The development of sustainable and environmentally friendly industrial processes is becoming very crucial and demanding for the rapid implementation of innovative bio-based technologies. Natural extreme environments harbor the potential for discovering and utilizing highly specific and efficient biocatalysts that are adapted to harsh conditions. This review focuses on extremophilic microorganisms and their enzymes (extremozymes) from various hot springs, shallow marine vents, and other geothermal habitats in Europe and the Caucasus region. These hot environments have been partially investigated and analyzed for microbial diversity and enzymology. Hotspots like Iceland, Italy, and the Azores harbor unique microorganisms, including bacteria and archaea. The latest results demonstrate a great potential for the discovery of new microbial species and unique enzymes that can be explored for the development of Circular Bioeconomy.Different screening approaches have been used to discover enzymes that are active at extremes of temperature (up 120 °C), pH (0.1 to 11), high salt concentration (up to 30%) as well as activity in the presence of solvents (up to 99%). The majority of published enzymes were revealed from bacterial or archaeal isolates by traditional activity-based screening techniques. However, the latest developments in molecular biology, bioinformatics, and genomics have revolutionized life science technologies. Post-genomic era has contributed to the discovery of millions of sequences coding for a huge number of biocatalysts. Both strategies, activity- and sequence-based screening approaches, are complementary and contribute to the discovery of unique enzymes that have not been extensively utilized so far.

An updated list of mosquito species in Armenia and Transcaucasian region responsible for Dirofilaria transmission: A review.

Canine dirofilariasis is a world-wide distributed mosquito-borne helminthiasis that has a potential zoonotic impact. This disease is a serious problem in Southern Caucasus region, including Armenia. Average extensity of Dirofilaria infection in canids in Armenia is 26.9%. At present, 77 mosquito species (Diptera: Culicidae) are presumed to have a role in the transmission of dirofilariasis. 80 species of Culicidae family mosquitoes are registered in Southern Caucasus Region, and 31 of them are described in Armenia. The following species of Culicidae can serve as vectors of Dirofilaria spp. in Armenia: Aedes vexans, Ae. caspius, Ae. albopictus, Ae. geniculatus, Culex pipiens, Cx. theileri, Cx. modestus, Anopheles maculipennis s.s., An. claviger, An. hyrcanus, An. superpictus, Coquillettidia richardi, Culiseta annulata and Uranotaenia unguiculta. We see a risk of transmission in active foci of dirofilariasis, as well as for human infection in Armenia. Comprehensive research should be conducted on detection of microfilariae in the target mosquito species and in target localities.

Synopsis of gastropod-associated nematodes of Ciscaucasia (Russian Federation) with the description of a new species of Pellioditis Dougherty, 1953 (syn. Phasmarhabditis Andrássy, 1976).

Caucasus is known as one of the few biodiversity hotspots in Europe and is characterised by rich gastropod fauna while the nematode fauna in association with gastropods has remained largely understudied. Surveys conducted in 2019 and 2021 in the North Caucasus of the Russian Federation (Stavropol Upland and western and central parts of Krasnodar Krai) has revealed the presence of three new species of Pellioditis, a facultative parasite of land gastropods, and two species of obligate parasites, the intestinal parasite Angiostoma kimmeriense and a new, still undescribed species of a larval ectoparasite Alloionema sp. The new associations of Cruznema sp. and Rhabditophanes sp. with land gastropods were recorded for the first time in the Russian Federation. The new species of Pellioditis Dougherty, 1953 described here is based on the analysis of morphology and molecular studies of two distant and morphologically distinct strains, thermalis and sindicae. Pellioditis thermalis n. sp. was characterised by females possessing a tail of about 95-100 µm long, broadly conical in shape in the thermalis and sindicae strains, with a rounded anterior part and a subulate terminal part as long as the former; prominent phasmids located at the mid-tail, equatorial vulva position, a lateral field of three ridges (four incisions), males with spicules featuring a hole at the distal tip, ensheathed infective juveniles with average length 717 µm in the thermals strain and 771 µm in the sindicae strain, and exsheathed ones 644 µm and 682 µm, respectively. ITS-based phylogenetic analyses revealed that all Pellioditis species found in Ciscaucasia and Transcaucasia probably belong to two separate clades, with independent evolutionary histories of colonisation of this area. The entire Caucasus range area appears to serve as a biodiversity hotspot for the genus Pellioditis, presumably due to its complicated geological history and repeated isolation events for its terrestrial mollusc hosts.

The state of the population of narrow-clawed crayfish in Lake Sevan (Armenia) under multiple stress conditions.

The narrow-clawed crayfish is a crayfish species that was accidentally introduced into the ecosystem of Lake Sevan in the 1980s. Soon it became one of the most preferred fisheries in the lake and an important link in the food chain by successfully replacing the endemic fish subspecies Sevan khramicarp (Capoeta sevangi, De Filippi, 1865) in the chain of detritivores. However, recently, the stock declines dramatically, associated with two main threats: the impact of burn-spot disease and an increase in fishing pressure on its population. To estimate the state of population under multiple stress conditions, we investigated the dynamics of stock, the size/age and sex structure, the fecundity, and the health status of the population. A comparative analysis of oxidative stress biomarkers (superoxide dismutase, catalase, glutathione-S-transferase activities and reduced glutathione, thiobarbituric acid reactive substance contents) showed significant differences between healthy and infected individuals. Another indirect effect of the disease, which probably leads to a decrease in the stock, was an increase in the proportion of immature females. Also, we observed some decrease in the infection rate along with the decline in the density of crayfish. However, stock reduction and some changes in the population may also be caused by a strong bloom of cyanobacteria.

Evidence of an additional centre of apple domestication in Iran, with contributions from the Caucasian crab apple Malus orientalis Uglitzk. to the cultivated apple gene pool.

Divergence processes in crop-wild fruit tree complexes in pivotal regions for plant domestication such as the Caucasus and Iran remain little studied. We investigated anthropogenic and natural divergence processes in apples in these regions using 26 microsatellite markers amplified in 550 wild and cultivated samples. We found two genetically distinct cultivated populations in Iran that are differentiated from Malus domestica, the standard cultivated apple worldwide. Coalescent-based inferences showed that these two cultivated populations originated from specific domestication events of Malus orientalis in Iran. We found evidence of substantial wild-crop and crop-crop gene flow in the Caucasus and Iran, as has been described in apple in Europe. In addition, we identified seven genetically differentiated populations of wild apple (M. orientalis), not introgressed by the cultivated apple. Niche modelling combined with genetic diversity estimates indicated that these wild populations likely resulted from range changes during past glaciations. This study identifies Iran as a key region in the domestication of apple and M. orientalis as an additional contributor to the cultivated apple gene pool. Domestication of the apple tree therefore involved multiple origins of domestication in different geographic locations and substantial crop-wild hybridization, as found in other fruit trees. This study also highlights the impact of climate change on the natural divergence of a wild fruit tree and provides a starting point for apple conservation and breeding programmes in the Caucasus and Iran.

Zoogeographic significance of Dmanisi large mammal assemblage.

We undertake a comparative mammalian zoogeographic analysis with the aim of revealing the extent to which the Dmanisi Early Pleistocene large mammal assemblage resembles, at the genus level, African, Arabian, and Eurasian localities of similar age. The inclusion of Old World Pliocene and Pleistocene mammalian faunas provides us with insights into the provincial origins of specific mammalian taxa and permits us to assess the relative affiliation of the Dmanisi mammalian faunas to other faunas in the Old World. Our analysis also allows us to consider hypotheses about the timing and direction of zoogeographic connections between western Eurasia and Africa during the Early Pleistocene. We utilize multiple zoogeographic analytical tools as a cross-comparison of Dmanisi with 42 other Eurasian and African mammalian-bearing localities between 2.7 and 0.7 Ma. Overall, we find that Dmanisi compares most closely with a subgroup of Greek, Italian, and Spanish localities that are slightly younger than Dmanisi itself. This could suggest a progressive dispersal from East to West of the large mammal communities during the late Early Pleistocene and the first occurrence at Dmanisi, and then later in Western Europe, of some taxa such as Stephanorhinus ex gr. etruscus-hundsheimensis, Equus altidens, Bison georgicus, Soergelia minor, Megantereon whitei, Canis borjgali, Canis (Xenocyon) lycaonoides. Dmanisi's habitats included drier areas, probably of open wooded savannah and grassland and by mountainous to semiarid rocky terrain. There is evidence that Dmanisi records short intervals of increased aridity in the middle part of the succession contemporaneous with the occurrence of Homo.

Small mammals (Insectivora, Rodentia, Lagomorpha) from the Early Pleistocene hominin-bearing site of Dmanisi (Georgia).

Small mammals (insectivores, rodents, and lagomorphs) from Dmanisi are here reviewed for the first time and used as a tool for paleoenvironmental proxies. The small mammal faunal list is composed of shrews (Beremendia fissidens, cf. Beremendia minor, Crocidura kornfeldi), hamsters (Cricetulus sp., Allocricetus bursae), gerbils (Parameriones aff. obeidiyensis), murids (Apodemus cf. atavus), arvicolids (Mimomys pliocaenicus, Mimomys aff. pusillus), and pikas (Ochotona sp.). A paleoenvironmental reconstruction based on the habitat weighting method has been applied to the rodent assemblage. According to this method, the most common elements indicate an open-dry habitat (36.5%), followed by water edge (25.7%) and rocky (21.0%) elements. Open-wet (15.5%) and woodland elements (1.3%) are rare. Therefore, the habitat occupied by the hominids of Dmanisi was characterized by the prevalence of arid conditions, from steppe or semi-desert to open Mediterranean forest, with stony or rocky substrate and bushy areas. The presence of permanent aquatic environments is also documented. From a biogeographic point of view, the small mammal community from Dmanisi is composed mainly by Western or Central Asian elements, with a poor representation of European elements (Mimomys, Apodemus). It is concluded that Dmanisi hominins most possibly had ecological requirements which were different from those of the Early Pleistocene hominins from Western Europe, which settled on wetter habitats. It could be also possible that Dmanisi hominins entered Southern Caucasus at an interglacial phase before the deposition of the Dmanisi site.

Early Pleistocene stratigraphy, sedimentary environments, and formation contexts at Dmanisi in the Georgian Caucasus.

The Early Pleistocene site of Dmanisi is now well known for its large number of fossils of early Homo erectus as well as associated artifacts and faunal remains, recovered mainly in pipe-related geologic features. Testing in the M5 unit 100 m to the west of the main excavations revealed a thick stratigraphy with no evidence of pipes or gullies, indicating that the geologic record at Dmanisi included spatially distinct sedimentary environments that needed further investigation. Here we report the results of a geoarchaeological program to collect data bearing on contexts and formation processes over a large area of the promontory. That work has defined over 40,000 m2 of in situ deposits with artifacts and faunas. Stratum A ashes bury the uppermost Mashavera Basalt, which we have dated to 1.8 Ma in the M5 block. The Stratum A deposits contain stratified occupations that accumulated quickly and offer good potential for recovery of in situ materials. Stratum B1 deposits above the A/B unconformity include all of the pipe and gully facies at Dmanisi, reflecting a brief but very intense phase of geomorphic change. Those deposits contain the majority of faunas and all of the hominin fossils. B1 slope facies offer excellent formation contexts away from the piped area, and all B1 deposits are sealed by Stratum B2 over the whole promontory. Strata B2 to B5 register a return to slope facies, with no further evidence of pipes or gullies. Those deposits also present excellent contexts for recovery of in situ occupations. Overall, Dmanisi's geologic history preserves an exceptional record of the activities and environmental context of occupations during the first colonization of Eurasia.

Yersinia pestis strains isolated in natural plague foci of Caucasus and Transcaucasia in the context of the global evolution of species.

BACKGROUND: Plague is a highly dangerous vector-borne infectious disease that has left a significant mark on history of humankind. There are 13 natural plague foci in the Caucasus, located on the territory of the Russian Federation, Azerbaijan, Armenia and Georgia. We performed whole-genome sequencing of Y. pestis strains, isolated in the natural foci of the Caucasus and Transcaucasia. Using the data of whole-genome SNP analysis and Bayesian phylogeny methods, we carried out an evolutionary-phylogeographic analysis of modern population of the plague pathogen in order to determine the phylogenetic relationships of Y. pestis strains from the Caucasus with the strains from other countries. RESULTS: We used 345 Y. pestis genomes to construct a global evolutionary phylogenetic reconstruction of species based on whole-genome SNP analysis. The genomes of 16 isolates were sequenced in this study, the remaining 329 genomes were obtained from the GenBank database. Analysis of the core genome revealed 3315 SNPs that allow differentiation of strains. The evolutionary phylogeographic analysis showed that the studied Y. pestis strains belong to the genetic lineages 0.PE2, 2.MED0, and 2.MED1. It was shown that the Y. pestis strains isolated on the territory of the East Caucasian high-mountain, the Transcaucasian high-mountain and the Priaraksinsky low-mountain plague foci belong to the most ancient of all existing genetic lineages - 0.PE2. CONCLUSIONS: On the basis of the whole-genome SNP analysis of 345 Y. pestis strains, we describe the modern population structure of the plague pathogen and specify the place of the strains isolated in the natural foci of the Caucasus and Transcaucasia in the structure of the global population of Y. pestis. As a result of the retrospective evolutionary-phylogeographic analysis of the current population of the pathogen, we determined the probable time frame of the divergence of the genetic lineages of Y. pestis, as well as suggested the possible paths of the historical spread of the plague pathogen.

The dynamics of phytoplankton seasonal development and its horizontal distribution in Lake Sevan (Armenia).

High-altitude freshwater lakes are experiencing ever-increasing risk of harmful algal blooms (HABs) on the face of climate change and a growing demand on agricultural production. The biggest alpine lake of the Caucasus, Lake Sevan, has "blooming" recently almost every year. Thus, the study of phytoplankton community' development patterns in Lake Sevan is gaining urgency. The aim of the work has been the study of the seasonal dynamics of quantitative and qualitative characteristics of phytoplankton in Lake Sevan. Also, we have tried to determine the features of horizontal distribution of phytoplankton within different seasons with the focus on Cyanobacteria distribution to identify current spatial-temporal features of HABs in Lake Sevan. Seasonal ground data collected from the photic zone of 178 stations in 2016-2018 was analysed and spatially interpolated. The results of analysis of seasonal dynamics of phytoplankton groups abundance have revealed the increased role of Cyanobacteria in the algal "blooms". Particularly, HABs were led by the dominant species of the genus Dolichospermum/Anabaena that are potentially toxic. Univariate analysis of variance with the post hoc Tukey test has proved the significance of changes in the quantitative parameters of phytoplankton development within years with the peak in 2018. Some antagonistic relations between the groups of phytoplankton under the HAB events were also shown through factorial and correlation analysis. Spatial interpolations revealed very limited extents of HABs compared with "blooms" led by Bacillariophyta species. HABs were mainly occurring in the littoral zone in a close proximity to the estuaries of Lake Sevan major tributaries.

Genetic Diversity of Species of Microtus Generic Group (Arvicolinae, Rodentia): New Data from the Greater Caucasus.

Using the cytochrome b gene (1143 bp), species identification and the phylogenetic analysis of voles of the generic group Microtus from the eastern part of the Greater Caucasus, including the Ismayilli, Khizi, and Balakan Districts of Azerbaijan, have been carried out. Three species, the Major's pine vole (M. majori), the social vole (M. socialis), and the common vole (M. arvalis form obscurus), have been identified, and five new haplotypes have been described for them. Genetic analysis with the inclusion of the new data showed that for each of the species, the physiographic conditions of the Greater Caucasus played a certain role (isolation, migration route or refugium) during the formation of the modern genetic structure. The obtained results indicate that any new data from the Caucasus could be of critical importance for the reconstruction of the evolutionary history of the modern biodiversity both within the region itself and in adjacent territories.

[Analysis of the provision of medical personnel in the subjects of the North Caucasus Federal District].

The article presents the results of a comparative analysis of the provision of medical personnel. Differences in the indicators of provision with specialists of various profiles have been studied. It is noted that in the North Caucasian Federal District the total values ​​of the medical service density indicator are lower than in the Russian Federation by 2.1%. The highest rates of provision with doctors are registered in the republics of Ingushetia with an increase of 32%, and in the republic of North Ossetia. Higher values ​​of the provision indicator with the heads of the organization and their deputies were established in the North Caucasus Federal District than in the Russian Federation. At the same time, in most subjects of the North Caucasus Federal District there is a shortage of specialists in the following specialties: anesthesiologists-resuscitators, pediatric surgeons, neonatologists, pediatricians, psychiatrists, radiologists, epidemiologists. However, the indicator of provision with dentists in the North Caucasus Federal District exceeded the Russian one by 2 times. Based on the analysis, the authors present recommendations, including the need to eliminate the shortage of doctors in a number of specialties, increase the admission to residency in them, strengthen social support measures, temporarily restrict the admission of applicants in the specialty of dentistry, etc.

A revised AMS and tephra chronology for the Late Middle to Early Upper Paleolithic occupations of Ortvale Klde, Republic of Georgia.

The nature and timing of the shift from the Late Middle Paleolithic (LMP) to the Early Upper Paleolithic (EUP) varied geographically, temporally, and substantively across the Near East and Eurasia; however, the result of this process was the archaeological disappearance of Middle Paleolithic technologies across the length and breadth of their geographic distribution. Ortvale Klde rockshelter (Republic of Georgia) contains the most detailed LMP-EUP archaeological sequence in the Caucasus, an environmentally and topographically diverse region situated between southwest Asia and Europe. Tephrochronological investigations at the site reveal volcanic ash (tephra) from various volcanic sources and provide a tephrostratigraphy for the site that will facilitate future correlations in the region. We correlate one of the cryptotephra layers to the large, caldera-forming Nemrut Formation eruption (30,000 years ago) from Nemrut volcano in Turkey. We integrate this tephrochronological constraint with new radiocarbon dates and published ages in an OxCal Bayesian age model to produce a revised chronology for the site. This model increases the ages for the end of the LMP (∼47.5-44.2 ka cal BP) and appearance of the EUP (∼46.7-43.6 ka cal BP) at Ortvale Klde, which are earlier than those currently reported for other sites in the Caucasus but similar to estimates for specific sites in southwest Asia and eastern Europe. These data, coupled with archaeological, stratigraphic, and taphonomic observations, suggest that at Ortvale Klde, (1) the appearance of EUP technologies of bone and stone has no technological roots in the preceding LMP, (2) a LMP population vacuum likely preceded the appearance of these EUP technologies, and (3) the systematic combination of tephra correlations and absolute dating chronologies promises to substantially improve our inter-regional understanding of this critical time interval of human evolution and the potential interconnectedness of hominins at different sites.

Reducing persecution is more effective for restoring large carnivores than restoring their prey.

Large carnivores are currently disappearing from many world regions because of habitat loss, prey depletion, and persecution. Ensuring large carnivore persistence requires safeguarding and sometimes facilitating the expansion of their populations. Understanding which conservation strategies, such as reducing persecution or restoring prey, are most effective to help carnivores to reclaim their former ranges is therefore important. Here, we systematically explored such alternative strategies for the endangered Persian leopard (Panthera pardus saxicolor) in the Caucasus. We combined a rule-based habitat suitability map and a spatially explicit leopard population model to identify potential leopard subpopulations (i.e., breeding patches), and to test the effect of different levels of persecution reduction and prey restoration on leopard population viability across the entire Caucasus ecoregion and northern Iran (about 737,000 km2 ). We identified substantial areas of potentially suitable leopard habitat (~120,000 km2 ), most of which is currently unoccupied. Our model revealed that leopards could potentially recolonize these patches and increase to a population of >1,000 individuals in 100 yr, but only in scenarios of medium to high persecution reduction and prey restoration. Overall, reducing persecution had a more pronounced effect on leopard metapopulation viability than prey restoration: Without conservation strategies to reduce persecution, leopards went extinct from the Caucasus in all scenarios tested. Our study highlights the importance of persecution reduction in small populations, which should hence be prioritized when resources for conservation are limited. We show how individual-based, spatially explicit metapopulation models can help in quantifying the recolonization potential of large carnivores in unoccupied habitat, designing adequate conservation strategies to foster such recolonizations, and anticipating the long-term prospects of carnivore populations under alternative scenarios. Our study also outlines how data scarcity, which is typical for threatened range-expanding species, can be overcome with a rule-based habitat map. For Persian leopards, our projections clearly suggest that there is a large potential for a viable metapopulation in the Caucasus, but only if major conservation actions are taken towards reducing persecution and restoring prey.