Understanding the Influence of Host Radiation on Symbiont Speciation through Parasites of Species Flocks.

(Adaptive) radiations have attracted evolutionary biologists for a long time as ideal model systems to study patterns and processes of often rapid speciation. However, whereas a wealth of (sometimes already genome-scale) data is available for host radiations, very few studies target the patterns of diversification in their symbionts, even though they would be excellent models to study symbiont speciation. Our review summarizes what little is known about general patterns of symbiont diversification in often iconic adaptive host radiations and to what extent these patterns are dependent on the evolutionary trajectories of their hosts. We identify research gaps that need to be addressed in the future and discuss the potential of approaches not yet typically used in these study systems, such as epidemiological disease modeling and new omics technologies, for significantly advancing our understanding of these complex eco-evolutionary relationships.

One-carbon metabolism nutrients impact the interplay between DNA methylation and gene expression in liver, enhancing protein synthesis in Atlantic salmon.

Supplementation of one-carbon (1C) metabolism micronutrients, which include B-vitamins and methionine, is essential for the healthy growth and development of Atlantic salmon (Salmo salar). However, the recent shift towards non-fish meal diets in salmon aquaculture has led to the need for reassessments of recommended micronutrient levels. Despite the importance of 1C metabolism in growth performance and various cellular regulations, the molecular mechanisms affected by these dietary alterations are less understood. To investigate the molecular effect of 1C nutrients, we analysed gene expression and DNA methylation using two types of omics data: RNA sequencing (RNA-seq) and reduced-representation bisulphite sequencing (RRBS). We collected liver samples at the end of a feeding trial that lasted 220 days through the smoltification stage, where fish were fed three different levels of four key 1C nutrients: methionine, vitamin B6, B9, and B12. Our results indicate that the dosage of 1C nutrients significantly impacts genetic and epigenetic regulations in the liver of Atlantic salmon, particularly in biological pathways related to protein synthesis. The interplay between DNA methylation and gene expression in these pathways may play an important role in the mechanisms underlying growth performance affected by 1C metabolism.

Unravelling the temporal and spatial variation of fungal phylotypes from embryo to adult stages in Atlantic salmon.

Early microbial colonization has a profound impact on host physiology during different stages of ontogeny. Although several studies have focused on early bacterial colonization and succession, the composition and role of fungal communities are poorly known in fish. Here, we sequenced the internal transcribed spacer 2 (ITS2) region of fungi to profile the mycobiome associated with the eggs, hatchlings and intestine of Atlantic salmon at various freshwater and marine stages. In most of the stages studied, fungal diversity was lower than bacterial diversity. There were several stage-specific fungal phylotypes belonging to different stages of ontogeny but some groups, such as Candida tropicalis, Saccharomyces cerevisiae, Alternaria metachromatica, Davidiella tassiana and Humicola nigrescens, persisted during successive stages of ontogeny. We observed significant changes in the intestinal fungal communities during the first feeding. Prior to first feeding, Humicola nigrescens dominated, but Saccharomyces cerevisiae (10 weeks post hatch) and Candida tropicalis (12 weeks post hatch) became dominant subsequently. Seawater transfer resulted in a decrease in alpha diversity and an increase in Candida tropicalis abundance. We also observed notable variations in beta diversity and composition between the different farms. Overall, the present study sheds light on the fungal communities of Atlantic salmon from early ontogeny to adulthood. These novel findings will also be useful in future studies investigating host-microbiota interactions in the context of developing better nutritional and health management strategies for Atlantic salmon farming.

Exploring the Effects of Acute Stress Exposure on Lumpfish Plasma and Liver Biomarkers.

This study aimed to expand knowledge on lumpfish stress physiology by investigating the effects of acute stress on primary (i.e., cortisol) and secondary (e.g., metabolites) stress responses, as well as oxidative stress biomarkers, from stress exposure to a recovery phase. The results showed that the lumpfish physiological response to 1 min air exposure is mild, in line with recent studies, and comparable to that described for white sturgeons. Cortisol seems to be the most reliable acute stress biomarker in lumpfish, with a significant increase in plasma 30 min after stress exposure, returning to resting levels 2 h after exposure. In contrast, glucose and lactate were not significantly altered by short-term air exposure. Effects on hepatic energy mobilisation were also detected following the acute stress. This study showed that acute 1 min air exposure seems tolerable, allowing a swift recovery. However, more studies on the impacts of air exposure and repeated acute stressors on lumpfish stress and immune responses are required to develop industry standards for lumpfish health and welfare monitoring.

DNA hydroxymethylation differences underlie phenotypic divergence of somatic growth in Nile tilapia reared in common garden.

Phenotypic plasticity of metabolism and growth are essential for adaptation to new environmental conditions, such as those experienced during domestication. Epigenetic regulation plays a key role in this process but the underlying mechanisms are poorly understood, especially in the case of hydroxymethylation. Using reduced representation 5-hydroxymethylcytosine profiling, we compared the liver hydroxymethylomes in full-sib Nile tilapia with distinct growth rates (3.8-fold difference) and demonstrated that DNA hydroxymethylation is strongly associated with phenotypic divergence of somatic growth during the early stages of domestication. The 2677 differentially hydroxymethylated cytosines between fast- and slow-growing fish were enriched within gene bodies (79%), indicating a pertinent role in transcriptional regulation. Moreover, they were found in genes involved in biological processes related to skeletal system and muscle structure development, and there was a positive association between somatic growth and 5hmC levels in genes coding for growth factors, kinases and receptors linked to myogenesis. Single nucleotide polymorphism analysis revealed no genetic differentiation between fast- and slow-growing fish. In addition to unveiling a new link between DNA hydroxymethylation and epigenetic regulation of growth in fish during the initial stages of domestication, this study suggests that epimarkers may be applied in selective breeding programmes for superior phenotypes.

Host habitat rather than evolutionary history explains gut microbiome diversity in sympatric stickleback species.

Host-associated microbiota can influence host phenotypic variation, fitness and potential to adapt to local environmental conditions. In turn, both host evolutionary history and the abiotic and biotic environment can influence the diversity and composition of microbiota. Yet, to what extent environmental and host-specific factors drive microbial diversity remains largely unknown, limiting our understanding of host-microbiome interactions in natural populations. Here, we compared the intestinal microbiota between two phylogenetically related fishes, the three-spined stickleback (Gasterosteus aculeatus) and the nine-spined stickleback (Pungitius pungitius) in a common landscape. Using amplicon sequencing of the V3-V4 region of the bacterial 16S rRNA gene, we characterised the α and ß diversity of the microbial communities in these two fish species from both brackish water and freshwater habitats. Across eight locations, α diversity was higher in the nine-spined stickleback, suggesting a broader niche use in this host species. Habitat was a strong determinant of ß diversity in both host species, while host species only explained a small fraction of the variation in gut microbial composition. Strong habitat-specific effects overruled effects of geographic distance and historical freshwater colonisation, suggesting that the gut microbiome correlates primarily with local environmental conditions. Interestingly, the effect of habitat divergence on gut microbial communities was stronger in three-spined stickleback than in nine-spined stickleback, possibly mirroring the stronger level of adaptive divergence in this host species. Overall, our results show that microbial communities reflect habitat divergence rather than colonisation history or dispersal limitation of host species.

Microbial oil, alone or paired with ß-glucans, can control hypercholesterolemia in a zebrafish model.

Dyslipidemia is often associated with unhealthy dietary habits, and many mammalian studies have explored the mode of action of certain bioactive compounds such as ß-glucans and n-3 PUFAs to understand their potential to normalize the lipid metabolism. There are only a few investigations that adopted omic approaches to unveil their combined effect on hypercholesterolemia. Zebrafish (Danio rerio) was used as a model organism to reveal the efficacy of Schizochytrium oil and ß-glucans (from Euglena gracilis and Phaeodactylum tricornutum) against cholesterol-rich diet induced dyslipidemia. One of the folowing four diets was fed to a particular group of fish: a control high-cholesterol diet, a Schizochytrium oil diet or one of the two diets containing the oil and ß-glucan. The plasma HDL, expression of hepatic genes linked to, among others, ferric ion binding and plasma phosphatidylcholines were higher and plasma cholesterol esters and triacylglycerols were lower in the microbial oil-fed fish compared to the fish fed high cholesterol diet. While the fish fed a mix of microbial oil and Euglena ß-glucan had lower plasma triacylglycerols and expression of hepatic genes linked to PPAR signaling pathway and enriched biosynthesis of plasma unsaturated fatty acids, the fish fed microbial oil-Phaeodactylum ß-glucan combination had lower abundance of triacylglycerols rich in saturated and mono-unsaturated fatty acids and cholesterol esters in the plasma.

Protective mechanisms of a microbial oil against hypercholesterolemia: evidence from a zebrafish model.

A Western diet elevates the circulating lipoprotein and triglyceride levels which are the major risk factors in cardiovascular disease (CVD) development. Consumption of long-chain omega-3 fatty acids can stall the disease progression. Although these fatty acids can significantly impact the intestine under a hypercholesterolemic condition, the associated changes have not been studied in detail. Therefore, we investigated the alterations in the intestinal transcriptome along with the deviations in the plasma lipids and liver histomorphology of zebrafish offered DHA- and EPA-rich oil. Fish were allocated to 4 dietary treatments: a control group, a high cholesterol group and microbial oil groups with low (3.3%) and high (6.6%) inclusion levels. We quantified the total cholesterol, lipoprotein and triglyceride levels in the plasma. In addition, we assessed the liver histology, intestinal transcriptome and plasma lipidomic profiles of the study groups. The results suggested that higher levels of dietary microbial oil could control the CVD risk factor indices in zebrafish plasma. Furthermore, microbial oil-fed fish had fewer liver vacuoles and higher mRNA levels of genes involved in ß-oxidation and HDL maturation. Analyses of the intestine transcriptome revealed that microbial oil supplementation could influence the expression of genes altered by a hypercholesterolemic diet. The plasma lipidomic profiles revealed that the higher level of microbial oil tested could elevate the long-chain poly-unsaturated fatty acid content of triglyceride species and lower the concentration of several lysophosphatidylcholine and diacylglycerol molecules. Our study provides insights into the effectiveness of microbial oil against dyslipidemia in zebrafish.

Potential of algae-derived alginate oligosaccharides and ß-glucan to counter inflammation in adult zebrafish intestine.

Alginate oligosaccharides (AOS) are natural bioactive compounds with anti-inflammatory properties. We performed a feeding trial employing a zebrafish (Danio rerio) model of soybean-induced intestinal inflammation. Five groups of fish were fed different diets: a control (CT) diet, a soybean meal (SBM) diet, a soybean meal+ß-glucan (BG) diet and 2 soybean meal+AOS diets (alginate products differing in the content of low molecular weight fractions - AL, with 31% < 3kDa and AH, with 3% < 3kDa). We analyzed the intestinal transcriptomic and plasma metabolomic profiles of the study groups. In addition, we assessed the expression of inflammatory marker genes and histological alterations in the intestine. Dietary algal ß-(1, 3)-glucan and AOS were able to bring the expression of certain inflammatory genes altered by dietary SBM to a level similar to that in the control group. Intestinal transcriptomic analysis indicated that dietary SBM changed the expression of genes linked to inflammation, endoplasmic reticulum, reproduction and cell motility. The AL diet suppressed the expression of genes related to complement activation, inflammatory and humoral response, which can likely have an inflammation alleviation effect. On the other hand, the AH diet reduced the expression of genes, causing an enrichment of negative regulation of immune system process. The BG diet suppressed several immune genes linked to the endopeptidase activity and proteolysis. The plasma metabolomic profile further revealed that dietary SBM can alter inflammation-linked metabolites such as itaconic acid, taurochenodeoxycholic acid and enriched the arginine biosynthesis pathway. The diet AL helped in elevating one of the short chain fatty acids, namely 2-hydroxybutyric acid while the BG diet increased the abundance of a vitamin, pantothenic acid. Histological evaluation revealed the advantage of the AL diet: it increased the goblet cell number and length of villi of the intestinal mucosa. Overall, our results indicate that dietary AOS with an appropriate amount of < 3kDa can stall the inflammatory responses in zebrafish.

Differentiation of the Organoleptic Volatile Organic Compound Profile of Three Edible Seaweeds.

The inclusion of seaweeds in daily-consumption food is a worthy-of-attention challenge due to their high nutritional value and potential health benefits. In this way, their composition, organoleptic profile, and toxicity must be assessed. This work focuses on studying the volatile organic compounds (VOCs) emitted by three edible seaweeds, Grateloupia turuturu, Codium tomentosum, and Bifurcaria bifurcata, with the aim of deepening the knowledge regarding their organoleptic profiles. Nine samples of each seaweed were prepared in glass vials, and the emitted headspace was analyzed, for the first time, with a gas chromatography-ion mobility spectrometry device, a highly sensitive technology. By statistically processing the collected data through PCA, it was possible to accurately differentiate the characteristic patterns of the three seaweeds with a total explained variance of 98%. If the data were pre-processed through PLS Regression, the total explained variance increased to 99.36%. The identification of 13 VOCs was accomplished through a developed database of compounds. These outstanding values in addition to the identification of the main emissions of VOCs and the utilization of a never-before-used technology prove the capacity of GC-IMS to differentiate edible seaweeds based solely on their volatile emissions, increase the knowledge regarding their organoleptic profiles, and provide an important step forward in the inclusion of these highly nutritional ingredients in the human diet.

CircPrime: a web-based platform for design of specific circular RNA primers.

BACKGROUND: Circular RNAs (circRNAs) are covalently closed-loop RNAs with critical regulatory roles in cells. Tens of thousands of circRNAs have been unveiled due to the recent advances in high throughput RNA sequencing technologies and bioinformatic tools development. At the same time, polymerase chain reaction (PCR) cross-validation for circRNAs predicted by bioinformatic tools remains an essential part of any circRNA study before publication. RESULTS: Here, we present the CircPrime web-based platform, providing a user-friendly solution for DNA primer design and thermocycling conditions for circRNA identification with routine PCR methods. CONCLUSIONS: User-friendly CircPrime web platform ( http://circprime.elgene.net/ ) works with outputs of the most popular bioinformatic predictors of circRNAs to design specific circular RNA primers. CircPrime works with circRNA coordinates and any reference genome from the National Center for Biotechnology Information database).

Genome-wide hydroxymethylation profiles in liver of female Nile tilapia with distinct growth performance.

The mechanisms underlying the fast genome evolution that occurs during animal domestication are poorly understood. Here, we present a genome-wide epigenetic dataset that quantifies DNA hydroxymethylation at single nucleotide resolution among full-sib Nile tilapia (Oreochromis niloticus) with distinct growth performance. In total, we obtained 355 million, 75 bp reads from 5 large- and 5 small-sized fish on an Illumina NextSeq500 platform. We identified several growth-related genes to be differentially hydroxymethylated, especially within gene bodies and promoters. Previously, we proposed that DNA hydroxymethylation greatly affects the earliest responses to adaptation and potentially drives genome evolution through its targeted enrichment and elevated nucleotide transversion rates. This dataset can be analysed in various contexts (e.g., epigenetics, evolution and growth) and compared to other epigenomic datasets in the future, namely DNA methylation and histone modifications. With forthcoming advancements in genome research, this hydroxymethylation dataset will also contribute to better understand the epigenetic regulation of key genomic features, such as cis-regulatory and transposable elements.

The complete mitochondrial genome of the Atlantic spiny lumpsucker Eumicrotremus spinosus (Fabricius, 1776).

The complete mitogenome of the Atlantic spiny lumpsucker (Eumicrotremus spinosus) was generated using the PacBio Sequel II HiFi sequencing platform. The mitogenome assembly has a length of 19,281 bp and contains 13 protein-coding sequences, 22 tRNA genes, 2 rRNA genes, one control region containing the D-loop (2383 bp) and a duplicate control region (1133 bp) Phylogenetic analysis using maximum likelihood revealed that E. spinosus is closely related to the Siberian lumpsucker (E. asperrimus). The mitogenome of the spiny lumpsucker will be useful in population genomics and systematic studies of Cyclopteridae, Liparidae, and Cottidae.

The novel circular RNA CircMef2c is positively associated with muscle growth in Nile tilapia.

Muscle growth in teleosts is a complex biological process orchestrated by numerous protein-coding genes and non-coding RNAs. A few recent studies suggest that circRNAs are involved in teleost myogenesis, but the molecular networks involved remain poorly understood. In this study, an integrative omics approach was used to determine myogenic circRNAs in Nile tilapia by quantifying and comparing the expression profile of mRNAs, miRNAs, and circRNAs in fast muscle from full-sib fish with distinct growth rates. There were 1947 mRNAs, 9 miRNAs, and 4 circRNAs differentially expressed between fast- and slow-growing individuals. These miRNAs can regulate myogenic genes and have binding sites for the novel circRNA circMef2c. Our data indicate that circMef2c may interact with three miRNAs and 65 differentially expressed mRNAs to form multiple competing endogenous RNA networks that regulate growth, thus providing novel insights into the role of circRNAs in the regulation of muscle growth in teleosts.

The Prevalence of COVID-19 Fog and the Impact on Quality of Life After SARS-CoV-2 Infection (QoL-COVID): A Cross Sectional Study.

INTRODUCTION: Coronavirus has an impact on both the physical and mental health of individuals. The literature regarding the patient's health status post-SARS-CoV-2 is still scarce with limited data on the prevalence of residual symptoms and quality of life (QoL) after the infection. The aim of this study was to understand the impact of SARS-CoV-2 on patient QoL, and remaining symptoms. MATERIAL AND METHODS: Single center cross-sectional study of patients who had been admitted to our COVID-19 ward between March 2020 and March 2021. By applying a QoL questionnaire (EQ-5D-5L) we assessed the overall sample, at three time points and in different groups of patients: those admitted to the intensive care unit (ICU) and the elderly. RESULTS: A total of 125 participants were included in our study. Most patients who were admitted had a severe course of disease (51%), with 22% of admissions to the ICU, with 8% requiring prone ventilation, 10% experiencing thrombotic complications and 18% of nosocomial infections throughout the admission. As for persistent symptoms related with COVID-19 fog, the most frequent were fatigue (57%), memory loss (52%) and insomnia (50%). Regarding QoL, the average decrease was 0.08 ± 0.2 in the index and 8.7 ± 19 in the Visual Analogue Scale (VAS). The QoL index decrease correlated with age, chronic obstructive pulmonary disease, asthma and heart failure, and all persistent symptoms, significantly. QoL VAS correlated significantly with fatigue, mood changes, difficulty concentrating and memory loss. The decrease in QoL and the persistent symptoms remained overall stable over the three time points. The ICU group showed no statistically significant difference in QoL, but the most frequently persistent symptoms were mood changes and attention disturbances. However, the elderly experienced a worsening in QoL expressed by index (0.69 ± 0.3 vs 0.8 ± 0.2, p-value = 0.01). CONCLUSION: A decrease in QoL was observed following SARS-CoV-2 infection, correlating with both chronic conditions and persistent symptoms. The lack of difference through time points of both QoL and persistent symptoms suggests a long-standing effect.

Co-Administration of Albumin and Furosemide in Acute Heart Failure with Diuretics Resistance.

Acute heart failure is a frequent cause of hospital admission in Portugal, and has an increasing tendency given the aging population. Although most admissions for acute heart failure are caused by congestive conditions, not all patients have a congestive phenotype, reflecting the complexity of a process with multiple pathophysiological pathways. The use of diuretics, usually loop diuretics, is the mainstay of treatment for congestion. However, many patients develop resistance, thus constituting a challenge with no consensual solution to date, despite extensive debate over the years. Despite its frequent use in clinical practice, the co-administration of albumin and furosemide remains controversial in the management of patients with acute heart failure, hypoalbuminemia, and diuretic resistance. This review addresses the pathophysiological mechanisms of congestion in patients with acute heart failure and explores the theoretical basis that supports the co-administration of albumin and furosemide in this clinical context. It is intended to clarify the potential benefit of the combined approach in this specific population and identify possible gaps in the literature that could be the subject of future studies.

Versão Brasileira do Questionário de Satisfação com a Prótese (SAT-PRO/Br): validade estrutural, validade concorrente, consistência interna e estabilidade / Brazilian version of the Prosthesis Satisfaction Questionnaire (SAT-PRO/Br): structural validity, concurrent validity, internal consistency and stability

Objetivo: Analisar as propriedades psicométricas do SAT-PRO/Br através da observação da validade estrutural e concorrente, consistência interna e estabilidade. Método: A amostra deste estudo transversal foi consecutiva, não probabilística, constituída por 128 idosos com amputação de membro inferior, com amputação unilateral e que utilizavam a prótese a pelo menos um ano. As propriedades psicométricas foram avaliadas através da validade estrutural (Comparative Fit Index- CFI, Tucker-Lewis Index-TLI, Root Means Square Error of Approximation-RMSEA e Standardized Root Mean Residual-SRMR), validade concorrente utilizando a versão brasileira da Trinity Amputation and Prosthesis Experience Scales - Revised (TAPES-R), além da consistência interna dos itens pelo alfa de Cronbach e estabilidade pelo Intraclass Correlacion Coefficient (ICC). Resultados: O SAT-PRO/Br e a TAPES-R apresentaram forte correlação em relação a validade concorrente. A estabilidade variou de 0,85 a 0,91 através do ICC. Os índices de modelo do ajuste apresentaram valores de CFI de 0,991, TLI de 0,989, RMSEA de 0,045 e o SRMR de 0,074. Observou-se uma boa consistência interna com alfa de Cronbach total de 0.91. Conclusão: As propriedades psicométricas deste estudo sobre o SAT-PRO/Br levam a concluir que esta versão é válida, confiável e apresenta boa consistência interna e estabilidade para ser aplicada em idosos brasileiros amputados de membro inferior.

Objective: To analyze the psychometric properties of the SAT-PRO/Br through the observation of structural and concurrent validity, internal consistency and stability. Method: The sample of this cross-sectional study was consecutive, non-probabilistic, consisting of 128 elderly with lower limb amputation, with unilateral amputation and who used the prosthesis for at least one year. The psychometric properties were evaluated through structural validity (Comparative Fit Index- CFI, Tucker-Lewis Index-TLI, Root Means Square Error of Approximation-RMSEA and Standardized Root Mean Residual-SRMR), concurrent validity using the Brazilian version of Trinity Amputation and Prosthesis Experience Scales - Revised (TAPES-R), in addition to the internal consistency of the items by Cronbach's alpha and stability by the Intraclass Correlacion Coefficient (ICC). Results: The SAT-PRO/Br and TAPES-R showed a strong correlation in relation to concurrent validity. Stability ranged from 0.85 to 0.91 across the ICC. The fit model indices showed CFI values of 0.991, TLI of 0.989, RMSEA of 0.045 and SRMR of 0.074. A good internal consistency was observed with a total Cronbach's alpha of 0.91. Conclusion: The psychometric properties of this study on the SAT-PRO/Br lead to the conclusion that this version is valid, reliable and has good internal consistency and stability to be applied to elderly Brazilians with lower limb amputees.

Developmental defects and behavioral changes in a diet-induced inflammation model of zebrafish.

Soybean meal evokes diet-induced intestinal inflammation in certain fishes. Although the molecular aspects of soybean-induced intestinal inflammation in zebrafish are known, the impact of the inflammatory diet on fish behavior remain largely underexplored. We fed zebrafish larvae with three diets - control, soybean meal and soybean meal with ß-glucan to gain deeper insight into the behavioral changes associated with the soybean meal-induced inflammation model. We assessed the effect of the diets on the locomotor behavior, morphological development, oxygen consumption and larval transcriptome. Our study revealed that dietary soybean meal can reduce the locomotor activity, induce developmental defects and increase the oxygen demand in zebrafish larvae. Transcriptomic analysis pointed to the suppression of genes linked to visual perception, organ development, phototransduction pathway and activation of genes linked to the steroid biosynthesis pathway. On the contrary, ß-glucan, an anti-inflammatory feed additive, counteracted the behavioral and phenotypic changes linked to dietary soybean. Although we did not identify any differentially expressed genes from the soybean meal alone fed group vs soybean meal + ß-glucan-fed group comparison, the unique genes from the comparisons of the two groups with the control likely indicate reduction in inflammatory cytokine signaling, inhibition of proteolysis and induction of epigenetic modifications by the dietary glucan. Furthermore, we found that feeding an inflammatory diet at the larval stage can lead to long-lasting developmental defects. In conclusion, our study reveals the extra-intestinal manifestations associated with soybean meal-induced inflammation model.

Ancient DNA Reveals Maternal Philopatry of the Northeast Eurasian Brown Bear (Ursus arctos) Population during the Holocene.

Significant palaeoecological and paleoclimatic changes that took place during Late Pleistocene-Early Holocene transition are considered important factors that led to megafauna extinctions. Unlike many other species, the brown bear (Ursus arctos) has survived this geological time. Despite the fact that several mitochondrial DNA clades of brown bears became extinct at the end of the Pleistocene, this species is still widely distributed in Northeast Eurasia. Here, using the ancient DNA analysis of a brown bear individual that inhabited Northeast Asia in the Middle Holocene (3460 ± 40 years BP) and comparative phylogenetic analysis, we show a significant mitochondrial DNA similarity of the studied specimen with modern brown bears inhabiting Yakutia and Chukotka. In this study, we clearly demonstrate the maternal philopatry of the Northeastern Eurasian U. arctos population during the several thousand years of the Holocene.