Ancient DNA Analysis of the Oldest Canid Species from the Siberian Arctic and Genetic Contribution to the Domestic Dog

Modern Arctic Siberia provides a wealth of resources for archaeological, geological, and paleontological research to investigate the population dynamics of faunal communities from the Pleistocene, particularly as the faunal material coming from permafrost has proven suitable for genetic studies. In order to examine the history of the Canid species in the Siberian Arctic, we carried out genetic analysis of fourteen canid remains from various sites, including the well-documented Upper Paleolithic Yana RHS and Early Holocene Zhokhov Island sites. Estimated age of samples range from as recent as 1,700 years before present (YBP) to at least 360,000 YBP for the remains of the extinct wolf, Canis cf. variabilis. In order to examine the genetic affinities of ancient Siberian canids species to the domestic dog and modern wolves, we obtained mitochondrial DNA control region sequences and compared them to published ancient and modern canid sequences. The older canid specimens illustrate affinities with pre-domestic dog/wolf lineages while others appear in the major phylogenetic clades of domestic dogs. Our results suggest a European origin of domestic dog may not be conclusive and illustrates an emerging complexity of genetic contribution of regional wolf breeds to the modern Canis gene pool

Multiwavelength behaviour of the blazar 3C 279: Decade-long study from γ -ray to radio

We report the results of decade-long (2008-2018) γ -ray to 1 GHz radio monitoring of the blazar 3C 279, including GASP/WEBT, Fermi and Swift data, as well as polarimetric and spectroscopic data. The X-ray and γ -ray light curves correlate well, with no delay ≳ 3 h, implying general cospatiality of the emission regions. The γ -ray-optical flux-flux relation changes with activity state, ranging from a linear to amore complex dependence. The behaviour of the Stokes parameters at optical and radio wavelengths, including 43 GHz Very Long Baseline Array images, supports either a predominantly helical magnetic field or motion of the radiating plasma along a spiral path. Apparent speeds of emission knots range from 10 to 37c, with the highest values requiring bulk Lorentz factors close to those needed to explain γ -ray variability on very short time-scales. The MgII emission line flux in the 'blue' and 'red' wings correlates with the optical synchrotron continuum flux density, possibly providing a variable source of seed photons for inverse Compton scattering. In the radio bands, we find progressive delays of the most prominent light-curve maxima with decreasing frequency, as expected from the frequency dependence of the τ= 1 surface of synchrotron self-absorption. The global maximum in the 86 GHz light curve becomes less prominent at lower frequencies, while a local maximum, appearing in 2014, strengthens toward decreasing frequencies, becoming pronounced at ∼5 GHz. These tendencies suggest different Doppler boosting of stratified radio-emitting zones in the jet. © 2020 The Author(s).We thank the referee for attentive reading and comments that helped to improve presentation of the manuscript. The data collected by the WEBT collaboration are stored in the WEBT archive at the Osservatorio Astrofisico di Torino -INAF (ht tp://www.oato.inaf.it/blazars/webt/); for questions regarding their availability, please contact the WEBT President Massimo Villata([email protected]).TheSt.Petersburg University team acknowledges support from Russian Science Foundation grant 17-12-01029. The research at BU was supported in part by National Science Foundation grant AST-1615796 and NASA Fermi Guest Investigator grants 80NSSC17K0649, 80NSSC19K1504, and 80NSSC19K1505. The PRISM camera at Lowell Observatory was developed by K. Janes et al. at BU and Lowell Observatory, with funding from the NSF, BU, and Lowell Observatory. The emission-line observations made use of the DCT at Lowell Observatory, supported by Discovery Communications, Inc., BU, the University of Maryland, the University of Toledo, and Northern Arizona University. The VLBA is an instrument of the National Radio Astronomy Observatory. The National Radio Astronomy Observatory is a facility of the US NSF, operated under cooperative agreement by Associated Universities, Inc. This research has used data from the UMRAO which was supported by the University of Michigan; research at this facility was supported by NASA under awards NNX09AU16G, NNX10AP16G, NNX11AO13G, and NNX13AP18G, and by the NSF under award AST-0607523. The Steward Observatory spectropolarimetric monitoring project was supported by NASA Fermi Guest Investigator grants NNX08AW56G, NNX09AU10G, NNX12AO93G, and NNX15AU81G. The Torino group acknowledges financial contribution from agreement ASI-INAF n.2017-14-H.0 and from contract PRIN-SKA-CTA-INAF 2016. I.A. acknowledges support by a Ramon y Cajal grant (RYC-2013-14511) of the 'Ministerio de Ciencia, Innovacion, y Universidades (MICIU)' of Spain and from MCIU through the 'Center of Excellence Severo Ochoa' award for the Instituto de Astrofisica de Andalucia-CSIC (SEV-20170709). Acquisition and reduction of the POLAMI and MAPCAT data were supported by MICIU through grant AYA2016-80889-P. The POLAMI observations were carried out at the IRAM 30-m Telescope, supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain). The MAPCAT observations were carried out at theGerman-Spanish Calar Alto Observatory, jointly operated by the Max-Plank-Institut fur Astronomie and the Instituto de Astrofisica de Andalucia-CSIC. The study is based partly on data obtained with the STELLA robotic telescopes in Tenerife, an AIP facility jointly operated by AIP and IAC. The OVRO 40-m monitoring program is supported in part by NASA grants NNX08AW31G, NNX11A043G, and NNX14AQ89G, and NSF grants AST-0808050 and AST-1109911. TH was supported by the Academy of Finland projects 317383 and 320085. AZT-24 observations were made within an agreement between Pulkovo, Rome and Teramo observatories. The Submillimeter Array is a joint project between the Smithsonian Astrophysical Observatory and the Academia Sinica Institute of Astronomy and Astrophysics and is funded by the Smithsonian Institution and the Academia Sinica. The Abastumani team acknowledges financial support by the Shota Rustaveli National Science Foundation under contract FR/217950/16. r This research was partially supported by the Bulgarian National Science Fund of the Ministry of Education and Science under grants DN 081/2016, DN 18-13/2017, KP-06-H28/3 (2018), and KP-06-PN38/1 (2019), Bulgarian National Science Programme 'Young Scientists and Postdoctoral Students 2019', Bulgarian National Science Fund under grant DN18-10/2017 and National RI Roadmap Projects DO1-157/28.08.2018 and DO1-153/28.08.2018 of the Ministry of Education and Science of the Republic of Bulgaria. GD and OV gratefully acknowledge observing grant support from the Institute of Astronomy and Rozhen National Astronomical Observatory via bilateral joint research project `Study of ICRF radio-sources and fast variable astronomical objects' (head -G. Damljanovic). This work was partly supported by the National Science Fund of the Ministry of Education and Science of Bulgaria under grant DN 08-20/2016, and by project RD-08-37/2019 of the University of Shumen. This work is a part of projects nos 176011, 176004, and 176021, supported by theMinistry of Education, Science and Technological Development of the Republic of Serbia. MGM acknowledges support through the Russian Government Program of Competitive Growth of Kazan Federal University. The Astronomical Observatory of the Autonomous Region of the Aosta Valley (OAVdA) is managed by the Fondazione Clement Fillietroz-ONLUS, which is supported by the Regional Government of the Aosta Valley, the Town Municipality of Nus and the 'Unite des Communes vald 'otainesMont-Emilius'. The research at the OAVdA was partially funded by several `Research and Education' annual grants from Fondazione CRT. This article is partly based on observations made with the IAC80 and TCS telescopes operated by the Instituto de Astrofisica de Canarias in the Spanish Observatorio del Teide on the island of Tenerife. A part of the observations were carried out using theRATAN-600 scientific equipment (SAO of the Russian Academy of Sciences)

Особенности течения гепатокардиального синдрома у больных гипертрофической кардиомиопатией кошек

The issues of changes in clinical, laboratory and instrumental parameters in cats with hepatocardial syndrome formed against the background of hypertrophic cardiomyopathy were studied. It is known that in high-bred cats with congestive heart failure, secondary hepatopathy can develop and progress. It was shown that hepatocardial syndrome occurs in 33.7 % of cats, out of the total number of patients with hypertrophic cardiomyopathy (n = 83). It has been established that hepatocardial complications in cats are a risk factor for a more severe course of hypertrophic cardiomyopathy. Hepatocardial syndrome in cats with hypertrophic cardiomyopathy is characterized by severe hypothermia, circulatory and respiratory failure. In sick animals, an increase in frequency of breathing during sleep was recorded (33.3±9.3 versus 17.9±1.8 times/min; p < 0.001). Domestic cats with hepatocardial syndrome had a decrease in mean arterial blood pressure (100.2±19.3 versus 107.2±19.1 mm Hg; p < 0.05), sinus tachycardia (200.3±19.6 17.8 times/min; p < 0.001), which leads to a significant decrease in PQ intervals (57.9±9.9 versus 64.9±9.9 ms; p < 0.001) and QT intervals (168.9±17, 2 vs 157.5±18.6 ms; p < 0.001). Sick cats had a significant increase in the time of refilling of capillaries with blood, slowdown in intraventricular conduction, increase in voltage of ventricular and atrial complex on electrocardiograms, expansion of pulmonary vein, significant dilatation of left atrium, extreme concentric hypertrophy of left ventricle, increase in transverse contractility of myocardium of left ventricle and decrease in longitudinal contractility myocardium of left and right ventricles, cardiomyocyte cytolysis syndrome, cholestasis, and hypoalbuminemia.Рассматриваются вопросы изменения клинических, лабораторных и инструментальных параметров у кошек при развитии гепатокардиального синдрома, который сформировался на фоне гипертрофической кардиомиопатии. Известно, что у высокопородистых кошек при развитии застойной сердечной недостаточности может развиваться и прогрессировать вторичная гепатопатия. Показано, что гепатокардиальный синдром встречается у 33,7 % кошек от общего числа больных гипертрофической кардиомиопатией ( n = 83). Установлено, что гепатокардиальные осложнения у кошек являются фактором риска более тяжелого течения гипертрофической кардиомиопатии. Гепатокардиальный синдром у больных гипертрофической кардиомиопатией кошек характеризуется тяжелой гипотермией, недостаточностью кровообращения и респираторной системы. У больных животных регистрировали повышение частоты дыхания во сне (33,3 ± 9,3 против 17,9 ± 1,8 раз/мин; р < 0,001). У домашних кошек при гепатокардиальном синдроме развивается снижение среднего артериального давления крови (100,2 ± 19,3 против 107,2 ± 19,1 мм рт. ст; р < 0,05), синусовая тахикардия (200,3 ± 19,6 против 187,2 ± 17,8 раз/мин; р < 0,001), что приводит к достоверному снижению интервалов PQ (57,9 ± 9,9 против 64,9 ± 9,9 мс; р < 0,001) и QT (168,9 ± 17,2 против 157,5 ± 18,6 мс; р < 0,001). У больных кошек установлено существенное повышение времени обратного наполнения капилляров кровью, замедление внутрижелудочковой проводимости, повышение вольтажа желудочкового и предсердного комплекса на электрокардиограммах, расширение легочной вены, значительная дилатация левого предсердия, экстремальная концентрическая гипертрофия левого желудочка, повышение поперечной сократимости миокарда левого желудочка и снижение продольной контрактильности миокарда левого и правого желудочка, синдром цитолиза кардиомиоцитов, холестаз, а также гипоальбуминемия

Особенности клинической манифестации субкомпенсированного дисбактериоза кишечника кошек при оценке эффективности его коррекции

Formation and reproduction of gut microbiome begins at birth, while change in its composition depends mainly on various genetic, nutritional and environmental factors. The article considers the features of clinical manifestation of subcompensated intestinal dysbiosis in cats in assessing the effectiveness of its treatment. The studies were carried out on the basis of Department of Veterinary Medicine, RUDN University, and the clinical work was conducted at private veterinary clinics: ‘Avettura’, ‘Epiona’, ‘In the World with Animals’. Cats were selected for the experiment as they arrived at the initial appointment at veterinary clinics. The diagnosis of suspected intestinal dysbacteriosis was made considering anamnesis, clinical examination, and microbiological tests. The severity of intestinal dysbacteriosis was assessed on the results of clinical and laboratory studies. During the research, clinical and diagnostic approaches for subcompensated intestinal dysbacteriosis in cats were improved. Furthermore, effective ways of its treatment were developed. For subcompensated intestinal dysbacteriosis, administration of ‘Lactobifadol’ probiotic, ‘Vetelakt’ prebiotic and ‘Azoksivet’ immunomodulator showed the greatest therapeutic effect, which led to an overall clinical improvement in 5.50 days. Therapeutic efficacy of B 3 regimen was also clearly evidenced by the positive changes in intestinal microbiota and hematological blood parameters during the pharmacorrection. Improvement of clinical diagnostic approaches, prognosis of intestinal dysbiosis of varying severity and treatment effectiveness in cats require will allow to study intestinal dysbiotic disorders in other animal speciesФормирование и размножение микробиома кишечника начинается с рождения, в то время как изменение его состава зависит главным образом от различных генетических, пищевых и экологических факторов. Приведены особенности клинической манифестации субкомпенсированного дисбактериоза кишечника кошек при оценке эффективности его коррекции. Исследования проведены на базе департамента ветеринарной медицины Российского университета дружбы народов, а клиническая часть работы выполнена на базе частных клиник ветеринарной медицины: «Аветтура», «Эпиона», «В мире с животными». Кошек в эксперимент подбирали по мере их поступления на первичный прием в ветклиники. Диагноз при подозрении на дисбактериоз кишечника ставили комплексно с учетом данных анамнеза, клинического осмотра, а также микробиологических исследований. Оценку степени тяжести дисбактериоза кишечника осуществляли на основании проведенных клинико-лабораторных исследований. В ходе исследования усовершенствованы клинико-диагностические подходы при субкомпенсированном дисбактериозе кишечника у кошек, а на основании этого разработаны эффективные пути его коррекции. Показано, что при субкомпенсированном дисбактериозе кишечника назначение пробиотика «Лактобифадола» в комплексе с пребиотиком «Ветелакт» и иммуномодулятором «Азоксивет» показывает наибольший терапевтический эффект, что приводит к общему клиническому улучшению уже на 5,5 сутки. О терапевтической эффективности схемы В3 наглядно свидетельствует также позитивная динамика содержимого микробиоты кишечника и гематологических показателей крови в процессе проведения фармакокоррекции. Совершенствование клинико-диагностических подходов и прогнозирование при дисбактериозе кишечника у кошек различной степени тяжести, а также оценка эффективности его коррекции создают предпосылки для дальнейшего изучения дисбиотических нарушений кишечного тракта у других видов животных

Ancient DNA Analysis of the Oldest Canid Species from the Siberian Arctic and Genetic Contribution to the Domestic Dog

<div><p>Modern Arctic Siberia provides a wealth of resources for archaeological, geological, and paleontological research to investigate the population dynamics of faunal communities from the Pleistocene, particularly as the faunal material coming from permafrost has proven suitable for genetic studies. In order to examine the history of the Canid species in the Siberian Arctic, we carried out genetic analysis of fourteen canid remains from various sites, including the well-documented Upper Paleolithic Yana RHS and Early Holocene Zhokhov Island sites. Estimated age of samples range from as recent as 1,700 years before present (YBP) to at least 360,000 YBP for the remains of the extinct wolf, <i>Canis</i> cf. <i>variabilis</i>. In order to examine the genetic affinities of ancient Siberian canids species to the domestic dog and modern wolves, we obtained mitochondrial DNA control region sequences and compared them to published ancient and modern canid sequences. The older canid specimens illustrate affinities with pre-domestic dog/wolf lineages while others appear in the major phylogenetic clades of domestic dogs. Our results suggest a European origin of domestic dog may not be conclusive and illustrates an emerging complexity of genetic contribution of regional wolf breeds to the modern <i>Canis</i> gene pool.</p></div

Median-joining network of dog specimens for the mitochondrial DNA control region.

<p>Black circles indicate samples from our study. Sequences analyzed in the network span nucleotide positions 15547–15705. Clade A is highlighted in light gray and the Duvanny Yar sample S504 is noted in the network. The bottom-right cluster highlighted with a dashed line circle includes the samples S805, S806, S809, and S501.</p

Median-joining network of ancient canid specimens for the mitochondrial DNA control region.

<p>Black circles indicate samples from our study (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125759#pone.0125759.t001" target="_blank">Table 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125759#pone.0125759.s008" target="_blank">S6 Table</a> for sample ID). Sequences analyzed in the network span nucleotide positions 15561–15789.</p

Location of the sites studied.

<p>Corresponding numbers and information are provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125759#pone.0125759.t001" target="_blank">Table 1</a>.</p

Median-joining network of wolf specimens for the mitochondrial DNA control region.

<p>Black circles indicate samples from our study. Sequences analyzed in the network span nucleotide positions 15547–15792. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125759#pone.0125759.t001" target="_blank">Table 1</a> for the sample IDs from this study. Notable haplotypes include GQ509 (GenBank Accession No. GQ376509; Ural mountains of Russia [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125759#pone.0125759.ref059" target="_blank">59</a>]), JW237, 240, 255, 257 (GenBank Accession No. AB480736-AB480742, AB500700; <i>Canis lupus hodophilax</i>, Japan [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125759#pone.0125759.ref054" target="_blank">54</a>]), and LU51 (GenBank Accession No. AY812735; New Mexico, USA [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125759#pone.0125759.ref057" target="_blank">57</a>]).</p

Coordinated Loss and Acquisition of NK Cell Surface Markers Accompanied by Generalized Cytokine Dysregulation in COVID-19

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is accompanied by a dysregulated immune response. In particular, NK cells, involved in the antiviral response, are affected by the infection. This study aimed to investigate circulating NK cells with a focus on their activation, depletion, changes in the surface expression of key receptors, and functional activity during COVID-19, among intensive care unit (ICU) patients, moderately ill patients, and convalescents (CCP). Our data confirmed that NK cell activation in patients with COVID-19 is accompanied by changes in circulating cytokines. The progression of COVID-19 was associated with a coordinated decrease in the proportion of NKG2D+ and CD16+ NK cells, and an increase in PD-1, which indicated their exhaustion. A higher content of NKG2D+ NK cells distinguished surviving patients from non-survivors in the ICU group. NK cell exhaustion in ICU patients was additionally confirmed by a strong negative correlation of PD-1 and natural cytotoxicity levels. In moderately ill patients and convalescents, correlations were found between the levels of CD57, NKG2C, and NKp30, which may indicate the formation of adaptive NK cells. A reduced NKp30 level was observed in patients with a lethal outcome. Altogether, the phenotypic changes in circulating NK cells of COVID-19 patients suggest that the intense activation of NK cells during SARS-CoV-2 infection, most likely induced by cytokines, is accompanied by NK cell exhaustion, the extent of which may be critical for the disease outcome