Genetic insights into the social organization of Neanderthals.

Genomic analyses of Neanderthals have previously provided insights into their population history and relationship to modern humans1-8, but the social organization of Neanderthal communities remains poorly understood. Here we present genetic data for 13 Neanderthals from two Middle Palaeolithic sites in the Altai Mountains of southern Siberia: 11 from Chagyrskaya Cave9,10 and 2 from Okladnikov Cave11-making this one of the largest genetic studies of a Neanderthal population to date. We used hybridization capture to obtain genome-wide nuclear data, as well as mitochondrial and Y-chromosome sequences. Some Chagyrskaya individuals were closely related, including a father-daughter pair and a pair of second-degree relatives, indicating that at least some of the individuals lived at the same time. Up to one-third of these individuals' genomes had long segments of homozygosity, suggesting that the Chagyrskaya Neanderthals were part of a small community. In addition, the Y-chromosome diversity is an order of magnitude lower than the mitochondrial diversity, a pattern that we found is best explained by female migration between communities. Thus, the genetic data presented here provide a detailed documentation of the social organization of an isolated Neanderthal community at the easternmost extent of their known range.

Archaeological evidence for two separate dispersals of Neanderthals into southern Siberia.

Neanderthals were once widespread across Europe and western Asia. They also penetrated into the Altai Mountains of southern Siberia, but the geographical origin of these populations and the timing of their dispersal have remained elusive. Here we describe an archaeological assemblage from Chagyrskaya Cave, situated in the Altai foothills, where around 90,000 Middle Paleolithic artifacts and 74 Neanderthal remains have been recovered from deposits dating to between 59 and 49 thousand years ago (age range at 95.4% probability). Environmental reconstructions suggest that the Chagyrskaya hominins were adapted to the dry steppe and hunted bison. Their distinctive toolkit closely resembles Micoquian assemblages from central and eastern Europe, including the northern Caucasus, more than 3,000 kilometers to the west of Chagyrskaya Cave. At other Altai sites, evidence of earlier Neanderthal populations lacking associated Micoquian-like artifacts implies two or more Neanderthal incursions into this region. We identify eastern Europe as the most probable ancestral source region for the Chagyrskaya toolmakers, supported by DNA results linking the Neanderthal remains with populations in northern Croatia and the northern Caucasus, and providing a rare example of a long-distance, intercontinental population movement associated with a distinctive Paleolithic toolkit.

A high-coverage Neandertal genome from Chagyrskaya Cave.

We sequenced the genome of a Neandertal from Chagyrskaya Cave in the Altai Mountains, Russia, to 27-fold genomic coverage. We show that this Neandertal was a female and that she was more related to Neandertals in western Eurasia [Prüfer et al., Science 358, 655-658 (2017); Hajdinjak et al., Nature 555, 652-656 (2018)] than to Neandertals who lived earlier in Denisova Cave [Prüfer et al., Nature 505, 43-49 (2014)], which is located about 100 km away. About 12.9% of the Chagyrskaya genome is spanned by homozygous regions that are between 2.5 and 10 centiMorgans (cM) long. This is consistent with the fact that Siberian Neandertals lived in relatively isolated populations of less than 60 individuals. In contrast, a Neandertal from Europe, a Denisovan from the Altai Mountains, and ancient modern humans seem to have lived in populations of larger sizes. The availability of three Neandertal genomes of high quality allows a view of genetic features that were unique to Neandertals and that are likely to have been at high frequency among them. We find that genes highly expressed in the striatum in the basal ganglia of the brain carry more amino-acid-changing substitutions than genes expressed elsewhere in the brain, suggesting that the striatum may have evolved unique functions in Neandertals.

Nebulized Non-Immunogenic Staphylokinase in the Mice Acute Lung Injury Model.

Acute lung injury (ALI) as a model of acute respiratory distress syndrome is characterized by inflammation, complex coagulation, and hematologic abnormalities which result in the formation of fibrin-platelet microthrombi in the pulmonary vessels with the rapid development of progressive respiratory dysfunction. We hypothesize that a nebulized fibrinolytic agent, non-immunogenic staphylokinase (nSta), may be useful for ALI therapy. First, the effect of the nebulized nSta (0.2 mg/kg, 1.0 mg/kg, or 2.0 mg/kg) on the coagulogram parameters was studied in healthy rats. ALI was induced in mice by nebulized administration of lipopolysaccharide (LPS) at a dose of 10 mg/kg. nSta (0.2 mg/kg, 0.4 mg/kg or 0.6 mg/kg) was nebulized 30 min, 24 h, and 48 h after LPS administration. The level of pro-inflammatory cytokines was determined in the blood on the 8th day after LPS and nSta administration. The assessment of lung damage was based on their weighing and microscopic analysis. Fibrin/fibrinogen deposition in the lungs was determined by immunohistochemistry. After nSta nebulization in healthy rats, the fibrinogen blood level as well as activated partial thromboplastin time and prothrombin time did not change. In the nebulized ALI model, the mice showed an increase in lung weight due to their edema and rising fibrin deposition. An imbalance of proinflammatory cytokines was also found. Forty percent of mice with ALI without nSta nebulization had died. Nebulized nSta at a dose of 0.2 mg/kg reduced the severity of ALI: a decrease in interstitial edema and inflammatory infiltration was noted. At a dose of 0.4 mg/kg of nebulized nSta, the animals showed no peribronchial edema and the bronchi had an open clear lumen. At a dose of 0.6 mg/kg of nebulized nSta, the manifestations of ALI were completely eliminated. A significant dose-dependent reduction of the fibrin-positive areas in the lungs of mice with ALI was established. Nebulized nSta had a normalizing effect on the proinflammatory cytokines in blood- interleukin (IL)-1α, IL-17A, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). These data showed the effectiveness of nebulized nSta and the perspectives of its clinical usage in COVID-19 patients with acute respiratory distress syndrome (ARDS).

Metabolomic Markers for Predicting Preeclampsia in the First Trimester of Pregnancy: A Retrospective Study.

We sought to identify the characteristic metabolite profile of blood plasma samples obtained from patients with preeclampsia. Direct high-resolution mass spectrometry was used to analyze samples from 79 pregnant women, 34 of whom had preeclampsia. We performed a comparative analysis of the metabolite profiles and found that they differed between pregnant women with and without preeclampsia. Lipids and sugars were identified as components of the metabolite profile that are likely to be associated with the development of preeclampsia. While PE was established only in the third trimester, a set of metabolites specific for the third trimester, including 2-(acetylamino)-1,5-anhydro-2-deoxy-4-O-b-D-galactopyranosyl-D-arabino-Hex-1-enitol, N-Acetyl-D-glucosaminyldiphosphodolichol, Cer(d18:0/20:0), and allolithocholic acid, was already traced in the first trimester. These components are also likely involved in lipid metabolism disorders and the development of oxidative stress.

Dietary evidence from Central Asian Neanderthals: A combined isotope and plant microremains approach at Chagyrskaya Cave (Altai, Russia).

Neanderthals are known primarily from their habitation of Western Eurasia, but they also populated large expanses of Northern Asia for thousands of years. Owing to a sparse archaeological record, relatively little is known about these eastern Neanderthal populations. Unlike in their western range, there are limited zooarchaeological and paleobotanical studies that inform us about the nature of their subsistence. Here, we perform a combined analysis of carbon and nitrogen stable isotopes on bone collagen and microbotanical remains in dental calculus to reconstruct the diet of eastern Neanderthals at Chagyrskaya Cave in the Altai Mountains of Southern Siberia, Russia. Stable isotopes identify one individual as possessing a high trophic level due to the hunting of large- and medium-sized ungulates, while the analysis of dental calculus also indicates the presence of plants in the diet of this individual and others from the site. These findings indicate eastern Neanderthals may have had broadly similar subsistence patterns to those elsewhere in their range.

High-Density Lipoproteins as Homeostatic Nanoparticles of Blood Plasma.

It is well known that blood lipoproteins (LPs) are multimolecular complexes of lipids and proteins that play a crucial role in lipid transport. High-density lipoproteins (HDL) are a class of blood plasma LPs that mediate reverse cholesterol transport (RCT)-cholesterol transport from the peripheral tissues to the liver. Due to this ability to promote cholesterol uptake from cell membranes, HDL possess antiatherogenic properties. This function was first observed at the end of the 1970s to the beginning of the 1980s, resulting in high interest in this class of LPs. It was shown that HDL are the prevalent class of LPs in several types of living organisms (from fishes to monkeys) with high resistance to atherosclerosis and cardiovascular disorders. Lately, understanding of the mechanisms of the antiatherogenic properties of HDL has significantly expanded. Besides the contribution to RCT, HDL have been shown to modulate inflammatory processes, blood clotting, and vasomotor responses. These particles also possess antioxidant properties and contribute to immune reactions and intercellular signaling. Herein, we review data on the structure and mechanisms of the pleiotropic biological functions of HDL from the point of view of their evolutionary role and complex dynamic nature.

Organization of left-right coordination of neuronal activity in the mammalian spinal cord: Insights from computational modelling.

KEY POINTS: Coordination of neuronal activity between left and right sides of the mammalian spinal cord is provided by several sets of commissural interneurons (CINs) whose axons cross the midline. Genetically identified inhibitory V0D and excitatory V0V CINs and ipsilaterally projecting excitatory V2a interneurons were shown to secure left-right alternation at different locomotor speeds. We have developed computational models of neuronal circuits in the spinal cord that include left and right rhythm-generating centres interacting bilaterally via three parallel pathways mediated by V0D , V2a-V0V and V3 neuron populations. The models reproduce the experimentally observed speed-dependent left-right coordination in normal mice and the changes in coordination seen in mutants lacking specific neuron classes. The models propose an explanation for several experimental results and provide insights into the organization of the spinal locomotor network and parallel CIN pathways involved in gait control at different locomotor speeds. ABSTRACT: Different locomotor gaits in mammals, such as walking or galloping, are produced by coordinated activity in neuronal circuits in the spinal cord. Coordination of neuronal activity between left and right sides of the cord is provided by commissural interneurons (CINs), whose axons cross the midline. In this study, we construct and analyse two computational models of spinal locomotor circuits consisting of left and right rhythm generators interacting bilaterally via several neuronal pathways mediated by different CINs. The CIN populations incorporated in the models include the genetically identified inhibitory (V0D ) and excitatory (V0V ) subtypes of V0 CINs and excitatory V3 CINs. The model also includes the ipsilaterally projecting excitatory V2a interneurons mediating excitatory drive to the V0V CINs. The proposed network architectures and CIN connectivity allow the models to closely reproduce and suggest mechanistic explanations for several experimental observations. These phenomena include: different speed-dependent contributions of V0D and V0V CINs and V2a interneurons to left-right alternation of neural activity, switching gaits between the left-right alternating walking-like activity and the left-right synchronous hopping-like pattern in mutants lacking specific neuron classes, and speed-dependent asymmetric changes of flexor and extensor phase durations. The models provide insights into the architecture of spinal network and the organization of parallel inhibitory and excitatory CIN pathways and suggest explanations for how these pathways maintain alternating and synchronous gaits at different locomotor speeds. The models propose testable predictions about the neural organization and operation of mammalian locomotor circuits.

Operation regimes of spinal circuits controlling locomotion and role of supraspinal drives and sensory feedback.

Locomotion in mammals is directly controlled by the spinal neuronal network, operating under the control of supraspinal signals and somatosensory feedback that interact with each other. However, the functional architecture of the spinal locomotor network, its operation regimes, and the role of supraspinal and sensory feedback in different locomotor behaviors, including at different speeds, remain unclear. We developed a computational model of spinal locomotor circuits receiving supraspinal drives and limb sensory feedback that could reproduce multiple experimental data obtained in intact and spinal-transected cats during tied-belt and split-belt treadmill locomotion. We provide evidence that the spinal locomotor network operates in different regimes depending on locomotor speed. In an intact system, at slow speeds (< 0.4 m/s), the spinal network operates in a non-oscillating state-machine regime and requires sensory feedback or external inputs for phase transitions. Removing sensory feedback related to limb extension prevents locomotor oscillations at slow speeds. With increasing speed and supraspinal drives, the spinal network switches to a flexor-driven oscillatory regime and then to a classical half-center regime. Following spinal transection, the model predicts that the spinal network can only operate in the state-machine regime. Our results suggest that the spinal network operates in different regimes for slow exploratory and fast escape locomotor behaviors, making use of different control mechanisms.

Operation of spinal sensorimotor circuits controlling phase durations during tied-belt and split-belt locomotion after a lateral thoracic hemisection.

Locomotion is controlled by spinal circuits that interact with supraspinal drives and sensory feedback from the limbs. These sensorimotor interactions are disrupted following spinal cord injury. The thoracic lateral hemisection represents an experimental model of an incomplete spinal cord injury, where connections between the brain and spinal cord are abolished on one side of the cord. To investigate the effects of such an injury on the operation of the spinal locomotor network, we used our computational model of cat locomotion recently published in eLife (Rybak et al., 2024) to investigate and predict changes in cycle and phase durations following a thoracic lateral hemisection during treadmill locomotion in tied-belt (equal left-right speeds) and split-belt (unequal left-right speeds) conditions. In our simulations, the "hemisection" was always applied to the right side. Based on our model, we hypothesized that following hemisection, the contralesional ("intact", left) side of the spinal network is mostly controlled by supraspinal drives, whereas the ipsilesional ("hemisected", right) side is mostly controlled by somatosensory feedback. We then compared the simulated results with those obtained during experiments in adult cats before and after a mid-thoracic lateral hemisection on the right side in the same locomotor conditions. Our experimental results confirmed many effects of hemisection on cat locomotion predicted by our simulations. We show that having the ipsilesional hindlimb step on the slow belt, but not the fast belt, during split-belt locomotion substantially reduces the effects of lateral hemisection. The model provides explanations for changes in temporal characteristics of hindlimb locomotion following hemisection based on altered interactions between spinal circuits, supraspinal drives, and somatosensory feedback.

Distinct roles of spinal commissural interneurons in transmission of contralateral sensory information.

Crossed reflexes (CR) are mediated by commissural pathways transmitting sensory information to the contralateral side of the body, but the underlying network is not fully understood. Commissural pathways coordinating the activities of spinal locomotor circuits during locomotion have been characterized in mice, but their relationship to CR is unknown. We show the involvement of two genetically distinct groups of commissural interneurons (CINs) described in mice, V0 and V3 CINs, in the CR pathways. Our data suggest that the exclusively excitatory V3 CINs are directly involved in the excitatory CR, and show that they are essential for the inhibitory CR. In contrast, the V0 CINs, a population that includes excitatory and inhibitory CINs, are not directly involved in excitatory or inhibitory CRs but down-regulate the inhibitory CR. Our data provide insights into the spinal circuitry underlying CR in mice, describing the roles of V0 and V3 CINs in CR.

Distinct roles of spinal commissural interneurons in transmission of contralateral sensory information.

Crossed reflexes are mediated by commissural pathways transmitting sensory information to the contralateral side of the body, but the underlying network is not fully understood. Commissural pathways coordinating the activities of spinal locomotor circuits during locomotion have been characterized in mice, but their relationship to crossed reflexes is unknown. We show the involvement of two genetically distinct groups of commissural interneurons (CINs) described in mice, V0 and V3 CINs, in the crossed reflex pathways. Our data suggest that the exclusively excitatory V3 CINs are directly involved in the excitatory crossed reflexes and show that they are essential for the inhibitory crossed reflexes. In contrast, the V0 CINs, a population that includes excitatory and inhibitory CINs, are not directly involved in excitatory or inhibitory crossed reflexes but downregulate the inhibitory crossed reflexes. Our data provide insights into the spinal circuitry underlying crossed reflexes in mice, describing the roles of V0 and V3 CINs in crossed reflexes.

Motoneuronal and muscle synergies involved in cat hindlimb control during fictive and real locomotion: a comparison study.

We compared the activity profiles and synergies of spinal motoneurons recorded during fictive locomotion evoked in immobilized decerebrate cat preparations by midbrain stimulation to the activity profiles and synergies of the corresponding hindlimb muscles obtained during forward level walking in cats. The fictive locomotion data were collected in the Spinal Cord Research Centre, University of Manitoba, and provided by Dr. David McCrea; the real locomotion data were obtained in the laboratories of M. A. Lemay and B. I. Prilutsky. Scatterplot representation and minimum spanning tree clustering algorithm were used to identify the possible motoneuronal and muscle synergies operating during both fictive and real locomotion. We found a close similarity between the activity profiles and synergies of motoneurons innervating one-joint muscles during fictive locomotion and the profiles and synergies of the corresponding muscles during real locomotion. However, the activity patterns of proximal nerves controlling two-joint muscles, such as posterior biceps and semitendinosus (PBSt) and rectus femoris (RF), were not uniform in fictive locomotion preparations and differed from the activity profiles of the corresponding two-joint muscles recorded during forward level walking. Moreover, the activity profiles of these nerves and the corresponding muscles were unique and could not be included in the synergies identified in fictive and real locomotion. We suggest that afferent feedback is involved in the regulation of locomotion via motoneuronal synergies controlled by the spinal central pattern generator (CPG) but may also directly affect the activity of motoneuronal pools serving two-joint muscles (e.g., PBSt and RF). These findings provide important insights into the organization of the spinal CPG in mammals, the motoneuronal and muscle synergies engaged during locomotion, and their afferent control.

Contribution of Afferent Feedback to Adaptive Hindlimb Walking in Cats: A Neuromusculoskeletal Modeling Study.

Mammalian locomotion is generated by central pattern generators (CPGs) in the spinal cord, which produce alternating flexor and extensor activities controlling the locomotor movements of each limb. Afferent feedback signals from the limbs are integrated by the CPGs to provide adaptive control of locomotion. Responses of CPG-generated neural activity to afferent feedback stimulation have been previously studied during fictive locomotion in immobilized cats. Yet, locomotion in awake, behaving animals involves dynamic interactions between central neuronal circuits, afferent feedback, musculoskeletal system, and environment. To study these complex interactions, we developed a model simulating interactions between a half-center CPG and the musculoskeletal system of a cat hindlimb. Then, we analyzed the role of afferent feedback in the locomotor adaptation from a dynamic viewpoint using the methods of dynamical systems theory and nullcline analysis. Our model reproduced limb movements during regular cat walking as well as adaptive changes of these movements when the foot steps into a hole. The model generates important insights into the mechanism for adaptive locomotion resulting from dynamic interactions between the CPG-based neural circuits, the musculoskeletal system, and the environment.

High-density lipoprotein remodeling by phospholipid nanoparticles improves cholesterol efflux capacity and protects from atherosclerosis.

The efficiency of cholesterol efflux from cells promoted by high-density lipoproteins (HDLs) depends on HDL concentration and functional properties. The term "dysfunctional HDL" describes HDLs with impaired protective properties. Cholesterol efflux capacity (CEC) of HDL is reduced in patients with atherosclerosis, but the exact mechanisms underlying this impairment are not well characterized. Enriching HDLs with phospholipids (PLs) improves CEC. Herein, we assessed the potential of PL nanoparticles in improving HDL functionality. We lipidated HDL subfractions by incubating with PL nanoparticles containing soybean polyunsaturated phosphatidylcholine. Incubating blood plasma with PL nanoparticles resulted in the dose-dependent lipidation of all HDL subfractions. Changes in apolipoprotein A1 (apoA-1) and PL concentrations were the most prominent in the HDL2 fraction. Concentrations of PL in the HDL3 fraction and the fraction with a density > 1.21 g/mL increased by 30-50%, whereas apoA-1 levels decreased. We hypothesized that PL nanoparticles may cause HDL remodeling that can improve their functions. The CECs of lipidated HDLs were analyzed by incubating apolipoprotein B (apoB)-depleted plasma with 3H-cholesterol-labeled THP-1 macrophages. The findings revealed a two-fold increase in cholesterol efflux compared with native apoB-depleted plasma. Moreover, intravenous administration of PL nanoparticles restored lipid profiles and effectively protected blood vessels from atherosclerosis progression in cholesterol-fed rabbits compared with that of fenofibrate and atorvastatin. PL nanoparticles also protected against atherosclerosis and decreased the atherogenic index. Altogether, these results indicate that PL nanoparticles can be used to correct the lipid composition and CEC of HDLs. DATA AVAILABILITY: Additional data can be provided upon reasonable request from the date of publication of this article within 5 years. The request should be sent to the author-correspondent at the address cd95@mail.ru.

Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4·5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial.

BACKGROUND: Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and selectivity to fibrin. We aimed to assess the safety and efficacy of a single intravenous bolus of non-immunogenic staphylokinase compared with alteplase in patients with acute ischaemic stroke within 4·5 h after symptom onset. METHODS: We did a randomised, open-label, multicentre, parallel-group, non-inferiority trial in 18 clinical sites in Russia. We included patients aged 18 years and older with a diagnosis of acute ischaemic stroke (up to 25 points on the National Institutes of Health Stroke Scale). The study drug had to be administered within 4·5 h after the onset of symptoms. Patients were randomly assigned to receive either non-immunogenic staphylokinase (10 mg) or alteplase (0·9 mg/kg, maximum 90 mg), both administered intravenously. The randomisation sequence was created by an independent biostatistician using computer-generated random numbers. 84 blocks (block size of four) of opaque sealed envelopes were numbered sequentially from 1 to 336 and were opened in numerical order. Patients were unaware of their assigned treatment and were assessed by the study investigators who were also unaware of the treatment assignment on all trial days. Emergency department staff, who administered the assigned drug and opened the envelopes, were not masked to treatment. The primary efficacy endpoint was a favourable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. The margin of non-inferiority was established as 16% for the difference in mRS score of 0-1 on day 90. Non-inferiority was tested using Welch's t-test for the primary outcome only. Endpoints were analysed in the per-protocol population, which comprised all randomly assigned patients who completed treatment without any protocol violations; this population was identical to the intention-to-treat population. This trial is completed and registered at ClinicalTrials.gov, NCT03151993. FINDINGS: Of 385 patients recruited from March 18, 2017, to March 23, 2019, 336 (87%) were included in the trial. 168 (50%) patients were randomly assigned to receive non-immunogenic staphylokinase and 168 (50%) to receive alteplase. The median duration of follow-up was 89 days (IQR 89-89). 84 (50%) of 168 patients in the non-immunogenic staphylokinase group had a favourable outcome at day 90 compared with 68 (40%) of 168 patients in the alteplase group (odds ratio [OR] 1·47, 95% CI 0·93 to 2·32; p=0·10). The difference in the rate of favourable outcome at day 90 was 9·5% (95% CI -1·7 to 20·7) and the lower limit did not cross the margin of non-inferiority (pnon-inferiority <0·0001). Symptomatic intracranial haemorrhage occurred in five (3%) patients in the non-immunogenic staphylokinase group and in 13 (8%) patients in the alteplase group (p=0·087). On day 90, 17 (10%) patients in the non-immunogenic staphylokinase group and 24 (14%) patients in the alteplase group had died (p=0·32). 22 (13%) patients in the non-immunogenic staphylokinase group had serious adverse events, compared with 37 (22%) patients in the alteplase group (p=0·044). INTERPRETATION: Non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Future studies are needed to continue to assess the safety and efficacy of non-immunogenic staphylokinase in patients with acute ischaemic stroke within the 4·5 h time window, and to assess the drug in patients with acute ischaemic stroke outside this time window with reperfusion CT or magnetic resonance angiography followed by thrombectomy if necessary. FUNDING: The Russian Academy of Sciences.

A Whole-Body Musculoskeletal Model of the Mouse.

Neural control of movement cannot be fully understood without careful consideration of interactions between the neural and biomechanical components. Recent advancements in mouse molecular genetics allow for the identification and manipulation of constituent elements underlying the neural control of movement. To complement experimental studies and investigate the mechanisms by which the neural circuitry interacts with the body and the environment, computational studies modeling motor behaviors in mice need to incorporate a model of the mouse musculoskeletal system. Here, we present the first fully articulated musculoskeletal model of the mouse. The mouse skeletal system has been developed from anatomical references and includes the sets of bones in all body compartments, including four limbs, spine, head and tail. Joints between all bones allow for simulation of full 3D mouse kinematics and kinetics. Hindlimb and forelimb musculature has been implemented using Hill-type muscle models. We analyzed the mouse whole-body model and described the moment-arms for different hindlimb and forelimb muscles, the moments applied by these muscles on the joints, and their involvement in limb movements at different limb/body configurations. The model represents a necessary step for the subsequent development of a comprehensive neuro-biomechanical model of freely behaving mice; this will close the loop between the neural control and the physical interactions between the body and the environment.

Human Chr18 transcriptome dataset combined from the Illumina HiSeq, ONT MinION, and qPCR data.

The chromosome-centric dataset was created by applying several technologies of transcriptome profiling. The described dataset is available at NCBI repository (BioProject ID PRJNA635536). The dataset referred to the same type of tissue, cell lines, transcriptome sequencing technologies, and was accomplished in a period of 8 years (the first data were obtained in 2013 while the last ones - in 2020). The high-throughput sequencing technologies were employed along with the quantitative PCR (qPCR) approach, for data generation using the gene expression level assessment. qPCR was performed for a limited group of genes, encoded on human chromosome 18, for the Russian part of the Chromosome-Centric Human Proteome Project. The data of high-throughput sequencing are provided as Excel spreadsheets, where the data on FPKM and TMP values were evaluated for the whole transcriptome with both Illumina HiSeq and Oxford Nanopore Technologies MinION sequencing.

Metabolomic diagnostics and human digital image.

The existing clinical laboratory practice has limitations in terms of specificity and sensitivity of diagnosis, making the introduction of new methods in medicine more topical. Application of 'omics' technologies, especially metabolomics, allows overcoming these limitations. The composition of blood metabolites reflects the physical state of an organism at the molecular level. The analysis of blood metabolome can serve as effective means of diagnosis, implementation of which in healthcare is timely and relevant. This paper demonstrates the versatility of metabolomic diagnostics, its applicability to various diseases. We discussed the standard of human digital image, which includes the metabolomic data sufficient to make an accurate assessment of general health and carry out precision diagnostics of a wide range of diseases.