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Abstract The information about the reasons for sports career (SC) termination among athletes is of significant importance, as it provides a theoretical foundation to prevent early withdrawal. A sociological survey was conducted among 76 former male artistic gymnasts who have ended their careers to determine the causes of SC termination. As a result, 11 different reasons for SC termination were identified. The most frequent reasons include sports injuries (35.52%), mandatory military service (31.57%), and employment (25.0%). The least mentioned reasons are coach-related issues (5.26%), health problems (2.63%), and age (2.63%). The survey offers a broader understanding of why Armenian athletes terminate their sports careers. This insight will enable the governing bodies of Armenian gymnastics and sports to provide targeted assistance to adult artistic gymnasts, helping to prevent early withdrawal in the future. Podatki o razlogih za prekinitev športne poti pri športnikih so bistvenega pomena, saj predstavljajo splošno osnovo za preprečevanje predčasne opustitve. Med 76 nekdanjimi orodnimi telovadci, ki so končali športno pot, smo izvedli sociološko raziskavo, da bi ugotovili vzroke za prekinitev športne poti. Ugotovljenih je bilo 11 različnih razlogov. Najpogostejši razlogi so športne poškodbe (35,52 %), obvezno služenje vojaškega roka (31,57 %) in zaposlitev (25,0 %). Najmanj omenjeni razlogi so težave z vaditeljem (5,26 %), zdravstvene težave (2,63 %) in starost (2,63 %). Raziskava ponuja širše razumevanje, zakaj armenski športniki prekinejo svojo športno pot. Ta vpogled bo vodstvenim organom armenske telovadbe in športa omogočil, da zagotovijo ciljno usmerjeno pomoč odraslim orodnim telovadcem, kar bo pomagalo preprečiti zgodnjo opustitev v prihodnosti.

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. The pathological hallmark of PD is loss of dopaminergic neurons and the presence of aggregated α-synuclein, primarily in the substantia nigra pars compacta (SNpc) of the midbrain. However, the molecular mechanisms that underlie the pathology in different cell types is not currently understood. Here, we present a single nucleus transcriptome analysis of human post-mortem SNpc obtained from 15 sporadic Parkinson’s Disease (PD) cases and 14 Controls. Our dataset comprises ∼84K nuclei, representing all major cell types of the brain, allowing us to obtain a transcriptome-level characterization of these cell types. Importantly, we identify multiple subpopulations for each cell type and describe specific gene sets that provide insights into the differing roles of these subpopulations. Our findings reveal a significant decrease in neuronal cells in PD samples, accompanied by an increase in glial cells and T cells. Subpopulation analyses demonstrate a significant depletion of tyrosine hydroxylase ( TH ) enriched astrocyte, microglia and oligodendrocyte populations in PD samples, as well as TH enriched neurons, which are also depleted. Moreover, marker gene analysis of the depleted subpopulations identified 28 overlapping genes, including those associated with dopamine metabolism (e.g., ALDH1A1, SLC6A3 & SLC18A2 ). Overall, our study provides a valuable resource for understanding the molecular mechanisms involved in dopaminergic neuron degeneration and glial responses in PD, highlighting the existence of novel subpopulations and cell type-specific gene sets.

Poly (ADP-ribose) polymerase 1 (PARP1) has high therapeutic value as biomolecular target for research and development of small molecules with antineoplastic activity, since it is upregulated in many cancers, especially in ovarian and BRCA 1/2 mutated breast cancers. Decades of investigation of PARP inhibitors (PARPi) have led to the approval of several drug compounds, however clinical application of PARPi in cancer therapy is limited due to a number of factors, including low selectivity, weak affinity and undesired side effects. Thus, identification of novel drug-like chemical compounds with alternatives to the known PARPi chemical scaffolds, binding modes and interaction patterns with amino acid residues in the active site is of high therapeutic importance. In this study we applied a combination of ligand- and structure-based virtual screening approaches with the goal of identification of novel potential PARPi.

The vascular endothelial growth factor receptor 2 (VEGFR-2) is largely recognized as a potent therapeutic molecular target for the development of angiogenesis-related tumor treatment. Tumor growth, metastasis and multidrug resistance highly depends on the angiogenesis and drug discovery of the potential small molecules targeting VEGFR-2, with the potential anti-angiogenic activity being of high interest to anti-cancer research. Multiple small molecule inhibitors of the VEGFR-2 are approved for the treatment of different type of cancers, with one of the most recent, tivozanib, being approved by the FDA for the treatment of relapsed or refractory advanced renal cell carcinoma (RCC). However, the endogenous and acquired resistance of the protein, toxicity of compounds and wide range of side effects still remain critical issues, which lead to the short-term clinical effects and failure of antiangiogenic drugs. We applied a combination of computational methods and approaches for drug design and discovery with the goal of finding novel, potential and small molecule inhibitors of VEGFR2, as alternatives to the known inhibitors’ chemical scaffolds and components. From studying several of these compounds, the derivatives of pyrido[1,2-a]pyrimidin-4-one and isoindoline-1,3-dione in particular were identified.

Noradrenaline (norepinephrine) is known to modulate many physiological functions and behaviors. In this study, we tested to what extent astrocytes, a type of glial cell, participate in noradrenergic signaling in mouse primary visual cortex (V1). Astrocytes are essential partners of neurons in the central nervous system. They are central to brain homeostasis, but also dynamically regulate neuronal activity, notably by relaying and regulating neuromodulator signaling. Indeed, astrocytes express receptors for multiple neuromodulators, including noradrenaline, but the extent to which astrocytes are involved in noradrenergic signaling remains unclear. To test whether astrocytes are involved in noradrenergic neuromodulation in mice, we knocked down the major noradrenaline receptor in astrocytes, the α1A- adrenoreceptor. Using this model, we found that the α1A-adrenoreceptor is involved in triggering intracellular calcium transients in astrocytes, which are generally thought to underlie astrocyte function. To test if impaired α1A-adrenoreceptor signaling in astrocytes affected the function of neuronal circuits in V1, we used electrophysiological measurements and found that noradrenergic signaling through astrocyte α1A-adrenoreceptor controls the basal level of inhibition and regulates plasticity in V1 by potentiating synaptic responses in circuits involved in visual information processing. The α1A-adrenoreceptor (α1A-NAR) is the major α1-NAR in primary visual cortex (V1) α1A-NAR signaling triggers astrocyte Ca2+ responses in V1. Astrocyte α1A-NARs play a key role in regulating basal inhibitory transmission and are crucial for LTP induction in V1

Parkinsons Disease (PD) is the second most common neurodegenerative disorder and is generally characterized by impaired motor functions. It currently affects 6.3 million people aged 60 years and more, worldwide. The pathological hallmarks of PD are Lewy bodies (abnormal aggregation of α-synuclein inside cells), which are observed primarily in the substantia nigra (SN) region of the midbrain. It is yet not known how different cell types in SN respond during PD and what are the molecular mechanisms underlying neurodegeneration. To address this question, we generated a large-scale single cell transcriptomics dataset from human post-mortem SN tissue of 29 donors including 15 sporadic cases and 14 controls. We obtained data for a total of ~80K nuclei, representing major cell types of the brain (including neurons, astrocytes, microglia and oligodendrocytes). Pathway and differential gene expression analysis revealed multicellular character of PD pathology involving major cellular response from neuronal and glial cells.Competing Interest StatementTGB is CEO at The Bioinformatics CRO and Senior Director of Bioinformatics at bit.bio. DRT received speaker honorary or travel reimbursement from Biogen (USA) and UCB (Brussels, Belgium), and collaborated with Novartis Pharma AG (Basel, Switzerland), Probiodrug (Halle (Saale), Germany), GE Healthcare (Amersham, UK), and Janssen Pharmaceutical Companies (Beerse, Belgium).

The Armenian highlands encompasses rugged and environmentally diverse landscapes and is characterized by a mosaic of distinct ecological niches and large temperature gradients. Strong seasonal fluctuations in resource availability along topographic gradients likely prompted Pleistocene hominin groups to adapt by adjusting their mobility strategies. However, the role that elevated landscapes played in hunter-gatherer settlement systems during the Late Pleistocene (Middle Palaeolithic [MP]) remains poorly understood. At 1640 m above sea level, the MP site of Kalavan 2 (Armenia) is ideally positioned for testing hypotheses involving elevation-dependent seasonal mobility and subsistence strategies. Renewed excavations at Kalavan 2 exposed three main occupation horizons and ten additional low densities lithic and faunal assemblages. The results provide a new chronological, stratigraphical, and paleoenvironmental framework for hominin behaviors between ca. 60 to 45 ka. The evidence presented suggests that the stratified occupations at Kalavan 2 locale were repeated ephemerally most likely related to hunting in a high-elevation within the mountainous steppe landscape.

Daily data collection during archaeological fieldwork forms the basis for later interpretation and analysis. Across the world, we observe a wide variety of digital data collection methods and tools employed during fieldwork. Here, we detail the daily practices at four recent survey and excavation projects in the South Caucasian country of Armenia. As archaeology continues to become ever more digital, it is useful to consider these day-to-day recording processes at a typical field project. We provide details on both the types of data collected and the ways they are collected so as to foreground these topics. Finally, we reflect on how our work is currently impacted by digital changes and how it may continue to change in the future.