Spermatogenesis-Specific Features of the Meiotic Program in Caenorhabditis elegans

In most sexually reproducing organisms, the fundamental process of meiosis is implemented concurrently with two differentiation programs that occur at different rates and generate distinct cell types, sperm and oocytes. However, little is known about how the meiotic program is influenced by such contrasting developmental programs. Here we present a detailed timeline of late meiotic prophase during spermatogenesis in Caenorhabditis elegans using cytological and molecular landmarks to interrelate changes in chromosome dynamics with germ cell cellularization, spindle formation, and cell cycle transitions. This analysis expands our understanding C. elegans spermatogenesis, as it identifies multiple spermatogenesis-specific features of the meiotic program and provides a framework for comparative studies. Post-pachytene chromatin of spermatocytes is distinct from that of oocytes in both composition and morphology. Strikingly, C. elegans spermatogenesis includes a previously undescribed karyosome stage, a common but poorly understood feature of meiosis in many organisms. We find that karyosome formation, in which chromosomes form a constricted mass within an intact nuclear envelope, follows desynapsis, involves a global down-regulation of transcription, and may support the sequential activation of multiple kinases that prepare spermatocytes for meiotic divisions. In spermatocytes, the presence of centrioles alters both the relative timing of meiotic spindle assembly and its ultimate structure. These microtubule differences are accompanied by differences in kinetochores, which connect microtubules to chromosomes. The sperm-specific features of meiosis revealed here illuminate how the underlying molecular machinery required for meiosis is differentially regulated in each sex

Betahistine in vestibular vertigo and VIRTUOSO post-marketing observational program

The article tells about the specifics of vestibular vertigo and clinical manifestations of diseases commonly associated with dizziness. The efficacy, safety and good tolerability of betahistine hydrochloride (Betaserc) in various diseases characterized by vestibular vertigo is demonstrated. The design of the VIRTUOSO observational program to evaluate Betaserc effects in patients with vertigo in routine clinical practice, is described. The authors note that the study results will help to further assess the efficacy and safety of Betaserc and determine in which diseases the drug is most often used in Russia and Ukraine

Vascular cognitive impairment: pathophysiological mechanisms, insights into structural basis, and perspectives in specific treatments

Vladimir A Parfenov,1 Olga D Ostroumova,2,3 Tatiana M Ostroumova,1 Alexey I Kochetkov,2 Victoria V Fateeva,4 Kristina K Khacheva,4 Gulnara R Khakimova,5 Oleg I Epstein61Department of Neurology, Federal State Autonomous Educational Institution of Higher Education, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russian Federation; 2Laboratory of Clinical Pharmacology and therapy, Federal State Budgetary Educational Institution of Higher Education “N.I. Pirogov Russian National Research Medical University” of the Ministry of Health of the Russian Federation, Russian Clinical and Research Center of Gerontology, Moscow, Russia; 3Department of Clinical Pharmacology, Internal Medicine and Propaedeutics I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; 4Medical Information Department, OOO NPF Materia Medica Holding, Moscow, Russian Federation; 5Research and Analytical Division of Scientific Research and Development Department, Moscow, Russian Federation; 6Laboratory of Physiologicaly Active Substances, Department of Molecular and Cellular Pathophysiology, Research Institute of General Pathology and Pathophysiology, Moscow, Russian FederationAbstract: Vascular cognitive impairment (VCI) and vascular dementia are the most common forms of cognitive disorder associated with cerebrovascular disease and related to increased morbidity and mortality among the older population. Growing evidence suggests the contribution of blood-pressure variability, cardiac arrhythmia, hyperactivation of the renin–angiotensin–aldosterone system, endothelial dysfunction, vascular remodeling and stiffness, different angiopathies, neural tissue homeostasis, and systemic metabolic disorders to the pathophysiology of VCI. In this review, we focus on factors contributing to cerebrovascular disease, neurovascular unit alterations, and novel approaches to cognitive improvement in patients with cognitive decline. One of the important factors associated with the neuronal causes of VCI is the S100B protein, which can affect the expression of cytokines in the brain, support homeostasis, and regulate processes of differentiation, repair, and apoptosis of the nervous tissue. Since the pathological basis of VCI is complex and diverse, treatment affecting the mechanisms of cognitive disorders should be developed. The prospective role of a novel complex drug consisting of released–active antibodies to S100 and to endothelial NO synthase in VCI treatment is highlighted.Keywords: vascular cognitive impairment, cerebrovascular disease, neurovascular unit, endothelial dysfunction, S100 protei

Chromosome number and secondary chromosomal associations in wild populations of Geranium pratense L. from the cold deserts of Lahaul-Spiti (India)

In this work we studied the meiotic chromosome number and details of secondary chromosomal associations recorded for the first time in Geranium pratense L. from the alpine environments in the cold deserts of Lahaul­Spiti (India). All the presently studied individuals of the species existed at 4x level (x = 14). The present chromosome count of n = 28 in the species adds a new cytotype to the already existing diploid chromosome count of 2n = 28 from the Eastern Himalayas and outside of India. Out of the six accessions scored presently four showed normal meiotic course. However, two accessions investigated from Mud, 3800 m and Koksar, 3140 m depicted abnormal meiotic course due to the presence of multivalents and univalents, and secondary associations of bivalents/chromosomes. The secondary chromosomal associations in the species existed among bivalents/chromosomes were noticed in the PMCs at prophase­I (diakinesis) and persisted till the separation of sister chromatids at M­II. The variation in the number of bivalents/chromosomes involved in the secondary associations at M­I (2–8) and A­I/M­II (2–12) has also been recorded. The occurrence of such secondary associations of bivalents/ chromosomes in G. pratense which existed at 4x level indicated the secondary polyploid nature of the species.Впервые изучены мейотическое число хромосом и особенности вторичных хромосомных ассоциаций растений Geranium pratense L., растущих на альпийских высотах холодных пустынь Lahaul-Spiti (Индия). Все изученные особи были 4х (x = 14). Хромосомный набор n = 28 у этого вида добавляет новый цитотип к уже существующему диплоидному хромосомному набору 2n = 28 из Восточных Гималаев и за пределами Индии. Из шести изученных образцов у четырех установлен нормальный ход мейоза. В то же время два образца из районов Mud, 3800 м, и Koksar, 3140 м демонстрировали аномальное течение мейоза из-за наличия мульти- и унивалентов и вторичные ассоциации биваленты/хромосомы. Вторичные хромосомные ассоциации были замечены в профазе І (диакинез) и существовали до разделения сестринских хроматид на стадии M-II. Отмечена также изменчивость числа бивалентов/хромосом, вовлеченных во вторичные ассоциации на стадиях M­I (2–8) и A­I/M­II (2–12). Наличие у G. pratense таких вторичных ассоциаций, которые существуют на уровне 4x, указывает на вторичную полиплоидную природу этого вида.Вперше вивчено мейотичне число хромосом і особливості вторинних хромосомних асоціацій рослин Geranium pratense L., що ростуть на аль-пійських висотах холодних пустель Lahaul-Spiti (Індія. Всі досліджені особини були 4х (х = 14). Хромосомний набірn = 28 у цього виду додає новий цитотип до вже існуючого диплоїдного хромосомного набору n = 28 зі Східних Гімалаїв та за межами Індії. З шести вивчених зразків у чотирьох був нормальний хід мейозу. У той же час два зразки з районів Mud, 3800 м, і Koksar, 3140 м демонстрували аномальний перебіг мейозу через наявність мульти- та унівалентів і вторинні асоціації біваленти/хромосоми. Вторинні хромосомні асоціації спостерігались в профазі І (діакінез) і існували до поділу сестринських хроматид на стадії M-II. Зазначено також мінливість числа бівалентів/хромосом, залучених у вторинні асоціації на стадіях M­I (2–8) і A­I/M­II (2–12). Наявність у G. pratense таких вторинних асоціацій, які існують на рівні 4x, вказує на вторинну поліплоїдну природу цього виду