Errors in chromosome segregation during oogenesis and early embryogenesis

Errors in chromosome segregation occurring during human oogenesis and early embryogenesis are very common. Meiotic chromosome development during oogenesis is subdivided into three distinct phases. The crucial events, including meiotic chromosome pairing and recombination, take place from around 11 weeks until birth. Oogenesis is then arrested until ovulation, when the first meiotic division takes place, with the second meiotic division not completed until after fertilization. It is generally accepted that most aneuploid fetal conditions, such as trisomy 21 Down syndrome, are due to maternal chromosome segregation errors. The underlying reasons are not yet fully understood. It is also clear that superimposed on the maternal meiotic chromosome segregation errors, there are a large number of mitotic errors taking place post-zygotically during the first few cell divisions in the embryo. In this chapter, we summarise current knowledge of errors in chromosome segregation during oogenesis and early embryogenesis, with special reference to the clinical implications for successful assisted reproduction

Hypotensive therapy of arterial hypertension in chronic limb ischemia and acute thrombotic occlusion

The aim of the investigation was to evaluate the efficacy and safety of the treatment of arterial hypertension syndrome in patients with peripheral arterial disease of the lower and upper extremities and to analyze the efficiency of the effect of operative revascularization of the limb arteries on the course of arterial hypertension.Цель исследования – оценить эффективность и безопасность лечения синдрома артериальной гипертензии у больных с заболеваниями периферических артерий нижних и верхних конечностей и проанализировать эффективность воздействия оперативной реваскуляризации артерий конечностей на характер течения артериальной гипертензии

Resistance to antihypertensive therapy in hypertensive patients. The value of the renal and hemodynamic factors

In order to assess the significance of renal, renovascular lesions and dysfunctions in the development and progression of severe and resistant to combination antihypertensive therapy (GRA), arterial hypertension (AH) in 286 patients with primary hypertension of 1-3 degrees of severity, including 105 patients from the II century, and Article III. with signs of RAG. Use the classification AG European medical societies ES HI ESC 2013 (6). In 87 patients diagnosed with hypertension 1 severity, age from 27 to 65 years, on average 49,5 ± 1,4 years, 36 men, women - 51.2 patients with hypertension severity was 82, the age from 34 to 68 years, on average 58,4 ± 3,0 years, 38 men and women - 44; AH 3 tbsp. -117 people, 49 men, women - 68, age from 42 to 72 years, on average 58,3 ± 3,8 years. Target values of blood pressure (120/80 mm Hg or less) achieved on such antihypertensive therapy in 87 patients with I st. and 29 with hypertension II degree. - They were 1 study group - PN). Partial normalization of blood pressure - a level not higher than 140/90 mm Hg It was in 65 patients (53 with hypertension II degree, and 12 with Stage III AH.) - Group 2 - CHN. In 105 patients (with Stage II St.- 34 and 83 с Stage III AH. Failed to achieve a sustainable normalization of blood pressure, even when using a 3-4 component complex antihypertensive therapy on the results of blood pressure measurements over 6-8 office hours reached 180 GARDEN and (or) diastolic blood pressure of 110 mm Hg .st. - Group 3 patients - resistant AG (RAG). Resistance for hypertension was considered in cases with SBP above 180 mmHg. Art., Dad - above 110 mm Hg. St., in the absence of normalization on the background of a complex, three-component antihypertensive therapy and the worsening of concomitant coronary, cerebrovascular and renal failure, as well as the progression of visual impairment. We performed a comprehensive study of the function and structure of the MBC, which included urine and urinary sediment analysis by Nechiporenko on Zimnitsky, renal excretion and endogenous creatinine clearance. Diagnostics included dynamic renal scintigraphy, static renal scintigraphy, ultrasound of the kidneys and of the MBC, according to testimony - excretory urography, computed tomography of the adrenal glands, aortography and renal angiography. Found that patients with resistant ongoing combination antihypertensive therapy is different from the patients with stable disease rate of violations absorptive-excretory function - secretion and excretion of one or both kidneys, without significantly reducing function azotovyvedeniya. Renal artery stenosis is 4-5 times more frequently detected in patients with stable and malignant primary hypertension than in patients with labile its passage, and all vascular lesions, including pathology of the infrarenal aorta and the renal vein, almost 2 times more often. A number of forms of congenital and acquired diseases of the renal arteries and veins (7 species) were detected only in patients with resistant hypertension. Identification of the mechanisms of renal and renovascular hypertension severe allow some patients to increase the effectiveness of antihypertensive drug therapy or to achieve complete control of blood pressure.С целью оценки значимости почечных, вазоренальных поражений и дисфункций в развитии и прогрессировании тяжелой и резистентной к комбинированной гипотензивной терапии (РАГ) артериальной гипертензии (АГ) у 286 больных с первичной АГ 1 -3 степени тяжести, в том числе у 105 больных II ст. и III ст. с признаками РАГ. Использовали классификацию АГ европейских медицинских обществ ЕОГ/ЕОК, 2013 [6]. У 87 больных диагностировали АГ 1 степени тяжести, возраст от 27 до 65 лет, в среднем 49,5+1,4 года, мужчин 36, женщин - 5 1 . Больных с АГ 2 степени тяжести было 82 .возраст от 34 до 68 лет, в среднем 58,4+ 3,0 года, мужчин 38 и женщин - 44; с АГ 3 ст. -1 1 7 человек, мужчин 49, женщин - 68,возраст от 42 до 72 лет, в среднем 58,3+3,8 года. Целевых значений уровня АД (120/80 мм рт.ст. и ниже) удалось достичь на такой гипотензивной терапии у 87 больных I ст. и у 29 с АГ II ст. - они составили 1 группу исследования - ПН). Частичная нормализация АД - с уровнем не выше 140/90 мм рт.ст. была у 65 больных ( у 53 с АГ II ст. и у 12 с АГ III ст.) - 2 группа - ЧН. У 105 больных (с АГ II ст.- 34 и у 83 с АГ III ст. не удалось добиться устойчивой нормализации АД, даже при использовании 3-4 компонентной комплексной гипотензивной терапии уровень АД по результатам 6-8 офисных измерений за сутки достигал САД 180 и (или) ДАД 110мм рт .ст.- 3 группа больных - резистентной АГ (РАГ). Резистентным течение АГ считали в случаях с уровнем сАД выше 180 мм рт. ст., дАД - выше 110 мм рт. ст., при отсутствии нормализации на фоне проводимой комплексной, трехкомпонентной гипотензивной терапии и ухудшении течения сопутствующей коронарной, цереброваскулярной и почечной недостаточности, а также при прогрессировании нарушений зрения. Выполняли комплексное исследование функции и структуры органов МВС, которое включало исследование мочи и мочевого осадка, анализ по Нечипоренко, по Зимницкому, почечное выведение и клиренс эндогенного креатинина. Инструментальная диагностика включала динамическую сцинтиграфию почек, статическую сцинтиграфию почек, ультразвуковое исследование почек и органов МВС, по показаниям - экскреторную урографию, компьютерную томографию надпочечников, аортографию и ангиографию сосудов почек. Установили, что больных с резистентных к проводимой комбинированной гипотензивной терапией, отличала от больных со стабильным течением заболевания частота нарушений поглотительно-выделительной функции - секреции и экскреции одной или двух почек, без существенного снижения функции азотовыведения. Стенозы почечных артерий в 4-5 раз чаще выявлялись у больных со стабильной и злокачественной первичной гипертензией, чем у больных с лабильным ее течением, а все сосудистые поражения, включая патологию инфраренального отдела аорты и почечных вен, почти в 2 раза чаще. Целый ряд форм врожденной и приобретенной патологии почечных артерий и вен (7 видов) выявлялись только у больных с резистентной гипертензией. Идентификация вазоренальных и нефрогенных механизмов тяжелой артериальной гипертензии позволяла у части больных повысить эффективность медикаментозной гипотензивной терапии или добиться полного контроля АД

Combining transcriptional profiling and genetic linkage analysis to uncover gene networks operating in hematopoietic stem cells and their progeny

Stem cells are unique in that they possess both the capacity to self-renew and thereby maintain their original pool as well as the capacity to differentiate into mature cells. In the past number of years, transcriptional profiling of enriched stem cell populations has been extensively performed in an attempt to identify a universal stem cell gene expression signature. While stem-cell-specific transcripts were identified in each case, this approach has thus far been insufficient to identify a universal group of core “stemness” genes ultimately responsible for self-renewal and multipotency. Similarly, in the hematopoietic system, comparisons of transcriptional profiles between different hematopoietic cell stages have had limited success in revealing core genes ultimately responsible for the initiation of differentiation and lineage specification. Here, we propose that the combined use of transcriptional profiling and genetic linkage analysis, an approach called “genetical genomics”, can be a valuable tool to assist in the identification of genes and gene networks that specify “stemness” and cell fate decisions. We review past studies of hematopoietic cells that utilized transcriptional profiling and/or genetic linkage analysis, and discuss several potential future applications of genetical genomics

Does Selection against Transcriptional Interference Shape Retroelement-Free Regions in Mammalian Genomes?

BACKGROUND: Eukaryotic genomes are scattered with retroelements that proliferate through retrotransposition. Although retroelements make up around 40 percent of the human genome, large regions are found to be completely devoid of retroelements. This has been hypothesised to be a result of genomic regions being intolerant to insertions of retroelements. The inadvertent transcriptional activity of retroelements may affect neighbouring genes, which in turn could be detrimental to an organism. We speculate that such retroelement transcription, or transcriptional interference, is a contributing factor in generating and maintaining retroelement-free regions in the human genome. METHODOLOGY/PRINCIPAL FINDINGS: Based on the known transcriptional properties of retroelements, we expect long interspersed elements (LINEs) to be able to display a high degree of transcriptional interference. In contrast, we expect short interspersed elements (SINEs) to display very low levels of transcriptional interference. We find that genomic regions devoid of long interspersed elements (LINEs) are enriched for protein-coding genes, but that this is not the case for regions devoid of short interspersed elements (SINEs). This is expected if genes are subject to selection against transcriptional interference. We do not find microRNAs to be associated with genomic regions devoid of either SINEs or LINEs. We further observe an increased relative activity of genes overlapping LINE-free regions during early embryogenesis, where activity of LINEs has been identified previously. CONCLUSIONS/SIGNIFICANCE: Our observations are consistent with the notion that selection against transcriptional interference has contributed to the maintenance and/or generation of retroelement-free regions in the human genome

miR-135A Regulates Preimplantation Embryo Development through Down-Regulation of E3 Ubiquitin Ligase Seven in Absentia Homolog 1A (SIAH1A) Expression

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules capable of regulating transcription and translation. Previously, a cluster of miRNAs that are specifically expressed in mouse zygotes but not in oocytes or other preimplantation stages embryos are identified by multiplex real-time polymerase chain reaction-based miRNA profiling. The functional role of one of these zygote-specific miRNAs, miR-135a, in preimplantation embryo development was investigated. Methodology/Principal Findings: Microinjection of miR-135a inhibitor suppressed first cell cleavage in more than 30% of the zygotes. Bioinformatics analysis identified E3 Ubiquitin Ligase Seven In Absentia Homolog 1A (Siah1a) as a predicted target of miR-135a. Western blotting and 3′UTR luciferase functional assays demonstrated that miR-135a down-regulated the expression of Siah1 in HeLa cells and in mouse zygotes. Siah1a was expressed in preimplantation embryos and its expression pattern negatively correlated with that of miR-135a. Co-injection of Siah1a-specific antibody with miR-135a inhibitor partially nullified the effect of miR-135a inhibition. Proteasome inhibition by MG-132 revealed that miR-135a regulated proteasomal degradation and potentially controlled the expression of chemokinesin DNA binding protein (Kid). Conclusions/Significance: The present study demonstrated for the first time that zygotic specific miRNA modulates the first cell cleavage through regulating expression of Siah1a. © 2011 Pang et al.published_or_final_versio

Cortical Mechanics and Meiosis II Completion in Mammalian Oocytes Are Mediated by Myosin-II and Ezrin-Radixin-Moesin (ERM) Proteins

Analysis of mouse oocyte mechanics shows that effective tension drops 6-fold from prophase I to metaphase II; the metaphase II egg has a 2.5-fold tension differential between the cortex over the spindle and the opposite cortex. Manipulation of actin, myosin-II, or ERMs alters tension levels and induces spindle abnormalities during meiosis II

Nlrp2, a Maternal Effect Gene Required for Early Embryonic Development in the Mouse

Maternal effect genes encode proteins that are produced during oogenesis and play an essential role during early embryogenesis. Genetic ablation of such genes in oocytes can result in female subfertility or infertility. Here we report a newly identified maternal effect gene, Nlrp2, which plays a role in early embryogenesis in the mouse. Nlrp2 mRNAs and their proteins (∼118 KDa) are expressed in oocytes and granulosa cells during folliculogenesis. The transcripts show a striking decline in early preimplantation embryos before zygotic genome activation, but the proteins remain present through to the blastocyst stage. Immunogold electron microscopy revealed that the NLRP2 protein is located in the cytoplasm, nucleus and close to nuclear pores in the oocytes, as well as in the surrounding granulosa cells. Using RNA interference, we knocked down Nlrp2 transcription specifically in mouse germinal vesicle oocytes. The knockdown oocytes could progress through the metaphase of meiosis I and emit the first polar body. However, the development of parthenogenetic embryos derived from Nlrp2 knockdown oocytes mainly blocked at the 2-cell stage. The maternal depletion of Nlrp2 in zygotes led to early embryonic arrest. In addition, overexpression of Nlrp2 in zygotes appears to lead to normal development, but increases blastomere apoptosis in blastocysts. These results provide the first evidence that Nlrp2 is a member of the mammalian maternal effect genes and required for early embryonic development in the mouse

Changes in kidney function and premorbid nephrologic anamnesis in patients with COVID-19, complicated by pneumonia

Coronavirus is an infection that affects not only the human immune and respiratory systems. COVID-19 has similar symptoms to that of acute respiratory infections and influenza, with complications of a new coronavirus infection affecting the heart, kidneys and other internal organs. Patients with chronic kidney disease (CKD) belong to the group of particularly high risk of COVID-19 infection and high lethality in the development of the disease. This is due to the fact that the cause of CKD is the main population diseases (diabetes mellitus, hypertension, obesity, atherosclerosis), as well as old age, which themselves contribute to high morbidity and mortality from COVID-19. Objective. To evaluate the frequency of development of renal function disorders and their semiotics in patients with COVID-19, complicated by pneumonia, who were hospitalized in the Moscow multidisciplinary hospital for diagnosis and treatment, as well as their pre-morbid background, the frequency of chronic pathology of the urinary system and disorders of carbohydrate metabo-lism and diabetes. Material and methods. The data were analyzed from 206 patients (82 men and 124 women) aged 26 to 97 years (average age 56.8±6.1 years) undergoing treatment in the 3rd department of Clinical Hospital No. 15 named after O.M. Filatov. 197 patients were discharged from the hospital, 6 patients died. CKD classifications were used from 2006 and 2013 years for division of patients into groups. There were 2 groups of patients of different ages: the 1st group — 78 patients (31 men, 47 women) aged 26—60 years (average age 48.6 years); the 2nd group — 128 patients (51 men, 77 women) aged 61—97 years (average age 74.2 years). The kidney ultrasound was performed on a Lojik-400 ultrasound scanner («General Electric», USA). In total, kidney ultrasound was carried out on 26 patients. The glomerular filtration rate (GFR) was calculated using the Cockroft-Golt formu-la, taking into account the level of creatinine concentration in blood serum, age and sex of the patient. The concentration of cre-atinine in the blood serum was determined by the method of O. Shyuk with sodium picrate on a spectrophotometer Getpremier (USA). Results. GFR was on average 23.7% higher (