МІКРОБІОМ У ФІЗІОЛОГІЇ ЛЮДИНИ

Basic facts concerning human microbiome. Long-term coevolution of the human organism and microbe community has led to the formation of an additional anatomical structure in the human body that was named microbiome. This unique microbe structure has a complex organ organization that functions in mutual consent with all other human organs and systems. Localization of microbiome in the human body. All biotopes of the human body (oral cavity, hair, nose, ears, urogenital system, skin, eyes, gastrointestinal tract, and bronchopulmonary system) have their own unique and specific microbe complex that consists of specialized microbes with various functions. Besides, all these local microbiomes are in continuous interactions with each other and with macroorganism making the united superorganism system. Microbiome functional activity. Microbiome takes active part in realization of a wide spectrum of vitally important physiological processes, including energetic homeostasis and metabolism, synthesis of vitamins and other significant nutrients, endocrine signaling, preventing pathogen colonization, regulation of immune function, metabolism of xenobiotics, toxins, carcinogens and other harmful substances. Most these functions are closely connected and tightly implicated with human physiology. Changes of microbiome during ontogenesis. Microbiome formation begins long before childbirth and continues 2–3 years after it. In the course of the organism maturation and aging, microbiome changes appreciably. Microbiome improvement at all stages of human life is of the utmost importance for improving health of all age group population. Microbiome damages in etiology of human diseases. Numerous investigations showed that microbiome changes are associated with a large spectrum of gastrointestinal and systemic diseases, including inflammatory intestinal diseases, asthma, obesity, metabolic syndrome, cardiovascular pathology, autoimmune, neurobehavioral and many other diseases. Modern approaches to microbiome improvement. To date, many different methods of therapeutic influence on microbiome have been proposed: changing diet, applying probiotics, prebiotics or their complexes (synbiotics), using functional foodstuffs, carrying out fecal transplantation etc. The authors propose universal approaches to prophylaxes of microbiome disturbances and its reversal in people of different age categories; its efficiency has been convincingly demonstrated in clinics.Загальні відомості про мікробіом людини. В результаті тривалої коеволюції людини з мікробним співтовариством сконструйовано і вдосконалено додаткову анатомічну структуру тіла людини, яка отримала назву мікробіом. Цей унікальний мікробний орган має складну органну структуру, функціонуючу у взаємній згоді з усіма іншими органами та системами людини. Локалізація мікробіому в тілі людини. Всі біотопи тіла людини (ротова порожнина, волосся, ніс, вуха, сечостатеві шляхи, шкіра, очі, шлунково-кишковий тракт, бронхо-легенева системи) містять свій власний унікальний специфічний складний мікробний комплекс, що складається зі спеціалізованих мікробів з різними функціями. При цьому всі локальні мікробіоми перебувають у постійній взаємодії між собою і з макроорганізмом, утворюючи єдину надорганізмову систему. Функціональна активність мікробіому. Мікробіом бере активну участь в реалізації широкого спектра життєво важливих фізіологічних процесів, включаючи енергетичний гомеостаз і метаболізм, синтез вітамінів та інших важливих нутрієнтів, ендокринну сигналізацію, регуляцію імунної функції, метаболізм ксенобіотиків, токсинів, канцерогенів та інших шкідливих сполук, запобігає колонізації патогенами. Більшість цих функцій взаємопов’язана та тісно переплетена з фізіологією людини. Зміни мікробіому в онтогенезі. Процес формування мікробіому починається задовго до народження дитини і продовжується 2-3 роки після народження. У міру дорослішання та старіння організму спостерігаються помітні зміни мікробіому. Підтримка мікробіому на всіх етапах життя людини має величезне значення для поліпшення здоров’я населення всіх вікових категорій. Місце мікробіомних порушень в етіології захворювань людини. Багатьма дослідженнями показано, що зміни в мікробіомі асоціюються з широким спектром шлунково-кишкових і системних захворювань, включаючи запальні хвороби кишечнику, астму, ожиріння, метаболічний синдром, серцево-судинну патологію, автоімунні, нейроповедінкові, та з багатьма іншими хворобами. Сучасні підходи до оздоровлення мікробіому. Сьогодні пропонуються різні методи терапевтичного впливу на мікробіом: зміна дієти, застосування пробіотиків, пребіотиків або їх комплексів (синбіотиків), продуктів функціонального харчування, ентеросорбентів, проведення фекальної трансплантації та ін. Авторами запропоновані універсальні підходи до профілактики мікробіомних порушень та їх усунення в осіб різних вікових категорій, ефективність яких переконливо доведена клінікою

Two females with mutations in USP9X highlight the variable expressivity of the intellectual disability syndrome

The genetic causes of intellectual disability (ID) are heterogeneous and include both chromosomal and monogenic etiologies. The X-chromosome is known to contain many ID-related genes and males show a marked predominance for intellectual disability. Here we report two females with syndromic intellectual disability. The first individual was relatively mild in her presentation with mild-moderate intellectual disability, hydronephrosis and altered pigmentation along the lines of Blaschko without additional congenital anomalies. A second female presented shortly after birth with dysmorphic facial features, post-axial polydactyly and, on follow-up assessment, demonstrated moderate intellectual disability. Chromosomal studies for Individual 1 identified an X-chromosome deletion due to a de novo pericentric inversion; the inversion breakpoint was associated with deletion of the 5′UTR of the USP9X, a gene which has been implicated in a syndromic intellectual disability affecting females. The second individual had a de novo frameshift mutation detected by whole-exome sequencing that was predicted to be deleterious, NM_001039590.2 (USP9X): c.4104_4105del (p.(Arg1368Serfs*2)). Haploinsufficiency of USP9X in females has been associated with ID and congenital malformations that include heart defects, scoliosis, dental abnormalities, anal atresia, polydactyly, Dandy Walker malformation and hypoplastic corpus callosum. The extent of the congenital malformations observed in Individual 1 was less striking than Individual 2 and other individuals previously reported in the literature, and suggests that USP9X mutations in females can have a wider spectrum of presentation than previously appreciated

Influence of gel bentonite on physiological indicators of the white laboratory mice.

The evaluation of the effect of lifelong usage of sodium form of gel bentonite on some physiological parameters of mice (body weight, feed and water intake, general condition, change in coordination of movements, state of wool, fertility and mortality) was performed on 110 white laboratory mice (BALB / c line). This experimental study was carried out in two replicates. To accomplish this task, the mice were divided into two groups: control – the animals were on a standard diet, and experimental – they used water with the addition of sodium form of bentonite gel (0.5-1%). It was found that prolonged intake of bentonite gel by laboratory animals neither led to an excessive increase in their weight (the weight gain of the experimental group did not differ statistically significantly from the control group, p≤0.05), nor did it cause acute or chronic intoxication. It is also shown that the constant use of bentonite has a positive effect on the organism of experimental mice, which is expressed in the decrease of animal mortality, increase of life expectancy and pronounced positive effect on fertility functions (increase in the number of offspring). Based on the obtained data it can be assumed that the continuous intake of bentonite by the animal organism is one of the factors of their microbiome improvement, which affects on a plenty of physiological functions, including animals reproduction. It is possible that smectite sorbents also enrich the body of mice by certain essential mineral elements (silicon, etc.) and has cytomucoprotective properties concerning the mucous membranes of the macroorganism

Influence of gel bentonite on physiological indicators of the white laboratory mice.

The evaluation of the effect of lifelong usage of sodium form of gel bentonite on some physiological parameters of mice (body weight, feed and water intake, general condition, change in coordination of movements, state of wool, fertility and mortality) was performed on 110 white laboratory mice (BALB / c line). This experimental study was carried out in two replicates. To accomplish this task, the mice were divided into two groups: control – the animals were on a standard diet, and experimental – they used water with the addition of sodium form of bentonite gel (0.5-1%). It was found that prolonged intake of bentonite gel by laboratory animals neither led to an excessive increase in their weight (the weight gain of the experimental group did not differ statistically significantly from the control group, p≤0.05), nor did it cause acute or chronic intoxication. It is also shown that the constant use of bentonite has a positive effect on the organism of experimental mice, which is expressed in the decrease of animal mortality, increase of life expectancy and pronounced positive effect on fertility functions (increase in the number of offspring). Based on the obtained data it can be assumed that the continuous intake of bentonite by the animal organism is one of the factors of their microbiome improvement, which affects on a plenty of physiological functions, including animals reproduction. It is possible that smectite sorbents also enrich the body of mice by certain essential mineral elements (silicon, etc.) and has cytomucoprotective properties concerning the mucous membranes of the macroorganism

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Reducing the probability of false positive research findings by pre-publication validation – Experience with a large multiple sclerosis database

<p>Abstract</p> <p>Background</p> <p>Published false positive research findings are a major problem in the process of scientific discovery. There is a high rate of lack of replication of results in clinical research in general, multiple sclerosis research being no exception. Our aim was to develop and implement a policy that reduces the probability of publishing false positive research findings.</p> <p>We have assessed the utility to work with a pre-publication validation policy after several years of research in the context of a large multiple sclerosis database.</p> <p>Methods</p> <p>The large database of the Sylvia Lawry Centre for Multiple Sclerosis Research was split in two parts: one for hypothesis generation and a validation part for confirmation of selected results. We present case studies from 5 finalized projects that have used the validation policy and results from a simulation study.</p> <p>Results</p> <p>In one project, the "relapse and disability" project as described in section II (example 3), findings could not be confirmed in the validation part of the database. The simulation study showed that the percentage of false positive findings can exceed 20% depending on variable selection.</p> <p>Conclusion</p> <p>We conclude that the validation policy has prevented the publication of at least one research finding that could not be validated in an independent data set (and probably would have been a "true" false-positive finding) over the past three years, and has led to improved data analysis, statistical programming, and selection of hypotheses. The advantages outweigh the lost statistical power inherent in the process.</p

Expression of the Multiple Sclerosis-Associated MHC Class II Allele HLA-DRB1*1501 Is Regulated by Vitamin D

Multiple sclerosis (MS) is a complex trait in which allelic variation in the MHC class II region exerts the single strongest effect on genetic risk. Epidemiological data in MS provide strong evidence that environmental factors act at a population level to influence the unusual geographical distribution of this disease. Growing evidence implicates sunlight or vitamin D as a key environmental factor in aetiology. We hypothesised that this environmental candidate might interact with inherited factors and sought responsive regulatory elements in the MHC class II region. Sequence analysis localised a single MHC vitamin D response element (VDRE) to the promoter region of HLA-DRB1. Sequencing of this promoter in greater than 1,000 chromosomes from HLA-DRB1 homozygotes showed absolute conservation of this putative VDRE on HLA-DRB1*15 haplotypes. In contrast, there was striking variation among non–MS-associated haplotypes. Electrophoretic mobility shift assays showed specific recruitment of vitamin D receptor to the VDRE in the HLA-DRB1*15 promoter, confirmed by chromatin immunoprecipitation experiments using lymphoblastoid cells homozygous for HLA-DRB1*15. Transient transfection using a luciferase reporter assay showed a functional role for this VDRE. B cells transiently transfected with the HLA-DRB1*15 gene promoter showed increased expression on stimulation with 1,25-dihydroxyvitamin D3 (P = 0.002) that was lost both on deletion of the VDRE or with the homologous “VDRE” sequence found in non–MS-associated HLA-DRB1 haplotypes. Flow cytometric analysis showed a specific increase in the cell surface expression of HLA-DRB1 upon addition of vitamin D only in HLA-DRB1*15 bearing lymphoblastoid cells. This study further implicates vitamin D as a strong environmental candidate in MS by demonstrating direct functional interaction with the major locus determining genetic susceptibility. These findings support a connection between the main epidemiological and genetic features of this disease with major practical implications for studies of disease mechanism and prevention