6-gene promoter methylation assay is potentially applicable for prostate cancer clinical staging based on urine collection following prostatic massage

The detection of prostate cancer (PCa) biomarkers in bodily fluids, a process known as liquid biopsy, is a promising approach and particularly beneficial when performed in urine samples due to their maximal non‑invasiveness requirement of collection. A number of gene panels proposed for this purpose have allowed discrimination between disease‑free prostate and PCa; however, they bear no significant prognostic value. With the purpose to develop a gene panel for PCa diagnosis and prognosis, the methylation status of 17 cancer-associated genes were analyzed in urine cell‑free DNA obtained from 31 patients with PCa and 33 control individuals using methylation‑specific polymerase chain reaction (MSP). Among these, 13 genes indicated the increase in methylation frequency in patients with PCa compared with controls. No prior association has been reported between adenomatosis polyposis coli 2 (APC2), homeobox A9, Wnt family member 7A (WNT7A) and N‑Myc downstream‑regulated gene 4 protein genes with PCa. The 6‑gene panel consisting of APC2, cadherin 1, forkhead box P1, leucine rich repeat containing 3B, WNT7A and zinc family protein of the cerebellum 4 was subsequently developed providing PCa detection with 78% sensitivity and 100% specificity. The number of genes methylated (NGM) value introduced for this panel was indicated to rise monotonically from 0.27 in control individuals to 4.6 and 4.25 in patients with highly developed and metastatic T2/T3 stage cancer, respectively. Therefore, the approach of defining the NGM value may not only allow for the detection of PCa, but also provide a rough evaluation of tumor malignancy and metastatic potential by non‑invasive MSP analysis of urine samples

Експериментальне дослідження впливу часткового діелектричного заповнення на електродинамічні характеристики та розміри прямокутного хвилеводу:

The results of an experimental study of the effect of partial dielectric filling (PDF) on the electrodynamic characteristics and dimensions of a rectangular waveguide are presented. The results of the experimental study are compared with the calculated ones obtained using an approximate method for determining the effective permittivity and propagation constant of a partially filled waveguide (PWF) presented in [1]. The approximate method differs from the existing ones in that it is not necessary to solve transcendental dispersion equations to determine the propagation constant in a rectangular waveguide with a PDF. In particular, the results of a theoretical calculation of the dependences of the size of the wide wall of the PWF with cross-sectional dimensions of 23 × 10 mm on the change in the fill factor along the wide wall of the waveguide at a frequency of 10 GHz, the wavelength, the wave impedance of the PWF, and the propagation constant on the change in the fill factor along the wide wall, waveguide in the frequency band 6–14 GHz for modification 2–1–2 (thin dielectric plates near the side walls) and 1–2 (thin dielectric plate near one side wall) for the H10 type wave are presented. Experimental studies were carried out using a laboratory setup consisting of a signal generator, a voltage ratio meter, a measuring line based on a rectangular waveguide, to the output of which a short circuit was connected. Dielectric plates (PTFE Ф4) 10 mm wide, 2 mm and 4 mm thick, and 253 mm long were installed inside the rectangular waveguide of the measuring line. The maximum relative error of the results of experimental studies for modifications 2-1-2, 1-2 does not exceed 15%, in particular, for modification 2-1-2 it is less than for 1-2. The presented results confirm the feasibility and high accuracy of calculating the electrodynamic characteristics of the PWF by the approximate method [1]. The reliability and validity of the results obtained is ensured by a sufficiently high convergence of the calculation results with the experimental ones, under boundary conditions with known results, the convergence of the obtained formulas in units of measurement.Представлены результаты экспериментального исследования влияния частичного диэлектрического заполнения (ЧДЗ) на электродинамические характеристики и размеры прямоугольного волновода. Результаты экспериментального исследования сравниваются с расчетными, полученными с помощью приближенного метода определения эффективной диэлектрической проницаемости и постоянной распространения частично заполненного волновода (ЧЗВ), представленного в [1]. Приближенный метод отличается от существующих тем, что для определения постоянной распространения в прямоугольном волноводе с ЧДЗ не нужно решать трансцендентные дисперсионные уравнения. В частности, приводятся результаты теоретического расчета зависимостей размера широкой стенки ЧЗВ с размерами поперечного сечения 23×10 мм от изменения коэффициента заполнения вдоль широкой стенки волновода на частоте 10 ГГц, длины волны, поперечного волнового сопротивления ЧЗВ и постоянной распространения от изменения коэффициента заполнения вдоль широкой стенки волновода в полосе частот 6 – 14 ГГц для модификации 2–1–2 (тонкие диэлектрические пластины возле боковых стенок) и 1–2 (тонкая диэлектрическая пластина возле одной боковой стенки) для волны типа Н10. Экспериментальные исследования проведены с помощью лабораторной установки, состоящей из генератора сигналов, измеретителя отношений напряжений, измерительной линии на базе прямоугольного волновода, к выходу которой присоединялся короткозамыкатель. Внутрь прямоугольного волновода измерительной линии устанавливались диэлектрические пластины (фторопласт Ф4) шириной 10 мм, толщиной 2 мм и 4 мм, длиной 253 мм. Максимальная относительная погрешность результатов экспериментальных исследований для модификаций 2-1-2, 1-2 не превышает 15 %, в частности для модификации 2-1-2 она меньше, чем для 1-2. Представленные результаты подтверждают целесообразность и высокую точность расчетов электродинамических характеристик ЧЗВ приближенным методом [1]. Достоверность и обоснованность полученных результатов обеспечивается достаточно высокой сходимостью результатов расчета с экспериментальными, при граничных условиях с известными результатами, сходимостью полученных формул по единицам измерения.Представлено результати експериментального дослідження впливу часткового діелектричного заповнення (ЧДЗ) на електродинамічні характеристики та розміри прямокутного хвилеводу. Результати експериментального дослідження порівнюються із розрахунковими, отриманими за допомогою наближеного методу визначення ефективної діелектричної проникності та сталої поширення частково заповненого хвилеводу (ЧЗХ), представленого в [1]. Зокрема наводяться результати теоретичного розрахунку залежностей розміру широкої стінки ЧЗХ із розмірами поперечного перерізу 23×10 мм від коефіцієнта заповнення уздовж широкої стінки хвилеводу на частоті 10 ГГц, довжини хвилі, хвильового опору ЧЗХ та сталої поширення від коефіцієнта заповнення вздовж широкої стінки хвилеводу у смузі частот 6 – 14 ГГц для модифікацій ЧЗХ 2–1–2 (тонкі діелектричні пластини біля бокових стінок) та 1–2 (тонка діелектрична пластина біля однієї бокової стінки) для хвилі типу Н10. Експериментальні дослідження проведено за допомогою лабораторної установки, яка складалась з генератора НВЧ сигналів, вимірювальної лінії (на базі прямокутного хвилеводу), металевого короткозамикача та вимірювача відношення напруг. Всередину прямокутного хвилеводу вимірювальної лінії встановлювались діелектричні пластини з фторопласту Ф4 шириною 10 мм, товщиною 2 мм та 4 мм, довжиною 25,3 см. Максимальна відносна похибка результатів експериментальних досліджень для модифікацій 2–1–2, 1–2 не перевищує 15 %, зокрема для модифікації 2–1–2 вона менша ніж для 1–2. Отримані експериментальні результати підтвердили достатньо високу точність наближеного методу розрахунку ЧЗХ, наведеного у роботі [1]

Core Proteome of the Minimal Cell: Comparative Proteomics of Three Mollicute Species

Mollicutes (mycoplasmas) have been recognized as highly evolved prokaryotes with an extremely small genome size and very limited coding capacity. Thus, they may serve as a model of a ‘minimal cell’: a cell with the lowest possible number of genes yet capable of autonomous self-replication. We present the results of a comparative analysis of proteomes of three mycoplasma species: A. laidlawii, M. gallisepticum, and M. mobile. The core proteome components found in the three mycoplasma species are involved in fundamental cellular processes which are necessary for the free living of cells. They include replication, transcription, translation, and minimal metabolism. The members of the proteome core seem to be tightly interconnected with a number of interactions forming core interactome whether or not additional species-specific proteins are located on the periphery. We also obtained a genome core of the respective organisms and compared it with the proteome core. It was found that the genome core encodes 73 more proteins than the proteome core. Apart of proteins which may not be identified due to technical limitations, there are 24 proteins that seem to not be expressed under the optimal conditions

Circadian Clock Genes Contribute to the Regulation of Hair Follicle Cycling

Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK–regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes

Genome-Wide and Phase-Specific DNA-Binding Rhythms of BMAL1 Control Circadian Output Functions in Mouse Liver

Temporal mapping during a circadian day of binding sites for the BMAL1 transcription factor in mouse liver reveals genome-wide daily rhythms in DNA binding and uncovers output functions that are controlled by the circadian oscillator

Timeless Links Replication Termination to Mitotic Kinase Activation

The mechanisms that coordinate the termination of DNA replication with progression through mitosis are not completely understood. The human Timeless protein (Tim) associates with S phase replication checkpoint proteins Claspin and Tipin, and plays an important role in maintaining replication fork stability at physical barriers, like centromeres, telomeres and ribosomal DNA repeats, as well as at termination sites. We show here that human Tim can be isolated in a complex with mitotic entry kinases CDK1, Auroras A and B, and Polo-like kinase (Plk1). Plk1 bound Tim directly and colocalized with Tim at a subset of mitotic structures in M phase. Tim depletion caused multiple mitotic defects, including the loss of sister-chromatid cohesion, loss of mitotic spindle architecture, and a failure to exit mitosis. Tim depletion caused a delay in mitotic kinase activity in vivo and in vitro, as well as a reduction in global histone H3 S10 phosphorylation during G2/M phase. Tim was also required for the recruitment of Plk1 to centromeric DNA and formation of catenated DNA structures at human centromere alpha satellite repeats. Taken together, these findings suggest that Tim coordinates mitotic kinase activation with termination of DNA replication

Body weight, metabolism and clock genes

Biological rhythms are present in the lives of almost all organisms ranging from plants to more evolved creatures. These oscillations allow the anticipation of many physiological and behavioral mechanisms thus enabling coordination of rhythms in a timely manner, adaption to environmental changes and more efficient organization of the cellular processes responsible for survival of both the individual and the species. Many components of energy homeostasis exhibit circadian rhythms, which are regulated by central (suprachiasmatic nucleus) and peripheral (located in other tissues) circadian clocks. Adipocyte plays an important role in the regulation of energy homeostasis, the signaling of satiety and cellular differentiation and proliferation. Also, the adipocyte circadian clock is probably involved in the control of many of these functions. Thus, circadian clocks are implicated in the control of energy balance, feeding behavior and consequently in the regulation of body weight. In this regard, alterations in clock genes and rhythms can interfere with the complex mechanism of metabolic and hormonal anticipation, contributing to multifactorial diseases such as obesity and diabetes. The aim of this review was to define circadian clocks by describing their functioning and role in the whole body and in adipocyte metabolism, as well as their influence on body weight control and the development of obesity

Генетический анализ вируса гриппа А / Н1N1 "пандемический" в условиях эпидемии

Genetic analysis of pandemic influenza A / H1N1 virus during epidemia.Генетический анализ вируса гриппа А / Н1N1 "пандемический" в условиях эпидемии