Polo-like kinase acts as a molecular timer that safeguards the asymmetric fate of spindle microtubule-organizing centers

The microtubules that form the mitotic spindle originate from microtubule-organizing centers (MTOCs) located at either pole. After duplication, spindle MTOCs can be differentially inherited during asymmetric cell division in organisms ranging from yeast to humans. Problems with establishing predetermined spindle MTOC inheritance patterns during stem cell division have been associated with accelerated cellular aging and the development of both cancer and neurodegenerative disorders. Here, we expand the repertoire of functions Polo-like kinase family members fulfill in regulating pivotal cell cycle processes. We demonstrate that the Plk1 homolog Cdc5 acts as a molecular timer that facilitates the timely and sequential recruitment of two key determinants of spindle MTOCs distribution, that is the γ-tubulin complex receptor Spc72 and the protein Kar9, and establishes the fate of these structures, safeguarding their asymmetric inheritance during Saccharomyces cerevisiae mitosis.

An Artificial Vibrissa-Like Sensor for Detection of Flows

In nature, there are several examples of sophisticated sensory systems to sense flows, e.g., the vibrissae of mammals. Seals can detect the flow of their prey, and rats are able to perceive the flow of surrounding air. The vibrissae are arranged around muzzle of an animal. A vibrissa consists of two major components: a shaft (infector) and a follicle–sinus complex (receptor), whereby the base of the shaft is supported by the follicle-sinus complex. The vibrissa shaft collects and transmits stimuli, e.g., flows, while the follicle-sinus complex transduces them for further processing. Beside detecting flows, the animals can also recognize the size of an object or determine the surface texture. Here, the combination of these functionalities in a single sensory system serves as paragon for artificial tactile sensors. The detection of flows becomes important regarding the measurement of flow characteristics, e.g., velocity, as well as the influence of the sensor during the scanning of objects. These aspects are closely related to each other, but, how can the characteristics of flow be represented by the signals at the base of a vibrissa shaft or by an artificial vibrissa-like sensor respectively? In this work, the structure of a natural vibrissa shaft is simplified to a slender, cylindrical/tapered elastic beam. The model is analyzed in simulation and experiment in order to identify the necessary observables to evaluate flows based on the quasi-static large deflection of the sensor shaft inside a steady, non-uniform, laminar, in-compressible flow.

Polo-like kinase Cdc5 regulates Spc72 recruitment to spindle pole body in the methylotrophic yeast Ogataea polymorpha

Cytoplasmic microtubules (cMT) control mitotic spindle positioning in many organisms, and are therefore pivotal for successful cell division. Despite its importance, the temporal control of cMT formation remains poorly understood. Here we show that unlike the best-studied yeast Saccharomyces cerevisiae, position of pre-anaphase nucleus is not strongly biased toward bud neck in Ogataea polymorpha and the regulation of spindle positioning becomes active only shortly before anaphase. This is likely due to the unstable property of cMTs compared to those in S. cerevisiae. Furthermore, we show that cMT nucleation/anchoring is restricted at the level of recruitment of the γ-tubulin complex receptor, Spc72, to spindle pole body (SPB), which is regulated by the polo-like kinase Cdc5. Additionally, electron microscopy revealed that the cytoplasmic side of SPB is structurally different between G1 and anaphase. Thus, polo-like kinase dependent recruitment of γ-tubulin receptor to SPBs determines the timing of spindle orientation in O. polymorpha.

Структура та розвиток судин брижі кишечнику

The review of the results of various scientific studies, reflecting the processes of age formation of morphological and functional features of the mesenteric intestinal vessels, is presented. In this case, it has been shown that the formation of the microcirculatory channel of mesentery begins in its separate segments. Firstly, there are separate arterial and venous loops, in the middle of which one can see the capillaries. The branched net of capillaries is gradually formed and the number of arterioles and venules increases, and their diameter also increases. This process is closely related to the age-related growth of the area of the mesentery segments themselves.The process of changing the conditions of the external and internal environment of the organism (starvation, gravitational influences, hypodynamia) causes the formation of morphological reactions from the side of the vessels of the microcirculatory channel of the intestinal wall and ripples that have a phase character.Nerve trunks can be often satellites of vessels. Since they approach the intestinal wall, their number and thickness significantly decreases. Sympathetic nerve trunks around the vessels form a highly developed plexus, in which both non-myelin and myelin fibers are detected. A great number of these fibers further includes the nerve mesh on the border between the outer and middle (muscle) vessels of the vessels. The density and structure of these nerve plexuses is significantly different in the arterial and venous vessels of mesentery.In addition to nerve fibers in the outer envelope of the vessels, the complex receptor structures of different sizes can also occur. In the surface layers of the outer vascular, or in the connective tissue around it, nerve cells are found, which are either single or micro-nodes. The neurons found can be divided by structure into: multipole or pseudo-unipolar. The arteries, which supply blood to the anterior sections of the intestine, are characterized by a greater saturation of the nerve cells compared with the vessels carrying the blood to its caudal regions. Embryonic development of the nervous structures of the vascular wall is closely related to the development of the vessels themselves, and especially the formation of their muscular membrane. The main trend of this process is directed to the gradual complication of the nervous components, which is reflected in the functional capabilities of the vessels.

Vasopressin in Pediatric Critical Care

Vasopressin is a unique hormone with complex receptor physiology and numerous physiologic functions beyond its well-known vascular actions and osmoregulation. While vasopressin has in the past been primarily used in the management of diabetes insipidus and acute gastrointestinal bleeding, an increased understanding of the physiology of refractory shock, and the role of vasopressin in maintaining cardiovascular homeostasis prompted a renewed interest in the therapeutic roles for this hormone in the critical care setting. Identifying vasopressin-deficient individuals for the purposes of assessing responsiveness to exogenous hormone and prognosticating outcome has expanded research into the evaluation of vasopressin and its precursor, copeptin as useful biomarkers. This review summarizes the current evidence for vasopressin in critically ill children, with a specific focus on its use in the management of shock. We outline important considerations and current guidelines, when considering the use of vasopressin or its analogues in the pediatric critical care setting.

Modulation of pulmonary fibrosis by IL-13Rα2

Pulmonary fibrosis is a progressive and fatal disease that involves the remodeling of the distal airspace and the lung parenchyma, which results in compromised gas exchange. The median survival time once diagnosed is less than three years. Interleukin (IL)-13 has been shown to play a role in a number of inflammatory and fibrotic diseases. IL-13 modulates its effector functions via a complex receptor system that includes the IL-4 receptor (R) α, IL-13Rα1, and the IL-13Rα2. IL-13Rα1 binds IL-13 with low affinity, yet, when it forms a complex with IL-4α, it binds with much higher affinity, inducing the effector functions of IL-13. IL-13Rα2 binds IL-13 with high affinity but has a short cytoplasmic tail and has been shown to act as a nonsignaling decoy receptor. Transfection of fibroblasts and epithelial cells with IL-13Rα2 inhibited the IL-13 induction of soluble collagen, TGF-β, and CCL17. Adenoviral overexpression of IL-13Rα2 in the lung reduced bleomycin-induced fibrosis. Our work shows that overexpression of IL-13Rα2 inhibits the IL-13 induction of fibrotic markers in vitro and inhibits bleomycin-induced pulmonary fibrosis. In summary our study highlights the antifibrotic nature of IL-13Ra2.