“TMEM16K is an interorganelle regulator of endosomal sorting”

Communication between organelles is essential for their cellular homeostasis. Neurodegeneration reflects the declining ability of neurons to maintain cellular homeostasis over a lifetime1. The endolysosomal pathway plays a prominent role in this process by regulating protein and lipid sorting and degradation2. Here, we report that TMEM16K, an endoplasmic reticulum lipid scramblase3 causative for spinocerebellar ataxia (SCAR10), is an interorganelle regulator of the endolysosomal pathway. We identify endosomal transport as a major functional cluster of TMEM16K in proximity biotinylation proteomics analyses. TMEM16K forms contact sites with endosomes, reconstituting split-GFP with small GTPase RAB7. Our study further implicates TMEM16K lipid scrambling activity in endosomal sorting at these sites. Loss of TMEM16K function led to impaired endosomal retrograde transport and neuromuscular function, one of the symptoms of SCAR10. Thus, TMEM16K-containing ER-endosome contact sites represent clinically relevant platforms for regulating endosomal sorting.

17β-estradiol alters mRNA co-expression after murine muscle injury and mild hypobaria

Here, we assessed the effects of 17β-estradiol exposure on mRNA co-expression patterns of muscle tissue during recovery in a closed muscle crush injury and hypobaria exposure murine model. Eighteen ovariectomized placebo-treated and 18 ovariectomized 17β-estradiol-treated female mice underwent closed muscle crush injury and hypobaric simulated flight. The mice recovered for 32, 96, or 192 h, and then were euthanized. Their harvested injured lateral gastrocnemius muscles underwent microarray analysis. We used weighted gene co-expression network analysis to construct a co-expression network for the control mice, and then applied the same network to the estrogen-treated mice. We compared the relationships between co-expression in gene modules over time between the two experimental groups. Enriched functional cluster analyses of significant co-expression network modules document a variety of different pathways of interest. Some of the functional cluster enrichments within several of the significantly correlated modules are related to the formation and function of microtubules. Our findings demonstrate that following a closed muscle crush injury in a murine model, the presence of 17β-estradiol alters mRNA co-expression patterns over time. It appears that estrogen promotes the expression of mRNA related to microtubule activity within the cytoskeleton of myofibers and in movement of organelles and receptors. Further study is needed, but the enrichment of these microtubule-related pathways may be integral in the muscle tissue regeneration process, and thus suggests that the presence of estrogen may promote muscle recovery through the work of the microtubules. Impact statement This study uses a murine model to address the clinical situation of transporting soldiers or civilians who have sustained skeletal muscle trauma by air. Our findings show that crush-injured muscle tissue of ovariectomized, 17β-estradiol-treated mice exposed to mild hypobaric hypoxia exhibited mRNA co-expression patterns among pathways associated with microtubule-dependent processes. Palmitoylation and other pathways necessary for movement of estrogen receptors to the cell membrane were also differentially enriched in the estrogen-treated mice. These first findings reframe the discussion regarding estrogen effects during muscle recovery from an inflammation-oriented inquiry to that of a structural, cytoskeletal inquiry and support additional research to understand the non-inflammation-related influences of estrogen during muscle recovery. Also, these results may suggest a role for estrogen or estrogen-like substances to treat muscle trauma.

Collagen-Chitosan- Glycerol-HPMC Composite as Cornea Artificial Candidate

The number of blindness is tend to be increased year by year. One of the blindness cause is cornea ulcer.The cause of cornea ulcer is bacteria, fungi, and herpes simplex virus. Cornea transplantation is the only treatment which could widely accepted for blindness. Transplant by donor network becomes the only treatment that is acceptable on a large for blindness. However, treatment donor transplants have many shortcomings in complications post surgery such as host response, donor limitations, incompatibility and the length of time healing. As technology develops, there are many corneal substitutes based on natural ingredients derived from collagen or their derivatives because they promise better properties in biocompatibility. The aim of research are to conduct the synthesis and characterization of collagen- chitosan- glycerol - HPMC as artificial cornea such functional cluster test, cytotoxycity test, morphological test and antibacterial test. Based on functional cluster test, there are functional groups of all components of composite materials. While from cytotoxicity test, all samples have a percentage of living cells above 85%. The morphology test is showed that the pore size of sample B with composition collagen-chitosan-glycerol-HPMC is in accordance with the standard pore size for keratoprothesis. Sample A (collagen-chitosan-glycerol) and sample B (collagen-chitosan-glycerol-HPMC) have strong antibacterial properties.Biocomposite of collagen-chitosan-glycerol could be considered as artificial cornea due to the proximity with the corneal characteristics.

Mechanism of Organization and Development of a Cluster

The latest trends of integration of the Central and Eastern Europe countries in the global economy increase the need for regional specialization and for the assertion on the markets through competitive advantages based on innovation, knowledge transfer and a rational use of resources. A certainway to meet these needs is to create clusters. This paper focuses on studying the principles and mechanisms of organizing a cluster and aims at developing a functional cluster creation and development algorithm. This paper deals with the study of the principles and mechanisms of cluster organization and aims at the development of a functional cluster creation and development algorithm. By using the logical reasoning method, bibliographic research and indirect observation, we have developed a mechanism of a cluster organization based on three basic stages: preparation, initiation and development. The knowledge and efficient implementation of this algorithm can help to create a network of innovation clusters capable to bring regional economic benefits. The mechanism proposed in this paper can be used in the promotion of cluster initiatives in all countries of Central and Eastern Europe, including Moldova, Ukraine and Romania. Keywords: cluster, support policies, funding mechanism

Bioinformatic Analysis of a “Functional Cluster” Probably Related to Retinitis Pigmentosa

Background: Retinitis pigmentosa is an eye hereditary disease caused by photoreceptor death. One of the biggest problem is represented by its genetic heterogeneity, which has not yet allowed us to found all causative genes and how known ones could influence each other, leading to retinitis etiopathogenesis. Objective: To propose the possible relation between the “functional cluster” of vision dark adaptation, made of five phototransductional genes (RCVRN, GNB1, GNGT1, GRK7 and ARRB1), and retinitis pigmentosa onset. Methods: A bioinformatic approach was exploited: the starting point was searching through online database as PubMed and EMBASE to acquire information about the state of art of these gene. This step was followed by an in-silico analysis, performed by softwares as Cytoscape and Genecards Suite Plus, articulated in three phases: I) identification of common pathways and genes involved in; II) collection of previously detected genes; III) deep analysis of intersected genes and implication into etiopathogenesis of analzyed disease. Results: The whole in-silico analysis showed that all five gene products cooperate during phototransductional activation, expecially in the dark adaptation. Interestingly, the most exciting aspect regards the direct relation with several known retinitis pigmentosa causative genes, in form of protein interactions or other pathway correlations. Conclusion: Pathway analysis permitted us to hypothesize a possible role of analyzed genes in retinitis pigmentosa etiopathogenesis, also considering the key activity of their encoded proteins. Next step will be validating our hypotesis with functional assays to ensure the real meaning of this possible association, leading to new potential retinitis pigmentosa causative genes.

Criteria and methods for monitoring threats to economic security in the economy sectors in the conditions of external determinants transformation

The authors analyzed works of domestic and foreign scientists who studied the issue. The results of the work: first, the analysis of the methods applied for monitoring of threats to economic security (from the standpoint of system, resource, functional, cluster, and situational, cyclic and process approaches) is made and their advantages and drawbacks with regard to the specifics of the development of the forest sector of the Russian economy are identified.