A new locus for otosclerosis, OTSC8, maps to the pericentromeric region of chromosome 9

Otosclerosis is a common disorder of the otic capsule resulting in hearing impairment in 0.3–0.4% of the Caucasian population. The aetiology of the disease remains unclear. In most cases, otosclerosis can be considered as a complex disease. In some cases, the disease is inherited as an autosomal dominant trait, sometimes with reduced penetrance. To date, seven autosomal dominant loci have been reported, but none of the disease-causing genes has been identified. In this study, we present the results of a genome-wide linkage analysis in a large Tunisian family segregating autosomal dominant otosclerosis. Linkage analysis localised the responsible gene to chromosome 9p13.1-9q21.11 with a maximal LOD score of 4.13, and this locus was named OTSC8. Using newly generated short tandem repeat polymorphism markers, we mapped this new otosclerosis locus to a 34.16 Mb interval between the markers D9S970 and D9S1799. This region comprises the pericentromeric region on both arms of chromosome 9, a highly complex region containing many duplicated sequences. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Impact of abiotic factors on some biological indices of Cyprinus carpio (L., 1758) in Ghrib dam lake, (Algeria)

This study was conducted with a sample of 733 Cyprinus carpio collected between May 2013 and February 2016 from the ecosystem lake in the Ghrib dam which is eutrophic. Cyprinus carpio in this dam is characterized by a single fractional spawning that begins in the spring and ends in the late summer. The distributions of the viscerosomatic and gonadosomatic indices decrease between the spring and summer seasons. These periods correspond to the spawning period and the biological break of this species. They progressively increase between autumn and winter when the biological activity of the species returns. The hepatosomatic index progressively decreases between the spring and the summer when the hepatic reserves are used for reproduction. The repletion index shows that the trophic activity of C. carpio is intense in the spring. The condition factor varies between 1.1 and 1.35. The evolution of the biological indices of both sexes is well stressed in well‐defined periods according to the seasons. The values are weak for males and high for females. The redundancy analysis allows the characterization of the influence of the physico‐chemical parameters of the dam water, especially the role of the nutritious elements, in the biological seasonal cycle of C. carpio.     

Chromatin restoration following nucleotide excision repair involves the incorporation of ubiquitinated H2A at damaged genomic sites

Restoration of functionally intact chromatin structure following DNA damage processing is crucial for maintaining genetic and epigenetic information in human cells. Here, we show the UV-induced uH2A foci formation in cells lacking XPC, DDB2, CSA or CSB, but not in cells lacking XPA, XPG or XPF indicating that uH2A incorporation relied on successful damage repair occurring through either GGR or TCR sub-pathway. In contrast, XPA, XPG or XPF were not required for formation of γH2AX foci in asynchronous cells. Notably, the H2A ubiquitin ligase Ring1B, a component of Polycomb repressor complex 1, did not localize at DNA damage sites. However, histone chaperone CAF-1 showed distinct localization to the damage sites. Knockdown of CAF-1 p60 abolished CAF-1 as well as uH2A foci formation. CAF-1 p150 was found to associate with NER factors TFIIH, RPA p70 and PCNA in chromatin. These data demonstrate that successful NER of genomic lesions and prompt CAF-1-mediated chromatin restoration link uH2A incorporation at the sites of damage repair within chromatin.     

Concentration- and time-dependent effects of enoxaparin on human adenocarcinomic epithelial cell line A549 proliferation in vitro

Non-small cell lung cancer (NSCLC) is a major health problem. Surgery is the only potential curative treatment, in spite of the high recurrence and mortality rates. Low molecular weight heparins (LMWH) have been suggested to have a positive impact on the outcome of various cancers, mainly attributed to their anticoagulant properties; yet a direct antineoplastic effect has not been excluded. We thought to evaluate the direct effect of the LMWH enoxaparin on the human lung adenocarcinomic epithelial cell line A549 and to determine potential antiproliferative and antimetastatic effects that could guide future trials. A549 cells were cultured with different concentrations of enoxaparin (1-30 U/mL). Cell counting was performed at 24, 48, and 72 h. Detection of c-Myc protein and CD44 protein was performed by electrophoresis and Western blotting. Statistical analysis was performed using paired Student's t tests. Cell counts were decreased with increasing concentrations and time of exposure to enoxaparin. This corresponds to decreased expression of c-Myc and CD44. In conclusion, enoxaparin displayed a direct dose and exposure duration dependent suppressor effect on A549 cell proliferation and the expression of both c-Myc and CD44 in vitro, suggesting reduced proliferative and metastatic potentials of these cells.     

Aminoguanidine Changes Hippocampal Expression of Apoptosis-Related Genes,Improves Passive Avoidance Learning and Memory in Streptozotocin-Induced Diabetic Rats

Cognitive dysfunction occurs in patients with diabetes mellitus. The objective of this study was to examine whether bilateral intrahippocampal CA1 (intra-CA1) injection of aminoguanidine (AG) can either affect the Bcl-2 family gene expression or reduce the diabetic imposing abnormalities of passive avoidance learning (PAL) and memory. Rats were divided into five groups: control (C), control treated with normal saline (CS), control treated with AG (S-AG), diabetics (D), and diabetics treated with AG (D-AG). Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg). AG (30 μg/rat) or vehicle was administered intra-CA1 bilaterally at the onset of hyperglycemia. PAL was assessed 7 weeks later. Animals were killed, and hippocampus was dissected following the behavioral test. The expressions of Bax, Bcl-2, and Bcl-xl mRNAs were measured using semiquantitative RT-PCR technique. The result of passive avoidance task showed that AG significantly improved the cognitive performance in diabetic rats. Moreover, AG treatment decreased the levels of Bcl-2 and Bcl-x_L expressions in diabetic group. The ratio of Bax/Bcl-2 and Bax/Bcl-x_L decreased significantly in AG-treated diabetic animals. In conclusion, initial treatment with AG by intra-CA1 micro-injection improves the impaired passive avoidance task in STZ-induced diabetic rats which may be related to the decreased Bax/Bcl-2 and Bax/Bcl-x_L ratios.     

Bile acid supplementation improves established liver steatosis in obese mice independently of glucagon-like peptide-1 secretion

Bile acids or its derivatives may influence non-alcoholic fatty liver disease development through multiple mechanisms. Intestinal L-cells secrete glucagon-like peptide-1 (GLP-1) and can be activated by bile acids (BA) influencing insulin resistance and hepatic steatosis development and progression. The aim of the present study was to assess the effects of cholic acid (CA) or ursodeoxycholic acid (UDCA) administration on portal and systemic levels of GLP-1 in genetically obese mice with established hepatic steatosis. Eight-week-old ob/ob mice were fed CA or UDCA during 4 weeks. Systemic and portal GLP-1 levels were measured as well as glucose tolerance test, serum and biliary parameters, hepatic triglyceride content, liver histology, and hepatic gene expression of relevant genes related to bile secretion. Eight-week-old ob/ob mice exhibited marked obesity, hyperinsulinemia, and fasting hyperglycemia. Administration of both CA and UDCA was associated to decreased hepatic triglyceride content and complete reversion of histological steatosis. BA-fed animals did not exhibit significant differences in glucose tolerance. In addition, neither CA nor UDCA administration significantly influenced portal or systemic GLP-1 levels. CA and UDCA strongly ameliorated established fatty liver in ob/ob mice independently of the GLP-1 incretin pathway. Thus, the anti-steatotic action of these bile acids is likely related to direct hepatic effects.     

Validation of Monte Carlo multithreading TOpas 3.6 software in order to simulate the 6 MV Elekta Synergy MLCi2 platform linac

BackgroundMonte Carlo simulation is generally appreciated as an extraordinary technique to investigate particle physics processes and interactions in nuclear medicine and Radiation Therapy. The present task validates a new methodology of Monte Carlo simulation based on the Multithreading technique to reduce CPU time to simulate a 6 MV photon beam provided by the Elekta Synergy MLCi2 platform medical linear accelerator treatment head utilizing TOpas version 3.6 Monte Carlo software and the Slurm Marwan cluster.Materials and methodsThe simulation includes the linear accelerator (LINAC) major components. Calculations are performed for the photon beam with several treatment field sizes varying from 3 × 3 to 10 × 10 cm² at a 100 cm of distance from the source to the surface of the IBA dosimetry water box. The simulation was wholly approved by comparison with experimental distributions. To evaluate simulation accuracy, gamma index formalism for (2%/2mm) and (3%/2mm) criteria, Distance To Agreement DTA, and the estimator standard error ɛ and ɛ_max are used.ResultsGood agreement between simulations and measurements was observed for depth doses and lateral dose profiles, respectively. The gamma index comparisons also highlighted this agreement; more than 97% of the points for all simulations satisfy the quality assurance criteria of (2%/2mm). Regarding calculation performance, the event processing speed is faster using Gate-[mp] compared to TOpas-[mt] mode when running the identical simulation code for both.ConclusionsConsequently, according to the achieved results, the proposed methodology shows the first validation of TOpas in radiotherapy linacs simulations and a reduction in calculation time, capping simulation accuracy as much as possible. For this reason, this software is recommended to be serviceable for Treatment Planning Systems (TPS) purposes.     

DNA taxonomy of the potamid freshwater crabs from Northern Africa (Decapoda,Potamidae)

The Mediterranean area, from southern Balkans to western Maghreb, is inhabited by the Potamon subgenus Euthelphusa, with three currently recognised species. The Maghrebian species P. (E.) algeriense is isolated from other Potamon species by the Mediterranean Sea and the Sahara Desert, and nearly no molecular data are currently available for this taxon. Present study investigated the mtDNA and nuDNA diversity in Potamon algeriense s.l. with the aims of exploring its molecular diversity pattern throughout its known distribution range, and testing the possible presence of cryptic taxa currently lumped under this binomen. The phylogenetic and DNA taxonomy analyses showed the presence of two well-supported clades of species rank within P. algeriense s.l, with an eastern clade including the populations from Tunisia and Numidia, and a western, highly structured clade including the populations from central Algeria and Morocco. In agreement with a typical Maghrebian biogeographic pattern, the distribution of these two species shows a clear east–west divide, with a disjunction zone located in Kabylia, and a strong link between molecular diversity and segregation within different hydrographical basins is evident. The Maghreb thus proved to host an unexpectedly high genetic diversity of, and to constitute a biodiversity hot-spot for, the Potamon subgenus Euthelphusa. In the light of the existence of two well-characterised species currently lumped under P. algeriense s.l., and of their noteworthy molecular structuring, the status of Maghrebian Potamon populations should be re-assessed for both the species present in the area, which are to be considered as independent management units.