First person – Chady Hakim

First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Chady Hakim is first author on ‘ Extensor carpi ulnaris muscle shows unexpected slow-to-fast fiber-type switch in Duchenne muscular dystrophy dogs’, published in DMM. Chady is a Research Assistant Professor in the lab of Dongsheng Duan at the University of Missouri, Colombia, MO, USA, investigating the preclinical development of gene therapy for Duchenne muscular dystrophy (DMD), with a particular interest in using the canine DMD model.

Rdh54/Tid1 inhibits Rad51-Rad54-mediated D-loop formation and limits D-loop length

Displacement loops (D-loops) are critical intermediates formed during homologous recombination. Rdh54 (a.k.a. Tid1), a Rad54 paralog in Saccharomyces cerevisiae, is well-known for its role with Dmc1 recombinase during meiotic recombination. Yet contrary to Dmc1, Rdh54/Tid1 is also present in somatic cells where its function is less understood. While Rdh54/Tid1 enhances the Rad51 DNA strand invasion activity in vitro, it is unclear how it interplays with Rad54. Here, we show that Rdh54/Tid1 inhibits D-loop formation by Rad51 and Rad54 in an ATPase-independent manner. Using a novel D-loop Mapping Assay, we further demonstrate that Rdh54/Tid1 uniquely restricts the length of Rad51-Rad54-mediated D-loops. The alterations in D-loop properties appear to be important for cell survival and mating-type switch in haploid yeast. We propose that Rdh54/Tid1 and Rad54 compete for potential binding sites within the Rad51 filament, where Rdh54/Tid1 acts as a physical roadblock to Rad54 translocation, limiting D-loop formation and D-loop length.

Detection of the DNA primary structure modifications induced by the base analog 6-n-hydroxylaminopurine in the alpha-test in yeast saccharomyces cerevisiae

Background. The alpha-test allows to detect inherited genetic changes of different types, as well as phenotypic expression of primary DNA lesions before the lesions are fixed by repair. Here we investigate ability of the alpha-test to detect base modifications induced by 6-N-hydroxylaminopurine (HAP) and determine frequency of inherited and non-inherited genetic changes in yeast strains treated with HAP. Materials and methods. The alpha-test is based on mating type regulation and detects cell type switch from to a in heterothallic yeast Saccharomyces cerevisiae. The frequency of mating type switching reflects level of both spontaneous and induced by a mutagen DNA instability. The alpha-test may be performed in two variants: illegitimate hybridization and cytoduction. Conducting both complementary tests and analysis of phenotypes of the illegitimate hybrids and cytoductants allows to detect the full spectrum of genetic events that lead to mating type switching, such as chromosome III loss and chromosome III arm loss, mutations and temporary lesions, recombination and conversion. Results. HAP increases the frequency of illegitimate hybridization by 5-fold, and illegitimate cytoduction by 10-fold. A large proportion of the primary lesions induced by HAP causes temporary mating type switch and the remainder parts are converted into inherited point mutations. Conclusion. The alpha-test can detect HAP-induced base modifications and may be used to investigate the ratio between correct and error-prone processing of such primary DNA lesions. Like other genetic toxicology tests the alpha-test has limitations, which are discussed.

ANALISIS KETINGGIAN TOOL PUNCH RIVET TERHADAP HASIL RIVET ING CONTACT PADA SWITCH LAMPU REM MOTOR TIPE C8EA

The product of CBEA Terminal B / B2 Assy is one of the C8EA type Switch components used for brake light switches on two-wheeled vehicles. In the manufacturing process often experience Contact Crack. Contact Crack problems occur in the rivet ing process. This study aims to reduce / eliminate the contact Crack problem, the method used is to conduct research on variations in the height of the punch in the rivet ing process. The initial height of the punch before the research is 49.10 mm, in this study the height of the punch to be examined is 48.60 mm, 48.70 mm, 48.80 mm, 48.90 mm and 49.00 mm. The results obtained for the most appropriate punch height are the height of 48.60 mm with the contact Crack ratio of 3/20, the size of the Crack & contact size entered into the standard, the flexural strength is still standard and the average hardness produced is 92.52 HV which is included in the maximum standard.

Rdh54/Tid1 Inhibits Rad51-Rad54-Mediated D-loop Formation and Limits D-loop Length

ABSTRACTDisplacement loops (D-loops) are intermediates formed during homologous recombination that play a pivotal role in the fidelity of repair. Rdh54 (a.k.a. Tid1), a Rad54 paralog in Saccharomyces cerevisiae, is well-known for its role with Dmc1 recombinase during meiotic recombination. Yet contrary to Dmc1, Rdh54 is also present in somatic cells where its function is less understood. While Rdh54 enhances the Rad51 DNA strand invasion activity in vitro, it is unclear how it interplays with Rad54-mediated invasions. Here, we show that Rdh54 inhibits D-loop formation by Rad51 and Rad54 in an ATPase-independent manner. Using a novel D-loop Mapping Assay, we further demonstrate that Rdh54 uniquely restricts the lengths of Rad54-mediated D-loops. The alterations in D-loop properties appear to be important for cell survival and mating-type switch in haploid yeast, whereas Rdh54 expression is suppressed in diploids. We propose that Rdh54 and Rad54 compete for potential binding sites within the Rad51 filament, where Rdh54 acts as a physical roadblock to Rad54’s translocation activity, limiting D-loop formation and D-loop length.

Nozzle Wear and Pressure Rise in Heating Volume of Self-blast Type Ultra-high Pressure Nitrogen Arc

This paper reports on experiments with ultra-high pressure nitrogen arcs in a self-blast type switch design. The effect of filling pressure on nozzle mass loss and pressure-rise in the heating volume were investigated. An arc current peak of 130 A at 190 Hz and a fixed inter-electrode gap of 50 mm were used throughout the experiment. The arc burns inside a polytetrafluoroethylene nozzle with a gas outflow vent in the middle. Nitrogen filling pressure of 1 bar, 20 bar, and 40 bar was tested, which also covers the supercritical region. Moreover, to study the effect of vent size on blow pressure near current zero, three different vent dimensions were investigated. <span> By increasing the filling pressure, the energy deposited in the arc increases as a result of increased arcing voltage</span>. It was observed that the pressure-rise in the heating volume is linked to the filling pressure, while the vent size plays a crucial role in the blow pressure near current zero. The nozzle mass loss per unit energy deposited in the arc is found to be independent of the filling pressure.

Ca2+-Calcineurin-NFAT pathway mediates the effect of thymol on oxidative metabolism and fiber-type switch in skeletal muscle

Thymol is a major component of thyme, and it has been reported that thymol administration reduces body weight, plasma insulin and blood glucose in type-2 diabetes.