Expression profiling of WD40 family genes including DDB1- and CUL4- associated factor (DCAF) genes in mice and human suggests important regulatory roles in testicular development and spermatogenesis.

BACKGROUND: The WD40-repeat containing proteins, including DDB1-CUL4-associated factors (DCAFs), are abundant and conserved proteins that play important roles in different cellular processes including spermatogenesis. DCAFs are subset of WD40 family proteins that contain WDxR motif and have been proposed to function as substrate receptor for Cullin4-RING-based E3 ubiquitin ligase complexes to recruit diverse proteins for ubiquitination, a vital process in spermatogenesis. Large number of WD40 genes has been identified in different species including mouse and human. However, a systematic expression profiling of WD40 genes in different tissues of mouse and human has not been investigated. We hypothesize that large number of WD40 genes may express highly or specifically in the testis, where their expression is uniquely regulated during testis development and spermatogenesis. Therefore, the objective of this study is to mine and characterize expression patterns of WD40 genes in different tissues of mouse and human with particular emphasis on DCAF genes expressions during mouse testicular development. RESULTS: Publically available RNA sequencing (RNA seq) data mining identified 347 and 349 WD40 genes in mouse and human, respectively. Hierarchical clustering and heat map analyses of RNA seq datasets revealed differential expression patterns of WD40 genes with around 60-73% of the genes were highly or specifically expressed in testis. Similarly, around 74-83% of DCAF genes were predominantly or specifically expressed in testis. Moreover, WD40 genes showed distinct expression patterns during embryonic and postnatal testis development in mice. Finally, different germ cell populations of testis showed specific patterns of WD40 genes expression. Predicted gene ontology analyses revealed more than 80% of these proteins are implicated in cellular, metabolic, biological regulation and cell localization processes. CONCLUSIONS: We have identified large number of WD40 family genes that are highly or specifically expressed in the testes of mouse and human. Moreover, WD40 genes have distinct expression patterns during embryonic and postnatal development of the testis in mice. Further, different germ cell populations within the testis showed specific patterns of WD40 genes expression. These results provide foundation for further research towards understanding the functional genomics and molecular mechanisms of mammalian testis development and spermatogenesis.

Awareness of fitness to drive among cardiologists in Saudi Arabia.

OBJECTIVES: To assess the perception and awareness of cardiologists in Saudi Arabia about medical fitness to drive in different cardiovascular diseases. Methods: The study is a cross-sectional survey-based study between June 2018 and July 2018. Cardiologists were asked to complete a self-administered questionnaire inquiring about awareness of driving fitness and educating patients regarding driving risks in specific cardiovascular conditions. Results: A total of 194 cardiologists completed the study survey; there were 30.4% consultants, 59.3% specialists, and 10.3% residents. Out of 195, 72% were aware of the existence of particular international driving regulations for cardiovascular diseases, whereas 28% were not aware. Although, no Saudi guidelines assessing fitness-to-drive are available, 11% of the participants claimed awareness of such regulations. Interestingly, we found that cardiologists had never or rarely educated their patients regarding the potential risks of driving: 49% in symptomatic angina, 47% when ejection fraction is ≤35%, 39% in symptomatic valvular diseases, 26% after cardioverter defibrillators implantation, and 23% after non-elective percutaneous coronary interventions. Conclusion: There is a lack of awareness among cardiologists in Saudi Arabia about international guidelines regarding medical driving fitness. This study highlights the necessity of formulating appropriate national driving regulations for cardiovascular diseases.

Are cardiac patients in Saudi Arabia provided adequate instructions when they should not drive?

OBJECTIVE: Driving capability can be significantly affected by different heath disorders; cardiovascular diseases (CVDs) should be considered when assessing patients for medical fitness to drive (MFTD). The aim of this study was to evaluate the awareness of Saudi patients about driving recommendations and to assess the incidence of motor vehicle accidents (MVAs) among cardiac patients. MATERIALS AND METHODS: We conducted a cross-sectional survey-based study. Male patients diagnosed with CVDs and who were visiting outpatient departments were invited to complete a questionnaire regarding their awareness of driving recommendations. Patients' demographics, clinical diagnosis, echocardiography parameters, and time-to-CVD diagnosis were all obtained from the patients' medical records. Women were excluded because it was illegal for women to drive in Saudi Arabia during the study period. RESULTS: In total, 800 men were included, with a mean age of 54 ± 12 years. Driving counseling had been provided to 241 participants (30%). Of these, 207 (25%) were advised not to drive for a period of between one week and six months. Five percent of the patients had a history of MVAs during the follow-up period of 6.2 ± 4 years. We found that the presence of a dyspnea ≥2, according to the New York Heart Association (NYHA), and a history of loss of consciousness (syncope/pre-syncope) were significantly associated with accidents (46% vs. 20%, P < 0.0001 and 41% vs. 10%, P < 0.0001, respectively). CONCLUSION: Patient-physician discussion about MFTD was only performed with 30% of the patients with CVDs in Saudi Arabia. Dyspnea NYHA class ≥2 or a prior history of syncope were significantly associated with the incidence of MVAs.

Protective potential of thymoquinone against peroxynitrite induced modifications in histone H2A: In vitro studies.

Peroxynitrite (ONOO-) is a reactive oxidant involved in numerous pathological conditions. Thymoquinone (TQ) is an active constituent of Nigella sativa and is reported to have anti-disease activities, but its role on ONOO- has never been investigated. This study was undertaken to investigate the role of TQ on ONOO--induced damage of histone-H2A. Our novel data showed TQ significantly inhibited ONOO--induced oxidative damage in histone-H2A. ONOO- induces UV-hypochromicity of histone-H2A, whereas TQ reversed this effect to hyperchromicity. Tyrosine fluorescence was significantly reduced by ONOO- and was significantly increased upon TQ treatment. TQ reduces ONOO--induced hydrophobicity in histone-H2A and also reduces thermal stability of ONOO--histone H2A complex. SDS-PAGE of native histone-H2A showed a single band, which disappeared when treated with ONOO- alone. This changed was retained when protein samples were treated with TQ. Similar protective effects of TQ were found when protein carbonyl contents were estimated. In conclusion, this is the first study that shows the potential of TQ against ONOO--induced damaged of histone-H2A. TQ inhibits oxidative modification of tyrosine, lysine, arginine, proline and threonine in histone-H2A. These results have importance for the development of novel therapeutic strategies for the treatment of disorders, where ONOO- plays a role.