Serine 39 in the GTP-binding domain of Drp1 is involved in shaping mitochondrial morphology.

Continuous fusion and fission are critical for mitochondrial health. In this study, we further characterize the role played by dynamin-related protein 1 (Drp1) in mitochondrial fission. We show that a single amino acid change in Drp1 at position 39 from serine to alanine (S39A) within the GTP-binding (GTPase) domain results in a fused mitochondrial network in human SH-SY5Y neuroblastoma cells. Interestingly, the phosphorylation of Ser-616 and Ser-637 of Drp1 remains unaffected by the S39A mutation, and mitochondrial bioenergetic profile and cell viability in the S39A mutant were comparable to those observed in the control. This leads us to propose that the serine 39 residue of Drp1 plays a crucial role in mitochondrial distribution through its involvement in the GTPase activity. Furthermore, this amino acid mutation leads to structural anomalies in the mitochondrial network. Taken together, our results contribute to a better understanding of the function of the Drp1 protein.

Stable knockdown of Drp1 improves retinoic acid-BDNF-induced neuronal differentiation through global transcriptomic changes and results in reduced phosphorylation of ERK1/2 independently of DUSP1 and 6.

Background: Dynamin-related protein Drp1 -a major mitochondrial fission protein- is widely distributed in the central nervous system and plays a crucial role in regulating mitochondrial dynamics, specifically mitochondrial fission and the organelle's shaping. Upregulated Drp1 function may contribute to the pathological progression of neurodegenerative diseases by dysregulating mitochondrial fission/ fusion. The study aims to investigate the effects of Drp1 on retinoic acid-BDNF-induced (RA-BDNF) neuronal differentiation and mitochondrial network reorganization in SH-SY5Y neuroblastoma cells. Methods: We generated an SH-SY5Y cell line with stably depleted Drp1 (shDrp1). We applied RNA sequencing and analysis to study changes in gene expression upon stable Drp1 knockdown. We visualized the mitochondria by transmission electron microscopy and used high-content confocal imaging to characterize and analyze cell morphology changes and mitochondrial network reorganization during neuronal differentiation. Results: shDrp1 cells exhibited fused mitochondrial ultrastructure with perinuclear clustering. Stable knockdown of Drp1 resulted in the upregulation of genes involved in nervous system development. High content analysis showed improved neurite outgrowth, segmentation, and extremities in differentiated shDrp1 cells. Neuronal differentiation was associated with a significant reduction in ERK1/2 phosphorylation, and ERK1/2 phosphorylation was independent of the dual specificity phosphatases DUSP1/6 in shDrp1 cells. Differentiated control underwent mitochondrial morphology remodeling, whereas differentiated shDrp1 cells retained the highly fused mitochondria and developed long, elongated structures. The shDrp1 cells responded to specific apoptotic stimuli like control in vitro, suggesting that Drp1 is not a prerequisite for apoptosis in SH-SY5Y cells. Moreover, Drp1 downregulation reduced the formation of toxic mHtt aggregates in vitro. Discussion: Our results indicate that Drp1 silencing enhances RA-BDNF-induced neuronal differentiation by promoting transcriptional and mitochondrial network changes in undifferentiated cells. We also demonstrate that the suppression of Drp1 reduces toxic mHtt aggregate formation in vitro, suggesting protection against neurotoxicity. Thus, Drp1 may be an attractive target for further investigation in future strategies to combat neurodegenerative diseases.

Factors Associated With HIV Preventive Behavior Among Adults in Majang Zone of Gambella Region, Southwest Ethiopia.

Background: HIV-positive people can spread the virus through unprotected sex; however, HIV can be avoided if populations are educated about the risks. In underdeveloped nations, evidence suggests that the ABC method for HIV prevention is quite effective. As a result, the goal of this study was to determine the magnitude of HIV prevention behavior among adults in the Majang zone of Southwest Ethiopia, as well as the factors that influence it. Methods: A community-based cross-sectional study was carried out from March 1st to May 31st, 2019. The data were collected through a face-to-face interview using a modified validated questionnaire among systematically selected study participants. The collected data were coded and entered using Epidata manager version 4.0.2.101 and analyzed using SPSS version 21. A logistic regression analysis was computed to determine the association using crude and adjusted odds ratios at 95% confidence intervals. The level of significance was declared at a p-value less than 0.05. Results: Of the 772 adults interviewed, the proportion of adults who had good HIV preventive behavior was 51.8%, 95% CI [48.3-55.3%]. Two hundred forty (31.9%) were used abstinence as a type of HIV preventive behavior followed by being faithful (16.1%) and consistent condom use (7.3%). The study also found that respondents with the age group ≥27 years old (AOR = 1.56, 95% CI [1.3-3.12]), marital status (being married (AOR = 6.30, 95% CI [4.48-11.4]), and divorced/widowed (AOR = 5.50, 95% CI [2.60-12.4]) and having good knowledge of HIV prevention methods (AOR = 2.18, 95% CI [1.71-4.00]) were the factors associated with good HIV preventive behavior. Conclusion and Recommendation: In the study area, overall HIV prevention behavior was average. The characteristics linked with successful HIV prevention behavior among adults in the Majang community included increasing age, being married or divorced/widowed, and having a solid understanding of HIV prevention approaches. As a result, policy-level and multi-sectorial intervention approaches from all stakeholders are necessary to develop short- and long-term strategies to address the problem and improve the community's quality of life.

The role of traditional birth attendants and problem of integration with health facilities in remote rural community of West Omo Zone 2021: exploratory qualitative study.

BACKGROUND: Mothers in rural Ethiopian communities prefer giving birth at home. In developing countries, traditional birth attendants play an important role in reducing the maternal mortality rate. In Ethiopia, however, their role during pregnancy, childbirth, the postnatal period, and their integration with health professionals is not clearly defined. This study aimed to explore the role of traditional birth attendants in feto-maternal care during pregnancy, childbirth, and the postnatal period, and integration with health professionals in the West Omo Zone, southern Ethiopia. METHODS: A qualitative descriptive design was used with triangulation of methods and data sources. We conducted in-depth interviews with traditional birth attendants, key informant interviews with health care professionals and community or religious leaders, and two focus group discussions with multiparous pregnant women. Each interview and focus group discussion was tape-recorded and the data obtained were transcribed and translated into English for analysis. The analysis was done based on thematic analysis framework. RESULTS: Traditional birth attendants stated that they used herbal remedies to treat nausea and vomiting, decrease pain during labor, and increase pregnant women's desire to push. The absence of incentives for their work, shortage of logistics, and lack of training was mentioned as challenges to the continuity of their roles. All study participants explained the importance of training traditional birth attendants on maternal and child health in rural communities. However, health care professionals reported that few traditional birth attendants advised mothers about traditional practices such as milk tooth extraction and uvulectomy. CONCLUSION AND RECOMMENDATION: Traditional birth attendants continued their roles despite the existing challenges. There was no integration between TBA and the formal health care system. The need for training traditional birth attendants has been emphasized by all study participants and its impact on reducing feto-maternal death was recognized by health care professionals. Therefore, the federal ministry of health should works better for the development of TBAs to scale up their skills across all regions in the country.

The Effect of Palm Oil-Fried Street Kokor on Liver and Kidney Biomarkers of Swiss Albino Mice.

BACKGROUND: Foods fried with oils at streets contain many harmful substances for health. Locally fried foods are consumed commonly in our society, yet their health effect is not studied. OBJECTIVE: To assess the effect of palm oil-fried street kokor on liver and kidney biomarkers of Swiss Albino mice. METHODS: Thirty-two male and female Swiss Albino mice with the age of 10-12 weeks old were divided randomly into four groups of eight members with equal male and female subgroups. The control group (group I) received only a standard pellet, and the experimental groups (group II, group III, and group IV) received 10%, 20%, and 30% kokor of their daily food consumption, respectively. At the end of the 6th week, they were sacrificed by thoracoabdominal incision after anesthetizing by diethyl ether. Blood was taken from each mouse by cardiac puncture and analyzed for liver and kidney function tests. RESULT: The serum levels of liver damage biomarkers (alanine transaminase (ALT) and aspartate transaminase (AST)) and kidney damage biomarkers (urea and creatinine) of experimental groups were increased significantly relative to the control groups (P < 0.05). Level of biochemical profiles increased as the dose of kokor increased. CONCLUSIONS: Palm oil-fried street kokor damaged the liver and kidney of the mice, and the damage was exacerbated as the dose of kokor increased.