Search

Mitochondria are hubs of metabolism and signaling and play an important role in tumorigenesis, therapeutic resistance, and metastasis in many cancer types. Various laboratory models of cancer demonstrate the extraordinary dynamics of mitochondrial structure, but little is known about the role of mitochondrial structure in resistance to anticancer therapy. We previously demonstrated the importance of mitochondrial structure and oxidative phosphorylation in the survival of chemotherapy-refractory triple negative breast cancer (TNBC) cells. As TNBC is a highly aggressive breast cancer subtype with few targeted therapy options, conventional chemotherapies remain the backbone of early TNBC treatment. Unfortunately, approximately 45% of TNBC patients retain substantial residual tumor burden following chemotherapy, associated with abysmal prognoses. Using an orthotopic patient-derived xenograft mouse model of human TNBC, we compared mitochondrial structures between treatment-naïve tumors and residual tumors after conventional chemotherapeutics were administered singly or in combination. We reconstructed 1,750 mitochondria in three dimensions from serial block-face scanning electron micrographs, providing unprecedented insights into the complexity and intra-tumoral heterogeneity of mitochondria in TNBC. Following exposure to carboplatin or docetaxel given individually, residual tumor mitochondria exhibited significant increases in mitochondrial complexity index, area, volume, perimeter, width, and length relative to treatment-naïve tumor mitochondria. In contrast, residual tumors exposed to those chemotherapies given in combination exhibited diminished mitochondrial structure changes. Further, we document extensive intra-tumoral heterogeneity of mitochondrial structure, especially prior to chemotherapeutic exposure. These results highlight the potential for structure-based monitoring of chemotherapeutic responses and reveal potential molecular mechanisms that underlie chemotherapeutic resistance in TNBC.

The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LDs) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. For example, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and the proteins that modulate organelle contact sites. However, how mitochondria-LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age-related changes in LD morphology and mitochondria-lipid interactions in BAT. We examined the three-dimensional morphology of mitochondria and LDs in young (3-month) and aged (2-year) murine BAT using serial block face-scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Our analyses showed reductions in LD volume, area, and perimeter in aged samples in comparison to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for the mitochondria interacting with LDs. Overall, these data define the nature of LD morphology and organelle-organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology with mitochondrial function, metabolism, and bioactivity in aged BAT., (© 2024 The Author(s). Journal of Cellular Physiology published by Wiley Periodicals LLC.)

The sorting and assembly machinery (SAM) Complex is responsible for assembling β-barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity. While the role of Sam50 in mitochondrial structure and metabolism in skeletal muscle remains unclear, this study aims to investigate its impact. Serial block-face-scanning electron microscopy and computer-assisted 3D renderings were employed to compare mitochondrial structure and networking in Sam50-deficient myotubes from mice and humans with wild-type (WT) myotubes. Furthermore, autophagosome 3D structure was assessed in human myotubes. Mitochondrial metabolic phenotypes were assessed using Gas Chromatography-Mass Spectrometry-based metabolomics to explore differential changes in WT and Sam50-deficient myotubes. The results revealed increased mitochondrial fragmentation and autophagosome formation in Sam50-deficient myotubes compared to controls. Metabolomic analysis indicated elevated metabolism of propanoate and several amino acids, including ß-Alanine, phenylalanine, and tyrosine, along with increased amino acid and fatty acid metabolism in Sam50-deficient myotubes. Furthermore, impairment of oxidative capacity was observed upon Sam50 ablation in both murine and human myotubes, as measured with the XF24 Seahorse Analyzer. Collectively, these findings support the critical role of Sam50 in establishing and maintaining mitochondrial integrity, cristae structure, and mitochondrial metabolism. By elucidating the impact of Sam50-deficiency, this study enhances our understanding of mitochondrial function in skeletal muscle., (© 2024 The Author(s). Journal of Cellular Physiology published by Wiley Periodicals LLC.)

Frequent climate variability and change had the strongest direct influences on the availability and accessibility of food through reducing agricultural productivity and cropping patterns. Despite the Ethiopian government having made substantial efforts to boost production and productivity through the introduction of Climate Smart Agriculture Practices (CSAPs), the implementation of these practices by smallholder wheat farmers has remained low. This study, therefore, tried to investigate the determinants of the adoption of CSAPs in Northwestern Ethiopia. The primary data were gathered from 385 randomly selected wheat producers (including 702 plot-level observations). The CSAPs considered in this investigation were wheat row planting, crop rotation, and improved wheat varieties. The factors that influence the adoption of CSAPs were determined using a multivariate probit (MVP) model. The results revealed that the age of the sampled wheat producer farmers, education level of sampled wheat farmers, livestock holding, contact with development agents, credit access, off-farm activities participation, distance to input supply institution, slope of the plot, and soil fertility status of the plot were the major determinants of the adoption of CSAPs. The study suggested that policy-makers and stakeholders should strengthen farmers' skills by providing sufficient and effective short-term training. Moreover, encouraging mixed crop-livestock production systems, strengthening credit access, development agents, and access to near-input supply institutions are required to scale-up the adoption of CSAPs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LD) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. Particularly, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and proteins that modulate organelle contact sites. However, how mitochondria-LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age-related changes in LD morphology and mitochondria-lipid interactions in BAT. We examined the three-dimensional morphology of mitochondria and LDs in young (3-month) and aged (2-year) murine BAT using serial block face-scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Analysis showed reductions in LD volume, area, and perimeter in aged samples compared to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for mitochondria interacting with LD lipids. Overall, these data define the nature of LD morphology and organelle-organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology and mitochondrial functionality, metabolism, and bioactivity in aged BAT., Competing Interests: Declaration of interests The authors have no Conflicts of Interest to declare.

Background: Many countries need to accelerate their progress to achieve the sustainable development goal target of neonatal death. It is still high in Ethiopia. Thus, this study aimed to assess the mortality predictors and length of hospital stay among Neonates admitted to the Neonatal Intensive Care Unit of Gurage zone public Hospitals., Method: In this study, a facility-based retrospective follow-up study was applied among 375 neonates admitted to the NICU of selected public hospitals in the Gurage zone from June 1, 2019 to June 30, 2021. The researchers used Epi-Data entry 3.1 for the data entry and then exported it to STATA version 14 for analysis. The Kaplan-Meier survival curve and log-rank test were used to estimate and compare the survival time of categorical variables, respectively., Result: The researchers observed about 85 (22.7% with 95%CI: 18.7, 27.2) deaths from the 2305 person-days follow-up. The median survival time was 14 days. The overall incidence density rate was 36.9 per 1000 person-days observed (95%CI: 29.8, 45.6). Perinatal asphyxia (AHR: 2.9[CI: 1.8; 4.8]), cesarean section as a mode of delivery (AHR: 1.1[CI; 1.01; 1.15]), maternal age of greater or equal to 35 years (AHR: 1.1[95% CI: 1.01, 1.15]), and twin pregnancy (AHR: 2.3[95% CI: 1.2, 4.3]) were predictors of neonatal mortality., Conclusion: The survival rate of neonates was higher compared to other studies. So, to reduce the burden of neonatal mortality, health care providers should give special attention to twin pregnancies, neonates delivered via cesarean section, and neonates with a problem of perinatal asphyxia., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

This study addresses the question whether an 'attention reminder' in discrete choice experiments (DCE) affects preferences, willingness to pay (WTP), and attribute non-attendance (ANA). We report on an experiment which elicited preferences for livestock market facilities from 960 randomly selected farm households in Ethiopia. Basic diagnostic comparisons of the estimations showed that taste parameters are significantly different and the WTP values of two (out of eight) facilities are different between before and after the reminder. Latent class model based ANA analysis revealed that the reminder has increased fully compensatory choice behavior [full attention] among sample respondents. The mixed logit models estimated in WTP space also showed that the WTP values are slightly smaller for most of the facilities after the reminder. In terms of relative importance, veterinary clinic, fenced shed, and watering trough facilities are the three livestock market facilities valued most by the farm households both before and after the reminder. Our results imply that researchers studying behaviors of rural communities in developing countries using DCEs might be able to address issues related to heuristics if they reminded respondents of the need to pay attention to all elements in the experiment unless understanding the choice decision making process itself is the point of interest. Empirically, livestock market development initiatives need to take into account farmers' clear and consistent prioritization of the market facilities., Competing Interests: The authors have declared that no competing interests exist.