Dissecting structure and function of the monovalent cation/H+ antiporters Mdm38 and Ylh47 in Saccharomyces cerevisiae.

Saccharomyces cerevisiae Mdm38 and Ylh47 are homologs of the Ca2+/H+ antiporter Letm1, a candidate gene for seizures associated with Wolf-Hirschhorn syndrome in humans. Mdm38 is important for K+/H+ exchange across the inner mitochondrial membrane and contributes to membrane potential formation and mitochondrial protein translation. Ylh47 also localizes to the inner mitochondrial membrane. However, knowledge of the structures and detailed transport activities of Mdm38 and Ylh47 is limited. In this study, we conducted characterization of the ion transport activities and related structural properties of Mdm38 and Ylh47. Growth tests using Na+/H+ antiporter-deficient Escherichia coli strain TO114 showed that Mdm38 and Ylh47 had Na+ efflux activity. Measurement of transport activity across E. coli-inverted membranes showed that Mdm38 and Ylh47 had K+/H+, Na+/H+, and Li+/H+ antiport activity, but unlike Letm1, they lacked Ca2+/H+ antiport activity. Deletion of the ribosome-binding domain resulted in decreased Na+ efflux activity in Mdm38. Structural models of Mdm38 and Ylh47 identified a highly conserved glutamic acid in the pore-forming membrane-spanning region. Replacement of this glutamic acid with alanine, a non-polar amino acid, significantly impaired the ability of Mdm38 and Ylh47 to complement the salt sensitivity of E. coli TO114. These findings not only provide important insights into the structure and function of the Letm1-Mdm38-Ylh47 antiporter family but by revealing their distinctive properties also shed light on the physiological roles of these transporters in yeast and animals. IMPORTANCE: The inner membrane of mitochondria contains numerous ion transporters, including those facilitating H+ transport by the electron transport chain and ATP synthase to maintain membrane potential. Letm1 in the inner membrane of mitochondria in animals functions as a Ca2+/H+ antiporter. However, this study reveals that homologous antiporters in mitochondria of yeast, Mdm38 and Ylh47, do not transport Ca2+ but instead are selective for K+ and Na+. Additionally, the identification of conserved amino acids crucial for antiporter activity further expanded our understanding of the structure and function of the Letm1-Mdm38-Ylh47 antiporter family.

Insights regarding skin regeneration in non-amniote vertebrates: Skin regeneration without scar formation and potential step-up to a higher level of regeneration.

Skin wounds are among the most common injuries in animals and humans. Vertebrate skin is composed of an epidermis and dermis. After a deep skin injury in mammals, the wound heals, but the dermis cannot regenerate. Instead, collagenous scar tissue forms to fill the gap in the dermis, but the scar does not function like the dermis and often causes disfiguration. In contrast, in non-amniote vertebrates, including fish and amphibians, the dermis and skin derivatives are regenerated after a deep skin injury, without a recognizable scar remaining. Furthermore, skin regeneration can be compared with a higher level of organ regeneration represented by limb regeneration in these non-amniotes, as fish, anuran amphibians (frogs and toads), and urodele amphibians (newts and salamanders) have a high capacity for organ regeneration. Comparative studies of skin regeneration together with limb or other organ regeneration could reveal how skin regeneration is stepped up to a higher level of regeneration. The long history of regenerative biology research has revealed that fish, anurans, and urodeles have their own strengths as models for regeneration studies, and excellent model organisms of these non-amniote vertebrates that are suitable for molecular genetic studies are now available. Here, we summarize the advantages of fish, anurans, and urodeles for skin regeneration studies with special reference to three model organisms: zebrafish (Danio rerio), African clawed frog (Xenopus laevis), and Iberian ribbed newt (Pleurodele waltl). All three of these animals quickly cover skin wounds with the epidermis (wound epidermis formation) and regenerate the dermis and skin derivatives as adults. The availability of whole genome sequences, transgenesis, and genome editing with these models enables cell lineage tracing and the use of human disease models in skin regeneration phenomena, for example. Zebrafish present particular advantages in genetics research (e.g., human disease model and Cre-loxP system). Amphibians (X. laevis and P. waltl) have a skin structure (keratinized epidermis) common with humans, and skin regeneration in these animals can be stepped up to limb regeneration, a higher level of regeneration.

Publication Productivity in Central Asia and Countries of the Former Soviet Union.

INTRODUCTION: Despite the significant number of research institutions and rich scientific heritage, published research from Central Asia (Kazakhstan, Uzbekistan, Kyrgyzstan, Tajikistan, and Turkmenistan) is traditionally underrepresented in international scientific literature. The goal of this paper was to analyze publication patterns in Central Asian countries, and to explore the factors that contributed to the publication productivity in Kazakhstan. METHODS: Publication productivity was evaluated using data generated by the SCImago Journal & Country Rank over the period of 1996-2014 for all of the 15 former Soviet Union Republics for all subject categories. Country specific data, including total population, gross domestic product (GDP) per capita, research and development (R&D) expenditure (% of GDP), number of reserchers (per million people), was abstracted from World Bank data. ANOVA and ANCOVA analyses compared the mean number of publications among Central Asian countries. Separate analyses was done for publication patterns in the health sciences. Multiple comparisons were performed using Tukey method. RESULTS: The analysis of publication productivity showed significant discrepancies in the number of published documents among the Central Asian countries. Kazakhstan demonstrated a significant increase in the number of published documents in the period of 1996-2014, mainly in the areas of natural and multidisciplinary sciences. Our analyses also showed that the number of publications are siginicantly associated with GDP and population size. CONCLUSIONS: We identified large gaps in publication productivity among the Central Asian countries. The association between publication rate with GDP and population size indicates there is a need to adjust for these factors when planning research policy.