Preservation of renal function in chronic diabetes by enhancing glomerular glucose metabolism

Diabetic nephropathy (DN) affects approximately 30–40% of patients with type 1 (T1DM) and type 2 diabetes (T2DM). It is a major cause of end-stage renal disease (ESRD) for the developed world. Hyperglycemia and genetics are major causal factors for the initiation and progression of DN. Multiple abnormalities in glucose and mitochondrial metabolism induced by diabetes likely contribute to the severity of DN. Recent clinical studies in people with extreme duration of T1DM (>?50 years, Joslin Medalist Study) have supported the importance of endogenous protective factors to neutralize the toxic effects of hyperglycemia on renal and other vascular tissues. Using renal glomeruli from these patients (namely Medalists) with and without DN, we have shown the importance of increased glycolytic flux in decreasing the accumulation of glucose toxic metabolites, improving mitochondrial function, survival of glomerular podocytes, and reducing glomerular pathology. Activation of a key glycolytic enzyme, pyruvate kinase M2 (PKM2), resulted in the normalization of renal hemodynamics and mitochondrial and glomerular dysfunction, leading to the mitigation of glomerular pathologies in several mouse models of DN.     

Analysis of B chromosome nondisjunction induced by the <Emphasis Type="Italic">r-X1</Emphasis> deficiency in maize

The maize B chromosome typically undergoes nondisjunction during the second microspore division. For normal A chromosomes, the r-X1 deficiency in maize can induce nondisjunction during the second megaspore and first microspore divisions. However, it is not known whether the r-X1 deficiency also induces nondisjunction of the maize B chromosome during these cell divisions. To answer this question, chromosome numbers were determined in the progeny of r-X1/R-r female parents carrying two B chromosomes. Some of the r-X1-lacking progeny (21.2%) contained zero or two B chromosomes. However, a much higher percentage of the r-X1-containing progeny (43.4%) exhibited zero or two B chromosomes, but none displayed more than two B chromosomes. Thus, the results indicated that the r-X1 deficiency could also induce nondisjunction of the B chromosome during the second megaspore division; moreover, the B chromosome in itself could undergo nondisjunction during the same division. In addition, pollen grains from plants with two B chromosomes lacking or exhibiting the r-X1 deficiency were compared via pollen fluorescence in situ hybridization (FISH) using a B chromosome-specific probe. The results revealed that the r-X1 deficiency could induce the occurrence of B chromosome nondisjunction during the first microspore division and that the B chromosome in itself could undergo nondisjunction during the same division at a lower frequency. Our data shed more light on the behavior of the maize B chromosome during cell division.     

Insights into the karyotype evolution and speciation of the beetle <Emphasis Type="Italic">Euchroma gigantea</Emphasis> (Coleoptera: Buprestidae)

Euchroma Dejean, 1833 (Buprestidae: Coleoptera) is a monotypic genus comprising the species Euchroma gigantea, with populations presenting a degree of karyotypic variation/polymorphism rarely found within a single taxonomic (specific) unit, as well as drastically incompatible meiotic configurations in populations from extremes of the species range. To better understand the complex karyotypic evolution of E. gigantea, the karyotypes of specimens from five populations in Brazil were investigated using molecular cytogenetics and phylogenetic approaches. Herein, we used FISH with histone genes as well as sequencing of the COI to determine differential distribution of markers and relationships among populations. The analyses revealed new karyotypes, with variability for chromosome number and morphology of multiple sex chromosome mechanisms, occurrence of B chromosome variants (punctiform and large ones), and high dispersion of histone genes in different karyotypes. These data indicate that chromosomal polymorphism in E. gigantea is greater than previously reported, and that the species can be a valuable model for cytogenetic studies. The COI phylogenetic and haplotype analyses highlighted the formation of three groups with chromosomally polymorphic individuals. Finally, we compared the different karyotypes and proposed a model for the chromosomal evolution of this species. The species E. gigantea includes at least three cytogenetically polymorphic lineages. Moreover, in each of these lineages, different chromosomal rearrangements have been fixed. Dispersion of repetitive sequences may have favored the high frequency of these rearrangements, which could be related to both adaptation of the species to different habitats and the speciation process.     

Treatment Beliefs Underlying Intended Treatment Choices in Knee and Hip Osteoarthritis

Purpose

Patients’ beliefs about treatment modalities for knee and hip osteoarthritis (OA) will underlie their treatment choices. Based on the Theory of Planned Behavior, it is hypothesized that patients’ beliefs, subjective norm, and perceived behavioral control guide their treatment choices. Also, symptom severity and one’s inherent tendency to approach or avoid situations are assumed to play a role. The objective of this study was to test whether these variables were associated with intended treatment choices in knee and hip OA.

Methods

Patients with knee and hip OA were randomly selected from hospital patient records. They completed the Treatment beliefs in OsteoArthritis questionnaire to assess positive and negative treatment beliefs regarding five treatment modalities: physical activities, pain medication, physiotherapy, injections, and arthroplasty. Other measures were intention, subjective norm, perceived behavioral control (ASES), symptom severity (WOMAC), and the person’s general tendency to approach or avoid situations (RR/BIS scales). Three models were tested using path analyses to examine the hypothesized associations.

Results

Participants were 289 patients. Positive treatment beliefs and subjective norm were consistently associated with intended treatment choice across all treatment modalities. Negative treatment beliefs were associated with intended treatment choices for pain medication and arthroplasty. Other associations were not significant.

Conclusions

This is the first study testing the Theory of Planned Behavior in the context of treatment choices in OA. Findings suggest that foremost positive beliefs about treatment modalities and the norms of one’s social environment guide a specific treatment choice. Unexpectedly, symptom severity was not related to intended treatment choices.