Diabetogenic diet-induced insulin resistance associates with lipid droplet proteins and adipose tissue secretome,but not with sexual dimorphic adipose tissue fat accumulation in Wistar rats

The role of sexual dimorphic adipose tissue fat accumulation in the development of insulin resistance is well known. However, whether vitamin A status and/or its metabolic pathway display any sex- or depot (visceral/subcutaneous)-specific pattern and have a role in sexual dimorphic adipose tissue development and insulin resistance are not completely understood. Therefore, to assess this, 5 weeks old Wistar male and female rats of eight from each sex were provided either control or diabetogenic (high fat, high sucrose) diet for 26 weeks. At the end, consumption of diabetogenic diet increased the visceral fat depots (p < 0.001) in the males and subcutaneous depot (p < 0.05) in the female rats, compared to their sex-matched controls. On the other hand, it caused adipocyte hypertrophy (p < 0.05) of visceral depot (retroperitoneal) in the females and subcutaneous depot of the male rats. Although vitamin A levels displayed sex- and depot-specific increase due to the consumption of diabetogenic diet, the expression of most of its metabolic pathway genes in adipose depots remained unaltered. However, the mRNA levels of some of lipid droplet proteins (perilipins) and adipose tissue secretory proteins (interleukins, lipocalin-2) did display sexual dimorphism. Nonetheless, the long-term feeding of diabetogenic diet impaired the insulin sensitivity, thus affected glucose clearance rate and muscle glucose-uptake in both the sexes of rats. In conclusion, the chronic consumption of diabetogenic diet caused insulin resistance in the male and female rats, but did not corroborate with sexual dimorphic adipose tissue fat accumulation or its vitamin A status.     

A comparative genomics study of genetic products potentially encoding ladderane lipid biosynthesis

Background  

The fatty acids of anaerobic ammonium oxidizing (anammox) bacteria contain linearly concatenated cyclobutane moieties, so far unique to biology. These moieties are under high ring strain and are synthesised by a presently unknown biosynthetic pathway.     

Functional Genomic Identification of Genes Required for Male Gonadal Differentiation in Caenorhabditis elegans

The Caenorhabditis elegans somatic gonad develops from a four-cell primordium into a mature organ that differs dramatically between the sexes in overall morphology (two arms in hermaphrodites and one in males) and in the cell types comprising it. Gonadal development in C. elegans is well studied, but regulation of sexual differentiation, especially later in gonadal development, remains poorly elucidated. To identify genes involved in this process, we performed a genome-wide RNAi screen using sex-specifically expressed gonadal GFP reporters. This screen identified several phenotypic classes, including ∼70 genes whose depletion feminized male gonadal cells. Among the genes required for male cell fate specification are Wnt/β-catenin pathway members, cell cycle regulators, and genes required for mitotic spindle function and cytokinesis. We find that a Wnt/β-catenin pathway independent of extracellular Wnt ligand is essential for asymmetric cell divisions and male differentiation during gonadal development in larvae. We also find that the cell cycle regulators cdk-1 and cyb-3 and the spindle/cytokinesis regulator zen-4 are required for Wnt/β-catenin pathway activity in the developing gonad. After sex is determined in the gonadal primordium the global sex determination pathway is dispensable for gonadal sexual fate, suggesting that male cell fates are promoted and maintained independently of the global pathway during this period.THE Caenorhabditis elegans gonad derives from a simple primordium of four cells that coalesces during embryogenesis and contains two somatic gonad precursors (SGPs), Z1 and Z4, flanking two germline precursors, Z2 and Z3 (Kimble and Hirsh 1979). The SGPs undergo very different developmental programs in each sex, involving sexually dimorphic cell lineages and migrations and sex-specific cellular differentiation. The result is a two-armed bilaterally symmetrical gonad in the adult hermaphrodite or a single-armed asymmetric gonad in the adult male. The high degree of sexual dimorphism of the mature organ and variety of cellular events that occur sex specifically during its development make the C. elegans gonad an outstanding model for sex-specific organogenesis.Development of the somatic gonad occurs in two phases. The early phase defines the gonadal axes and establishes the precursors of the major gonadal cell types. This takes place during the first larval stage (L1), beginning shortly after hatching with the first division of the SGPs. In both sexes SGP division is asymmetric in terms of both the sizes and the fates of the daughter cells, and establishes the proximal/distal axis of the gonad (Hirsh et al. 1976; Kimble and Hirsh 1979). The global sex determination pathway establishes the future sex of the gonad around the time of hatching (Klass et al. 1976; Nelson et al. 1978), and sexual dimorphism is already apparent when the SGPs divide: the size asymmetry of the SGP daughters is much more pronounced in males than hermaphrodites. In both sexes the asymmetry of the first SGP division requires a Wnt/β-catenin pathway. Mutations compromising this pathway cause a “symmetrical sisters” phenotype in which both daughters adopt the same fate (Miskowski et al. 2001; Siegfried and Kimble 2002; Phillips and Kimble 2009). Sex specificity is imposed on the SGPs by the global sex determining gene tra-1 (Hodgkin 1987) and the gonad-specific sex determining gene fkh-6 (Chang et al. 2004). These genes play opposing roles in SGP sex determination, with tra-1 feminizing and fkh-6 masculinizing the somatic gonad, and they also act redundantly to promote mitotic proliferation of the SGP lineage (Chang et al. 2004). SGP sex determination is linked to cell cycle progression by cyclin D, which is required to overcome repression of fkh-6 expression in the SGPs by E2F (Tilmann and Kimble 2005).The later phase of gonadal development involves the elongation of the gonad, together with cellular proliferation and differentiation, and lasts from L2 to adulthood. During L2 the somatic cells enlarge and leader cells (distal tip cells in the hermaphrodite, linker cell in the male) begin long-range migrations that extend the gonad. During L3, somatic gonad cell division resumes in both sexes, leading to the formation of differentiated somatic cell types by the end of L3 or beginning of L4. Gonadal morphogenesis is completed and gametogenesis begins during L4 (Kimble and Hirsh 1979).Although SGP division and much of hermaphrodite gonadal development have been well studied (Hubbard and Greenstein 2000), sexual cell fate specification in the somatic gonad is more poorly understood, particularly after the L1 stage. Despite the importance of fkh-6 in promoting male differentiation, it is expressed in males only during early L1 and null mutants have incomplete gonadal sex reversal. We have therefore performed a genome-wide RNAi screen to identify additional genes required after hatching for gonadal development in each sex. Among the advantages of this approach is the ability to identify gonadal regulators that also are essential for embryonic development. To our knowledge this is the first functional genomic study of gonadal sex differentiation.The screen identified many genes whose depletion disrupts gonadogenesis in each sex and nearly 70 genes whose depletion causes gonadal feminization in males. Prominent among this latter class were components of a Wnt/β-catenin pathway, cell cycle regulators, and genes involved in mitotic spindle function and cytokinesis. We find that Wnt/β-catenin activity continues in both sexes after SGP division and is required for male cell fate commitment in the gonad. We also find that the cyclin-dependent kinase cdk-1 and its cognate cyclin cyb-3 as well as the mitotic spindle regulator zen-4 are required for gonadal Wnt/β-catenin pathway activity, providing a potential new link between the cell cycle, asymmetric division, and sexual differentiation. The feminization caused by depletion of Wnt/β-catenin pathway components or cdk-1 is independent of the global sex determination pathway, suggesting that sexual fates in the male gonad remain plastic after the primary sex determination decision.     

Analysis of cardiac signals using spatial filling index and time-frequency domain

Background  

Analysis of heart rate variation (HRV) has become a popular noninvasive tool for assessing the activities of the autonomic nervous system (ANS). HRV analysis is based on the concept that fast fluctuations may specifically reflect changes of sympathetic and vagal activity. It shows that the structure generating the signal is not simply linear, but also involves nonlinear contributions. These signals are essentially non-stationary; may contain indicators of current disease, or even warnings about impending diseases. The indicators may be present at all times or may occur at random in the time scale. However, to study and pinpoint abnormalities in voluminous data collected over several hours is strenuous and time consuming.     

Evolution of transposable elements: an IS10 insertion increases fitness in Escherichia coli

Strains of Escherichia coli carrying Tn10, a transposon consisting of two IS10 insertion sequences flanking a segment encoding for a tetracycline-resistance determinant, gain a competitive advantage in chemostat cultures. All Tn10-bearing strains that increase in frequency during competition have a new IS10 insertion that is found in the same location in the genome of those strains. We mapped, by a gradient of transmission, the position of the new IS10 insertion. We examined 11 isolates whose IS10 insertion was deleted by recombinational crossing- over, and in all cases the competitive fitness of the isolates was decreased. These results show that the IS10-generated insertion increases fitness in chemostat cultures. We named the insertion fit::IS10 and suggest that transposable elements may speed the rate of evolution by promoting nonhomologous recombination between preexisting variations within a genome and thereby generating adaptive variation.      

Molecular evolution of the ZFY and ZNF6 gene families

Members of the ZFY and ZNF6 gene families have been cloned from species representing different taxa and different modes of sex determination. Comparisons of these genes show the ZFY-like and ZNF6 sequences to be strongly conserved across marsupials, birds, and lepidosaurians. Sequence analyzed by neighbor-joining indicated that both gene families are monophyletic with a high bootstrap value. Pairing of sequences from males and females of nonmammalian species showed there to be no significant difference between male and female sequences from a single species, consistent with autosomal locations. The molecular distances between murine Zfy-1, Zfy-2, and other ZFY-like sequences suggested that Zfy genes have undergone a period of rapid evolutionary change not seen in human ZFY.