Fish oil supplementation for two generations increases insulin sensitivity in rats

We investigated the effect of fish oil supplementation for two consecutive generations on insulin sensitivity in rats. After the nursing period (21 days), female rats from the same prole were divided into two groups: (a) control group and (b) fish oil group. Female rats were supplemented with water (control) or fish oil at 1 g/kg body weight as a single bolus for 3 months. After this period, female rats were mated with male Wistar rats fed on a balanced chow diet (not supplemented). Female rats continued to receive supplementation throughout gestation and lactation periods. The same treatment was performed for the next two generations (G1 and G2). At 75 days of age, male offspring from G1 and G2 generations from both groups were used in the experiments. G1 rats did not present any difference with control rats. However, G2 rats presented reduction in glycemia and lipidemia and improvement in in vivo insulin sensitivity (model assessment of insulin resistance, insulin tolerance test) as well as in vitro insulin sensitivity in soleus muscle (glucose uptake and metabolism). This effect was associated with increased insulin-stimulated p38 MAP kinase phosphorylation and lower n-6/n-3 fatty acid ratio, but not with activation of proteins from insulin signaling (IR, IRS-1 and Akt). Global DNA methylation was decreased in liver but not in soleus muscle. These results suggest that long-term fish oil supplementation improves insulin sensitivity in association with increased insulin-stimulated p38 activation and decreased n-6:n-3 ratio in skeletal muscle and decreased global DNA methylation in liver.     

Meaningful traits for grouping plant species across arid ecosystems

Grouping species may provide some degree of simplification to understand the ecological function of plants on key ecosystem processes. We asked whether groups of plant species based on morpho-chemical traits associated with plant persistence and stress/disturbance resistance reflect dominant plant growth forms in arid ecosystems. We selected twelve sites across an aridity gradient in northern Patagonia. At each site, we identified modal size plants of each dominant species and assessed specific leaf area (SLA), plant height, seed mass, N and soluble phenol concentration in green and senesced leaves at each plant. Plant species were grouped according with plant growth forms (perennial grasses, evergreen shrubs and deciduous shrubs) and plant morphological and/or chemical traits using cluster analysis. We calculated mean values of each plant trait for each species group and plant growth form. Plant growth forms significantly differed among them in most of the morpho-chemical traits. Evergreen shrubs were tall plants with the highest seed mass and soluble phenols in leaves, deciduous shrubs were also tall plants with high SLA and the highest N in leaves, and perennial grasses were short plants with high SLA and low concentration of N and soluble phenols in leaves. Grouping species by the combination of morpho-chemical traits yielded 4 groups in which species from one growth form prevailed. These species groups differed in soluble phenol concentration in senesced leaves and plant height. These traits were highly correlated. We concluded that (1) plant height is a relevant synthetic variable, (2) growth forms adequately summarize ecological strategies of species in arid ecosystems, and (3) the inclusion of plant morphological and chemical traits related to defenses against environmental stresses and herbivory enhanced the potential of species grouping, particularly within shrubby growth forms.     

Synthesis,Characterization and in vitro Studies of a Cathepsin B‐Cleavable Prodrug of the VEGFR Inhibitor Sunitinib

Since several decades, the prodrug concept has raised considerable interest in cancer research due to its potential to overcome common problems associated with chemotherapy. However, for small‐molecule tyrosine kinase inhibitors, which also cause severe side effects, hardly any strategies to generate prodrugs for therapeutic improvement have been reported so far. Here, we present the synthesis and biological investigation of a cathepsin B‐cleavable prodrug of the VEGFR inhibitor sunitinib. Cell viability assays and Western blot analyses revealed, that, in contrast to the non‐cathepsin B‐cleavable reference compound, the prodrug shows activity comparable to the original drug sunitinib in the highly cathepsin B‐expressing cell lines Caki‐1 and RU‐MH. Moreover, a cathepsin B cleavage assay confirmed the desired enzymatic activation of the prodrug. Together, the obtained data show that the concept of cathepsin B‐cleavable prodrugs can be transferred to the class of targeted therapeutics, allowing the development of optimized tyrosine kinase inhibitors for the treatment of cancer.     

Population genetic structure and connectivity of the seagrass Thalassia hemprichii in the Western Indian Ocean is influenced by predominant ocean currents

This study is the first large‐scale genetic population study of a widespread climax species of seagrass, Thalassia hemprichii, in the Western Indian Ocean (WIO). The aim was to understand genetic population structure and connectivity of T. hemprichii in relation to hydrodynamic features. We genotyped 205 individual seagrass shoots from 11 sites across the WIO, spanning over a distance of ~2,700 km, with twelve microsatellite markers. Seagrass shoots were sampled in Kenya, Tanzania (mainland and Zanzibar), Mozambique, and Madagascar: 4–26°S and 33–48°E. We assessed clonality and visualized genetic diversity and genetic population differentiation. We used Bayesian clustering approaches (TESS) to trace spatial ancestry of populations and used directional migration rates (DivMigrate) to identify sources of gene flow. We identified four genetically differentiated groups: (a) samples from the Zanzibar channel; (b) Mozambique; (c) Madagascar; and (d) the east coast of Zanzibar and Kenya. Significant pairwise population genetic differentiation was found among many sites. Isolation by distance was detected for the estimated magnitude of divergence (D_EST), but the three predominant ocean current systems (i.e., East African Coastal Current, North East Madagascar Current, and the South Equatorial Current) also determine genetic connectivity and genetic structure. Directional migration rates indicate that Madagascar acts as an important source population. Overall, clonality was moderate to high with large differences among sampling sites, indicating relatively low, but spatially variable sexual reproduction rates. The strongest genetic break was identified for three sites in the Zanzibar channel. Although isolation by distance is present, this study suggests that the three regionally predominant ocean current systems (i.e., East African Coastal Current, North East Madagascar Current, and the South Equatorial Current) rather than distance determine genetic connectivity and structure of T. hemprichii in the WIO. If the goal is to maintain genetic connectivity of T. hemprichii within the WIO, conservation planning and implementation of marine protection should be considered at the regional scale—across national borders.     

Internalization of weight bias: Implications for binge eating and emotional well-being

Objective: This study examined the relationship between internalization of negative weight‐based stereotypes and indices of eating behaviors and emotional well‐being in a sample of overweight and obese women. Research Method and Procedures: The sample was comprised of 1013 women who belonged to a national, non‐profit weight loss organization. Participants completed an on‐line battery of self‐report questionnaires measuring frequency of weight stigmatization and coping responses to deal with bias and symptoms of depression and self‐esteem, attitudes about weight and obesity, and binge eating behaviors. In addition, participants were asked to list the most common weight‐based stereotypes and whether they believed them to be true or false. Results: Participants who believed that weight‐based stereotypes were true reported more frequent binge eating and refusal to diet in response to stigma experiences compared with those who reported stereotypes to be false. The degree to which participants believed stereotypes to be true or false was not related to types or amount of stigma experiences reported, self‐esteem, depression, or attitudes toward obese persons. In addition, engaging in weight loss strategies as a response to bias was not predicted by stereotype beliefs or by actual stigma experiences, regardless of the amount or types of stigma reported. Discussion: These findings suggest that obese individuals who internalize negative weight‐based stereotypes may be particularly vulnerable to the negative impact of stigma on eating behaviors and also challenge the notion that stigma may motivate obese individuals to engage in efforts to lose weight. This study highlights a new area of research that warrants attention to better understand weight stigma and its potential consequences for health.     

Sexual signal loss in field crickets maintained despite strong sexual selection favoring singing males

Evolutionary biologists commonly seek explanations for how selection drives the emergence of novel traits. Although trait loss is also predicted to occur frequently, few contemporary examples exist. In Hawaii, the Pacific field cricket (Teleogryllus oceanicus) is undergoing adaptive sexual signal loss due to natural selection imposed by eavesdropping parasitoids. Mutant male crickets (“flatwings”) cannot sing. We measured the intensity of sexual selection on wing phenotype in a wild population. First, we surveyed the relative abundance of flatwings and “normal‐wings” (nonmutants) on Oahu. Then, we bred wild‐mated females’ offspring to determine both female genotype with respect to the flatwing mutation and the proportion of flatwing males that sired their offspring. We found evidence of strong sexual selection favoring the production of song: females were predominantly homozygous normal‐wing, their offspring were sired disproportionately by singing males, and at the population level, flatwing males became less common following a single sexual selection event. We report a selection coefficient describing the total (pre‐ and postcopulatory) sexual selection favoring normal‐wing males in nature. Given the maintenance of the flatwing phenotype in Hawaii in recent years, this substantial sexual selection additionally suggests an approximate strength of opposing natural selection that favors silent males.     

Structure of an engineered intein reveals thiazoline ring and provides mechanistic insight

We have engineered an intein which spontaneously and reversibly forms a thiazoline ring at the native N-terminal Lys-Cys splice junction. We identified conditions to stablize the thiazoline ring and provided the first crystallographic evidence, at 1.54 Å resolution, for its existence at an intein active site. The finding bolsters evidence for a tetrahedral oxythiazolidine splicing intermediate. In addition, the pivotal mutation maps to a highly conserved B-block threonine, which is now seen to play a causative role not only in ground-state destabilization of the scissile N-terminal peptide bond, but also in steering the tetrahedral intermediate toward thioester formation, giving new insight into the splicing mechanism. We demonstrated the stability of the thiazoline ring at neutral pH as well as sensitivity to hydrolytic ring opening under acidic conditions. A pH cycling strategy to control N-terminal cleavage is proposed, which may be of interest for biotechnological applications requiring a splicing activity switch, such as for protein recovery in bioprocessing.