Effects of visible-light irradiation on vitreous structure in the presence of a photosensitizer

Sensitized photo-induced changes of vitreous structure were investigated using both in vivo and in vitro model systems. In the former, rabbit eyes were injected with the photosensitizer riboflavin, and in the latter, calf vitreous samples were treated with riboflavin or Methylene Blue prior to irradiation with white light. The active species of oxygen, i.e. singlet oxygen, superoxide anion, hydroxyl radical and hydrogen peroxide, generated by the photodynamic action of the sensitizer, caused significant liquefaction of the calf vitreous in vitro. There was little liquefaction of the rabbit vitreous in vivo, suggesting the presence of a protective mechanism in vivo. hyaluronidase induced significantly greater liquefaction in vitro than either Methylene Blue or riboflavin. This study suggests that loss of gel vitreous structure can result from extensive depolymerization of hyaluronidase by hyaluronidase and less drastic conformation and molecular weight changes in the photosensitized reactions. Although light-induced liquefaction was less marked than enzyme-induced liquefaction, the mechanism of the former is more pertinent to age-related vitreous synchysis.     

Evidence-Based Nutrition Interventions Improved Adolescents’ Knowledge and Behaviors in Indonesia

Adolescence is a nutritionally vulnerable and critical life stage. However, few programs and policies focus on improving adolescent nutrition in Indonesia. To address this gap, we implemented a gender-responsive package of interventions: (1) breakfast and weekly iron-folic acid supplementation (WIFS), (2) a school-based nutrition education program, and (3) a social behavior change communication strategy. We surveyed 514 adolescents at baseline (2019) and endline (2020) in Klaten and Lombok Barat districts in Indonesia. The survey included a knowledge assessment on nutrition, as well as indicators of attitudes and behaviors on diet, physical activity, and WIFS. We employed multivariable linear and logistic regression to test for pre–post intervention differences. Overall knowledge was significantly higher post-intervention (β: 3.3; 95% confidence interval [CI]: 2.6, 3.9). Diet diversity was high at both timepoints, however, at post-intervention there was significantly higher odds of consuming vitamin A-rich fruits and vegetables (Odds Ratio [OR]: 1.5; 95% CI: 1.1, 2.0) and lower odds of consuming sugar-sweetened beverages (OR: 0.4; 95% CI: 0.3, 0.5). Post-intervention, there was higher odds of reporting 60 min of daily physical activity (OR: 2.3; 95% CI: 1.7, 3.2) and WIFS among girls (OR: 6.7; 95% CI: 1.5, 30.9). The package of interventions may be a promising first step to improving adolescent nutrition in Indonesia.     

Age-related oxidative decline of mitochondrial functions in rat brain is prevented by long term oral antioxidant supplementation

A combination of antioxidants (N-acetyl cysteine, α-lipoic acid, and α-tocopherol) was selected for long term oral supplementation study in rats for protective effects on age-related mitochondrial alterations in the brain. Four groups of rats were chosen: young control (6–7 months); aged rats (22–24 months); aged rats (22–24 months) on daily antioxidant supplementation from 18 month onwards and young rats (6–7 months) on daily antioxidant supplementation from 2 month onwards. The brain mitochondrial functional parameters, status of antioxidant enzymes and accumulation of oxidative damage markers were measured in the four groups of rats. A significant decrease in complex IV activity and a loss of transmembrane potential and phosphorylation capacity along with an increased accumulation of oxidative damage markers and compromised antioxidant enzyme status were noticed in aged rat brain mitochondria as compared to that in young controls, but in aged rats supplemented with oral antioxidants the mitochondrial alterations were largely prevented. Antioxidant supplementation in young rats had no effect on mitochondrial parameters investigated in this study. The results have implications in biochemical and functional deficits of brain during aging as well as in neurodegenerative disorders.     

Outer membrane protein A (OmpA) from Shigella flexneri 2a: A promising subunit vaccine candidate

Shigellosis is the leading cause of childhood mortality and morbidity. Despite many years of extensive research a practical vaccine is not yet available against the disease. Recent studies illustrate that bacterial outer membrane proteins are budding target as vaccine antigen. Outer membrane proteins A (OmpA) are among the most immunodominant antigens in the outer membrane of gram negative bacteria and possess many characteristics desired of a vaccine candidate. We observe that OmpA of Shigella flexneri 2a is crossreactive and common antigen among Shigella spp. and the epitope is widely exposed on the cell surface as well as capable of evoking protective immunity in mice. The protective immunity involves participation of both the humoral and cellular immune responses, since OmpA boosts rapid induction of IgG and IgA in both the systemic and mucosal compartments and also activates Th1 cells. The immunopotentiating activity of OmpA is mediated by its ability to bind and stimulate macrophages and up-regulate the surface expression of MHCII, CD80 and CD40, leading to activation of CD4⁺ T cells to secrete cytokines and express chemokine receptor and IL-12Rβ2, thereby orchestrating the bridge between innate and adaptive immune responses. This ability is dependent on Toll-like receptor 2 (TLR2), as demonstrated by lack of response by TLR2 knockdown macrophages to OmpA. Hence this property of OmpA to link innate and adaptive immunity via TLR2 offers a novel vista to develop vaccine against shigellosis.     

From the Cover: Rational design of helical architectures

Nature has mastered the art of creating complex structures through self-assembly of simpler building blocks. Adapting such a bottom-up view provides a potential route to the fabrication of novel materials. However, this approach suffers from the lack of a sufficiently detailed understanding of the noncovalent forces that hold the self-assembled structures together. Here we demonstrate that nature can indeed guide us, as we explore routes to helicity with achiral building blocks driven by the interplay between two competing length scales for the interactions, as in DNA. By characterizing global minima for clusters, we illustrate several realizations of helical architecture, the simplest one involving ellipsoids of revolution as building blocks. In particular, we show that axially symmetric soft discoids can self-assemble into helical columnar arrangements. Understanding the molecular origin of such spatial organisation has important implications for the rational design of materials with useful optoelectronic applications.     

Contractile dysfunction in hypertrophied hearts with deficient insulin receptor signaling: possible role of reduced capillary density

Diabetics have worse outcomes than nondiabetics after a variety of cardiac insults. We tested the hypothesis that impaired insulin receptor signaling in myocytes worsens cardiac remodeling and function following injury, even in the absence of hyperglycemia. Mice with cardiomyocyte-restricted knock out of the insulin receptor (CIRKO) and wild type (WT) mice were treated with isoproterenol (ISO) for 2 or 5 days. Heart rates and cardiac mass increased comparably following ISO in WT and CIRKO mice. After 5 days, WT hearts were hyperdynamic by echocardiographic and left ventricular pressure measurements. However, CIRKO hearts had a blunted increase in contractility and relaxation following ISO. Interestingly, single myocytes isolated from both CIRKO ISO and WT ISO hearts had increased cellular shortening with prolonged time to peak shortening vs. respective shams. Thus, loss of myocytes or extramyocyte factors, rather than intrinsic dysfunction of surviving myocytes, caused the blunted inotropic response in ISO treated CIRKO hearts. Indeed, CIRKO ISO mice had increased troponin release after 2 days and greater interstitial and sub-endocardial fibrosis at 5 days than did ISO WT. Apoptosis assessed by TUNEL and caspase staining was increased in CIRKO ISO compared to WT ISO hearts; however, very few of the apoptotic nuclei were clearly in cardiac myocytes. After 5 days of ISO treatment, VEGF expression was increased in WT but not in CIRKO hearts. In keeping with this finding, capillary density was reduced in CIRKO ISO relative to WT ISO. Basal expression of hypoxia-inducible factor-1alpha was lower in CIRKO vs. WT hearts and may explain the blunted VEGF response. Thus, absence of insulin receptor signaling in the cardiac myocyte worsens catecholamine-mediated myocardial injury, at least in part, via mechanisms that tend to impair myocardial blood flow and increase ischemic injury.