Effect of enrichment of maize meal with nicotinic acid and riboflavin upon the Vitamin and protein nutritional status of young school-going and pre-school children

A series of experiments was undertaken to investigate the feasibility of enriching maize meal with nicotinic acid and riboflavin. First the necessary level of enrichment was established and then the efficacy of such enrichment of maize was tested in the field on children and young adults. This report deals with the results of an experiment designed to establish whether such an enrichment scheme would have any detrimental effects on· young growing children with marginal protein calorie malnutrition. As in the previous experiments, a marked improvement in the nicotinic acid and riboflavin status was found in the experimental group. These biochemical findings were in conformity with the improvement in clinical status found. Moreover, such enrichment did not have any noticeable adverse effects. The hypothesis that vitamin enrichment could cause growth stimulation, and thus aggravate an existing marginal protein deficiency state, could not in any way be substantiated. The enrichment of maize meal with riboflavin and nicotinic acid during milling has been shown conclusively to be highly effective in improving the vitamin nutritional status while at the same time not harming the protein nutritional status of young children. Since the previous experiments proved it to be economically and technologically feasible, it is now strongly recommended that such an enrichment scheme be introduced on a national basis with the least possible delay.S. Afr. Med. J., 48, 1641 (1974)

Flipping the odds of drug development success through human genomics

Drug development depends on accurately identifying molecular targets that both play a causal role in a disease and are amenable to pharmacological action by small molecule drugs or bio-therapeutics, such as monoclonal antibodies. Errors in drug target specification contribute to the extremely high rates of drug development failure. Integrating knowledge of genes that encode druggable targets with those that influence susceptibility to common disease has the potential to radically improve the probability of drug development success

The origin of life: chemical evolution of a metabolic system in a mineral honeycomb?

For the RNA-world hypothesis to be ecologically feasible, selection mechanisms acting on replicator communities need to be invoked and the corresponding scenarios of molecular evolution specified. Complementing our previous models of chemical evolution on mineral surfaces, in which selection was the consequence of the limited mobility of macromolecules attached to the surface, here we offer an alternative realization of prebiotic group-level selection: the physical encapsulation of local replicator communities into the pores of the mineral substrate. Based on cellular automaton simulations we argue that the effect of group selection in a mineral honeycomb could have been efficient enough to keep prebiotic ribozymes of different specificities and replication rates coexistent, and their metabolic cooperation protected from extensive molecular parasitism. We suggest that mutants of the mild parasites persistent in the metabolic system can acquire useful functions such as replicase activity or the production of membrane components, thus opening the way for the evolution of the first autonomous protocells on Earth

The druggable genome and support for target identification and validation in drug development

Target identification (determining the correct drug targets for a disease) and target validation (demonstrating an effect of target perturbation on disease biomarkers and disease end points) are important steps in drug development. Clinically relevant associations of variants in genes encoding drug targets model the effect of modifying the same targets pharmacologically. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome-wide association studies to an updated set of genes encoding druggable human proteins, to agents with bioactivity against these targets, and, where there were licensed drugs, to clinical indications. We used this set of genes to inform the design of a new genotyping array, which will enable association studies of druggable genes for drug target selection and validation in human disease

Do female association preferences predict the likelihood of reproduction?

Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (<i>Xiphophorus helleri</i>) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

Does consultation improve decision-making?

This paper reports an experiment designed to test whether prior consultation within a group affects subsequent individual decision-making in tasks where demonstrability of correct solutions is low. In our experiment, subjects considered two paintings created by two different artists and were asked to guess which artist made each painting. We observed answers given by individuals under two treatments: In one, subjects were allowed the opportunity to consult with other participants before making their private decisions; in the other, there was no such opportunity. Our primary findings are that subjects in the first treatment evaluate the opportunity to consult positively, but they perform significantly worse and earn significantly less

About intrinsic transversality of pairs of sets

The article continues the study of the ‘regular’ arrangement of a collection of sets near a point in their intersection. Such regular intersection or, in other words, transversality properties are crucial for the validity of qualification conditions in optimization as well as subdifferential, normal cone and coderivative calculus, and convergence analysis of computational algorithms. One of the main motivations for the development of the transversality theory of collections of sets comes from the convergence analysis of alternating projections for solving feasibility problems. This article targets infinite dimensional extensions of the intrinsic transversality property introduced recently by Drusvyatskiy, Ioffe and Lewis as a sufficient condition for local linear convergence of alternating projections. Several characterizations of this property are established involving new limiting objects defined for pairs of sets. Special attention is given to the convex case

Improved Immunodetection of Endogenous α-Synuclein

α-Synuclein is a key molecule in understanding the pathogenesis of neurodegenerative α-synucleinopathies such as Parkinson's disease. Despite extensive research, however, its precise function remains unclear partly because of a difficulty in immunoblotting detection of endogenous α-synuclein. This difficulty has largely restricted the progress for α-synucleinopathy research. Here, we report that α-synuclein monomers tend to easily detach from blotted membranes, resulting in no or very poor detection. To prevent this detachment, a mild fixation of blotted membranes with paraformaldehyde was applied to the immunoblotting method. Amazingly, this fixation led to clear and strong detection of endogenous α-synuclein, which has been undetectable by a conventional immunoblotting method. Specifically, we were able to detect endogenous α-synuclein in various human cell lines, including SH-SY5Y, HEK293, HL60, HeLa, K562, A375, and Daoy, and a mouse cell line B16 as well as in several mouse tissues such as the spleen and kidney. Moreover, it should be noted that we could clearly detect endogenous α-synuclein phosphorylated at Ser-129 in several human cell lines. Thus, in some tissues and cultured cells, endogenous α-synuclein becomes easily detectable by simply fixing the blotted membranes. This improved immunoblotting method will allow us to detect previously undetectable endogenous α-synuclein, thereby facilitating α-synuclein research

Hospitalized poisonings after renal transplantation in the United States

BACKGROUND: The national incidence of and risk factors for hospitalized poisonings in renal transplant recipients has not been reported. METHODS: Historical cohort study of 39,628 renal transplant recipients in the United States Renal Data System between 1 July 1994 and 30 June 1998. Associations with time to hospitalizations for a primary diagnosis of poisonings (ICD-9 codes 960.x-989.x) within three years after renal transplant were assessed by Cox Regression. RESULTS: The incidence of hospitalized poisonings was 2.3 patients per 1000 person years. The most frequent causes of poisonings were immunosuppressive agents (25.3%), analgesics/antipyretics (14.1%), psychotropic agents (10.0%), and insulin/antidiabetic agents (7.1%). In Cox Regression analysis, low body mass index (BMI, <21.6 vs. >28.3 kg/m(2), adjusted hazard ratio (AHR), 3.02, 95% CI, 1.45–6.28, and allograft rejection, AHR 1.83, 95% CI, 1.15–2.89, were the only factors independently associated with hospitalized poisonings. Hospitalized poisonings were independently associated with increased mortality (AHR, 1.54, 95% CI 1.22–1.92, p = 0.002). CONCLUSIONS: Hospitalized poisonings were associated with increased mortality after renal transplantation. However, almost all reported poisonings in renal transplant recipients were due to the use of prescribed medications. Allograft rejection and low BMI were the only independent risk factors for poisonings identified in this population

Defective Peripheral Nerve Development Is Linked to Abnormal Architecture and Metabolic Activity of Adipose Tissue in Nscl-2 Mutant Mice

BACKGROUND: In mammals the interplay between the peripheral nervous system (PNS) and adipose tissue is widely unexplored. We have employed mice, which develop an adult onset of obesity due to the lack the neuronal specific transcription factor Nscl-2 to investigate the interplay between the nervous system and white adipose tissue (WAT). METHODOLOGY: Changes in the architecture and innervation of WAT were compared between wildtype, Nscl2-/-, ob/ob and Nscl2-/-//ob/ob mice using morphological methods, immunohistochemistry and flow cytometry. Metabolic alterations in mutant mice and in isolated cells were investigated under basal and stimulated conditions. PRINCIPAL FINDINGS: We found that Nscl-2 mutant mice show a massive reduction of innervation of white epididymal and paired subcutaneous inguinal fat tissue including sensory and autonomic nerves as demonstrated by peripherin and neurofilament staining. Reduction of innervation went along with defects in the formation of the microvasculature, accumulation of cells of the macrophage/preadipocyte lineage, a bimodal distribution of the size of fat cells, and metabolic defects of isolated adipocytes. Despite a relative insulin resistance of white adipose tissue and isolated Nscl-2 mutant adipocytes the serum level of insulin in Nscl-2 mutant mice was only slightly increased. CONCLUSIONS: We conclude that the reduction of the innervation and vascularization of WAT in Nscl-2 mutant mice leads to the increase of preadipocyte/macrophage-like cells, a bimodal distribution of the size of adipocytes in WAT and an altered metabolic activity of adipocytes