Mechanism of nicotinic acid transport in human liver cells: experiments with HepG2 cells and primary hepatocytes

This study reports on the functional expression of a specific, high-affinity carrier-mediated mechanism for the transport of niacin (nicotinic acid) in human liver cells. Both human-derived liver HepG2 cells and human primary hepatocytes were used as models in these investigations. The initial rate of transport of nicotinic acid into HepG2 cells was found to be acidic pH, temperature, and energy dependent; it was, however, Na(+) independent in nature. Evidence for the existence of a carrier-mediated system that is specific for [(3)H]nicotinic acid transport was found and included the following: 1) saturability as a function of concentration with an apparent K(m) of 0.73 +/- 0.16 microM and V(max) of 25.02 +/- 1.45 pmol.mg protein(-1).3 min(-1), 2) cis-inhibition by unlabeled nicotinic acid and nicotinamide but not by unrelated organic anions (lactate, acetate, butyrate, succinate, citrate, and valproate), and 3) trans-stimulation of [(3)H]nicotinic acid efflux by unlabeled nicotinic acid. Transport of the vitamin into human primary hepatocytes occurs similarly via an acidic pH-dependent and specific carrier-mediated process. Inhibitors of the Ca(2+)-calmodulin-mediated pathway (but not modulators of the PKC-, PKA-, and protein tyrosine kinase-mediated pathways) inhibited nicotinic acid transport into both HepG2 cells and human primary hepatocytes. Maintenance of HepG2 cells (for 48 h) in growth medium oversupplemented with nicotinic acid (or nicotinamide) did not affect the subsequent transport of [(3)H]nicotinic acid into HepG2 cells. These results show, for the first time, the existence of a specific and regulated membrane carrier-mediated system for nicotinic acid transport in human liver cells.     

Enhanced Degradation of Petroleum Hydrocarbons in Corn-Steep-Liquor-Treated Soil Microcosm

The efficiency of corn steep liquor (CSL) as a potential stimulant for remediation of hydrocarbon-contaminated soil was evaluated in soil microcosms. Chronically polluted soil samples treated with CSL, water, and un untreated control were compared over a period of 42 days. There were remarkable changes in the physicochemical status of the soil in the CSL-treated set-up with noticeable utilization of essential nutrients such as nitrogen, phosphorus, and potassium. Percentage hydrocarbon utilizers showed a concomitant increase with hydrocarbon utilization in CSL-treated (0.05–0.16%) and water-treated (0.02–0.12%) set-ups, while no significant changes occurred in the untreated control. Gas chromatographic fingerprints showed complete disappearance of the lower-fraction alkanes C₇, C₈, C₉, and C₁₁ within 21 days, as well as some higher fractions, significantly C₁₆ and C₂₉, in the CSL-treated set-up. In the CSL-treated set-up, 77.9% of hydrocarbon was degraded, while the corresponding values for the water-treated and untreated control were 40.55 and 30.6%, respectively. The percentage aliphatic components degraded differed significantly in the CSL-treated, water-treated, and untreated set-ups. The n-C₁₇/pristane and n-C₁₈/phytane ratios in the CSL-treated set-up were 1.298 and 1.153, respectively, on day 0, but at the end of the treatability period, the values had dropped drastically to 0.182 and 0.585, respectively. The results of this study show that corn steep liquor is a potential material for bioremediation of hydrocarbon-polluted sites.     

The Functional Connectivity Landscape of the Human Brain

Functional brain networks emerge and dissipate over a primarily static anatomical foundation. The dynamic basis of these networks is inter-regional communication involving local and distal regions. It is assumed that inter-regional distances play a pivotal role in modulating network dynamics. Using three different neuroimaging modalities, 6 datasets were evaluated to determine whether experimental manipulations asymmetrically affect functional relationships based on the distance between brain regions in human participants. Contrary to previous assumptions, here we show that short- and long-range connections are equally likely to strengthen or weaken in response to task demands. Additionally, connections between homotopic areas are the most stable and less likely to change compared to any other type of connection. Our results point to a functional connectivity landscape characterized by fluid transitions between local specialization and global integration. This ability to mediate functional properties irrespective of spatial distance may engender a diverse repertoire of cognitive processes when faced with a dynamic environment.     

Assessment of initiation of breastfeeding practice in Kassala,Eastern Sudan: a community-based study

Background

The World Health Organization (WHO) encourages early initiation of breastfeeding within the first hour after birth with the objective of saving children’s lives. There are few published research papers about factors associated with the initiation of breastfeeding in Sudan.The aim of this study was to investigate the prevalence of and factors associated with the timely initiation of breastfeeding among mothers with children two years and under in Kassala, Eastern Sudan.

Methods

A community-based cross-sectional study was conducted from December 2016 to March 2017. Mothers were interviewed using a structured questionnaire.

Results

A total of 250 mother-child pairs participated in the study. The mean (standard deviation) of maternal age and children’s age was 27.1 (5.68) years and 11.9 (6.9) months, respectively.Of the 250 mothers, 218 (87.2%) initiated breastfeeding within the first hour. In multivariable logistic regression analysis, factors associated with the delay of breastfeeding initiation were having a male baby (Adjusted Odds Ratio [AOR] 3.90, 95% Confidence Interval [CI]1.33, 11.47), and mothers with medical disorders (AOR 5.07, 95% CI 1.22, 21.16).

Conclusion

There was a high prevalence of early initiation of breastfeeding. An association with delayed initiation of breastfeeding was found amongst mothers who had medical disorders and those who had a male infant. Wherever possible, early initiation of breastfeeding should be promoted for all infants, regardless of gender.

     

Fibroblast Growth Factor Receptors as Novel Therapeutic Targets in SNF5-Deleted Malignant Rhabdoid Tumors

Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers arising in brain, kidney and soft tissues, which are characterized by loss of the tumor suppressor SNF5/SMARCB1. MRTs are poorly responsive to chemotherapy and thus a high unmet clinical need exists for novel therapies for MRT patients. SNF5 is a core subunit of the SWI/SNF chromatin remodeling complex which affects gene expression by nucleosome remodeling. Here, we report that loss of SNF5 function correlates with increased expression of fibroblast growth factor receptors (FGFRs) in MRT cell lines and primary tumors and that re-expression of SNF5 in MRT cells causes a marked repression of FGFR expression. Conversely, siRNA-mediated impairment of SWI/SNF function leads to elevated levels of FGFR2 in human fibroblasts. In vivo, treatment with NVP-BGJ398, a selective FGFR inhibitor, blocks progression of a murine MRT model. Hence, we identify FGFR signaling as an aberrantly activated oncogenic pathway in MRTs and propose pharmacological inhibition of FGFRs as a potential novel clinical therapy for MRTs.     

Caseoperoxidase,mixed β-casein–SDS–hemin–imidazole complex: a nano artificial enzyme

A novel peroxidase-like artificial enzyme, named “caseoperoxidase”, was biomimetically designed using a nano artificial amino acid apo-protein hydrophobic pocket. This four-component nano artificial enzyme containing heme–imidazole–β-casein–SDS exhibited high activity growth and k_cat performance toward the native horseradish peroxidase demonstrated by the steady state kinetics using UV–vis spectrophotometry. The hydrophobicity and secondary structure of the caseoperoxidase were studied by ANS fluorescence and circular dichroism spectroscopy. Camel β-casein (Cβ-casein) was selected as an appropriate apo-protein for the heme active site because of its innate flexibility and exalted hydrophobicity. This selection was confirmed by homology modeling method. Heme docking into the newly obtained Cβ-casein structure indicated one heme was mainly incorporated with Cβ-casein. The presence of a main electrostatic site for the active site in the Cβ-casein was also confirmed by experimental methods through Wyman binding potential and isothermal titration calorimetry. The existence of Cβ-casein protein in this biocatalyst lowered the suicide inactivation and provided a suitable protective role for the heme active-site. Additional experiments confirmed the retention of caseoperoxidase structure and function as an artificial enzyme.     

Genetic Diversity of Newcastle Disease Virus in Wild Birds and Pigeons in West Africa

In West and Central Africa, virulent Newcastle disease virus (NDV) strains of the recently identified genotypes XIV, XVII, and XVIII are enzootic in poultry, representing a considerable threat to the sector. The increasing number of reports of virulent strains in wild birds at least in other parts of the world raised the question of a potential role of wild birds in the spread of virulent NDV in sub-Saharan Africa as well. We investigated 1,723 asymptomatic birds sampled at live-bird markets and sites important for wild-bird conservation in Nigeria and 19 sick or dead wild birds in Côte d''Ivoire for NDV class I and II. Typical avirulent wild-type genotype I strains were found in wild waterfowl in wetlands in northeastern Nigeria. They were unrelated to vaccine strains, and the involvement of inter- or intracontinental migratory birds in their circulation in the region is suggested. Phylogenetic analyses also revealed that genotype VI strains found in pigeons, including some putative new subgenotype VIh and VIi strains, were introduced on multiple separate occasions in Nigeria. A single virulent genotype XVIII strain was found in a dead wild bird in Côte d''Ivoire, probably as a result of spillover from sick poultry. In conclusion, screening of wild birds and pigeons for NDV revealed the presence a variety of virulent and avirulent strains in West Africa but did not provide strong evidence that wild birds play an important role in the spread of virulent strains in the region.     

RKIP: Much more than Raf Kinase inhibitory protein

From its discovery as a phosphatidylethanolamine‐binding protein in bovine brain to its designation as a physiological inhibitor of Raf kinase protein, RKIP has emerged as a critical molecule for maintaining subdued, well‐orchestrated cellular responses to stimuli. The disruption of RKIP in a wide range of pathologies, including cancer, Alzheimer's disease, and pancreatitis, makes it an exciting target for individualized therapy and disease‐specific interventions. This review attempts to highlight recent advances in the RKIP field underscoring its potential role as a master modulator of many pivotal intracellular signaling cascades that control cellular growth, motility, apoptosis, genomic integrity, and therapeutic resistance. Specific biological and functional niches are highlighted to focus future research towards an enhanced understanding of the multiple roles of RKIP in health and disease. J. Cell. Physiol. 228: 1688–1702, 2013. © 2013 Wiley Periodicals, Inc.