How the Intestinal Peptide Transporter PEPT-1 Contributes to an Obesity Phenotype in Caenorhabditits elegans

Background: Amino acid absorption in the form of di- and tripeptides is mediated by the intestinal proton-coupled peptide transporter PEPT-1 (formally OPT-2) in Caenorhabditits elegans. Transporter-deficient animals (pept-1(lg601)) show impaired growth, slowed postembryonal development and major changes in amino acid status. Principal Findings: Here we demonstrate that abolished intestinal peptide transport also leads to major metabolic alterations that culminate in a two fold increase in total body fat content. Feeding of C. elegans with [U- 13 C]-labelled E. coli revealed a decreased de novo synthesis of long-chain fatty acids in pept-1(lg601) and reduced levels of polyunsaturated fatty acids. mRNA profiling revealed increased transcript levels of enzymes/transporters needed for peroxisomal b-oxidation and decreased levels for those required for fatty acid synthesis, elongation and desaturation. As a prime and most fundamental process that may account for the increased fat content in pept-1(lg601) we identified a highly accelerated absorption of free fatty acids from the bacterial food in the intestine. Conclusions: The influx of free fatty acids into intestinal epithelial cells is strongly dependent on alterations in intracellular pH which is regulated by the interplay of PEPT-1 and the sodium-proton exchanger NHX-2. We here provide evidence for a central mechanism by which the PEPT-1/NHX-2 system strongly influences the in vivo fat content of C. elegans. Loss of PEPT-1 decreases intestinal proton influx leading to a higher uptake of free fatty acids with fat accumulation whereas loss of NHX

CCDC3: A new p63 target gene involved in regulation of liver lipid metabolism

TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, induces the expression of CCDC3 mRNA level by directly binding to the p63 consensus DNA binding sequence within the CCDC3 enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity but induced by metformin, an anti-diabetic drug that activates p63. Also, the expression of CCDC3 is positively correlated with TAp63 levels, but inversely with ΔNp63 levels, during adipocyte differentiation. Interestingly, CCDC3, as a secreted protein, targets liver cancer cells and increases long chain polyunsaturated fatty acids, but decreases ceramide in the cells. CCDC3 alleviates glucose intolerance, insulin resistance, and fatty liver (steatosis) formation in transgenic CCDC3 mice on the high-fat diet by markedly reducing hepatic PPARγ expression and consequently leading to a drastic decrease of the PPARγ target gene, CIDEA, and other genes involved in de novo lipogenesis and of lipid droplets formation in their livers. Similar results are reproduced by hepatic expression of ectopic CCDC3 in mice on high-fat diet. Altogether, these results demonstrate that CCDC3 modulates liver lipid metabolism by inhibiting liver de novo lipogenesis as a downstream player of the p63 network

Effects of Overexpression and Inhibited Expression of Thymosin, an Actin‐interacting Protein from Bombyx Mori, on BmNPV Proliferation and Replication

Previous study showed that exogenously applied recombinant thymosin from Bombyx mori (BmTHY) reduces B. mori nucleopolyhedrovirus (BmNPV) proliferation in silkworm. Which stands to reason that BmTHY in B. mori is crucial for the defense against BmNPV. However, little is known about the effect of endogenously overexpressed or repressed BmTHY on B. mori resistance to virus infection. To study this issue, we constructed an overexpression and inhibited expression systems of BmTHY in BmN cells. The viral titer and the analysis from the quantitative real‐time polymerase chain reaction (PCR) revealed that overexpression of BmTHY decreased the copies of BmNPV gene gp41, which goes over to inhibit the proliferation of BmNPV in BmN cells, while the inhibited expression of BmTHY significantly enhanced viral proliferation in infected BmN cells. These results indicated that endogenous BmTHY can inhibit BmNPV proliferation and replication in infected BmN cells. Furthermore, Co‐IP showed that BmTHY could bind to actin in BmN cells. Also, the overexpression or inhibited expression of BmTHY shifted the ratio of F/G‐actin in infected BmN cells. Lastly, the BmTHY, an actin‐interacting protein, might be one of the key host factors against BmNPV, which inhibits viral proliferation and replication in BmN cells

Increasing bladder capacity by foot stimulation in rats with spinal cord injuries

Abstract Background This study was to explore the possibility that foot stimulation increased bladder capacity(BC) in rats with neurogenic bladder secondary to T10 spinal cord injuries. Methods In 20 awake rats (stimulation group) with T10 spinal cord injuries, 5 repeat cystometrograms (CMGs) were recorded. The 1st and 2nd CMGs were performed without stimulation. The 3rd, 4th, and 5th CMGs were done separately with 1 T, 2 T, and 4 T stimulation, respectively, through a pair of pad electrodes on the skin of the hind foot. In the control group of 20 rats, 5 repeat CMGs were recorded without foot stimulation. The threshold (T) was the minimal stimulation intensity to induce an observable toe twitch. Results In the stimulation group, foot stimulation with 2 T significantly increased the BC an additional 68.9% ± 20.82% (p < 0.05). Foot stimulation with 4 T increased the BC an additional 120.9% ± 24.82% (p < 0.05). Compared with the control group, BC in the 1st, 2nd, and 3rd (1 T) CMG had no significant difference in the stimulation group, but the 4th (2 T) and 5th (4 T) CMGs were significantly increased (p < 0.05). Conclusions Electrical stimulation of the foot was effective in inhibiting reflex bladder activity and increasing bladder capacity in spinal cord injury rats

Highly Efficient and Visible Light Responsive Heterojunction Composites as Dual Photoelectrodes for Photocatalytic Fuel Cell

In the present work, a novel photocatalytic fuel cell (PFC) system involving a dual heterojunction photoelectrodes, viz. polyaniline/TiO2 nanotubes (PANI/TiO2 NTs) photoanode and CuO/Co3O4 nanorods (CuO/Co3O4 NRs) photocathode, has been designed. Compared to TiO2 NTs electrode of PFC, the present heterojunction design not only enhances the visible light absorption but also offers the higher efficiency in degrading Rhodamine B–a model organic pollutant. The study includes an evaluation of the dual performance of the photoelectrodes as well. Under visible-light irradiation of 3 mW cm−2, the cell composed of the photoanode PANI/TiO2 NTs and CuO/Co3O4 NRs photocathode forms an interior bias of +0.24 V within the PFC system. This interior bias facilitated the transfer of electrons from the photoanode to photocathode across the external circuit and combined with the holes generated therein along with a simultaneous power production. In this manner, the separation of electron/hole pair was achieved in the photoelectrodes by releasing the holes and electrons of PANI/TiO2 NTs photoanode and CuO/Co3O4 NRs photocathode, respectively. Using this PFC system, the degradation of Rhodamine B in aqueous media was achieved to an extent of 68.5% within a reaction duration of a four-hour period besides a simultaneous power generation of 85 μA cm−2

Substance use and self-medication during pregnancy and associations with socio-demographic data: A cross-sectional survey

Objective: To identify women vulnerable to substance use and self-medication during pregnancy based on associations with socio-demographic data. Methods: Data were collected in person, with self-developed questionnaires, from pregnant women (n = 422) in Chengdu, China, from July to November 2012. Multivariate logistic regression analysis was used to reveal associations with socio-demographic parameters. Results: Higher educational background, being employed, and higher educational background of the mother were associated with a 37% [odds ratio (OR):0.63, 95%CI:0.45–0.89], 65% (OR:0.35, 95%CI:0.13–0.94), and 29% (OR: 0.71, 95%CI:0.53–0.96) less likelihood of alcohol use, respectively. Adverse pregnancy outcome was associated with a 2.13-fold (OR: 2.13, 95%CI: 1.07–4.25) greater likelihood of alcohol use. Young age and higher educational background were associated with an 11% (OR: 0.89, 95%CI: 0.81–0.98) and 31% (OR:0.69, 95%CI:0.49–0.98) less likelihood of cigarette smoking, respectively. Conclusion: Socio-demographic parameters were associated with substance use during pregnancy and warrants targeted health education provided by nurses to pregnant women