Pig pancreas may be a therapeutic resource for human diabetic patients. However, this potential is hindered by a lack of knowledge of the molecular events of pig pancreas development. In this study, the embryonic day 60, neonate and 6-month protein profiles of pig pancreas were ascertained at using two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-time of flight mass spectrometry. Twenty four proteins were differentially expressed during pig pancreas development. Among them, 12 spots increased and 7 spots decreased according to development. The expression of 5 protein were highest at birth. Expression of digestive enzymes including trypsin, pancreatic triacylglycerol lipase and pancreatic alpha-amylase was elevated in adults, whereas chymotrypsins were highly expressed in neonates. Proteins that were abundantly expressed during gestation were alpha-1-antitrypsin, alpha-fetoprotein and transferrins. Taken together, we found out that several proteins were significantly up- or down- regulated from pig pancreas based on developmental stage. This study will provide basis for understanding development of pig pancreas.

Extracorporeal membranous oxygenation is proposed for abdominal organ procurement from donation after circulatory determination of death (DCD). In France, the national Agency of Biomedicine supervises the procurement of kidneys from DCD, specifying the durations of tolerated warm and cold ischemia. However, no study has determined the optimal conditions of this technique. The aim of this work was to develop a preclinical model of DCD using abdominal normothermic oxygenated recirculation (ANOR). In short, our objectives are to characterize the mechanisms involved during ANOR and its impact on abdominal organs.

"Mushroom alcohol," or 1-octen-3-ol, is a common fungal volatile organic compound (VOC) that has been studied for its flavor properties, its effects on fungal spore germination, mushroom development, and as a signaling agent for insects. Far less is known about its effects on plants. We exposed Arabidopsis thaliana seeds, under conditions conducive to germination, to high (10 and 100 mg/1) and low concentrations (1, 2, and 3 mg/1) of racemic, S, and R forms of 1-octen-3-ol for 3 days. In addition, 1-, 2-, 3-, and 4-week-old A.thaliana plants also were exposed to 1 mg/1 of the compounds for the same period of time. Seedling formation was retarded with all tested levels of exposure to 1-octen-3-ol for both enantiomers and the racemer, while 95% of unexposed control seeds germinated to seedling within 3 days. There was a dose-dependent response in the reduction of seedling formation between 1 mg/1 and 3 mg/1 of exposure. When exposed seeds were removed from the VOC, nearly all resumed germination. Young plants exposed to 1 mg/1 of the R and S enantiomers of 1-octen-3-ol exhibited a mild inhibition of growth and chlorophyll production at 2 and 3 weeks but not at 4 weeks.

Underlying mechanisms regulating angiogenesis in ovarian cancer have not been completely elucidated. Evidence suggests that the TP53 tumor suppressor pathway and tumor microenvironment play integral roles. We utilized microarray technology to study the interaction between TP53 mutational status and hypoxia on angiogenic gene expression.

Shiga toxin (Stx)-producing Escherichia coli (STEC) are pathogenic E. coli causing diarrhea, hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). STEC are characterized by a constellation of virulence factors additional to Stx and have long been regarded as capable to cause HC and HUS when possessing the ability of inducing the attaching and effacing (A/E) lesion to the enterocyte, although strains isolated from such severe infections sometimes lack this virulence feature. Interestingly, the capability to cause the A/E lesion is shared with another E. coli pathogroup, the Enteropathogenic E. coli (EPEC). In the very recent times, a different type of STEC broke the scene causing a shift in the paradigm for HUS-associated STEC. In 2011, a STEC O104:H4 caused a large outbreak with more than 800 HUS and 50 deaths. Such a strain presented the adhesion determinants of Enteroaggregative E. coli (EAggEC). We investigated the possibility that, besides STEC and EAggEC, other pathogenic E. coli could be susceptible to infection with stx-phages. A panel of stx2-phages obtained from STEC isolated from human disease was used to infect experimentally E. coli strains representing all the known pathogenic types, including both diarrheagenic E. coli (DEC) and extra-intestinal pathogenic E. coli (ExPEC). We observed that all the E. coli pathogroups used in the infection experiments were susceptible to the infection. Our results suggest that the stx2-phages used may not have specificity for E. coli adapted to the intestinal environment, at least in the conditions used. Additionally, we could only observe transient lysogens suggesting that the event of stable stx2-phage acquisition occurs rarely.

The emergence of antibiotic-resistant bacterial strains has become a global crisis and is vulnerable for the exploration of alternative antibacterial therapies. The present study emphasizes the use of bacteriophage for the treatment of multidrug resistant P. aeruginosa. P. aeruginosa was used to induce septicemia in streptozotocin (STZ) induced diabetic and nondiabetic mice by intraperitoneal (i.p.) injection of 3 × 10(8) CFU, resulting in a fatal bacteremia within 48 hrs. A single i.p. injection of 3 × 10(9) PFU phage GNCP showed efficient protection in both diabetic (90%) and nondiabetic (100%) bacteremic mice. It was further noted that the protection rate was reduced in diabetic mice when phage GNCP was administered after 4 h and 6 h of lethal bacterial challenge. In contrast, nondiabetic bacteremic mice were rescued even when treatment was delayed up to 20 h after lethal bacterial challenge. Evaluation of results confirmed that a single intraperitoneal injection of the phage dose (3 × 10(9) PFU/mL) was more effective than the multiple doses of imipenem. These results uphold the efficacy of phage therapy against pernicious P. aeruginosa infections, especially in cases of immunocompromised host.

Osmotic and ionic stresses were the primary and instant damage produced by salt stress. They can also bring about other secondary stresses. Soybean is an important economic crop and the wild soybean aroused increasing attention for its excellent performance in salt resistance. For this reason, we compared the different performances of Glycine max L. (ZH13) and Glycine soja L. (BB52) in both young and mature seedlings, hoping to clarify the specific reasons. Our research revealed that, compared to the cultivated soybean, the wild soybean was able to maintain higher water potential and relative water content (RWC), accumulate more amount of proline and glycine betaine, reduce the contents of Na(+) and Cl(-) by faster efflux, and cut down the efflux of the K(+) as well as keep higher K(+)/Na(+) ratio. And what is more is that, almost all the excel behaviors became particularly obvious under higher NaCl concentration (300 mM). Therefore, according to all the detections and comparisons, we concluded that the wild soybean had different tolerance mechanisms and better salt resistance. It should be used as eminent germplasm resource to enhance the resistant ability of cultivated soybean or even other crops.

Being an integral part of basic, translational and clinical research, the demand for primary human hepatocytes (PHH) is continuously growing while the availability of tissue resection material for the isolation of metabolically competent PHH remains limited. To overcome current shortcomings, this study evaluated the use of explanted diseased organs from liver transplantation patients as a potential source of PHH. Therefore, PHH were isolated from resected surgical specimens (Rx-group; n = 60) and explanted diseased livers obtained from graft recipients with low labMELD-score (Ex-group; n = 5). Using established protocols PHH were subsequently cultured for a period of 7 days. The viability and metabolic competence of cultured PHH was assessed by the following parameters: morphology and cell count (CyQuant assay), albumin synthesis, urea production, AST-leakage, and phase I and II metabolism. Both groups were compared in terms of cell yield and metabolic function, and results were correlated with clinical parameters of tissue donors. Notably, cellular yields and viabilities were comparable between the Rx- and Ex-group and were 5.3±0.5 and 2.9±0.7×106 cells/g liver tissue with 84.3±1.3 and 76.0±8.6% viability, respectively. Moreover, PHH isolated from the Rx- or Ex-group did not differ in regards to loss of cell number in culture, albumin synthesis, urea production, AST-leakage, and phase I and II metabolism (measured by the 7-ethoxycoumarin-O-deethylase and uracil-5'-diphosphate-glucuronyltransferase activity). Likewise, basal transcript expressions of the CYP monooxygenases 1A1, 2C8 and 3A4 were comparable as was their induction when treated with a cocktail that consisted of 3-methylcholantren, rifampicin and phenobarbital, with increased expression of CYP 1A1 and 3A4 mRNA while transcript expression of CYP 2C8 was only marginally changed. In conclusion, the use of explanted diseased livers obtained from recipients with low labMELD-score might represent a valuable source of metabolically competent PHH which are comparable in viability and function to cells obtained from specimens following partial liver resection.

The combination of gold and copper is a good way to pull down the cost of gold and ameliorate the instability of copper. Through shape control, the synergy of these two metals can be better exploited. Here, we report an aqueous phase route to the synthesis of pentacle gold-copper alloy nanocrystals with fivefold twinning, the size of which can be tuned in the range from 45 to 200 nm. The growth is found to start from a decahedral core, followed by protrusion of branches along twinning planes. Pentacle products display strong localized surface plasmon resonance peaks in the near-infrared region. Under irradiation by an 808-nm laser, 70-nm pentacle nanocrystals exhibit a notable photothermal effect to kill 4T1 murine breast tumours established on BALB/c mice. In addition, 70-nm pentacle nanocrystals show better catalytic activity than conventional citrate-coated 5-nm Au nanoparticles towards the reduction of p-nitrophenol to p-aminophenol by sodium borohydride.

It is known that physico/chemical alterations on biomaterial surfaces have the capability to modulate cellular behavior, affecting early tissue repair. Such surface modifications are aimed to improve early healing response and, clinically, offer the possibility to shorten the time from implant placement to functional loading. Since FAK and Src are intracellular proteins able to predict the quality of osteoblast adhesion, this study evaluated the osteoblast behavior in response to nanometer scale titanium surface texturing by monitoring FAK and Src phosphorylations.

Little is known about the interactions between the default mode network (DMN) subregions in relapsing-remitting multiple sclerosis (RRMS). This study used diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) to examine alterations of long white matter tracts in paired DMN subregions and their functional connectivity in RRMS patients.

The activity of ammonia-oxidizing archaea (AOA) leads to the loss of nitrogen from soil, pollution of water sources and elevated emissions of greenhouse gas. To date, eight AOA genomes are available in the public databases, seven are from the group I.1a of the Thaumarchaeota and only one is from the group I.1b, isolated from hot springs. Many soils are dominated by AOA from the group I.1b, but the genomes of soil representatives of this group have not been sequenced and functionally characterized. The lack of knowledge of metabolic pathways of soil AOA presents a critical gap in understanding their role in biogeochemical cycles. Here, we describe the first complete genome of soil archaeon Candidatus Nitrososphaera evergladensis, which has been reconstructed from metagenomic sequencing of a highly enriched culture obtained from an agricultural soil. The AOA enrichment was sequenced with the high throughput next generation sequencing platforms from Pacific Biosciences and Ion Torrent. The de novo assembly of sequences resulted in one 2.95 Mb contig. Annotation of the reconstructed genome revealed many similarities of the basic metabolism with the rest of sequenced AOA. Ca. N. evergladensis belongs to the group I.1b and shares only 40% of whole-genome homology with the closest sequenced relative Ca. N. gargensis. Detailed analysis of the genome revealed coding sequences that were completely absent from the group I.1a. These unique sequences code for proteins involved in control of DNA integrity, transporters, two-component systems and versatile CRISPR defense system. Notably, genomes from the group I.1b have more gene duplications compared to the genomes from the group I.1a. We suggest that the presence of these unique genes and gene duplications may be associated with the environmental versatility of this group.

Oral squamous cell carcinoma (OSCC) is a leading malignancy worldwide; the overall 5-year survival rate is approximately 50%. A variety of proteins in Toll-like receptors (TLRs) pathway have been related with the risk of OSCC. However, the influence of genetic variations in TLRs pathway genes on OSCC susceptibility is unclear. Previous studies mainly focused on the coding region of genes, while the UTR region remains unstudied. In the current study, a bioinformatics approach was performed to select candidate single nucleotide polymorphisms (SNPs) on microRNA binding sites of TLRs pathway genes related with OSCC. After screening 90 OSCC related TLRs pathway genes, 16 SNPs were selected for genotyping. We found that rs5030486, the polymorphisms on 3' UTR of TRAF6, was significantly associated with OSCC risk. AG genotype of TRAF6 was strongly associated with a decreased risk of OSCC (OR = 0.252; 95% CI = 0.106, 0.598; p = 0.001). In addition, AG genotype was also related with a reduced risk of OSCC progression both in univariable analysis (HR = 0.303, 95% CI = 0.092, 0.995) and multivariable analysis (HR = 0.272, 95% CI = 0.082, 0.903). Furthermore, after detecting the mRNA expression level of TRAF6 in 24 OSCC patients, we found that TRAF6 expression level was significantly different between patients carrying different genotypes at locus rs5030486 (p = 0.013), indicating that rs5030486 of TRAF6 might contribute to OSCC risk by altering TRAF6 expression level. In general, these data indicated that SNP rs5030486 could be a potential bio-marker for OSCC risk and our results might provide new insights into the association of polymorphisms within the non-coding area of genes with cancers.

We performed a genome-wide association study (GWAS) of 1550 North American celiac disease cases and 3084 controls. Twelve SNPs, distributed across four regions (3p21.31, 4q27, 6q15, 6q25), were significantly associated with disease (p-value <1.0×10-7), and a further seven SNPs, across four additional regions (1q24.3, 10p15.1, 6q22.31, 17q21.32) had suggestive evidence (1.0×10-7 < p-value < 1.0×10-6). This study replicated a previous suggestive association within FRMD4B (3p14.1), confirming it as a celiac disease locus. All four regions with significant associations and two regions with suggestive results (1q24.3, 10p15.1) were known disease loci. The 6q22.31 and 10p11.23 regions were not replicated. A total of 410 SNPs distributed across the eight significant and suggestive regions were tested for association with dermatitis herpetiformis and microscopic colitis. Preliminary, suggestive statistical evidence for association with the two traits was found at chromosomes 3p21.31, 6q15, 6q25, 1q24.3 and 10p11.23, with future studies being required to validate the reported associations.

Mobile health (mHealth) has undergone exponential growth in recent years. Patients and healthcare professionals are increasingly using health-related applications, at the same time as concerns about ethical issues, bias, conflicts of interest and privacy are emerging. The general aim of this paper is to provide an overview of the current state of development of mHealth.

Circulating tumor cells (CTCs) are cancer cells that can be isolated via liquid biopsy from blood and can be phenotypically and genetically characterized to provide critical information for guiding cancer treatment. Current analysis of CTCs is hindered by the throughput, selectivity and specificity of devices or assays used in CTC detection and isolation.

Magnetic resonance colonography (MRC) has been developed to assess inflammatory bowel diseases. We aimed to assess the feasibility of MRC in rats with TNBS-induced chronic colitis and to confront imaging results with fibrosis and stenosing features of the model.

Throughout postnatal development, the gastric epithelium expresses Transforming Growth Factor beta1 (TGFβ1), but it is also exposed to luminal peptides that are part of milk. During suckling period, fasting promotes the withdrawal of milk-born molecules while it stimulates gastric epithelial cell proliferation. Such response can be reversed by exogenous TGFβ1, as it directly affects cell cycle through the regulation of p27 levels. We used fasting condition to induce the hyperproliferation of gastric epithelial cells in 14-day-old Wistar rats, and evaluated the effects of TGFβ1 gavage on p27 expression, phosphorylation at threonine 187 (phospho-p27Thr187) and degradation. p27 protein level was reduced during fasting when compared to suckling counterparts, while phospho-p27Thr187/p27 ratio was increased. TGFβ1 gavage reversed this response, which was confirmed through immunostaining. By using a neutralizing antibody against TGFβ1, we found that it restored the p27 and phosphorylation levels detected during fasting, indicating the specific role of the growth factor. We noted that neither fasting nor TGFβ1 changed p27 expression, but after cycloheximide administration, we observed that protein synthesis was influenced by TGFβ1. Next, we evaluated the capacity of the gastric mucosa to degrade p27 and we recorded a higher concentration of the remaining protein in pups treated with TGFβ1, suggesting augmented stability under this condition. Thus, we showed for the first time that luminal TGFβ1 increased p27 levels in the rat gastric mucosa by up- regulating translation and reducing protein degradation. We concluded that such mechanisms might be used by rapidly proliferating cells to respond to milk-born TGFβ1 and food restriction.

Catalpol, an iridoid glucoside extracted from the traditional Chinese herbal medicine, Rehmannia glutinosa, is reported to exert neuroprotective, anti-inflammatory, anti-tumor and anti-apoptotic effects. The main aim of the present study was to investigate whether catalpol ameliorates experimental acute pancreatitis (AP) induced by sodium taurocholate (STC). AP was induced in rats via retrograde injection of 4% STC (0.1 mL/100 g) into the biliopancreatic duct. Rats were pre-treated with saline or catalpol (50 mg/kg) 2 h before STC injection. At 12, 24 and 48 h after injection, the severity of AP was evaluated using biochemical and morphological analyses. Pretreatment with catalpol led to a significant reduction in serum amylase and lipase activities, pancreatic histological damage, myeloperoxidase (MPO) activity, interleukin (IL)-1β, IL-6 and TNF-α levels, and activation of nuclear factor kappa B (NF-κB). Moreover, administration of catalpol increased the viability of pancreatic acinar cells and inhibited NF-κB expression in vitro. Our results collectively support the potential of catalpol as a highly effective therapeutic agent for treatment of AP.

Multi-color stochastic optical reconstruction microscopy (STORM) is routinely performed; however, the various approaches for achieving multiple colors have important caveats. Color cross-talk, limited availability of spectrally distinct fluorophores with optimal brightness and duty cycle, incompatibility of imaging buffers for different fluorophores, and chromatic aberrations impact the spatial resolution and ultimately the number of colors that can be achieved. We overcome these complexities and develop a simple approach for multi-color STORM imaging using a single fluorophore and sequential labelling. In addition, we present a simple and versatile method to locate the same region of interest on different days and even on different microscopes. In combination, these approaches enable cross-talk-free multi-color imaging of sub-cellular structures.