Molecular cloning and preliminary functional analysis of six RING-between-ring (RBR) genes in grass carp (Ctenopharyngodon idellus)

Ubiquitination is a post-translational modification of proteins that is widely present in eukaryotic cells. There is increasing evidence that ubiquitinated proteins play crucial roles in the immune response process. In mammals, RING-between-RING (RBR) proteins play a key role in regulating immune signaling as the important E3 ubiquitin ligases during ubiquitination. However, the function of RBR in fish is still unclear. In the present study, six RBR genes (RNF19A, RNF19B, RNF144AA, RNF144AB, RNF144B and RNF217) of grass carp (Ctenopharyngodon idellus) were cloned and characterized. Similar to mammals, all six members of RBR family contained RING, inbetween-ring (IBR) and transmembrane (TM) domains. These genes were constitutively expressed in all studied tissues, but the relative expression level differed. Following grass carp reovirus(GCRV) infection, the expression of six RBR genes in liver, gill, spleen and intestine significantly altered. Additionally, their expression in Ctenopharyngodon idellus kidney (CIK) cells was significantly increased after GCRV infection. And deficiency of RNF144B in CIK with small interference RNA (siRNA) up-regulated polyinosinic:polycytidylic acid poly(I:C))- induced inflammatory cytokines production, including 1FN-I, TNF-alpha, IL-6, and transcription factor IRF3, which demonstrated that RNF144B was a negative regulator of inflammatory cytokines. Our results suggested that the RBR might play a vital role in regulating immune signaling and laid the foundation for the further mechanism research of RBR in fishes

Efficient Commitment to Functional CD34+ Progenitor Cells from Human Bone Marrow Mesenchymal Stem-Cell-Derived Induced Pluripotent Stem Cells

The efficient commitment of a specialized cell type from induced pluripotent stem cells (iPSCs) without contamination from unknown substances is crucial to their use in clinical applications. Here, we propose that CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential, could be efficiently obtained from iPSCs derived from human bone marrow mesenchymal stem cells (hBMMSC-iPSCs) with defined factors. By treatment with a cocktail containing mesodermal, hematopoietic, and endothelial inducers (BMP4, SCF, and VEGF, respectively) for 5 days, hBMMSC-iPSCs expressed the mesodermal transcription factors Brachyury and GATA-2 at higher levels than untreated groups (P<0.05). After culturing with another hematopoietic and endothelial inducer cocktail, including SCF, Flt3L, VEGF and IL-3, for an additional 7–9 days, CD34+ progenitor cells, which were undetectable in the initial iPSC cultures, reached nearly 20% of the total culture. This was greater than the relative number of progenitor cells produced from human-skin-fibroblast-derived iPSCs (hFib-iPSCs) or from the spontaneous differentiation groups (P<0.05), as assessed by flow cytometry analysis. These induced cells expressed hematopoietic transcription factors TAL-1 and SCL. They developed into various hematopoietic colonies when exposed to semisolid media with hematopoietic cytokines such as EPO and G-CSF. Hematopoietic cell lineages were identified by phenotype analysis with Wright-Giemsa staining. The endothelial potential of the cells was also verified by the confirmation of the formation of vascular tube-like structures and the expression of endothelial-specific markers CD31 and VE-CADHERIN. Efficient induction of CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential with defined factors, provides an opportunity to obtain patient-specific cells for iPSC therapy and a useful model for the study of the mechanisms of hematopoiesis and drug screening

A quantitative study of salinity effect on water diffusion in n-alkane phases: From pore-scale experiments to molecular dynamic simulation

Numerous mechanisms have been proposed to untangle the effect of a low concentration of dissolved salts in the water flooding medium. One potential mechanism for enhanced oil movement is proposed with osmosis effect, however, the process of water transport through the oil phase, due to a salinity contrast, is not fully understood. In our study, we used three aqueous solutions and two alkanes in a series of microfluidic experiments with hydrophobically coated glass micro-chips for mimicking the low-salinity waterflooding process in an oil-wet rock formation. We created multiple systems of low-salinity water-alkane/high-salinity water in the porous micromodel, and afterward, continuously monitored the domain for 70 h. We noted that ionic strength and the hydrocarbon chain length both played important roles in water diffusion. A salinity contrast of 1.7 g/L-170 g/L caused a higher water volumetric flux than 50 g/L-170 g/L for both alkanes. The difference in water volumetric fluxes for those two contrasts were not proportional to the salinity contrast during the experimental period. There was no simple relationship between the chain length of hydrocarbon and water volumetric flux. Moreover, to investigate the effect of salinity on water behavior in heptane, we conducted molecular dynamic (MD) simulations by considering three different concentrations in the high-salinity water region featuring our experiments. The results indicated that high salinity limited the water diffusion from high-salinity phase into the oil phase and reduced the possibility of water entering the heptane phase. Therefore, the net flux of water from the pure water side to the salty waterside was enhanced

Tissue distribution and elimination of C-14 apixaban in rats

Abbreviations used: AUC, area under the plasma concentration-time curve; BCRP, breast cancer resistance protein; BLQ, below limit of quantitation; LSC, liquid scintillation counting; LC/MS, liquid chromatography/mass spectrometry; MS/MS, tandem mass spectrometry; Mrp, multidrug resistance protein; LLOQ, low limit of quantitation; P-gp, Pglycoprotein; PK, pharmacokinetics; QWBA, Whole-body autoradiography; SD, SpragueDawley rats. ABSTRACT Apixaban, a potent and highly selective factor Xa inhibitor, is currently under development for treatment of arterial and venous thrombotic diseases. The distribution, metabolism, and elimination of C-14 apixaban were investigated in male, female, pregnant and lactating rats following single oral doses. Tissue distribution of radioactivity in rats was measured using quantitative whole-body autoradiography. Following single oral administration, radioactivity distributed quickly in rats with C max at 1 h for most tissues. The elimination t 1/2 of radioactivity in blood was 1.7 to 4.2 h. The blood AUC of radioactivity was similar between male and female rats and was slightly higher in pregnant and lower in lactating rats. The radioactivity concentration in tissues involved in elimination was greater than blood with the highest concentration in gastrointestinal tracts, liver, urinary bladder/contents, and lowest level in brains. In pregnant rats, the whole-body autoradiogram showed that low levels of radioactivity were present in fetal blood, liver, and kidney, and were much lower than the radioactivity in respective maternal organs. Fecal route was the major (74% of dose) and urinary was minor pathway (14%) for apixaban elimination. Following single oral doses of C-14 apixaban to lactating rats, apixaban exhibited extensive lacteal excretion with apixaban as the major component. In summary, tissue distribution of apixaban in rats was extensive, but with limited transfer to fetal and brain tissues and extensive secretion into rat milk with parent drug as the major component. Milk excretion could account for 10% of apixaban dose, which was comparable to urinary elimination in rats. Tissue distribution and drug excretion of apixaban are consistent with a moderately permeable drug that is a substrate for P-gp and BCRP efflux transporters

Robust and Task-Independent Spatial Profile of the Visual Word Form Activation in Fusiform Cortex

Written language represents a special category of visual information. There is strong evidence for the existence of a cortical region in ventral occipitotemporal cortex for processing the visual form of written words. However, due to inconsistent findings obtained with different tasks, the level of specialization and selectivity of this so called visual word form area (VWFA) remains debated. In this study, we examined category selectivity for Chinese characters, a non-alphabetic script, in native Chinese readers. In contrast to traditional approaches of examining response levels in a restricted predefined region of interest (ROI), a detailed distribution of the BOLD signal across the mid-fusiform cortical surface and the spatial patterns of responses to Chinese characters were obtained. Results show that a region tuned for Chinese characters could be consistently found in the lateral part of the left fusiform gyrus in Chinese readers, and this spatial pattern of selectivity for written words was not influenced by top-down tasks such as phonological or semantic modulations. These results provide strong support for the robust spatial coding of category selective response in the mid-fusiform cortex, and demonstrate the utility of the spatial distribution analysis as a more meaningful approach to examine functional magnetic resonance imaging (fMRI) data

Discussion on the thermal conductivity enhancement of nanofluids

Increasing interests have been paid to nanofluids because of the intriguing heat transfer enhancement performances presented by this kind of promising heat transfer media. We produced a series of nanofluids and measured their thermal conductivities. In this article, we discussed the measurements and the enhancements of the thermal conductivity of a variety of nanofluids. The base fluids used included those that are most employed heat transfer fluids, such as deionized water (DW), ethylene glycol (EG), glycerol, silicone oil, and the binary mixture of DW and EG. Various nanoparticles (NPs) involving Al2O3 NPs with different sizes, SiC NPs with different shapes, MgO NPs, ZnO NPs, SiO2 NPs, Fe3O4 NPs, TiO2 NPs, diamond NPs, and carbon nanotubes with different pretreatments were used as additives. Our findings demonstrated that the thermal conductivity enhancements of nanofluids could be influenced by multi-faceted factors including the volume fraction of the dispersed NPs, the tested temperature, the thermal conductivity of the base fluid, the size of the dispersed NPs, the pretreatment process, and the additives of the fluids. The thermal transport mechanisms in nanofluids were further discussed, and the promising approaches for optimizing the thermal conductivity of nanofluids have been proposed

Clear Genetic Distinctiveness between Human- and Pig-Derived Trichuris Based on Analyses of Mitochondrial Datasets

The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions

Personers upplevelser av att leva med IBS

Bakgrund: Att leva med Irritable Bowel Syndrome (IBS) innebär en stor utmaning i det vardagliga livet. Personerna kan bli funktionshindrade på grund av de livslånga symtomen som IBS medför trots att IBS i sig inte är livshotande. Många personer med IBS upplever idag att information om egenvård från sjukvården är bristfällig, att de inte blir tagna på allvar, och att deras egna upplevelser förbises. Eftersom sjuksköterskan kommer i kontakt med dessa personer i sin yrkesutövning kan det anses vara användbart att ha kunskaper om dessa personers upplevelser för att bättre kunna bemöta dem och öka deras välbefinnande och livskvalitet. Syfte: Syftet var att belysa personers upplevelser av att leva med Irritable Bowel Syndrome. Metod: Studien genomfördes som en litteraturstudie med kvalitativ ansats som baserades på sju artiklar och analyserades enligt Graneheim och Lundmans tolkning av innehållsanalys. Resultat: I resultatet framkom fem kategorier av upplevelser; Olika känslouttryck, att acceptera den förändrade vardagen, önskan om förståelse och stöd, påverkan på integritet och självkänsla och social isolering och utanförskap. Slutsats: Denna studie har visat att personer med IBS har ett behov av att bli förstådda av sjukvården. Sjuksköterskan kan genom att öka sin kunskap om personers livsvärld och upplevelser av att leva med IBS bidra till att fler personer får stöd och hjälp från sjukvården. Detta gör det möjligt att erbjuda en mer välanpassad vård och ge personerna en högre känsla av välbefinnande och livskvalitet än vad de upplever idag