Fish Oil Enhances Recovery of Intestinal Microbiota and Epithelial Integrity in Chronic Rejection of Intestinal Transplant

The intestinal chronic rejection (CR) is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity.. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions.Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation

Effects of tachyplesin on proliferation and differentiation of human hepatocellular carcinoma SMMC-7721 cells

AIM: To investigate the antitumor activities of tachyplesin on human hepatocellular carcinoma (HCC) cells. METHODS: Tachyplesin, isolated from acid extracts of Chinese horseshoe crab ( Tachypleus tridentatus) hemocytes, was used to treat the human HCC cell line SMMC-7721. Effects of tachyplesin on the proliferation of SMMC-7721 cells were measured with trypan blue dye exclusion test and HE staining. The morphology and ultrastructure of the cells were examined by light microscopy and transmission electron microscopy, respectively. The activities of gamma-glutamyltransferase (gamma-GT) and tyrosine aminotransferase (TAT) were assayed with biochemical methods. The levels of alpha fetoprotein (alpha-FP), proliferating cell nuclear antigen (PCNA), p21(WAF1/CIP1) and c-myc were examined by immunocytochemistry. RESULTS: After treatment with tachyplesin 3.0 mg/L, the proliferation of SMMC-7721 cells was inhibited significantly, with the cell growth inhibitory rate amounted to 55.57% and the maximum cell mitotic index declined by 43.68%. The morphology and ultrastructure underwent restorational alteration. The activity of gamma-GT declined while TAT activity increased obviously, and the levels of alpha-FP and PCNA decreased. Moreover, the expression of p21(WAF1/CIP1) protein was up-regulated and that of c-myc protein was down-regulated. CONCLUSION: Tachyplesin could effectively inhibit the proliferation of hepatocarcinoma cells, reverse the malignant morphological and ultrastructural characteristics, alter the levels of enzymes and antigens, regulate the expression of differentiation-associated oncogene and tumor suppressor gene, and induce hepatocarcinama cell differentiation

Differential neutrino condensation onto cosmic structure

Astrophysical techniques have pioneered the discovery of neutrino mass properties. Current cosmological observations give an upper bound on neutrino masses by attempting to disentangle the small neutrino contribution from the sum of all matter using precise theoretical models. We discover the differential neutrino condensation effect in our TianNu N-body simulation. Neutrino masses can be inferred using this effect by comparing galaxy properties in regions of the universe with different neutrino relative abundance (i.e. the local neutrino to cold dark matter density ratio). In “neutrino-rich” regions, more neutrinos can be captured by massive halos compared to “neutrino-poor” regions. This effect differentially skews the halo mass function and opens up the path to independent neutrino mass measurements in current or future galaxy surveys

Ultraconserved Elements in the Olig2 Promoter

. basal promoter and found that it represses expression in undifferentiated embryonic stem cells. expression during development

Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.

Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex

Predatory protists reduce bacteria wilt disease incidence in tomato plants

Soil organisms are affected by the presence of predatory protists. However, it remains poorly understood how predatory protists can affect plant disease incidence and how fertilization regimes can affect these interactions. Here, we characterise the rhizosphere bacteria, fungi and protists over eleven growing seasons of tomato planting under three fertilization regimes, i.e conventional, organic and bioorganic, and with different bacterial wilt disease incidence levels. We find that predatory protists are negatively associated with disease incidence, especially two ciliophoran Colpoda OTUs, and that bioorganic fertilization enhances the abundance of predatory protists. In glasshouse experiments we find that the predatory protist Colpoda influences disease incidence by directly consuming pathogens and indirectly increasing the presence of pathogen-suppressive microorganisms in the soil. Together, we demonstrate that predatory protists reduce bacterial wilt disease incidence in tomato plants via direct and indirect reductions of pathogens. Our study provides insights on the role that predatory protists play in plant disease, which could be used to design more sustainable agricultural practices

Genome wide association for substance dependence: convergent results from epidemiologic and research volunteer samples

<p>Abstract</p> <p>Background</p> <p>Dependences on addictive substances are substantially-heritable complex disorders whose molecular genetic bases have been partially elucidated by studies that have largely focused on research volunteers, including those recruited in Baltimore. Maryland. Subjects recruited from the Baltimore site of the Epidemiological Catchment Area (ECA) study provide a potentially-useful comparison group for possible confounding features that might arise from selecting research volunteer samples of substance dependent and control individuals. We now report novel SNP (single nucleotide polymorphism) genome wide association (GWA) results for vulnerability to substance dependence in ECA participants, who were initially ascertained as members of a probability sample from Baltimore, and compare the results to those from ethnically-matched Baltimore research volunteers.</p> <p>Results</p> <p>We identify substantial overlap between the home address zip codes reported by members of these two samples. We find overlapping clusters of SNPs whose allele frequencies differ with nominal significance between substance dependent <it>vs </it>control individuals in both samples. These overlapping clusters of nominally-positive SNPs identify 172 genes in ways that are never found by chance in Monte Carlo simulation studies. Comparison with data from human expressed sequence tags suggests that these genes are expressed in brain, especially in hippocampus and amygdala, to extents that are greater than chance.</p> <p>Conclusion</p> <p>The convergent results from these probability sample and research volunteer sample datasets support prior genome wide association results. They fail to support the idea that large portions of the molecular genetic results for vulnerability to substance dependence derive from factors that are limited to research volunteers.</p

Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells

It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions

Probe R-parity violating stop resonance at the LHeC

We investigate the possibility of detecting single sqaurk production at the proposed LHeC collider, in the framework of R-parity violating supersymmetry. Taking advantage of the enhancement of the direct resonance production of squark and the distinctive kinematics distributions of $\tilde{q}\rightarrow l q$ two body decay final states, the LHeC provides excellent opportunities of probing R-violating $\hat{L}\hat{Q}\hat{D}$ interactions at unprecedented level compared to all the knowledge derived from indirect low energy nucleon measurements. If no apparent deviation from SM predictions on high invariant mass of muon and b-quark final states at the LHeC with 1$fb^{-1}$ data, the sensitivities on $\hat{L}\hat{Q}\hat{D}$ coupling constant $\lambda^{'}_{131} \times \lambda^{'}_{233}$ can be improved by nearly four orders, at energy scale about 100 GeV.Comment: 9 pages, 8 figure