Claudins in intestines

Intestines are organs that not only digest food and absorb nutrients, but also provide a defense barrier against pathogens and noxious agents ingested. Tight junctions (TJs) are the most apical component of the junctional complex, providing one form of cell-cell adhesion in enterocytes and playing a critical role in regulating paracellular barrier permeability. Alteration of TJs leads to a number of pathophysiological diseases causing malabsorption of nutrition and intestinal structure disruption, which may even contribute to systemic organ failure. Claudins are the major structural and functional components of TJs with at least 24 members in mammals. Claudins have distinct charge-selectivity, either by tightening the paracellular pathway or functioning as paracellular channels, regulating ions and small molecules passing through the paracellular pathway. In this review, we have discussed the functions of claudin family members, their distribution and localization in the intestinal tract of mammals, their alterations in intestine-related diseases and chemicals/agents that regulate the expression and localization of claudins as well as the intestinal permeability, which provide a therapeutic view for treating intestinal diseases

Unfolding grain size effects in barium titanate ferroelectric ceramics

Grain size effects on the physical properties of polycrystalline ferroelectrics have been extensively studied for decades; however there are still major controversies regarding the dependence of the piezoelectric and ferroelectric properties on the grain size. Dense BaTiO3 ceramics with different grain sizes were fabricated by either conventional sintering or spark plasma sintering using micro- and nano-sized powders. The results show that the grain size effect on the dielectric permittivity is nearly independent of the sintering method and starting powder used. A peak in the permittivity is observed in all the ceramics with a grain size near 1μm and can be attributed to a maximum domain wall density and mobility. The piezoelectric coefficient d33 and remnant polarization Pr show diverse grain size effects depending on the particle size of the starting powder and sintering temperature. This suggests that besides domain wall density, other factors such as back fields and point defects, which influence the domain wall mobility, could be responsible for the different grain size dependence observed in the dielectric and piezoelectric/ferroelectric properties. In cases where point defects are not the dominant contributor, the piezoelectric constant d33 and the remnant polarization Pr increase with increasing grain size

ConservedPrimers 2.0: A high-throughput pipeline for comparative genome referenced intron-flanking PCR primer design and its application in wheat SNP discovery

<p>Abstract</p> <p>Background</p> <p>In some genomic applications it is necessary to design large numbers of PCR primers in exons flanking one or several introns on the basis of orthologous gene sequences in related species. The primer pairs designed by this target gene approach are called "intron-flanking primers" or because they are located in exonic sequences which are usually conserved between related species, "conserved primers". They are useful for large-scale single nucleotide polymorphism (SNP) discovery and marker development, especially in species, such as wheat, for which a large number of ESTs are available but for which genome sequences and intron/exon boundaries are not available. To date, no suitable high-throughput tool is available for this purpose.</p> <p>Results</p> <p>We have developed, the ConservedPrimers 2.0 pipeline, for designing intron-flanking primers for large-scale SNP discovery and marker development, and demonstrated its utility in wheat. This tool uses non-redundant wheat EST sequences, such as wheat contigs and singleton ESTs, and related genomic sequences, such as those of rice, as inputs. It aligns the ESTs to the genomic sequences to identify unique colinear exon blocks and predicts intron lengths. Intron-flanking primers are then designed based on the intron/exon information using the Primer3 core program or BatchPrimer3. Finally, a tab-delimited file containing intron-flanking primer pair sequences and their primer properties is generated for primer ordering and their PCR applications. Using this tool, 1,922 bin-mapped wheat ESTs (31.8% of the 6,045 in total) were found to have unique colinear exon blocks suitable for primer design and 1,821 primer pairs were designed from these single- or low-copy genes for PCR amplification and SNP discovery. With these primers and subsequently designed genome-specific primers, a total of 1,527 loci were found to contain one or more genome-specific SNPs.</p> <p>Conclusion</p> <p>The ConservedPrimers 2.0 pipeline for designing intron-flanking primers was developed and its utility demonstrated. The tool can be used for SNP discovery, genetic variation assays and marker development for any target genome that has abundant ESTs and a related reference genome that has been fully sequenced. The ConservedPrimers 2.0 pipeline has been implemented as a command-line tool as well as a web application. Both versions are freely available at <url>http://wheat.pw.usda.gov/demos/ConservedPrimers/</url>.</p

The Intermediate Scale MSSM, the Higgs Mass and F-theory Unification

Even if SUSY is not present at the Electro-Weak scale, string theory suggests its presence at some scale M_{SS} below the string scale M_s to guarantee the absence of tachyons. We explore the possible value of M_{SS} consistent with gauge coupling unification and known sources of SUSY breaking in string theory. Within F-theory SU(5) unification these two requirements fix M_{SS} ~ 5 x 10^{10} GeV at an intermediate scale and a unification scale M_c ~ 3 x 10^{14} GeV. As a direct consequence one also predicts the vanishing of the quartic Higgs SM self-coupling at M_{SS} ~10^{11} GeV. This is tantalizingly consistent with recent LHC hints of a Higgs mass in the region 124-126 GeV. With such a low unification scale M_c ~ 3 x 10^{14} GeV one may worry about too fast proton decay via dimension 6 operators. However in the F-theory GUT context SU(5) is broken to the SM via hypercharge flux. We show that this hypercharge flux deforms the SM fermion wave functions leading to a suppression, avoiding in this way the strong experimental proton decay constraints. In these constructions there is generically an axion with a scale of size f_a ~ M_c/(4\pi)^2 ~ 10^{12} GeV which could solve the strong CP problem and provide for the observed dark matter. The prize to pay for these attractive features is to assume that the hierarchy problem is solved due to anthropic selection in a string landscape.Comment: 48 pages, 8 figures. v3: further minor correction

Structure of hadron resonances with a nearby zero of the amplitude

We discuss the relation between the analytic structure of the scattering amplitude and the origin of an eigenstate represented by a pole of the amplitude.If the eigenstate is not dynamically generated by the interaction in the channel of interest, the residue of the pole vanishes in the zero coupling limit. Based on the topological nature of the phase of the scattering amplitude, we show that the pole must encounter with the Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the dynamical component of the eigenstate is small if a CDD zero exists near the eigenstate pole. We show that the line shape of the resonance is distorted from the Breit-Wigner form as an observable consequence of the nearby CDD zero. Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio

Limitations of the MELD score in predicting mortality or need for removal from waiting list in patients awaiting liver transplantation

<p>Abstract</p> <p>Background</p> <p>Decompensated cirrhosis is associated with a poor prognosis and liver transplantation provides the only curative treatment option with excellent long-term results. The relative shortage of organ donors renders the allocation algorithms of organs essential. The optimal strategy based on scoring systems and/or waiting time is still under debate.</p> <p>Methods</p> <p>Data sets of 268 consecutive patients listed for single-organ liver transplantation for nonfulminant liver disease between 2003 and 2005 were included into the study. The Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores of all patients at the time of listing were used for calculation. The predictive ability not only for mortality on the waiting list but also for the need for withdrawal from the waiting list was calculated for both scores. The Mann-Whitney-U Test was used for the univariate analysis and the AUC-Model for discrimination of the scores.</p> <p>Results</p> <p>In the univariate analysis comparing patients who are still on the waiting list and patients who died or were removed from the waiting list due to poor conditions, the serum albumin, bilirubin INR, and CTP and MELD scores as well as the presence of ascites and encephalopathy were significantly different between the groups (p < 0.05), whereas serum creatinine and urea showed no difference.</p> <p>Comparing the predictive abilities of CTP and MELD scores, the best discrimination between patients still alive on the waiting list and patients who died on or were removed from the waiting list was achieved at a CTP score of ≥9 and a MELD score of ≥14.4. The sensitivity and specificity to identify mortality or severe deterioration for CTP was 69.0% and 70.5%, respectively; for MELD, it was 62.1% and 72.7%, respectively. This result was supported by the AUC analysis showing a strong trend for superiority of CTP over MELD scores (AUROC 0.73 and 0.68, resp.; p = 0.091).</p> <p>Conclusion</p> <p>The long term prediction of mortality or removal from waiting list in patients awaiting liver transplantation might be better assessed by the CTP score than the MELD score. This might have implications for the development of new improved scoring systems.</p

Ceramic on ceramic bearing fractures in total hip arthroplasty : an analysis of data from the national joint registry

Aims: Ceramic-on-ceramic (CoC) bearings in total hip arthroplasty (THA) are commonly used but concerns exist regarding ceramic fracture. This study aims to report the risk of revision for fracture of modern CoC bearings and identify factors that might influence this risk, using data from the National Joint Registry (NJR). Patients and Methods: We analysed data on 111,681 primary CoC THA’s and 182 linked revisions for bearing fracture recorded in NJR. We used implant codes to identify ceramic bearing composition and generated Kaplan-Meier estimates for implant survivorship. Logistic regression analyses were performed for implant size and patient specific variables to determine any associated risks for revision. Results: 99.8% of bearings were CeramTec Biolox® products. Revisions for fracture were linked to 7 of 79,442 (0.009%) Biolox® Delta heads, 38 of 31,982 (0.119%) Biolox® Forte heads, 101 of 80,170 (0.126%) Biolox® Delta liners and 35 of 31,258 (0.112%) Biolox® Forte liners. Regression analysis of implant size revealed smaller heads had significantly higher odds of fracture (χ2=68.0, p<0.0001). The highest fracture risk were observed in the 28mm Biolox® Forte subgroup (0.382%). There were no fractures in the 40mm head group for either ceramic type. Liner thickness was not predictive of fracture (p=0.67). BMI was independently associated with revision for both head fractures (OR 1.09 per unit increase, p=0.031) and liner fractures (OR 1.06 per unit increase, p=0.006). Conclusions: We report the largest study of CoC bearing fractures to date. The risk of revision for CoC bearing fracture is very low, however previous studies have underestimated this risk. There is good evidence that the latest generation of ceramic has greatly reduced the odds of head fracture but not of liner fracture. Small head size and high patient BMI are associated with an increased risk of ceramic bearing fracture

Inhibition of Melanoma Growth by Subcutaneous Administration of hTERTC27 Viral Cocktail in C57BL/6 Mice

hTERTC27 is a 27 kDa C-terminal polypeptide of human telomerase reverse transcriptase that has previously been shown to reduce tumorigenicity of HeLa cells and suppress growth of xenografted glioblastoma in nude mice. Although ectopic expression of hTERTC27 upregulated genes that are involved in apoptosis, cell cycle, and immune response, the mechanism for hTERTC27-induced tumor suppression has not been completely elucidated. Since hTERT was identified as a universal tumor-associated antigen, we hypothesize that hTERTC27 inhibits tumor growth in vivo through activation of anti-tumor immune response. Immunocompetent C57BL/6 mice were used for mouse B16 melanoma model. Mice bearing B16 melanoma were administered rAAV-/rAdv viral cocktail expressing hTERTC27, and tumor growth was monitored after viral cocktail treatment. Blood and splenocytes were used to determine the level of cytokines and the activity of immune cells, respectively. B16 tumor growth was significantly inhibited by subcutaneous administration of a single dose of 1.5×10(11) vg rAAV-hTERTC27 and 2.5×10(9) pfu rAdv-hTERTC27 viral cocktail (rAAV-/rAdv-hTERTC27). The population and cytotoxicity of NK cells in the mice were significantly augmented by rAAV-/rAdv-hTERTC27 treatment, and selective depletion of the NK cell population in mice by intraperitoneal injection of anti-GM1 antibody abrogated the growth suppression of melanoma induced by rAAV-/rAdv-hTERTC27 administration. Activation of NK cells by administration of rAAV-/rAdv-hTERTC27 is critical for growth suppression of melanoma in mouse model.published_or_final_versio

Human RNA Polymerase II-Association Factor 1 (hPaf1/PD2) Regulates Histone Methylation and Chromatin Remodeling in Pancreatic Cancer

Change in gene expression associated with pancreatic cancer could be attributed to the variation in histone posttranslational modifications leading to subsequent remodeling of the chromatin template during transcription. However, the interconnected network of molecules involved in regulating such processes remains elusive. hPaf1/PD2, a subunit of the human PAF-complex, involved in the regulation of transcriptional elongation has oncogenic potential. Our study explores the possibility that regulation of histone methylation by hPaf1 can contribute towards alteration in gene expression by nucleosomal rearrangement. Here, we show that knockdown of hPaf1/PD2 leads to decreased di- and tri-methylation at histone H3 lysine 4 residues in pancreatic cancer cells. Interestingly, hPaf1/PD2 colocalizes with MLL1 (Mixed Lineage Leukemia 1), a histone methyltransferase that methylates H3K4 residues. Also, a reduction in hPaf1 level resulted in reduced MLL1 expression and a corresponding decrease in the level of CHD1 (Chromohelicase DNA-binding protein 1), an ATPase dependent chromatin remodeling enzyme that specifically binds to H3K4 di and trimethyl marks. hPaf1/PD2 was also found to interact and colocalize with CHD1 in both cytoplasmic and nuclear extracts of pancreatic cancer cells. Further, reduced level of CHD1 localization in the nucleus in hPaf1/PD2 Knockdown cells could be rescued by ectopic expression of hPaf1/PD2. Micrococcal nuclease digestion showed an altered chromatin structure in hPaf1/PD2-KD cells. Overall, our results suggest that hPaf1/PD2 in association with MLL1 regulates methylation of H3K4 residues, as well as interacts and regulates nuclear shuttling of chromatin remodeling protein CHD1, facilitating its function in pancreatic cancer cells

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente