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

What two models may teach us about duality violations in QCD

Though the operator product expansion is applicable in the calculation of current correlation functions in the Euclidean region, when approaching the Minkowskian domain, violations of quark-hadron duality are expected to occur, due to the presence of bound-state or resonance poles. In QCD finite-energy sum rules, contour integrals in the complex energy plane down to the Minkowskian axis have to be performed, and thus the question arises what the impact of duality violations may be. The structure and possible relevance of duality violations is investigated on the basis of two models: the Coulomb system and a model for light-quark correlators which has already been studied previously. As might yet be naively expected, duality violations are in some sense "maximal" for zero-width bound states and they become weaker for broader resonances whose poles lie further away from the physical axis. Furthermore, to a certain extent, they can be suppressed by choosing appropriate weight functions in the finite-energy sum rules. A simplified Ansatz for including effects of duality violations in phenomenological QCD sum rule analyses is discussed as well.Comment: 17 pages, 6 figures; version to appear in JHE

Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor

Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis

General Form of the Color Potential Produced by Color Charges of the Quark

Constant electric charge $e$ satisfies the continuity equation $\partial_\mu j^{\mu}(x)= 0$ where $j^\mu(x)$ is the current density of the electron. However, the Yang-Mills color current density $j^{\mu a}(x)$ of the quark satisfies the equation $D_\mu[A] j^{\mu a}(x)= 0$ which is not a continuity equation ($\partial_\mu j^{\mu a}(x)\neq 0$) which implies that a color charge $q^a(t)$ of the quark is not constant but it is time dependent where $a=1,2,...8$ are color indices. In this paper we derive general form of color potential produced by color charges of the quark. We find that the general form of the color potential produced by the color charges of the quark at rest is given by \Phi^a(x) =A_0^a(t,{\bf x}) =\frac{q^b(t-\frac{r}{c})}{r}\[\frac{{\rm exp}[g\int dr \frac{Q(t-\frac{r}{c})}{r}] -1}{g \int dr \frac{Q(t-\frac{r}{c})}{r}}\]_{ab} where $dr$ integration is an indefinite integration, ~~ $Q_{ab}(\tau_0)=f^{abd}q^d(\tau_0)$, ~~$r=|{\vec x}-{\vec X}(\tau_0)|$, ~~$\tau_0=t-\frac{r}{c}$ is the retarded time, ~~$c$ is the speed of light, ~~${\vec X}(\tau_0)$ is the position of the quark at the retarded time and the repeated color indices $b,d$(=1,2,...8) are summed. For constant color charge $q^a$ we reproduce the Coulomb-like potential $\Phi^a(x)=\frac{q^a}{r}$ which is consistent with the Maxwell theory where constant electric charge $e$ produces the Coulomb potential $\Phi(x)=\frac{e}{r}$.Comment: Final version, two more sections added, 45 pages latex, accepted for publication in JHE

Minimum sample size for external validation of a clinical prediction model with a binary outcome

In prediction model research, external validation is needed to examine an existing model's performance using data independent to that for model development. Current external validation studies often suffer from small sample sizes and consequently imprecise predictive performance estimates. To address this, we propose how to determine the minimum sample size needed for a new external validation study of a prediction model for a binary outcome. Our calculations aim to precisely estimate calibration (Observed/Expected and calibration slope), discrimination (C-statistic), and clinical utility (net benefit). For each measure, we propose closed-form and iterative solutions for calculating the minimum sample size required. These require specifying: (i) target SEs (confidence interval widths) for each estimate of interest, (ii) the anticipated outcome event proportion in the validation population, (iii) the prediction model's anticipated (mis)calibration and variance of linear predictor values in the validation population, and (iv) potential risk thresholds for clinical decision-making. The calculations can also be used to inform whether the sample size of an existing (already collected) dataset is adequate for external validation. We illustrate our proposal for external validation of a prediction model for mechanical heart valve failure with an expected outcome event proportion of 0.018. Calculations suggest at least 9835 participants (177 events) are required to precisely estimate the calibration and discrimination measures, with this number driven by the calibration slope criterion, which we anticipate will often be the case. Also, 6443 participants (116 events) are required to precisely estimate net benefit at a risk threshold of 8%. Software code is provided.</p

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Generalized quark-antiquark potential at weak and strong coupling

We study a two-parameter family of Wilson loop operators in N=4 supersymmetric Yang-Mills theory which interpolates smoothly between the 1/2 BPS line or circle and a pair of antiparallel lines. These observables capture a natural generalization of the quark-antiquark potential. We calculate these loops on the gauge theory side to second order in perturbation theory and in a semiclassical expansion in string theory to one-loop order. The resulting determinants are given in integral form and can be evaluated numerically for general values of the parameters or analytically in a systematic expansion around the 1/2 BPS configuration. We comment about the feasibility of deriving all-loop results for these Wilson loops.Comment: 43 pages: 15 comprising the main text and 25 for detailed appendice

Lower Miocene Stratigraphy along the Panama Canal and Its Bearing on the Central American Peninsula

Before the formation of the Central American Isthmus, there was a Central American Peninsula. Here we show that southern Central America existed as a peninsula as early as 19 Ma, based on new lithostratigraphic, biostratigraphic and strontium chemostratigraphic analyses of the formations exposed along the Gaillard Cut of the Panama Canal. Land mammals found in the Miocene Cucaracha Formation have similar body sizes to conspecific taxa in North America, indicating that there existed a terrestrial connection with North America that allowed gene flow between populations during this time. How long did this peninsula last? The answer hinges on the outcome of a stratigraphic dispute: To wit, is the terrestrial Cucaracha Formation older or younger than the marine La Boca Formation? Previous stratigraphic studies of the Panama Canal Basin have suggested that the Cucaracha Formation lies stratigraphically between the shallow-marine Culebra Formation and the shallow-to-upper-bathyal La Boca Formation, the latter containing the Emperador Limestone. If the La Boca Formation is younger than the Cucaracha Formation, as many think, then the peninsula was short-lived (1–2 m.y.), having been submerged in part by the transgression represented by the overlying La Boca Formation. On the other hand, our data support the view that the La Boca Formation is older than the Cucaracha Formation. Strontium dating shows that the La Boca Formation is older (23.07 to 20.62 Ma) than both the Culebra (19.83–19.12 Ma) and Cucaracha (Hemingfordian to Barstovian North American Land Mammal Ages; 19–14 Ma) formations. The Emperador Limestone is also older (21.24–20.99 Ma) than the Culebra and Cucaracha formations. What has been called the “La Boca Formation” (with the Emperador Limestone), is re-interpreted here as being the lower part of the Culebra Formation. Our new data sets demonstrate that the main axis of the volcanic arc in southern Central America more than likely existed as a peninsula connected to northern Central America and North America for much of the Miocene, which has profound implications for our understanding of the tectonic, climatic, oceanographic and biogeographic history related to the formation of the Isthmus of Panama

Five-loop renormalisation of QCD in covariant gauges

We present the complete set of vertex, wave function and charge renormalisation constants in QCD in a general simple gauge group and with the complete dependence on the covariant gauge parameter $\xi$ in the minimal subtraction scheme of conventional dimensional regularisation. Our results confirm all already known results, which were obtained in the Feynman gauge, and allow the extraction of other useful gauges such as the Landau gauge. We use these results to extract the Landau gauge five-loop anomalous dimensions of the composite operator $A^2$ as well as the Landau gauge scheme independent gluon, ghost and fermion propagators at five loops.Comment: 17 pages; FORM and Mathematica result files available with the source; corrected minor typos, added references, journal ref, 1 remark, 1 note and 1 additional result fil