XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)

Review on XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6), with data on DNA, on the protein encoded, and where the gene is implicated

Bond-order correlation energies for small Si-containing molecules compared with ab initio results from low-order Moller-Plesset perturbation theory

The present study of small molecules containing silicon has been motivated by (a) the considerable interest being shown currently in the kinetics and reactivity of such molecules, and (b) the biotechnological potential of silicon-derivate surfaces as substrates in the adsorption of, for instance, amino acids and proteins. Therefore, we have studied by (i) a semi-empirical approach and (ii) an ab initio procedure employing low-order Moller-Plesset perturbation theory, the molecular correlation energies of some neutral closed and open shell silicon-containing molecules in the series SiXnYm. Procedure (i) is shown to have particular merit for the correlation of the ionic members studied in the above series, while the ab initio procedures employed come into their own for neutral species.Comment: Mol. Phys., to be publishe

A supercritical elliptic problem in a cylindrical shell

We consider the problem $$-\Delta u=|u|^{p-2}u in \Omega, u=0 on \partial\Omega,$$ where $\Omega:=\{(y,z)\in\mathbb{R}^{m+1}\times\mathbb{R}^{N-m-1}: 0<a<|y|<b<\infty\}$, $0\leq m\leq N-1$ and $N\geq2$. Let $2_{N,m}^{\ast}:=2(N-m)/(N-m-2)$ if $m<N-2$ and $2_{N,m}^{\ast}:=\infty$ if $m=N-2$ or $N-1$. We show that $2_{N,m}^{\ast}$ is the true critical exponent for this problem, and that there exist nontrivial solutions if $2<p<2_{N,m}^{\ast}$ but there are no such solutions if $p\geq2_{N,m}^{\ast}$

MicroRNA Dysregulation in Colon Cancer Microenvironment Interactions: The Importance of Small Things in Metastases

The influence of the microenvironment through the various steps of cancer progression is signed by different cytokines and growth factors, that could directly affect cell proliferation and survival, either in cancer and stromal cells. In colon cancer progression, the cooperation between hypoxia, IL-6 and VEGF-A165 could regulate the DNA repair capacity of the cell, whose impairment is the first step of colon cancer development. This cooperation redirects the activity of proteins involved in the metabolic shift and cell death, affecting the cell fate. The pathways triggered by micro environmental factors could modulate cancer-related gene transcription, affecting also small non coding mRNA, microRNAs. MicroRNAs have emerged as key post-transcriptional regulators of gene expression, directly involved in human cancers. The present review will focus first on the intertwined connection between cancer microenvironment and aberrant expression of microRNAs which contribute to carcinogenesis. In particular, the epigenetic mechanisms triggered by tissue microenvironment will be discussed, in view of the recent identification of miRNAs able to directly or indirectly modulate the epigenetic machinery (epi-miRNAs) and that are involved in the epithelial to mesenchimal transition and metastases development

Heritability of the dimensions, compliance and distensibility of the human internal jugular vein wall

AIMS: The elasticity of the internal jugular vein (IJV) is a major determinant of cerebral venous drainage and right atrium venous return. However, the level of genetic determination of IJV dimensions, compliance and distensibility has not been studied yet. METHODS: 170 adult Caucasian twins (43 monozygotic [MZ] and 42 dizygotic [DZ] pairs) were involved from the Italian twin registry. Anteroposterior and mediolateral diameters of the IJV were measured bilaterally by ultrasonography. Measurements were made both in the sitting and supine positions, with or without Valsalva maneuver. Univariate quantitative genetic modeling was performed. RESULTS: Genetic factors are responsible for 30-70% of the measured properties of IJV at higher venous pressure even after adjustment for age and gender. The highest level of inheritance was found in the supine position regarding compliance (62%) and venous diameter during Valsalva (69%). Environmental and measurement-related factors instead are more important in the sitting position, when the venous pressure is low and the venous lumen is almost collapsed. The range of capacity changes between the lowest and highest intraluminal venous pressure (full distension range) are mainly determined by genetic factors (58%). CONCLUSIONS: Our study has shown substantial heritability of IJV biomechanics at higher venous pressures even after adjustment for age and gender. These findings yield an important insight to what degree the geometric and elastic properties of the vascular wall are formed by genetic and by environmental factors in humans

New Model of Macrophage Acquisition of the Lymphatic Endothelial Phenotype

Macrophage-derived lymphatic endothelial cell progenitors (M-LECPs) contribute to new lymphatic vessel formation, but the mechanisms regulating their differentiation, recruitment, and function are poorly understood. Detailed characterization of M-LECPs is limited by low frequency in vivo and lack of model systems allowing in-depth molecular analyses in vitro. Our goal was to establish a cell culture model to characterize inflammation-induced macrophage-to-LECP differentiation under controlled conditions.Time-course analysis of diaphragms from lipopolysaccharide (LPS)-treated mice revealed rapid mobilization of bone marrow-derived and peritoneal macrophages to the proximity of lymphatic vessels followed by widespread (∼50%) incorporation of M-LECPs into the inflamed lymphatic vasculature. A differentiation shift toward the lymphatic phenotype was found in three LPS-induced subsets of activated macrophages that were positive for VEGFR-3 and many other lymphatic-specific markers. VEGFR-3 was strongly elevated in the early stage of macrophage transition to LECPs but undetectable in M-LECPs prior to vascular integration. Similar transient pattern of VEGFR-3 expression was found in RAW264.7 macrophages activated by LPS in vitro. Activated RAW264.7 cells co-expressed VEGF-C that induced an autocrine signaling loop as indicated by VEGFR-3 phosphorylation inhibited by a soluble receptor. LPS-activated RAW264.7 macrophages also showed a 68% overlap with endogenous CD11b(+)/VEGFR-3(+) LECPs in the expression of lymphatic-specific genes. Moreover, when injected into LPS- but not saline-treated mice, GFP-tagged RAW264.7 cells massively infiltrated the inflamed diaphragm followed by integration into 18% of lymphatic vessels.We present a new model for macrophage-LECP differentiation based on LPS activation of cultured RAW264.7 cells. This system designated here as the "RAW model" mimics fundamental features of endogenous M-LECPs. Unlike native LECPs, this model is unrestricted by cell numbers, heterogeneity of population, and ability to change genetic composition for experimental purposes. As such, this model can provide a valuable tool for understanding the LECP and lymphatic biology

Molecular Dynamics Simulation of the Complex PBP-2x with Drug Cefuroxime to Explore the Drug Resistance Mechanism of Streptococcus suis R61

Drug resistance of Streptococcus suis strains is a worldwide problem for both humans and pigs. Previous studies have noted that penicillin-binding protein (PBPs) mutation is one important cause of β-lactam antibiotic resistance. In this study, we used the molecular dynamics (MD) method to study the interaction differences between cefuroxime (CES) and PBP2x within two newly sequenced Streptococcus suis: drug-sensitive strain A7, and drug-resistant strain R61. The MM-PBSA results proved that the drug bound much more tightly to PBP2x in A7 (PBP2x-A7) than to PBP2x in R61 (PBP2x-R61). This is consistent with the evidently different resistances of the two strains to cefuroxime. Hydrogen bond analysis indicated that PBP2x-A7 preferred to bind to cefuroxime rather than to PBP2x-R61. Three stable hydrogen bonds were formed by the drug and PBP2x-A7, while only one unstable bond existed between the drug and PBP2x-R61. Further, we found that the Gln569, Tyr594, and Gly596 residues were the key mutant residues contributing directly to the different binding by pair wise energy decomposition comparison. By investigating the binding mode of the drug, we found that mutant residues Ala320, Gln553, and Thr595 indirectly affected the final phenomenon by topological conformation alteration. Above all, our results revealed some details about the specific interaction between the two PBP2x proteins and the drug cefuroxime. To some degree, this explained the drug resistance mechanism of Streptococcus suis and as a result could be helpful for further drug design or improvement

Changes in agonist neural drive, hypertrophy and pre-training strength all contribute to the individual strength gains after resistance training.

PURPOSE: Whilst neural and morphological adaptations following resistance training (RT) have been investigated extensively at a group level, relatively little is known about the contribution of specific physiological mechanisms, or pre-training strength, to the individual changes in strength following training. This study investigated the contribution of multiple underpinning neural [agonist EMG (QEMGMVT), antagonist EMG (HEMGANTAG)] and morphological variables [total quadriceps volume (QUADSVOL), and muscle fascicle pennation angle (QUADSθ p)], as well as pre-training strength, to the individual changes in strength after 12 weeks of knee extensor RT. METHODS: Twenty-eight healthy young men completed 12 weeks of isometric knee extensor RT (3/week). Isometric maximum voluntary torque (MVT) was assessed pre- and post-RT, as were simultaneous neural drive to the agonist (QEMGMVT) and antagonist (HEMGANTAG). In addition QUADSVOL was determined with MRI and QUADSθ p with B-mode ultrasound. RESULTS: Percentage changes (∆) in MVT were correlated to ∆QEMGMVT (r = 0.576, P = 0.001), ∆QUADSVOL (r = 0.461, P = 0.014), and pre-training MVT (r = -0.429, P = 0.023), but not ∆HEMGANTAG (r = 0.298, P = 0.123) or ∆QUADSθ p (r = -0.207, P = 0.291). Multiple regression analysis revealed 59.9% of the total variance in ∆MVT after RT to be explained by ∆QEMGMVT (30.6%), ∆QUADSVOL (18.7%), and pre-training MVT (10.6%). CONCLUSIONS: Changes in agonist neural drive, quadriceps muscle volume and pre-training strength combined to explain the majority of the variance in strength changes after knee extensor RT (~60%) and adaptations in agonist neural drive were the most important single predictor during this short-term intervention

Differential Macrophage Polarization Promotes Tissue Remodeling and Repair in a Model of Ischemic Retinopathy

Diabetic retinopathy is the leading cause of visual loss in individuals under the age of 55. Umbilical cord blood (UCB)–derived myeloid progenitor cells have been shown to decrease neuronal damage associated with ischemia in the central nervous system. In this study we show that UCB-derived CD14+ progenitor cells provide rescue effects in a mouse model of ischemic retinopathy by promoting physiological angiogenesis and reducing associated inflammation. We use confocal microscopy to trace the fate of injected human UCB-derived CD14+ cells and PCR with species-specific probes to investigate their gene expression profile before and after injection. Metabolomic analysis measures changes induced by CD14+ cells. Our results demonstrate that human cells differentiate in vivo into M2 macrophages and induce the polarization of resident M2 macrophages. This leads to stabilization of the ischemia-injured retinal vasculature by modulating the inflammatory response, reducing oxidative stress and apoptosis and promoting tissue repair