Hydrostatic pressure induced Dirac semimetal in black phosphorus

Motivated by recent experimental observation of an hydrostatic pressure induced transition from semiconductor to semimetal in black phosphorus [Chen et al. in arXiv:1504.00125], we present the first principles calculation on the pressure effect of the electronic structures of black phosphorus. It is found that the band crossover and reversal at the Z point occur around the critical pressure Pc1=1.23 Gpa, and the band inversion evolves into 4 twofold-degenerate Dirac cones around the Z point, suggesting a 3D Dirac semimetal. With further increasing pressure the Dirac cones in the Gamma-Z line move toward the Gamma point and evolve into two hole-type Fermi pockets, and those in the Z-M lines move toward the M point and evolve into 2 hole-type Fermi pockets up to P=4.0 Gpa. It demonstrates clearly that the Lifshitz transition occurs at $P_{c1}$ from semiconductor to 3D Dirac semimetal protected by the nonsymmorphic space symmetry of bulk. This suggests the bright perspective of black phosphorus for optoelectronic and electronic devices due to its easy modulation by pressure.Comment: 7 pages, 9 figures, and 2 table

Potassium-Enriched Salt Substitutes: A Review of Recommendations in Clinical Management Guidelines

Excess dietary sodium intake and insufficient dietary potassium intake are both well-established risk factors for hypertension. Despite some successful initiatives, efforts to control hypertension by improving dietary intake have largely failed because the changes required are mostly too hard to implement. Consistent recent data from randomized controlled trials show that potassium-enriched, sodium-reduced salt substitutes are an effective option for improving consumption levels and reducing blood pressure and the rates of cardiovascular events and deaths. Yet, salt substitutes are inconsistently recommended and rarely used. We sought to define the extent to which evidence about the likely benefits and harms of potassium-enriched salt substitutes has been incorporated into clinical management by systematically searching guidelines for the management of hypertension or chronic kidney disease. We found incomplete and inconsistent recommendations about the use of potassium-enriched salt substitutes in the 32 hypertension and 14 kidney guidelines that we reviewed. Discussion among the authors identified the possibility of updating clinical guidelines to provide consistent advice about the use of potassium-enriched salt for hypertension control. Draft wording was chosen to commence debate and progress consensus building: strong recommendation for patients with hypertension - potassium-enriched salt with a composition of 75% sodium chloride and 25% potassium chloride should be recommended to all patients with hypertension, unless they have advanced kidney disease, are using a potassium supplement, are using a potassium-sparing diuretic, or have another contraindication. We strongly encourage clinical guideline bodies to review their recommendations about the use of potassium-enriched salt substitutes at the earliest opportunity

Identification and validation of oncologic miRNA biomarkers for Luminal A-like breast cancer

Introduction: Breast cancer is a common disease with distinct tumor subtypes phenotypically characterized by ER and HER2/neu receptor status. MiRNAs play regulatory roles in tumor initiation and progression, and altered miRNA expression has been demonstrated in a variety of cancer states presenting the potential for exploitation as cancer biomarkers. Blood provides an excellent medium for biomarker discovery. This study investigated systemic miRNAs differentially expressed in Luminal A-like (ER+PR+HER2/neu-) breast cancer and their effectiveness as oncologic biomarkers in the clinical setting. Methods: Blood samples were prospectively collected from patients with Luminal A-like breast cancer (n=54) and controls (n=56). RNA was extracted, reverse transcribed and subjected to microarray analysis (n=10 Luminal A-like; n=10 Control). Differentially expressed miRNAs were identified by artificial neural network (ANN) data-mining algorithms. Expression of specific miRNAs was validated by RQ-PCR (n=44 Luminal A; n=46 Control) and potential relationships between circulating miRNA levels and clinicopathological features of breast cancer were investigated. Results: Microarray analysis identified 76 differentially expressed miRNAs. ANN revealed 10 miRNAs for further analysis ( miR-19b, miR-29a, miR-93, miR-181a, miR-182, miR-223, miR-301a, miR-423-5p, miR-486-5 and miR-652 ). The biomarker potential of 4 miRNAs ( miR-29a, miR-181a , miR-223 and miR-652 ) was confirmed by RQ-PCR, with significantly reduced expression in blood of women with Luminal A-like breast tumors compared to healthy controls (p=0.001, 0.004, 0.009 and 0.004 respectively). Binary logistic regression confirmed that combination of 3 of these miRNAs ( miR-29a, miR-181a and miR-652 ) could reliably differentiate between cancers and controls with an AUC of 0.80. Conclusion: This study provides insight into the underlying molecular portrait of Luminal A-like breast cancer subtype. From an initial 76 miRNAs, 4 were validated with altered expression in the blood of women with Luminal A-like breast cancer. The expression profiles of these 3 miRNAs, in combination with mammography, has potential to facilitate accurate subtype- specific breast tumor detection

Cover to Volume 3

The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 or NGFIB). The aim of the present study was to investigate the pathways through which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not block it. Moreover, we report that treatment with the NF-κB inhibitor BAY11-7082 suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was found to be localized in the cytoplasm and only a fraction was translocated to the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased the proliferation rate of NIH3T3 cells; however, it did not affect the chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by PDGF-BB, suppresses cell growth on a solid surface, it increases anchorage-independent growth

Estrogen-dependent dynamic profile of eNOS-DNA associations in prostate cancer

In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa). To explore the role of nuclear eNOS in the acquisition of aggressive phenotype in PCa, we performed ChIP-Sequencing on chromatin-associated eNOS from cells from a primary tumor with poor outcome and from metastatic LNCaP cells. We found that: 1. the eNOS-bound regions (peaks) are widely distributed across the genome encompassing multiple transcription factors binding sites, including Estrogen Response Elements. 2. E2 increased the number of peaks, indicating hormone-dependent eNOS re-localization. 3. Peak distribution was similar with/without E2 with ≈ 55% of them in extragenic DNA regions and an intriguing involvement of the 5′ domain of several miRs deregulated in PCa. Numerous potentially novel eNOS-targeted genes have been identified suggesting that eNOS participates in the regulation of large gene sets. The parallel finding of downregulation of a cluster of miRs, including miR-34a, in PCa cells associated with poor outcome led us to unveil a molecular link between eNOS and SIRT1, an epigenetic regulator of aging and tumorigenicity, negatively regulated by miR-34a and in turn activating eNOS. E2 potentiates miR-34a downregulation thus enhancing SIRT1 expression, depicting a novel eNOS/SIRT1 interplay fine-tuned by E2-activated ER signaling, and suggesting that eNOS may play an important role in aggressive PCa

Demography and disorders of German Shepherd Dogs under primary veterinarycare in the UK

The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompassTM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompassTM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

Variable selection for large p small n regression models with incomplete data: Mapping QTL with epistases

<p>Abstract</p> <p>Background</p> <p>Identifying quantitative trait loci (QTL) for both additive and epistatic effects raises the statistical issue of selecting variables from a large number of candidates using a small number of observations. Missing trait and/or marker values prevent one from directly applying the classical model selection criteria such as Akaike's information criterion (AIC) and Bayesian information criterion (BIC).</p> <p>Results</p> <p>We propose a two-step Bayesian variable selection method which deals with the sparse parameter space and the small sample size issues. The regression coefficient priors are flexible enough to incorporate the characteristic of "large <it>p </it>small <it>n</it>" data. Specifically, sparseness and possible asymmetry of the significant coefficients are dealt with by developing a Gibbs sampling algorithm to stochastically search through low-dimensional subspaces for significant variables. The superior performance of the approach is demonstrated via simulation study. We also applied it to real QTL mapping datasets.</p> <p>Conclusion</p> <p>The two-step procedure coupled with Bayesian classification offers flexibility in modeling "large p small n" data, especially for the sparse and asymmetric parameter space. This approach can be extended to other settings characterized by high dimension and low sample size.</p