Hypoxia induced centrosome amplification underlies aggressive disease course in HPV-negative oropharyngeal squamous cell carcinoma

Human papillomavirus (HPV)-negative (-ve) oropharyngeal squamous cell carcinomas (OPSCCs) are associated with poorer overall survival (OS) compared to HPV-positive (+ve) OPSCCs. The major obstacle to improving outcomes of HPV -ve patients is the absence of good biomarkers. Herein, we investigated the role of centrosome amplification (CA) as a prognostic marker in HPV –ve OPSCCs. We first quantitatively assessed CA in OPSCC tumor samples and found that HPV -ve OPSCCs exhibit higher CA compared to HPV +ve OPSCCs, and was associated with poor OS even after adjusting for potentially confounding variables. Further, the expression of genes associated with hypoxia and CA was significantly higher in HPV -ve OPSCCs than in HPV +ve OPSCCs. We further uncovered a mechanism by which hypoxia-induced HIF-1α downregulates miR-34a resulting in cyclin D1 overexpression and rampant CA in HPV -ve OPSCCs. Our findings demonstrate that assessment of CA may aid in therapeutic decision-making for these patients

Unraveling the In-law conflict and its association with intimate partner violence in Chinese culture: narrative accounts of Chinese battered women

This paper analyzes in-law conflict and disagreements experienced by Chinese battered women, and investigates their association with intimate partner violence (IPV). Conflict between a daughter- and mother-in-law seems to be a common phenomenon in Chinese families. Twenty-two Chinese women aged from 25 to 69 (M=41) who had experienced in-law conflict were interviewed in a refuge for battered women in Hong Kong. While most of the women experienced conflict with their mother-in-law, some interviewees were also abused by their sisters-in-law. Additionally, one case involved a daughter and father-in-law conflict and another case encompassed a son-and mother-in-law conflict. From their experiences, some important aspects of conflict and disagreement between parents- and children-in-law were identified, including disputes over financial matters, conflicting lifestyles, battles over children, differences in gender role expectations and being a scapegoat of the husband. Using the analysis of narrative accounts of Chinese battered women, the effects of perceived Chinese culture and family dynamics on in-law conflict are studied. Implications of the study for prevention of, and intervention in, domestic violence, as well as future studies of IPV, are addressed.postprin

Evaluating the effects of turf-replacement programs in Los Angeles

Water utilities incentivize turf replacement to promote water conservation, but the effects of such programs have received limited evaluations. In 2014, the Metropolitan Water District of Southern California (MWD) undertook an unprecedented investment to incentive turf replacement throughout Southern California in response to a serious Statewide drought. MWD devoted $350 million to the program, resulting in more than 46,000 rebate payments (25,000 in Los Angeles County) to remove 15.3 million square meters of turf. The program implementation provided a unique opportunity to address research gaps on turf replacement implementation. We analyzed socioeconomic and spatial trends of program participants and assessed landscape changes from turf replacement using a random sample of properties (4% of LA County participants in 2014–16). Specifically, we used a novel and cost-effective approach Google Earth Street View to characterize landscapes in front yards and created a typology of land cover types. Results showed: post-replacement landscapes had a diversity of land cover types – diverse yards with several land cover types, as well as more homogenous yards with a single land cover such as woodchips, bare soil, gravel, and artificial turf. Analysis also indicated some evidence of “neighborhood adoption” effects. We describe the need for longitudinal studies to understand long-term effects of turf replacement and associated water use, and suggest that water utilities should also evaluate results in backyards, which requires site visits. This study provides a novel contribution that can be replicated over space and time to further knowledge of turf replacement program implementations and evaluation

Dimension Six Corrections to the Vector Sector of AdS/QCD Model

We study the effects of dimension six terms on the predictions of the holographic model for the vector meson form factors and determine the corrections to the electric radius, the magnetic and the quadrupole moments of the rho-meson. We show that the only dimension six terms which contribute nontrivially to the vector meson form factors are X^2F^2 and F^3. It appears that the effect from the former term is equivalent to the metric deformation and can change only masses, decay constants and charge radii of vector mesons, leaving the magnetic and the quadrupole moments intact. The latter term gives different contributions to the three form factors of the vector meson and changes the values of the magnetic and the quadrupole moments. The results suggest that the addition of the higher dimension terms improves the holographic model.Comment: 6 pages, RevTex, revised version, accepted for publication in Physics Letters

Role of LAB in Silage Fermentation: Effect on Nutritional Quality and Organic Acid Production—An Overview

Lactic acid bacteria (LAB) inocula play a key role in the preservation and fermentation of forage crops within inoculated silages. LAB is a significant group of the bacterial community as they successfully reduce pH, inhibit the survival of undesirable microorganisms and control nutrient loss in fermented silage. Ensiled plants and metabolites such as simple plant carbohydrates have been utilized by LAB (homo-fermentative and hetero-fermentative LAB) to initiate the production of organic acids including lactic and acetic acids. LAB as a biological silage additive provides stable feed value and secondary metabolic products during rapid anaerobic primary silage fermentation. They are able to ferment a large number of forage crops and also to reduce pH levels in fermented forages, which helps to suppress the growth of spoilage microorganisms. Furthermore, silage inoculants can enhance silage quality, nutritional recovery and shelf life of the inoculated product. When ingested silage, Lactobacilli in the rumen may degrade secondary plant metabolites as part of the rumen microbiota, along with endogenous enzymes. Also, the forages harvesting time are key factors in the development of essential metabolites particularly carbohydrates and proteins which is essential nutrition for LAB survival and production of organic acids. The higher population of LAB could reduce the pH faster and control of deleterious microbial growth in silage. This review presents LAB function in silage production and the potential impacts of its fermentative activity. In addition, the advantage of LAB additives in silage production is discussed, with a focus on recent literature

Molecular mechanisms that underpin EML4-ALK driven cancers and their response to targeted drugs

fusion between the EML4 (echinoderm microtubule-associated protein-like) and ALK (anaplastic lymphoma kinase) genes was identified in non-small cell lung cancer (NSCLC) in 2007 and there has been rapid progress in applying this knowledge to the benefit of patients. However, we have a poor understanding of EML4 and ALK biology and there are many challenges to devising the optimal strategy for treating EML4-ALK NSCLC patients. In this review, we describe the biology of EML4 and ALK, explain the main features of EML4-ALK fusion proteins and outline the therapies that target EML4-ALK. In particular, we highlight the recent advances in our understanding of the structures of EML proteins, describe the molecular mechanisms of resistance to ALK inhibitors and assess current thinking about combinations of ALK drugs with inhibitors that target other kinases or Hsp90

Modulation of Osteogenic and Myogenic Differentiation by a Phytoestrogen Formononetin via p38MAPK-Dependent JAK-STAT and Smad-1/5/8 Signaling Pathways in Mouse Myogenic Progenitor Cells

Formononetin (FN), a typical phytoestrogen has attracted substantial attention as a novel agent because of its diverse biological activities including, osteogenic differentiation. However, the molecular mechanisms underlying osteogenic and myogenic differentiation by FN in C2C12 progenitor cells remain unknown. Therefore the objective of the current study was to investigate the action of FN on myogenic and osteogenic differentiation and its impact on signaling pathways in C2C12 cells. FN significantly increased myogenic markers such as Myogenin, myosin heavy chains, and myogenic differentiation 1 (MyoD). In addition, the expression of osteogenic specific genes alkaline phosphatase (ALP), Run-related transcription factor 2(RUNX2), and osteocalcin (OCN) were up-regulated by FN treatment. Moreover, FN enhanced the ALP level, calcium deposition and the expression of bone morphogenetic protein isoform (BMPs). Signal transduction pathways mediated by p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-related kinases (ERKs), protein kinase B (Akt), Janus kinases (JAKs), and signal transducer activator of transcription proteins (STATs) in myogenic and osteogenic differentiation after FN treatment were also examined. FN treatment activates myogenic differentiation by increasing p38MAPK and decreasing JAK1-STAT1 phosphorylation levels, while osteogenic induction was enhanced by p38MAPK dependent Smad, 1/5/8 signaling pathways in C2C12 progenitor cells

TeV scale mirage mediation in NMSSM

We study the next-to-minimal supersymmetric standard model. We consider soft supersymmetry breaking parameters, which are induced by the mirage mediation mechanism of supersymmetry breaking. We concentrate on the mirage mediation, where the so-called mirage scale is the TeV scale. In this scenario, we can realize the up-type Higgs soft mass of O(200) GeV, while other masses such as gaugino masses and stop masses are heavy such as 1 TeV or more. Cancellation between the effective \mu-term and the down-type Higgs soft mass ameliorates the fine-tuning in the electroweak symmetry breaking even for \mu=O(500) GeV. The mixing between the doublet and singlet Higgs bosons is suppressed by (\lambda/\kappa)/tan\beta. Then the lightest doublet Higgs mass naturally reaches 125 GeV lifted by the new quartic coupling. The higgsino and singlino are light and their linear combination is the lightest superparticle.Comment: 24 pages, 24 figures, Numerical analysis is replaced with the version calculated by NMSSMTools. Comments and references are added on the suppressed doublet-singlet mixing and cases in which the 125 GeV boson is the 2nd lightest CP-even scalar. The version accepted by JHE