Implication of the overlap representation for modelling generalized parton distributions

Based on a field theoretically inspired model of light-cone wave functions, we derive valence-like generalized parton distributions and their double distributions from the wave function overlap in the parton number conserved s-channel. The parton number changing contributions in the t-channel are restored from duality. In our construction constraints of positivity and polynomiality are simultaneously satisfied and it also implies a model dependent relation between generalized parton distributions and transverse momentum dependent parton distribution functions. The model predicts that the t-behavior of resulting hadronic amplitudes depends on the Bjorken variable x_Bj. We also propose an improved ansatz for double distributions that embeds this property.Comment: 15 pages, 8 eps figure

Refractive-index sensing with ultra-thin plasmonic nanotubes

We study the refractive-index sensing properties of plasmonic nanotubes with a dielectric core and ultra-thin metal shell. The few-nm thin metal shell is described by both the usual Drude model and the nonlocal hydrodynamic model to investigate the effects of nonlocality. We derive an analytical expression for the extinction cross section and show how sensing of the refractive index of the surrounding medium and the figure-of-merit are affected by the shape and size of the nanotubes. Comparison with other localized surface plasmon resonance sensors reveals that the nanotube exhibits superior sensitivity and comparable figure-of-merit

Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity

Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Ethanol seeking triggered by environmental context is attenuated by blocking dopamine D1 receptors in the nucleus accumbens core and shell in rats

Conditioned behavioral responses to discrete drug-associated cues can be modulated by the environmental context in which those cues are experienced, a process that may facilitate relapse in humans. Rodent models of drug self-administration have been adapted to reveal the capacity of contexts to trigger drug seeking, thereby enabling neurobiological investigations of this effect. We tested the hypothesis that dopamine transmission in the nucleus accumbens, a neural structure that mediates reinforcement, is necessary for context-induced reinstatement of responding for ethanol-associated cues. Rats pressed one lever (active) for oral ethanol (0.1 ml; 10% v/v) in operant conditioning chambers distinguished by specific visual, olfactory, and tactile contextual stimuli. Ethanol delivery was paired with a discrete (4 s) light-noise stimulus. Responses on a second lever (inactive) were not reinforced. Behavior was then extinguished by withholding ethanol but not the discrete stimulus in a different context. Reinstatement, expressed as elevated responding for the discrete stimulus without ethanol delivery, was tested by placing rats into the prior self-administration context after administration of saline or the dopamine D1 receptor antagonist, SCH 23390 (0.006, 0.06, and 0.6 μg/side), into the nucleus accumbens core or shell. Compared with extinction responding, active lever pressing in saline-pretreated rats was enhanced by placement into the prior ethanol self-administration context. SCH 23390 dose-dependently reduced reinstatement after infusion into the core or shell. These findings suggest a critical role for dopamine acting via D1 receptors in the nucleus accumbens in the reinstatement of responding for ethanol cues triggered by placement into an ethanol-associated context

Are Bone and Muscle Changes from POWER PE, an 8-month In-school Jumping Intervention, Maintained at Three Years?

Our aim was to determine if the musculoskeletal benefits of a twice-weekly, school-based, jumping regime in healthy adolescent boys and girls were maintained three years later. Subjects of the original POWER PE trial (n = 99) were contacted and asked to undergo retesting three years after cessation of the intervention. All original measures were completed including: sitting height, standing height, weight, calcaneal broadband ultrasound attenuation (BUA), whole body, hip and spine bone mineral content (BMC), lean tissue mass, and fat mass. Physical activity was recorded with the bone-specific physical activity questionnaire (BPAQ) and calcium intake was estimated with a calcium-focussed food questionnaire. Maturity was determined by Tanner staging and estimation of the age of peak height velocity (PHV). Twenty-nine adolescents aged 17.3±0.4 years agreed to participate. Three years after the intervention, there were no differences in subject characteristics between control and intervention groups (p>0.05). Three-year change in weight, lean mass, and fat mass were similar between groups (p>0.05). There were no significant group differences in three-year change in BUA or BMC at any site (p>0.05), although the between-group difference in femoral neck BMC at follow-up exceeded the least significant change. While significant group differences were not observed three years after cessation of the intervention, changes in bone parameters occurred in parallel for intervention and control groups such that the original benefits of the intervention observed within the treatment group were sustained

The BH3 mimetic ABT-737 increases treatment efficiency of paclitaxel against hepatoblastoma

<p>Abstract</p> <p>Background</p> <p>The primary goal of current chemotherapy in hepatoblastoma (HB) is reduction of tumour volume and vitality to enable complete surgical resection and reduce risk of recurrence or metastatic disease. Drug resistance remains a major challenge for HB treatment. In some malignancies inhibition of anti-apoptotic pathways using small BH3 mimetic molecules like ABT-737 shows synergistic effects in combination with cystotoxic agents in vitro. Now we analysed toxicology and synergistic effects of this approach in HB cells and HB xenografts.</p> <p>Methods</p> <p>Viability was monitored in HB cells (HUH6 and HepT1) and fibroblasts treated with paclitaxel, ABT-737 and a combination of both in a MTT assay. HUH6 xenotransplants in NOD/LtSz-scid IL2Rγnull mice (NSG) were treated accordingly. Tumour volume and body weight were monitored. Xenografted tumours were analysed by histology and immunohistochemistry (Ki-67 and TUNEL assay).</p> <p>Results</p> <p>ABT-737 reduced viability in HUH6 and HepT1 cells cultures at concentrations above 1 μM and also enhanced the cytotoxic effect of paclitaxel when used in combination. Thereby paclitaxel could be reduced tenfold to achieve similar reduction of viability of tumour cells. In contrast no toxicity in fibroblasts was observed at the same regiments. Subcutaneous HB (HUH6) treated with paclitaxel (12 mg/kg body weight, n = 7) led to delayed tumour growth in the beginning of the experiment. However, tumour volume was similar to controls (n = 5) at day 25. Combination treatment with paclitaxel and ABT-737 (100 mg/kg, n = 8) revealed significantly 10 fold lower relative tumour volumes compared to control and paclitaxel groups. Paclitaxel dependent toxicity was observed in this mice strain.</p> <p>Conclusions</p> <p>Our results demonstrate enhancement of chemotherapy by using modulators of apoptosis. Further analyses should include improved pharmacological formulations of paclitaxel and BH3 mimetics in order to reduce toxicological effects. Sensitising HB to apoptosis may also render resistant HB susceptible to established chemotherapy regimens.</p

Alcohol and cardio-respiratory deaths in Chinese: a population-based case-control study of 32,462 older Hong Kong adults

Background: In observational studies moderate alcohol use reduces cardio-respiratory mortality. However observational studies may be biased by many factors including residual confounding by unmeasured differences between moderate alcohol users and other groups or by changes in alcohol use with ill-health and aging. We used two different analytic strategies in an under-studied population, i.e. southern Chinese, to provide an assessment of the specific impact of moderate alcohol use on mortality from ischemic heart disease (IHD) and chronic obstructive pulmonary diseases (COPD). Methods: In a population-based case-control study of all adult deaths in Hong Kong Chinese in 1998, we used adjusted logistic regression to compare alcohol use in decedents aged ≥ 60 years from IHD (2270) and COPD (1441) with 10,320 living and 9043 dead controls (all non-alcohol related deaths). We also examined whether the association of alcohol use with death from IHD or COPD varied with sex or smoking status. Results: Using living controls and adjusted for age, socio-economic status and lifestyle, occasional and moderate alcohol use were generally associated with lower mortality from IHD and COPD. However, using dead controls the protection of occasional and moderate alcohol use appeared to be limited to ever-smokers for IHD (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.46 to 0.73 for moderate compared to never-use in ever-smokers, but OR 1.07, 95% CI 0.76 to 1.50 in never-smokers), and possibly to men for COPD. High alcohol use was associated with lower IHD mortality and possibly with lower COPD mortality. Conclusion: High levels of alcohol use in an older Chinese population were associated with lower IHD mortality. Moderate alcohol use was less consistently protective against IHD mortality. Alcohol use was associated with lower COPD mortality particularly in men, either due to some yet to be clarified properties of alcohol or as the artefactual result of genetic selection into alcohol use in a Chinese population. Given the increasing use of alcohol in China with economic development, other designs and analytic strategies are needed to assess the impact of alcohol in this population, so that an evidence-based public health policy can be formulated.link_to_subscribed_fulltex

Against Modern Football: Mobilising Protest Movements in Social Media

Recent debates in sociology consider how Internet communications might catalyse leaderless, open-ended, affective social movements that broaden support and bypass traditional institutional channels to create change. We extend this work into the field of leisure and lifestyle politics with an empirical study of Internet-mediated protest movement, Stand Against Modern Football. We explain how social media facilitate communications that transcend longstanding rivalries, and engender shared affective frames that unite diverse groups against corporate logics. In examining grassroots organisation, communication and protest actions that span online and urban locations, we discover sustained interconnectedness with traditional social movements, political parties, the media and the corporate targets of protests. Finally, we suggest that Internet-based social movements establish stable forms of organisation and leadership at these networked intersections in order to advance instrumental programmes of change

Dermatitis and Aging-Related Barrier Dysfunction in Transgenic Mice Overexpressing an Epidermal-Targeted Claudin 6 Tail Deletion Mutant

The barrier function of the skin protects the mammalian body against infection, dehydration, UV irradiation and temperature fluctuation. Barrier function is reduced with the skin's intrinsic aging process, however the molecular mechanisms involved are unknown. We previously demonstrated that Claudin (Cldn)-containing tight junctions (TJs) are essential in the development of the epidermis and that transgenic mice overexpressing Cldn6 in the suprabasal layers of the epidermis undergo a perturbed terminal differentiation program characterized in part by reduced barrier function. To dissect further the mechanisms by which Cldn6 acts during epithelial differentiation, we overexpressed a Cldn6 cytoplasmic tail deletion mutant in the suprabasal compartment of the transgenic mouse epidermis. Although there were no gross phenotypic abnormalities at birth, subtle epidermal anomalies were present that disappeared by one month of age, indicative of a robust injury response. However, with aging, epidermal changes with eventual chronic dermatitis appeared with a concomitant barrier dysfunction manifested in increased trans-epidermal water loss. Immunohistochemical analysis revealed aberrant suprabasal Cldn localization with marked down-regulation of Cldn1. Both the proliferative and terminal differentiation compartments were perturbed as evidenced by mislocalization of multiple epidermal markers. These results suggest that the normally robust injury response mechanism of the epidermis is lost in the aging Involucrin-Cldn6-CΔ196 transgenic epidermis, and provide a model for evaluation of aging-related skin changes