Molecular evolution of the hyaluronan synthase 2 gene in mammals: implications for adaptations to the subterranean niche and cancer resistance

The naked mole-rat (NMR) Heterocephalus glaber is a unique and fascinating mammal exhibiting many unusual adaptations to a subterranean lifestyle. The recent discovery of their resistance to cancer and exceptional longevity has opened up new and important avenues of research. Part of this resistance to cancer has been attributed to the fact that NMRs produce a modified form of hyaluronan—a key constituent of the extracellular matrix—that is thought to confer increased elasticity of the skin as an adaptation for living in narrow tunnels. This so-called high molecular mass hyaluronan (HMM-HA) stems from two apparently unique substitutions in the hyaluronan synthase 2 enzyme (HAS2). To test whether other subterranean mammals with similar selection pressures also show molecular adaptation in their HAS2 gene, we sequenced the HAS2 gene for 11 subterranean mammals and closely related species, and combined these with data from 57 other mammals. Comparative screening revealed that one of the two putatively important HAS2 substitutions in the NMR predicted to have a significant effect on hyaluronan synthase function was uniquely shared by all African mole-rats. Interestingly, we also identified multiple other amino acid substitutions in key domains of the HAS2 molecule, although the biological consequences of these for hyaluronan synthesis remain to be determined. Despite these results, we found evidence of strong purifying selection acting on the HAS2 gene across all mammals, and the NMR remains unique in its particular HAS2 sequence. Our results indicate that more work is needed to determine whether the apparent cancer resistance seen in NMR is shared by other members of the African mole-rat clade.National Research Foundation (South Africa

Universality for 2D Wedge Wetting

We study 2D wedge wetting using a continuum interfacial Hamiltonian model which is solved by transfer-matrix methods. For arbitrary binding potentials, we are able to exactly calculate the wedge free-energy and interface height distribution function and, thus, can completely classify all types of critical behaviour. We show that critical filling is characterized by strongly universal fluctuation dominated critical exponents, whilst complete filling is determined by the geometry rather than fluctuation effects. Related phenomena for interface depinning from defect lines in the bulk are also considered.Comment: 4 pages, 1 figur

Geometry dominated fluid adsorption on sculptured substrates

Experimental methods allow the shape and chemical composition of solid surfaces to be controlled at a mesoscopic level. Exposing such structured substrates to a gas close to coexistence with its liquid can produce quite distinct adsorption characteristics compared to that occuring for planar systems, which may well play an important role in developing technologies such as super-repellent surfaces or micro-fluidics. Recent studies have concentrated on adsorption of liquids at rough and heterogeneous substrates and the characterisation of nanoscopic liquid films. However, the fundamental effect of geometry has hardly been addressed. Here we show that varying the shape of the substrate can exert a profound influence on the adsorption isotherms allowing us to smoothly connect wetting and capillary condensation through a number of novel and distinct examples of fluid interfacial phenomena. This opens the possibility of tailoring the adsorption properties of solid substrates by sculpturing their surface shape.Comment: 6 pages, 4 figure

Nonperturbative versus perturbative effects in generalized parton distributions

Generalized parton distributions (GPDs) are studied at the hadronic (nonperturbative) scale within different assumptions based on a relativistic constituent quark model. In particular, by means of a meson-cloud model we investigate the role of nonperturbative antiquark degrees of freedom and the valence quark contribution. A QCD evolution of the obtained GPDs is used to add perturbative effects and to investigate the GPDs' sensitivity to the nonperturbative ingredients of the calculation at larger (experimental) scale.Comment: 17 pages, 10 figures; submitted to Phys. Rev.

Spin-Dependent Twist-Four Matrix Elements from g_1 Data in the Resonance Region

Matrix elements of spin-dependent twist-four operators are extracted from recent data on the spin-dependent g_1 structure function of the proton and deuteron in the resonance region. We emphasize the need to include the elastic contributions to the first moments of the structure functions at Q^2 < 2 GeV^2. The coefficients of the 1/Q^2 corrections to the Ellis-Jaffe sum rules are found to be 0.04 \pm 0.02 and 0.03 \pm 0.04 GeV^2 for the proton and neutron, respectively.Comment: 10 pages REVTeX, 4 figure

Ethnic In-Group Favoritism Among Minority and Majority Groups: Testing the Self-Esteem Hypothesis Among Preadolescents

The self-esteem hypothesis in intergroup relations, as proposed by social identity theory (SIT), states that successful intergroup discrimination enhances momentary collective self-esteem. This hypothesis is a source of continuing controversy. Furthermore, although SIT is increasingly used to account for children’s group attitudes, few studies have examined the hypothesis among children. In addition, the hypothesis’s generality makes it important to study among children from different ethnic groups. The present study, conducted among Dutch and Turkish preadolescents, examined momentary collective self-feelings as a consequence of ethnic group evaluations. The results tended to support the self-esteem hypothesis. In-group favoritism was found to have a self-enhancing effect among participants high in ethnic identification. This result was found for ethnic majority (Dutch) and minority (Turkish) participants.

Serendipity in context: Prioritised contextual browsing in large-scale digital libraries

In previous work we proposed a model of information-seeking behaviour in scholarly workset creation, combining and extend-ing established models by Bates, Ellis, and Wilson to encompass strategies for scholarly research in large-scale information systems. However, this model simplifies contextual browsing, a key aspect of information seeking in large-scale information systems, as a single, holistic, strategy. Here, we extend this model with granular strategies for contextual browsing, defining new modes to characterise contextual browsing as combinations of these strategies, which we show to be consistent with ser-endipitous discovery as described by Makri et al. We study the properties of prioritised contextual browsing as a mechanism for implementing these strategies. We describe the Compage framework, a proof-of-concept implementation for prioritised contextual browsing of Linked Data resources, using Jaccard similarity for prioritisation. Extending Compage, we develop a simulation environment in which we investigate the utility of prioritised contextual browsing over a large-scale digital library dataset. Our simulation applies three strategies for the traversal of contextual metadata: reset, unprioritised, and prioritised. Results empirically demonstrate the advantages of prioritised contextual browsing, and that elements of serendipity can be identified and incorporated within our information-seeking model. In doing so, we evaluate our model's suitability for this scenario, yielding a more detailed understanding of the strategies and modes of behaviour underlying contextual browsing

Chronic low back pain: a prospective study with 4 to 15 years follow-up after a multidisciplinary biopsychosocial rehabilitation program

BACKGROUND: Multidisciplinary biopsychosocial rehabilitation (MBR) in patients with chronic low back pain (CLBP) is superior to less intensive treatments for at least one year, but the long-term course of the disease is largely unknown. The primary aim of this study was to describe the long-term course of an MBR in relation to pain, disability, and quality of life from the beginning of an MBR to between 4 to 15 years after participation. The secondary aim was to explore the long-term course of an MBR in relation to physiological outcomes of functioning. METHODS: This was a observational study conducted at a university hospital. The cohort consisted of participants of a 3-week, CLBP-specific MBR program between August 2001 and January 2013. The North American Spine Society questionnaire (NASS) pain and disability scale was the primary patient -reported outcome measure (PROM). The NASS neurogenic symptoms scale and the Short-Form 36 (SF-36) health survey were secondary PROMs. Patients were assessed before entry to the MBR (T0), at entry (T1), at discharge (T2) and 4 to 15 years after discharge (T3). Effects were quantified by effect size (ES). Score differences were tested for significance using parametric or non-parametric tests and linear mixed models. RESULTS: Of 299 consecutive patients from the MBR program, 229 could be contacted. Of these, 84 declined participation, five did not meet the inclusion criteria, and 26 had incomplete data. Thus, 114 patients were included. The mean follow-up time was 9.2 years. At T3, patients exhibited beneficial effects for NASS pain and disability with a moderate ES (ES = 0.63; p < 0.001). The NASS neurogenic symptoms scale was stable. The SF-36 scales showed an improvement in the bodily pain domain (ES = 1.02; p < 0.001), but no significant changes for physical functioning, physical role, general health, vitality, social functioning, emotional role, or mental health. The physical health component summary was improved (ES = 0.40, p = 0.002), and the mental health summary was unchanged. The linear mixed model analysis confirmed improvements in pain and disability between T1 and T3 (p = 0.010). CONCLUSIONS: The results of this study suggest that there is a long-term benefit of MBR participation in patients with CLBP

Enumeration of CD4+ T-Cells Using a Portable Microchip Count Platform in Tanzanian HIV-Infected Patients

Background CD4+ T-lymphocyte count (CD4 count) is a standard method used to monitor HIV-infected patients during anti-retroviral therapy (ART). The World Health Organization (WHO) has pointed out or recommended that a handheld, point-of-care, reliable, and affordable CD4 count platform is urgently needed in resource-scarce settings. Methods HIV-infected patient blood samples were tested at the point-of-care using a portable and label-free microchip CD4 count platform that we have developed. A total of 130 HIV-infected patient samples were collected that included 16 de-identified left over blood samples from Brigham and Women's Hospital (BWH), and 114 left over samples from Muhimbili University of Health and Allied Sciences (MUHAS) enrolled in the HIV and AIDS care and treatment centers in the City of Dar es Salaam, Tanzania. The two data groups from BWH and MUHAS were analyzed and compared to the commonly accepted CD4 count reference method (FACSCalibur system). Results The portable, battery operated and microscope-free microchip platform developed in our laboratory (BWH) showed significant correlation in CD4 counts compared with FACSCalibur system both at BWH (r = 0.94, p<0.01) and MUHAS (r = 0.49, p<0.01), which was supported by the Bland-Altman methods comparison analysis. The device rapidly produced CD4 count within 10 minutes using an in-house developed automated cell counting program. Conclusions We obtained CD4 counts of HIV-infected patients using a portable platform which is an inexpensive (<$1 material cost) and disposable microchip that uses whole blood sample (<10 µl) without any pre-processing. The system operates without the need for antibody-based fluorescent labeling and expensive fluorescent illumination and microscope setup. This portable CD4 count platform displays agreement with the FACSCalibur results and has the potential to expand access to HIV and AIDS monitoring using fingerprick volume of whole blood and helping people who suffer from HIV and AIDS in resource-limited settings.Wallace H. Coulter Foundation (Young Investigation Award in Bioengineering Award)National Institutes of Health (U.S.) (NIH R01AI081534)National Institutes of Health (U.S.) (NIH R21AI087107)National Institutes of Health (U.S.) (NIH grant RR016482)National Institutes of Health (U.S.) (grant AI060354)National Institutes of Health (U.S.) (NIH Fogarty Fellowship