Identification of a non-purple tartrate-resistant acid phosphatase: an evolutionary link to Ser/Thr protein phosphatases?

BACKGROUND Tartrate-resistant acid phosphatases (TRAcPs), also known as purple acid phosphatases (PAPs), are a family of binuclear metallohydrolases that have been identified in plants, animals and fungi. The human enzyme is a major histochemical marker for the diagnosis of bone-related diseases. TRAcPs can occur as a small form possessing only the ~35 kDa catalytic domain, or a larger ~55 kDa form possessing both a catalytic domain and an additional N-terminal domain of unknown function. Due to its role in bone resorption the 35 kDa TRAcP has become a promising target for the development of anti-osteoporotic chemotherapeutics. FINDINGS A new human gene product encoding a metallohydrolase distantly related to the ~55 kDa plant TRAcP was identified and characterised. The gene product is found in a number of animal species, and is present in all tissues sampled by the RIKEN mouse transcriptome project. Construction of a homology model illustrated that six of the seven metal-coordinating ligands in the active site are identical to that observed in the TRAcP family. However, the tyrosine ligand associated with the charge transfer transition and purple color of TRAcPs is replaced by a histidine. CONCLUSION The gene product identified here may represent an evolutionary link between TRAcPs and Ser/Thr protein phosphatases. Its biological function is currently unknown but is unlikely to be associated with bone metabolism.This work was funded by the Royal Society of Tropical Medicine and Hygiene through a Dennis Burkitt Fellowship to JJM. ARD is supported by the Economic and Social Research Council. JJM is supported by a Wellcome Trust Research Training Fellowship (GR074833MA)

Striving for sustainable global democracy through a group decision-making process: a critical review of an online course to model transformative praxis

The Journal is an open access journal. All articles are made freely available to readers.Our open access policy is in in accordance with the Budapest Open Access Initiative (BOAI) definition - it means that articles have free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself.Sustainability is not simply about changing practices but more centrally about agreeing to change practices together’ (Flanagan et al. 2011). To achieve such ends, groups need to improve processes for making complex decisions together. The challenge faced recently in Copenhagen (including a large number of diverse participants in policy discussions) indicates the need for new ways to mprove discursive democracy. Poverty and climate change are ‘wicked’ problems (Rittel and Webber 1984) that comprise many diverse interrelated variables and that have a strong value and emotional dimension. The shortcomings of many approaches to these problems is that they are expert driven, do not involve the public in decision making, and have a narrow focus on technical issues. They do not consider issues in terms of their interrelated complexity with human cultural issues and values. This paper addresses the transboundary conundrum of how to address complex social and environmental challenges while engaging with people's diverse values and emotion

2014 Massachusetts Family Impact Seminar: A Lot On Our Plate; Chronic Health Threats in Massachusetts

A Lot on Our Plate: Chronic Health Threats in Massachusetts is the fifth Massachusetts Family Impact Seminar, and is designed to emphasize a family perspective in policymaking on issues related to childhood obesity, cardiovascular disease, and type 2 diabetes. In general, Family Impact Seminars analyze the consequences an issue, policy, or program may have for families

'Reaching the hard to reach' - lessons learned from the VCS (voluntary and community Sector). A qualitative study.

Background The notion 'hard to reach' is a contested and ambiguous term that is commonly used within the spheres of social care and health, especially in discourse around health and social inequalities. There is a need to address health inequalities and to engage in services the marginalized and socially excluded sectors of society. Methods This paper describes a pilot study involving interviews with representatives from eight Voluntary and Community Sector (VCS) organisations . The purpose of the study was to explore the notion of 'hard to reach' and perceptions of the barriers and facilitators to accessing services for 'hard to reach' groups from a voluntary and community sector perspective. Results The 'hard to reach' may include drug users, people living with HIV, people from sexual minority communities, asylum seekers, refugees, people from black and ethnic minority communities, and homeless people although defining the notion of the 'hard to reach' is not straight forward. It may be that certain groups resist engaging in treatment services and are deemed hard to reach by a particular service or from a societal stance. There are a number of potential barriers for people who may try and access services, including people having bad experiences in the past; location and opening times of services and how services are funded and managed. A number of areas of commonality are found in terms of how access to services for 'hard to reach' individuals and groups could be improved including: respectful treatment of service users, establishing trust with service users, offering service flexibility, partnership working with other organisations and harnessing service user involvement. Conclusions: If health services are to engage with groups that are deemed 'hard to reach' and marginalised from mainstream health services, the experiences and practices for engagement from within the VCS may serve as useful lessons for service improvement for statutory health services

Black Hole Spectroscopy: Testing General Relativity through Gravitational Wave Observations

Assuming that general relativity is the correct theory of gravity in the strong field limit, can gravitational wave observations distinguish between black hole and other compact object sources? Alternatively, can gravitational wave observations provide a test of one of the fundamental predictions of general relativity? Here we describe a definitive test of the hypothesis that observations of damped, sinusoidal gravitational waves originated from a black hole or, alternatively, that nature respects the general relativistic no-hair theorem. For astrophysical black holes, which have a negligible charge-to-mass ratio, the black hole quasi-normal mode spectrum is characterized entirely by the black hole mass and angular momentum and is unique to black holes. In a different theory of gravity, or if the observed radiation arises from a different source (e.g., a neutron star, strange matter or boson star), the spectrum will be inconsistent with that predicted for general relativistic black holes. We give a statistical characterization of the consistency between the noisy observation and the theoretical predictions of general relativity, together with a numerical example.Comment: 19 pages, 7 figure

Using high-density DNA methylation arrays to profile copy number alterations.

The integration of genomic and epigenomic data is an increasingly popular approach for studying the complex mechanisms driving cancer development. We have developed a method for evaluating both methylation and copy number from high-density DNA methylation arrays. Comparing copy number data from Infinium HumanMethylation450 BeadChips and SNP arrays, we demonstrate that Infinium arrays detect copy number alterations with the sensitivity of SNP platforms. These results show that high-density methylation arrays provide a robust and economic platform for detecting copy number and methylation changes in a single experiment. Our method is available in the ChAMP Bioconductor package: http://www.bioconductor.org/packages/2.13/bioc/html/ChAMP.html

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let