The CLC-5 2Cl-/H+ exchange transporter in endosomal function and Dent's disease

CLC-5 plays a critical role in the process of endocytosis in the proximal tubule of the kidney and mutations that alter protein function are the cause of Dent's I disease. In this X-linked disorder impaired reabsorption results in the wasting of calcium and low molecular weight protein to the urine, kidney stones, and progressive renal failure. Several different ion-transporting and protein clustering roles have been proposed as the physiological function of CLC-5 in endosomal membranes. At the time of its discovery, nearly 20 years ago, it was understandably assumed to be a chloride channel similar to known members of the CLC family, such as CLC-1, suggesting that chloride transport by CLC-5 was critical for endosomal function. Since then CLC-5 was found instead to be a 2Cl-/H+ exchange transporter with voltage-dependent activity. Recent studies have determined that it is this coupled exchange of protons for chloride, and not just chloride transport, which is critical for endosomal and kidney function. This review discusses the recent ideas that describe how CLC-5 might function in endosomal membranes, the aspects that we still do not understand, and where controversies remain

What are the prospects of 3D profiling systems applied to firearms and toolmark identification?

This paper details a comparative pilot study of 3D (three dimensional) imaging technologies for potential application in forensic firearms and toolmark identification; as such it reviews the most up-to-date profiling systems. In particular, the paper focuses on the application of 3D imaging and recording technology as applied to firearm identification, being a specialised field within the discipline of toolmark identification. Each technology under test employs a different technique or scientific principle to capture topographic data i.e. focus-variation microscopy, confocal microscopy, point laser profilometry and vertical scanning interferometry. To qualitatively establish the capabilities and limitations of each technology investigated, standard reference samples were used and a set of specific operational criteria devised for successful application in this field. The reference standard crucially included and centred on was the National Institute of Standards and Technology (NIST) ‘standard bullet’. This was to ensure that evaluation represented the practical examination of ballistic samples i.e. fired cartridge cases and bullets. It is concluded that focus-variation microscopy has potentially the most promising approach for a forensic laboratory instrument, in terms of functionality and 3D imaging performance, and is worthy of further investigation

The ideal energy of classical lattice dynamics

We define, as local quantities, the least energy and momentum allowed by quantum mechanics and special relativity for physical realizations of some classical lattice dynamics. These definitions depend on local rates of finite-state change. In two example dynamics, we see that these rates evolve like classical mechanical energy and momentum.Comment: 12 pages, 4 figures, includes revised portion of arXiv:0805.335

Penguin decays of B mesons

Penguin, or loop, decays of B mesons induce effective flavor-changing neutral currents, which are forbidden at tree level in the Standard Model. These decays give special insight into the CKM matrix and are sensitive to non-standard model effects. In this review, we give a historical and theoretical introduction to penguins and a description of the various types of penguin processes: electromagnetic, electroweak, and gluonic. We review the experimental searches for penguin decays, including the measurements of the electromagnetic penguins b -> s gamma and B -> K* gamma and gluonic penguins B -> K pi, B+ -> omega K+ and B -> eta' K, and their implications for the Standard Model and New Physics. We conclude by exploring the future prospects for penguin physics.Comment: 49 pages, LATEX, 30 embedded figures, submitted to Annual Reviews of Nuclear and Particle Scienc

Acoustic transmission through compound subwavelength slit arrays

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The angular dependence of the transmission of sound in air through four types of 2D slit-arrays formed of aluminium slats is explored, both experimentally and numerically. For a simple, subwavelength periodic slit-array, it is well known that Fabry-Perot-like wave-guide resonances, supported by the slit-cavities, hybridising with bound acoustic surface waves, result in ‘Enhanced Acoustic Transmission’ at frequencies determined by the length, width and separation of each slit-cavity. We demonstrate that altering the spacing or width of some of the slits to form a compound array (i.e. an array having a basis comprised of more than one slit) results in sharp dips in the transmission spectra, that may have a strong angular dependence. These features correspond to ‘phase resonances’, which have been studied extensively in the electromagnetic case. This geometry allows for additional near-field configurations compared to the simple array, whereby the field in adjacent cavities can be out-of-phase. Several types of compound slit-array are investigated; one such structure is optimised to minimise the effect of boundary-layer loss mechanisms present in each slit cavity, thereby achieving a deep, sharp transmission minimum in a broad maximumThe authors would like to thank the UK Ministry of Defence’s Defence Science and Technology Laboratorty (DSTL) for their financial support and permission to publis

From protest to agenda building: Description bias in media coverage of protest events in Washington, D.C

Social movements often seek to draw attention to issues they deem important by organizing public demonstrations with the aim of attracting mass media coverage. But only a small proportion of all public demonstrations receives any media attention. This article asks whether even the minimal coverage that demonstrations receive reveal any influence of social movements in shaping how issues are framed by the mass media. Analyzing newspaper and television news stories on Washington, D.C. protests held during 1982 and 1991, we ask whether news reports on protests are framed in ways consistent with the aims of protesters. Do demonstrators receive media coverage that highlights the issues about which they are concerned, or does coverage focus on the protest event itself, to the exclusion of the social issues that movements target? Our results support much of the surmising among media scholars, that even when movements succeed at obtaining the attention of mass media outlets, media reports portray protests in ways that may undermine social movement agendas. Despite this obstacle to communicating protest messages through demonstrations, movements engage in other forms of communication that can affect public interpretations of mass media frames

Evolution favors protein mutational robustness in sufficiently large populations

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations