Biophysical Approaches to Human Genetic Disease: ADSL Deficiency as a Model

Biophysical tools are becoming more useful in approaching human genetic disease. The pathogenic mechanisms behind many disorders have been attributed to protein loss of function or gain in toxic function. For example, changes in the protein Adenylosuccinate Lyase (ADSL) lead to ADSL deficiency, a disorder that causes symptoms ranging from epilepsy to expression of autistic features. Biophysics offers different tools to study intrinsic properties of proteins. We have applied such tools to study the enzyme kinetics and protein stability of ADSL and two mutations (R426H and R303C) to formulate better hypotheses regarding the pathogenic mechanism. Enzyme kinetic findings indicate a) non-linear dependences of the activities on the substrate ratios due to competitive binding and b) distinct differences in the behaviors of the different mutations. Preliminary stability measurements indicate a) there is an intermediate state in the folding pathway and a fourth state is necessary for modeling, b) R426H, a mutation that causes severe phenotypes, is less stable, c) there is no evidence of a gain in toxic function for either mutation. This complete work supports our hypothesis that there are multiple mechanisms of pathogenesis of ADSL deficiency including instability of the functional ADSL tetramer, aggregation of ADSL, or diminution of enzyme activity. The significance of this is that development of an effective therapy may depend upon which mechanism is active in a particular patient

CHANGING TOBACCO MARKETS: EFFECTS ON BURLEY TOBACCO FARMS

Three representative Tennessee tobacco farms are used to estimate farm-level impacts of (1) program continuation with further quota cuts, and (2) program elimination in 2000. Results indicate that program elimination has more potential to reduce farm income and that larger and more diversified farms are less affected in both scenarios.tobacco, farm-level analysis, representative farms, Tennessee agriculture, Agricultural and Food Policy, Crop Production/Industries,

POTENTIAL FARM-LEVEL IMPACTS OF PROPOSED FQPA IMPLEMENTATION: THE TENNESSEE CASE

This research estimates farm-level impacts of a potential ban on organophosphates and carbamates under the FQPA. Insecticide expenditure and first- and fifth-year yield impacts are estimated for five Tennessee representative farms. Results indicate that within five years, the ban could reduce net farm income on Tennessee farms by 16 to 46 percent.FQPA, organophosphates, carbamates, insecticides, farm-level analysis, Agricultural and Food Policy, Environmental Economics and Policy,

Muon-Spin Rotation Measurements of an Unusual Vortex-Glass Phase in the Layered Superconductor Bi2.15Sr1.85CaCu2O8+δ

Muon-spin rotation measurements, performed on the mixed state of the classic anisotropic superconductor Bi2.15Sr1.85CaCu2O8+δ, obtain quantities directly related to two- and three-body correlations of vortices in space. A novel phase diagram emerges from such local probe measurements of the bulk, revealing an unusual glassy state at intermediate fields which appears to freeze continuously from the equilibrium vortex liquid but differs both from the lattice and the conventional high-field vortex glass state in its structure.Publisher PDFPeer reviewe

Size-dependent reversal of grains in perpendicular magnetic recording media measured by small-angle polarized neutron scattering

Polarized small-angle neutron scattering has been used to measure the magnetic structure of a CoCrPt–SiOx thin-film data storage layer, contained within a writable perpendicular recording media, at granular (<10 nm) length scales. The magnetic contribution to the scattering is measured as the magnetization is reversed by an external field, providing unique spatial information on the switching process. A simple model of noninteracting nanomagnetic grains provides a good description of the data and an analysis of the grain-size dependent reversal provides strong evidence for an increase in magnetic anisotropy with grain diameter

Carcinogenesis in Prostate Cancer: The role of Long Non-Coding RNAs

LncRNAs appear to play a considerable role in tumourigenesis through regulating key processes in cancer cells such as proliferative signalling, replicative immortality, invasion and metastasis, evasion of growth suppressors, induction of angiogenesis and resistance to apoptosis. LncRNAs have been reported to play a role in prostate cancer, particularly in regulating the androgen receptor signalling pathway. In this review article, we summarise the role of 34 lncRNAs in prostate cancer with a particular focus on their role in the androgen receptor signalling pathway and the epithelial to mesenchymal transition pathway

"The fruits of independence": Satyajit Ray, Indian nationhood and the spectre of empire

Challenging the longstanding consensus that Satyajit Ray's work is largely free of ideological concerns and notable only for its humanistic richness, this article shows with reference to representations of British colonialism and Indian nationhood that Ray's films and stories are marked deeply and consistently by a distinctively Bengali variety of liberalism. Drawn from an ongoing biographical project, it commences with an overview of the nationalist milieu in which Ray grew up and emphasizes the preoccupation with colonialism and nationalism that marked his earliest unfilmed scripts. It then shows with case studies of Kanchanjangha (1962), Charulata (1964), First Class Kamra (First-Class Compartment, 1981), Pratidwandi (The Adversary, 1970), Shatranj ke Khilari (The Chess Players, 1977), Agantuk (The Stranger, 1991) and Robertsoner Ruby (Robertson's Ruby, 1992) how Ray's mature work continued to combine a strongly anti-colonial viewpoint with a shifting perspective on Indian nationhood and an unequivocal commitment to cultural cosmopolitanism. Analysing how Ray articulated his ideological positions through the quintessentially liberal device of complexly staged debates that were apparently free, but in fact closed by the scenarist/director on ideologically specific notes, this article concludes that Ray's reputation as an all-forgiving, ‘everybody-has-his-reasons’ humanist is based on simplistic or even tendentious readings of his work

State of the art: noninvasive imaging and management of neurovascular trauma

Neurotrauma represents a significant public health problem, accounting for a significant proportion of the morbidity and mortality associated with all traumatic injuries. Both blunt and penetrating injuries to cervicocerebral vessels are significant and are likely more common than previously recognized. Imaging of such injuries is an important component in the evaluation of individuals presenting with such potential injuries, made all the more important since many of the vascular injuries are clinically silent. Management of injuries, particularly those caused by blunt trauma, is constantly evolving. This article addresses the current state of imaging and treatment of such injuries

Compendium of Current Total Ionizing Dose Results and Displacement Damage Results for Candidate Spacecraft Electronics for NASA

Sensitivity of a variety of candidate spacecraft electronics to total ionizing dose and displacement damage is studied. Devices tested include optoelectronics, digital, analog, linear bipolar devices, and hybrid devices