Under the influence of genetics: how transdisciplinarity leads us to rethink social pathways to illness

This article describes both sociological and genetic theories of illness causation and derives propositions expected under each and under a transdisciplinary theoretical frame. The authors draw propositions from three theories -- fundamental causes, social stress processes, and social safety net theories -- and tailor hypotheses to the case of alcohol dependence. Analyses of a later wave of the Collaborative Study on the Genetics of Alcoholism reveal a complex interplay of the GABRA2 gene with social structural factors to produce cases meeting DSM/ICD diagnoses. Only modest evidence suggests that genetic influence works through social conditions and experiences. Further, women are largely unaffected in their risk for alcohol dependence by allele status at this candidate gene; family support attenuates genetic influence; and childhood deprivation exacerbates genetic predispositions. These findings highlight the essential intradisciplinary tension in the role of proximal and distal influences in social processes and point to the promise of focusing directly on dynamic, networked sequences that produce different pathways to health and illness

Expression and Comparative Genomics of Two Serum Response Factor Genes in Zebrafish

Serum response factor (SRF) is a single copy, highly conserved transcription factor that governs the expression of hundreds of genes involved with actin cytoskeletal organization, cellular growth and signaling, neuronal circuitry and muscle differentiation. Zebrafish have emerged as a facile and inexpensive vertebrate model to delineate gene expression, regulation, and function, and yet the study of SRF in this animal has been virtually unexplored. Here, we report the existence of two srf genes in zebrafish, with partially overlapping patterns of expression in 3 and 7 day old developing animals. The mammalian ortholog (srf1) encodes for a 520 amino acid protein expressed in adult vascular and visceral smooth muscle cells, cardiac and skeletal muscle, as well as neuronal cells. The second zebrafish srf gene (srf2), encoding for a presumptive protein of only 314 amino acids, is transcribed at lower levels and appears to be less widely expressed across adult tissues. Both srf genes are induced by the SRF coactivator myocardin and attenuated with a short hairpin RNA to mammalian SRF. Promoter studies with srf1 reveal conserved CArG boxes that are the targets of SRF-myocardin in embryonic zebrafish cells. These results reveal that SRF was duplicated in the zebrafish genome and that its protein expression in all three muscle cell types is highly conserved across vertebrate animals suggesting an ancient code for transcriptional regulation of genes unique to muscle cell lineages

Optical Frequency Measurement across a 104-Thz Gap with a Femtosecond Laser Frequency Comb

The frequency-domain mode comb of a Ti:sapphire femtosecond laser centered at 350 THz is broadened to 150 THz (full width at −30 dBc) by self-phase modulation in a single-mode optical fiber. By phase locking continuous-wave lasers to elements of the comb near 1064 and 778 nm, we measure the 104-THz frequency gap between these two lasers with a relative uncertainty of 2.7×10−11 in 1 s

Retention in care, resource utilization, and costs for adults receiving antiretroviral therapy in Zambia: a retrospective cohort study

BACKGROUND: Of the estimated 800,000 adults living with HIV in Zambia in 2011, roughly half were receiving antiretroviral therapy (ART). As treatment scale up continues, information on the care provided to patients after initiating ART can help guide decision-making. We estimated retention in care, the quantity of resources utilized, and costs for a retrospective cohort of adults initiating ART under routine clinical conditions in Zambia. METHODS: Data on resource utilization (antiretroviral [ARV] and non-ARV drugs, laboratory tests, outpatient clinic visits, and fixed resources) and retention in care were extracted from medical records for 846 patients who initiated ART at ≥15 years of age at six treatment sites between July 2007 and October 2008. Unit costs were estimated from the provider’s perspective using site- and country-level data and are reported in 2011 USD. RESULTS: Patients initiated ART at a median CD4 cell count of 145 cells/μL. Fifty-nine percent of patients initiated on a tenofovir-containing regimen, ranging from 15% to 86% depending on site. One year after ART initiation, 75% of patients were retained in care. The average cost per patient retained in care one year after ART initiation was $243 (95$194-$293), ranging from$184 (95% CI, $172-$195) to $304 (95$290-$319) depending on site. Patients retained in care one year after ART initiation received, on average, 11.4 months’ worth of ARV drugs, 1.5 CD4 tests, 1.3 blood chemistry tests, 1.4 full blood count tests, and 6.5 clinic visits with a doctor or clinical officer. At all sites, ARV drugs were the largest cost component, ranging from 38% to 84% of total costs, depending on site. CONCLUSIONS: Patients initiate ART late in the course of disease progression and a large proportion drop out of care after initiation. The quantity of resources utilized and costs vary widely by site, and patients utilize a different mix of resources under routine clinical conditions than if they were receiving fully guideline-concordant care. Improving retention in care and guideline concordance, including increasing the use of tenofovir in first-line ART regimens, may lead to increases in overall treatment costs

Flexible access to conformationally-locked bicyclic morpholines

A preparatively accessible route to a series of conformationally-locked bicyclic morpholines has been developed. This flexible approach allows for diversification in order for a small array of lead-like scaffolds to be synthesised from readily available key building blocks

Thermodynamics of nanodomain formation and breakdown in Scanning Probe Microscopy: Landau-Ginzburg-Devonshire approach

Thermodynamics of tip-induced nanodomain formation in scanning probe microscopy of ferroelectric films and crystals is studied using the Landau-Ginzburg-Devonshire phenomenological approach. The local redistribution of polarization induced by the biased probe apex is analyzed including the effects of polarization gradients, field dependence of dielectric properties, intrinsic domain wall width, and film thickness. The polarization distribution inside subcritical nucleus of the domain preceding the nucleation event is very smooth and localized below the probe, and the electrostatic field distribution is dominated by the tip. In contrast, polarization distribution inside the stable domain is rectangular-like, and the associated electrostatic fields clearly illustrate the presence of tip-induced and depolarization field components. The calculated coercive biases of domain formation are in a good agreement with available experimental results for typical ferroelectric materials. The microscopic origin of the observed domain tip elongation in the region where the probe electric field is much smaller than the intrinsic coercive field is the positive depolarization field in front of the moving counter domain wall. For infinitely thin domain walls local domain breakdown through the sample depth appears. The results obtained here are complementary to the Landauer-Molotskii energetic approach.Comment: 35 pages, 8 figures, suplementary attached, to be submitted to Phys. Rev.