Risk Factors Associated with False Positive HIV Test Results in a Low-Risk Urban Obstetric Population

Objective. To examine risk factors for false positive HIV enzyme immunoassay (EIA) testing at delivery. Study Design. A review of pregnant women who delivered at Parkland Hospital between 2005 and 2008 was performed. Patients routinely received serum HIV EIA testing at delivery, with positive results confirmed through immunofluorescent testing. Demographics, HIV, hepatitis B surface antigen (HBsAg), and rapid plasma reagin (RPR) results were obtained. Statistical analyses included Pearson's chi-square and Student's t-test. Results. Of 47,794 patients, 47,391 (99%) tested negative, 145 (0.3%) falsely positive, 172 (0.4%) positive, and 86 (0.2%) equivocal or missing HIV results. The positive predictive value of EIA was 54.3%. Patients with false positive results were more likely nulliparous (43% versus 31%, P < 0.001) and younger (23.9 ± 5.7 versus 26.2 ± 5.9 years, P < 0.001). HIV positive patients were older than false positive patients and more likely positive for HBsAg and RPR. Conclusion. False positive HIV testing at delivery using EIA is associated with young maternal age and nulliparity in this population

Molecular architecture of Gαo and the structural basis for RGS16-mediated deactivation

Heterotrimeric G proteins relay extracellular cues from heptahelical transmembrane receptors to downstream effector molecules. Composed of an α subunit with intrinsic GTPase activity and a βγ heterodimer, the trimeric complex dissociates upon receptor-mediated nucleotide exchange on the α subunit, enabling each component to engage downstream effector targets for either activation or inhibition as dictated in a particular pathway. To mitigate excessive effector engagement and concomitant signal transmission, the Gα subunit's intrinsic activation timer (the rate of GTP hydrolysis) is regulated spatially and temporally by a class of GTPase accelerating proteins (GAPs) known as the regulator of G protein signaling (RGS) family. The array of G protein-coupled receptors, Gα subunits, RGS proteins and downstream effectors in mammalian systems is vast. Understanding the molecular determinants of specificity is critical for a comprehensive mapping of the G protein system. Here, we present the 2.9 Å crystal structure of the enigmatic, neuronal G protein Gαo in the GTP hydrolytic transition state, complexed with RGS16. Comparison with the 1.89 Å structure of apo-RGS16, also presented here, reveals plasticity upon Gαo binding, the determinants for GAP activity, and the structurally unique features of Gαo that likely distinguish it physiologically from other members of the larger Gαi family, affording insight to receptor, GAP and effector specificity

On the Surface Structure of Strange Superheavy Nuclei

Bound, strange, neutral superheavy nuclei, stable against strong decay, may exist. A model effective field theory calculation of the surface energy and density of such systems is carried out assuming vector meson couplings to conserved currents and scalar couplings fit to data where it exists. The non-linear relativistic mean field equations are solved assuming local baryon sources. The approach is calibrated through a successful calculation of the known nuclear surface tension.Comment: 12 pages, 9 figure

The acquisition of Sign Language: The impact of phonetic complexity on phonology

Research into the effect of phonetic complexity on phonological acquisition has a long history in spoken languages. This paper considers the effect of phonetics on phonological development in a signed language. We report on an experiment in which nonword-repetition methodology was adapted so as to examine in a systematic way how phonetic complexity in two phonological parameters of signed languages — handshape and movement — affects the perception and articulation of signs. Ninety-one Deaf children aged 3–11 acquiring British Sign Language (BSL) and 46 hearing nonsigners aged 6–11 repeated a set of 40 nonsense signs. For Deaf children, repetition accuracy improved with age, correlated with wider BSL abilities, and was lowest for signs that were phonetically complex. Repetition accuracy was correlated with fine motor skills for the youngest children. Despite their lower repetition accuracy, the hearing group were similarly affected by phonetic complexity, suggesting that common visual and motoric factors are at play when processing linguistic information in the visuo-gestural modality

Gene Activation Using FLP Recombinase in C. elegans

The FLP enzyme catalyzes recombination between specific target sequences in DNA. Here we use FLP to temporally and spatially control gene expression in the nematode C. elegans. Transcription is blocked by the presence of an “off cassette” between the promoter and the coding region of the desired product. The “off cassette” is composed of a transcriptional terminator flanked by FLP recognition targets (FRT). This sequence can be excised by FLP recombinase to bring together the promoter and the coding region. We have introduced two fluorescent reporters into the system: a red reporter for promoter activity prior to FLP expression and a green reporter for expression of the gene of interest after FLP expression. The constructs are designed using the multisite Gateway system, so that promoters and coding regions can be quickly mixed and matched. We demonstrate that heat-shock-driven FLP recombinase adds temporal control on top of tissue specific expression provided by the transgene promoter. In addition, the temporal switch is permanent, rather than acute, as is usually the case for heat-shock driven transgenes. Finally, FLP expression can be driven by a tissue specific promoter to provide expression in a subset of cells that can only be addressed as the intersection of two available promoters. As a test of the system, we have driven the light chain of tetanus toxin, a protease that cleaves the synaptic vesicle protein synaptobrevin. We show that we can use this to inactivate synaptic transmission in all neurons or a subset of neurons in a FLP-dependent manner

The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine

Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78125/1/ten.teb.2009.0340.pd

Coordination of opposing sex-specific and core muscle groups regulates male tail posture during Caenorhabditis elegans male mating behavior

Background To survive and reproduce, animals must be able to modify their motor behavior in response to changes in the environment. We studied a complex behavior of Caenorhabditis elegans, male mating behavior, which provided a model for understanding motor behaviors at the genetic, molecular as well as circuit level. C. elegans male mating behavior consists of a series of six sub-steps: response to contact, backing, turning, vulva location, spicule insertion, and sperm transfer. The male tail contains most of the sensory structures required for mating, in addition to the copulatory structures, and thus to carry out the steps of mating behavior, the male must keep his tail in contact with the hermaphrodite. However, because the hermaphrodite does not play an active role in mating and continues moving, the male must modify his tail posture to maintain contact. We provide a better understanding of the molecular and neuro-muscular pathways that regulate male tail posture during mating. Results Genetic and laser ablation analysis, in conjunction with behavioral assays were used to determine neurotransmitters, receptors, neurons and muscles required for the regulation of male tail posture. We showed that proper male tail posture is maintained by the coordinated activity of opposing muscle groups that curl the tail ventrally and dorsally. Specifically, acetylcholine regulates both ventral and dorsal curling of the male tail, partially through anthelmintic levamisole-sensitive, nicotinic receptor subunits. Male-specific muscles are required for acetylcholine-driven ventral curling of the male tail but dorsal curling requires the dorsal body wall muscles shared by males and hermaphrodites. Gamma-aminobutyric acid activity is required for both dorsal and ventral acetylcholine-induced curling of the male tail and an inhibitory gamma-aminobutyric acid receptor, UNC-49, prevents over-curling of the male tail during mating, suggesting that cross-inhibition of muscle groups helps maintain proper tail posture. Conclusion Our results demonstrated that coordination of opposing sex-specific and core muscle groups, through the activity of multiple neurotransmitters, is required for regulation of male tail posture during mating. We have provided a simple model for regulation of male tail posture that provides a foundation for studies of how genes, molecular pathways, and neural circuits contribute to sensory regulation of this motor behavior

Optical Silencing of C. elegans Cells with Arch Proton Pump

BACKGROUND: Optogenetic techniques using light-driven ion channels or ion pumps for controlling excitable cells have greatly facilitated the investigation of nervous systems in vivo. A model organism, C. elegans, with its small transparent body and well-characterized neural circuits, is especially suitable for optogenetic analyses. METHODOLOGY/PRINCIPAL FINDINGS: We describe the application of archaerhodopsin-3 (Arch), a recently reported optical neuronal silencer, to C. elegans. Arch::GFP expressed either in all neurons or body wall muscles of the entire body by means of transgenes were localized, at least partially, to the cell membrane without adverse effects, and caused locomotory paralysis of worms when illuminated by green light (550 nm). Pan-neuronal expression of Arch endowed worms with quick and sustained responsiveness to such light. Worms reliably responded to repeated periods of illumination and non-illumination, and remained paralyzed under continuous illumination for 30 seconds. Worms expressing Arch in different subsets of motor neurons exhibited distinct defects in the locomotory behavior under green light: selective silencing of A-type motor neurons affected backward movement while silencing of B-type motor neurons affected forward movement more severely. Our experiments using a heat-shock-mediated induction system also indicate that Arch becomes fully functional only 12 hours after induction and remains functional for more than 24 hour. CONCLUSIONS/SGNIFICANCE: Arch can be used for silencing neurons and muscles, and may be a useful alternative to currently widely used halorhodopsin (NpHR) in optogenetic studies of C. elegans