930 research outputs found
Resolution of p-cresol methylhydroxylase into catalytically active subunits and reconstitution of the flavocytochrome
African Livestock Futures: Realizing the potential of livestock for food security, poverty reduction and the environment in Sub-Saharan Africa
Sensitivity and threshold dynamics of Pinus strobus and Quercus spp. in response to experimental and naturally-occurring severe droughts
Increased drought frequency and severity are a pervasive global threat, yet the capacity of mesic temperate forests to maintain resilience in response to drought remains poorly understood. We deployed a throughfall removal experiment to simulate a once in a century drought in New Hampshire, USA, which coupled with the region-wide 2016 drought, intensified moisture stress beyond that experienced in the lifetimes of our study trees. To assess the sensitivity and threshold dynamics of two dominant northeastern tree genera (Quercus and Pinus), we monitored sap flux density (Js), leaf water potential and gas exchange, growth, and intrinsic water use efficiency (iWUE) for one pretreatment year (2015) and two treatment years (2016-17). Results showed that Js in pine (P. strobus) declined abruptly at a soil moisture threshold of 0.15 m3m-3 , while oak’s (Q. rubra and Q. velutina) threshold was 0.11 m3m-3 — a finding consistent with pine’s more isohydric strategy. Nevertheless, once oaks’ moisture threshold was surpassed, Js declined abruptly, suggesting that while oaks are well-adapted to moderate drought, they are highly susceptible to extreme drought. The radial growth reduction in response to the 2016 drought was more than twice as great for pine than for oaks (50% vs. 18% respectively). Despite relatively high precipitation in 2017, the oaks’ growth continued to decline (low recovery), whereas pine showed neutral (treatment) or improved (control) growth. iWUE increased in 2016 for both treatment and control pines, but only in treatment oaks. Notably, pines exhibited a significant linear relationship between iWUE and precipitation across years, whereas the oaks only showed a response during the driest conditions, further underscoring the different sensitivity thresholds for these species. Our results provide new insights into how interactions between temperate forest tree species’ contrasting physiologies and soil moisture thresholds influence their responses and resilience to extreme drought
Acyclovir suppression to prevent recurrent genital herpes at delivery.
OBJECTIVE: To determine if suppressive acyclovir near term decreased the frequency of clinical recurrences at delivery in women with recurrent genital herpes simplex virus (HSV) infection. METHODS: We conducted a prospective, double-blind, randomized trial in 234 women with recurrent genital herpes. Women with genital infection of any frequency were enrolled. Patients received either suppressive oral acyclovir 400 mg three times daily or an identical placebo after 36 weeks' gestation. Clinical lesions were identified, and HSV cultures were obtained at delivery. The frequencies of clinical and subclinical HSV recurrences at delivery were evaluated. RESULTS: Six percent of patients treated with acyclovir, and 14% of patients treated with placebo had clinical HSV at delivery (p = 0.046). No patients in the acyclovir group had positive HSV cultures, compared with 6% of placebo-treated patients (p = 0.029). There was no significant difference in subclinical HSV shedding in the acyclovir group (0%) compared with the placebo-treated group (3%) (p = 0.102). CONCLUSIONS: Suppressive acyclovir therapy significantly decreased the incidence of clinical genital herpes and the overall incidence of HSV excretion at delivery in patients with previous herpes infection
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
Optometric Measurements Predict Performance but Not Comfort on a Virtual Object Placement Task With a Stereoscopic 3D Display
Twelve participants were tested on a simple virtual object precision placement task while viewing a stereoscopic 3D (S3D) display. Inclusion criteria included uncorrected or best corrected vision of 20/20 or better in each eye and stereopsis of at least 40 arc sec using the Titmus stereo test. Additionally, binocular function was assessed, including measurements of distant and near phoria (horizontal and vertical) and distant and near horizontal fusion ranges using standard optometric clinical techniques. Before each of six 30 minute experimental sessions, measurements of phoria and fusion ranges were repeated using a Keystone View Telebinocular and an S3D display, respectively. All participants completed experimental sessions in which the task required the precision placement of a virtual object in depth at the same location as a target object. Subjective discomfort was assessed using the Simulator Sickness Questionnaire (SSQ). Individual placement accuracy in S3D trials was significantly correlated with several of the binocular screening outcomes: viewers with larger convergent fusion ranges (measured at near distance), larger total fusion ranges (convergent plus divergent ranges, measured at near distance), and/or lower (better) stereoscopic acuity thresholds were more accurate on the placement task. No screening measures were predictive of subjective discomfort, perhaps due to the low levels of discomfort induced
L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis
Macrophage adhesion and stretching have been shown to induce interleukin (IL)-1β production, but the mechanism of this mechanotransduction remains unclear. Here we specify the molecular link between mechanical tension on tissue-resident macrophages and activation of the NLRP3 inflammasome, which governs IL-1β production. NLRP3 activation enhances antimicrobial defense, but excessive NLRP3 activity causes inflammatory tissue damage in conditions such as pulmonary fibrosis and acute respiratory distress syndrome. We find that the actin-bundling protein L-plastin (LPL) significantly enhances NLRP3 assembly. Specifically, LPL enables apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) oligomerization during NLRP3 assembly by stabilizing ASC interactions with the kinase Pyk2, a component of cell-surface adhesive structures called podosomes. Upon treatment with exogenous NLRP3 activators, lung-resident alveolar macrophages (AMs) lacking LPL exhibit reduced caspase-1 activity, IL-1β cleavage, and gasdermin-D processing. LP
Open radial artery harvesting better preserves endothelial function compared to the endoscopic approach
OBJECTIVES: Both the open and endovascular techniques are commonly used for harvesting the radial artery (ORAH and ERAH, respectively), and yet, very little is known about the effects of these 2 techniques on endothelial integrity and function of the radial artery (RA). The aim of this study was to assess the endothelial integrity and function of RA harvested using the 2 approaches. METHODS: Two independent surgical teams working in the same institution routinely use the RA for coronary artery bypass grafting exclusively employing either ORAH or ERAH. Thirty-nine consecutive patients were enrolled in this comparative study. Endothelial function after ORAH or ERAH was assessed by using the wire myograph system. The integrity of the RA endothelium was evaluated by immunohistochemical staining for erythroblast transformation specific-related gene. RESULTS: The vasodilation in response to acetylcholine was significantly higher in RA harvested with ORAH (P ≤ 0.001 versus ERAH). Endothelial integrity was not different between the 2 groups. CONCLUSIONS: ORAH is associated with a significantly higher endothelium-dependent vasodilation. Further investigation on the potential implications of these findings in terms of graft spasm and patency as well as clinical outcomes are needed
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
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