Proximate controls on semiarid soil greenhouse gas fluxes across 3 million years of soil development

Soils are important sources and sinks of three greenhouse gases (GHGs): carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O). However, it is unknown whether semiarid landscapes are important contributors to global fluxes of these gases, partly because our mechanistic understanding of soil GHG fluxes is largely derived from more humid ecosystems. We designed this study with the objective of identifying the important soil physical and biogeochemical controls on soil GHG fluxes in semiarid soils by observing seasonal changes in soil GHG fluxes across a three million year substrate age gradient in northern Arizona. We also manipulated soil nitrogen (N) and phosphorus availability with 7 years of fertilization and used regression tree analysis to identify drivers of unfertilized and fertilized soil GHG fluxes. Similar to humid ecosystems, soil N2O flux was correlated with changes in N and water availability and soil CO2 efflux was correlated with changes in water availability and temperature. Soil CH4 uptake was greatest in relatively colder and wetter soils. While fertilization had few direct effects on soil CH4 flux, soil nitrate was an important predictor of soil CH4 uptake in unfertilized soils and soil ammonium was an important predictor of soil CH4 uptake in fertilized soil. Like in humid ecosystems, N gas loss via nitrification or denitrification appears to increase with increases in N and water availability during ecosystem development. Our results suggest that, with some exceptions, the drivers of soil GHG fluxes in semiarid ecosystems are often similar to those observed in more humid ecosystems

Deep Brain Stimulation Improves Symptoms of Spasmodic Dysphonia Through Targeting of Thalamic Sensorimotor Connectivity.

BACKGROUND AND OBJECTIVES: Spasmodic dysphonia is a dystonia of the vocal chords producing difficulty with speech. Current hypotheses are that this is a condition of dysregulated thalamic sensory motor integration. A recent randomized controlled trial of thalamic deep brain stimulation (DBS) demonstrated its safety and efficacy. Our objective was to determine whether the outcome could be predicted by stimulation of thalamic sensorimotor areas and adjacent white matter connectivity as assessed by diffusion tractography. METHODS: A cohort of 6 participants undergoing thalamic DBS for adductor spasmodic dysphonia was studied. Electrodes were localized with the Lead-DBS toolbox. Group-based analyses were performed with atlases, coordinates, and using voxel-based symptom mapping. Diffusion tensor imaging (3 T, 64 directions, 2-mm isotropic) was used to perform individual probabilistic tractography (cerebellothalamic tract and pallidothalamic tract) and segmentation of the thalamus. Monopolar review was performed at 0.5 V and binarised as effective or ineffective. RESULTS: Effective contacts stimulated more of thalamic sensorimotor areas than ineffective contacts (P < .05, false discovery rate corrected). This effect was consistent across analytical and statistical techniques. Group-level and tractography analyses did not identify a specific "sweet spot" suggesting the benefit of DBS is derived from modulating individual thalamic sensorimotor areas. Stimulations at 1 year involved predicted thalamic sensorimotor regions with additional cerebellothalamic tract involvement. CONCLUSION: Stimulation of thalamic sensorimotor areas was associated with improvement in symptoms of spasmodic dysphonia. These data are consistent with DBS acting on pathophysiologically dysregulated thalamic sensorimotor integration in spasmodic dysphonia

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

Leadership and decision-making practices in public versus private universities in Pakistan

The goal of this study is to examine differences in leadership and decision-making practices in public and private universities in Pakistan, with a focus on transformational leadership (TL) and participative decision-making (PDM). We conducted semi-structured interviews with 46 deans and heads of department from two public and two private universities in Pakistan. Our findings indicate that leadership and decision-making practices are different in public and private universities. While differences were observed in all six types of TL-behaviour, the following three approaches emerged to be crucial in both public and private universities: (1) articulating a vision, (2) fostering the acceptance of group goals, and (3) high-performance expectations. In terms of PDM, deans and heads of department in public and private universities adopt a collaborative approach. However, on a practical level this approach is limited to teacher- and student-related matters. Overall, our findings suggest that the leadership and decision-making practices in Pakistani public and private universities are transformational and participative in nature

Criminal and Noncriminal Psychopathy: The Devil is in the Detail

Brooks, NS ORCiD: 0000-0003-1784-099XPsychopathy is prevalent and problematic in criminal populations, but is also found to be present in noncriminal populations. In 1992, Robert Hare declared that psychopaths may also “be found in the boardroom”, which has since been followed by an interest in the issue of noncriminal, or even successful, psychopathy. In this chapter, the paradox of criminal and noncriminal psychopathy is discussed with specific attention given to the similarities and differences that account for psychopathic personality across contexts. That psychopathy is a condition typified by a constellation of traits and behaviours requires wider research across diverse populations, and thus the streams of research related to criminal and noncriminal psychopathy are presented and the implications of these contrasting streams are explored

Immunization with Cocktail of HIV-Derived Peptides in Montanide ISA-51 Is Immunogenic, but Causes Sterile Abscesses and Unacceptable Reactogenicity

BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). METHODS: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51)Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. RESULTS: 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. CONCLUSIONS: The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000886

Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

<div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div

Characterization of the effects of cross-linking of macrophage CD44 associated with increased phagocytosis of apoptotic PMN

Control of macrophage capacity for apoptotic cell clearance by soluble mediators such as cytokines, prostaglandins and lipoxins, serum proteins, and glucocorticoids may critically determine the rate at which inflammation resolves. Previous studies suggested that macrophage capacity for clearance of apoptotic neutrophils was profoundly altered following binding of CD44 antibodies. We have used a number of different approaches to further define the mechanism by which CD44 rapidly and specifically augment phagocytosis of apoptotic neutrophils. Use of Fab ’ fragments unequivocally demonstrated a requirement for cross-linking of macrophage surface CD44. The molecular mechanism of CD44-augmented phagocytosis was shown to be opsonin-independent and to be distinct from the Mer/protein S pathway induced by glucocorticoids and was not functional for clearance of apoptotic eosinophils. CD44-cross-linking also altered macrophage migration and induced cytoskeletal re-organisation together with phosphorylation of paxillin and activation of Rac2. Investigation of signal transduction pathways that might be critical for CD44 augmentation of phagocytosis revealed that Ca 2+ signalling, PI-3 kinase pathways and altered cAMP signalling were not involved, but did implicate a key role for tyrosine phosphorylation events. Finally, although CD44 antibodies were able to augment phagocytosis of apoptotic neutrophils by murine peritoneal and bone marrow-derived macrophages, we did not observe a difference in the clearance of neutrophils following induction of peritonitis with thioglycollate in CD44-deficient animals. Together, these data demonstrate that CD4

The determinants of stroke phenotypes were different from the predictors (CHADS2 and CHA2DS2-VASc) of stroke in patients with atrial fibrillation: a comprehensive approach

<p>Abstract</p> <p>Background</p> <p>Atrial fibrillation (AF) is a leading cause of fatal ischemic stroke. It was recently reported that international normalized ratio (INR) levels were associated with infarct volumes. However, factors other than INR levels that affect stroke phenotypes are largely unknown. Therefore, we evaluated the determinants of stroke phenotypes (pattern and volume) among patients with AF who were not adequately anticoagulated.</p> <p>Methods</p> <p>We analyzed data pertaining to consecutive AF patients admitted over a 6-year period with acute MCA territory infarcts. We divided the patients according to DWI (diffusion-weighted imaging) lesion volumes and patterns, and the relationship between stroke predictors (the CHADS₂and CHA₂DS₂-VASc score), systemic, and local factors and each stroke phenotype were then evaluated.</p> <p>Results</p> <p>The stroke phenotypes varied among 231 patients (admission INR median 1.06, interquartile range (IQR) 1.00-1.14). Specifically, (1) the DWI lesion volumes ranged from 0.04-338.62 ml (median 11.86 ml; IQR, 3.07-44.20 ml) and (2) 46 patients had a territorial infarct pattern, 118 had a lobar/deep pattern and 67 had a small scattered pattern. Multivariate testing revealed that the CHADS₂and CHA₂DS₂-VASc score were not related to either stroke phenotype. Additionally, the prior use of antiplatelet agents was not related to the stroke phenotypes. Congestive heart failure and diastolic dysfunction were not associated with stroke phenotypes.</p> <p>Conclusions</p> <p>The results of this study indicated that the determinants of stroke phenotypes were different from the predictors (i.e., CHADS2 and CHA₂DS₂-VASc score) of stroke in patients with AF.</p