From Brain to Behavior: Hypertension's Modulation of Cognition and Affect

Accumulating evidence from animal models and human studies of essential hypertension suggest that brain regulation of the vasculature is impacted by the disease. Human neuroimaging findings suggest that the brain may be an early target of the disease. This observation reinforces earlier research suggesting that psychological factors may be one of the many contributory factors to the initiation of the disease. Alternatively or in addition, initial blood pressure increases may impact cognitive and/or affective function. Evidence for an impact of blood pressure on the perception and experience of affect is reviewed vis-a-vis brain imaging findings suggesting that such involvement in hypertensive individuals is likely

Perspectives on the Missiological Legacy of Martin Luther and the Protestant Reformation

Upon the occasion of the 500th anniversary Martin Luther’s publication of his 95 theses, this composite article brings together five perspectives on the missiological legacy of the reformer and the subsequent Protestant Reformation. The blend of voices makes clear that Luther and the subsequent Protestant Reformation do not have a simple missiological legacy but rather various legacies: theological, ecclesiological, political, and practical; some of which co-exist, and even collide, in the same ecclesiastical community. The scandalous legacy of a splintered and splintering church remains. Yet, demonstrations of mutual recognition, reciprocal respect, and genuine fellowship can be found in certain missiological circles

Prehypertensive blood pressures and regional cerebral blood flow independently relate to cognitive performance in midlife

Background High blood pressure is thought to contribute to dementia in late life, but our understanding of the relationship between individual differences in blood pressure ( BP ) and cognitive functioning is incomplete. In this study, cognitive performance in nonhypertensive midlife adults was examined as a function of resting BP and regional cerebral blood flow ( rCBF ) responses during cognitive testing. We hypothesized that BP would be negatively related to cognitive performance and that cognitive performance would also be related to rCBF responses within areas related to BP control. We explored whether deficits related to systolic BP might be explained by rCBF responses to mental challenge. Methods and Results Healthy midlife participants (n=227) received neuropsychological testing and performed cognitive tasks in a magnetic resonance imaging scanner. A pseudocontinuous arterial spin labeling sequence assessed rCBF in brain areas related to BP in prior studies. Systolic BP was negatively related to 4 of 5 neuropsychological factors (standardized β&gt;0.13): memory, working memory, executive function, and mental efficiency. The rCBF in 2 brain regions of interest was similarly related to memory, executive function, and working memory (standardized β&gt;0.17); however, rCBF responses did not explain the relationship between resting systolic BP and cognitive performance. Conclusions Relationships at midlife between prehypertensive levels of systolic BP and both cognitive and brain function were modest but suggested the possible value of midlife intervention. </jats:sec

Leadership in the British civil service: an interpretation

This article is essentially a polemic. The argument is that when politicians and officials now talk of ‘leadership’ in the British civil service they do not use that word in the way in which it was previously used. In the past leading civil servants, acting in partnership with ministers and within constitutional constraints, exercised leadership in the sense of setting example, inspiring confidence and encouraging loyalty. The loosening of traditional constitutional patterns, the marginalization of senior officials in the policy process and the emergence of business methods as the preferred model for public ­administration have led to a political and administrative environment in which leadership in the British civil service is now about encouraging patterns of behaviour which fit in with these changes. Leadership skills are now about ‘delivery’; they are not about motivation. It is time for politicians, officials and scholars to be open about this

OTS 1809+314 and the Gamma-Ray Burst GB 790325b

We present deep CCD images of the field containing the recurring Optical Transient Source (OTS) 1809+314 recently discovered on the archival plates of the Sonneberg Observatory. At the position of OTS 1809+314 we find no optical counterpart brighter tha V=24.0 24.5, rgunn = 22.0-22.5 and I = 22.0 22.5, and I = 22.0-22.5. In the zero proper motion limit our observations place severe constraints on possible quiescent counterparts. There is no compelling evidence to suggest an association between the historical optical transient source and the gamma-ray burst GB 790325b located ~ 5\u27 to the east of OTS 1809+314

PrkA controls peptidoglycan biosynthesisthrough the essential phosphorylation ofReoM

Peptidoglycan (PG) is the main component of bacterial cell walls and the target formany antibiotics. PG biosynthesis is tightly coordinated with cell wall growth and turnover, andmany of these control activities depend upon PASTA-domain containing eukaryotic-like serine/threonine protein kinases (PASTA-eSTK) that sense PG fragments. However, only a few PGbiosynthetic enzymes are direct kinase substrates. Here, we identify the conserved ReoM proteinas a novel PASTA-eSTK substrate in the Gram-positive pathogenListeria monocytogenes. Our datashow that the phosphorylation of ReoM is essential as it controls ClpCP-dependent proteolyticdegradation of the essential enzyme MurA, which catalyses the first committed step in PGbiosynthesis. We also identify ReoY as a second novel factor required for degradation of ClpCPsubstrates. Collectively, our data imply that the first committed step of PG biosynthesis is activatedthrough control of ClpCP protease activity in response to signals of PG homeostasis imbalance.Peer Reviewe

Nitrogen activation in a Mars-van Krevelen mechanism for ammonia synthesis on Co3Mo3N

Co3Mo3N is one of the most active catalysts for ammonia synthesis; however, little is known about the atomistic details of N2 adsorption and activation. Here we examine whether N2 can adsorb and activate at nitrogen surface vacancies. We have identified the most favorable sites for surface nitrogen vacancy formation and have calculated vacancy formation free energies (and concentrations) taking into account vacancy configurational entropy and the entropy of N2 at temperature and pressure conditions relevant to ammonia synthesis (380–550 °C, 100 atm) via a semiempirical approach. We show that 3-fold hollow bound nitrogen-containing (111)-surfaces have surprisingly high concentrations (1.6 × 1016 to 3.7 × 1016 cm–2) of nitrogen vacancies in the temperature range for ammonia synthesis. It is shown that these vacancy sites can adsorb and activate N2 demonstrating the potential of a Mars–van Krevelen type mechanism on Co3Mo3N. The catalytically active surface is one where 3f-hollow-nitrogens are bound to the molybdenum framework with a hexagonal array of embedded Co8 cobalt nanoclusters. We find that the vacancy-formation energy (VFE) combined with the adsorption energy can be used as a descriptor in the screening of materials that activate doubly and triply bonded molecules that are bound end-on at surface vacancies

A Brain Phenotype for Stressor‐Evoked Blood Pressure Reactivity

Background Individuals who exhibit large‐magnitude blood pressure (BP) reactions to acute psychological stressors are at risk for hypertension and premature death by cardiovascular disease. This study tested whether a multivariate pattern of stressor‐evoked brain activity could reliably predict individual differences in BP reactivity, providing novel evidence for a candidate neurophysiological source of stress‐related cardiovascular risk. Methods and Results Community‐dwelling adults (N=310; 30–51 years; 153 women) underwent functional magnetic resonance imaging with concurrent BP monitoring while completing a standardized battery of stressor tasks. Across individuals, the battery evoked an increase systolic and diastolic BP relative to a nonstressor baseline period (M ∆systolic BP/∆diastolic BP=4.3/1.9 mm Hg [95% confidence interval=3.7–5.0/1.4–2.3 mm Hg]). Using cross‐validation and machine learning approaches, including dimensionality reduction and linear shrinkage models, a multivariate pattern of stressor‐evoked functional magnetic resonance imaging activity was identified in a training subsample (N=206). This multivariate pattern reliably predicted both systolic BP (r=0.32; P<0.005) and diastolic BP (r=0.25; P<0.01) reactivity in an independent subsample used for testing and replication (N=104). Brain areas encompassed by the pattern that were strongly predictive included those implicated in psychological stressor processing and cardiovascular responding through autonomic pathways, including the medial prefrontal cortex, anterior cingulate cortex, and insula. Conclusions A novel multivariate pattern of stressor‐evoked brain activity may comprise a phenotype that partly accounts for individual differences in BP reactivity, a stress‐related cardiovascular risk factor

Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension

BACKGROUND: Inflammation is a feature of pulmonary arterial hypertension (PAH), and increased circulating levels of cytokines are reported in patients with PAH. However, to date, no information exists on the significance of elevated cytokines or their potential as biomarkers. We sought to determine the levels of a range of cytokines in PAH and to examine their impact on survival and relationship to hemodynamic indexes. METHODS AND RESULTS: We measured levels of serum cytokines (tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta, -2, -4, -5, -6, -8, -10, -12p70, and -13) using ELISAs in idiopathic and heritable PAH patients (n=60). Concurrent clinical data included hemodynamics, 6-minute walk distance, and survival time from sampling to death or transplantation. Healthy volunteers served as control subjects (n=21). PAH patients had significantly higher levels of interleukin-1beta, -2, -4, -6, -8, -10, and -12p70 and tumor necrosis factor-alpha compared with healthy control subjects. Kaplan-Meier analysis showed that levels of interleukin-6, 8, 10, and 12p70 predicted survival in patients. For example, 5-year survival with interleukin-6 levels of >9 pg/mL was 30% compared with 63% for patients with levels < or = 9 pg/mL (P=0.008). In this PAH cohort, cytokine levels were superior to traditional markers of prognosis such as 6-minute walk distance and hemodynamics. CONCLUSIONS: This study illustrates dysregulation of a broad range of inflammatory mediators in idiopathic and familial PAH and demonstrates that cytokine levels have a previously unrecognized impact on patient survival. They may prove to be useful biomarkers and provide insight into the contribution of inflammation in PAH