Membrane Protein Biogenesis in Ffh- or FtsY-Depleted Escherichia coli

BACKGROUND: The Escherichia coli version of the mammalian signal recognition particle (SRP) system is required for biogenesis of membrane proteins and contains two essential proteins: the SRP subunit Ffh and the SRP-receptor FtsY. Scattered in vivo studies have raised the possibility that expression of membrane proteins is inhibited in cells depleted of FtsY, whereas Ffh-depletion only affects their assembly. These differential results are surprising in light of the proposed model that FtsY and Ffh play a role in the same pathway of ribosome targeting to the membrane. Therefore, we decided to evaluate these unexpected results systematically. METHODOLOGY/PRINCIPAL FINDINGS: We characterized the following aspects of membrane protein biogenesis under conditions of either FtsY- or Ffh-depletion: (i) Protein expression, stability and localization; (ii) mRNA levels; (iii) folding and activity. With FtsY, we show that it is specifically required for expression of membrane proteins. Since no changes in mRNA levels or membrane protein stability were detected in cells depleted of FtsY, we propose that its depletion may lead to specific inhibition of translation of membrane proteins. Surprisingly, although FtsY and Ffh function in the same pathway, depletion of Ffh did not affect membrane protein expression or localization. CONCLUSIONS: Our results suggest that indeed, while FtsY-depletion affects earlier steps in the pathway (possibly translation), Ffh-depletion disrupts membrane protein biogenesis later during the targeting pathway by preventing their functional assembly in the membrane

Behavior adaptation for mobile robots via semantic map compositions of constraint-based controllers

Specifying and solving Constraint-based Optimization Problems (COP) has become a mainstream technology for advanced motion control of mobile robots. COP programming still requires expert knowledge to transform specific application context into the right configuration of the COP parameters (i.e., objective functions and constraints). The research contribution of this paper is a methodology to couple the context knowledge of application developers to the robot knowledge of control engineers, which, to our knowledge, has not yet been carried out. The former is offered a selected set of symbolic descriptions of the robots’ capabilities (its so-called “behavior semantics”) that are translated in control actions via “templates” in a “semantic map”; the latter contains the parameters that cover contextual dependencies in an application and robot vendor-independent way. The translation from semantics to control templates takes place in an “interaction layer” that contains 1) generic knowledge about robot motion capabilities (e.g., depending on the kinematic type of the robots), 2) spatial queries to extract relevant COP parameters from a semantic map (e.g., what is the impact of entering different types of “collision areas”), and 3) generic application knowledge (e.g., how the robots’ behavior is impacted by priorities, emergency, safety, and prudence). This particular design of, and interplay between, the application, interaction, and control layers provides a structured, conceptually simple approach to advance the complexity of mobile robot applications. Eventually, industry-wide cooperation between representatives of the application and control communities should result in an interaction layer with different standardized versions of semantic complexity.</p

Alterations in amygdala-prefrontal functional connectivity account for excessive worry and autonomic dysregulation in generalized anxiety disorder

Background: Generalized anxiety disorder (GAD) is characterized by the core symptom of uncontrollable worry. Functional magnetic resonance imaging studies link this symptom to aberrant functional connectivity between the amygdala and prefrontal cortex. Patients with GAD also display a characteristic pattern of autonomic dysregulation. Although frontolimbic circuitry is implicated in the regulation of autonomic arousal, no previous study to our knowledge combined functional magnetic resonance imaging with peripheral physiologic monitoring in these patients to test the hypothesis that core symptoms of worry and autonomic dysregulation in GAD arise from a shared underlying neural mechanism. Methods: We used resting-state functional magnetic resonance imaging and the measurement of parasympathetic autonomic function (heart rate variability) in 19 patients with GAD and 21 control subjects to define neural correlates of autonomic and cognitive responses before and after induction of perseverative cognition. Seed-based analyses were conducted to quantify brain changes in functional connectivity with the right and left amygdala. Results: Before induction, patients showed relatively lower connectivity between the right amygdala and right superior frontal gyrus, right paracingulate/anterior cingulate cortex, and right supramarginal gyrus than control subjects. After induction, such connectivity patterns increased in patients with GAD and decreased in control subjects, and these changes tracked increases in state perseverative cognition. Moreover, decreases in functional connectivity between the left amygdala and subgenual cingulate cortex and between the right amygdala and caudate nucleus predicted the magnitude of reduction in heart rate variability after induction. Conclusions: Our results link functional brain mechanisms underlying worry and rumination to autonomic dyscontrol, highlighting overlapping neural substrates associated with cognitive and autonomic responses to the induction of perseverative cognitions in patients with GAD

Behavior adaptation for mobile robots via semantic map compositions of constraint-based controllers

Specifying and solving Constraint-based Optimization Problems (COP) has become a mainstream technology for advanced motion control of mobile robots. COP programming still requires expert knowledge to transform specific application context into the right configuration of the COP parameters (i.e., objective functions and constraints). The research contribution of this paper is a methodology to couple the context knowledge of application developers to the robot knowledge of control engineers, which, to our knowledge, has not yet been carried out. The former is offered a selected set of symbolic descriptions of the robots’ capabilities (its so-called “behavior semantics”) that are translated in control actions via “templates” in a “semantic map”; the latter contains the parameters that cover contextual dependencies in an application and robot vendor-independent way. The translation from semantics to control templates takes place in an “interaction layer” that contains 1) generic knowledge about robot motion capabilities (e.g., depending on the kinematic type of the robots), 2) spatial queries to extract relevant COP parameters from a semantic map (e.g., what is the impact of entering different types of “collision areas”), and 3) generic application knowledge (e.g., how the robots’ behavior is impacted by priorities, emergency, safety, and prudence). This particular design of, and interplay between, the application, interaction, and control layers provides a structured, conceptually simple approach to advance the complexity of mobile robot applications. Eventually, industry-wide cooperation between representatives of the application and control communities should result in an interaction layer with different standardized versions of semantic complexity

Northern Eurasia Future Initiative (NEFI): facing the challenges and pathways of global change in the twenty-first century

During the past several decades, the Earth system has changed significantly, especially across Northern Eurasia. Changes in the socio-economic conditions of the larger countries in the region have also resulted in a variety of regional environmental changes that can have global consequences. The Northern Eurasia Future Initiative (NEFI) has been designed as an essential continuation of the Northern Eurasia Earth Science Partnership Initiative (NEESPI), which was launched in 2004. NEESPI sought to elucidate all aspects of ongoing environmental change, to inform societies and, thus, to better prepare societies for future developments. A key principle of NEFI is that these developments must now be secured through science-based strategies co-designed with regional decision-makers to lead their societies to prosperity in the face of environmental and institutional challenges. NEESPI scientific research, data, and models have created a solid knowledge base to support the NEFI program. This paper presents the NEFI research vision consensus based on that knowledge. It provides the reader with samples of recent accomplishments in regional studies and formulates new NEFI science questions. To address these questions, nine research foci are identified and their selections are briefly justified. These foci include warming of the Arctic; changing frequency, pattern, and intensity of extreme and inclement environmental conditions; retreat of the cryosphere; changes in terrestrial water cycles; changes in the biosphere; pressures on land use; changes in infrastructure; societal actions in response to environmental change; and quantification of Northern Eurasia’s role in the global Earth system. Powerful feedbacks between the Earth and human systems in Northern Eurasia (e.g., mega-fires, droughts, depletion of the cryosphere essential for water supply, retreat of sea ice) result from past and current human activities (e.g., large-scale water withdrawals, land use, and governance change) and potentially restrict or provide new opportunities for future human activities. Therefore, we propose that integrated assessment models are needed as the final stage of global change assessment. The overarching goal of this NEFI modeling effort will enable evaluation of economic decisions in response to changing environmental conditions and justification of mitigation and adaptation efforts

The endothelial cell markers von Willebrand Factor (vWF), CD31 and CD34 are lost in glomerulonephritis and no longer correlate with the morphological indices of glomerular sclerosis, interstitial fibrosis, activity and chronicity.

Endothelial cells (ECs) are active participants of an inflammatory process in glomeruli. EC damage has been shown to play an important role in the progression of glomerulonephritis (GN). The degree of glomerular and peritubular capillary loss in models of progressive renal disease correlates with the severity of glomerulosclerosis and interstitial fibrosis. The aim of our study was to analyze the association of vWF, CD31 and CD34 immunoreactivity with the morphological indices of glomerular sclerosis, interstitial fibrosis, activity and chronicity in GN. A cross-sectional study of 22 patients with GN was conducted. Conventional stains (hematoxylin-eosin, periodic acid Schiff and Trichrome GĂśmĂśri stains) and immunohistochemistry (vWF, CD31 and CD34) were employed on kidney biopsies. Activity and chronicity of GN, as well as glomerular segmental sclerosis and interstitial fibrosis, were evaluated according to a scoring system initially used for lupus nephritis and antineutrophil-cytoplasmic-antibody-associated vasculitis. Immunohistochemistry was assessed using a semi-quantitative score. Statistical analysis was performed using EpiInfo 6.04. The mean patient age was 46.68+/-14.09; 14 patients were male, and eight were female. Performing Spearman's rank correlation test, no correlation was found between each marker and glomerular segmental sclerosis, interstitial fibrosis, activity and chronicity, which suggests a loss of these markers and microvasculature involvement

Multiwavelength Monitoring of the BL Lacertae Object PKS 2155-304 in May 1994. II. The IUE Campaign

PKS 2155-304, the brightest BL Lac object in the ultraviolet sky, was monitored with the IUE satellite at ~1 hour time-resolution for ten nearly uninterrupted days in May 1994. The campaign, which was coordinated with EUVE, ROSAT, and ASCA monitoring, along with optical and radio observations from the ground, yielded the largest set of spectra and the richest short time scale variability information ever gathered for a blazar at UV wavelengths. The source flared dramatically during the first day, with an increase by a factor ~2.2 in an hour and a half. In subsequent days, the flux maintained a nearly constant level for ~5 days, then flared with ~35% amplitude for two days. The same variability was seen in both short- and long-wavelength IUE light curves, with zero formal lag (~<2 hr), except during the rapid initial flare, when the variations were not resolved. Spectral index variations were small and not clearly correlated with flux. The flux variability observed in the present monitoring is so rapid that for the first time, based on the UV emission alone, the traditional Delta L/Delta t limit indicating relativistic beaming is exceeded. The most rapid variations, under the likely assumption of synchrotron radiation, lead to a lower limit of 1 G on the magnetic field strength in the UV emitting region. These results are compared with earlier intensive monitoring of PKS 2155-304 with IUE in November 1991, when the UV flux variations had completely different characteristics.Comment: 45 pages, Latex, 11 PostScript figures, to appear in The Astrophysical Journa