HID-1 controls formation of large dense core vesicles by influencing cargo sorting and trans-Golgi network acidification

Large dense core vesicles (LDCVs) mediate the regulated release of neuropeptides and peptide hormones. They form at the trans-Golgi network (TGN), where their soluble content aggregates to form a dense core, but the mechanisms controlling biogenesis are still not completely understood. Recent studies have implicated the peripheral membrane protein HID-1 in neuropeptide sorting and insulin secretion. Using CRISPR/Cas9, we generated HID-1 KO rat neuroendocrine cells, and we show that the absence of HID-1 results in specific defects in peptide hormone and monoamine storage and regulated secretion. Loss of HID-1 causes a reduction in the number of LDCVs and affects their morphology and biochemical properties, due to impaired cargo sorting and dense core formation. HID-1 KO cells also exhibit defects in TGN acidification together with mislocalization of the Golgi-enriched vacuolar H+-ATPase subunit isoform a2. We propose that HID-1 influences early steps in LDCV formation by controlling dense core formation at the TGN.</jats:p

Large-area scanning probe nanolithography facilitated by automated alignment of probe arrays

A method for the automated alignment of scanning probe polymer pen arrays is reported. This system enables nanolithography over large (cm2) areas with high uniformity, with any misalignment being ≤0.0003°.</p

Aircraft and avionic related research required to develop an effective high-speed runway exit system

Research was conducted to increase airport capacity by studying the feasibility of the longitudinal separation between aircraft sequences on final approach. The multidisciplinary factors which include the utility of high speed exits for efficient runway operations were described along with recommendations and highlights of these studies

Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice

Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ−/−) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ−/− male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging

The barium isotopic fractions in five metal-poor stars

We provide measurements of the Ba isotopic fractions for five metal-poor stars derived with an LTE analysis using 1D model stellar atmospheres. We use high resolution (R\equiv{\lambda}/\Delta{\lambda}=90000-95000), very high signal-to-noise (S/N>500) spectra to determine the fraction of odd Ba isotopes (fodd) by measuring subtle asymmetries in the profile of the Ba ii line at 4554 {\AA}. We also use two different macroturbulent broadening techniques, Gaussian and radial-tangential, to model the Fe lines of each star, and propagate each technique to model macroturbulent broadening in the Ba 4554 {\AA} line. We conduct a 1D non-LTE (NLTE) treatment of the Fe lines in the red giant HD122563 and the subgiant HD140283 in an attempt to improve the fitting. We determine [Ba/Eu] ratios for the two giants in our study, HD122563 and HD88609, which can also be used to determine the relative contribution of the s- and r-processes to heavy-element nucleosynthesis, for comparison with fodd. We find fodd for HD122563, HD88609 and HD84937, BD+26\circ3578 and BD-04\circ3208 to be -0.12\pm0.07, -0.02\pm0.09, and -0.05\pm0.11, 0.08\pm0.08 and 0.18\pm0.08 respectively. This means that all stars examined here show isotopic fractions more compatible with an s-process dominated composition. The [Ba/Eu] ratios in HD122563 and HD88609 are found to be -0.20\pm0.15 and -0.47\pm0.15 respectively, which indicate instead an r-process signature. We report a better statistical fit to the majority of Fe profiles in each star when employing a radial-tangential broadening technique during our 1D LTE investigation. We have shown that, from a statistical point of view, one must consider using a radial-tangential broadening technique rather than a Gaussian one to model Fe line macroturbulences when working in 1D. No improvement to Fe line fitting is seen when employing a NLTE treatment.Comment: 12 pages, 4 figures, 6 tables. Accepted for publication in Astronomy & Astrophysic

Synuclein deficiency results in age-related respiratory and cardiovascular dysfunctions in mice

Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ−/−) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ−/− male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging

The CEOS Recovery Observatory Pilot

Over the course of the last decade, large populations living in vulnerable areas have led to record damages and substantial loss of life in mega-disasters ranging from the deadly Indian Ocean tsunami of 2004 and Haiti earthquake of 2010; the catastrophic flood damages of Hurricane Katrina in 2005 and the Tohoku tsunami of 2011, and the astonishing extent of the environmental impact of the Deepwater Horizon explosion in 2009. These major catastrophes have widespread and long-lasting impacts with subsequent recovery and reconstruction costing billions of euros and lasting years. While satellite imagery is used on an ad hoc basis after many disasters to support damage assessment, there is currently no standard practice or system to coordinate acquisition of data and facilitate access for early recovery planning and recovery tracking and monitoring. CEOS led the creation of a Recovery Observatory Oversight Team, which brings together major recovery stakeholders such as the UNDP and the World Bank/Global Facility for Disaster Reduction and Recovery, value-adding providers and leading space agencies. The principal aims of the Observatory are to: 1. Demonstrate the utility of a wide range of earth observation data to facilitate the recovery and reconstruction phase following a major catastrophic event; 2. Provide a concrete case to focus efforts in identifying and resolving technical and organizational obstacles to facilitating the visibility and access to a relevant set of EO data; and 3. Develop dialogue and establish institutional relationships with the Recovery phase user community to best target data and information requirements; The paper presented here will describe the work conducted in preparing for the triggering of a Recovery Observatory including support to rapid assessments and Post Disaster Needs Assessments by the EO community

Astrocytes modulate baroreflex sensitivity at the level of the nucleus of the solitary tract

Maintenance of cardiorespiratory homeostasis depends on autonomic reflexes controlled by neuronal circuits of the brainstem. The neurophysiology and neuroanatomy of these reflex pathways are well understood, however, the mechanisms and functional significance of autonomic circuit modulation by glial cells remain largely unknown. In experiments conducted in male laboratory rats we show that astrocytes of the nucleus tractus solitarii (NTS), the brain area that receives and integrates sensory information from the heart and blood vessels, respond to incoming afferent inputs with [Ca2+]i elevations. Astroglial [Ca2+]i responses are triggered by transmitters released by vagal afferents, glutamate acting at AMPA receptors and 5-HT acting at 5-HT2A receptors. In conscious freely behaving animals blockade of Ca2+-dependent vesicular mechanisms in NTS astrocytes by virally driven expression of a dominant-negative SNARE protein (dnSNARE) increased baroreflex sensitivity by 70% (p<0.001). The effect of compromised astroglial function was specific to the NTS as expression of dnSNARE in astrocytes of the ventrolateral brainstem had no effect. ATP considered the principle gliotransmitter and is released by vesicular mechanisms affected by dnSNARE expression. Consistent with this hypothesis, in anesthetized rats, activation P2Y1 purinoceptors in the NTS decreased baroreflex gain by 40% (p=0.031), while blockade of P2Y1 receptors increased baroreflex gain by 57% (p=0.018). These results suggest that glutamate and 5-HT released by NTS afferent terminals trigger Ca2+-dependent astroglial release of ATP to modulate baroreflex sensitivity via P2Y1 receptors. These data add to the growing body of evidence supporting an active role of astrocytes in the brain information processing

Brain metabolic sensing and metabolic signaling at the level of an astrocyte

Astrocytes support neuronal function by providing essential structural and nutritional support, neurotransmitter trafficking and recycling and may also contribute to brain information processing. In this article we review published results and report new data suggesting that astrocytes function as versatile metabolic sensors of central nervous system (CNS) milieu and play an important role in the maintenance of brain metabolic homeostasis. We discuss anatomical and functional features of astrocytes that allow them to detect and respond to changes in the brain parenchymal levels of metabolic substrates (oxygen and glucose), and metabolic waste products (carbon dioxide). We report data suggesting that astrocytes are also sensitive to circulating endocrine signals-hormones like ghrelin, glucagon-like peptide-1 and leptin, that have a major impact on the CNS mechanisms controlling food intake and energy balance. We discuss signaling mechanisms that mediate communication between astrocytes and neurons and consider how these mechanisms are recruited by astrocytes activated in response to various metabolic challenges. We review experimental data suggesting that astrocytes modulate the activities of the respiratory and autonomic neuronal networks that ensure adaptive changes in breathing and sympathetic drive in order to support the physiological and behavioral demands of the organism in ever-changing environmental conditions. Finally, we discuss evidence suggesting that altered astroglial function may contribute to the pathogenesis of disparate neurological, respiratory and cardiovascular disorders such as Rett syndrome and systemic arterial hypertension