Nitric oxide released from luminal s-nitroso-n-acetylcysteine increases gastric mucosal blood flow

Nitric oxide (NO)-mediated vasodilation plays a key role in gastric mucosal defense, and NO-donor drugs may protect against diseases associated with gastric mucosal blood flow (GMBF) deficiencies. In this study, we used the ex vivo gastric chamber method and Laser Doppler Flowmetry to characterize the effects of luminal aqueous NO-donor drug S-nitroso-N-acetylcysteine (SNAC) solution administration compared to aqueous NaNO2 and NaNO3 solutions (pH 7.4) on GMBF in Sprague-Dawley rats. SNAC solutions (600 μM and 12 mM) led to a rapid threefold increase in GMBF, which was maintained during the incubation of the solutions with the gastric mucosa, while NaNO2 or NaNO3 solutions (12 mM) did not affect GMBF. SNAC solutions (600 μM and 12 mM) spontaneously released NO at 37 °C at a constant rate of 0.3 or 14 nmol·mL-1·min-1, respectively, while NaNO2 (12 mM) released NO at a rate of 0.06 nmol·mL-1·min-1 and NaNO3 (12 mM) did not release NO. These results suggest that the SNAC-induced GMBF increase is due to their higher rates of spontaneous NO release compared to equimolar NaNO2 solutions. Taken together, our data indicate that oral SNAC administration is a potential approach for gastric acid-peptic disorder prevention and treatment.Nitric oxide (NO)-mediated vasodilation plays a key role in gastric mucosal defense, and NO-donor drugs may protect against diseases associated with gastric mucosal blood flow (GMBF) deficiencies. In this study, we used the ex vivo gastric chamber method and Laser Doppler Flowmetry to characterize the effects of luminal aqueous NO-donor drug S-nitroso-N-acetylcysteine (SNAC) solution administration compared to aqueous NaNO2 and NaNO3 solutions (pH 7.4) on GMBF in Sprague-Dawley rats. SNAC solutions (600 μM and 12 mM) led to a rapid threefold increase in GMBF, which was maintained during the incubation of the solutions with the gastric mucosa, while NaNO2 or NaNO3 solutions (12 mM) did not affect GMBF. SNAC solutions (600 μM and 12 mM) spontaneously released NO at 37 °C at a constant rate of 0.3 or 14 nmol·mL-1·min-1, respectively, while NaNO2 (12 mM) released NO at a rate of 0.06 nmol·mL-1·min-1 and NaNO3 (12 mM) did not release NO. These results suggest that the SNAC-induced GMBF increase is due to their higher rates of spontaneous NO release compared to equimolar NaNO2 solutions. Taken together, our data indicate that oral SNAC administration is a potential approach for gastric acid-peptic disorder prevention and treatment2034109412

Strings at the bottom of the deformed conifold

We present solutions of the equations of motion of macroscopic F and D strings extending along the non compact 4D sections of the conifold geometry and winding around the internal directions. The effect of the Goldstone modes associated with the position of the strings on the internal manifold can be seen as a current on the string that prevents it from collapsing and allows the possibility of static 4D loops. Its relevance in recent models of brane inflation is discussed.Comment: 9+1 page

Biphasic in vitro maturation with C-type natriuretic peptide enhances the developmental competence of juvenile-goat oocytes

In vitro embryo production success in juvenile animals is compromised due to their intrinsic lower oocyte quality. Conventional in vitro maturation (IVM) impairs oocyte competence by inducing spontaneous meiotic resumption. A series of experiments were performed to determine if maintaining meiotic arrest during a pre-maturation culture phase (pre-IVM) prior to conventional IVM improves oocyte competence of juvenile-goat (2 months old) cumulusoocyte complexes (COCs). In experiment 1, COCs were cultured with C-type natriuretic peptide (CNP; 0, 50, 100, 200 nM) for 6 and 8 h. Nuclear stage was assessed, revealing no differences in the incidence of germinal vesicle (GV) breakdown. In experiment 2, the same CNP concentrations were assessed plus 10 nM estradiol, the known upstream agonist activating expression of NPR2, the exclusive receptor of CNP. CNP (200 nM) plus estradiol increased the rate of oocytes at GV stage at 6 h compared to control group (74.7% vs 28.3%; P<0.05) with predominantly condensed chromatin configuration. In experiment 3, relative mRNA quantification revealed NPR2 expression was down-regulated after pre-IVM (6 h). In experiment 4, analysis of transzonal projections indicated that pre-IVM maintained cumulus-oocyte communication after oocyte recovery. For experiments 5 and 6, biphasic IVM (6 h pre-IVM with CNP and estradiol, plus 24 h IVM) and control IVM (24 h) were compared. Biphasic IVM increased intra-oocyte glutathione and decreased ROS, up-regulated DNA-methyltransferase 1 and pentraxin 3 expression and led to an increase in rate of blastocyst development compared to control group (30.2% vs 17.2%; P<0.05). In conclusion, a biphasic IVM, including a pre-IVM with CNP, maintains oocyte meiotic arrest for 6 h and enhances the embryo developmental competence of oocytes from juvenile goats

A social life cycle assessment of vanadium redox flow and lithium-ion batteries for energy storage

Battery energy storage systems (BESS) are expected to fulfill a crucial role in the renewable energy systems of the future. Within current regulatory frameworks, assessing the sustainability as well as the social risks for BESS should be considered. In this research we conducted a social life cycle assessment (S-LCA) of two BESS: the vanadium redox flow battery (VRFB) and the lithium-ion battery (LIB). The S-LCA was conducted based on the guidelines set by UNEP/SETAC and using the PSILCA v.3 database. It was found that most social risks related to the life cycle of the batteries are associated with the raw material extraction stage, while sectors related to chemicals also entail considerable risks. Workers are the stakeholder group affected most. These results apply to supply chains located in both China and Germany, but risks were lower for similar supply chains in Germany. An LIB with a nickel manganese cobalt oxide cathode is associated with considerably larger risks compared to a LIB with lithium manganese oxide cathode. For a VRFB life cycle with an increased vanadium price, the social risks were higher than those of the VRFB supply chain with a regular vanadium price. Our paper shows that S-LCA through the PSILCA database can provide interesting insights into the potential social risks associated with a certain product's life cycle. Generalizations of the results are not recommended, and one should be careful with assessments for technologies that have not yet matured due to the cost sensitivity of the methodology.Horizon 2020(H2020)875637Industrial Ecolog

Towards a more resource-efficient solar future in the EU: an actor-centered approach

Material constraints may slow the pace of energy transition if the materials intensity of renewable energy technologies remains the same. Innovations in solar photovoltaics (PV) can contribute to achieving lower material demands. In this research, the actor-centered institutionalism framework, transitions literature and the science-policy interface framework are used to analyze how the involved actors perceive the transition towards more resource-efficiency in solar PV, what their preferences are, and how government should support this transition. Altogether, resource-efficiency is not sufficiently supported, while it is considered extremely important in the future of solar PV according to various involved actors. Traditional silicon-based solar panels are locked-in into the current policy landscape. Actors prioritizing resource-efficiency interact in a niche space, while actors involved in traditional silicon-based PV form the regime. Improved alignment between science and policy actors would help ease disagreements and prevent or benefit from path-dependency, thus, supporting resource-efficiency in solar PV.​​​​​​​Industrial Ecolog

Approaches to implement safe by design in early product design through combining risk assessment and Life Cycle Assessment

The Safe by Design (SbD) concept aims to ensure the production, use and disposal of materials and products safely. While there is a growing interest in the potential of SbD to support policy commitments, such as the EU Green Deal and the Circular Economy Action Plan in Europe, methodological approaches and practical guidelines on SbD are, however, largely missing. The combined use of Life Cycle Assessment (LCA) and Risk Assessment (RA) is considered suitable to operationalize SbD over the whole life-cycle of a product. Here, we explore the potential of the combined use of LCA and RA at Technological Readiness Level (TRL) 1–6. We perform a review of the literature presenting and/or developing approaches that combine LCA and RA at early stages of product design. We identify that basic early-on-evaluations of safety (e.g., apply lifecycle thinking to assess risk hotspots, avoid use of hazardous chemicals, minimize other environmental impacts from chemicals) are more common, while more complex assessments (e.g., ex-ante LCA, control banding, predictive (eco)toxicology) require specialized expertise. The application of these simplified approaches and guidelines aims to avoid some obvious sources of risks and impacts at early stages. Critical gaps need to be addressed for wider application of SbD, including more studies in the product design context, developing tools and databases containing collated information on risk, greater collaboration between RA/LCA researchers and companies, and policy discussion on the expansion from SbD to Safe and Sustainable by Design (SSbD).Horizon 2020(H2020)875637Industrial EcologyEnvironmental Biolog

Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions.

Glucose is vital for life, serving as both a source of energy and carbon building block for growth. When glucose is limiting, alternative nutrients must be harnessed. To identify mechanisms by which cells can tolerate complete loss of glucose, we performed nutrient-sensitized genome-wide genetic screens and a PRISM growth assay across 482 cancer cell lines. We report that catabolism of uridine from the medium enables the growth of cells in the complete absence of glucose. While previous studies have shown that uridine can be salvaged to support pyrimidine synthesis in the setting of mitochondrial oxidative phosphorylation deficiency &lt;sup&gt;1&lt;/sup&gt; , our work demonstrates that the ribose moiety of uridine or RNA can be salvaged to fulfil energy requirements via a pathway based on: (1) the phosphorylytic cleavage of uridine by uridine phosphorylase UPP1/UPP2 into uracil and ribose-1-phosphate (R1P), (2) the conversion of uridine-derived R1P into fructose-6-P and glyceraldehyde-3-P by the non-oxidative branch of the pentose phosphate pathway and (3) their glycolytic utilization to fuel ATP production, biosynthesis and gluconeogenesis. Capacity for glycolysis from uridine-derived ribose appears widespread, and we confirm its activity in cancer lineages, primary macrophages and mice in vivo. An interesting property of this pathway is that R1P enters downstream of the initial, highly regulated steps of glucose transport and upper glycolysis. We anticipate that 'uridine bypass' of upper glycolysis could be important in the context of disease and even exploited for therapeutic purposes

Features of heavy physics in the CMB power spectrum

The computation of the primordial power spectrum in multi-field inflation models requires us to correctly account for all relevant interactions between adiabatic and non-adiabatic modes around and after horizon crossing. One specific complication arises from derivative interactions induced by the curvilinear trajectory of the inflaton in a multi-dimensional field space. In this work we compute the power spectrum in general multi-field models and show that certain inflaton trajectories may lead to observationally significant imprints of `heavy' physics in the primordial power spectrum if the inflaton trajectory turns, that is, traverses a bend, sufficiently fast (without interrupting slow roll), even in cases where the normal modes have masses approaching the cutoff of our theory. We emphasise that turning is defined with respect to the geodesics of the sigma model metric, irrespective of whether this is canonical or non-trivial. The imprints generically take the form of damped superimposed oscillations on the power spectrum. In the particular case of two-field models, if one of the fields is sufficiently massive compared to the scale of inflation, we are able to compute an effective low energy theory for the adiabatic mode encapsulating certain relevant operators of the full multi-field dynamics. As expected, a particular characteristic of this effective theory is a modified speed of sound for the adiabatic mode which is a functional of the background inflaton trajectory and the turns traversed during inflation. Hence in addition, we expect non-Gaussian signatures directly related to the features imprinted in the power spectrum.Comment: 41 pages, 6 figures, references updated, minor modifications. Version to appear in JCAP. v4: Equations (4.28) and (4.30) and Figures 5 and 6 correcte

Pulse Oximetry as an Aid to Rule Out Pneumonia among Patients with a Lower Respiratory Tract Infection in Primary Care.

Guidelines recommend chest X-rays (CXRs) to diagnose pneumonia and guide antibiotic treatment. This study aimed to identify clinical predictors of pneumonia that are visible on a chest X-ray (CXR+) which could support ruling out pneumonia and avoiding unnecessary CXRs, including oxygen saturation. A secondary analysis was performed in a clinical trial that included patients with suspected pneumonia in Swiss primary care. CXRs were reviewed by two radiologists. We evaluated the association between clinical signs (heart rate &gt; 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, abnormal auscultation, and oxygen saturation &lt; 95%) and CXR+ using multivariate analysis. We also calculated the diagnostic performance of the associated clinical signs combined in a clinical decision rule (CDR), as well as a CDR derived from a large meta-analysis (at least one of the following: heart rate &gt; 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, or abnormal auscultation). Out of 469 patients from the initial trial, 107 had a CXR and were included in this study. Of these, 26 (24%) had a CXR+. We found that temperature and oxygen saturation were associated with CXR+. A CDR based on the presence of either temperature ≥ 37.8 °C and/or an oxygen saturation level &lt; 95% had a sensitivity of 69% and a negative likelihood ratio (LR-) of 0.45. The CDR from the meta-analysis had a sensitivity of 92% and an LR- of 0.37. The addition of saturation &lt; 95% to this CDR increased the sensitivity (96%) and decreased the LR- (0.21). In conclusion, this study suggests that pulse oximetry could be added to a simple CDR to decrease the probability of pneumonia to an acceptable level and avoid unnecessary CXRs

Biphasic in vitro maturation with C-type natriuretic peptide enhances the developmental competence of juvenile-goat oocytes

In vitro embryo production success in juvenile animals is compromised due to their intrinsic lower oocyte quality. Conventional in vitro maturation (IVM) impairs oocyte competence by inducing spontaneous meiotic resumption. A series of experiments were performed to determine if maintaining meiotic arrest during a pre-maturation culture phase (pre-IVM) prior to conventional IVM improves oocyte competence of juvenile-goat (2 months old) cumulus-oocyte complexes (COCs). In experiment 1, COCs were cultured with C-type natriuretic peptide (CNP; 0, 50, 100, 200 nM) for 6 and 8 h. Nuclear stage was assessed, revealing no differences in the incidence of germinal vesicle (GV) breakdown. In experiment 2, the same CNP concentrations were assessed plus 10 nM estradiol, the known upstream agonist activating expression of NPR2, the exclusive receptor of CNP. CNP (200 nM) plus estradiol increased the rate of oocytes at GV stage at 6 h compared to control group (74.7% vs 28.3%; P<0.05) with predominantly condensed chromatin configuration. In experiment 3, relative mRNA quantification revealed NPR2 expression was down-regulated after pre-IVM (6 h). In experiment 4, analysis of transzonal projections indicated that pre-IVM maintained cumulus-oocyte communication after oocyte recovery. For experiments 5 and 6, biphasic IVM (6 h pre-IVM with CNP and estradiol, plus 24 h IVM) and control IVM (24 h) were compared. Biphasic IVM increased intra-oocyte glutathione and decreased ROS, up-regulated DNA-methyltransferase 1 and pentraxin 3 expression and led to an increase in rate of blastocyst development compared to control group (30.2% vs 17.2%; P<0.05). In conclusion, a biphasic IVM, including a pre-IVM with CNP, maintains oocyte meiotic arrest for 6 h and enhances the embryo developmental competence of oocytes from juvenile goats.Sandra Soto-Heras, Irene Menéndez-Blanco, Maria-Gracia Catalá, Dolors Izquierdo, Jeremy G. Thompson, Maria-Teresa Parami