Una nueva forma de energía cuantificada: Presentación de la polémica Loyarte-Loedel

Sobre la base de trabajos de investigación en física realizados en La Plata entre los años 1926 y 1935, presentamos el análisis de un caso en que las contribuciones locales, contemporáneas a investigaciones realizadas en Alemania, desataron un debate científico entre Ramón Loyarte y Enrique Loedel Palumbo, dos de los primeros físicos latinoamericanos. Tratando de hallar explicación a ciertas líneas de emisión del átomo de Mercurio, Loyarte conjeturó la existencia de estados cuánticos de rotación atómica, justificados por la aparición de un “potencial con entidad física”, constante, en las medidas experimentales de los potenciales de frenado. Esta hipótesis fue publicada en una prestigiosa revista alemana de la época, y dio origen a otros trabajos, extrapolando la cuantificación rotatoria a los átomos de mercurio ionizado, talio, y potasio. Fue el joven físico Loedel Palumbo quien refutó, mediante un exhaustivo estudio, la propuesta de Loyarte.Based on research in physics made in La Plata between years1926 and 1935, we present the analysis of a case in which local contributions, contemporary to researches in Germany, sparked a scientific debate between Ramón Loyarte and Enrique Loedel Palumbo, two of the first American physicists. Trying to find some explanation for the mercury atom emission lines, Loyarte conjectured the existence of quantum states of atomic rotation, justified by the appearance of a “constant potential with physical entity” in the experimental measurements of the potential breaking. This hypothesis was published in a prestigious German magazine, and gave rise to other papers, extrapolating the rotating quantification to atoms of ionized mercury, thallium, and potassium. It was the young physicist Loedel Palumbo who refuted, by an exhaustive study, Loyarte’s proposal.Fil: Von Reichenbach, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Andrini, Leandro Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentin

The structural features of the ligand-free moaA riboswitch and its ion-dependent folding

Riboswitches are structural elements of mRNA involved in the regulation of gene expression by responding to specific cellular metabolites. To fulfil their regulatory function, riboswitches prefold into an active state, the so-called binding competent form, that guarantees metabolite binding and allows a consecutive refolding of the RNA. Here, we describe the folding pathway to the binding competent form as well as the ligand free structure of the moaA riboswitch of E. coli. This RNA proposedly responds to the molybdenum cofactor (Moco), a highly oxygen-sensitive metabolite, essential in the carbon and sulfur cycles of eukaryotes. K+- and Mg2+-dependent footprinting assays and spectroscopic investigations show a high degree of structure formation of this RNA already at very low ion-concentrations. Mg2+ facilitates additionally a general compaction of the riboswitch towards its proposed active structure. We show that this fold agrees with the earlier suggested secondary structure which included also a long-range tetraloop/tetraloop-receptor like interaction. Metal ion cleavage assays revealed specific Mg2+-binding pockets within the moaA riboswitch. These Mg2+ binding pockets are good indicators for the potential Moco binding site, since in riboswitches, Mg2+ was shown to be necessary to bind phosphate-carrying metabolites. The importance of the phosphate and of other functional groups of Moco is highlighted by binding assays with tetrahydrobiopterin, the reduced and oxygen-sensitive core moiety of Moco. We demonstrate that the general molecular shape of pterin by its own is insufficient for the recognition by the riboswitch

An ephimeral acoustics laboratory at La Plata National University

Los años de la posguerra en Europa coincidieron con épocas de cambios en Argentina que, no obstante sus dificultades y fiel a su tradición de receptora de inmigrantes, dio refugio a numerosos científicos. Entre los físicos europeos que eligieron este destino para continuar su vida hubo muchos casos altamente beneficiosos para el país (Richard Gans, Guido Beck, Kurt Franz, Hans Schumacher, Livio Gratton, Manlio Abele y Gino Moretti), y también algunos que no respondieron a las expectativas puestas en ellos. Como el alemán Ronald Richter y otros de los que no se tiene tanto conocimiento, como el caso del polaco Estanislao Doliñski. En este trabajo abordaremos el estudio de la estadía de Doliñski en la ciudad de La Plata,remitiéndonos a fuentes documentales y testimoniales de sus contemporáneos en esta ciudad, donde viviódesde 1953 hasta 1960. El objetivo de este trabajo es analizar el contexto histórico e institucional del Departamento de Física de la Universidad Nacional de La Plataen ese lapso, para entender cuáles fueron las condiciones en que élfue recibido, qué contribuciones aportóa la universidad y cuáles fueron las circunstancias quecondujeron a terminar la relación laboral con la UNLP. Aunque su carrera profesional es mucho más amplia que la desarrollada en La Plata, daremos cuenta aquí de algunas de las actividades desarrolladas por Doliñski durante su estadía en el Departamentode Física.After IIWW, postwar years in Europe coincided with times of change in Argentina: in spite of its internal difficulties but still faithful to its tradition of receiving immigrants, the country gave refuge to many scientists. Among the European physicists who chose this destiny to continue their lives and work, many were highly beneficial for the country: Richard Gans, Guido Beck, Kurt Franz, Hans Schumacher, Livio Gratton, Manlio Abele and Gino Moretti. But some others did not fulfil the expectations placed on them, such as the German Ronald Richter, and others who are not as well known. This is the case of the Polish Estanislao Doliñski, who lived in La Plata city from 1953 to 1960 and was hired by the Department of Physics of the National University of La Plata. In this work we will study his stay in La Plata, basing our references on documentary and testimonial sources of contemporaries in the city. It is our purpose to analyze the historical and institutional context of the Department of Physics in that period, in order to understand the conditions in which he was received, what were his contributions to the University, and what were the circumstances that led him to terminate the employment relationship with the University. Although his professional career is much broader than that developed in La Plata, this report deals only about the activities carried out by Doliñski during his stay at the Department of Physics.Fil: Von Reichenbach, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentin

Differential Impact of Fluid Shear Stress and YAP/TAZ on BMP/TGF‐β Induced Osteogenic Target Genes

Bone is a remarkable dynamic structure, which integrates mechanical and biochemical signaling inputs. Interstitial fluid in the intramedullary space transmits signals derived from compression‐induced fluid shear stress (FSS) to stimulate osteoblasts for bone formation. Using a flow system and human osteoblasts, this study demonstrates how BMP/TGF‐β signaling integrates stimuli derived from FSS and YAP/TAZ and confirms these findings by transcriptome analyses. Here, FSS positively affects the phosphorylation of both SMAD1/5 and SMAD2/3, the respective BMP‐ and TGFβ‐R‐SMADs. Increase in phosphorylated SMAD1/5 levels affects distinct target genes, which are susceptible to low levels of phosphorylated SMADs (such as ID1–3) or dependent on high levels of phosphorylated SMAD1/5 (NOG, noggin). Thus, FSS lowers the threshold for genes dependent on high levels of phosphorylated SMAD1/5 when less BMP is available. While the impact of FSS on direct BMP target genes is independent of YAP/TAZ, FSS acts cooperatively with YAP/TAZ on TGF‐β target genes, which are shared by both pathways (such as CTGF). As mechanical stimuli are key in bone regeneration, their crosstalk to biochemical signaling pathways such as BMP and TGF‐β and YAP/TAZ acts on different levels, which allows now to think about new and more specified intervention strategies for age‐related bone loss

Atheroprone fluid shear stress-regulated ALK1-Endoglin-SMAD signaling originates from early endosomes

Background Fluid shear stress enhances endothelial SMAD1/5 signaling via the BMP9-bound ALK1 receptor complex supported by the co-receptor Endoglin. While moderate SMAD1/5 activation is required to maintain endothelial quiescence, excessive SMAD1/5 signaling promotes endothelial dysfunction. Increased BMP signaling participates in endothelial-to-mesenchymal transition and inflammation culminating in vascular diseases such as atherosclerosis. While the function of Endoglin has so far been described under picomolar concentrations of BMP9 and short-term shear application, we investigated Endoglin under physiological BMP9 and long-term pathophysiological shear conditions. Results We report here that knock-down of Endoglin leads to exacerbated SMAD1/5 phosphorylation and atheroprone gene expression profile in HUVECs sheared for 24 h. Making use of the ligand-trap ALK1-Fc, we furthermore show that this increase is dependent on BMP9/10. Mechanistically, we reveal that long-term exposure of ECs to low laminar shear stress leads to enhanced Endoglin expression and endocytosis of Endoglin in Caveolin-1-positive early endosomes. In these endosomes, we could localize the ALK1-Endoglin complex, labeled BMP9 as well as SMAD1, highlighting Caveolin-1 vesicles as a SMAD signaling compartment in cells exposed to low atheroprone laminar shear stress. Conclusions We identified Endoglin to be essential in preventing excessive activation of SMAD1/5 under physiological flow conditions and Caveolin-1-positive early endosomes as a new flow-regulated signaling compartment for BMP9-ALK1-Endoglin signaling axis in atheroprone flow conditions

Transport demand evolution in Europe – factors of change, scenarios and challenges

In the transport sector, where change comes with inertia and investments are made with a long term perspective, decision makers need to consider how the future may look like in the very long term. The work presented in this paper is a scenario analysis focusing on the evolution of transport demand towards 2050, aiming to identify related challenges for European industrial and policy players. It follows up on the work of other recent attempts to study the future of transport from a European perspective, integrating findings from these studies, updating new trends and applying a specific scenario analysis methodology relying also on expert consultation. The diversity of the scenarios created unfolds aspects of the future transport system with rather different outcomes on issues like the volume of transport, travel motives, the prevalent spatial scales of transport and logistics, people’s preferences towards different transport attributes, the relevancy of the State versus the private initiative in transport production, the level of competition, or the relative importance of environment and resource scarcity in setting an agenda for innovation and regulations. Beyond the subsequent challenges and opportunities identified in this work, the scenarios developed may be a useful basis for individual actors of distinct backgrounds to build their own specific futures, supporting them in defining strategies for the future.JRC.J.1-Economics of Climate Change, Energy and Transpor

Intra-articular corticosteroid for knee osteoarthritis.

BACKGROUND Knee osteoarthritis is a leading cause of chronic pain, disability, and decreased quality of life. Despite the long-standing use of intra-articular corticosteroids, there is an ongoing debate about their benefits and safety. This is an update of a Cochrane review first published in 2005. OBJECTIVES To determine the benefits and harms of intra-articular corticosteroids compared with sham or no intervention in people with knee osteoarthritis in terms of pain, physical function, quality of life, and safety. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE (from inception to 3 February 2015), checked trial registers, conference proceedings, reference lists, and contacted authors. SELECTION CRITERIA We included randomised or quasi-randomised controlled trials that compared intra-articular corticosteroids with sham injection or no treatment in people with knee osteoarthritis. We applied no language restrictions. DATA COLLECTION AND ANALYSIS We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain, function, quality of life, joint space narrowing, and risk ratios (RRs) for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis. MAIN RESULTS We identified 27 trials (13 new studies) with 1767 participants in this update. We graded the quality of the evidence as 'low' for all outcomes because treatment effect estimates were inconsistent with great variation across trials, pooled estimates were imprecise and did not rule out relevant or irrelevant clinical effects, and because most trials had a high or unclear risk of bias. Intra-articular corticosteroids appeared to be more beneficial in pain reduction than control interventions (SMD -0.40, 95% CI -0.58 to -0.22), which corresponds to a difference in pain scores of 1.0 cm on a 10-cm visual analogue scale between corticosteroids and sham injection and translates into a number needed to treat for an additional beneficial outcome (NNTB) of 8 (95% CI 6 to 13). An I(2) statistic of 68% indicated considerable between-trial heterogeneity. A visual inspection of the funnel plot suggested some asymmetry (asymmetry coefficient -1.21, 95%CI -3.58 to 1.17). When stratifying results according to length of follow-up, benefits were moderate at 1 to 2 weeks after end of treatment (SMD -0.48, 95% CI -0.70 to -0.27), small to moderate at 4 to 6 weeks (SMD -0.41, 95% CI -0.61 to -0.21), small at 13 weeks (SMD -0.22, 95% CI -0.44 to 0.00), and no evidence of an effect at 26 weeks (SMD -0.07, 95% CI -0.25 to 0.11). An I(2) statistic of ≥ 63% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.001), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.43). There was evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.05) or at least 100 participants per group (P=0.013), in trials that used concomittant viscosupplementation (P=0.08), and in trials that used concomitant joint lavage (P≤0.001).Corticosteroids appeared to be more effective in function improvement than control interventions (SMD -0.33, 95% CI -0.56 to -0.09), which corresponds to a difference in functions scores of -0.7 units on standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10 and translates into a NNTB of 10 (95% CI 7 to 33). An I(2) statistic of 69% indicated a moderate to large degree of between-trial heterogeneity. A visual inspection of the funnel plot suggested asymmetry (asymmetry coefficient -4.07, 95% CI -8.08 to -0.05). When stratifying results according to length of follow-up, benefits were small to moderate at 1 to 2 weeks after end of treatment (SMD -0.43, 95% CI -0.72 to -0.14), small to moderate at 4 to 6 weeks (SMD -0.36, 95% CI -0.63 to -0.09), and no evidence of an effect at 13 weeks (SMD -0.13, 95% CI -0.37 to 0.10) or at 26 weeks (SMD 0.06, 95% CI -0.16 to 0.28). An I(2) statistic of ≥ 62% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.004), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.52). We found evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.023), in unpublished trials (P=0.023), in trials that used non-intervention controls (P=0.031), and in trials that used concomitant viscosupplementation (P=0.06).Participants on corticosteroids were 11% less likely to experience adverse events, but confidence intervals included the null effect (RR 0.89, 95% CI 0.64 to 1.23, I(2)=0%). Participants on corticosteroids were 67% less likely to withdraw because of adverse events, but confidence intervals were wide and included the null effect (RR 0.33, 95% CI 0.05 to 2.07, I(2)=0%). Participants on corticosteroids were 27% less likely to experience any serious adverse event, but confidence intervals were wide and included the null effect (RR 0.63, 95% CI 0.15 to 2.67, I(2)=0%).We found no evidence of an effect of corticosteroids on quality of life compared to control (SMD -0.01, 95% CI -0.30 to 0.28, I(2)=0%). There was also no evidence of an effect of corticosteroids on joint space narrowing compared to control interventions (SMD -0.02, 95% CI -0.49 to 0.46). AUTHORS' CONCLUSIONS Whether there are clinically important benefits of intra-articular corticosteroids after one to six weeks remains unclear in view of the overall quality of the evidence, considerable heterogeneity between trials, and evidence of small-study effects. A single trial included in this review described adequate measures to minimise biases and did not find any benefit of intra-articular corticosteroids.In this update of the systematic review and meta-analysis, we found most of the identified trials that compared intra-articular corticosteroids with sham or non-intervention control small and hampered by low methodological quality. An analysis of multiple time points suggested that effects decrease over time, and our analysis provided no evidence that an effect remains six months after a corticosteroid injection

Unacylated-Ghrelin Impairs Hippocampal Neurogenesis and Memory in Mice and Is Altered in Parkinson’s Dementia in Humans

Blood-borne factors regulate adult hippocampal neurogenesis and cognition in mammals. We report that elevating circulating unacylated-ghrelin (UAG), using both pharmacological and genetic methods, reduced hippocampal neurogenesis and plasticity in mice. Spatial memory impairments observed in ghrelin-O-acyl transferase-null (GOAT/) mice that lack acyl-ghrelin (AG) but have high levels of UAG were rescued by acyl-ghrelin. Acyl-ghrelin-mediated neurogenesis in vitro was dependent on non-cell-autonomous BDNF signaling that was inhibited by UAG. These findings suggest that post-translational acylation of ghrelin is important to neurogenesis and memory in mice. To determine relevance in humans, we analyzed circulating AG:UAG in Parkinson disease (PD) patients diagnosed with dementia (PDD), cognitively intact PD patients, and controls. Notably, plasma AG:UAG was only reduced in PDD. Hippocampal ghrelin-receptor expression remained unchanged; however, GOAT+ cell number was reduced in PDD. We identify UAG as a regulator of hippocampal-dependent plasticity and spatial memory and AG:UAG as a putative circulating diagnostic biomarker of dementia