ATP is released from nerve terminals and from activated muscle fibres on stimulation of the rat phrenic nerve

Nerve stimulation increases the concentration of ATP in the synaptic cleft, which can act as a neurotransmitter or as a presynaptic neuromodulator. Using the luciferin-luciferase assay, we observed that the extracellular concentration of ATP increased by 11-26 nM over a basal concentration of 6 nM, in a frequency dependent manner (1-5 Hz), in the adult rat phrenic nerve-hemidiaphragm preparation. This ATP release depends on nerve activity since it was abolished by tetrodotoxin (1 [mu]M) and is strictly dependent on the presence of extracellular calcium. However, more than half of this nerve-evoked release of ATP is derived from activated muscle fibres since the selective post-synaptic nicotinic receptor antagonist, [alpha]-bungarotoxin (1 [mu]M), inhibited by over 60% the evoked release of ATP. The presently observed post-synaptic release of ATP together with the previously reported lack of post-synaptic effects of ATP and to the ability of ATP to act as a presynaptic modulator open the possibility that ATP may behave as a retrograde messenger at this neuromuscular junction.http://www.sciencedirect.com/science/article/B6T0G-47S6YPN-X/1/e09fe63a6ed4383fc2ed5996ece6ac4

Development of peach flower buds under low winter chilling conditions

Here, we reviewed both endogenous and exogenous factors involved in the processes of flower bud formation and flower development in peach, analyzing how they can be affected by climatic change in temperate zones, explored the expansion of peach to tropical or subtropical zones. The process of flower bud formation in peach differs between low winter chilling and temperate conditions. Although the main steps of flower development are maintained, the timing in which each one occurs is different, and some processes can be altered under low winter chilling conditions, with a great impact on fruit production and crop management. Further studies on flower bud induction and differentiation under warmer conditions are fundamental for addressing the alterations in flower bud development that negatively impact on next season’s harvest. In the future, horticulturalists and scientists will face several challenges, mainly how high temperatures affect the expression of the main genes regulating flower formation and how to improve crop management in these conditions

Assessment of Exercise Capacity in Post-COVID-19 Patients: How Is the Appropriate Test Chosen?

There is a wide range of sequelae affecting COVID-19 survivors, including impaired physical capacity. These sequelae can affect the quality of life and return to work of the active population. Therefore, one of the pillars of following-up is the evaluation of physical capacity, which can be assessed with field tests (such as the six-minute walk test, the one-minute standing test, the Chester step test, and the shuttle walking test) or laboratory tests (such as the cardiopulmonary exercise test). These tests can be performed in different contexts and have amply demonstrated their usefulness in the assessment of physical capacity both in post-COVID-19 patients and in other chronic respiratory, metabolic, cardiologic, or neurologic diseases. However, when traditional tests cannot be performed, physical function can be a good substitute, especially for assessing the effects of an intervention. For example, the Short Physical Performance Battery assessment and the Timed Up and Go assessment are widely accepted in older adults. Thus, the test should be chosen according to the characteristics of each subject

Ethnoarchaeology of hunter‐fisher‐gatherers societies in the Beagle Channel (Tierra del Fuego): ethnographical sources and social simulation

Research from the Beagle Channel (Tierra del Fuego) offers a rich ethnographic and historical record produced by the late inclusion of Tierra del Fuego in the industrial world (the Beagle Channel was discovered by R. Fitz- Roy in 1830). This is an interesting frame for using new techniques (social simulation by Agent Based Modelling (ABM)) to generate new hypotheses in archaeology. In this case, the hypothesis is focused on the role of social cooperation in Yámana hunter-fisher-gatherer societyEtnoarqueología de sociedades cazadoras-pescadoras-recolectoras en el canal Beagle (Tierra del Fuego): fuentes etnográficas y simulación social La investigación etnoarqueológica en el canal Beagle (Tierra del Fuego) ofrece un abundante registro documental etnográfico e histórico producto de su tardía incorporación al mundo industrial (el canal Beagle es descubierto por R. Fitz-Roy en 1830). Este marco posibilita la aplicación de técnicas novedosas (simulación social mediante “agent based modelling” (ABM)) para la generación de hipótesis a contrastar arqueológicamente. En el caso de nuestro proyecto esa hipótesis versa sobre el papel de la cooperación social en la sociedad cazadora-pescadora-recolectora YámanaEthnoarchéologie des sociétés de chasseurs-pêcheurs-cueilleurs dans le canal de Beagle (Tierra del Fuego): sources ethnographiques et simulation sociale La recherche ethnoarchéologique dans le Canal Beagle (Tierra del Fuego) offre un registre riche de documents historiques et ethnographiques come conséquence de son entrée tardive dans le monde industriel (le canal de Beagle est découvert par R. Fitz-Roy en 1830). Ce cadre permet l’application de nouvelles techniques (simulation sociale à l’aide de «modélisation de l’agent sur la base» (ABM)) pour générer des hypothèses à tester dans le registre archéologique. Pour notre projet cette hypothèse concerne le rôle de la coopération sociale dans les chasseur-pêcheur-cueilleurs YámanaMinisterio de Economía y Competitividad de España. Project: “Social and environmental transitions: Simulating the past to understand human behaviour (SimulPast) (CSD2010-00034)” and “Marcadores Arqueológicos de Relaciones Sociales: etnoarqueología de cazadores-recolectores en el Canal Beagle (HAR2009-06996)”. -Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina. Project: “Procesos de agregación social entre las sociedades cazadoras-recolectoras del canal Beagle: nuevas metodologías de análisis (PIP0706)”. -The Wenner-Gren Foundation for Anthropological Research. Project: “Social aggregation: a Yamana Society’s short-term episode to Analyse Social Interaction.

Effect of pulmonary hypertension on exercise tolerance in patients with COPD: a prognostic systematic review and meta-analysis

Background: Pulmonary hypertension (PH) is a frequent complication in patients with COPD. Objective: To determine if, in patients with COPD, the presence of PH decreases exercise tolerance. Methods: We included studies that analysed exercise tolerance using a cardiopulmonary exercise test (CPET) in patients with COPD with PH (COPD-PH) and without PH (COPD-nonPH). Two independent reviewers analysed the studies, extracted the data and assessed the quality of the evidence. Results: Of the 4915 articles initially identified, seven reported 257 patients with COPD-PH and 404 patients with COPD-nonPH. The COPD-PH group showed differences in peak oxygen consumption (V'O2peak ), -3.09 mL·kg-1·min-1 (95% CI -4.74 to -1.43, p=0.0003); maximum workload (Wmax), -20.5 W (95% CI -34.4 to -6.5, p=0.004); and oxygen pulse (O2 pulse), -1.24 mL·beat-1 (95% CI -2.40 to -0.09, p=0.03), in comparison to the group with COPD-nonPH. If we excluded studies with lung transplant candidates, the sensitivity analyses showed even bigger differences: V'O2 , -4.26 mL·min-1·kg-1 (95% CI -5.50 to -3.02 mL·kg-1·min-1, p<0.00001); Wmax, -26.6 W (95% CI -32.1 to -21.1 W, p<0.00001); and O2 pulse, -2.04 mL·beat-1 (95% CI -2.92 to -1.15 mL·beat-1, p<0.0001). Conclusion: Exercise tolerance was significantly lower in patients with COPD-PH than in patients with COPD-nonPH, particularly in nontransplant candidates

Attention deficit hyperactivity disorder: Genetic association study in a cohort of spanish children

Background: Attention deficit hyperactivity disorder (ADHD) has a strong genetic component. The study is aimed to test the association of 34 polymorphisms with ADHD symptomatology considering the role of clinical subtypes and sex in a Spanish population. Methods: A cohort of ADHD 290 patients and 340 controls aged 6–18 years were included in a case–control study, stratified by sex and ADHD subtype. Multivariate logistic regression was used to detect the combined effects of multiple variants. Results: After correcting for multiple testing, we found several significant associations between the polymorphisms and ADHD (p value corrected ≤0.05): (1) SLC6A4 and LPHN3 were associated in the total population; (2) SLC6A2, SLC6A3, SLC6A4 and LPHN3 were associated in the combined subtype; and (3) LPHN3 was associated in the male sample. Multivariable logistic regression was used to estimate the influence of these variables for the total sample, combined and inattentive subtype, female and male sample, revealing that these factors contributed to 8.5, 14.6, 2.6, 16.5 and 8.5 % of the variance respectively. Conclusions: We report evidence of the genetic contribution of common variants to the ADHD phenotype in four genes, with the LPHN3 gene playing a particularly important role. Future studies should investigate the contribution of genetic variants to the risk of ADHD considering their role in specific sex or subtype, as doing so may produce more predictable and robust modelsThis study was supported by the following research grants: Fundacion Alicia Koplowitz (4019-004), Biobank of Fundacion Jimenez Diaz Hospital (RD09/0076/00101, Instituto de Salud Carlos III) and the Centre for Biomedical Network Research on Rare Diseases -CIBERER (06/07/0036). The work of CG-S is supported by a Fundacion Conchita Rabago Gran

Efectos de la hipertensión pulmonar en la capacidad de ejercicio en pacientes con enfermedad pulmonar obstructiva crónica

Introduction: The impact of pulmonary hypertension (PH) on exercise tolerance in chronic obstructive pulmonary disease (COPD) has not been fully elucidated. It is necessary to characterize pulmonary hemodynamics in patients with moderate to severe COPD in order to improve their management. The aim of the study was to determine whether in COPD the presence of PH is associated with reduced exercise tolerance in a cohort of stable COPD patients. Methods: Cross-sectional analysis of 174 COPD patients clinically stable: 109 without PH and 65 with PH (COPD-PH). We assessed socio-demographic data, lung function, quality of life, dyspnea, cardiopulmonary exercise testing (CPET), constant workload endurance time (CWET), and six-minute walk test (6MWT). We elaborated a logistic regression model to explore the impact of PH on exercise capacity in COPD patients. Results: COPD-PH patients showed lower exercise capacity both at maximal (CPET) (43(20) versus 68(27) Watts and 50(19)% versus 71(18)% predicted peak oxygen consumption (VO2peak), COPD-PH and COPD, respectively), and at submaximal tests (6MWT) (382(94) versus 486(95) m). In addition, the COPD-PH group had lower endurance time than the non-PH COPD group (265(113) s and 295(164) s, respectively). Conclusions: The presence of PH is an independent factor that impairs exercise capacity in COPD. SPANISH Introducción: El impacto de la hipertensión pulmonar (HTP) en la tolerancia al ejercicio en la enfermedad pulmonar obstructiva crónica (EPOC) no se ha dilucidado en su totalidad. Es necesario caracterizar la hemodinámica pulmonar de los pacientes con EPOC moderada a grave para poder mejorar su manejo. El objetivo de este estudio fue determinar si la presencia de HTP en la EPOC se asociaba con una disminución en la tolerancia al ejercicio en una cohorte de pacientes con EPOC estable. Métodos: Estudio transversal de 174 pacientes con EPOC clínicamente estables: 109 de ellos no mostraban HTP y 65 de ellos sí (EPOC-HTP). Valoramos la información sociodemográfica, la función pulmonar, la calidad de vida, la disnea, realizamos una prueba de ejercicio cardiopulmonar (PECP), medimos el tiempo de tolerancia de ejercicio constante y realizamos de marcha de seis minutos (6MWT, por sus siglas en inglés). Elaboramos un modelo de regresión logística para explorar el impacto de la HTP en la capacidad de ejercicio de los pacientes con EPOC. Resultados: Los pacientes con EPOC-HTP mostraron una menor capacidad de ejercicio, tanto en las pruebas máximas (PECP) (43 (20) W frente a 68 (27) W y 50 (19)% frente a 71 (18)% de consumo de oxígeno máximo predicho (VO2 max), para pacientes con EPOC-HTP y pacientes con EPOC, respectivamente) como en las pruebas submáximas (6MWT) (382 (94) m frente a 486 (95) m). Además, el grupo de EPOC-HTP presentó un menor tiempo de resistencia que el grupo de EPOC sin HTP (265 (113) s y 295 (164) s, respectivamente). Conclusiones: La presencia de HTP es un factor independiente que afecta a la capacidad de ejercicio en la EPOC

Application of PEG400 in the one-pot synthesis of 7-[4-alkyl- or (hetero) aryl-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridines via SNAr and Cu(I)- Catalyzed Azide-Alkyne Cycloaddition and preliminary evaluation of their anti-tumour activity

Several novel 7-[4-alkyl- or (hetero)aryl-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridines were prepared in good to high yields, using the environmentally friendly solvent PEG400 in a one-pot procedure from 7- chlorothieno[3,2-b]pyridine to form the corresponding azide via SNAr with NaN3, followed by Cu(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) using different types of alkynes. This one-pot reaction in PEG400 starting from a halogenated heteroaromatic system is reported for the first time and demonstrated a wide scope of application for alkynes. Preliminary anti-tumour activity on human tumour cell lines using the prepared 1,4-di(hetero)aryl-1,2,3-triazoles was evaluated, together with their toxicity in non-tumour cells. Among the tested compounds the most promising one was a 2-ethynylpyridine derivative.Fundação para a Ciência e Tecnologia (FCT)–Portugal financially supports CQUM (UID/QUI/686/2019), CIMO-IPBragança (UID/ AGR/690/2019), the research project PTDC/QUI-QFI/28020/2017 (POCI-01-0145-FEDER-028020) also financed by European Regional Development Fund (ERDF), COMPETE2020 and Portugal2020, the PTNMR network also supported by Portugal2020 and the PhD grant of J.M.R. (SFRH/BD/115844/2016) also financed by ESF (European Social Fund) and HCOP (Human Capital Operational Programme).info:eu-repo/semantics/publishedVersio