An update of the chemiosmotic theory as suggested by possible proton currents inside the coupling membrane

Understanding how biological systems convert and store energy is a primary purpose of basic research. However, despite Mitchell's chemiosmotic theory, we are far from the complete description of basic processes such as oxidative phosphorylation (OXPHOS) and photosynthesis. After more than half a century, the chemiosmotic theory may need updating, thanks to the latest structural data on respiratory chain complexes. In particular, up-to date technologies, such as those using fluorescence indicators following proton displacements, have shown that proton translocation is lateral rather than transversal with respect to the coupling membrane. Furthermore, the definition of the physical species involved in the transfer (proton, hydroxonium ion or proton currents) is still an unresolved issue, even though the latest acquisitions support the idea that protonic currents, difficult to measure, are involved. Moreover, F o F 1 -ATP synthase ubiquitous motor enzyme has the peculiarity (unlike most enzymes) of affecting the thermodynamic equilibrium of ATP synthesis. It seems that the concept of diffusion of the proton charge expressed more than two centuries ago by Theodor von Grotthuss is to be taken into consideration to resolve these issues. All these uncertainties remind us that also in biology it is necessary to consider the Heisenberg indeterminacy principle, which sets limits to analytical questions

High Glucose Impairs Expression and Activation of MerTK in ARPE-19 Cells

MerTK (Mer Tyrosine Kinase) is a cell surface receptor that regulates phagocytosis of pho-toreceptor outer segments (POS) in retinal pigment epithelial (RPE) cells. POS phagocytosis is im-paired in several pathologies, including diabetes. In this study, we investigate whether hyperglyce-mic conditions may affect MerTK expression and activation in ARPE-19 cells, a retinal pigment epithelial cellular model. ARPE-19 cells were cultured in standard (CTR) or high-glucose (HG) me-dium for 24 h. Then, we analyzed: mRNA levels and protein expression of MerTK and ADAM9, a protease that cleaves the extracellular region of MerTK; the amount of cleaved Mer (sMer); and the ability of GAS6, a MerTK ligand, to induce MerTK phosphorylation. Since HG reduces miR-126 levels, and ADAM9 is a target of miR-126, ARPE-19 cells were transfected with miR-126 inhibitor or mimic; then, we evaluated ADAM9 expression, sMer, and POS phagocytosis. We found that HG reduced expression and activation of MerTK. Contextually, HG increased expression of ADAM9 and the amount of sMer. Overexpression of miR-126 reduced levels of sMer and improved phago-cytosis in ARPE-19 cells cultured with HG. In this study, we demonstrate that HG compromises MerTK expression and activation in ARPE-19 cells. Our results suggest that HG up-regulates ADAM9 expression, leading to increased shedding of MerTK. The consequent rise in sMer coupled to reduced expression of MerTK impairs binding and internalization of POS in ARPE-19 cells

Proceso y métodos de evaluación integrada participativa de degradación en agroecosistemas semiáridos. Un caso de estudio en un área protegida en el trópico seco nicaragüense

Los procesos de evaluación integrada y participativa son un buen marco metodológico-operativo para la toma de decisiones frente a cuestiones ambientales complejas que conciernen a socio-agroecosistemas de alto dinamismo e impredecibilidad a cambios y con intereses conflictivos de los actores implicados en su gestión. La finalidad del artículo es mostrar el potencial de la aplicación de un enfoque interdisciplinar e intercultural para desarrollar un proceso multiescala y multiobjetivo de evaluación comprehensiva y critica de la degradación ambiental de un sistema agrosilvopastoril semiárido en Nicaragua. Pese a que se trate de un proceso en curso, el artículo describe y reflexiona sobre los resultados metodológicos de los primeros dos años y discute como la combinación de métodos desde diferentes disciplinas y la integración de conocimientos han permitido explicitar las incertidumbres e ignorancias sobre la comprensión del sistema y los procesos de cambios socio-ecológicos locales, plantear y validar nuevas hipótesis de trabajo e obtener exactitud y relevancia de la evaluación de degradación. Asimismo el proceso participativo intenta incluir, en cada fase, la pluralidad de actores, con sus intereses y valoraciones y representaciones de futuro, para asegurar la calidad del proceso. Finalmente, el análisis de escenarios se demuestra útil instrumento para aclarar las posibles interfases de conflicto y compromiso o negociación entre actores, investigadores y tomadores de decisiones sobre opciones alternativas de gestión y desarrollo para el área.The integrated and participatory assessment processes are a good methodological and operational framework for decision making, facing to complexity on environmental issues when agro-ecosystems are highly dynamics and unpredictable to changes and there are plural and conflictive interests. This paper aims to investigate the potencial for such interdisciplinary and intercultural approach to develop a comprehensive and constructive multiscale and multiobjetive process of land degradation assessment in semiarid agro-ecosystems. Since the overall process is still on going, the research, applied to a case study in Nicaragua, describes and reflects on the experience through the first two years of work. The article argues that the integration between scientific and lay knowledge allows facing the uncertainties and ignorance in understanding complex systems and main processes of change, to propose and validate research hypothesis and to lead to both accurate and relevant assessment of land degradation. The participatory approach, using methods from a variety of disciplines, attempts to capture the plurality of relevant actors, with different objectives, values and representations of future, in order to assure quality of the process. Finally, the paper illustrates the usefulness of scenario analysis to explore the "arenas" of conflicts and negotiation between researchers, actors and decision makers on alternative management and development policies options

The Strange Case: The Unsymmetric Cisplatin-Based Pt(IV) Prodrug [Pt(CH3COO)Cl2(NH3)2(OH)] Exhibits Higher Cytotoxic Activity with respect to Its Symmetric Congeners due to Carrier-Mediated Cellular Uptake

The biological behavior of the axially unsymmetric antitumor prodrug (OC-6-44)-acetatodiamminedichloridohydroxidoplatinum(IV), 2, was deeply investigated and compared with that of analogous symmetric Pt(IV) complexes, namely, dihydroxido 1 and diacetato 3, which have a similar structure. The complexes were tested on a panel of human tumor cell lines. Complex 2 showed an anomalous higher cytotoxicity (similar to that of cisplatin) with respect to their analogues 1 and 3. Their reduction potentials, reduction kinetics, lipophilicity, and membrane affinity are compared. Cellular uptake and DNA platination of Pt(IV) complexes were deeply investigated in the sensitive A2780 human ovarian cancer cell line and in the corresponding resistant A2780cisR subline. The unexpected activity of 2 appears to be related to its peculiar cellular accumulation and not to a different rate of reduction or a different efficacy in DNA platination and/or efficiency in apoptosis induction. Although the exact mechanism of cell uptake is not fully deciphered, a series of naive experiments indicates an energy-dependent, carrier-mediated transport: the organic cation transporters (OCTs) are the likely proteins involved

Comparison of reflector concepts for a 250 GHz CARM cavity

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Formative Assessment and Professional Training: Reflections from a Mathematics course in Bioengineering

Bioengineering is currently considered an interdisciplinary professional field which provides solutions to different problems arising in the area of health care. Its strategic importance is widely acknowledged since its developments and proposals could help diminish the level of technological dependence in the sector. The fast pace of innovation in the area of biomedical technology gives rise to permanent reflection on the learning goals and teaching strategies proposed by educators in the different training stages of a bioengineer. In this context, learning assessment appears as a controversial issue which needs to be debated and rethought. This paper describes the reflections of teachers of a Mathematics course within a Bioengineering program around the question, What approach to assessment favors the student's participation, autonomy and training as a future bioengineer? The investigation was carried out in the framework of a Participatory Research Action project and helped us to redesign assessment activities from a different perspective.Fil: Carrere, C.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Milesi, S.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Lapyckyj, I.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Ravera, Emiliano Pablo. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Escher, L.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Miyara, A.. Universidad Nacional de Rosario; Argentina. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Pita, G.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; ArgentinaFil: Añino, M.. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; Argentin

The two-way relationship between food systems and the COVID19 pandemic: causes and consequences

[EN] CONTEXT: The COVID-19 pandemic has become one of the most pressing challenges for humanity. The pandemic is affecting all aspects of human lives and livelihoods, including food. In this context, new research shows the nexus between agri-food systems and the spread of emergent infectious diseases (EID) such as the coronavirus disease while at the same time, shows how the COVID-19 pandemics has heavily impacted food systems. OBJECTIVE: The aim of this work is to shed light and draw, through the case of COVID-19, the network of direct and indirect links and feedback loops between the globalised food system and pandemics. METHODS: We conducted a literature review. RESULTS AND CONCLUSIONS: As with climate change, food systems have a double relation with EID in general, and in particular with the present world health crisis linked to COVID-19. On the one hand, global agri-food systems, as currently organised, are a necessary step in the development of EID, through their impacts in land use changes, habitat fragmentation, biodiversity loss and climate change. On the other hand, COVID-19 has had and is having impacts on all food systems at all scales. The review shows that all activities of the food system (from production to consumption) as well as all pillars of food security (availability, access, use, stability) have been affected. The impacts of COVID-19 pandemic on food systems can be divided between direct impacts of the virus outbreak, and indirect impacts derived from the containment measures (e.g. lockdowns, mobility restrictions, shops closure) adopted at different levels (from local to global). While all food systems across the globe have been affected by the pandemic, it is argued that vulnerability is different for different types of food systems. Long food supply chains have been particularly affected by COVID-19 crisis, however, it is important to avoid universalization of impacts and responses as agri-food systems are characterised by a huge diversity and heterogeneity. The review concludes by pointing out that while the pandemic represents a challenge for the global food systems, this 'stress test' can be also seized as an opportunity to highlight vulnerabilities to be urgently addressed during the recovery period and speed up the transformation towards more sustainable and resilient food systems. SIGNIFICANCE: A food systems approach is essential to have a broader picture of the relationship of agri-food systems with zoonosis and their centrality in the pandemics and the derived socio-economic consequences.Elisa OterosRozas was funded by the Spanish Ministry of Science, Innovation and Universities (IJCI201734334) . Marina di Masso was funded by the Spanish Ministry of Science, Innovation and Universities (IJCI-2016-30769) Federica Ravera was funded by the Spanish Ministry of Science, Innovation and Universities (RYC2018025958I) .Rivera-Ferre, MG.; Lopez-I-Gelats, F.; Ravera, F.; Oteros-Rozas, E.; Di Masso, M.; Binimelis, R.; El Bilali, H. (2021). The two-way relationship between food systems and the COVID19 pandemic: causes and consequences. Agricultural Systems. 191. https://doi.org/10.1016/j.agsy.2021.10313419

Temperature dependence of steady-state and presteady-state kinetics of a type IIb Na+/Pi cotransporter

The temperature dependence of the transport kinetics of flounder Na(+)-coupled inorganic phosphate (P(i)) cotransporters (NaPi-IIb) expressed in Xenopus oocytes was investigated using radiotracer and electrophysiological assays. (32)P(i) uptake was strongly temperature-dependent and decreased by approximately 80% at a temperature change from 25 degrees C to 5 degrees C. The corresponding activation energy (E (a)) was approximately 14 kcal mol(-1) for the cotransport mode. The temperature dependence of the cotransport and leak modes was determined from electrogenic responses to 1 mM P(i) and phosphonoformic acid (PFA), respectively, under voltage clamp. The magnitude of the P(i)- and PFA-induced changes in holding current decreased with temperature. E (a) at -100 mV for the cotransport and leak modes was approximately 16 kcal mol(-1) and approximately 11 kcal mol(-1), respectively, which suggested that the leak is mediated by a carrier, rather than a channel, mechanism. Moreover, E (a) for cotransport was voltage-independent, suggesting that a major conformational change in the transport cycle is electroneutral. To identify partial reactions that confer temperature dependence, we acquired presteady-state currents at different temperatures with 0 mM P(i) over a range of external Na(+). The relaxation time constants increased, and the peak time constant shifted toward more positive potentials with decreasing temperature. Likewise, there was a depolarizing shift of the charge distribution, whereas the total available charge and apparent valency predicted from single Boltzmann fits were temperature-independent. These effects were explained by an increased temperature sensitivity of the Na(+)-debinding rate compared with the other voltage-dependent rate constants