Indirect ultraviolet photodesorption from CO:N2 binary ices - an efficient grain-gas process

UV ice photodesorption is an important non-thermal desorption pathway in many interstellar environments that has been invoked to explain observations of cold molecules in disks, clouds and cloud cores. Systematic laboratory studies of the photodesorption rates, between 7 and 14 eV, from CO:N2 binary ices, have been performed at the DESIRS vacuum UV beamline of the synchrotron facility SOLEIL. The photodesorption spectral analysis demonstrates that the photodesorption process is indirect, i.e. the desorption is induced by a photon absorption in sub-surface molecular layers, while only surface molecules are actually desorbing. The photodesorption spectra of CO and N2 in binary ices therefore depend on the absorption spectra of the dominant species in the subsurface ice layer, which implies that the photodesorption efficiency and energy dependence are dramatically different for mixed and layered ices compared to pure ices. In particular, a thin (1-2 ML) N2 ice layer on top of CO will effectively quench CO photodesorption, while enhancing N2 photodesorption by a factors of a few (compared to the pure ices) when the ice is exposed to a typical dark cloud UV field, which may help to explain the different distributions of CO and N2H+ in molecular cloud cores. This indirect photodesorption mechanism may also explain observations of small amounts of complex organics in cold interstellar environments.Comment: 21 pages 5 figure

Tolerance and autoimmunity: novel therapeutic approaches

La función primaria del sistema inmune es resguardar al individuo de los patógenos potencialmente dañinos que invaden el medio ambiente en el cual nos desarrollamos. Este cuenta con dos grandes ramas, la inmunidad innata y la adaptativa, ambas con la propiedad de diferenciar lo peligroso de aquello inofensivo. Estos procesos se hallan regulados por mecanismos homeostáticos que constituyen la tolerancia inmunológica, a los fines de limitar aquellos procesos prolongados y silenciar los potencialmente autoagresivos. Ante la falla de estos mecanismos de control, surgen las enfermedades autoinmunes. Avances en el conocimiento de la fisiopatología de estas entidades, han abierto un nuevo capítulo en el terreno de la inmunofarmacología. Su prometedor potencial actualmente nos ofrece novedosas herramientas terapéuticas para controlar y atenuar el daño causado por este tipo de respuestas. No obstante, debe continuarse la investigación en el campo de los agentes biológicos, ya que ninguno de ellos se encuentra libre de inconvenientes. Seguramente, futuros hallazgos se concretarán en futuros aciertos. Y los aciertos, en Medicina, equivalen a esperanza.The main function of the immune system is to protect the individual against potentially dangerous pathogens. It comprises innate and adaptive cellular and soluble components, both with the capacity to discriminate between harmful and harmless. These processes are regulated by homeostatic mechanisms that constitute the so-called immunological tolerance, which aims to limit the prolonged action of immune mediators and to silence the generation of potentially autoaggressive components. Failure to silence self-reactive T and B cells results in the generation of autoimmune disease. Recent advances in our knowledge of these pathological entities have opened a new chapter in the pharmacology of the immune system. Its promising potential currently offers new therapeutic agents to control and attenuate pathological tissue damage. Nevertheless, further research regarding these biologic agents is required, since they are not free from inconveniences. It is without question that upcoming findings in this field will instill hope into the quest for the “magic bullet”.Fil: Ciliberti, Esteban. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Carambia, Leandro. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Cavallin, Sebastian. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Cerda, Osvaldo L.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Poderoso, Juan J.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Wavelength-Dependent UV Photodesorption of Pure N2N_2 and O2O_2 Ices

Context: Ultraviolet photodesorption of molecules from icy interstellar grains can explain observations of cold gas in regions where thermal desorption is negligible. This non-thermal desorption mechanism should be especially important where UV fluxes are high. Aims: $N_2$ and $O_2$ are expected to play key roles in astrochemical reaction networks, both in the solid state and in the gas phase. Measurements of the wavelength-dependent photodesorption rates of these two infrared-inactive molecules provide astronomical and physical-chemical insights into the conditions required for their photodesorption. Methods: Tunable radiation from the DESIRS beamline at the SOLEIL synchrotron in the astrophysically relevant 7 to 13.6 eV range is used to irradiate pure $N_2$ and $O_2$ thin ice films. Photodesorption of molecules is monitored through quadrupole mass spectrometry. Absolute rates are calculated by using the well-calibrated CO photodesorption rates. Strategic $N_2$ and $O_2$ isotopolog mixtures are used to investigate the importance of dissociation upon irradiation. Results: $N_2$ photodesorption mainly occurs through excitation of the $b^1\sqcap_u$ state and subsequent desorption of surface molecules. The observed vibronic structure in the $N_2$ photodesorption spectrum, together with the absence of $N_3$ formation, supports that the photodesorption mechanism of $N_2$ is similar to CO, i.e., an indirect DIET (Desorption Induced by Electronic Transition) process without dissociation of the desorbing molecule. In contrast, $O_2$ photodesorption in the 7−13.6 eV range occurs through dissociation and presents no vibrational structure. Conclusions: Photodesorption rates of $N_2$ and $O_2$ integrated over the far-UV field from various star-forming environments are lower than for CO. Rates vary between $10^{-3}$ and $10^{-2}$ photodesorbed molecules per incoming photon.Astronom

Progesterone protective effects in neurodegeneration and neuroinflamation

Progesterone is a neuroprotective, promyelinating and antiinflammatory  factor for the nervous system. Here we discuss progesterone effects in models of  motoneuron degeneration and neuroinflammation. In neurodegeneration of the  Wobbler mouse, a subset of spinal cord motoneurons showed increased activity of  nitric oxide synthase (NOS), increased intramitochondrial NOS, decreased activity of  respiratory chain complexes and decreased activity and protein expression of Mnsuperoxide  dismutase type 2 (MnSOD2). Clinically, Wobblers suffered several  degrees of motor impairment. Progesterone treatment restored the expression of  neuronal markers, decreased the activity of NOS and enhanced complex I  respiratory activity and MnSOD2. Long-term treatment with progesterone increased  muscle strength, biceps weight and survival. Collectively, these data supported that  progesterone prevented neurodegeneration. To study progesterone effects in  neuroinflammation, we employed mice with experimental autoimmune  encephalomyelitis (EAE). EAE mice spinal cord showed increased mRNA levels of  the inflammatory mediators tumour necrosis factor α (TNFα) and its receptor TNFR1,  the microglial marker CD11b, iNOS and the toll-like receptor 4 (TLR4). Progesterone  pretreatment of EAE mice blocked the proinflammatory mediators, decreased Iba1+  microglial cells and attenuated clinical signs of EAE. Therefore, reactive glial cells  became targets of progesterone anti-inflammatory effects. These results open the  ground for testing the usefulness of neuroactive steroids for neurological disorders.Fil: de Nicola, Alejandro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Gonzalez Deniselle, Maria Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Garay, Laura Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Meyer, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Gargiulo Monachelli, Gisella Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Guennoun, Rachida. Inserm; Francia. Universite Paris Sud; FranciaFil: Schumacher, M.. Inserm; Francia. Universite Paris Sud; FranciaFil: Carreras, Maria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Poderoso, Juan José. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; Argentin

Mitochondrial nitric oxide in the signaling of cell integrated responses

Mitochondria are the specialized organelles for energy metabolism, but, as a typical example of system biology, they also activate a multiplicity of pathways that modulate cell proliferation and mitochondrial biogenesis or oppositely promote cell arrest and programmed cell death by a limited number of oxidative or nitrosative reactions. These reactions are influenced by matrix nitric oxide (NO) steady-state concentration, either from local production or by gas diffusion to mitochondria from the canonical sources. Likewise, in a range of ∼30-200 nM, NO turns mitochondrial O2 utilization down by binding to cytochrome oxidase and elicits a burst of superoxide anion and hydrogen peroxide that diffuses outside mitochondria. Depending on NO levels and antioxidant defenses, more or less H2O2 accumulates in cytosol and nucleus, and the resulting redox grading contributes to dual activation of proliferating and proapoptotic cascades, like ERK1/2 or p38 MAPK. Moreover, these sequential activating pathways participate in rat liver and brain development and in thyroid modulation of mitochondrial metabolism and contribute to hypothyroid phenotype through complex I nitration. On the contrary, lack of NO disrupts pathways like S-nitrosylation or H 2O2 production and likewise is a gateway to disease in amyotrophic lateral sclerosis with superoxide dismutase 1 mutations or to cancer proliferation.Fil: Carreras, Maria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Poderoso, Juan José. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin

Intercellular mitochondrial transfer through nanotubules is promoted by cyclic amp (cAMP) in rat astrocytes and human glioblastoma cells

Nanotubules (Tunneling nanotubules, TnTs) are cell membrane projectionsmade of F-actin fibers of nanometric diameter (up to 1 μm),which enable cytoplasmatic connections between cells. It has beenshown that mitochondria, other organelles, and cellular componentsare transferred by TnTs in several normal and tumor cell lines. TnTsestablishment has been extensively described in nervous systemcells, as neurons and astrocytes. Published evidence indicates theexistence of mitochondrial transfer through TnTs between differentcell types, such as normal and tumoral cells. Mitochondrial passagefrom normal to tumor cells restores oxidative metabolism, decreasingtumorigenic potential. A similar effect has been observed withcAMP, a very well-known astrocytes stellation promoter, which mediatesmitochondrial biogenesis and tumor growth inhibition. Mitochondrialtransfer within TnTs in nervous system cells have not beendemonstrated so far. Then, our goal was to analyze mitochondrialtrafficking through TnTs in normal and tumoral astrocytes and apossible effect of cAMP. We used normal rat astrocytes and humanglioblastoma U87 cells. Mitochondria and actin were probed with amito-targeted green fluorescent protein and phalloidin, respectively.Astrocytes and U87 were incubated with or without 8Br-cAMP(cAMP analogue). We analyzed images by confocal microscopy andmeasured the width of actin connections between cells. We analyzedeach culture separately; astrocytes and U87 establish thick projectionscontaining mitochondria but treatment with cAMP promotes anincrease of TnTs-like connections with mitochondria inside (controlvs cAMP: astrocytes: 2.07±0.71 vs 0.85±0.21 μm, ***p<0.05; U87:2.69±1.40 vs.0.84±0.22 μm, *p<0.05, ± SD, ANOVA, Tukey test).Thus, cAMP promotes TnTs-like structures and mitochondrial passagethrough them in normal astrocytes and glioblastoma cells, suggestinga role for intercellular mitochondrial transfer through TnTs instellation process.Fil: Helfenberger, Katia Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Benzo, Yanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Duarte, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Fuentes, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Poderoso, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Maloberti, Paula Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Poderoso, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaLXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina FisiologíaArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina FisiologíaSociedad Argentina de Inmunologí

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

Subcellular distribution of ERK phosphorylation in tyrosine and threonine depends on redox status in murine lung cells

Activation of ERK1/2 implies the phosphorylation of tyrosine (pTyr) and threonine (pThr) by MEK1/2; both reactions were thought to be cytoplasmic, promoting ERK to reach the nucleus where it activates several transcription factors. In addition, H 2 O 2 concentrations are known to modulate ERK intracellular translocation, which impacts on cellular proliferation. In this context, the objective of this work was to study the sequence of ERK phosphorylation under two redox conditions and to analyze a putative mitochondrial contribution to this process, in LP07 murine lung cells. A time-course of H 2 O 2 administration was used and ERK phosphorylation was analyzed in cytosol, mitochondria and nuclei. At 1μM H 2 O 2 , a proliferative redox stimulus, immunoblot revealed a fast and transient increase in cytosol pTyr and a sustained increase in mitochondrial pTyr content. The detection for pThr/pTyrERK (2pERK) showed in cytosol a marked increase at 5 minutes with a fast dephosphorylation after that time, for both H 2 O 2 concentrations. However, at 50 μM H 2 O 2 , an anti-proliferative condition, 2pERK was gradually retained in mitochondria. Interestingly, these results were confirmed by in vivo experiments using mice treated with a highly oxidizing agent [H 2 O 2 ]. By the use of two ERK2 mutant constructions, where Tyr and Thr were replaced by alanine, we confirmed that 2pERK relied almost completely on pThr183. Confocal microscopy confirmed ERK subcellular distribution dependence on the incidence of cytosolic pTyr and mitochondrial pThr at 1μM H 2 O 2 . This work shows for the first time, both in vitro and in vivo, an ERK cycle involving a cross-talk between cytosol and mitochondria phosphorylation events, which may play a significant role in cell cycle progression, proliferation or differentiation under two different redox conditions.Fil: Helfenberger, Katia Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Villalba, Nerina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Buchholz, Bruno. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Poderoso, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Gelpi, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Poderoso, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentin