REDUNDANT AND NON-REDUNDANT ROLES OF THE ENDOCYTIC ADAPTOR PROTEINS EPS15 AND EPS15L1 IN MAMMALS

Eps15 and Eps15L1 are two endocytic adaptor proteins involved in both clathrin-dependent and clathrin-independent endocytosis of receptor tyrosine kinases. Due to their homology, Eps15 and Eps15L1 are thought to be redundant in several cellular processes. Their redundancy, however, has never been demonstrated in in vivo model systems. Our laboratory has generated genetically engineered mice to unravel the physiological functions of Eps15 and Eps15L1. We found that Eps15-KO (knockout) mice were healthy and fertile, while Eps15L1-KO mice died at birth because of neural defects, showing the specific function of Eps15L1 in neuronal development. Importantly, Eps15/Eps15L1-DKO (double knockout) mice had a more severe phenotype, dying at midgestation, suggesting redundancy in one or more fundamental developmental programs. The aim of this thesis project was to investigate redundant and non-redundant roles of Eps15 and Eps15L1, with the final goal to unmask the underlying causes of embryo lethality of Eps15/Eps15L1-DKO mice. Since Eps15/Eps15L1-DKO mice displayed a Notch loss-of-function phenotype, accompanied by a downregulation of Notch target genes, our initial hypothesis was that Eps15 and Eps15L1 were redundantly required in the regulation of the Notch signalling. To address this issue, we set-up a co-culture model system to recapitulate Notch signalling. In detail, we used MEFs (mouse embryonic fibroblasts) derived from Eps15- and Eps15L1-KO mice as a model system for the signal-sending cell and we co-cultured them with CHO (chinese hamster ovary) cells expressing the Notch receptor, as signal receiving cells. We found that Eps15L1, but not Eps15, played a non-redundant role in Notch signalling activation. This finding indicated that impaired Notch signalling was not responsible for the more severe phenotype observed in Eps15/Eps15L1-DKO mice compared to single KO mice. Whether Eps15 and Eps15L1 are required in signal-receiving cells will be addressed, using MEFs as a model for the signal-receiving cell. We found that angiogenesis was seriously compromised in Eps15/Eps15L1-DKO mice and, therefore, hypothesized that impaired vascular development might be the major cause of midgestation lethality of these mice. To address this issue, we generated cDKO (conditional Eps15/Eps15L1-DKO mice), which lack Eps15 and Eps15L1 in endothelial and hematopoietic cells. We found that cDKO mice displayed vascular defects but did not recapitulate the severe phenotype of constitutive DKO mice. This finding indicated that impaired angiogenesis was not the major lethality cause of constitutive DKO mice. However, by in vitro studies in endothelial cells, we found that Eps15 and Eps15L1 redundantly regulated VEGFR-2 turnover, thus indicating a possible cell-autonomous function of the proteins in vascular homeostasis, even if not sufficient to cause embryo lethality when functionally impaired. Previous in vitro studies have demonstrated a role for Eps15 and Eps15L1 in the CDE (clathrin-dependent endocytosis) of EGFR (epidermal growth factor receptor) and TfR (transferrin receptor). To confirm this role in a clean background, we used MEFs as a model system. By using radioactive assays, we found that Eps15 and Eps15L1 redundantly regulate the CDE of TfR. Indeed, in DKO cells, the Ke (endocytic rate constant) of the TfR was reduced to ~50% and, as a consequence, surface levels of TfR were increased, while single KO cells showed only a minor, if any, defect. Moreover, in DKO cells, we found that the number of AP-2-positive structures (which label clathrin-structures that form during CDE) was increased, but the structures were significantly smaller in size. Whether the maturation of clathrin-coated structures is altered in DKO cells will be addressed by live imaging studies. Next, we asked whether the role of Eps15 and Eps15L1 in TfR internalization had a physiological relevance in vivo. In detail, since TfR is essential for the biology of erythroid cells, we investigated whether erythroid development was impaired in cDKO mice, lacking Eps15 and Eps15L1 in endothelial and hematopoietic cells. We found that these mice suffered from microcytic hypochromic anemia: RBCs (red blood cells) had reduced MCV (mean corpuscular volume) and high RDW (red blood cell distribution width, index of anisocytosis), and reticulocyte counts were higher. These findings suggest that Eps15 and Eps15L1 redundantly regulate erythroid development. However, since cDKO mice did not recapitulate the severe phenotype of constitutive DKO mice, altered erythroid development per se was not the only cause of the early lethality of constitutive DKO mice. Further studies are required to investigate whether altered development of Eps15/Eps15L1-DKO erytroid cells correlates with increased surface levels of TfR and reduced iron uptake. These findings, combined with previous data generated in our laboratory, highlight that Eps15 and Eps15L1 regulate several cellular processes, both in a redundant and in a non-redundant manner. Functional impairment of these processes, together with other unexplored processes, might addictively contribute to the DKO phenotype

Binge eating attitudes in community adolescent sample and relationships with interview-assessed attachment representations in girls: a multi-center study from North Italy

Purpose: To compare community girls at risk and not at risk for binge eating (BE) in attachment representations through a narrative interview and to test the predictive role of attachment pattern(s) on the risk of binge eating among community girls. Methods: From 772 community adolescents of both sexes (33% boys) screened through the Binge Eating Scale (BES), 112 girls between 14 and 18 years, 56 placed in a group at risk for binge eating (BEG), and 56 matched peers, not at risk (NBEG), were assessed in attachment representations through the Friends and Family Interview (FFI). Results: (1) Compared to NBEG, girls in the BEG showed more insecure-preoccupied classifications and scores, together with lower narrative coherence, mother\u2019s representation as a secure base/safe haven, reflective functioning, adaptive response, and more anger toward mother. (2) Both insecure-dismissing and preoccupied patterns predicted 15% more binge-eating symptoms in the whole sample of community girls. Conclusions: Insecure attachment representations are confirmed risk factors for more binge eating, affecting emotional regulation and leading to \u201cemotional eating\u201d, thus a dimensional assessment of attachment could be helpful for prevention and intervention. Implications and limits are discussed. Level of evidence: III. Evidence obtained from cohort or case\u2013control analytic studie

Decadal variations in NDVI and food production in India

In this study we use long-term satellite, climate, and crop observations to document the spatial distribution of the recent stagnation in food grain production affecting the water-limited tropics (WLT), a region where 1.5 billion people live and depend on local agriculture that is constrained by chronic water shortages. Overall, our analysis shows that the recent stagnation in food production is corroborated by satellite data. The growth rate in annually integrated vegetation greenness, a measure of crop growth, has declined significantly (p < 0.10) in 23 of the WLT cropland area during the last decade, while statistically significant increases in the growth rates account for less than 2. Inmost countries, the decade-long declines appear to be primarily due to unsustainable crop management practices rather than climate alone. One quarter of the statistically significant declines are observed in India, which with the world's largest population of food-insecure people and largest WLT croplands, is a leading example of the observed declines. Here we show geographically matching patterns of enhanced crop production and irrigation expansion with groundwater that have leveled off in the past decade. We estimate that, in the absence of irrigation, the enhancement in dry-season food grain production in India, during 1982-2002, would have required an increase in annual rainfall of at least 30 over almost half of the cropland area. This suggests that the past expansion of use of irrigation has not been sustainable. We expect that improved surface and groundwater management practices will be required to reverse the recent food grain production declines. © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland

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

FIRST LINE AVELUMAB IN PD-L1+VE METASTATIC OR LOCALLY ADVANCED UROTHELIAL CANCER (AUC) PATIENTS UNFIT FOR CISPLATIN (CIS): THE ARIES TRIAL

Background: Avelumab (ave) was approved as maintenance therapy after platinum-based first line (1L) therapy for patients (pts) with aUC based on ph. 3 Javelin Bladder 100 study (NCT02603432), showing significant overall survival (OS) improvement. Here we tested the activity of ave as 1L of therapy in pts with aUC and PD-L1+ve expression. Methods: ARIES is a single-arm, multi-site, open-label phase II trial. Enrolled pts had aUC, were cis-unfit (at least one of: ECOG-PS=2, CrCl &lt;60 mL/min, grade ⩾2 peripheral neuropathy/hearing loss, progression within 6-mos before the end of neo/adj chemo), had not previously received chemo for aUC and PD-L1⩾5% (SP263) centrally assessed. Pts received ave 10 mg/Kg IV Q2W until progression, unacceptable toxicity and withdrawal, whichever occurred first. The primary endpoint was the 1-year OS. Key secondary endpoints were median-OS, -PFS, ORR, DOR and safety. The outcome based on PDL1 expression &gt;10 has also been investigated. Results: A total of 198 eligible cis-unfit pts have been tested for PD-L1 and 71 (35.6%) have been found positive. Among enrolled patients (N=71), median age was 75 y, 35 (49.3%) had visceral disease, and 22 (31.0%) had ECOG-PS=2; 50 (70.4%) had CrCl &lt;60 mL/min and 9 (12.7%) progressed within 6-mos from the end of neo/adj chemo. At the cut-off data (Feb 2, 2022), median follow up was 10.0 mos and 14 patients are still on treatment. The median OS was 10.0 mos (95% CI, 5.5-14.5), and 43.0% of patients were alive at 1-year. The ORR for all patients was 24.0%; complete response, 8.5% (n=6); partial response, 15.5% (n=11). Clinical benefit was 43.6% (n=31). Median PFS was 2.0 mos (95% CI, 1.7-2.3). Among the 17 pts who had tumour response 13 had DOR &gt; 1y and 5 &gt; 2y. A total of 67 patients have been evaluated for CPS and among these 56 (83.6%) have been classified as high expression. The median OS was 11.0 mos (95%CI, 0.1 – 22.9) for those with high CPS and 7.0 mos (95%CI 2.8 – 11.2) for low CPS (p=0.13). The median PFS was 2.0 mos for both high and low CPS (p=0.34). Five (7.0%) grade 3 ave-related adverse events, and no treatment-related death were reported. Conclusions: Ave is active and safe in pts with cis-unfit, PD-L1+ve aUC and poor baseline characteristics

Comparison of Protein- or Amino Acid-Based Supplements in the Rehabilitation of Men with Severe Obesity: A Randomized Controlled Pilot Study

Background: Weight loss is associated with a reduction in all body compartments, including muscle mass (MM), and this effect produces a decrease in function and muscle strength. Our objective was to assess the impact of protein or amino acid supplements on MM loss in middle-aged men (age 35 kg/m2) during weight loss. Materials and Methods: We conducted a single-site randomized controlled trial (Clinicaltrials.gov NCT05143398) with 40 in-patient male subjects with severe obesity. Participants underwent an intervention program consisting of a low-calorie balanced diet and structured physical activity. They were randomly assigned to 4-week treatment groups: (1) control (CTR, N = 10), (2) protein (P, N = 10), (3) branched-chain amino acid (BCAA, N = 10), and (4) essential amino acid mixture with tricarboxylic acid cycle intermediates (PD-E07, N = 10) supplementation. Results: Following 4 weeks of intervention, all groups showed similar reductions in body weight compared to baseline. When examining the delta values, a notable increase in muscle mass (MM) was observed in the PD-E07 intervention group [MM (kg): 2.84 ± 3.57; MM (%): 3.63 ± 3.14], in contrast to the CTR group [MM (kg): −2.46 ± 3.04; MM (%): −0.47 ± 2.28], with a statistical significance of p = 0.045 and p = 0.023, respectively. However, the MM values for the P group [MM (kg): −2.75 ± 5.98, p = 0.734; MM (%): −0.44 ± 4.02, p = 0.990] and the BCAA group [MM (kg): −1 ± 3.3, p = 0.734; MM (%): 0.34 ± 2.85, p = 0.956] did not exhibit a statistically significant difference when compared to the CTR group. Conclusions: Amino acid-based supplements may effectively mitigate the loss of MM typically observed during weight reduction. Further validation through large-scale studies is necessary

Habitat structure: a fundamental concept and framework for urban soil ecology

Habitat structure is defined as the composition and arrangement of physical matter at a location. Although habitat structure is the physical template underlying ecological patterns and processes, the concept is relatively unappreciated and underdeveloped in ecology. However, it provides a fundamental concept for urban ecology because human activities in urban ecosystems are often targeted toward management of habitat structure. In addition, the concept emphasizes the fine-scale, on-the-ground perspective needed in the study of urban soil ecology. To illustrate this, urban soil ecology research is summarized from the perspective of habitat structure effects. Among the key conclusions emerging from the literature review are: (1) habitat structure provides a unifying theme for multivariate research about urban soil ecology; (2) heterogeneous urban habitat structures influence soil ecological variables in different ways; (3) more research is needed to understand relationships among sociological variables, habitat structure patterns and urban soil ecology. To stimulate urban soil ecology research, a conceptual framework is presented to show the direct and indirect relationships among habitat structure and ecological variables. Because habitat structure serves as a physical link between sociocultural and ecological systems, it can be used as a focus for interdisciplinary and applied research (e.g., pest management) about the multiple, interactive effects of urbanization on the ecology of soils

Global Food Security Support Analysis Data (GFSAD) at Nominal 1 km (GCAD) Derived from Remote Sensing in Support of Food Security in the Twenty-First Century: Current Achievements and Future Possibilities

The precise estimation of the global agricultural cropland— extents, areas, geographic locations, crop types, cropping intensities, and their watering methods (irrigated or rain-fed; type of irrigation)—provides a critical scientific basis for the development of water and food security policies (Thenkabail et al., 2010, 2011, 2012). By year 2100, the global human population is expected to grow to 10.4 billion under median fertility variants or higher under constant or higher fertility variants (Table 6.1) with over three-quarters living in developing countries and in regions that already lack the capacity to produce enough food. With current agricultural practices, the increased demand for food and nutrition would require about 2 billion hectares of additional cropland, about twice the equivalent to the land area of the United States, and lead to significant increases in greenhouse gas productions associated with agricultural practices and activities (Tillman et al., 2011). For example, during 1960–2010, world population more than doubled from 3 to 7 billion. The nutritional demand of the population also grew swiftly during this period from an average of about 2000 calories per day per person in 1960 to nearly 3000 calories per day per person in 2010. The food demand of increased population along with increased nutritional demand during this period was met by the “green revolution,” which more than tripled the food production, even though croplands decreased from about 0.43 ha per capita to 0.26 ha per capita (FAO, 2009). The increase in food production during the green revolution was the result of factors such as: (1) expansion of irrigated croplands, which had increased in 2000 from 130 Mha in the 1960s to between 278 Mha (Siebert et al., 2006) and 467 Mha (Thenkabail et al., 2009a,b,c), with the larger estimate due to consideration of cropping intensity; (2) increase in yield and per capita production of food (e.g., cereal production from 280 to 380 kg/person and meat from 22 to 34 kg/person (McIntyre, 2008); (3) new cultivar types (e.g., hybrid varieties of wheat and rice, biotechnology); and (4) modern agronomic and crop management practices (e.g., fertilizers, herbicide, pesticide applications)..

Regulation of extracellular ATP of human erythrocytes treated with α-hemolysin: Effects of cell volume, morphology, rheology and hemolysis

Alpha-hemolysin (HlyA) of uropathogenic strains of Escherichia coli irreversibly binds to human erythrocytes (RBCs) and triggers activation of ATP release and metabolic changes ultimately leading to hemolysis. We studied the regulation of extracellular ATP (ATPe) of RBCs exposed to HlyA. Luminometry was used to assess ATP release and ATPe hydrolysis, whereas changes in cell volume and morphology were determined by electrical impedance, ektacytometry and aggregometry. Exposure of RBCs to HlyA induced a strong increase of [ATPe] (3–36-fold) and hemolysis (1–44-fold), partially compensated by [ATPe] hydrolysis by ectoATPases and intracellular ATPases released by dead cells. Carbenoxolone, a pannexin 1 inhibitor, partially inhibited ATP release (43–67%). The un-acylated toxin ProHlyA and the deletion analog HlyA∆914-936 were unable to induce ATP release or hemolysis. For HlyA treated RBCs, a data driven mathematical model showed that simultaneous lytic and non-lytic release mainly governed ATPe kinetics, while ATPe hydrolysis became important after prolonged toxin exposure. HlyA induced a 1.5-fold swelling, while blocking this swelling reduced ATP release by 77%. Blocking ATPe activation of purinergic P2X receptors reduced swelling by 60–80%. HlyA-RBCs showed an acute 1.3–2.2-fold increase of Ca 2+ i, increased crenation and externalization of phosphatidylserine. Perfusion of HlyA-RBCs through adhesion platforms showed strong adhesion to activated HMEC cells, followed by rapid detachment. HlyA exposed RBCs exhibited increased sphericity under osmotic stress, reduced elongation under shear stress, and very low aggregation in viscous media. Overall results showed that HlyA-RBCs displayed activated ATP release, high but weak adhesivity, low deformability and aggregability and high sphericity.Fil: Leal Denis, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Lefevre, S.D.. Inserm; Francia. Université Paris Diderot - Paris 7; Francia. Université de la Réunion; Francia. Université des Antilles; Francia. Universite de Paris. Institut National de la Transfusion Sanguine.; FranciaFil: Alvarez, Cora Lilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; ArgentinaFil: Lauri, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Enrique, Nicolás Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; ArgentinaFil: Rinaldi, Debora Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Gonzalez-Lebrero, Rodolfo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Vecchio Dezillio, Leandro Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; ArgentinaFil: Espelt, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Stringa, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Muñoz Garay, C.. Universidad Nacional Autónoma de México; MéxicoFil: Milesi, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; ArgentinaFil: Ostuni, M.A.. Inserm; Francia. Université Paris Diderot - Paris 7; Francia. Université de la Réunion; Francia. Université des Antilles; Francia. Universite de Paris. Institut National de la Transfusion Sanguine.; FranciaFil: Herlax, Vanesa Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Schwarzbaum, Pablo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin