Bathyraja scaphiops, Cuphead Skate Pollom, R.; Charvet, P.; Chiaramonte, Gustavo Enrique; Cuevas, J.M.; Herman, K.; Paesch, L.; Pompert, J.; Rincon, G. The Cuphead Skate (Bathyraja scaphiops) is a medium-sized (to 117 cm total length) skate that occurs in the Southwest Atlantic from off Rio Grande do Sul, Brazil to Tierra del Fuego, Argentina and the Falkland Islands (Malvinas). It inhabits continental and insular shelves and slopes at depths of 30?925 m. It is targeted or captured as utilized bycatch in demersal trawl fisheries, including the southern Brazil otter trawl fishery, the Patagonian scallop and hake fisheries, and the Falkland Islands (Malvinas) targeted multi-species skate fishery. At the northern extent of its range in southern Brazil, it is captured in the otter trawl fishery which is intense; reductions in the population are suspected there but there are no data. In the Argentina-Uruguay Common Fishing Zone (AUCFZ), this species was captured frequently in commercial trawls between 1984 and 2009. On the shelf edge off Argentina between Buenos Aires and northern Santa Cruz, this species was present in 9% of research trawls in the area trawled by the Patagonian scallop fishery in 2010. In the Falkland Islands (Malvinas), this species made up an average of 3.5% of the catch in the multi-species skate fishery between 1993 and 2013, with no clear trend in catch-per-unit-effort over that time frame. Overall, although this species is subjected to substantial fishing pressure, it has remained common in catches and it may have refuge over rough substrates that are untrawlable. Although fisheries are likely leading to some reduction in population size, the level is not suspected to approach the thresholds for a threatened assessment. Therefore, the Cuphead Skate is assessed as Least Concern.

Sesamoids in Caudata and Gymnophiona (Lissamphibia): Absences and evidence Ponssa, María Laura; Abdala, Virginia Sara Luz An integrative definition of sesamoid bones has been recently proposed, highlighting their relationship with tendons and ligaments, their genetic origin, the influence of epigenetic stimuli on their development, and their variable tissue composition. Sesamoid bones occur mainly associated with a large number of mobile joints in vertebrates, most commonly in the postcranium. Here, we present a survey of the distribution pattern of sesamoids in 256 taxa of Caudata and Gymnophiona and 24 taxa of temnospondyls and lepospondyls, based on dissections, high-resolution X-ray computed tomography from digital databases and literature data. These groups have a pivotal role in the interpretation of the evolution of sesamoids in Lissamphibia and tetrapods in general. Our main goals were: (1) to contribute to the knowledge of the comparative anatomy of sesamoids in Lissamphibia; (2) to assess the evolutionary history of selected sesamoids. We formally studied the evolution of the observed sesamoids by optimizing them in the most accepted phylogeny of the group. We identified only three bony or cartilaginous sesamoids in Caudata: The mandibular sesamoid, which is adjacent to the jaw articulation; one located on the mandibular symphysis; and one located in the posterior end of the maxilla. We did not observe any cartilaginous or osseous sesamoid in Gymnophiona. Mapping analyses of the sesamoid dataset of urodeles onto the phylogeny revealed that the very conspicuous sesamoid in the mandibular symphysis of Necturus beyeri and Amphiuma tridactylum is an independent acquisition of these taxa. On the contrary, the sesamoid located between the maxilla and the lower jaw is a new synapomorphy that supports the node of Hydromantes platycephalus and Karsenia coreana. The absence of a mandibular sesamoid is plesiomorphic to Caudata, whereas it is convergent in seven different families. The absence of postcranial sesamoids in salamanders might reveal a paedomorphic pattern that would be visible in their limb joints.

Sobre el género Chaudoirina Mateu (Coleoptera: Carabidae): aspectos nomenclaturales y patrones de distribución de sus especies, con dos nuevas citas para Chile; On the genus Chaudoirina Mateu (Coleoptera: Carabidae), nomenclatural aspects and distribution patterns of its species, with two new citations for Chile Cid Arcos, Mauricio; Roig, Sergio Alberto El presente trabajo busca clarificar aspectos nomenclaturales de Chaudoirina, proporcionar una clave e ilustraciones para identificar sus especies y entregar datos sobre su distribución, citando a C. vianai y C. orfilai para Chile

Length-weight relationship of fish from high mountain freshwater environments of the central Andes, Argentina; Relación largo-peso de peces de ambientes de agua dulce de alta montaña de los Andes centrales, Argentina Rios, Juan Manuel; Teixeira de Mello, Franco This study provides the length-weight relationship in four nonnative and one nativefish species of the central Andes, Argentina. The only species showing positive allometricgrowth was the native torrent catfish Hatcheria macraei.; Este estudio proporciona las relaciones largo-peso para cuatro especies de peces exóticas y una nativa de los Andes centrales, Argentina. La única especie que mostró un crecimiento alométrico positivo fue la especie nativa bagre torrente Hatcheria macraei.

The xenarthrans of Honduras: new records, main threats, and comments on their conservation status; Los xenartros de Honduras: nuevos registros, principales amenazas y comentarios sobre su estado de conservación Turcios Casco, Manfredo A.; Ávila Palma, Hefer D.; Martínez, Marcio; Trejo Ordoñez, Eduardo J.; Meza Flores, David E.; Castañeda, Franklin; King, Travis; Thornton, Daniel; Superina, Mariella The Xenarthra are one of the least studied mammalian groups in Honduras. Their ecology, natural history, and distribution in the country are poorly known. Here we compile and discuss, for the first time, the available information about the seven species of Xenarthra that occur in Honduras. We also present new distribution records and comment on their main threats. The lack of specific scientific studies, poaching, illegal traffic, cultural beliefs, and deforestation are among the main threats to xenarthrans in Honduras.; Xenarthra es uno de los grupos de mamíferos menos estudiados en Honduras, y de los que menos se sabe sobre su ecología, historia natural y distribución en el país. Aquí recopilamos y discutimos, por primera vez, la información disponible de cada una de las siete especies de Xenarthra que ocurren en Honduras. También presentamos nuevos registros de distribución y comentamos sobre las principales amenazas. La falta de estudios científicos, la cacería y el tráfico ilegal, creencias culturales y la deforestación están entre algunas de las principales amenazas para los xenartros en Honduras.

Recalibrating immunity in cancer and autoimmune inflammation by lectin-driven regulatory circuits Bach, Camila Agustina; Cutine, Anabela María; Laporte, Lorena; Mahmoud, Yamil Damián; Manselle Cocco, Montana Nicolle; Massaro, Mora; Merlo, Joaquín Pedro; Perrotta, Ramiro Martin; Sarbia, Nicolás; Veigas, Florencia; Rabinovich, Gabriel Adrián Endogenous lectins play key roles in cell homeostasis by decoding the informationencrypted in glycans present on the cell surface or extracellular matrix. Galectins, a familyof soluble lectins, have emerged as central regulators of innate and adaptive immuneresponses. In this article we review seminal work demonstrating the immunoregulatoryroles of Galectin-1 (Gal-1), a proto-type member of the galectin family, and highlightcentral mechanisms that control its functions in cancer and autoimmune inflammation.Understanding the cellular pathways that control Gal-1 expression and function in tumorand inflammatory microenvironments will set the bases for the design of rational therapiesbased on positive or negative modulation of this endogenous lectin in cancer andautoimmune diseases.

Influence of the N atom and its position on electron photodetachment of deprotonated indole and azaindole Noble, Jennifer Anna; Marceca, Ernesto José; Dedonder, Claude; Jouvet, Christophe Electron photodetachment of cold deprotonated indole and azaindole anions has been studied by use of a mass-selective photofragmentation spectrometer capable of negative ion and neutral particle detection. The electron affinities of the indolyl radical and the 5-, 6- A nd 7-azaindolyl radicals have been measured with an uncertainty of less than 0.002 eV. The presence of the nitrogen atom in the six-membered ring of the azaindolide anions stabilises the electron by 0.3 to 0.4 eV, i.e. about 10-15%, compared to the indolide anion. No fragmentation was observed in either the anionic or radical forms of the species studied. The appearance of dipole-bound states in the spectra of deprotonated 6- A nd 7-azaindole anions allowed us to analyse the vibrational structure of the neutral 6- A nd 7-azaindolyl radicals produced following photodetachment. Although no dipole-bound states were clearly identified for deprotonated indole or 5-azaindole, the shape of the photodetachment threshold suggests the presence of a very weakly dipole-bound state or dipole resonance, which cannot be resolved with our laser resolution.

The Moderate Alcohol and Cardiovascular Health Trial (MACH15): Design and methods for a randomized trial of moderate alcohol consumption and cardiometabolic risk Spiegelman, Donna; Lovato, Laura C.; Khudyakov, Polyna; Wilkens, Trine L.; Adebamowo, Clement A.; Adebamowo, Sally N.; Appel, Lawrence J.; Beulens, Joline W.J.; Coughlin, Janelle W.; Dragsted, Lars Ove; Edenberg, Howard J; Eriksen, Jane N.; Estruch, Ramon; Grobbee, Diederick E.; Gulayin, Pablo Elías; Irazola, Vilma; Krystal, John H.; Lazo, Mariana; Murray, Margaret M.; Rimm, Eric B.; Schrieks, Ilse C.; Williamson, Jeff D.; Mukamal, Kenneth J. Background: Observational studies have documented lower risks of coronary heart disease and diabetes among moderate alcohol consumers relative to abstainers, but only a randomized clinical trial can provide conclusive evidence for or against these associations. Aim: The purpose of this study was to describe the rationale and design of the Moderate Alcohol and Cardiovascular Health Trial, aimed to assess the cardiometabolic effects of one alcoholic drink daily over an average of six years among adults 50 years or older. Methods: This multicenter, parallel-arm randomized trial was designed to compare the effects of one standard serving (∼11–15 g) daily of a preferred alcoholic beverage to abstention. The trial aimed to enroll 7800 people at high risk of cardiovascular disease. The primary composite endpoint comprised time to the first occurrence of non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalized angina, coronary/carotid revascularization, or total mortality. The trial was designed to provide >80% power to detect a 15% reduction in the risk of the primary outcome. Secondary outcomes included diabetes. Adverse effects of special interest included injuries, congestive heart failure, alcohol use disorders, and cancer. Results: We describe the design, governance, masking issues, and data handling. In three months of field center activity until termination by the funder, the trial randomized 32 participants, successfully screened another 70, and identified ∼400 additional interested individuals. Conclusions: We describe a feasible design for a long-term randomized trial of moderate alcohol consumption. Such a study will provide the highest level of evidence for the effects of moderate alcohol consumption on cardiovascular disease and diabetes, and will directly inform clinical and public health guidelines.

El significado de las últimas palabras: las notas suicidas como acciones comunicativas: Buenos Aires, 1859-1888; The meaning of the last words: suicide notes as a communicative actions: Buenos Aires, 1859-1888 Arroyo, Julián En el presente artículo abordamos, desde una perspectiva histórica y sociocultural, un conjunto de casos de suicidio ocurridos en la ciudad de Buenos Aires entre 1859 y 1888, con el fin de estudiar las cartas de los que se quitaban la vida. Entendemos estos escritos como acciones comunicativas que tenían diferentes significados, y transmitían mensajes a los integrantes de la red vincular del suicida. En relación con este propósito general, uno de nuestros objetivos específicos es explorar las circunstancias, preocupaciones y conflictos que formaban parte del contexto en el que estos textos fueron elaborados. Es decir, nos proponemos dar pasos orientados a responder la siguiente pregunta: ¿en qué situaciones era más frecuente que los suicidas dejaran registradas sus últimas palabras? Tomando como punto de partida los indicios extraídos de los sumarios judiciales, en este trabajo mostramos que las cartas aparecían de forma más frecuente en expedientes que narraban una serie de hechos particulares. Asimismo, sostenemos que estas explicaciones verosímiles de los actos suicidas, y las notas asociadas a estos, eran enunciadas a partir de los horizontes de expectativas que tenían los hombres y mujeres de la ciudad de Buenos Aires durante el último tercio del siglo XIX.; In this article we study, from a historical and sociocultural perspective, a set of suicide cases that occurred in the city of Buenos Aires between 1859 and 1888 to analyze the letters left by those who committed suicide. We understand these writings as communicative actions that had different meanings, and transmitted messages to the members of the deceased's social network. Also, one of our specific objectives is to explore the circumstances, concerns and conflicts that were part of the context in which these texts were produced. In other words, we seek to answer the following question: in which situations did suicide notes appear more frequently? Based on the evidence from the the judicial summaries, in this paper we show that letters appeared more frequently in files that narrated a series of particular events. Likewise, we argue that these plausible explanations of suicidal acts, and the notes associated with them, were stated based on the expectations of men and women from Buenos Aires during the last third of the 19th century.

El Archivo Histórico del Agua del Departamento General de Irrigación de la Provincia de Mendoza, Argentina; The Historical Archive of Water of the General Department of Irrigation of the Province of Mendoza, Argentina Martin, Facundo Damian; Healey, Mark; Fili, Juan Pablo; Parise Schneider, Nicolás; Engelman, Anabella Ayelén En este artículo presentamos el Archivo Histórico del Agua (AHA) del Departamento General de Irrigación perteneciente a la Provincia de Mendoza. Para esto realizamos un recorrido por la historia de las instituciones productoras de los archivos, caracterizamos los principales fondos hallados y delineamos los desafíos y oportunidades que implica el des-cubrimiento de fuentes históricas poco visibles o no analizadas hasta el momento.; This article presents the Historical Water Archive of the General Irrigation Department of the provincial government of Mendoza, Argentina. The article begins with the historical development of the institutions producing the archive, then surveys the main collections it contains, and sketches the challenges and opportunities of un-covering historical sources barely visible or analyzed until the present.

La expansión agrícola en el cinturón verde de la Ciudad de Mendoza: Aportes sobre la trayectoria de las explotaciones agropecuarias en el caso de Fray Luis Beltrán; Agricultural expansion in Mendoza's city green belt: Contributions on the trajectory of farms in the case of Fray Luis Beltrán Dalmasso, Caterina; Mussetta, Paula Cecilia Las transformaciones territoriales del Área Metropolitana de Mendoza han impactado en su cinturón verde. Sin embargo, estudios recientes indican que, pese a la expansión urbana, la superficie cultivada se ha mantenido relativamente estable e identifican que los productores que salen de un sitio, se relocalizan en otras zonas menos competitivas. Bajo una metodología cuanti-cualitativa, este trabajo profundiza en las particularidades de la dinámica territorial en Fray Luis Beltrán (Maipú), distrito que en los últimos años ha registrado un importante crecimiento de superficie cultivada. Desde un enfoque territorial, el artículo da cuenta del proceso de expansión agrícola en este distrito e identifica las condiciones territoriales que lo habilitan. Encuentra, además, que dicho proceso es protagonizado por actores locales que cuentan con larga trayectoria en el cinturón verde de Mendoza. Como resultado, el estudio destaca que el avance de la horticultura en Fray Luis Beltrán no es un fenómeno directa o linealmente impulsado por la relocalización de las fincas urbanizadas. Asimismo, resalta la conformación de un modelo de horticultura que se distingue de la existente en otras áreas del cinturón verde, así como de procesos expansivos generados en otras áreas productivas.; Transformations of Mendoza Metropolitan Area have impacted the green belt. Recent studies indicate that despite urban expansion, the cultivated area has remained relatively stable. Additionally, they identify a trend that would indicate that producers who leave one site are relocating to other less competitive areas. Applying a quantitative-qualitative methodology, this work examines the particularities of the territorial dynamics in Fray Luis Beltrán (Maipú), a district that in recent years has registered a significant growth in cultivated area. Taking a territorial approach, this article reports the process of agricultural expansion in this district and identifies the conditions that enable it. It also finds that this process is led by local actors with a long trajectory in Mendoza's green belt. The study highlights that the advance of horticulture in Fray Luis Beltrán is not a direct or linear phenomenon driven by the relocation of urbanized farms. Furthermore, it points out the conformation of a horticulture model that differs from the existing one in other areas of the green belt, as well as from expansive processes generated in other productive areas.

Tratamiento quirúrgico en acromegalia: experiencia en Córdoba; Surgical treatment in acromegaly: Experience in Córdoba Rendón, Matilde Inés; Cecenarro, Laura Anahi; Andrada, Marta Cecilia; Barovero, Mariela Susana; Bertolino, María Lorena; Cagliolo, Mariela; Carpentieri, Agata Rita; Damilano, Roxana Analía; De Battista, Juan Carlos; Estario, Paula; Fernández, Silvia; Marquez, Maria Eugenia; Monteserin, Natalia; Quintero, María Lorena; Sala, Claudia Susana; Sosa, Gabriela Alejandra; Surraco, María Elena; de Paul, Ana Lucia; Szafryk de Mereshian, Paula Maria; Fux Otta, Carolina La acromegalia tiene una prevalencia de 35-70/millón. La cirugía transesfenoidales el tratamiento de elección, siendo la tasa de remisión del 80% en microadenomas y 50% en macroadenomas. Debido a la falta de registros, nos propusimos evaluar los resultados quirúrgicos en Córdoba y determinar factores predictivos de remisión.Métodos: Estudio retrospectivo-descriptivo de pacientes con cirugía como primera línea terapéutica. Criterios de remisión: normalización de IGF1 para edad/sexo, con GH ≤1,0 g/L.TestX2 y test exacto de Fisher y p<0,05.Resultados:Se incluyeron 38 pacientes: 61% mujeres y 39% hombres; edad promedio 45 años. Motivos de consulta más frecuentes: cefalea y crecimiento acral (26%), alteraciones visuales (20%). El 84% de los tumores fueron macroadenomas. De 37 pacientes, 54% se sometierona cirugía microscópica, 38% endoscópica y 8% transcraneal. El 29% evidenció complicaciones postquirúrgicas, siendo la diabetes insípida la más frecuente (10%). El porcentaje de las mismas fue: cirugía transcraneal el 33%, endoscópica 29% y microscópica 25% (p= 0,557). La remisión bioquímica a los 6 meses fue de 34% y a los 12 meses 55% (p=0,0001). Sin diferencias significativas entre la vía endoscópica y microscópica (p=0,071). De 36 pacientes el 31% evidenció resección tumoral completa. La mejoría clínicasubjetiva fue del 88%. No hubo factores predictivos de remisión bioquímica estadísticamente significativos. La remisión bioquímica con la cirugía fue similar a la bibliografía. No encontramos factores predictivos deremisión pero un número mayor de casos podría modificar estos resultados; Acromegaly prevalence is 35-70 / million. Transsphenoidal surgery is the first-line treatment, with a remission rate of 80% for microadenomas and 50% for macroadenomas. Our aim was to evaluate the surgical results in Córdoba and determine predictive remission factors due to the lack of records. Methods: Retrospective-descriptive study of patients with surgery as the first therapeutic line. Remission criteria: IGF1 normalization for age/sex, with GH ≤1.0 g/L. Test X2 and Fisher´s exact test with p<0.05. Results: 38 patients were included: 61% women and 39% men; Average age 45 years. Most frequent chief complaint: headache and acral growth (26%), visual disturbances (20%). Macroadenomas were the 84% of the tumors. Of 37 patients, 54% underwent microscopic surgery, 38% endoscopic and 8% transcranial. The 29% of patients showed post-operative complications and diabetes insipidus was the most frequent (10%). The percentage of them was: 33% transcranial surgery, 29% endoscopic and 25% microscopic (p = 0.557). The biochemical remission at 6 months was 34% and at 12 months 55% (p= 0.0001). No significant differences between the endoscopic and microscopic approach (p = 0.071). Of 36 patients, 31% showed complete tumor resection. The subjective clinical improvement was 88%. There weren´t predictive remission factors with significant differences. Conclusion: The surgical biochemical remission was similar to the bibliography. We didn´t find predictive remission factors but a larger number of patients could modify these results.Key words: acromegaly; neurosurgery; postoperative complications; remission induction

Role of VAMP7-Dependent Secretion of Reticulon 3 in Neurite Growth Wojnacki, José; Nola, Sébastien; Bun, Philippe; Cholley, Béatrice; Filippini, Francesca; Pressé, Mary T.; Lipecka, Joanna; Man Lam, Sin; N'guyen, Julie; Simon, Axelle; Ouslimani, Amine; Shui, Guanghou; Fader Kaiser, Claudio Marcelo; Colombo, Maria Isabel; Guerrera, Ida Chiara; Galli, Thierry VAMP7 is involved in autophagy and in exocytosis-mediated neurite growth, two yet unconnected cellular pathways. Here, we find that nutrient restriction and activation of autophagy stimulate axonal growth, while autophagy inhibition leads to loss of neuronal polarity. VAMP7 knockout (KO) neuronal cells show impaired neurite growth, whereas this process is increased in autophagy-null ATG5 KO cells. We find that endoplasmic reticulum (ER)-phagy-related LC3-interacting-region-containing proteins Atlastin 3 and Reticulon 3 (RTN3) are more abundant in autophagy-related protein ATG5 KO and less abundant in VAMP7 KO secretomes. Treatment of neuronal cells with ATG5 or VAMP7 KO conditioned medium does not recapitulate the effect of these KOs on neurite growth. A nanobody directed against VAMP7 inhibits axonal overgrowth induced by nutrient restriction. Furthermore, expression of the inhibitory Longin domain of VAMP7 impairs the subcellular localization of RTN3 in neurons. We propose that VAMP7-dependent secretion of RTN3 regulates neurite growth.

Patagones en el mapa del Amazonas de Samuel Fritz (1707); Patagones no mapa do Amazonas de Samuel Fritz (1707); Patagonians on Samuel Fritz's map of the Amazon (1707); Patagons dans la carte de l’Amazone de Samuel Fritz (1707) Martinez, Carolina Desde las perspectivas abiertas por la historia cultural y la historia de la cartografía, este trabajo examina la iconografía presente en el mapa de El Gran Rio Marañón o Amazonas, realizado por el padre jesuita Samuel Fritz e impreso en el Colegio Máximo de la ciudad de Quito en 1707. A diferencia de los enfoques historiográficos que han visto en las imágenes que ilustran la cartela del mapa un reflejo del trabajo misional de la Compañía de Jesús en la cuenca del Amazonas, el análisis de las figuras centrales del mapa revela que sus orígenes se encuentran en la experiencia de los holandeses que navegaron el área magallánico-fueguina hacia fines del siglo XVI. El trabajo se centra, entonces, en los procesos de producción y circulación de aquellas imágenes cartográficas que, desplazadas de sus contextos originales de producción, devinieron representativas de América meridional en su totalidad cuando no de la región amazónica en particular.

Las familias toman la calle en el barrio: Acción colectiva, participación política y disputas simbólicas en torno a lo escolar; Families take up the streets in the neighborhood: Collective action, political participation and symbolic disputes over what counts as “schooling” Meo, Analía Inés; Heras Monner Sans, Ana Ines En este ensayo argumentamos que la toma de la calle, literal y simbólica, llevada adelante por familias de una escuela primaria, es una acción política auto-organizada. Para ello, hemos mapeado el campo local de posicionamientos conceptuales y examinamos una acción de las familias, llamada LaMesita por sus creadorxs, con el propósito de analizar las particularidades que este accionar colectivo asume, así como evidenciar de qué modo su estudio enriquece al emergente -aunque aún marginal- corpus de investigaciones sobre las formas de auto-organización de familias en el ámbito escolar. El análisis de este caso nos servirá para reflexionar críticamente sobre los estudios de la acción política en el campo escolar y apuntar a la necesidad de prestar más atención a las intervenciones locales,; This essay argues that a group of families of a primary school takes the street and this material and symbolic intervention is a self-organised political action. On the one hand, we map out conceptual positions in Argentina around collective action in the field of schooling. On the other, we examine the features, scope, and effects of one collective action called by its creators LaMesita. This piece evidences how the study of the latter enriches the emergent (although still marginal) body of research on self-organised political action of families in primary schooling. This case will help us to critically reflect on the studies on political action around compulsory schooling. Furthermore, it allows us to argue for the need to pay more attention to local, every day and face to face interactions in order to recognise the variety of forms that struggles over the legitimate participation in schooling take place.

Amphiphilic ionic liquids as sustainable components to formulate promising vesicles to be used in nanomedicine Falcone, Ruben Dario; Correa, Nestor Mariano; Silber, Juana J. Ionic Liquids (ILs) are an interesting category of compounds particularly because of the possibility to easily synthesize them with different attractive properties, in the lab. The interest for ILs with amphiphilic character (IL-like surfactants) has been growing up because of versatility in creating useful supramolecular assemblies. In this short review, the current state of IL-like surfactants to prepare vesicles in water is described. Particularly, the focus has been put on the experiments performed by South American researchers using protic and aprotic surfactants. Finally, it summarizes some preliminary results obtained in our lab about the application in nanomedicine that these novel vesicles can offer.

Testosterone-loaded GM1 micelles targeted to the intracellular androgen receptor for the specific induction of genomic androgen signaling Peinetti, Nahuel; Cuello Rubio, Mariana Micaela; Sosa, Liliana del Valle; Scalerandi, María Victoria; Alasino, Roxana Valeria; Peyret, Victoria; de Nicola, Juan Pablo; Beltramo, Dante Miguel; Quintar, Amado Alfredo; Maldonado, Cristina Alicia Androgens play a central role in homeostatic and pathological processes of the prostate gland. At the cellular level, testosterone activates both the genomic signaling pathway, through the intracellular androgen receptor (AR), and membrane-initiated androgen signaling (MIAS), by plasma membrane receptors. We have previously shown that the activation of MIAS induces uncontrolled proliferation and fails to stimulate the beneficial immunomodulatory effects of testosterone in prostatic cells, becoming necessary to investigate if genomic signaling mediates homeostatic effects of testosterone. However, the lack of specific modulators for genomic androgen signaling has delayed the understanding of this mechanism. In this article, we demonstrate that monosialoganglioside (GM1) micelles are capable of delivering testosterone into the cytoplasm to specifically activate genomic signaling. Stimulation with testosterone-loaded GM1 micelles led to the activation of androgen response element (ARE)-regulated genes in vitro as well as to the recovery of normal prostate size and histology after castration in mice. In addition, these micelles avoided MIAS, as demonstrated by the absence of rapid signaling pathway activation and the inability to induce uncontrolled cell proliferation. In conclusion, our results validate a novel tool for the specific activation of genomic androgen signaling and demonstrate the importance of selective pathway activation in androgen-mediated proliferation.

Cancer immunotherapy–related adverse events: causes and challenges Blidner, Ada Gabriela; Choi, Jennifer Ailen; Cooksley, Tim; Dougan, Michael; Glezerman, Ilya; Ginex, Pamela; Girotra, Monica; Gupta, Dipti; Johnson, Douglas; Shannon, Vickie R.; Suarez Almazor, Maria; Rapoport, Bernardo L.; Anderson, Ronald Despite the success and ongoing promise of monoclonal antibody–targeted immune checkpoint inhibitor immunotherapy of advanced malignancies, in particular, antibodies directed against CTLA-4 and PD-1/PD-L1, the development of immune-related adverse events (irAEs) remains a constraint of this type of therapy. Although rarely fatal, the occurrence of irAEs may necessitate discontinuation of immunotherapy, as well as administration of corticosteroids or other immunosuppressive therapies that may not only compromise efficacy but also predispose for development of opportunistic infection. Clearly, retention of efficacy of immune checkpoint–targeted therapies with concurrent attenuation of immune-mediated toxicity represents a formidable challenge. In this context, the current brief review examines mechanistic relationships between these events, as well as recent insights into immunopathogenesis, and strategies which may contribute to resolving this issue. These sections are preceded by brief overviews of the discovery and functions of CTLA-4 and PD-1, as well as the chronology of the development of immunotherapeutic monoclonal antibodies which target these immune checkpoint inhibitors.

A plausible extension of standard penalty, streamline upwind and immersed boundary techniques to the improved element-free Galerkin-based solution of incompressible Navier–Stokes equations Álvarez Hostos, Juan Carlos; Cruchaga, Marcela A.; Fachinotti, Victor Daniel; Zambrano Carrillo, Javier Alexander; Zamora Ramirez, Esteban Alonso The present work has been conducted in order to propose the extension of standard penalty and stabilization techniques to the improved element-free Galerkin (IEFG) method, for the numerical solution of incompressible fluid flow problems. In principle, the numerical procedures to be implemented in this communication have been conceived for finite element method (FEM)-based solutions, and these include the reduced integration penalty method (RIPM), the streamline upwind Petrov–Galerkin (SUPG) scheme, and a penalty-based immersed boundary method (PBIBM) for the imposition of essential boundary conditions along internal fluid–solid interfaces. The linear momentum balance and mass conservation equations have been coupled via the RIPM, in order to obtain a global weak formulation where the IEFG model is entirely developed in terms of improved moving least squares (IMLS) approximations of the velocity field. A detailed explanation concerning the appropriate extension of both the RIPM and SUPG procedures to the context of IEFG formulations, has also been provided. The resulting formulation has been applied to the solution of two well-known benchmark problems: i) Lid-driven square cavity flow, and ii) Flow past a fixed cylinder. Regarding the flow past a fixed cylinder benchmark problem, the fluid–solid interaction has been imposed as an internal immersed boundary condition via the PBIBM. The feasibility and reliability of implementing the RIPM, SUPG and PBIBM procedures in the IEFG formulation, have been proven by comparison with experimental and mesh-based numerical results reported in the literature. The results obtained in this study have revealed that a proper extension of the aforementioned penalty and stabilization techniques to the IEFG formulation, allows the achievement of accurate and stable numerical results during the solution of incompressible fluid-dynamics problems.

From town to town: Predicting the taxonomic, functional and phylogenetic diversity of birds using NDVI Leveau, Lucas Matias; Isla, Federico Ignacio; Bellocq, Maria Isabel Biodiversity mapping in urban areas is imperative for their conservation. Remote sensors produce environmental information, such as the Normalized Difference Vegetation Index (NDVI), an indicator of vegetation cover in urban areas. NDVI can be used to predict the taxonomic, functional and phylogenetic bird diversity in urban areas. Moreover, a predictive model constructed in one city can be used to predict the bird diversity in other cities. The objectives of this study were: 1) to construct and evaluate predictive models between NDVI and taxonomic, functional and phylogenetic diversity of birds in Mar del Plata city, Argentina; and 2) to extrapolate these models to two other cities in the region: Balcarce and Miramar. Generalized additive models were applied to relate bird diversity variations to NDVI. In Mar del Plata, the taxonomic and functional diversity increased with increasing NDVI values, and the predictive models explained 64–81% of the taxonomic and functional diversity variation. The models correctly predicted taxonomic and functional diversity values in additional transects not included in the models, although they had a low predictive power of phylogenetic diversity. The models constructed in Mar del Plata adequately predicted the spatial variation of species diversity (Shannon index) in Balcarce and Miramar, the spatial variation of species richness in Balcarce, and the variation of functional diversity in Miramar. Our analysis revealed that a predictive model of bird diversity based on NDVI patterns created in one city can also depict the expected species diversity in other cities, being a time-saving and cost-effective method to create a tool for urban biodiversity conservation.