Preferential expression of the transcription coactivator HTIF1alpha gene in acute myeloid leukemia and MDS-related AML

HTIF1α, a transcription coactivator which is able to mediate RARα activity and functionally interact with PML, is encoded by a gene on chromosome 7q32–34, which is a critical region in acute myeloid leukemias (AML). With the assumption that this gene may be related to AML, we investigated the HTIF1α DNA structure and RNA expression in leukemic cells from 36 M1–M5 AML patients (28 ‘de novo’ and eight ‘secondary’ to myelodysplastic syndrome (MDS)). Abnormal HTIF1α DNA fragments were never found, whereas loss of HTIF1α DNA was observed in the patients with chromosome 7q32 deletion and translocation, and in one case without detectable chromosome 7 abnormality. HTIF1α RNA was found in acute myelocytic leukemic blasts, and was almost undetectable in normal mononuclear cells. The expression varied among the patients: higher in M1 to M3 subtypes, with the highest values in M1; low levels were constantly observed in M4 and M5 AML. In addition, HTIF1α was significantly overexpressed in MDS-related AML (MDR-AML), but not in MDS. We also found that HTIF1α expression was high in myeloid cell lines. In myeloblastic HL60 and promyelocytic NB4 cells, induced to differentiate along the monocytic–macrophage pathway by TPA or vitamin D3, HTIF1α expression decreased, whereas it was maintained at high levels on induction to granulocytic differentiation by RA or DMSO. In K562 cells, HTIF1α RNA levels did not change after hemin-induced erythroid differentiation. These results suggest that HTIF1α could play a role in myeloid differentiation, being distinctly regulated in hematopoietic lineages

Is it possible to study paleoenvironmental changes in Alpine spring habitats? A few examples from the south-eastern Alps (NE Italy)

Palaeolimnological techniques were applied to spring habitats in the Trentino Region (NE Italy) as a test in order to reconstruct past environmental changes in these crucial and fragile milieus. Three different sites were selected from a database of more than one hundred on the basis of morphological, geological, and biological factors, including human impact evaluation: Nambrone, Paul and Madonnina Val Lomasona. Sampling was performed by adapting standard lake-sediment coring methods, and the retrieved sediment was described and subsampled following standard "lake" procedures. Field work and sedimentological analyses revealed clear influence from nearby fluvial environment for the Nambrone site, whereas Paul and Madonnina Val Lomasona were selected for further analyses (e.g., dating, diatoms, chironomids). Lead-210 and Caesium-137 dating methods were used to obtain a chronological framework, in addition to historical information on land use and other events in the area. The upper part of the Paul sequence presented organic rich sediment compatible with spring environments, but the lower and essentially detrital part appeared to record alluvial deposition, probably linked to extraordinary flood events (1882, 1966). This interpretation is indirectly confirmed by the records of the fallout nuclides Caesium-137 and Lead-210, that were both unfortunately concentrated in the topmost 1 cm, making it impossible to construct a normal age-depth profile. Madonnina Val Lomasona sedimentological and biological indicators point to a marked change around ca 5 cm, dividing the sequence in two units, corresponding to different environmental conditions. Although the interpretation of the dating results is not completely straightforward, the assembled data suggest that the upper 5 cm of the record represents ca the last 50 years. During this period we found typical limnocrenic, clear-water spring conditions, while before 1960s the coexistence of lotic and lentic chironomid species including several opportunistic ones and the low richness, emphasized the presence of a disturbance (e.g., highly variable flow and/or trophic conditions), as confirmed also by diatom assemblages and sedimentological features. The recorded disturbance is probably linked to a water-level change due to the local land use, as also testified by historical data. The results of this study support the idea that carefully selected spring sites might be approached with adapted palaeolimnological techniques to extract valuable palaeoenvironmental information. However, it also highlighted the low percentage of "good sites" (1%) and considerable difficulties in coring and sampling without disturbing the sediment

What are children like?: Historical constructions and social meanings of childhood among educators and caregivers

En este trabajo presentamos una serie de reflexiones emergentes de nuestra experiencia de trabajo durante el año 2019, en dos salas cuna localizadas en diferentes sectores (zona sureste y noroeste) de la ciudad de Córdoba, Argentina. Nos proponemos abordar los sentidos de infancia de docentes y cuidadoras que desempeñan allí sus funciones. Partimos de entender la infancia como una construcción social y cultural. Así también, reconocemos el atravesamiento de diferentes miradas filosóficas y epistemológicas en la construcción de imágenes estereotipadas de que aún hoy se disputan en las instituciones sociales y en el sentido común. El abordaje se realizó mediante una metodología expresivo-creativa, con el objeto de propiciar modos de indagación y reflexión que excedan al lenguaje hablado, para repensar el lugar de la infancia en nuestras sociedades. Con este propósito desarrollamos encuentros/talleres con docentes y cuidadoras de salas cuna, que dieron lugar a la problematización de algunos preconceptos que emergen desde la mirada adulto-céntrica hegemónica y la “infancia idealizada” del discurso publicitario. Los diferentes sentidos que emergen a lo largo de este trabajo, se presentan no como opuestos, sino que se rearticulan permeando las posibilidades de ser y hacer de niños/as. Estos modelos estereotipados obturan la comprensión de la complejidad que presentan las infancias “reales”, otorgándoles un lugar particular en el orden social en contraposición y subordinación al mundo adulto. Por ello, proponemos abordar otro paradigma de infancia, no solo como una propuesta teórica, sino desde su carácter ético, político, social y cultural.In this paper, we present a series of reflections that emerge from our work experience during the year 2019, in two salas cunas (nurseries) located in different areas of the city of Córdoba, Argentina -southeast and northwest. We propose to address the meanings and feelings associated to childhood developed by teachers and caregivers who work there. We start from the notion of childhood as a social and cultural construction. We also acknolwledge the junction of different philosophical and epistemological views in the construction of stereotyped images of childhood, which are still disputed in social institutions and common sense. The study was conducted through an expressive-creative methodology, with the aim of promoting modes of inquiry and reflection that exceed the spoken language, in order to rethink the place of childhood in our societies. To this end, we hosted meetings/workshops with teachers and caregivers of daycare centers, which gave rise to the problematization of some preconceptions emerging from the hegemonic adult-centric view and the "idealized childhood" of the advertising discourse. The different meanings that emerge throughout this work are not presented as opposite ones, but rather as rearticulated concepts permeating the possibilities of being and doing as children. These stereotyped models obstruct the understanding of the complexity presented by "real" childhood, thus assigning it a particular place in the social order as opposed and subordinated to the adult world. Therefore, we propose to address another paradigm of childhood, not only as a theoretical proposal, but also as one viewed from its ethical, political, social and cultural character.Fil: Angeli, María Julia. Universidad Nacional de Cordoba. Instituto de Estudios En Comunicacion, Expresion y Tecnologias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Estudios En Comunicacion, Expresion y Tecnologias.; ArgentinaFil: Simoni, María Laura. Universidad Nacional de Córdoba. Facultad de Medicina. Escuela de Nutrición; Argentin

Activation Effects of Carnosine- and Histidine-Containing Dipeptides on Human Carbonic Anhydrases: A Comprehensive Study

l-Carnosine (beta-Ala-l-His) and several other histidine-containing peptides, including two N-methylated forms on the imidazole ring (l-anserine and l-balenine), two derivatives modified on the carboxyl function (carcinine and l-carnosinamide), two analogues differing in the length of the N-terminal residue (l-homocarnosine and Gly-l-His) and the N-acetyl derivatives, were investigated as activators of four isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The four human isoforms hCA I, II, VA and IX were activated in the low to high micromolar range, with a rather complex structure activity relationship. A performed computational study allowed us to rationalize these results and to propose a binding mode of these activators within the enzyme active site. Similarly to other CA activators, the here studied peptides could find relevant pharmacological applications such as in the management of CA deficiencies, for therapy memory and enhancing cognition or for artificial tissues engineering

¿Cómo son los/as niños/as? Construcciones históricas y sentidos sociales de infancia en docentes y cuidadoras de sala cuna

En este trabajo presentamos una serie de reflexiones emergentes de nuestra experiencia de trabajo durante el año 2019, en dos salas cuna localizadas en diferentes sectores (zona sureste y noroeste) de la ciudad de Córdoba, Argentina. Nos proponemos abordar los sentidos de infancia de docentes y cuidadoras que desempeñan allí sus funciones. Partimos de entender la infancia como una construcción social y cultural. Así también, reconocemos el atravesamiento de diferentes miradas filosóficas y epistemológicas en la construcción de imágenes estereotipadas de que aún hoy se disputan en las instituciones sociales y en el sentido común. El abordaje se realizó mediante una metodología expresivo-creativa, con el objeto de propiciar modos de indagación y reflexión que excedan al lenguaje hablado, para repensar el lugar de la infancia en nuestras sociedades. Con este propósito desarrollamos encuentros/talleres con docentes y cuidadoras de salas cuna, que dieron lugar a la problematización de algunos preconceptos que emergen desde la mirada adulto-céntrica hegemónica y la “infancia idealizada” del discurso publicitario. Los diferentes sentidos que emergen a lo largo de este trabajo, se presentan no como opuestos, sino que se rearticulan permeando las posibilidades de ser y hacer de niños/as. Estos modelos estereotipados obturan la comprensión de la complejidad que presentan las infancias “reales”, otorgándoles un lugar particular en el orden social en contraposición y subordinación al mundo adulto. Por ello, proponemos abordar otro paradigma de infancia, no solo como una propuesta teórica, sino desde su carácter ético, político, social y cultural

DO NASAL DILATORS IMPROVE ENDURANCE PERFORMANCE IN HORSES?

Objetivo. O objetivo deste estudo foi identificar o efeito do dilatador nasal externo (DNE) sobre parâmetros fisiológicos de equinos submetidos a exercício submáximo a campo. Utilizaram-se seis cavalos atletas treinados para provas de vinte quilômetros. Os animais participaram de ambos os grupos, NodiG (sem dilatador nasal) e WidiG (com dilatador nasal) com uma semana de intervalo. Eles foram divididos aleatoriamente para definir o grupo em que começariam o primeiro teste. Realizou-se o teste a campo a 5,5 m/s durante uma hora, percorrendo vinte quilômetros ao todo. Hora do teste, cavaleiro e pista foram sempre os mesmos para todos os animais e momentos. As variáveis fisiológicas avaliadas foram frequências cardíaca e respiratória e lactato sanguíneo em repouso (T0), após dez quilômetros (T1) e vinte quilômetros (T2) e minutos minutos após o final do teste (T3). As frequências cardíaca e respiratória foram maiores de acordo com o exercício em ambos os grupos, mostrando valores diferentes entre T0/T1, T0/T2, T1/T3 e T2/T3. O lactato sanguíneo apresentou um padrão diferente das demais variáveis, com valores maiores entre T0/T1, T0/T2 e T0/T3 também para ambos os grupos. Nenhuma variável foi afetada pelo dispositivo em todos os equinos. Os resultados mostraram que o DNE não melhorou a capacidade aeróbica em cavalos de enduro. PALAVRAS-CHAVES: Dilatador nasal, equinos, frequência cardíaca, lactato sanguíneo

Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII

Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid residues paving the entrance of hCA catalytic site. Herein, we report the synthesis of a small series of new coumarin derivatives 7-11, 15, 17 prepared via classical Pechmann condensation starting from resorcinol derivatives and suitable β-ketoesters. The evaluation of inhibitory activity revealed that these compounds possessed nanomolar affinity and high selectivity towards tumour-associated hCA IX and XII over cytosolic hCA I and hCA II isoforms. To investigate the binding mode of these new coumarin-inspired inhibitors, the most active compounds 10 and 17 were docked within hCA XII catalytic cleft