The role of weighing-bathing sequence and postmenstrual age in eliciting adaptive/maladaptive responses in very low birth weight preterm infants

Purpose: In the neonatal intensive care unit, preterm infants are exposed to several stressful stimuli. Inappropriate stimulation led to high risk for short- and long-term neurocognitive disabilities. This study aimed to evaluate whether the sequence of execution of weighing/bathing nursing procedures and postmenstrual age (PMA) have any effect on preterm infants' stress responses. Design and Methods: Prospective cross-sectional study on a sample of 21 preterm infants. Responses to the procedures were assessed using an observational sheet based on Als's Synactive Theory of Development. Autonomic and motor responses were scored according to five-point Likert scales. The order of execution of weighing/bathing nursing procedures and PMA were documented. Effects of weighing/bathing execution sequence and PMA on autonomic and motor response scores were analyzed by linear multiple regression analysis. Results: The sequence of execution had a significant effect on the autonomic score during weighing (p =.035), evidencing more stress when weighing was executed first. A higher level of stress response on the autonomic score during both weighing (p =.015) and bathing (p =.018) procedure was independently associated with a lower infant PMA. Conclusions and Practice Implications: The real-time recognition of adaptive/maladaptive responses allows nurses to personalize their approach to preterm infants, taking into account PMA and adjusting the appropriate sequence of execution of weighing/bathing nursing procedures

The evolutionary history of the polyQ tract in huntingtin sheds light on its functional pro-neural activities

: Huntington's disease is caused by a pathologically long (>35) CAG repeat located in the first exon of the Huntingtin gene (HTT). While pathologically expanded CAG repeats are the focus of extensive investigations, non-pathogenic CAG tracts in protein-coding genes are less well characterized. Here, we investigated the function and evolution of the physiological CAG tract in the HTT gene. We show that the poly-glutamine (polyQ) tract encoded by CAGs in the huntingtin protein (HTT) is under purifying selection and subjected to stronger selective pressures than CAG-encoded polyQ tracts in other proteins. For natural selection to operate, the polyQ must perform a function. By combining genome-edited mouse embryonic stem cells and cell assays, we show that small variations in HTT polyQ lengths significantly correlate with cells' neurogenic potential and with changes in the gene transcription network governing neuronal function. We conclude that during evolution natural selection promotes the conservation and purity of the CAG-encoded polyQ tract and that small increases in its physiological length influence neural functions of HTT. We propose that these changes in HTT polyQ length contribute to evolutionary fitness including potentially to the development of a more complex nervous system

MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs

MAGE-A genes are a subfamily of the melanoma antigen genes (MAGEs), whose expression is restricted to tumor cells of different origin and normal tissues of the human germline. Although the specific function of individual MAGE-A proteins is being currently explored, compelling evidence suggest their involvement in the regulation of different pathways during tumor progression. We have previously reported that MageA2 binds histone deacetylase (HDAC)3 and represses p53-dependent apoptosis in response to chemotherapeutic drugs. The promyelocytic leukemia (PML) tumor suppressor is a regulator of p53 acetylation and function in cellular senescence. Here, we demonstrate that MageA2 interferes with p53 acetylation at PML-nuclear bodies (NBs) and with PMLIV-dependent activation of p53. Moreover, a fraction of MageA2 colocalizes with PML-NBs through direct association with PML, and decreases PMLIV sumoylation through an HDAC-dependent mechanism. This reduction in PML post-translational modification promotes defects in PML-NBs formation. Remarkably, we show that in human fibroblasts expressing RasV12 oncogene, MageA2 expression decreases cellular senescence and increases proliferation. These results correlate with a reduction in NBs number and an impaired p53 response. All these data suggest that MageA2, in addition to its anti-apoptotic effect, could have a novel role in the early progression to malignancy by interfering with PML/p53 function, thereby blocking the senescence program, a critical barrier against cell transformation. © 2012 Macmillan Publishers Limited. All rights reserved.Fil: Peche, L. Y.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; ItaliaFil: Scolz, M.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; ItaliaFil: Ladelfa, Maria Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Monte, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Schneider, C.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; Italia. Università di Udine; Itali