Stress induced polarization of immune-neuroendocrine phenotypes in Gallus gallus

Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals’ interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-γ and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.Fil: Nazar, Franco Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Estevez, Inma. Centro de Investigación. Neiker - Tecnalia; EspañaFil: Correa, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Marin, Raul Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

Clothing, race and identity : sumptuary laws in colonial Spanish America

On holidays and other festive occasions, Andean peoples in the Spanish Viceroyalty of Peru liked to dress up. According to sixteenth - century documents, wealthy Amerindians in Lima, Quito and other colonial cities enjoyed wearing a combination of European and Andean garments, sometimes made of silk and other expensive, imported fabrics. Their sartorial exuberance annoyed local Spaniards, who issued repeated orders prohibiting Amerindians from wearing a range of garments containing silk, velvet, Holland cloth, lace and other embellishments. The indigenous elite did not accept these prohibitions without protest. In 1593, members of the Amerindian community in Quito wrote to Emperor Philip II to complain that ‘as conquered people it sometimes happens that officials and other people undress them and take their clothing, saying that they can wear only cotton, which causes them much trouble and vexation

Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer

Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing this kinase, through either RNA interference or CRISPR, sensitized tumor cells to chemotherapy and hindered metastasis in vitro and in vivo in a tail vein injection model. Drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduced all effects of RSK4 silencing in vitro and in/ex vivo using lung cancer xenograft and genetically engineered mouse models and bladder tumor explants. Through x-ray structure determination and Markov transient and Deuterium exchange analyses, we identified the allosteric binding site and revealed how this compound blocks RSK4 kinase activation through binding to an allosteric site and mimicking a kinase autoinhibitory mechanism involving the RSK4’s hydrophobic motif. Last, we show that patients undergoing chemotherapy and adhering to prophylactic levofloxacin in the large placebo-controlled randomized phase 3 SIGNIFICANT trial had significantly increased (P = 0.048) long-term overall survival times. Hence, we suggest that RSK4 inhibition may represent an effective therapeutic strategy for treating lung and bladder cancer

Extracellular vesicles at the heart of cell-cell communication

Extracellular vesicles are cargoes able to transport important information from one cell to another, allowing the organism to respond to external stimuli. This thesis focused on the heart, and how vesicles released from the contractile cells, cardiomyocytes, can affect the behaviour of cells forming arteries and veins, endothelial cells. The research showed how an unhealthy enlarged cardiomyocyte release vesicles can have a molecular content different form the healthy counterpart. The unhealthy cells express in their cargoes a small RNA, called miRNA-200c that has a detrimental effect on the behaviour of endothelial cells. Moreover, it was showed that in mice with enlarged hearts, inhibiting the expression of miR-200c had beneficial effects on endothelial remodelling and restored cardiac function. The next step was to visualise the vesicles in the heart; for this purpose a system that resembles a light switch was used. When a cell receives a vesicle, it will switch its colour from red to green allowing us to visualise it. This tracking system gave a better insight of the extracellular vesicles biology, release and uptake

Non-coding RNAs in cardiac hypertrophy

Heart failure is one of the largest contributors to disease burden and healthcare outflow in the Western world. Despite significant progress in the treatment of heart failure, disease prognosis remains very poor, with the only curative therapy still being heart transplantation. To counteract the current situation, efforts have been made to better understand the underlying molecular pathways in the progression of cardiac disease towards heart failure, and to link the disease to novel therapeutic targets such as non-coding RNAs. The non-coding part of the genome has gained prominence over the last couple of decades, opening a completely new research field and establishing different non-coding RNAs species as fundamental regulators of cellular functions. Not surprisingly, their dysregulation is increasingly being linked to pathology, including to cardiac disease. Pre-clinically, non-coding RNAs have been shown to be of great value as therapeutic targets in pathological cardiac remodelling and also as diagnostic/prognostic biomarkers for heart failure. Therefore, it is to be expected that non-coding RNA-based therapeutic strategies will reach the bedside in the future and provide new and more efficient treatments for heart failure. Here, we review recent discoveries linking the function andmolecular interactions of non-coding RNAs with the pathophysiology of cardiac hypertrophy and heart failure.</p

Aristotle's illusion in Parkinson's disease: evidence for normal interdigit tactile perception.

Sensory alterations, a common feature of such movement disorders as Parkinson's disease (PD) and dystonia, could emerge as epiphenomena of basal ganglia dysfunction. Recently, we found a selective reduction of tactile perception (Aristotle's illusion, the illusory doubling sensation of one object when touched with crossed fingers) in the affected hand of patients with focal hand dystonia. This suggests that reduced tactile illusion might be a specific feature of this type of dystonia and could be due to abnormal somatosensory cortical activation. The aim of the current study was to investigate whether Aristotle's illusion is reduced in the affected hand of patients with PD. We tested 15 PD patients, in whom motor symptoms were mainly localised to one side of the body, and 15 healthy controls. Three pairs of fingers were tested in crossed (evoking the illusion) or parallel position (not evoking the illusion). A sphere was placed in the contact point between the two fingers and the blindfolded participants had to say whether they felt one or two stimuli. Stimuli were applied on the affected and less or unaffected side of the PD patients. We found no difference in illusory perception between the PD patients and the controls, nor between the more affected and less/unaffected side, suggesting that Aristotle's illusion is preserved in PD. The retained tactile illusion in PD and its reduction in focal hand dystonia suggest that the basal ganglia, which are dysfunctional in both PD and dystonia, may not be causally involved in this function. Instead, the level of activation between digits in the somatosensory cortex may be more directly involved. Finally, the similar percentage of illusion in the more affected and less or unaffected body sides indicates that the illusory perception is not influenced by the presence or amount of motor symptoms

Demographic and clinical data of patients.

<p>a  =  Unified Parkinson’s Disease Rating Scale – III part (motor evaluation).</p><p>b  =  Hoehn & Yahr staging scale.</p