Humanin promotes tumor progression in experimental triple negative breast cancer

Humanin (HN) is a mitochondrial-derived peptide with cytoprotective effect in many tissues. Administration of HN analogs has been proposed as therapeutic approach for degenerative diseases. Although HN has been shown to protect normal tissues from chemotherapy, its role in tumor pathogenesis is poorly understood. Here, we evaluated the effect of HN on the progression of experimental triple negative breast cancer (TNBC). The meta-analysis of transcriptomic data from The Cancer Genome Atlas indicated that HN and its receptors are expressed in breast cancer specimens. By immunohistochemistry we observed up-regulation of HN in TNBC biopsies when compared to mammary gland sections from healthy donors. Addition of exogenous HN protected TNBC cells from apoptotic stimuli whereas shRNA-mediated HN silencing reduced their viability and enhanced their chemo-sensitivity. Systemic administration of HN in TNBC-bearing mice reduced tumor apoptotic rate, impaired the antitumor and anti-metastatic effect of chemotherapy and stimulated tumor progression, accelerating tumor growth and development of spontaneous lung metastases. These findings suggest that HN may exert pro-tumoral effects and thus, caution should be taken when using exogenous HN to treat degenerative diseases. In addition, our study suggests that HN blockade could constitute a therapeutic strategy to improve the efficacy of chemotherapy in breast cancer.Fil: Moreno Ayala, Mariela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Gottardo, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Zuccato, Camila Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Pidre, Matias Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Nicola Candia, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Asad, Antonela Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Imsen, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Romanowski, Victor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Creton, Aldo. Hospital Italiano de La Plata; ArgentinaFil: Isla Larrain, Marina Teresita. Hospital Italiano de La Plata; ArgentinaFil: Seilicovich, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentin

Mycobacterium tuberculosis ecology in Venezuela: epidemiologic correlates of common spoligotypes and a large clonal cluster defined by MIRU-VNTR-24

<p>Abstract</p> <p>Background</p> <p>Tuberculosis remains an endemic public health problem, but the ecology of the TB strains prevalent, and their transmission, can vary by country and by region. We sought to investigate the prevalence of <it>Mycobacterium tuberculosis </it>strains in different regions of Venezuela. A previous study identified the most prevalent strains in Venezuela but did not show geographical distribution nor identify clonal genotypes. To better understand local strain ecology, we used spoligotyping to analyze 1298 <it>M. tuberculosis </it>strains isolated in Venezuela from 1997 to 2006, predominantly from two large urban centers and two geographically distinct indigenous areas, and then studied a subgroup with MIRU-VNTR 24 loci.</p> <p>Results</p> <p>The distribution of spoligotype families is similar to that previously reported for Venezuela and other South American countries: LAM 53%, T 10%, Haarlem 5%, S 1.9%, X 1.2%, Beijing 0.4%, and EAI 0.2%. The six most common shared types (SIT's 17, 93, 605, 42, 53, 20) accounted for 49% of the isolates and were the most common in almost all regions, but only a minority were clustered by MIRU-VNTR 24. One exception was the third most frequent overall, SIT 605, which is the most common spoligotype in the state of Carabobo but infrequent in other regions. MIRU-VNTR homogeneity suggests it is a clonal group of strains and was named the "Carabobo" genotype. Epidemiologic comparisons showed that patients with SIT 17 were younger and more likely to have had specimens positive for Acid Fast Bacilli on microscopy, and patients with SIT 53 were older and more commonly smear negative. Female TB patients tended to be younger than male patients. Patients from the high incidence, indigenous population in Delta Amacuro state were younger and had a nearly equal male:female distribution.</p> <p>Conclusion</p> <p>Six SIT's cause nearly half of the cases of tuberculosis in Venezuela and dominate in nearly all regions. Strains with SIT 17, the most common pattern overall may be more actively transmitted and SIT 53 strains may be less virulent and associated with reactivation of past infections in older patients. In contrast to other common spoligotypes, strains with SIT 605 form a clonal group centered in the state of Carabobo.</p

Psychophysische und neurophysiologische Korrelate übungsinduzierter kortikaler Veränderungen in der Fokalen Handdystonie als Modell von Gehirnplastizität beim Menschen

Cortical plasticity appears to be involved in the etiology of focal hand dystonia, a very often task-specific sensorimotor disorder. The simultaneous two-point finger discrimination of some affected patients was evaluated. Dystonic musicians showed loss of perceptual symmetry between dystonic and non-affected hands. These changes were specific to their dystonic zones. Homologous asymmetries were not observed in writer s cramp, another form of focal hand dystonia. Using Magnetoencephalography (MEG), a smaller distance between the representations of the digits in the somatosensory cortex of the affected hand of dystonic musicians compared to the hands of non-affected individuals was demonstrated. A behavioral intervention produced long-term reduction of symptoms in some affected musicians, and their subjective ratings were highly correlated with objective data depicting changes in smoothness of finger movements. Pre- to post-treatment changes in somatosensory cortex were measured using whole head MEG. It was found that effective treatment with Sensory Motor Retuning (SMR) leads to alterations in functional organization of the somatosensory cortex. After treatment, somatosensory relationships of the individual fingers of the affected hand were similar to the non-affected side, and more ordered according to homuncular principles. The observed physiologic changes correlated with behavioral data obtained with a displacement dexterity device. These results confirmed that sensory anomalies are associated with focal hand dystonia and extend far beyond of the affected task. Cortical changes in parallel with emergent neurological dysfunction may be reversed by context specific intensive training protocols. It was demonstrated that cortical plasticity in response to behavioral interventions can be successfully assessed using non-invasive neuroimaging techniques. Some possible mechanisms of cortical plasticity mediating all of the observed changes were discussed

Tecnología limpia como alternativa a la técnica de cianuración de oro con cianuro de sodio que impacta el medio ambiente en el procesamiento de minerales de oro en la actividad minera informal en el Perú

La actividad minera informal del oro, se ha extendido a lo largo y ancho de todo el país, con una práctica artesanal e informal que afecta e impacta al medio ambiente y sobre todo al ser humano. Es una actividad que influye en la economía del País, soluciona la falta de trabajo, pero su actividad está fuera de la formalidad, es un problema a solucionar por el estado con políticas adecuada de formalización de los mineros informales. El Presente estudio está orientado a Solucionar los Impactos Ambientales que Causa el Uso del Cianuro de sodio en el Tratamiento de los minerales Auríferos con la Técnica de la Cianuración Convencional que utilizan los Mineros Informales para Recuperar el Oro a partir de los Minerales que extraen de las Minas. Actualmente se Aplica la Cianuración para beneficiar los Minerales de Oro, su alta recuperación y su Fácil aplicación permite que miles de Informales mineros, así como Empresas Cuasi-informales, Usen el Cianuro de sodio, que es un Reactivo altamente Peligroso y que está Considerado como Sustancia Contaminante en la Legislación Ambiental Peruana. La Presente Tesis Doctoral se Orienta a resolver el Problema Ambiental ocasionado por el Cianuro de Sodio que Impacta al Medio ambiente, proponiendo Tecnologías Limpias en la Recuperación del Oro de los minerales auríferos Producidos por la Minería Informal

Representational cortex in musicians : plastic alterations in response to musical practice

The lifelong ability to adapt to environmental needs is based on the capacity of the central nervous system for plastic alterations. In a series of neurophysiological experiments, we studied the impact of music and musical training in musicians on the specific functional organization in auditory and somatosensory representational cortex. In one such study, subjects listened to music from which one specific spectral frequency was removed. This led to rapid and reversible adaptation of neuronal responses in auditory cortex. Further experimental evidence demonstrated that long years of practice and training by professional musicians to enable them to reach their capacity is associated with enlarged cortical representations in the somatosensory and auditory domains. This tuning of neuronal representations was specifically observed for musical tones and was absent when pure sinusoidal tones were used as stimuli. In the somatosensory cortex, plastic changes proved to be specific for the fingers frequently used and stimulated. These changes were not detected in the fingers of the hand that were not involved in playing the particular instrument. Neuroplastic alterations also may be driven into a domain where they may become maladaptive. The clinical syndrome of focal hand dystonia that may occur in musicians who engage in forceful practice may be one such consequence. We will discuss the possibilities of reversing maladaptive responses leading to the successful treatment of focal hand dystonia, which relies on basic research about cortical reorganization. This example elucidates how neuroscientific progress can guide the development of practice guidelines and therapeutic measures for the benefit of professional musicians

Changing the Brain through Therapy for Musicians Hand Dystonia

Focal hand dystonia is a disorder in which sensory and motor anomalies emerge that appear to be grounded in maladaptive routes of cortical plasticity. Remodeling cortical networks through sensory-motor retuning (SMR), we achieved long-term reduction in the symptoms of focal hand dystonia. Magnetoencephalography confirmed that SMR modified the representational cortex of the fingers, whereby the representation of the affected hand was reorganized so that it resembled more the organization of the non-affected side. Furthermore, we observed differences in abnormal tactile acuity between patients with musician s cramp and those with writer s cramp: Using twopoint finger discrimination, dystonic musicians showed perceptual asymmetry between hands, while writer s cramp patients did not. To further evaluate the occurrence of collateral disturbances in focal dystonia, we assessed the clinical histories of 101 affected musicians. An important finding from this study was that dystonic musicians who play a similar first and second instrument reported a continuous worsening of their symptoms. In addition, collateral disturbances appeared with a shorter delay when more than one instrument was played. Taken together, these studies suggest that (1) neurological dysfunction can be reversed by context-specific training protocols, (2) specific symptomatic and etiological differences among various forms of focal hand dystonia might result from different behavioral experiences and their central representation, and (3) the spread of symptoms might be prevented by avoiding training that implies movement patterns similar to the main affected task, and by reducing the amount of task-associated movement behavior

Effective behavioral treatment of focal hand dystonia in musicians alters somatosensory cortical organization

New perspectives in neurorehabilitation suggest that behavioral treatments of movement disorders may modify the functional organization of central somatosensory neural networks. On the basis of the assumption that use-dependent reorganization in these networks contributes to the fundamental abnormalities seen in focal dystonia, we treated 10 affected musicians and measured the concomitant somatosensory changes by using whole-head magnetoencephalography. We found that effective treatment, using the method of sensory motor retuning, leads to alterations in the functional organization of the somatosensory cortex. Specifically, before treatment, somatosensory relationships of the individual fingers differ between the affected and unaffected hands, whereas after treatment, finger representations contralateral to the dystonic side become more similar to the less-affected side. Further, somatosensory finger representations are ordered more according to homuncular principles after treatment. In addition, the observed physiologic changes correlated with behavioral data. These results confirm that plastic changes in parallel with emergent neurological dysfunction may be reversed by context-specific, intensive training-based remediation

Repeated stage exposure reduces music performance anxiety

BackgroundHigh heart rate (HR) and restlessness are two important features of music performance anxiety (MPA). In a case report of a cellist suffering from this condition, we showed that HR and restlessness decreased after repeated live performances of the same musical excerpt, thereby positively modulating objective performance criteria and subjective components. Here, we largely replicate these results in a group of 18 string players reporting MPA. MethodsObjective measurement devices included a miniaturized electrocardiogram monitor and three 3-axis accelerometer loggers. Subjective measures included the Multidimensional Mental Health Questionnaire (MDBF) and a customized visual analogue scale (VAS) questionnaire for MPA. Non-artistic performance errors were assessed by music experts using a composite score for technical playing errors (i.e., intonation errors, omission of notes, and bowing noise). Data were collected from each study participant during three brief public solo performances of the same musical excerpt, with each performance occurring before a new audience on the same day. ResultsFrom the 1st to the 3rd performance, HR, VAS, and playing error scores decreased significantly. MDBF (RU scale) showed a significant increase in calmness from the 1st to the 3rd performance on stage. HR and RU, VAS, and RU, as well as bow acceleration and overall duration of playing correlated significantly across participants and performances. Discussion and conclusionWe conclude that repeated stage exposure significantly reduces HR as well as restlessness and playing errors linked to MPA. Public performances are still successful when HR is significantly higher than during rest periods. These results underscore the importance of stage training to become accustomed to realistic public self-exposure. Musicians - especially students - should consider this component of stage training as an integral part of their practice routine. Therefore, stage training can reduce MPA, promote better live performances and prevent stress-related mental disorders and physical injuries. These result from excessive self-exercise strategies common in musicians experiencing MPA. HR monitoring should be an integral part of evaluating the effectiveness of interventions for better MPA management and efficient performance training.ISSN:1664-107

A portable and low-cost fMRI compatible pneumatic system for the investigation of the somatosensensory system in clinical and research environments

There still is a need for devices that allow reproducible stimulation of skin areas of the human body. We constructed a stimulation system and tested it by using brief pneumatic stimulation to the right thumb of nine healthy volunteers. BOLD-signals in response to tactile stimulation with frequencies of 1, 3 and 5Hz were measured using a 3 T MRI scanner. The stimulation device consists of synthetic membranes connected to plastic tubes capable of carrying compressed air, and an electronic component, which controls the on- and off-switching of an electromagnetic valve. The valve near the MR-scanner did not lower the image quality. Primary somatosensory activation contralateral to the stimulation site was reliably detected in response to a stimulus magnitude of 3.5 bar in all volunteers. 1Hz stimulation resulted in higher maximal percentage BOLD-signal changes. Our device is an easy-to-construct, low-cost and portable tool suitable for research and clinical environments. It permits passive non-painful stimulation relevant for clinical assessments and is also compatible with magnetoencephalography (MEG) and electroencephalography (EEG). In basic and clinical research, this device therefore contributes to meaningful comparisons between results obtained with different techniques

Data_Sheet_1_Repeated stage exposure reduces music performance anxiety.docx

BackgroundHigh heart rate (HR) and restlessness are two important features of music performance anxiety (MPA). In a case report of a cellist suffering from this condition, we showed that HR and restlessness decreased after repeated live performances of the same musical excerpt, thereby positively modulating objective performance criteria and subjective components. Here, we largely replicate these results in a group of 18 string players reporting MPA.MethodsObjective measurement devices included a miniaturized electrocardiogram monitor and three 3-axis accelerometer loggers. Subjective measures included the Multidimensional Mental Health Questionnaire (MDBF) and a customized visual analogue scale (VAS) questionnaire for MPA. Non-artistic performance errors were assessed by music experts using a composite score for technical playing errors (i.e., intonation errors, omission of notes, and bowing noise). Data were collected from each study participant during three brief public solo performances of the same musical excerpt, with each performance occurring before a new audience on the same day.ResultsFrom the 1st to the 3rd performance, HR, VAS, and playing error scores decreased significantly. MDBF (RU scale) showed a significant increase in calmness from the 1st to the 3rd performance on stage. HR and RU, VAS, and RU, as well as bow acceleration and overall duration of playing correlated significantly across participants and performances.Discussion and conclusionWe conclude that repeated stage exposure significantly reduces HR as well as restlessness and playing errors linked to MPA. Public performances are still successful when HR is significantly higher than during rest periods. These results underscore the importance of stage training to become accustomed to realistic public self-exposure. Musicians – especially students – should consider this component of stage training as an integral part of their practice routine. Therefore, stage training can reduce MPA, promote better live performances and prevent stress-related mental disorders and physical injuries. These result from excessive self-exercise strategies common in musicians experiencing MPA. HR monitoring should be an integral part of evaluating the effectiveness of interventions for better MPA management and efficient performance training.</p