STAT3, a hub protein of cellular signaling pathways, is triggered by β-hexaclorocyclohexane

Background: Organochlorine pesticides (OCPs) are widely distributed in the environment and their toxicity is mostly associated with the molecular mechanisms of endocrine disruption. Among OCPs, particular attention was focused on the effects of β-hexaclorocyclohexane (β-HCH), a widely common pollutant. A detailed epidemiological study carried out on exposed population in the “Valle del Sacco” found correlations between the incidence of a wide range of diseases and the occurrence of β-HCH contamination. Taking into account the pleiotropic role of the protein signal transducer and activator of transcription 3 (STAT3), its function as a hub protein in cellular signaling pathways triggered by β-HCH was investigated in different cell lines corresponding to tissues that are especially vulnerable to damage by environmental pollutants. Materials and Methods: Human prostate cancer (LNCaP), human breast cancer (MCF-7 and MDA-MB 468), and human hepatoma (HepG2) cell lines were treated with 10 µM β-HCH in the presence or absence of specific inhibitors for different receptors. All samples were subjected to analysis by immunoblotting and RT-qPCR. Results and Conclusions: The preliminary results allow us to hypothesize the involvement of STAT3, through both its canonical and non-canonical pathways, in response to β-HCH. Moreover, we ascertained the role of STAT3 as a master regulator of energy metabolism via the altered expression and localization of HIF-1α and PKM2, respectively, resulting in a Warburg-like effect

Rhythmicity of mood symptoms in individuals at risk for psychiatric disorders

Despite emerging evidence that disruption in circadian rhythms may contribute to the pathophysiology of psychiatric disorders, there is a significant knowledge gap on the rhythmicity of psychological symptoms. Here, we aimed at investigating the rhythmicity of mood symptoms in individuals at risk for psychiatric disorders. 391 Brazilian and 317 Spanish participants completed the Self-Reporting Questionnaire-20 for non-psychotic mental disorders; the Mood Rhythm Instrument was used to assess rhythmicity of mood symptoms and the Munich ChronoType Questionnaire to assess sleep patterns. We found that the rhythmicity of specific mood-related symptoms and behaviors, particularly pessimism and motivation to exercise, were associated with being at risk for psychiatric disorders, even after controlling for sleep timing, sleep deficit, and season of data collection. We also found that the peak of some mood symptoms and behaviors were different between individuals at high vs. low risk for psychiatric disorders, with specific differences between countries. These results are consistent with previous research showing that circadian misalignment is associated with higher risk for mental health conditions. These findings also suggest that lifestyle changes preventing circadian misalignment might be useful to reduce the risk of psychiatric disorders, where cultural differences must be taken into account

Validation of the English version of the Mood Rhythm Instrument

Background: Disruption of biological rhythms has been linked to the pathophysiology of mental disorders. However, little is known regarding the rhythmicity of mood symptoms due to the lack of validated clinical questionnaires. A better understanding of the rhythmicity of mood symptoms can help identifying individuals whose severity of mood symptoms follows an altered circadian rhythm. The objective of this study was to validate the English version of the Mood Rhythm Instrument (MRhI), a self-reported measure of self-perceived rhythmicity of mood symptoms and behaviours, in a sample of the general population from Canada. Methods: After the translation process, the final English version of the Mood Rhythm Instrument (MRhI-English) was applied on participants recruited at McMaster University and St. Joseph's Healthcare Hamilton campuses. Individuals were also asked to answer the Reduced Morningness-Eveningness Questionnaire (rMEQ). Results: Four hundred one individuals completed the English version of the MRhI and the rMEQ. The MRhI-English presented a Cronbach's alpha of 0.75. The factorial analysis grouped the MRhI-15 items in 3 factors (cognitive, affective and somatic), with affective items having a lower frequency of self-reported 24-h peaks. Comparison between sexes showed that women reported a higher frequency of daily peaks in irritability, anxiety, sadness and talking to friends, while men exhibited peaks more frequently in problem-solving, sexual arousal and motivation to exercise. Conclusions: Our findings suggest that the English version of the MRhI displayed good internal consistency. Future directions will include the use of the MRhI instrument in individuals with mood disorders, aiming to provide a better understanding of the relationship between daily patterns of mood variability and mental health outcomes

Rhythmicity of mood symptoms in idividuals at risk for psychiatric disorders

Despite emerging evidence that disruption in circadian rhythms may contribute to the pathophysiology of psychiatric disorders, there is a significant knowledge gap on the rhythmicity of psychological symptoms. Here, we aimed at investigating the rhythmicity of mood symptoms in individuals at risk for psychiatric disorders. 391 Brazilian and 317 Spanish participants completed the Self-Reporting Questionnaire-20 for non-psychotic mental disorders; the Mood Rhythm Instrument was used to assess rhythmicity of mood symptoms and the Munich ChronoType Questionnaire to assess sleep patterns. We found that the rhythmicity of specific mood-related symptoms and behaviors, particularly pessimism and motivation to exercise, were associated with being at risk for psychiatric disorders, even after controlling for sleep timing, sleep deficit, and season of data collection. We also found that the peak of some mood symptoms and behaviors were different between individuals at high vs. low risk for psychiatric disorders, with specific differences between countries. These results are consistent with previous research showing that circadian misalignment is associated with higher risk for mental health conditions. These findings also suggest that lifestyle changes preventing circadian misalignment might be useful to reduce the risk of psychiatric disorders, where cultural differences must be taken into account

SMART: An Application Framework for Real Time Big Data Analysis on Heterogeneous Cloud Environments

International audienceThe amount of data that human activities generate poses a challenge to current computer systems. Big data processing techniques are evolving to address this challenge, with analysis increasingly being performed using cloud-based systems. Emerging services, however, require additional enhancements in order to ensure their applicability to highly dynamic and heterogeneous environments and facilitate their use by Small & Medium-sized Enterprises (SMEs). Observing this landscape in emerging computing system development, this work presents Small & Medium-sized Enterprise Data Analytic in Real Time (SMART) for addressing some of the issues in providing compute service solutions for SMEs. SMART offers a framework for efficient development of Big Data analysis services suitable to small and medium-sized organizations, considering very heterogeneous data sources, from wireless sensor networks to data warehouses, focusing on service composability for a number of domains. This paper presents the basis of this proposal and preliminary results on exploring application deployment on hybrid infrastructure

Ribonucleoprotein Assembly Defects Correlate with Spinal Muscular Atrophy Severity and Preferentially Affect a Subset of Spliceosomal snRNPs

Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival motor neuron (SMN) protein. SMN together with Gemins2-8 and unrip proteins form a macromolecular complex that functions in the assembly of small nuclear ribonucleoproteins (snRNPs) of both the major and the minor splicing pathways. It is not known whether the levels of spliceosomal snRNPs are decreased in SMA. Here we analyzed the consequence of SMN deficiency on snRNP metabolism in the spinal cord of mouse models of SMA with differing phenotypic severities. We demonstrate that the expression of a subset of Gemin proteins and snRNP assembly activity are dramatically reduced in the spinal cord of severe SMA mice. Comparative analysis of different tissues highlights a similar decrease in SMN levels and a strong impairment of snRNP assembly in tissues of severe SMA mice, although the defect appears smaller in kidney than in neural tissue. We further show that the extent of reduction in both Gemin proteins expression and snRNP assembly activity in the spinal cord of SMA mice correlates with disease severity. Remarkably, defective SMN complex function in snRNP assembly causes a significant decrease in the levels of a subset of snRNPs and preferentially affects the accumulation of U11 snRNP—a component of the minor spliceosome—in tissues of severe SMA mice. Thus, impairment of a ubiquitous function of SMN changes the snRNP profile of SMA tissues by unevenly altering the normal proportion of endogenous snRNPs. These findings are consistent with the hypothesis that SMN deficiency affects the splicing machinery and in particular the minor splicing pathway of a rare class of introns in SMA

Prospective Assessment of Daily Patterns of Mood-Related Symptoms

Background: The Mood Rhythm Instrument (MRI) is a new self-report questionnaire that aims to assess, the presence, and timing of daily patterns of mood-related symptoms. Here, we examined the reliability of the MRI against a prospective daily investigation over the course of 15 days. As a secondary aim, we examined whether the number of items with a perceived daily pattern correlated with severity of depressive symptoms and psychological well-being.Methods: Thirty-two participants recruited from the general population were asked to prospectively fill out a daily version of the MRI (MRI-d) for 15 days. On the 16th day, they filled out the MRI, the Beck Depression Inventory (BDI) and the World Health Organization 5-item well-being index (WHO-5).Results: The MRI showed high agreement with the MRI-d, which suggests that the MRI is a valid tool to assess daily patterns of mood symptoms. The number of mood symptoms perceived as having daily peaks correlated positively with BDI scores and negatively with WHO-5 scores.Conclusions: The MRI might be a valid tool to investigate the presence of daily patterns and the timing of mood-related factors.The MRI does not seem to be influenced by recall or recency biases. Future studies should test the usefulness of this new clinical instrument in individuals with mood disorders, as well as its ability to detect changes in the daily timing of mood symptoms before and after treatment

Differential Expression Profile and Genetic Variants of MicroRNAs Sequences in Breast Cancer Patients

The technology available for cancer diagnosis and prognosis is not yet satisfactory at the molecular level, and requires further improvements. Micro RNAs (miRNAs) have been recently reported as useful biomarkers in diseases including cancer. We performed a miRNA expression profiling study using peripheral blood from breast cancer patients to detect and identify characteristic patterns. A total of 100 breast cancer patients and 89 healthy patients were recruited for miRNA genotyping and expression profiling. We found that hs-miR-196a2 in premenopausal patients, and hs-miR-499, hs-miR-146a and hs-miR-196a2 in postmenopausal patients, may discriminate breast cancer patients from healthy individuals. In addition, we found a significant association between two microRNA polymorphisms (hs-miR-196a2 and hs-miR-499) and breast cancer risk. However, no significant association between the hs-miR-146a gene and breast cancer risk was found. In summary, the study demonstrates that peripheral blood miRNAs and their expression and genotypic profiles can be developed as biomarkers for early diagnosis and prognosis of breast cancer

Spanish translation of the mood rhythm instrument : novel approach to mood evaluation

Introduction: The Mood Rhythm Instrument (MRI) is a questionnaire developed to assess the circadian rhythm of mood-related behaviors. The aim of this study was to translate this instrument from Brazilian Portuguese into Spanish. Methods: The translation process consisted of forward translation, adjustment, back translation, back translation review and harmonization. Results: Comparing the initial Spanish translation and the final Spanish version, there were no semantic differences and the items were not changed. Conclusions: The Spanish version of the MRI is ready to be tested in a Spanish population. In the future, assessing and comparing mood-related behaviors in transcultural studies will be possible