Miracle-dz/UniFAR-FTUs huggingface dataset:
The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-kB activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.
Spatiotemporal Variation in Environmental Vibrio cholerae in an Estuary in Southern Coastal Ecuador

Cholera emergence is strongly linked to local environmental and ecological context. The 1991–2004 pandemic emerged in Perú and spread north into Ecuador’s El Oro province, making this a key site for potential re-emergence. Machala, El Oro, is a port city of 250,000 inhabitants, near the Peruvian border. Many livelihoods depend on the estuarine system, from fishing for subsistence and trade, to domestic water use. In 2014, we conducted biweekly sampling for 10 months in five estuarine locations, across a gradient of human use, and ranging from inland to ocean. We measured water-specific environmental variables implicated in cholera growth and persistence: pH, temperature, salinity, and algal concentration, and evaluated samples in five months for pathogenic and non-pathogenic Vibrio cholerae, by polymerase chain reaction (PCR). We found environmental persistence of pandemic strains O1 and O139, but no evidence for toxigenic strains. Vibrio cholerae presence was coupled to algal and salinity concentration, and sites exhibited considerable seasonal and spatial heterogeneity. This study indicates that environmental conditions in Machala are optimal for cholera re-emergence, with risk peaking during September, and higher risk near urban periphery low-income communities. This highlights a need for surveillance of this coupled cholera–estuarine system to anticipate potential future cholera outbreaks.
Real-Time Detection of Illegal File Transfers in the Cloud

There has been a prolific rise in the popularityof cloud storage in recent years. While cloud storage offersmany advantages such as flexibility and convenience, users arenow unable to tell or control the actual locations of their data. This limitation may affect users' confidence and trust in thestorage provider, or even be unsuitable for storing data withstrict location requirements. To address this issue, we proposean illegal file transfer detection framework that constantlymonitors the real-time file transfers in the cloud and is capableof detecting potential illegal transfers which moves sensitivedata outside the ("legal") boundaries specified by the fileowner. The main idea is to classifying multiple users' location preferences when making the data storage arrangement inthe cloud nodes. We model the legal file transfers amongnodes as a weighted graph and then maximize the probabilityof storing data items of similar privacy preferences in thesame region. Then we leverage the socket monitoring functionsprovided by LAST-HDFS (a recent location-aware Hadoop filestorage system) to monitor the real-time communication amongcloud nodes. Based on our legal file transfer graph and thedetected communication, we propose an approach to calculatethe probability of the detected transfer to be illegal.
Efficacy and Safety of Phytosomal Curcumin in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial

Abstract Objective Non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by excess lipid deposition in the hepatic tissue and subsequent oxidative and inflammatory damage. Curcumin is a dietary polyphenol with lipid-modifying, antioxidant and anti-inflammatory properties. This study aimed to evaluate the efficacy and safety of supplementation with phytosomal curcumin in subjects with NAFLD. Methods Patients diagnosed with NAFLD (grades 1–3 according to liver ultrasonography) were randomly assigned to the curcumin (phytosomal form; 1 000 mg/day in 2 divided doses) (n=50) or placebo group (n=52) for a period of 8 weeks. All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, hepatic enzymes, and liver ultrasonography were assessed at baseline and after 8 weeks of follow-up. Results 87 subjects (n=44 and 43 in the curcumin and control group, respectively) completed the trial. Supplementation with curcumin was associated with a reduction in body mass index (−0.99±1.25 vs. − 0.15±1.31 in the curcumin and placebo groups, respectively; p=0.003) and waist circumference (−1.74±2.58 vs. −0.23±3.49 in the curcumin and placebo groups, respectively; p=0.024). Ultrasonographic findings were improved in 75.0% of subjects in the curcumin group, while the rate of improvement in the control group was 4.7% (p<0.001). Serum levels of aspartate aminotransferase and alanine aminotransferase were reduced by the end of trial in the curcumin group (p<0.001) but elevated in the control group (p<0.001). Curcumin was safe and well tolerated during the course of trial. Conclusion Short-term supplementation with curcumin improves liver fat and transaminase levels in patients with NAFLD.
Using complexity science to examine three dynamic patterns of intimate partner violence.

INTRODUCTION The partner violence literature describes 3 dominant models of dynamics of partner aggression: cycle of violence, family systems theory, and Duluth model (power and control wheel). Complexity science describes 3 patterns of system dynamics: periodic, chaotic, and random. Are these parallel patterns? In this analysis, investigators calculated dynamic patterns (periodic, chaotic, and random) using 84 daily reports of male-to-female aggression and assessed the "fit" between time-series-derived patterns of male partners' violent behaviors and literature-based models of violence dynamics. METHOD Participants were 200 women in moderately violent intimate relationships who completed a telephone survey about their relationships every day for 12 weeks. They also completed baseline and end-of-study surveys and maintained telephone contact with the study team weekly. Of 200 participants, 135 women provided enough data to be assigned to period, chaotic, or random groups. RESULTS Group membership included 16 women in periodic, 40 in chaotic, and 79 in random groups. Consistent with the cycle of violence, periodic women found violence to be predictable and controllable. Consistent with the Duluth model, women in the random group found violence to be unpredictable and out of their control, occurring with high frequency. The chaotic group had the lowest frequency and severity of violence, lowest stress and arguments, and the highest marital satisfaction. DISCUSSION The most common dynamic pattern in partner violence is random, which exhibits high frequency and unpredictability of aggression. Complexity science suggests interventions in random systems have unpredictable outcomes, posing great challenges for clinicians who work with victims of violence.
Biomaterials for Enhancing Neuronal Repair

As they differentiate from neuroblasts, nascent neurons become highly polarized and elongate. Neurons extend and elaborate fine and fragile cellular extensions that form circuits enabling long-distance communication and signal integration within the body. While other organ systems are developing, projections of differentiating neurons find paths to distant targets. Subsequent post-developmental neuronal damage is catastrophic because the cues for reinnervation are no longer active. Advances in biomaterials are enabling fabrication of micro-environments that encourage neuronal regrowth and restoration of function by recreating these developmental cues. This mini-review considers new materials that employ topographical, chemical, electrical, and/or mechanical cues for use in neuronal repair. Manipulating and integrating these elements in different combinations will generate new technologies to enhance neural repair.
Enhancing Transcriptomic Data Mining with Semantic Ranking: Towards a new Functional Spectral Representation

In biomedical domains, high throughput technologies pro- duce large amount of transcriptomic data used for studying comportment of genes. The analysis and the interpretation of such data require impor- tant databases and e cient mining methods, in order to extract speci c biological functions belonging to a group of genes of an expression pro le. To this aim, we propose here a new approach for mining transcriptomic data combining domain knowledge and classi cation methods. Firstly, we propose the de nition of Fuzzy Di erential Gene Expression Pro les (FD-GEP) based on fuzzy classi cation and a di erential de nition be- tween the considered biological situations. Secondly, we will use our pre- viously de ned e cient semantic similarity measure (called IntelliGO), that is applied on Gene Ontology (GO) annotation terms, for comput- ing semantic and functional similarities between genes of the resulting FD-GEP and well known genetic markers involved in the development of cancers. After that, the similarity matrices will be used to introduce a novel Functional Spectral Representation (FSR) calculated through a semantic ranking of genes regarding their similarities with the tumoral markers. The FSR representation should help expert to interpret by a new way transcriptomic data and infer new genes having similar biolog- ical functions regarding well known diseases. Availability: The semantic similarity measure
The effects of nutrients on mood

Abstract A recent major theory was that a meal high in carbohydrate increased the rate that tryptophan enters the brain, leading to an increase in the level of the neurotransmitter serotonin that modulates mood. Although such a mechanism may be important under laboratory conditions it is unlikely to be of significance following the eating of any typical meal. As little as 2–4% of the calories of a meal as protein will prevent an increased availability of tryptophan. Arguably the food with the greatest impact on mood is chocolate. Those who crave chocolate tend to do so when they feel emotionally low. There have been a series of suggestions that chocolate's mood elevating properties reflect ‘drug-like’ constituents including anandamines, caffeine, phenylethylamine and magnesium. However, the levels of these substances are so low as to preclude such influences. As all palatable foods stimulate endorphin release in the brain this is the most likely mechanism to account for the elevation of mood. A deficiency of many vitamins is associated with psychological symptoms. In some elderly patients folate deficiency is associated with depression. In four double-blind studies an improvement in thiamine status was associated with improved mood. Iron deficiency anaemia is common, particularly in women, and is associated with apathy, depression and rapid fatigue when exercising.
Chapter 1 Hearing Loss in Children with Congenital Cytomegalovirus Infection

Sensorineural hearing loss (SNHL) is a common birth defect. The genetic origins of SNHL can be identified in half of the prelingual cases; in the others, SNHL is caused by environmental or unidentified genetic factors. The most common environmental cause of SNHL is congenital cytomegalovirus (CMV) infection. CMV is also the most common cause of intrauterine and congenital viral infection, affecting 0.5% to 2.5% of all live neonates [1]. While 90% of CMVinfected children are asymptomatic at birth, 10% of those exhibit clinically apparent sequelae at birth, including SNHL, mental retardation, motor disability, and microcephaly [1-4]. Recent studies have revealed that children with asymptomatic congenital CMV infection are at risk of late-onset SNHL and/or deterioration of SNHL during early childhood. These developments may not appear until months or even years following birth. The frequency of SNHL associated with asymptomatic congenital CMV infection reportedly ranges from 13% to 24% [5-9]. Although asymptomatic CMV infection is associated with a lower incidence of SNHL than symptomatic CMV infection, SNHL caused by congenital CMV often remains undiagnosed because maternal screening for CMV infection is not routinely conducted and the detection of SNHL during newborn hearing screening (NHS) tests is difficult [7, 10].
Introgression of Physiological Traits for a Comprehensive Improvement of Drought Adaptation in Crop Plants

Burgeoning population growth, industrial demand, and the predicted global climate change resulting in erratic monsoon rains are expected to severely limit fresh water availability for agriculture both in irrigated and rainfed ecosystems. In order to remain food and nutrient secure, agriculture research needs to focus on devising strategies to save water in irrigated conditions and to develop superior cultivars with improved water productivity to sustain yield under rainfed conditions. Recent opinions accruing in the scientific literature strongly favor the adoption of a “trait based” crop improvement approach for increasing water productivity. Traits associated with maintenance of positive tissue turgor and maintenance of increased carbon assimilation are regarded as most relevant to improve crop growth rates under water limiting conditions and to enhance water productivity. The advent of several water saving agronomic practices notwithstanding, a genetic enhancement strategy of introgressing distinct physiological, morphological, and cellular mechanisms on to a single elite genetic background is essential for achieving a comprehensive improvement in drought adaptation in crop plants. The significant progress made in genomics, though would provide the necessary impetus, a clear understanding of the “traits” to be introgressed is the most essential need of the hour. Water uptake by a better root architecture, water conservation by preventing unproductive transpiration are crucial for maintaining positive tissue water relations. Improved carbon assimilation associated with carboxylation capacity and mesophyll conductance is important in sustaining crop growth rates under water limited conditions. Besides these major traits, we summarize the available information in literature on classifying various drought adaptive traits. We provide evidences that Water-Use Efficiency when introgressed with moderately higher transpiration, would significantly enhance growth rates and water productivity in rice through an improved photosynthetic capacity.
Changes in the Common Carotid Artery after Radiotherapy: Wall Thickness, Calcification, and Atherosclerosis

Background and Purpose Since the long-term survival rate has improved in laryngeal cancer patients who receive radiotherapy, concerns about postradiation complications (including carotid atherosclerosis) have increased. We followed changes in the common carotid artery (CCA) after radiotherapy and identified the underlying risk factors. Methods Consecutive patients with laryngeal cancer who underwent radiotherapy between January 1999 and December 2009 and who had received computed tomography (CT) both pre- and postradiotherapy were enrolled. Changes in the wall thickness and in the vessel and lumen areas as well as the presence of calcification or atherosclerosis were investigated. Demographics and risk factors were compared between patients with and without atherosclerosis at follow-up CT. Results In total, 125 patients were enrolled. The wall thickness had increased and the lumen area had decreased several months after radiotherapy. These changes were not associated with vascular risk factors and were not progressive. Calcification and atherosclerosis were observed in 37 (29.6%) and 71 (56.8%) patients, respectively. Diabetes was associated with calcification (p=0.02). The prevalence of hyperlipidemia was higher in patients with atherosclerosis (28.2% vs. 11.1%, p=0.02) and for a longer period postradiation [62.7±32.1 vs. 40.0±24.2 months (mean±SD), p<0.001]. Atherosclerosis occurred mostly in the middle portion of the CCA (n=31, 24.6%), followed by the proximal CCA at the intrathoracic level (n=26, 20.6%) and the distal CCA (n=6, 4.8%). Positive remodeling was also observed, but this was less common in patients with calcification (p=0.02). Conclusions Various types of postradiation changes occur in the CCA and can be easily observed in postradiation CT. The prevalence and burden of postradiation atherosclerosis increased in a close relationship with baseline cholesterol levels and the time after radiotherapy. Postradiation atherosclerosis was observed at unusual sites of the CCA.
Individual and Neighborhood Stressors, Air Pollution and Cardiovascular Disease

Psychosocial and environmental stress exposures across the life course have been shown to be relevant in the development of cardiovascular disease (CVD). Assessing more than one stressor from different domains (e.g., individual and neighborhood) and across the life course moves us towards a more integrated picture of how stress affects health and well-being. Furthermore, these individual and neighborhood psychosocial stressors act on biologic pathways, including immune function and inflammatory response, which are also impacted by ubiquitous environmental exposures such as air pollution. The objective of this study is to evaluate the interaction between psychosocial stressors, at both the individual and neighborhood level, and air pollution on CVD. This study used data from the 2009–2011 Behavioral Risk Factor Surveillance System (BRFSS) from Washington State. Adverse childhood experiences (ACEs) measured at the individual level, and neighborhood deprivation index (NDI) measured at the zip code level, were the psychosocial stressors of interest. Exposures to three air pollutants—particulate matter (both PM2.5 and PM10) and nitrogen dioxide (NO2)—were also calculated at the zip code level. Outcome measures included several self-reported CVD-related health conditions. Both multiplicative and additive interaction quantified using the relative excess risk due to interaction (RERI), were evaluated. This study included 32,151 participants in 502 unique zip codes. Multiplicative and positive additive interactions were observed between ACEs and PM10 for diabetes, in models adjusted for NDI. The prevalence of diabetes was 1.58 (95% CI: 1.40, 1.79) times higher among those with both high ACEs and high PM10 compared to those with low ACEs and low PM10 (p-value = 0.04 for interaction on the multiplicative scale). Interaction was also observed between neighborhood-level stressors (NDI) and air pollution (NO2) for the stroke and diabetes outcomes on both multiplicative and additive scales. Modest interaction was observed between NDI and air pollution, supporting prior literature on the importance of neighborhood-level stressors in cardiovascular health and reinforcing the importance of NDI on air pollution health effects. ACEs may exert health effects through selection into disadvantaged neighborhoods and more work is needed to understand the accumulation of risk in multiple domains across the life course.
Induced pluripotent stem cell modelling of HLHS underlines the contribution of dysfunctional NOTCH signalling to impaired cardiogenesis

Abstract Hypoplastic left heart syndrome (HLHS) is among the most severe forms of congenital heart disease. Although the consensus view is that reduced flow through the left heart during development is a key factor in the development of the condition, the molecular mechanisms leading to hypoplasia of left heart structures are unknown. We have generated induced pluripotent stem cells (iPSC) from five HLHS patients and two unaffected controls, differentiated these to cardiomyocytes and identified reproducible in vitro cellular and functional correlates of the HLHS phenotype. Our data indicate that HLHS-iPSC have a reduced ability to give rise to mesodermal, cardiac progenitors and mature cardiomyocytes and an enhanced ability to differentiate to smooth muscle cells. HLHS-iPSC-derived cardiomyocytes are characterised by a lower beating rate, disorganised sarcomeres and sarcoplasmic reticulum and a blunted response to isoprenaline. Whole exome sequencing of HLHS fibroblasts identified deleterious variants in NOTCH receptors and other genes involved in the NOTCH signalling pathway. Our data indicate that the expression of NOTCH receptors was significantly downregulated in HLHS-iPSC-derived cardiomyocytes alongside NOTCH target genes confirming downregulation of NOTCH signalling activity. Activation of NOTCH signalling via addition of Jagged peptide ligand during the differentiation of HLHS-iPSC restored their cardiomyocyte differentiation capacity and beating rate and suppressed the smooth muscle cell formation. Together, our data provide firm evidence for involvement of NOTCH signalling in HLHS pathogenesis, reveal novel genetic insights important for HLHS pathology and shed new insights into the role of this pathway during human cardiac development.