Miracle-dz/UniFAR-FTUs huggingface dataset:
HTLV-1 basic leucine zipper factor protects cells from oxidative stress by upregulating expression of Heme Oxygenase I

Adult T-cell Leukemia (ATL) is a lymphoproliferative disease of CD4+ T-cells infected with Human T-cell Leukemia Virus type I (HTLV-1). With the exception of allogeneic hematopoietic stem cell transplantation, there are no effective treatments to cure ATL, and ATL cells often acquire resistance to conventional chemotherapeutic agents. Accumulating evidence shows that development and maintenance of ATL requires key contributions from the viral protein, HTLV-1 basic leucine zipper factor (HBZ). In this study we found that HBZ activates expression of Heme Oxygenase 1 (HMOX-1), a component of the oxidative stress response that functions to detoxify free heme. Transcription of HMOX1 and other antioxidant genes is regulated by the small Mafs. These cellular basic leucine zipper (bZIP) factors control transcription by forming homo- or heterodimers among themselves or with other cellular bZIP factors that then bind Maf responsive elements (MAREs) in promoters or enhancers of antioxidant genes. Our data support a model in which HBZ activates HMOX1 transcription by forming heterodimers with the small Mafs that bind MAREs located in an upstream enhancer region. Consistent with this model, we found that HMOX-1 is upregulated in HTLV-1-transformed T-cell lines and confers these cells with resistance to heme-induced cytotoxicity. In this context, HBZ-mediated activation of HMOX-1 expression may contribute to resistance of ATL cells to certain chemotherapeutic agents. We also provide evidence that HBZ counteracts oxidative stress caused by two other HTLV-1-encoded proteins, Tax and p13. Tax induces oxidative stress as a byproduct of driving mitotic expansion of infected cells, and p13 is believed to induce oxidative stress to eliminate infected cells that have become transformed. Therefore, in this context, HBZ-mediated activation of HMOX-1 expression may facilitate transformation. Overall, this study characterizes a novel function of HBZ that may support the development and maintenance of ATL.
Mitochondrial Network State Scales mtDNA Genetic Dynamics

Mitochondrial DNA (mtDNA) mutations cause severe congenital diseases but may also be associated with healthy aging. mtDNA is stochastically replicated and degraded, and exists within organelles which undergo dynamic fusion and fission. The role of the resulting mitochondrial networks in the time evolution of the cellular proportion of mutated mtDNA molecules (heteroplasmy), and cell-to-cell variability in heteroplasmy (heteroplasmy variance), remains incompletely understood. Heteroplasmy variance is particularly important since it modulates the number of pathological cells in a tissue. Here, we provide the first wide-reaching theoretical framework which bridges mitochondrial network and genetic states. We show that, under a range of conditions, the (genetic) rate of increase in heteroplasmy variance and de novo mutation are proportionally modulated by the (physical) fraction of unfused mitochondria, independently of the absolute fission–fusion rate. In the context of selective fusion, we show that intermediate fusion:fission ratios are optimal for the clearance of mtDNA mutants. Our findings imply that modulating network state, mitophagy rate, and copy number to slow down heteroplasmy dynamics when mean heteroplasmy is low could have therapeutic advantages for mitochondrial disease and healthy aging.
Dietary restriction induces posttranscriptional regulation of longevity genes

By modulating posttranscriptional processes, including RNA editing, miRNA biogenesis, and intron retention, dietary restriction enacts some of its pro-longevity benefits in Caenorhabditis elegans through posttranscriptional regulation of gene expression. Dietary restriction (DR) increases life span through adaptive changes in gene expression. To understand more about these changes, we analyzed the transcriptome and translatome of Caenorhabditis elegans subjected to DR. Transcription of muscle regulatory and structural genes increased, whereas increased expression of amino acid metabolism and neuropeptide signaling genes was controlled at the level of translation. Evaluation of posttranscriptional regulation identified putative roles for RNA-binding proteins, RNA editing, miRNA, alternative splicing, and nonsense-mediated decay in response to nutrient limitation. Using RNA interference, we discovered several differentially expressed genes that regulate life span. We also found a compensatory role for translational regulation, which offsets dampened expression of a large subset of transcriptionally down-regulated genes. Furthermore, 3′ UTR editing and intron retention increase under DR and correlate with diminished translation, whereas trans-spliced genes are refractory to reduced translation efficiency compared with messages with the native 5′ UTR. Finally, we find that smg-6 and smg-7, which are genes governing selection and turnover of nonsense-mediated decay targets, are required for increased life span under DR.
Qualitative Assessment of Color M-Mode Signals in the Evaluation of Left Ventricular Diastolic Function: A Proof of Concept Study.

OBJECTIVES Although the most recent American Society of Echocardiography guidelines are a major step forward in echocardiographic evaluation of diastolic function, the ability to differentiate between normal and abnormal function remains challenging. The authors aimed to determine whether qualitative assessments of color M-mode flow displays could be a useful parameter in the evaluation of left ventricular (LV) diastolic dysfunction. DESIGN Retrospective observational study. SETTING Tertiary care level hospital. PARTICIPANTS The study comprised echocardiographic data from 105 consecutive patients. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS Patients were allocated into the following 3 groups according to the LV diastolic function based on current American Society of Echocardiography recommendation guidelines for LV diastolic dysfunction classification: group I-normal function (n = 40); group II-early relaxation abnormalities (grade I) (n = 50), and group III-elevated LV pressures (grade II) (n = 15). Patients with normal diastolic function were younger (45 ± 14 y) than those with diastolic dysfunction (group II: 64 ± 10 y and group III: 56 ± 15 y) (p < 0.05). Volumetric echocardiographic parameters and mitral inflow and mitral annulus tissue Doppler imaging measures were significantly different among the 3 studied groups (p < 0.05). Interestingly, qualitative assessment of color M-mode flows displayed distinctive signals based on the left ventricle filling properties. Intraobserver and interobserver variability to determine the reliability of these signals were robust (weighted kappa 0.84 ± 0.11 and 0.65 ± 0.13, respectively). CONCLUSION Qualitative assessment of color M-mode flow displays offers simple and reliable information of potential usefulness in the evaluation of LV diastolic function.
Whole Body Vibration-Induced Omental Macrophage Polarization and Fecal Microbiome Modification in a Murine Model

Human nutrient metabolism, developed millions of years ago, is anachronistic. Adaptive features that offered survival advantages are now great liabilities. The current dietary pattern, coupled with massively reduced physical activities, causes an epidemic of obesity and chronic metabolic diseases, such as type 2 diabetes mellitus. Chronic inflammation is a major contributing factor to the initiation and progression of most metabolic and cardiovascular diseases. Among all components of an innate immune system, due to their dual roles as phagocytic as well as antigen-presenting cells, macrophages play an important role in the regulation of inflammatory responses, affecting the body’s microenvironment and homeostasis. Earlier studies have established the beneficial, anti-inflammatory effects of whole body vibration (WBV) as a partial exercise mimetic, including reversing the effects of glucose intolerance and hepatic steatosis. Here for the first time, we describe potential mechanisms by which WBV may improve metabolic status and ameliorate the adverse consequences through macrophage polarization and altering the fecal microbiome.
Characterization of DSM-IV Opioid Dependence Among Individuals of European Ancestry.

OBJECTIVE The opioid epidemic in the United States has led to unprecedented increases in morbidity and mortality, posing a serious public health crisis. Although twin and family studies, as well as genome-wide association studies (GWAS), all identify significant genetic factors contributing to opioid dependence, no studies to date have estimated marker-based heritability estimates of opioid dependence. The goal of the current study was to use a large, genetically imputed, case/control sample of 4,064 participants (after quality control and imputation) with genome-wide data to estimate the unbiased heritability tagged by single nucleotide polymorphisms (SNPs). METHOD Study data were part of the Genome-wide Study of Heroin Dependence obtained via the Database for Genotypes and Phenotypes (dbGaP). Genomic-Relatedness-Matrix Restricted Maximum Likelihood with adjustment for minor allele frequency (MAF) and linkage disequilibrium (LD; GREML-LDMS) was used to determine the variation in opioid dependence attributable to common SNPs from imputed data. Mixed linear models were used in an exploratory GWAS to assess effects of single SNPs. RESULTS At least 45% of the variance in opioid dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, was attributable to common SNPs, after stratifying to account for differences in MAF and LD across the genome. Most of the genetic variance was tagged by SNPs in the 1%-9% MAF range and in low LD with other SNPs in the region. Two markers in LOC101927293 survived multiple-testing correction (i.e., q value < .05). CONCLUSIONS Nearly half of the variation in opioid dependence can be attributed to common SNPs. Most of this variation is due to rare variants in low LD with other markers in the region.
Improving Detection of Multiple Sclerosis Lesions in the Posterior Fossa Using an Optimized 3D-FLAIR Sequence at 3T

BACKGROUND AND PURPOSE: There is no consensus regarding the best MR imaging sequence for detecting MS lesions. The aim of our study was to assess the diagnostic value of optimized 3D-FLAIR in the detection of infratentorial MS lesions compared with an axial T2-weighted imaging, a 3D-FLAIR with factory settings, and a 3D double inversion recovery sequence. MATERIALS AND METHODS: In this prospective study, 27 patients with confirmed MS were included. Two radiologists blinded to clinical data independently read the following sequences: axial T2WI, 3D double inversion recovery, standard 3D-FLAIR with factory settings, and optimized 3D-FLAIR. The main judgment criterion was the overall number of high-signal-intensity lesions in the posterior fossa; secondary objectives were the assessment of the reading confidence and the measurement of the contrast. A nonparametric Wilcoxon test was used to compare the MR images. RESULTS: Twenty-two patients had at least 1 lesion in the posterior fossa. The optimized FLAIR sequence detected significantly more posterior fossa lesions than any other sequence: 7.5 versus 5.8, 4.8, and 4.1 (P values of .04, .03, and .03) with the T2WI, the double inversion recovery, and the standard FLAIR, respectively. The reading confidence index was significantly higher with the optimized FLAIR, and the contrast was significantly higher with the optimized FLAIR than with the standard FLAIR and the double inversion recovery. CONCLUSIONS: An optimized 3D-FLAIR sequence improved posterior fossa lesion detection in patients with MS.
Level-2 visuo-spatial perspective-taking and interoception – More evidence for the embodiment of perspective-taking

Level-2 visuo-spatial perspective-taking is an embodied process during which the perspective-taker mentally simulates a movement of his or her body into the location of the target. Evidence for the embodiment of this process so far exclusively stems from congruency effects in visuo-spatial perspective-taking experiments. Here, additional triangulation for the embodiment of this process is provided from an interindividual differences perspective. In a cross-sectional observational study, participants completed a behavioral level-2 visuo-spatial perspective-taking task and the heartbeat tracking task, which measures interoceptive accuracy and sensibility. Interoceptive accuracy is the objective ability to accurately perceive signals from within the body. In the present study, interoceptive accuracy was quantified by comparing the number of actual heartbeats observed via electrocardiographic recording to subjectively perceived heartbeats during that time. This measure was related to faster perspective-taking and better overall perspective-taking performance. Interoceptive sensibility refers to subjective beliefs about interoceptive abilities. Here, confidence in the estimated number of heartbeats served as a measure if interoceptive sensibility. Finally, the correspondence between interoceptive accuracy and sensibility is referred to as interoceptive awareness. Interoceptive sensibility and awareness were unrelated to perspective-taking. The study is a demonstration of the role interindividual differences in different facets of interoception play for embodied cognition. Implications for future research on links between embodied cognition and interoception are outlined and critically discussed.
The Role of Genetic Variants (rs869109213 and rs2070744) Of the eNOS Gene and BglII in the α2 Subunit of the α2β1 Integrin Gene in Diabetic Retinopathy in a Tunisian Population

ABSTRACT Purpose: In this study, we investigated the association of two polymorphisms (rs869109213 and rs2070744) in the eNOS gene and one polymorphism BglII in the α2β1 integrin gene (ITGA2) with the risk of diabetic retinopathy (DR) in a Tunisian population. Methods: The study investigated of 110 type 2 diabetes mellitus (T2DM) and 127 DR patients. The genotypes of the eNOS 4b/4a (rs869109213) and −786T/C (rs2070744) polymorphisms and of the BglII polymorphism of ITGA2 were studied using the PCR or PCR-RFLP method. Results: The genotype distributions of the two polymorphisms in eNOS 4b4a and eNOS (−786T/C) were significantly different between T2DM and DR patients (p < .004 and p = .033, respectively). These polymorphisms were associated with the risk of DR (OR = 2.65, 95%CI [1.45–4.84], p = .002) for the eNOS 4b4a genotype and (OR = 2.43, 95%CI [1.06 − 5.56], p = .036) for the CC genotype of the eNOS gene (−786T/C). Similarly, the genotype distribution of the BglII polymorphism was significantly different between the two groups studied (p = .037). This polymorphism was associated with an increased risk of DR (OR = 4.03, 95% CI [1.17 − 7.85], p = .022) for BglII(+/+). Conclusion: The present study suggests that the polymorphisms 4b4a and −786T/C in the eNOS gene might be associated with DR. In addition, the BglII polymorphism in the ITGA2 gene was a risk factor for DR.
Recent Advances in Biotransformation of Saponins

Saponins are a class of glycosides whose aglycones can be either triterpenes or helical spirostanes. It is commonly recognized that these active ingredients are widely found in various kinds of advanced plants. Rare saponins, a special type of the saponins class, are able to enhance bidirectional immune regulation and memory, and have anti-lipid oxidation, anticancer, and antifatigue capabilities, but they are infrequent in nature. Moreover, the in vivo absorption rate of saponins is exceedingly low, which restricts their functions. Under such circumstances, the biotransformation of these ingredients from normal saponins—which are not be easily adsorbed by human bodies—is preferred nowadays. This process has multiple advantages, including strong specificity, mild conditions, and fewer byproducts. In this paper, the biotransformation of natural saponins—such as ginsenoside, gypenoside, glycyrrhizin, saikosaponin, dioscin, timosaponin, astragaloside and ardipusilloside—through microorganisms (Aspergillus sp., lactic acid bacteria, bacilli, and intestinal microbes) will be reviewed and prospected.
Selection of Level-Dependent Hearing Protectors for Use in An Indoor Shooting Range

The high sound pressure level generated by impulse noise produced in an indoor shooting range makes it necessary to protect the hearing of the people it affects. Due to the need for verbal communication during training at a shooting range, level-dependent hearing protectors are useful. The objective of this study was to answer the question of whether it is possible to properly protect the hearing of a shooting instructor using level-dependent hearing protectors. The noise parameters were measured in the places where the instructor was present at the shooting range. The division of a specific group of trained shooters into subgroups consisting of three or six simultaneously shooting individuals did not significantly affect the exposure of the shooting instructor to the noise. An assessment of noise reduction was carried out for eight models of earmuffs and two variants of earplugs, using computational methods for the selection of hearing protectors. Among the noise parameters, both the A-weighted equivalent sound pressure level and the C-weighted peak sound pressure level were taken into account. Depending on the assessment criterion adopted, a sufficient reduction in impulse noise was provided by either four or six out of the 10 hearing protectors included in the study.
Fruit and Vegetable Consumption in Overweight or Obese Individuals: A Meta-Analysis

Researchers have shown that fruit and vegetable consumption (FVC) promotes weight loss and prevents weight gain, thereby reducing risks for chronic health conditions. We conducted a meta-analysis to examine the overall effects of FVC interventions on weight loss for those with body-mass index (BMI) >25; we follow-up with moderator analyses to determine if effects varied based on participants, interventions, methods, or source characteristics. Extensive literature searches were conducted, resulting in 16 studies and providing 17 comparisons, across 3,719 participants. The overall summary effect was large (−2.81kg; p<.001). Several moderators were significant for increased weight loss: low socio-economic status (−4.99kg; p<.001), higher baseline BMI (slope=−0.29; p=.047), longer interventions (slope=0.012; p<.001), and recruitment setting [health care/programs (−3.7kg; p<.001); work/academic settings (−5.2kg: p<.001)]. Future researchers should investigate varying intervention lengths and examine specific needs of subgroups—higher versus lower socio-economic status, and overweight versus obese.
Concepts and limitations for learning developmental trajectories from single cell genomics

ABSTRACT Single cell genomics has become a popular approach to uncover the cellular heterogeneity of progenitor and terminally differentiated cell types with great precision. This approach can also delineate lineage hierarchies and identify molecular programmes of cell-fate acquisition and segregation. Nowadays, tens of thousands of cells are routinely sequenced in single cell-based methods and even more are expected to be analysed in the future. However, interpretation of the resulting data is challenging and requires computational models at multiple levels of abstraction. In contrast to other applications of single cell sequencing, where clustering approaches dominate, developmental systems are generally modelled using continuous structures, trajectories and trees. These trajectory models carry the promise of elucidating mechanisms of development, disease and stimulation response at very high molecular resolution. However, their reliable analysis and biological interpretation requires an understanding of their underlying assumptions and limitations. Here, we review the basic concepts of such computational approaches and discuss the characteristics of developmental processes that can be learnt from trajectory models. Summary: This Review describes the concepts and use of computational approaches to infer cellular trajectories from single cell expression data and discusses the applications of these approaches to the study of development and disease.
Cytotoxic activity of the seaweed compound fucosterol, alone and in combination with 5-fluorouracil, in colon cells using 2D and 3D culturing

ABSTRACT Colorectal cancer (CRC) is one of the most frequently occurring carcinomas which require effective therapies. Fucosterol is a sterol present in marine brown seaweeds with several biological activities. However, the influence of fucosterol in CRC remains to be determined. Thus, the aim of this study was to examine the anticancer activity of fucosterol alone and in combination with 5-fluorouracil (5-Fu) on two human CRC cell lines (HCT116 and HT29) and compared with cytotoxicity in one normal colon fibroblast cell line (CCD-18co) in monolayer (2D). The effect of fucosterol alone or in combination with 5-Fu was further assessed using HT29 multicellular spheroids (3D). Data demonstrated that fucosterol alone or combined with 5-Fu decreased cell viability in HT29 cells in 2D cultures without inducing cytotoxic in normal colon cells. The combination, fucosterol, and 5-Fu, also inhibited cell proliferation, clonogenic potential and cell migration without producing cell death in 2D. In multicellular spheroids, the combination fucosterol plus 5-Fu at the same concentrations used in 2D was not effective demonstrating that under the tested conditions the 3D model was more resistant than the 2D model. Taken together, these findings suggest that fucosterol might be a promising alternative to enhance the cytotoxic and anti-invasive actions of 5-Fu in colon cancer cells without consequent major adverse effects in normal cells. Our results also reinforce the need to include more complex 3D culture models in the initial stages of drug screening.
Rapid Communication: Plasma Interleukin-35 in Children with Autism

In autism spectrum disorders (ASD) many individuals have co-morbid immune dysregulation that can lead to inflammation in the brain and periphery. The novel cytokine interleukin (IL)-35 has described anti-inflammatory properties; however, the plasma levels of IL-35 in children with ASD have never been investigated. The plasma levels of IL-35 were measured by an enzyme-linked immunosorbent assay in 30 children with ASD and 39 typically developing (TD) controls. In the current study, we found that plasma IL-35 levels were significantly decreased in children with ASD compared with TD children. Furthermore, lower IL-35 levels were associated with worse behaviors as assessed using the aberrant behavior checklist. These findings are in line with other observations of decreased regulatory cytokines such as transforming growth factor beta and IL-10 in ASD, and associations with severity of behaviors. In conclusion, regulating the expression of IL-35 may provide a new possible target for the treatment of immune issues in ASD to address an imbalance between pro- and anti-inflammatory signals that alter the behavioral phenotype.
Ambulatory detection of sleep apnea using a non‐contact biomotion sensor

The high prevalence of obstructive sleep apnea has led to increasing interest in ambulatory diagnosis. The SleepMinder™ (SM) is a novel non‐contact device that employs radiofrequency wave technology to assess the breathing pattern, and thereby estimate obstructive sleep apnea severity. We assessed the performance of SleepMinder™ in the home diagnosis of obstructive sleep apnea.