Miracle-dz/UniFAR-FTUs huggingface dataset:
MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells

Significance Gains of the MYC gene are the most common imbalances in cancer and are associated with poor prognosis, particularly in B-cell lymphoma. Recent advances in DNA sequencing have revealed the existence of thousands of long noncoding RNAs (lncRNAs) with unknown functional relevance. We have here identified a MYC-regulated lncRNA that we named MYC-induced long noncoding RNA (MINCR) that has a strong correlation with MYC expression in cancer. We show that MINCR is functional and controls cell cycle progression by influencing the expression of MYC-regulated cell cycle genes. MINCR is, therefore, a novel player in MYC’s transcriptional network, with the potential to open new therapeutic windows in the fight against malignant lymphoma and, possibly, all cancers that rely on MYC expression. Despite the established role of the transcription factor MYC in cancer, little is known about the impact of a new class of transcriptional regulators, the long noncoding RNAs (lncRNAs), on MYC ability to influence the cellular transcriptome. Here, we have intersected RNA-sequencing data from two MYC-inducible cell lines and a cohort of 91 B-cell lymphomas with or without genetic variants resulting in MYC overexpression. We identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated in the same direction by MYC in the model cell lines. Among them, we focused on a lncRNA that we named MYC-induced long noncoding RNA (MINCR), showing a strong correlation with MYC expression in MYC-positive lymphomas. To understand its cellular role, we performed RNAi and found that MINCR knockdown is associated with an impairment in cell cycle progression. Differential gene expression analysis after RNAi showed a significant enrichment of cell cycle genes among the genes down-regulated after MINCR knockdown. Interestingly, these genes are enriched in MYC binding sites in their promoters, suggesting that MINCR acts as a modulator of the MYC transcriptional program. Accordingly, MINCR knockdown was associated with a reduction in MYC binding to the promoters of selected cell cycle genes. Finally, we show that down-regulation of Aurora kinases A and B and chromatin licensing and DNA replication factor 1 may explain the reduction in cellular proliferation observed on MINCR knockdown. We, therefore, suggest that MINCR is a newly identified player in the MYC transcriptional network able to control the expression of cell cycle genes.
Major histocompatibility complex variation at class II DQA locus in the brown hare (Lepus europaeus)

The major histocompatability complex (MHC) is a multigene family of receptors that bind and present antigenic peptides to T‐cells. Genes of the MHC are characterized by an outstanding genetic polymorphism, which is considered to be maintained by positive selection. Sites involved in peptide binding form binding pockets (P) that are collectively termed the peptide‐binding region (PBR). In this study, we examined the level of MHC genetic diversity within and among natural populations of brown hare (Lepus europaeus) from Europe and Anatolia choosing for analysis of the second exon of the DQA locus, one of the most polymorphic class II loci. We aimed at an integrated population genetic analysis of L. europeaus by (i) correlating MHC polymorphism to genetic variability and phylogenetic status estimated previously from maternally (mtDNA) and biparentally (allozymes, microsatellites) inherited loci; and (ii) comparing full‐length exon amino acid polymorphism with functional polymorphism in the PBR and the binding pockets P1, P6 and P9. A substantial level of DQA exon 2 polymorphism was detected with two completely different set of alleles between the Anatolian and European populations. However, the phylogeny of full‐length exon 2 Leeu‐DQA alleles did not show a strong phylogeographic signal. The presence of balancing selection was supported by a statistically significant excess of nonsynonymous substitutions over synonymous in the PBR and a trans‐species pattern of evolution detected after phylogenetic reconstruction. The differentiating patterns detected between genetic and functional polymorphism, i.e. the number and the distribution of pocket variants within and among populations, indicated a hierarchical action of selection pressures.
Tenax extraction mimics benthic and terrestrial bioavailability of organic compounds

Biota to sediment accumulation factors (BSAFs) are widely used to describe the potential accumulation of organic contaminants in organisms. From field studies it is known that these BSAFs can vary dramatically between sediments of different origin, which is possibly explained by the variation in bioavailability of organic contaminants in sediments. In the present study it is shown that the variability in BSAF values for different sediment samples obtained at two Dutch freshwater sites could largely be explained by the variation in Tenax‐extractable concentrations in these sediments. Variations of a factor of about 50 could be explained. The ratio between concentrations in biota and Tenax‐extractable concentrations in sediment varied slightly between sediments and contaminant class, but was close to the theoretically expected value of 2. This is a strong indication that Tenax‐extractable concentrations of contaminants in sediments are an excellent indicator of available concentrations.
Expression of T-cell-associated serine proteinase 1 during murine Leishmania major infection correlates with susceptibility to disease

The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis.
The Importance of Epidemiology in Dental Medicine

Over the last decades, dental caries and periodontal diseases have been the most common oral disorders affecting 60-90% of schoolchildren and 5-20% of middleaged adults [4,5]. Oral pathologies represent, because of their high incidence, one of the major health problems among children and adolescents. However, if early prevented and adequately treated, dental caries and periodontal diseases are both easily controlled, having reduced economical costs and important health benefits. Thus, rather than preventing this pathologies, it is important to promote oral health in an overall strategic context [2]. The application of epidemiological research in the study of rare diseases is also important to understand the main risk factors and distribution of the disease. Only with correct health research the health professional can develop the correct diagnosis, treatment and future prevention of a disease with the establishment of correct guidelines to be applied [6].
Prediction of human sperm penetrating ability using computerized motion parameters

The sperm penetration assay (SPA) is used to assess male fertilizing potential but it is tedious and costly. Computer analysis could replace the need for the SPA in some cases, if computerized sperm motility parameters are highly predictive of SPA performance. The objective of this study was to determine whether computerized motility parameters from fresh semen samples could be used to predict SPA performance. Computer automated semen analysis (CASA; CellSoft, Cryo Resources) was used to quantitate sperm concentration (CONC), percent motility (MOT), curvilinear velocity (VEL), linearity of swimming trajectory (LIN), mean amplitude of lateral head displacement (ALH), and beat/cross frequency (B/CF). The SPA was performed using either Biggers, Whitten, and Whittingham's medium (BWW) or TEST‐yolk buffer (TYB). Patients were divided into three groups depending on SPA performance: group 1, BWW‐treated, 0% versus > 0% penetration; group 2, TYB‐treated, 0% versus > 0% penetration; and group 3, TYB‐treated, < 20% versus ≥ 20% penetration. SPA performance was highly correlated with CONC, MOT, VEL, and B/CF. CONC, MOT, VEL, and B/CF were significantly higher for patients who penetrated in the SPA than for those who failed to penetrate. Discriminant function analysis (DFA) successfully classified 76% of all patients treated with TYB (group 2) who penetrated and 86% of nonpenetrators based on their computerized motility parameters. For group 2 DFA predicted that 93 men would penetrate in the SPA with TYB. Of these, 90 (96%) successfully penetrated at least one egg. It is concluded that DFA of computerized motility parameters can accurately predict whether a patient will penetrate (> 0%) in the TYB‐treated SPA.
UP-REGULATION OF APICAL SODIUM CHLORIDE COTRANSPORTER AND BASOLATERAL CHLORIDE CHANNELS ARE RESPONSIBLE FOR THE MAINTENANCE OF SALT SENSITIVE HYPERTENSION

Department of Internal Medicine, Chair of Nephrology, Faculty of Medicine, Second University of Napoli (Italy), Prassis Research Institute, Sigma Tau, Milan (Italy), Department of Physiology, University of Tuebingen (Germany), Institute of Anatomy and Physiology, University of Zurich (Switzerland), Chair of Nephrology, Ateneo Vita e Salute, S. Raffaele Hospital, Milan (Italy),**Department of Pharmacology, Paracelsius Medical University, Salzburg (Austria), *Department of Biomolecular Sciences and Biotechnology, Free University of Milan (Italy).
Three Novel IGFALS Gene Mutations Resulting in Total ALS and Severe Circulating IGF-I/IGFBP-3 Deficiency in Children of Different Ethnic Origins

Background/Aims: To date, four mutations in the IGFALS gene have been reported. We now describe two children of different ethnic background with total acid-labile subunit (ALS) and severe circulating IGF-I/IGFBP-3 deficiencies resulting from three novel mutations in the IGFALS gene. Patients/Methods: Serum and DNA of patients were analyzed. Results: Case 1 is a 12-year-old boy of Mayan origin. Case 2 is a 5-year-old girl of Jewish/Eastern European (Polish, Russian, Austrian-Hungarian)/Icelandic/European (French, English) ancestry. The reported cases had moderate short stature (–2.91 and –2.14 SDS, respectively), nondetectable serum ALS and extremely low serum concentrations of IGF-I and IGFBP-3. Case 1 harbored a novel homozygous 1308_1316 dup9 mutation in a highly conserved leucine-rich repeat (LRR) 17 motif of exon 2, representing an in-frame insertion of 3 amino acids, LEL. Case 2 harbored a novel heterozygous C60S/L244F mutation in exon 2, located within a highly conserved LRR 1 and LRR 9, respectively. Conclusions: The identification of additional novel IGFALS mutations, resulting in severe IGF-I/IGFBP-3 and ALS deficiencies, supports IGFALS as a candidate gene of the GH/IGF system, implicated in the pathogenesis of primary IGF deficiency, and represents an important part of its differential diagnosis.
TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity

Significance This study shows that neurodegenerative changes induced by α-synuclein in midbrain dopamine neurons in vivo can be blocked through activation of the autophagy-lysosome pathway. Using an adeno-associated virus model of Parkinson disease to overexpress α-synuclein in the substantia nigra, we show that genetic [transcription factor EB (TFEB) and Beclin-1 overexpression] or pharmacological (rapalog) manipulations that enhance autophagy protect nigral neurons from α-synuclein toxicity, but inhibiting autophagy exacerbates α-synuclein toxicity. The results provide a mechanistic link between α-synuclein toxicity and impaired TFEB function, and identify TFEB as a target for therapies aimed at neuroprotection and disease modification in Parkinson disease. The aggregation of α-synuclein plays a major role in Parkinson disease (PD) pathogenesis. Recent evidence suggests that defects in the autophagy-mediated clearance of α-synuclein contribute to the progressive loss of nigral dopamine neurons. Using an in vivo model of α-synuclein toxicity, we show that the PD-like neurodegenerative changes induced by excess cellular levels of α-synuclein in nigral dopamine neurons are closely linked to a progressive decline in markers of lysosome function, accompanied by cytoplasmic retention of transcription factor EB (TFEB), a major transcriptional regulator of the autophagy-lysosome pathway. The changes in lysosomal function, observed in the rat model as well as in human PD midbrain, were reversed by overexpression of TFEB, which afforded robust neuroprotection via the clearance of α-synuclein oligomers, and were aggravated by microRNA-128–mediated repression of TFEB in both A9 and A10 dopamine neurons. Delayed activation of TFEB function through inhibition of mammalian target of rapamycin blocked α-synuclein induced neurodegeneration and further disease progression. The results provide a mechanistic link between α-synuclein toxicity and impaired TFEB function, and highlight TFEB as a key player in the induction of α-synuclein–induced toxicity and PD pathogenesis, thus identifying TFEB as a promising target for therapies aimed at neuroprotection and disease modification in PD.
Meta-analysis Cancer : A Case-Control Study , Systematic Review , and Recreational Physical Activity and Epithelial Ovarian

It remains unclear whether physical activity is associated with epithelial ovarian cancer risk. We therefore examined the association between recreational physical activity and risk of ovarian cancer in a national population-based case-control study in Australia. We also systematically reviewed all the available evidence linking physical activity with ovarian cancer to provide the best summary estimate of the association. The case-control study included women ages 18 to 79 years with a new diagnosis of invasive (n = 1,269) or borderline (n = 311) epithelial ovarian cancer identified through a network of clinics, physicians, and state cancer registries throughout Australia. Controls (n = 1,509) were randomly selected from the national electoral roll and were frequency matched to cases by age and state. For the systematic review, we identified eligible studies using Medline, the ISI Science Citation Index, and manual review of retrieved references, and included all case-control or cohort studies that permitted assessment of an association between physical activity (recreational/ occupational/sedentary behavior) and histologically confirmed ovarian cancer. Meta-analysis was restricted to the subset of these studies that reported on recreational physical activity. In our case-control study, we observed weakly inverse or null associations between recreational physical activity and risk of epithelial ovarian cancer overall. There was no evidence that the effects varied by tumor behavior or histologic subtype. Twelve studies were included in the metaanalysis, which gave summary estimates of 0.79 (95% confidence interval, 0.70-0.85) for case-control studies and 0.81 (95% confidence interval, 0.57-1.17) for cohort studies for the risk of ovarian cancer associated with highest versus lowest levels of recreational physical activity. Thus, pooled results from observational studies suggest that a modest inverse association exists between level of recreational physical activity and the risk of ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2321–30)
Phase I studies of imatinib mesylate combined with cisplatin and irinotecan in patients with small cell lung carcinoma

Small cell lung carcinoma (SCLC) cell lines commonly express KIT and its ligand, stem cell factor, suggesting an autocrine loop promoting cell growth. Imatinib inhibits KIT kinase activity. SCLC cells treated with imatinib in vitro undergo cell cycle arrest. Imatinib reduces resistance to irinotecan in vitro. Common metabolic pathways suggest there may be drug interactions between imatinib and irinotecan or cisplatin. In the current study, the authors investigated the feasibility of combining these drugs in the treatment of patients with SCLC.
Rifampin and Rifabutin Resistance Mechanism inHelicobacter pylori

ABSTRACT Eighty-one clinical isolates of Helicobacter pylorishowed no resistance to rifampin (MIC range, 0.032 to 2 μg/ml; MIC at which 50% of isolates are inhibited [MIC50], 0.25 μg/ml). The MIC50 of rifabutin was 0.008 μg/ml (n = 16). All resistant laboratory mutants of H. pylori ATCC 43504 showed amino acid exchanges in codons 524 to 545 or codon 585 of the rpoB gene, corresponding to the gene sequences from Mycobacterium tuberculosis andEscherichia coli.
Sequence-controlled RNA self-processing: computational design, biochemical analysis, and visualization by AFM

Reversible chemistry allowing for assembly and disassembly of molecular entities is important for biological self-organization. Thus, ribozymes that support both cleavage and formation of phosphodiester bonds may have contributed to the emergence of functional diversity and increasing complexity of regulatory RNAs in early life. We have previously engineered a variant of the hairpin ribozyme that shows how ribozymes may have circularized or extended their own length by forming concatemers. Using the Vienna RNA package, we now optimized this hairpin ribozyme variant and selected four different RNA sequences that were expected to circularize more efficiently or form longer concatemers upon transcription. (Two-dimensional) PAGE analysis confirms that (i) all four selected ribozymes are catalytically active and (ii) high yields of cyclic species are obtained. AFM imaging in combination with RNA structure prediction enabled us to calculate the distributions of monomers and self-concatenated dimers and trimers. Our results show that computationally optimized molecules do form reasonable amounts of trimers, which has not been observed for the original system so far, and we demonstrate that the combination of theoretical prediction, biochemical and physical analysis is a promising approach toward accurate prediction of ribozyme behavior and design of ribozymes with predefined functions.
Mechanism of nuclear movements in a multinucleated cell

Multinucleated cells are important in many organisms but the mechanisms governing the movements of nuclei sharing a common cytoplasm are not understood. In the hyphae of the plant pathogenic fungus Ashbya gossypii, nuclei move back and forth, occasionally bypassing each other, and, preventing the formation of nuclear clusters, this is essential for genetic stability. These movements depend on cytoplasmic microtubules emanating from the nuclei, that are pulled by dynein motors anchored at the cortex. Using 3D stochastic simulations with parameters constrained by the literature, we predict the cortical anchors density from the characteristics of nuclear movements. Altogether, the model accounts for the complex nuclear movements seen in vivo, using a minimal set of experimentally determined ingredients. Interestingly, these ingredients power the oscillations of the anaphase spindle in budding yeast, but in A. gossypii this system is not restricted to a specific nuclear cycle stage, possibly as a result of adaptation to hyphal growth and multinuclearity.
A Wide Variety of Clostridium perfringens Type A Food-Borne Isolates That Carry a Chromosomal cpe Gene Belong to One Multilocus Sequence Typing Cluster

ABSTRACT Of 98 suspected food-borne Clostridium perfringens isolates obtained from a nationwide survey by the Food and Consumer Product Safety Authority in The Netherlands, 59 strains were identified as C. perfringens type A. Using PCR-based techniques, the cpe gene encoding enterotoxin was detected in eight isolates, showing a chromosomal location for seven isolates and a plasmid location for one isolate. Further characterization of these strains by using (GTG)5 fingerprint repetitive sequence-based PCR analysis distinguished C. perfringens from other sulfite-reducing clostridia but did not allow for differentiation between various types of C. perfringens strains. To characterize the C. perfringens strains further, multilocus sequence typing (MLST) analysis was performed on eight housekeeping genes of both enterotoxic and non-cpe isolates, and the data were combined with a previous global survey covering strains associated with food poisoning, gas gangrene, and isolates from food or healthy individuals. This revealed that the chromosomal cpe strains (food strains and isolates from food poisoning cases) belong to a distinct cluster that is significantly distant from all the other cpe plasmid-carrying and cpe-negative strains. These results suggest that different groups of C. perfringens have undergone niche specialization and that a distinct group of food isolates has specific core genome sequences. Such findings have epidemiological and evolutionary significance. Better understanding of the origin and reservoir of enterotoxic C. perfringens may allow for improved control of this organism in foods.
Relationships among training stress, mood and dehydroepiandrosterone sulphate/cortisol ratio in female cyclists

Abstract In this study, we examined the effect of rapidly increased training volume and intensity on hormonal responses (salivary cortisol [C] and urinary dehydroepiandrosterone sulphate [DHEA-S]) and recovery-stress state perceived by 12 female cyclists. Over the 4-day experimental period, there was an average increase in training load of approximately 122% compared with that during the previous 12 days. Scores on subscales of the Recovery Stress Questionnaire for Athletes increased for the somatic component of stress (Fatigue, Emotional Stress and Social Stress; P < 0.05) and decreased the factor indicating recovery (General Well Being; P < 0.05) after the heavy training period. The training programme increased resting concentrations of salivary cortisol (P < 0.05) and decreased the DHEA-S/C ratio (P < 0.05). The increase in training load of cyclists was correlated with this hormonal ratio (r = −0.48, P < 0.05). Changes in resting cortisol concentration as a result of heavy training stress were positively related to the change in Physical Complaints (r = 0.69, P < 0.01). Negative relationships were also found between changes in the DHEA-S/C ratio and changes in the somatic component of stress. The present results suggest that there is a dose–response relationship between increased training load, resting DHEA-S/C ratio and subjective assessment of stress and recovery, implying that this ratio could be used as an indicator of training status in female athletes.