Miracle-dz/UniFAR-FTUs huggingface dataset:
Fatty Acid Synthase Inhibitor C75 Ameliorates Experimental Colitis

Abnormalities of lipid metabolism through overexpression of fatty acid synthase (FASN), which catalyzes the formation of long-chain fatty acids, are associated with the development of inflammatory bowel disease (IBD). C75 is a synthetic α-methylene-γ-butyrolactone compound that inhibits FASN activity. We hypothesized that C75 treatment could effectively reduce the severity of experimental colitis. Male C57BL/6 mice were fed 4% dextran sodium sulfate (DSS) for 7 d. C75 (5 mg/kg body weight) or dimethyl sulfoxide (DMSO) (vehicle) was administered intraperitoneally from d 2 to 6. Clinical parameters were monitored daily. Mice were euthanized on d 8 for histological evaluation and measurements of colon length, chemokine, cytokine and inflammatory mediator expression. C75 significantly reduced body weight loss from 23% to 15% on d 8, compared with the vehicle group. The fecal bleeding, diarrhea and colon histological damage scores in the C75-treated group were significantly lower than scores in the vehicle animals. Colon shortening was significantly improved after C75 treatment. C75 protected colon tissues from DSS-induced apoptosis by inhibiting caspase-3 activity. Macrophage inflammatory protein 2, keratinocyte-derived chemokine, myeloperoxidase activity and proinflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β and IL-6) in the colon were significantly downregulated in the C75-treated group, compared with the vehicle group. Treatment with C75 in colitis mice inhibited the elevation of FASN, cyclooxygenase-2 and inducible nitric oxide synthase expression as well as IκB degradation in colon tissues. C75 administration alleviates the severity of colon damage and inhibits the activation of inflammatory pathways in DSS-induced colitis. Thus, inhibition of FASN may represent an attractive therapeutic potential for treating IBD.
Catholics, Protestants, and Testamentary Charity in Seventeenth-Century Lyon and Nimes

There have been many studies of Catholic and public charity in seventeenth-century France' and a number of accounts of Protestant charity as part of the history of Protestant churches.2 It is the purpose of this study to complement my study of charitable institutions in Lyon and Nimes, published in French Historical Studies, VIII (Spring, 1974), by comparing sample testamentary charity of Catholics and Protestants in the two cities as evidence of the attitude of individuals to charity.3 This study also reflects the changing patterns of charity and the impact on charity of the rivalry between the two faiths. The major reason for the choice of Lyon and Nimes for this comparison was the fact that Lyon was a devoutly Catholic
Treatment with recombinant placental growth factor (PlGF) enhances both angiogenesis and arteriogenesis and improves survival after myocardial infarction.

BACKGROUND Placental growth factor (PlGF), a homolog of vascular endothelial growth factor, is reported to stimulate angiogenesis and arteriogenesis in pathological conditions. It was recently demonstrated that PlGF is rapidly produced in myocardial tissue during acute myocardial infarction (MI). However, the effects of exogenous PlGF administration on the healing process after MI are not fully understood. The purpose of the present study was to examine whether PlGF treatment has therapeutic potential in MI. METHODS AND RESULTS Recombinant human PlGF (rhPlGF: 10 microg) was administered continuously for 3 days in a mouse model of acute MI. rhPlGF treatment significantly improved survival rate after MI and preserved cardiac function relative to control mice. The numbers of CD31-positive cells and alpha-smooth muscle actin-positive vessels in the infarct area were significantly increased in the rhPlGF group. Endothelial progenitor cells (Flk-1(+)Sca-1(+) cells) were mobilized by rhPlGF into the peripheral circulation. Furthermore, rhPlGF promoted the recruitment of GFP-labeled bone marrow cells to the infarct area, but only a few of those migrating cells differentiated into endothelial cells. CONCLUSIONS Exogenous PlGF plays an important role in healing processes by improving cardiac function and stimulating angiogenesis following MI. It can be considered as a new therapeutic molecule.
Evolutionary conservation of vertebrate notochord genes in the ascidian Ciona intestinalis

To reconstruct a minimum complement of notochord genes evolutionarily conserved across chordates, we scanned the Ciona intestinalis genome using the sequences of 182 genes reported to be expressed in the notochord of different vertebrates and identified 139 candidate notochord genes. For 66 of these Ciona genes expression data were already available, hence we analyzed the expression of the remaining 73 genes and found notochord expression for 20. The predicted products of the newly identified notochord genes range from the transcription factors Ci‐XBPa and Ci‐miER1 to extracellular matrix proteins. We examined the expression of the newly identified notochord genes in embryos ectopically expressing Ciona Brachyury (Ci‐Bra) and in embryos expressing a repressor form of this transcription factor in the notochord, and we found that while a subset of the genes examined are clearly responsive to Ci‐Bra, other genes are not affected by alterations in its levels. We provide a first description of notochord genes that are not evidently influenced by the ectopic expression of Ci‐Bra and we propose alternative regulatory mechanisms that might control their transcription. genesis 46:697–710, 2008. © 2008 Wiley‐Liss, Inc.
A One Year Prospective Comparison of Kidney Growth and Function in Children Recipients of Grafts From Children and Adults

Background. Renal grafts have demonstrated capacity to adapt to the recipient. The aim of this study was to assess the growth of renal grafts transplanted to children, during the first year posttransplant. Methods. We conducted a 1 year prospective study comparing the growth of renal grafts from children and adults donors transplanted in children, and correlated this growth with graft function. Two groups were studied: (a) group 1—32 children transplanted with pediatric deceased kidneys from donors younger than 16 years and (b) group 2—31 children transplanted with organs from adult living donors. Anthropometric assessment, sonographic measurement of the graft, and serum creatinine at 1 week, 1, 6, and 12 months posttransplantation were performed. Results. Children from group 1 presented an 18% increase in graft volume after the sixth month of transplant, whereas in group 2 grafts presented a 14% reduction in volume, mainly during the first month; the variation in renal diameters was not uniform. Children from group 1 presented a glomerular filtration rate (GFR) increase during the follow-up (46–102 mL/min/1.73 m2). After 1 year, GFR and graft volume were similar. Growth of individuals from both groups was comparable. Conclusions. In the short term, pediatric kidneys raise volume and GFR, whereas adult kidneys slightly lower volume and GFR when transplanted in children. Taking our and other studies results into consideration, we can hypothesize that in addition to compensatory hypertrophy, pediatric grafts are likely capable of continued somatic growth.
Disruption of the NF‐κB/NLRP3 connection by melatonin requires retinoid‐related orphan receptor‐α and blocks the septic response in mice

We determined the NF‐κB‐ and NOD‐like receptor (NLR)P3‐dependent molecular mechanisms involved in sepsis and evaluated the role of retinoid‐related orphan receptor (ROR)‐α in melatonin's anti‐inflammatory actions. Western blot, RT‐PCR, ELISA, and spectrophotometric analysis revealed that NF‐κB and NLRP3 closely interact, leading to proinflammatory and pro‐oxidant status in heart tissue of septic C57BL/6J mice. Moreover, mitochondrial oxygen consumption was reduced by 80% in septic mice. In vivo and in vitro analysis showed that melatonin administration blunts NF‐κB transcriptional activity through a sirtuinl‐dependent NF‐κB deacetylation in septic mice. Melatonin also decreased NF‐κB‐dependent proinflammatory response and restored redox balance and mitochondrial homeostasis, thus inhibiting the NLRP3 inflammasome. In an important finding, the inhibition of NF‐κB by melatonin, but not that of NLRP3, was blunted in RORαsg/sg mice, indicating that functional RORα transcription factor is necessary for the initiation of the innate immune response against inflammation. Our results are evidence of the NF‐κB/NLRP3 connection during sepsis and identify NLRP3 as a novel molecular target for melatonin. The multiple molecular targets of melatonin in this study explain its potent anti‐inflammatory efficacy against systemic innate immune activation and herald a promising therapeutic application for melatonin in the treatment of sepsis. —García, J. A. , Volt, H. , Venegas, C. , Doerrier, C. , Escames, G. , López. , L. C. , Acuña‐Castroviejo, D. Disruption of the NF‐κB/NLRP3 connection by melatonin requires retinoid‐related orphan receptor‐α and blocks the septic response in mice. FASEB J. 29, 3863‐3875 (2015). www.fasebj. org
The Interaction of Four Genes in the Inflammation Pathway Significantly Predicts Prostate Cancer Risk

It is widely hypothesized that the interactions of multiple genes influence individual risk to prostate cancer. However, current efforts at identifying prostate cancer risk genes primarily rely on single-gene approaches. In an attempt to fill this gap, we carried out a study to explore the joint effect of multiple genes in the inflammation pathway on prostate cancer risk. We studied 20 genes in the Toll-like receptor signaling pathway as well as several cytokines. For each of these genes, we selected and genotyped haplotype-tagging single nucleotide polymorphisms (SNP) among 1,383 cases and 780 controls from the CAPS (CAncer Prostate in Sweden) study population. A total of 57 SNPs were included in the final analysis. A data mining method, multifactor dimensionality reduction, was used to explore the interaction effects of SNPs on prostate cancer risk. Interaction effects were assessed for all possible n SNP combinations, where n = 2, 3, or 4. For each n SNP combination, the model providing lowest prediction error among 100 cross-validations was chosen. The statistical significance levels of the best models in each n SNP combination were determined using permutation tests. A four-SNP interaction (one SNP each from IL-10, IL-1RN, TIRAP, and TLR5) had the lowest prediction error (43.28%, P = 0.019). Our ability to analyze a large number of SNPs in a large sample size is one of the first efforts in exploring the effect of high-order gene-gene interactions on prostate cancer risk, and this is an important contribution to this new and quickly evolving field.
Differential requirements for Fgf3 and Fgf8 during mouse forebrain development

Multiple Fgfs are expressed during formation and patterning of the telencephalon in vertebrates. Fgf8 has been shown to control the size of the telencephalon and the development of signaling centers in zebrafish and mouse. Next to Fgf8, Fgf3 also influences telencephalic gene expression in the zebrafish. Moreover, Fgf3 and Fgf8 have been shown to have combinatorial functions during forebrain development in this species. Here, we have examined telencephalic development in Fgf3 null mouse mutants and embryos that lack both Fgf3 and Fgf8 in their forebrain. In contrast to zebrafish, Fgf3 mutants show normal forebrain development and expression of telencephalic marker genes. Although double mutants for Fgf3 and Fgf8 show a further reduction of forebrain size no additional changes of telencephalic gene expression are observed compared with Fgf8 mutants. Therefore unlike in zebrafish, Fgf3 is not required for mouse forebrain development whereas Fgf8 has a central role during this process. Developmental Dynamics 237:3417–3423, 2008. © 2008 Wiley‐Liss, Inc.
Molecular Mechanisms That Contribute to Horizontal Transfer of Plasmids by the Bacteriophage SPP1

Natural transformation and viral-mediated transduction are the main avenues of horizontal gene transfer in Firmicutes. Bacillus subtilis SPP1 is a generalized transducing bacteriophage. Using this lytic phage as a model, we have analyzed how viral replication and recombination systems contribute to the transfer of plasmid-borne antibiotic resistances. Phage SPP1 DNA replication relies on essential phage-encoded replisome organizer (G38P), helicase loader (G39P), hexameric replicative helicase (G40P), recombinase (G35P) and in less extent on the partially dispensable 5′→3′ exonuclease (G34.1P), the single-stranded DNA binding protein (G36P) and the Holliday junction resolvase (G44P). Correspondingly, the accumulation of linear concatemeric plasmid DNA, and the formation of transducing particles were blocked in the absence of G35P, G38P, G39P, and G40P, greatly reduced in the G34.1P, G36P mutants, and slightly reduced in G44P mutants. In contrast, establishment of injected linear plasmid DNA in the recipient host was independent of viral-encoded functions. DNA homology between SPP1 and the plasmid, rather than a viral packaging signal, enhanced the accumulation of packagable plasmid DNA. The transfer efficiency was also dependent on plasmid copy number, and rolling-circle plasmids were encapsidated at higher frequencies than theta-type replicating plasmids.
Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM‐domain structures: one binds BAF and the other binds DNA

The nuclear envelope proteins LAP2, emerin and MAN1 share a conserved ∼40‐residue ‘LEM’ motif. Loss of emerin causes Emery–Dreifuss muscular dystrophy. We have solved the solution NMR structure of the constant region of human LAP2 (residues 1–168). Human LAP21–168 has two structurally independent, non‐interacting domains located at residues 1–50 (‘LAP2‐N’) and residues 111–152 (LEM‐domain), connected by an ∼60‐residue flexible linker. The two domains are structurally homologous, comprising a helical turn followed by two helices connected by an 11–12‐residue loop. This motif is shared by subdomains of T4 endonuclease VII and transcription factor rho, despite negligible (≤15%) sequence identity. NMR chemical shift mapping demonstrated that the LEM‐domain binds BAF (barrier‐to‐autointegration factor), whereas LAP2‐N binds DNA. Both binding surfaces comprise helix 1, the N‐terminus of helix 2 and the inter‐helical loop. Binding selectivity is determined by the nature of the surface residues in these binding sites, which are predominantly positively charged for LAP2‐N and hydrophobic for the LEM‐domain. Thus, LEM and LEM‐like motifs form a common structure that evolution has customized for binding to BAF or DNA.
Intakes of Fruits, Vegetables, and Related Vitamins and Lung Cancer Risk: Results from the Shanghai Men's Health Study (2002–2009)

Most epidemiological studies evaluating the association of fruit and vegetable intakes on lung cancer risk were conducted in North American and European countries. We investigated the association of intakes of fruits, vegetables, dietary vitamins A and C, and folate with lung cancer risk among 61,491 adult Chinese men who were recruited into the Shanghai Men's Health Study, a population-based, prospective cohort study. Baseline dietary intake was assessed through a validated food frequency questionnaire during in-home visits. Multivariate Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of lung cancer risk associated with dietary intakes. During a median follow-up of 5.5 yr, 359 incident lung cancer cases accrued after the first year of follow-up and 68.8% of them were current smokers. Intakes of green leafy vegetables, β-carotene-rich vegetables, watermelon, vitamin A, and carotenoids were inversely associated with lung cancer risk; the corresponding HR (95% CI) comparing the highest with the lowest quartiles were 0.72 (0.53–0.98), 0.69 (0.51–0.94), 0.65 (0.47–0.90), 0.63 (0.44–0.88), and 0.64 (0.46–0.88). Intake of all fruits and vegetables combined was marginally associated with lower risk. Our study suggests that the consumption of carotenoid-rich vegetables is inversely associated with lung cancer risk.
[Neferine protects endothelial cells against damages induced by LPC and relationship with asymmetric dimethylarginine].

OBJECTIVE To investigate the protective effect of neferine against damages of endothelial cells induced by lysophos-phatidylcholine (LPC) and the relationship with asymmetric dimethylarginine (ADMA). METHOD The human umbilical vein endothelial cells (HUVEC-12) were treated with LPC (10 mg x L(-1)) for 24 h to establish the model of endothelial cells damages; HUVECs were prior exposed to neferine (0.1, 1.0 or 10.0 micromol x L(-1) ) for 1 h, and then exposed to LPC in the presence of the neferine for 24 h. At the end of the experiment, the cultured medium was collected for measuring the concentration of nitric oxide (NO), aleic dialdehyde (MDA) as well as ADMA and the cells were collected for measuring the level of intracellular reactive oxygen species (ROS). RESULT Compared with control group, exposure of endothelial cells to LPC (10 mg x L(-1)) for 24 h significantly increased the concentration of MDA and ADMA in the medium and the level of intracellular ROS and coinstantaneously significantly decreased the concentration of NO in the medium. Neferine (0.1, 1.0 or 10.0 micromol x L(-1)) significantly inhibited the elevated concentration of MDA, ADMA as well as the level of intracellular ROS and coinstantaneously significantly attenuated the decreased level of NO induced by LPC. CONCLUSION Neferine can protect the endothelial cells against damages induced by LPC and the protective effect is related to the decrease of the concentration of ADMA.
Development and Validation of a Multifactor Mindfulness Scale in Youth: The Comprehensive Inventory of Mindfulness Experiences–Adolescents (CHIME-A)

Mindfulness-based interventions show consistent benefits in adults for a range of pathologies, but exploration of these approaches in youth is an emergent field, with limited measures of mindfulness for this population. This study aimed to investigate whether multifactor scales of mindfulness can be used in adolescents. A series of studies are presented assessing the performance of a recently developed adult measure, the Comprehensive Inventory of Mindfulness Experiences (CHIME) in 4 early adolescent samples. Study 1 was an investigation of how well the full adult measure (37 items) was understood by youth (N = 292). Study 2 piloted a revision of items in child friendly language with a small group (N = 48). The refined questionnaire for adolescents (CHIME-A) was then tested in Study 3 in a larger sample (N = 461) and subjected to exploratory factor analysis and a range of external validity measures. Study 4 was a confirmatory factor analysis in a new sample (N = 498) with additional external validity measures. Study 5 tested temporal stability (N = 120). Results supported an 8-factor 25-item measure of mindfulness in adolescents, with excellent model fit indices and sound internal consistency for the 8 subscales. Although the CFA supported an overarching factor, internal reliability of a combined total score was poor. The development of a multifactor measure represents a first step toward testing developmental models of mindfulness in young people. This in turn will aid construction of evidence based interventions that are not simply downward derivations of adult mindfulness programs.
A bioclinical prognostic model using MYC and BCL2 predicts outcome in relapsed/refractory diffuse large B-cell lymphoma

The objective of this study was to create a bioclinical model, based on clinical and molecular predictors of event-free and overall survival for relapsed/refractory diffuse large B-cell lymphoma patients treated on the Canadian Cancer Trials Group (CCTG) LY12 prospective study. In 91 cases, sufficient histologic material was available to create tissue microarrays and perform immunohistochemistry staining for CD10, BCL6, MUM1/IRF4, FOXP1, LMO2, BCL2, MYC, P53 and phosphoSTAT3 (pySTAT3) expression. Sixty-seven cases had material sufficient for fluorescent in situ hybridization (FISH) for MYC and BCL2. In addition, 97 formalin-fixed, paraffin-embedded tissue samples underwent digital gene expression profiling (GEP) to evaluate BCL2, MYC, P53, and STAT3 expression, and to determine cell-of-origin (COO) using the Lymph2Cx assay. No method of determining COO predicted event-free survival (EFS) or overall survival (OS). Factors independently associated with survival outcomes in multivariate analysis included primary refractory disease, elevated serum lactate dehydrogenase (LDH) at relapse, and MYC or BCL2 protein or gene expression. A bioclinical score using these four factors predicted outcome with 3-year EFS for cases with 0–1 vs. 2–4 factors of 55% vs. 16% (P<0.0001), respectively, assessing MYC and BCL2 by immunohistochemistry, 46% vs. 5% (P<0.0001) assessing MYC and BCL2 messenger ribonucleic acid (mRNA) by digital gene expression, and 42% vs. 21% (P=0.079) assessing MYC and BCL2 by FISH. This proposed bioclinical model should be further studied and validated in other datasets, but may discriminate relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients who could benefit from conventional salvage therapy from others who require novel approaches. The LY12 study; clinicaltrials.gov Identifier: 00078949.
Hospital implementation of resuscitation guidelines and review of CPR training programmes: a nationwide study

This study aimed to investigate cardiopulmonary resuscitation (CPR) guideline implementation and CPR training in hospitals. This nationwide study included mandatory resuscitation protocols from each Danish hospital. Protocols were systematically reviewed for adherence to the European Resuscitation Council (ERC) 2010 guidelines and CPR training in each hospital. Data were included from 45 of 47 hospitals. Adherence to the ERC basic life support (BLS) algorithm was 49%, whereas 63 and 58% of hospitals adhered to the recommended chest compression depth and rate. Adherence to the ERC advanced life support (ALS) algorithm was 81%. Hospital BLS course duration was [median (interquartile range)] 2.3 (1.5–2.5) h, whereas ALS course duration was 4.0 (2.5–8.0) h. Implementation of ERC 2010 guidelines on BLS is limited in Danish hospitals 2 years after guideline publication, whereas the majority of hospitals adhere to the ALS algorithm. CPR training differs among hospitals.
Antimycotic Effect of the Essential Oil of Aloysia Triphylla against Candida Species Obtained from Human Pathologies

The research of alternative substances to treat infections caused by Candida species is a need. Aromatic plants have the ability to produce secondary metabolites, such as essential oils (EO). The antimicrobial properties of Aloysia triphylla (L'Her.) Britton (cedrón) EO has been previously described. The aims of this work were to determine the antimicrobial activity and the effect on the cell structure of the EO of A. triphylla against Candida sp isolated from human illnesses. The EO was obtained by hydrodistillation of A. triphylla leaves. The minimum inhibitory concentration (MIC) was performed with microdilution method and the minimum fungicidal concentration (MFC) was determined. A. triphylla EO's showed antifungal activity against all yeast: C. albicans, C. dubliniensis, C. glabrata, C. krusei, C. guillermondii, C. parapsilosis and C. tropicalis which were resistant to fluconazol (150 mg/mL). The range of MIC values was from: 35 to 140 μg/mL and the MFC: 1842 to 2300μg/mL. The time of killing at the MFC against C. albicans (3 × 105 UFC/mL) was 140 min. The dates of OD620 and OD260 suggest lysis and loss of absorbing material, respectively. The HROM shows distortion in morphology and shape of the cell, with large vacuoles in the cytoplasm. These studies clearly show that A. triphylla EO is a promising alternative for the treatment of candidiasis.