Miracle-dz/UniFAR-FTUs huggingface dataset:
Interphase Cytogenetic Analysis of Lymphoma‐Associated Chromosomal Breakpoints in Primary Diffuse Large B‐Cell Lymphomas of the Central Nervous System

Primary central nervous system lymphomas (PCNSLs) are germinal center-derived diffuse large B-cell lymphomas (DLBCLs) arising in and remaining confined to the brain, the pathogenesis of which is poorly understood. We investigated 13 PCNSLs from immunocompetent patients by means of interphase cytogenetics on cryopreserved cells derived from stereotactic biopsies. Interphase fluorescence in situ hybridization (FISH) was performed for the detection of structural alterations affecting the IGH (14q32), IGK (2p12), IGL (22q11), BCL6 (3q27), MYC (8q24), CCND1 (11q13), MLT, and BCL2 (both 18q21) loci. Signal constellations indicating breakpoints within the IGH and IGK locus were detected in 5 and 1 PCNSLs, respectively. There was no evidence for a t(8;14), t(11;14), or t(14;18) in this series of tumors. Breakpoints in the BCL6 locus were observed in 3 of the 13 cases, and nuclear Bcl-6 protein expression was detected in 6 of 9 PCNSLs, including those with genomic alterations of the encoding locus. Gains of 18q21 represented the most frequent imbalances present in more than one third of all cases. Interestingly, these gains included the MLT gene. Thus, this study provides the first evidence for recurrent chromosomal translocations in PCNSLs. While they share similarities with extracerebral DLBCL with respect to the presence of IGH translocations, they appear to differ in the usage of translocation partner genes, which remain to be identified.
Reciprocal interference between the sequence-specific core and nonspecific C-terminal DNA binding domains of p53: implications for regulation

The tumor suppressor p53 has two DNA binding domains: a central sequence-specific domain and a C-terminal sequence-independent domain. Here, we show that binding of large but not small DNAs by the C terminus of p53 negatively regulates sequence-specific DNA binding by the central domain. Four previously described mechanisms for activation of specific DNA binding operate by blocking negative regulation. Deletion of the C terminus of p53 activates specific DNA binding only in the presence of large DNA. Three activator molecules (a small nucleic acid, a monoclonal antibody against the p53 C terminus, and a C-terminal peptide of p53) stimulate sequence-specific DNA binding only in the presence of both large DNA and p53 with an intact C terminus. Our findings argue that interactions of the C terminus of p53 with genomic DNA in vivo would prevent p53 binding to specific promoters and that cellular mechanisms to block C-terminal DNA binding would be required.
Genetic disruption of protein kinase C (cid:1) reduces endotoxin-induced lung injury

Genetic disruption of protein kinase C (cid:1) reduces endotoxin-induced lung injury. Am J Physiol Lung Cell Mol Physiol 303: L880–L888, 2012. 2012; doi:10.1152/ajplung.00169. 2012. —The pathogenesis of acute lung injury and acute respiratory distress syndrome is characterized by sequestration of leukocytes in lung tissue, disruption of capillary integrity, and pulmonary edema. PKC (cid:1) plays a critical role in RhoA-mediated endothelial barrier function and inﬂammatory responses. We used mice with genetic deletion of PKC (cid:1) (PKC (cid:1) (cid:2) / (cid:2) ) to assess the role of PKC (cid:1) in susceptibility to LPS-induced lung injury and pulmonary edema. Under baseline conditions or in settings of increased capillary hydrostatic pressures, no differences were noted in the ﬁltration coefﬁcients ( k f ) or wet-to-dry weight ratios between PKC (cid:1) (cid:3) / (cid:3) and PKC (cid:1) (cid:2) / (cid:2) mice. However, at 24 h after exposure to LPS, the k f values were signiﬁcantly higher in lungs isolated from PKC (cid:1) (cid:3) / (cid:3) than PKC (cid:1) (cid:2) / (cid:2) mice. In addition, bronchoalveolar lavage ﬂuid obtained from LPS-exposed PKC (cid:1) (cid:3) / (cid:3) mice displayed increased protein and cell content compared with LPS-exposed PKC (cid:1) (cid:2) / (cid:2) mice, but similar changes in inﬂammatory cytokines were measured. His-tology indicated elevated LPS-induced cellularity and inﬂammation within PKC (cid:1) (cid:3) / (cid:3) mouse lung parenchyma relative to PKC (cid:1) (cid:2) / (cid:2) mouse lungs. Transient overexpression of catalytically inactive PKC (cid:1) cDNA in the endothelium signiﬁcantly attenuated LPS-induced endothelial barrier dysfunction in vitro and increased k f lung values in PKC (cid:1) (cid:3) / (cid:3) mice. However, transient overexpression of wild-type PKC (cid:1) cDNA in PKC (cid:1) (cid:2) / (cid:2) mouse lung vasculature did not alter the protective effects of PKC (cid:1) deﬁciency against LPS-induced acute lung injury. We conclude that PKC (cid:1) plays a role in the pathological progression of endotoxin-induced lung injury, likely mediated through modulation of inﬂammatory signaling and pulmonary vascular barrier function.
Ligand-Induced Repression of the Glucocorticoid Receptor Gene Is Mediated by an NCoR1 Repression Complex Formed by Long-Range Chromatin Interactions with Intragenic Glucocorticoid Response Elements

ABSTRACT Glucocorticoids are among the most potent and effective agents for treating inflammatory diseases and hematological cancers. However, subpopulations of patients are often resistant to steroid therapy, and determining the molecular mechanisms that contribute to glucocorticoid resistance is thus critical to addressing this clinical problem affecting patients with chronic inflammatory disorders. Since the cellular level of the glucocorticoid receptor (GR) is a critical determinant of glucocorticoid sensitivity and resistance, we investigated the molecular mechanisms mediating repression of glucocorticoid receptor gene expression. We show here that glucocorticoid-induced repression of GR gene expression is mediated by inhibition of transcription initiation. This process is orchestrated by the recruitment of agonist-bound GR to exon 6, followed by the assembly of a GR-NCoR1-histone deacetylase 3-containing repression complex at the transcriptional start site of the GR gene. A functional negative glucocorticoid response element (nGRE) in exon 6 of the GR gene and a long-range interaction occurring between this intragenic response element and the transcription start site appear to be instrumental in this repression. This autoregulatory mechanism of repression implies that the GR concentration can coordinate repression with excess ligand, regardless of the combinatorial associations of tissue-specific transcription factors. Consequently, the chronic nature of inflammatory conditions involving long-term glucocorticoid administration may lead to constitutive repression of GR gene transcription and thus to glucocorticoid resistance.
Effects of ectostriatal lesions on natural concept, pseudoconcept, and artificial pattern discrimination in pigeons

Abstract Pigeons were trained on four different visual discrimination tasks: (1) concept of natural stimuli (food vs. non-food object discrimination); (2) arbitrary classification of natural stimuli (pseudoconcept); (3) concept of artificial stimuli (triangles generated by computer graphics); and (4) discrimination of one pair of artificial stimuli. Then, lesions of the ectostriatum were carried out. The ectostriatal lesions impaired the arbitrary classification of natural stimuli and the concept of artificial pattern but did not impair the natural concept or the simple discrimination of fixed two stimuli. Lesions in the neostriatum did not cause deficits in any discrimination task. The birds had to learn individual stimuli for the arbitrary classification of stimuli and the stimulus generalization test after the artificial pattern concept discrimination indicated that the pigeons formed a concept more complicated than “triangle” in human language. These results suggest that the ectostriatum plays a role in task discrimination that requires much visual processing to classify stimuli.
SFN gain in broadcast networks

For broadcast networks, the Single-Frequency Network (SFN) mode is an alternative to the well-known Multi-Frequency Network (MFN) mode, where instead of transmitters operating at different frequencies, all base stations use the same frequency. Besides an expected improvement of the quality of service due to the more homogeneous distribution of received signal strength, some areas will also show a degraded quality caused by the SFN echoes. In this paper, the SFN gain is defined as a parameter describing potential gain or interference. An unambiguous methodology to obtain the actual SFN gain is presented and the variation of the gain is investigated for a DVB-H network as a function of the signal strength difference received from different transmitters. This SFN gain can be used for coverage planning of future broadcast networks.
Systemic Sclerosis Fibroblasts Show Specific Alterations of Interferon-γ and Tumor Necrosis Factor-α-induced Modulation of Interleukin 6 and Chemokine Ligand 2

Objective. We evaluated the effect of interferon-γ (IFN-γ) and/or tumor necrosis factor-α (TNF-α) on the secretion of prototype proinflammatory cytokine interleukin 6 (IL-6), compared to T-helper 1 [Th1; chemokine (C-X-C motif) ligand 10 (CXCL10)] or Th2 [chemokine (C-C motif) ligand 2 (CCL2)] chemokines, in primary cultured fibroblasts from patients with systemic sclerosis (SSc) at an early stage of the disease. Methods. Fibroblast cultures from 5 SSc patients (disease duration < 2 yrs) and 5 healthy controls were evaluated for the production of IL-6, CXCL10, and CCL2 at the basal level and after stimulation with IFN-γ and/or TNF-α. Results. SSc fibroblasts basally produced higher levels of IL-6 than controls, while no difference was observed about CCL2 and CXCL10. TNF-α was able to dose-dependently induce IL-6 and CCL2 secretion in SSc, but not in control fibroblasts. By stimulation with increasing doses of IFN-γ, SSc fibroblasts were induced to secrete CCL2 and CXCL10, while no effect was observed on IL-6. The combination of IFN-γ and TNF-α induced a strong secretion of IL-6 and CCL2 in SSc fibroblasts but not in controls. In contrast, the synergistic effect of IFN-γ and TNF-α on CXCL10 secretion was similar in SSc fibroblasts and in controls. Conclusion. SSc fibroblasts participate in the self-perpetuation of inflammation by releasing IL-6, CXCL10, and CCL2 under the influence of IFN-γ and/or TNF-α. SSc fibroblasts are more active than controls in the secretion of IL-6 at baseline, and in the production of IL-6 and CCL2 under the combined IFN-γ/TNF-α stimulation.
Case Study of Factors Influencing Jobs Satisfaction in Two Malaysian Universities

This work identifies the factors that measure job satisfaction of fac­ulty members at two selected and major universities in Malaysia, using ten major factors corresponding to job satisfac­tion using the Herzberg Two-factor Theory to determine how these selected factors are related to job satisfaction of Malaysian faculty members. The conclusions drawn from this study are that the major sources of job satisfaction for Malaysian faculty members are shown to be policy, administration, and salary. The relevant sources of dissatisfaction are personal achievement, personal growth, interpersonal relations, recognition, responsibili­ty, supervision, the work itself, and the overall working conditions. This study has a number of practical implications for institutional administrators, because if the educational institution has no instrument designed to measure faculty perceptions of their jobs and work, these administrators could elect to use the same instrument that investigates the areas of job satisfaction to gain similar results.
Phytochemical screening and effects of methanol extract of Carica papaya stem bark in alloxan induced diabetic rats

The phytochemical screening and hypoglycemic effect of Carica papaya stem bark in alloxan-induced diabetic albino rats was investigated. Phytochemical analysis of the methanolic extract of Carica papaya revealed the presence of steroids, phenolics, glycosides, alkaloids, saponins, flavonoids and tannins. The hypoglycemic activity of the same extract of Carica papaya stem bark was compared with that of a known antidiabetic standard drug-glibenclamide in alloxan induced diabetic rat models. There was a significant (p<0.05) reduction in blood glucose concentration (mg/dl) by the methanolic extract of Carica papaya stem bark (500mg/kg bw) and glibenclamide (0.6mg/kg bw) from 388.21 ± 17.40 to 103.25 ± 6.79 and 365.00 ± 15.98 to 95.50 ± 3.96 respectively. The blood glucose of the induced diabetic but non treated rats increased from 307.50 ± 22.35 to 509.45 ± 50.57 while for non-induced rats, no significant changes were observed. The extract and the standard drug also prevented further body weight loss in treated diabetic rats compared to the untreated. The purpose of this study is to ascertain scientifically, the claim that the plant part has antidiabetic potentials. The results obtained from this study indicate that the methanolic extract of Carica papaya contains bioactive substances with hypoglycemic potency. Thus, providing scientific link for the plant part to be processed for oral hypoglycemic remedy.
Scalable RFM-enriched Representation Learning for Churn Prediction

Most of the recent studies on churn prediction in telco utilize social networks built on top of the call (and/or SMS) graphs to derive informative features. However, extracting features from large graphs, especially structural features, is an intricate process both from a methodological and computational perspective. Due to the former, feature extraction in the current literature has mainly been addressed in an ad-hoc and hand-crafted manner. Due to the latter, the full potential of the structural information is unexploited. In this work, we incorporate both interaction and structural information by devising two different ways of enriching original graphs with interaction information, delineated by the well-known RFM model. We circumvent the process of extensive manual feature engineering by enriching the networks and improving the scalability of the renowned node2vec approach to learn node representations. The obtained results demonstrate that our enriched network outperforms baseline RFM-based methods.
Epithelial and Mesenchymal Subpopulations Within Normal Basal Breast Cell Lines Exhibit Distinct Stem Cell/Progenitor Properties

It has been proposed that epithelial–mesenchymal transition (EMT) in mammary epithelial cells and breast cancer cells generates stem cell features, and that the presence of EMT characteristics in claudin‐low breast tumors reveals their origin in basal stem cells. It remains to be determined, however, whether EMT is an inherent property of normal basal stem cells, and if the presence of a mesenchymal‐like phenotype is required for the maintenance of all their stem cell properties. We used nontumorigenic basal cell lines as models of normal stem cells/progenitors and demonstrate that these cell lines contain an epithelial subpopulation (“EpCAM+,” epithelial cell adhesion molecule positive [EpCAMpos]/CD49fhigh) that spontaneously generates mesenchymal‐like cells (“Fibros,” EpCAMneg/CD49fmed/low) through EMT. Importantly, stem cell/progenitor properties such as regenerative potential, high aldehyde dehydrogenase 1 activity, and formation of three‐dimensional acini‐like structures predominantly reside within EpCAM+ cells, while Fibros exhibit invasive behavior and mammosphere‐forming ability. A gene expression profiling meta‐analysis established that EpCAM+ cells show a luminal progenitor‐like expression pattern, while Fibros most closely resemble stromal fibroblasts but not stem cells. Moreover, Fibros exhibit partial myoepithelial traits and strong similarities with claudin‐low breast cancer cells. Finally, we demonstrate that Slug and Zeb1 EMT‐inducers control the progenitor and mesenchymal‐like phenotype in EpCAM+ cells and Fibros, respectively, by inhibiting luminal differentiation. In conclusion, nontumorigenic basal cell lines have intrinsic capacity for EMT, but a mesenchymal‐like phenotype does not correlate with the acquisition of global stem cell/progenitor features. Based on our findings, we propose that EMT in normal basal cells and claudin‐low breast cancers reflects aberrant/incomplete myoepithelial differentiation. STEM CELLS 2012; 30:292–303.
Evolution of Mammalian Chitinase(-Like) Members of Family 18 Glycosyl Hydrolases

Family 18 of glycosyl hydrolases encompasses chitinases and so-called chi-lectins lacking enzymatic activity due to amino acid substitutions in their active site. Both types of proteins widely occur in mammals although these organisms lack endogenous chitin. Their physiological function(s) as well as evolutionary relationships are still largely enigmatic. An overview of all family members is presented and their relationships are described. Molecular phylogenetic analyses suggest that both active chitinases (chitotriosidase and AMCase) result from an early gene duplication event. Further duplication events, followed by mutations leading to loss of chitinase activity, allowed evolution of the chi-lectins. The homologous genes encoding chitinase(-like) proteins are clustered in two distinct loci that display a high degree of synteny among mammals. Despite the shared chromosomal location and high homology, individual genes have evolved independently. Orthologs are more closely related than paralogues, and calculated substitution rate ratios indicate that protein-coding sequences underwent purifying selection. Substantial gene specialization has occurred in time, allowing for tissue-specific expression of pH optimized chitinases and chi-lectins. Finally, several family 18 chitinase-like proteins are present only in certain lineages of mammals, exemplifying recent evolutionary events in the chitinase protein family.
Orphan receptor COUP‐TF I antagonizes retinoic acid‐induced neuronal differentiation

Chicken ovalbumin upstream promoter‐transcription factors (COUP‐TF) are expressed in the developing nervous system and interact with nuclear hormone receptors to regulate expression of different genes. The role of COUP‐TF orphan receptors in neurogenesis is virtually unknown. To study the possible function of COUP‐TF I during neuronal differentiation, we generated COUP‐TF I overexpressing teratocarcinoma PCC7 cell lines and analyzed retinoic acid (RA)‐induced neuronal differentiation of these cells. COUP‐TF I overexpression results in the blockade of morphological differentiation after induction to differentiate. COUP‐TF I represses expression of micro‐tubule‐associated protein 2 (MAP2) gene and delays induction of growth‐associated protein 43 (GAP43) gene expression. In contrast, expression of the neurofilament light subunit (NF‐L) gene is not affected by COUP‐TF I overexpression during neuronal differentiation. Also, cells overexpressing COUP‐TF I do not stop proliferating after RA and dBcAMP treatment and possess suppressed transcriptional activation from different RA response elements. These results suggest that COUP‐TF I plays an important role in regulating RA‐induced neuronal differentiation. © 1995 Wiley‐Liss, Inc.
ON THE LOW HERITABILITY OF LIFE‐HISTORY TRAITS

Life‐history traits such as longevity and fecundity often show low heritability. This is usually interpreted in terms of Fisher's fundamental theorem to mean that populations are near evolutionary equilibrium and genetic variance in total fitness is low. We develop the causal relationship between metric traits and life‐history traits to show that a life‐history trait is expected to have a low heritability whether or not the population is at equilibrium. This is because it is subject to all the environmental variation in the metric traits that affect it plus additional environmental variation. There is no simple prediction regarding levels of additive genetic variance in life‐history traits, which may be high at equilibrium. Several other patterns in the inheritance of life‐history traits are readily predicted from the causal model. These include the strength of genetic correlations between life‐history traits, levels of nonadditive genetic variance, and the inevitability of genotype‐environment interaction.
Disease Activity Score on 28 Joints and Polypharmacy Are Independent Predictors for Health-Related Quality of Life Evaluated by INCAVISA in Patients With Rheumatoid Arthritis

ObjectiveThe aim of this study was to investigate the main factors associated to a diminished health-related quality of life (HRQoL) evaluated by INCAVISA (Health-Related Quality of Life Inventory for Latin American Patients) in patients with rheumatoid arthritis (RA). MethodsFemale, 18 years or older, RA (American College of Rheumatology 1987 criteria and American College of Rheumatology/European League against Rheumatism 2010 criteria) patients who attended the outpatient rheumatology department of the Hospital Civil “Dr. Juan I. Menchaca,” Guadalajara, Mexico, matched with healthy controls were included. Patients with any known comorbidities or treatment with antidepressive drugs were excluded. Trained physicians performed the RA clinical evaluation and INCAVISA. All data were analyzed using SPSS 21.0 software (SPSS Inc, Chicago, IL); P < 0.05 was considered statistically significant. ResultsPatients with polypharmacy (≥3 drugs) had a lower HRQoL by INCAVISA. The number of drugs, total comorbidities, and DAS-28 (Disease Activity Score on 28 Joints) were negatively correlated with total INCAVISA. In multivariate analysis, DAS-28 and polypharmacy were independent predictors for a negative perception of HRQoL evaluated by INCAVISA in RA patients. ConclusionsDisease activity and disability secondary to RA have a negative impact in the HRQoL. Other factors such as the number of drugs prescribed to these patients have been shown to be important for the negative perception of their HRQoL evaluated by INCAVISA.
Temporal resolution of two‐tracked NF‐κB activation by Legionella pneumophila

The intracellular pathogen Legionella pneumophila activates the transcription factor NF‐κB in macrophages and human epithelial cells, contributing to cytokine production and anti‐apoptosis. The former is important for the innate immune response to infection, the latter for intracellular replication by securing host cell survival. Here, we demonstrate biphasic activation of NF‐κB by L. pneumophila in human epithelial cells, using a p65‐GFP expressing variant of A549 cells. Early in infection, a strong but transient nuclear translocation of p65 was observed. Only flagellin‐deficient (ΔfliA and ΔflaA) mutants could not induce this first, TLR5 and MyD88‐dependent activation. The second p65 translocation event, however, is a long‐term activation, independent of flagellin, TLR5 and MyD88, and marked by permanent nuclear localization of p65‐GFP without oscillation for 30 h. Persistent p65 translocation also involved degradation of IκBα and upregulation of anti‐apoptotic genes. L. pneumophila mutants lacking a functional Dot/Icm secretion system (ΔdotA; ΔicmB/dotO), Dot/Icm effectors (ΔsdbA; ΔlubX) and two bacterial effector mutants (ΔenhC; ΔptsP) could not induce persistent p65 translocation. Strikingly, all these mutants were deficient in intracellular replication in A549 cells. Our data underline the strong connection between NF‐κB activation and intracellular replication and hints at an active interference of NF‐κB signalling by L. pneumophila.