Miracle-dz/UniFAR-FTUs huggingface dataset:
Oncogenes and Tumor Suppressors p 53 Maintains Baseline Expression of Multiple Tumor Suppressor Genes

TP53 is the most commonly mutated tumor suppressor gene and its mutation drives tumorigenesis. Using ChIP-seq for p53 in the absence of acute cell stress, we found that wild-type but not mutant p53 binds and activates numerous tumor suppressor genes, including PTEN, STK11(LKB1), miR-34a, KDM6A(UTX), FOXO1, PHLDA3, and TNFRSF10B through consensus binding sites in enhancers and promoters. Depletion of p53 reduced expression of these target genes, and analysis across 18 tumor types showed that mutation of TP53 associated with reduced expression of many of these genes. Regarding PTEN, p53 activated expression of a luciferase reporter gene containing the p53-consensus site in the PTEN enhancer, and homozygous deletion of this region in cells decreased PTEN expression and increased growth and transformation. These findings show that p53 maintains expression of a team of tumor suppressor genes that may together with the stress-induced targets mediate the ability of p53 to suppress cancer development. p53 mutations selected during tumor initiation and progression, thus, inactivate multiple tumor suppressor genes in parallel, which could account for the high frequency of p53 mutations in cancer. Implications: In this study, we investigate the activities of p53 under normal low-stress conditions and discover that p53 is capable of maintaining the expression of a group of important tumor suppressor genes at baseline, many of which are haploinsufficient, which could contribute to p53-mediated tumor suppression. Mol Cancer Res; 1–12. 2017 AACR.
Human mesenchymal stromal cell-derived extracellular vesicles alleviate renal ischemic reperfusion injury and enhance angiogenesis in rats.

BACKGROUND Mesenchymal stromal cells (MSCs) derived extracellular vesicles (EVs) were regarded as a potent medium for kidney injury repair and angiogenesis were regarded as an important step in tissue regeneration. However, the pro-angiogenesis effect of MSC-EVs in ischemia-reperfusion induced kidney injury and its potential mechanisms have yet to be determined. METHODS EVs were isolated from the medium of human umbilical cord-derived MSCs (huMSCs) were injected in rats intravenously after unilateral kidney ischemia. Animals were sacrificed at 24 h and 2 weeks after injury. The renal functions and histology staining were examined to assess the therapeutic effect of the EVs. Moreover, we investigated the pro-angiogenesis effects of EVs in injured kidneys and tested the angiogenesis-related factors to further illuminate the probable mechanisms. RESULTS It was observed that EVs could reduce cell apoptosis and enhances proliferation 24 h after kidney injury, meanwhile renal function was improved and the histological lesion was mitigated. Moreover, renal VEGF was up-regulated by EVs and HIF-1α was down-regulated. Further, the increase of capillary vessel density and reduce of renal fibrosis was observed after 2 weeks. In vitro, EVs could deliver human VEGF directly to renal tubular epithelial cells (TECs) and increase VEGF levels. Most important, all the beneficial effects of EVs were abrogated by RNase treated except for the delivery of human VEGF. CONCLUSIONS Human MSC-EVs could protect against ischemic/reperfusion injury induced kidney injury through pro-angiogenesis effects in HIF-1α independent manner, and both the delivery of pro-angiogenesis related VEGF and RNAs were involved in this process.
Differential Role for c-Rel and C/EBPβ/δ in TLR-Mediated Induction of Proinflammatory Cytokines1

TLR stimulation triggers a signaling pathway via MyD88 and IL-1R-associated kinase 4 that is essential for proinflammatory cytokine induction. Although NF-κB has been shown to be one of the key transcriptional regulators of these cytokines, evidence suggests that other factors may also be important. In this study, we showed that MyD88-deficient macrophages have defective c-Rel activation, which has been linked to IL-12p40 induction, but not IL-6 or TNF-α. We also investigated other transcription factors and showed that C/EBPβ and C/EBPδ expression was limited in MyD88- or IL-1R-associated kinase 4-deficient macrophages treated with LPS. Importantly, the absence of both C/EBPβ and C/EBPδ resulted in the impaired induction of proinflammatory cytokines stimulated by several TLR ligands. Our results identify c-Rel and C/EBPβ/δ as important transcription factors in a MyD88-dependent pathway that regulate the induction of proinflammatory cytokines.
Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans.

In vivo glucose uptake can occur via two mechanisms, namely, insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). Although the principal tissue sites for IMGU are skeletal muscle, the tissue sites for NIMGU at a given serum glucose concentration are not known. To examine this issue, rates of whole body glucose uptake (Rd) were measured at basal and during glucose clamp studies performed at euglycemia (approximately 90 mg/dl) and hyperglycemia (approximately 220 mg/dl) in six lean healthy men. Studies were performed during hyperinsulinemia (approximately 70 microU/ml) and during somatostatin-induced insulinopenia to measure IMGU and NIMGU, respectively. During each study, leg glucose balance (arteriovenous catheter technique) was also measured. With this approach, rates of whole body skeletal muscle IMGU and NIMGU can be estimated, and the difference between overall Rd and skeletal muscle glucose uptake represents non-skeletal muscle Rd. The results indicate that approximately 20% of basal Rd is into skeletal muscle. During insulinopenia approximately 86% of body NIMGU occurs in non-skeletal muscle tissues at euglycemia. When hyperglycemia was created, whole body NIMGU increased from 128 +/- 6 to 213 +/- 18 mg/min (P less than 0.01); NIMGU into non-skeletal muscle tissues was 134 +/- 11 and 111 +/- 6 mg/min at hyperglycemia and euglycemia, respectively, P = NS. Therefore, virtually all the hyperglycemia induced increment in NIMGU occurred in skeletal muscle. During hyperinsulinemia, IMGU in skeletal muscle represented 75 and 95% of body Rd, at euglycemia and hyperglycemia, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
Effect of Sodium Depletion on the Release of [3H]Norepinephrine from Central and Peripheral Tissue of Wistar‐Kyoto and Spontaneously Hypertensive Rats

To study the relationship between sodium intake, the sympathetic nervous system, and hypertension, we studied the effects of a 7–9 day dietary restriction of sodium in three different ages of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Field-stimulated [3H]norepinephrine ([3H]NE) release was measured in portal vein, anterior hypothalamus. and the A2 region of the nucleus tractus solitarius (NTS) of 5− to 6-, 10− to 11-, and 28− to 30− week-old SHR and age-matched WKY. A low-sodium diet (0.05% Na control 0.5%; Na+) significantly lowered stimulated [3H]NE. release from portal vein and anterior hypothalamus in SHR and WKY at all three ages. However, release from the A2 region was not altered by sodium restriction. The results of the present study suggest that lowered dietary sodium can selectively alter norepinephrine release in both the peripheral and central sympathetic nervous system of SHR and WKY. The results also suggest that the SHR at 5–6 weeks are more sensitive to altered dietary sodium than are age-matched WKY.
Therapy Strategies, Personality Orientation and Recovery from Alcoholism

The Conceptual Level (CL) matching model which previously predicted the immediate response of alcoholics to group psychotherapy was tested in a follow-up study of drinking behaviour. Seventy percent of patients matched to their therapist in terms of CL were found to have stopped drinking a year after treatment. By comparison, only 50 percent of the mismatched patients had stopped. Furthermore, after-care matching was related to recovery: matched patients (high CL with out-of-town care and low CL with in-town care) showed a 71 percent recovery rate, while mismatched patients showed a 49 percent rate. The overall recovery rate was 61 percent for the 94 alcoholics studied.
Le tissu adipeux : approfondissement des connaissances fondamentales du tissu et de son compartiment vasculaire stromal, intérêt clinique pour la chirurgie plastique

L’objectif de cette these etait d’ameliorer les connaissances fondamentales sur le tissu adipeux, organe qui est au cœur de la pratique des chirurgiens plasticiens. En effet, ce tissu peut etre transplante de facon autologue afin de combler une perte de substance (role volumateur des adipocytes) mais egalement servir a des fins de regeneration tissulaire en lien avec les cellules de la fraction vasculaire stromale (FVS) et tout particulierement des cellules stromales mesenchymateuses (CSM). Ces cellules s’obtiennent apres lipoaspiration du tissu par une digestion enzymatique de la graisse obtenue. Il s’avere que les connaissances disponibles sur ces CSM sont essentiellement issues d’etudes in vitro apres une phase de culture cellulaire plus ou moins longue et ainsi les proprietes in vivo sont mal connues. Ce travail a donc consiste a caracteriser l’heterogeneite du compartiment stromal natif du tissu adipeux obtenu apres digestion enzymatique. Nous avons isole deux populations stromales natives distinctes : les ASC (CD34+), en grande majorite, et des cellules pericytaires (CD146+). Ces 2 types cellulaires differaient dans leurs phenotypes, leurs potentiels de clonogenecite et leurs proprietes immunomodulatrices in vitro et in vivo. Nous avons ensuite compare la digestion enzymatique du tissu aux techniques de digestion mecanique utilisable au sein de nos blocs operatoires. Nous avons demontre que ces nouvelles techniques permettaient bien de produite les cellules de la FVS dont des CSM, cellules particulierement interessante pour des gestes de regeneration tissulaire. De plus, l’ensemble des techniques de laboratoire acquise au cours de ce travail nous ont permis d’investiguer le role des techniques de lipoaspiration utilise en chirurgie plastique sur le tissu adipeux. Nous avons demontre par cytometrie de flux et par immunofluorescence in situ qu’une partie de la trame microvasculaire etait conservee. L’ensemble de ces resultats viennent s’ajouter aux donnees cliniques demontrant que la lipoaspiration du tissu est un geste permettant d’etre plus conservateur pour le tissu et pourrait expliquer des taux de complications moindre apres chirurgie de contour de la silhouette.
Modeling the cognitive representation of basic three-dimensional spatial relations in visual short-term memory

For the prospective design of human-machine interfaces in an engineering design process, basic principles and parameters of human cognitive performance need to be known. This paper describes the results of a study that assesses parameters for the accuracy of the mental representation of basic three-dimensional spatial relations in visual short-term memory. In a laboratory experiment, 13 subjects reproduced from memory the position of a sphere relative to a second landmark. The stimuli were presented on a stereoscopic display. The mental representation of spatial relations is noisy and therefore is determined by probability density functions. The experimental results are compared with Monte Carlo simulations of stochastic models of the mental representation using hypothesized probability density functions that represent different noise models. The reported values for the parameters have important implications for the design of stereoscopic three-dimensional visualizations in human- computer interaction.
Impact of acute stress on human brain microstructure: An MR diffusion study of earthquake survivors

A characterization of the impact of natural disasters on the brain of survivors is critical for a better understanding of posttraumatic responses and may inform the development of more effective early interventions. Here we report alterations in white matter microstructure in survivors soon after Wenchuan earthquake in China in 2008. Within 25 days after the Wenchuan earthquake, 44 healthy survivors were recruited and scanned on a 3T MR imaging system. The survivors were divided into two groups according to their self‐rating anxiety scale (SAS) score, including the SAS(+) (SAS > 55 after correction) group and “SAS(−)” (SAS < 55 after correction) group. Thrity‐two healthy volunteers were also recruited as control group before earthquake. Individual maps of fractional anisotropy (FA) were calculated and voxel‐based analysis (VBA) was performed to allow the comparison between survivors and controls using ANCOVAs in SPM2. In addition, a correlation between SAS score and regional FA value was examined using Pearson's correlation analysis in SPSS 11.5. Compared with the healthy cohort, the whole group of 44 survivors showed significantly decreased FA values in the right prefrontal lobe, the parietal lobe, the basal ganglia, and the right parahippocampus. These effects did not appear to depend on self‐rating anxiety. For the first time we provide evidence that acute trauma altered cerebral microstructure within the limbic system; furthermore, these alterations are evident shortly after the traumatic event, highlighting the need for early evaluation and intervention for trauma survivors. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.
MATURATION OF POLIOVIRUS RNA WITH CAPSID PROTEIN CODED BY HETEROLOGOUS ENTEROVIRUSES.

guanidine requirement of dependent virus. This suggests that guanidine acts on virus-induced proteins by influencing their synthesis, configuration and/or function. The accompanying paper" shows that supporting virus can also cause maturation of dependent virus RNA within heterologous capsid protein. Summary. -Evidence is presented that the early enzymes induced in HeLa cells by infection with type 1 or type 2 poliovirus or Coxsackie B1 virus can support replication of the RNA of guanidine-dependent type 1 poliovirus which superinfects the same cells.
ROS kinase fusions are not common in Chinese patients with cholangiocarcinoma.

OBJECTIVE To investigate the expressions of different forms of ROS fusions in Chinese patients with cholangiocarcinoma (CCA). METHODS RT-PCR was employed to examine formalin-fixed and paraffin-embedded CCA samples from stage I-IV patients for detection of ROS fusions involving Fused in Glioblastoma (FIG), solute carrier protein (SLC34A2) and major histocompatibility complex class II invariant chain (CD74). Serpin peptidase inhibitor clade A member 1 (SERPINA1) was detected as the reference gene. RESULTS In all the 56 CCA samples, 80.4% (45/56) were positive for SERPINA1 expression as evaluable samples. Of these evaluable samples, none expressed the ROS fusions. CONCLUSION ROS fusions are not common in Chinese CCA patients.
Ordered mesoporous polymers and homologous carbon frameworks: amphiphilic surfactant templating and direct transformation.

Organic porous materials—a class of advanced materials— possess enormous potential for many high-tech applications, such as bioreactors, dielectrics, sensors, microelectrophoresis, thermal insulation, and catalysts. In general, they can be prepared by phase separation, and a hard templating approach, such as those employing colloidal particles. Phase separation can be derived from organic– organic phases, while the pore structures can be formed after etching, or by dissolving one block (A) from the assembled block copolymer (A–B). However, most of the resulting porous polymer structures are disordered with wide pore size distributions because of the contraction and swelling from changes in volume, as well as the structured defects formed during template removal. Large porosities have rarely been reported. Furthermore, the resistance of the pore structure to heat and solvents is rather low because the materials are formed by weak van der Waals forces and physical twists between polymer chains, which means that the framework is not connected by covalent bonds. Recently, a procedure for cross-linking lyotropic liquid crystals (LLC) in water was introduced to prepare periodic porous organic mesostructures. Unfortunately, polymerization only occurs between nearest neighboring head groups, and the mesostructured channels are fully occupied with solution. Therefore, it is not surprising that porosity has yet to be reported. Carbon materials, including nanotubes and fullerenes, have attracted considerable attention because of their remarkable properties. The traditional carbonization process for active carbon and related materials can only generate
Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times

Aim To determine clinical correlations to intraocular vascular endothelial growth factor A (VEGF-A) suppression times (VSTs) on the treatment of neovascular age-related macular degeneration (nAMD) with ranibizumab (Lucentis) or aflibercept (Eylea). Methods Seven of 89 treatment-naïve nAMD eyes showed persistent choroidal neovascular membrane (CNV) activity throughout a spectral domain optical coherence tomography (SD-OCT)-driven pro re nata (PRN) regimen of intravitreal ranibizumab injections over 28±4 months. The treatment was switched to PRN aflibercept injections and patients were followed for another 15±2 months. A total of 160 aqueous humour specimens were collected before the intravitreal injections, and their VEGF-A concentrations were assayed by Luminex multiplex bead analysis (Luminex, Austin, Texas, USA). Intraocular VEGF-A concentrations were correlated to CNV activity shown by SD-OCT. Results The mean duration of suppression of VEGF-A concentrations in aqueous humour below the lower limit of quantification of our assay was 34±5 (26–69) days for ranibizumab and 67±14 (49–89) days for aflibercept (p<0.001). The percentual reduction of central retinal volume (CRV) 6 weeks after injection was higher for aflibercept compared with ranibizumab (p=0.009). The time point of clinical re-activity occurred about 50% earlier than the respective VST for each ranibizumab and aflibercept. Conclusions The VST under aflibercept treatment exceeded that under ranibizumab treatment by a factor of 2. This difference correlated with differential clinical CRV reduction 6 weeks after the respective injection. For both medications, clinical activity was found at a time point as early as 50% of the individual VST. Trial registration number NCT01213667, post-results
Utility of flow cytometry immunophenotyping for the diagnosis and classification of lymphoma in community hospital clinical needle aspiration/biopsies.

CONTEXT Flow cytometry immunophenotyping (FC) of needle aspiration/biopsy (NAB) samples has been reported to be useful for the diagnosis and classification of lymphoma in university and cancer center-based settings. Nevertheless, there is no agreement on the utility of these methods. OBJECTIVE To further define the utility of adjunctive FC of clinical NAB for the diagnosis and classification of lymphoma, and to determine if this approach is practicable in a routine clinical practice setting. SETTING A community-based hospital. METHODS Clinical NABs were submitted for adjunctive FC between June 1996 and September 1999 if initial smears were suspicious for lymphoma. Smears and cell block or needle core tissues were routinely processed and paraffin-section immunostains were performed if indicated. The final diagnosis was determined by correlating clinical and pathologic data, and the revised European-American classification criteria were used to subtype lymphomas. RESULTS Needle aspiration/biopsies from 60 different patients were submitted for FC. Final diagnoses were lymphoma (n = 38), other neoplasm (n = 15), benign (n = 6), or insufficient (n = 1). For 38 lymphomas (20 primary, 18 recurrent), patients ranged in age from 32 to 86 years (mean, 62 years); samples were obtained from the retroperitoneum (n = 11), lymph node (n = 9), abdomen (n = 8), mediastinum (n = 6), or other site (n = 4); and lymphoma subtypes were indolent B-cell (n = 20; 2 small lymphocytic, 14 follicle center, 4 not subtyped), aggressive B-cell (n = 14; 3 mantle cell, 10 large cell, 1 not subtyped), B-cell not further specified (n = 2), or Hodgkin disease (n = 2). For the diagnosis of these lymphomas, FC was necessary in 20 cases, useful in 14 cases, not useful in 2 cases, and misleading in 2 cases. Thirty-two of 36 lymphoma patients with follow-up data received antitumor therapy based on the results of NAB plus FC. CONCLUSIONS Adjunctive FC of NABs is potentially practicable in a community hospital, is necessary or useful for the diagnosis and subtyping of most B-cell lymphomas, and can help direct lymphoma therapy. Repeated NAB or surgical biopsy is necessary for diagnosis or treatment in some cases.
Passive smoking in childhood. Respiratory conditions and pulmonary function in Tecumseh, Michigan.

The relationship of passive smoking to respiratory conditions and pulmonary function was assessed using a cross-sectional design in the defined population of Tecumseh, Michigan. The study population was made up of 3,482 children who were 0 to 19 yr of age at the 1962-1965 examination and for whom questionnaire information was available for both parents. Nearly 62% of children in this age group were exposed at the time of examination to at least 1 parent who smoked. Passive exposure to cigarette smoke was associated with an elevated prevalence of phlegm, wheeze, asthma, and chest colds among males and wheeze, bronchitis, and chest colds among females. Using logistic regression, offspring were shown to be 1.5 to 2.0 times more likely to have a respiratory condition if both their parents currently smoked than if both parents never smoked. FEV1, and FVC among males and Vmax50 among females were significantly lower by 5% in nonsmokers 10 to 19 yr of age whose parents were current smokers compared with similar offspring of never smoking parents. Respiratory conditions were generally more frequent and the level of lung function was generally lower for males from households where only mothers smoked compared with males from households where only fathers smoked, although sample size was limited. In females similar relationships were less consistent. Differences tended to be larger and more often significant for males than for females when respiratory symptoms and illnesses were examined. (ABSTRACT TRUNCATED AT 250 WORDS)