Miracle-dz/UniFAR-FTUs huggingface dataset:
FOXO1 and TCF7L2 genes involved in metastasis and poor prognosis in clear cell renal cell carcinoma

The goal of this study was to identify genes related to the metastasis of clear cell renal cell carcinoma (CRCC). We analyzed copy number alterations in renal tissue specimens of patients with CRCC patients with or without metastasis by using high‐resolution single‐nucleotide polymorphism (SNP) arrays and then integrated these data with gene expression profiling data obtained using oligonucleotide microarrays. The expression levels of target genes were determined by quantitative real‐time RT‐PCR (qRT‐PCR) with an independent tumor set. An analysis of specimens from 23 CRCC cases with SNP arrays revealed that hemizygous deletions at 10q and 13q were found only in cases of metastatic disease. We found the homozygous deletion of TCF7L2 at 10q25.2 in an aggressive case that had hemizygous deletions at 10q. In addition, a qRT‐PCR analysis of TCF7L2 mRNA levels in tumor samples revealed significantly lower levels in patients with metastasis when compared with those without metastasis. FOXO1 was identified as a down‐regulated gene in the minimal overlapping region of the 13q hemizygous deletion in CRCC. Decreased FOXO1 expression was significantly correlated with metastasis and poor survival outcome. Knockdown of FOXO1 inhibited apoptosis after doxorubicin treatment in CRCC cells and reduced the expression of downstream genes involved in cell proliferation (CDKN1B) and survival (BCL2L11). Lower levels of FOXO1 expression were associated with decreased expression of CDKN1B and BCL2L11 in CRCC specimens. We conclude that FOXO1 and TCF7L2 are involved in metastasis and that molecules in these signaling pathways may be targets for diagnostic procedures and therapies for CRCC. © 2010 Wiley‐Liss, Inc.
Chinese tea consumption is associated with longer telomere length in elderly Chinese men

Environmental and lifestyle factors that affect oxidative stress and inflammation may influence telomere length (TL). There are limited data to relate the effect of dietary components on TL. The present study examined the association between food groups and TL in a sample of elderly Chinese. In a sample of 2006 Chinese (976 men and 1030 women) aged 65 years and over, TL was measured by quantitative real-time PCR and daily intake of food groups was assessed by a validated FFQ. Linear regression and analysis of covariance were used to examine the association between food group intake and TL, with adjustment for demographic and lifestyle factors. In men, only Chinese tea consumption was significantly associated with TL after adjustment for demographics and lifestyle factors (P = 0·002). Mean difference in TL for those in the highest quartile of Chinese tea consumption (>3 cups/d or >750 ml/d) as compared with those in the lowest quartile of Chinese tea consumption ( ≤ 0·28 cups/d or ≤ 70 ml/d) was 0·46 kb, corresponding to approximately a difference of 5 years of life. In women, intake of fats and oils was borderline and negatively associated with TL after adjustment for demographic and lifestyle factors (P = 0·037). In conclusion, Chinese tea consumption was positively associated with TL in elderly Chinese men.
Critical Conversations: How Independent School Alumni Describe the Schooling Experiences That Facilitated Their Understanding of Race and Ethnicity

The United States is becoming more racially diverse. In spite of this increasing diversity, many American schools still remain segregated. Far too many young people are receiving an education without learning the critical skills needed to live, work, and lead in a complex, diverse, and stratified society. Graduating students who know how to positively interact with people from different racial and ethnic backgrounds are essential to American democracy. This qualitative phenomenological study investigated how independent school alumni (ISA) described the schooling experiences that facilitated their understanding of race and ethnicity. Intergroup dialogue provided a theoretical lens through which to examine ISA schooling experiences that led to racial and ethnic understanding. This study employed four data gathering techniques: (a) demographic profile sheets, (b) semi-structured interviews, (c) field notes, and, (d) document collection. Data were analyzed using multiple rounds of coding to identify emerging themes. The findings reveal that school social environments facilitate racial and ethnic understanding; racial awareness occurs both inside and outside the classroom through formal instruction and extracurricular activities and programs; racialized activities and spaces lead to the development of personal connections with people from different backgrounds; privilege and power highlight a social divide that intersects race and socioeconomic class; and different levels of readiness to interact with diverse people is indicated in post-secondary settings. Implications for school teachers and leaders as well as for future research are addressed. Degree Type Dissertation Degree Name Doctor of Education (EdD) Department Executive Leadership First Supervisor Jeannine Dingus-Eason Second Supervisor Chris Henry Hinesley Subject Categories Education This dissertation is available at Fisher Digital Publications: http://fisherpub.sjfc. edu/education_etd/251 Critical Conversations: How Independent School Alumni Describe the Schooling Experiences That Facilitated Their Understanding of Race and Ethnicity
Sororin pre‐mRNA splicing is required for proper sister chromatid cohesion in human cells

Sister chromatid cohesion, which depends on cohesin, is essential for the faithful segregation of replicated chromosomes. Here, we report that splicing complex Prp19 is essential for cohesion in both G2 and mitosis, and consequently for the proper progression of the cell through mitosis. Inactivation of splicing factors SF3a120 and U2AF65 induces similar cohesion defects to Prp19 complex inactivation. Our data indicate that these splicing factors are all required for the accumulation of cohesion factor Sororin, by facilitating the proper splicing of its pre‐mRNA. Finally, we show that ectopic expression of Sororin corrects defective cohesion caused by Prp19 complex inactivation. We propose that the Prp19 complex and the splicing machinery contribute to the establishment of cohesion by promoting Sororin accumulation during S phase, and are, therefore, essential to the maintenance of genome stability.
Infection by Tubercular Mycobacteria Is Spread by Nonlytic Ejection from Their Amoeba Hosts

To generate efficient vaccines and cures for Mycobacterium tuberculosis, we need a far better understanding of its modes of infection, persistence, and spreading. Host cell entry and the establishment of a replication niche are well understood, but little is known about how tubercular mycobacteria exit host cells and disseminate the infection. Using the social amoeba Dictyostelium as a genetically tractable host for pathogenic mycobacteria, we discovered that M. tuberculosis and M. marinum, but not M. avium, are ejected from the cell through an actin-based structure, the ejectosome. This conserved nonlytic spreading mechanism requires a cytoskeleton regulator from the host and an intact mycobacterial ESX-1 secretion system. This insight offers new directions for research into the spreading of tubercular mycobacteria infections in mammalian cells.
Blood pressure reduction after gastric bypass surgery is explained by a decrease in cardiac output.

Blood pressure (BP) decreases in the first weeks after Roux-and-Y gastric bypass surgery. Yet the pathophysiology of the BP-lowering effects observed after gastric bypass surgery is incompletely understood. We evaluated BP, systemic hemodynamics, and baroreflex sensitivity in 15 obese women[mean age 42 ± 7 standard deviation (SD) yr, body mass index 45 ± 6 kg/m2] 2 wk before and 6 wk following Roux-and-Y gastric bypass surgery. Six weeks after gastric bypass surgery, mean body weight decreased by 13 ± 5 kg (10%, P < 0.001). Office BP decreased from 137 ± 10/86 ± 6 to 128 ± 12/81 ± 9 mmHg (P < 0.001, P < 0.01), while daytime ambulatory BP decreased from 128 ± 14/80 ± 9 to 114 ± 10/73 ± 6 mmHg (P = 0.01, P = 0.05), whereas nighttime BP decreased from 111 ± 13/66 ± 7 to 102 ± 9/62 ± 7 mmHg (P = 0.04, P < 0.01). The decrease in BP was associated with a 1.6 ± 1.2 l/min (20%, P < 0.01) decrease in cardiac output (CO), while systemic vascular resistance increased (153 ± 189 dyn·s·cm-5, 15%, P < 0.01). The maximal ascending slope in systolic blood pressure decreased (192 mmHg/s, 19%, P = 0.01), suggesting a reduction in left ventricular contractility. Baroreflex sensitivity increased from 9.0 [6.4-14.3] to 13.8 [8.5-19.0] ms/mmHg (median [interquartile range]; P < 0.01) and was inversely correlated with the reductions in heart rate (R = -0.64, P = 0.02) and CO (R = -0.61, P = 0.03). In contrast, changes in body weight were not correlated with changes in either BP or CO. The BP reduction following Roux-and-Y gastric bypass surgery is correlated with a decrease in CO independent of changes in body weight. The contribution of heart rate to the reduction in CO together with enhanced baroreflex sensitivity suggests a shift toward increased parasympathetic cardiovascular control. NEW & NOTEWORTHY The reason for the decrease in blood pressure (BP) in the first weeks after gastric bypass surgery remains to be elucidated. We show that the reduction in BP following surgery is caused by a decrease in cardiac output. In addition, the maximal ascending slope in systolic blood pressure decreased suggesting a reduction in left ventricular contractility and cardiac workload. These findings help to understand the physiological changes following gastric bypass surgery and are relevant in light of the increased risk of heart failure in these patients.
Mesenchymal Stromal Cells for Treatment of Acute Steroid‐Refractory Graft Versus Host Disease: Clinical Responses and Long‐Term Outcome

Acute graft‐versus‐host disease (aGvHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Steroid‐resistant aGvHD is associated with poor outcome, and no commonly accepted salvage therapy is available for its treatment. Here, we report 58 adult patients treated with mesenchymal stromal cells (MSCs) as salvage therapy for steroid‐refractory aGvHD. Third‐party MSCs expanded in platelet lysate‐containing medium were transfused at a median dose of 0.99 × 106 cells per kg b.wt. A median of two MSC infusions were administered to each patient. Median time between the onset of aGvHD and the first infusion of MSCs was 12 days (range, 6–62 days). Most patients (79%) had grade IV aGvHD. Five patients showed complete response, five showed very good partial response, 17 showed partial response, and 31 showed no response. The estimated probability of survival after 1 year was 19%, and median survival was 69 days. Overall survival was not significantly different from that of a historical cohort of patients receiving alternative salvage therapy and no MSC infusions. In conclusion, MSC treatment on top of conventional immunosuppression was associated with an overall response rate of 47% but improved outcome in terms of survival remains to be shown. Stem Cells 2016;34:357–366
Characterisation of Structures in Salivary Secretion Film Formation. An Experimental Study with Atomic Force Microscopy

The purpose of the present study was to characterise the structure dynamics of pure salivary secretions retained on controlled surfaces with different surface energies in the early stage of salivary film formation. Germanium prisms prepared to have either low surface energy or medium surface energy were incubated in fresh secretions of either human parotid saliva (HPS) or human submandibular/sublingual saliva (HSMSLS) for 15, 90, and 180 min. After controlled rinsing with distilled water, the surfaces were air dried and thereafter imaged with atomic force microscopy (AFM). The amount of adsorbed material and the size of the structures detected increased with increased saliva exposure time. The film thicknesses varied from 10 to 150 nm, and both HPS and HSMSLS films contained structures with diameters varying from 40 nm to 2 μm. Some of these were clustered into special formations. The HPS films exhibited a more granular morphology than the HSMSLS films. Furthermore, branched lines were detected on the low surface energy germanium prisms incubated in saliva. The results indicate that exposure time, surface energy, and type of salivary secretion all are factors affecting the adsorption characteristics of salivary films.
Usefulness of LDAEP to Predict Tolerability to SSRIs in Major Depressive Disorder: A Case Report

We report here a patient with major depressive disorder who experienced severe adverse effects after the administration of SSRIs (serotonin selective reuptake inhibitors) without improvement of his depressive symptoms. These adverse effects disappeared and his depressive symptoms improved after discontinuation of the SSRIs and the administration of tianeptine. The patient exhibited a low value for the loudness dependent of auditory evoked potentials (LDAEP) -0.14 at baseline, which means that his central serotonergic neurotransmission was already highly active. We assumed that it was this high serotonergic activity that rendered him unresponsive to SSRIs, and brought on him the adverse effects, and that the tianeptine was effective due to the lack of serotonin reuptake inhibitory action. Thus, we suggest that LDAEP can be used to predict an individual patient's tolerability and clinical response to SSRIs in major depression.
'I just love youth work!' Emotional labour, passion and resistance

This article is inspired by findings from a small-scale study in which grassroots street-based youth workers talked about their love and passion for their work and their affection for young people. Emotional engagement could be seen as intrinsic to youth work and necessary for building relationships with young people, but how might we think about workers’ emotions as youth work is increasingly governed by market principles? This article explores the relevance of emotional labour, the theory that workers’ emotional efforts are controlled and exploited by employers in the pursuit of profit. Such analyses have a renewed relevance as private sector organisations and practices enter youth work, but may not adequately account for the potentially positive political role of emotions. The article concludes by suggesting that passion might play a role in resisting the dehumanisation of youth work.
Cyclic AMP- and Cyclic GMP-dependent Protein Kinases Differ in Their Regulation of Cyclic AMP Response Element-dependent Gene Transcription*

The ability of cGMP-dependent protein kinases (cGKs) to activate cAMP response element (CRE)-dependent gene transcription was compared with that of cAMP-dependent protein kinases (cAKs). Although both the type Iβ cGMP-dependent protein kinase (cGKIβ) and the type II cAMP-dependent protein kinase (cAKII) phosphorylated the cytoplasmic substrate VASP (vasodilator- and A kinase-stimulatedphosphoprotein) to a similar extent, cyclic nucleotide regulation of CRE-dependent transcription was at least 10-fold higher in cAKII-transfected cells than in cGKIβ-transfected cells. Overexpression of each kinase in mammalian cells resulted in a cytoplasmic localization of the unactivated enzyme. As reported previously, the catalytic (C) subunit of cAKII translocated to the nucleus following activation by 8-bromo-cyclic AMP. However, cGKIβ did not translocate to the nucleus upon activation by 8-bromo-cyclic GMP. Replacement of an autophosphorylated serine (Ser79) of cGKIβ with an aspartic acid resulted in a mutant kinase with constitutive kinase activity in vitroand in vivo. The cGKIβS79D mutant localized to the cytoplasm and was only a weak activator of CRE-dependent gene transcription. However, an amino-terminal deletion mutant of cGKIβ was found in the nucleus as well as the cytoplasm and was a strong activator of CRE-dependent gene transcription. These data suggest that the inability of cGKs to translocate to the nucleus is responsible for the differential ability of cAKs and cGKs to activate CRE-dependent gene transcription and that nuclear redistribution of cGKs is not required for NO/cGMP regulation of gene transcription.
Association with Ets-1 Causes Ligand- and AF2-Independent Activation of Nuclear Receptors

ABSTRACT The vitamin D receptor (VDR) normally functions as a ligand-dependent transcriptional activator. Here we show that, in the presence of Ets-1, VDR stimulates the prolactin promoter in a ligand-independent manner, behaving as a constitutive activator. Mutations in the AF2 domain abolish vitamin D-dependent transactivation but do not affect constitutive activation by Ets-1. Therefore, in contrast with the actions of vitamin D, activation by Ets-1 is independent of the AF2 domain. Ets-1 also conferred a ligand-independent activation to the estrogen receptor and to peroxisome proliferator-activated receptor α. In addition, Ets-1 cooperated with the unliganded receptors to stimulate the activity of reporter constructs containing consensus response elements fused to the thymidine kinase promoter. There is a direct interaction of the receptors with Ets-1 which requires the DNA binding domains of both proteins. Interaction with Ets-1 induces a conformational change in VDR which can be detected by an increased resistance to proteolytic digestion. Furthermore, a retinoid X receptor-VDR heterodimer in which both receptors lack the core C-terminal AF2 domain can recruit coactivators in the presence, but not in the absence, of Ets-1. This suggests that Ets-1 induces a conformational change in the receptor which creates an active interaction surface with coactivators even in the AF2-defective mutants. These results demonstrate the existence of a novel mechanism, alternative to ligand binding, which can convert an unliganded receptor from an inactive state into a competent transcriptional activator.
University-Industry Research Partnerships and Intellectual Property

The tradeoff between providing incentives for the production of new ideas and information and ensuring that spillovers from that research flow to others is likely to lead to different methods of organizing research efforts in different spheres depending on the relative importance of “appropriability” versus the benefits of full and costless knowledge diffusion. In particular, as Paul David has often argued, the “open science” community has evolved a rather different approach to rewards for and spillovers from the production of information goods than that suggested by a conventional economic property rights analysis, one based on rapid publication and dissemination in order to achieve a prior claim as the inventor. Because this kind of system for securing rewards to investments in research is so different from that to which most industrial firms operate, it is not surprising that tensions arise in settings where the conventions of one world (private industry) come up against the conventions of another (public R&D and university science). The paper reviews the evidence that this is the case and then discusses the case of cumulative innovation, where the IP problem is particularly salient.
Scurvy: A new problem for patients with chronic GVHD involving mucous membranes; an easy problem to resolve

Vitamin C deficiency in developed countries is typically observed in patients with unique clinical conditions such as cystic fibrosis or anorexia nervosa, or in patients on long‐term tube feeds. We report here a clinical observation in six pediatric and adolescent patients (median age 17.5 yr, range 9.8–23.5 yr) with chronic GVHD with mucous membrane involvement found to be vitamin C deficient. These patients' baseline serum vitamin C levels ranged from <0.12 to 0.94 mg/dL (normal value 0.20–1.90 mg/dL), with a mean level 0.56 ± 0.36 mg/dL and a median level 0.6 mg/dL. Among these patients, signs and symptoms of mucositis failed to respond to standard chronic GVHD therapy. After receiving treatment with 2000 mg of ascorbic acid by mouth, daily patients displayed increased serum vitamin C levels. Clinically, this correlated with a remarkable improvement in patients' mucositis and ability to eat.
Physicians’ Perceptions of Barriers to Cardiovascular Disease Risk Factor Control among Patients with Diabetes: Results from the Translating Research into Action for Diabetes (TRIAD) Study

Introduction: Many patients with diabetes have poorly controlled blood glucose, lipid, or blood pressure levels, increasing their risk for cardiovascular disease (CVD) and other complications. Relatively little is known about what physicians perceive to be barriers to good CVD risk factor control or their own role in helping patients achieve good control. Methods: We interviewed 34 primary care physicians in 4 states to assess their perceptions of patients’ barriers to CVD risk factor control. Interviews were coded and analyzed for emergent themes. Results: Physicians attributed barriers primarily to patients (socioeconomic issues, competing medical conditions, and lack of motivation) or to health system barriers (cost of care or lack of a multidisciplinary team). Physicians also expressed high levels of frustration with their efforts to address barriers. Conclusions: Physicians felt that barriers to CVD risk factor control often were beyond their abilities to address. Training physicians or other members of the primary health care team to address patients’ personal barriers and health system barriers to good control could help alleviate high frustration levels, improve relationships with patients, and improve the treatment of diabetes. Supporting such efforts with adequate reimbursement should be a focus of health care reform.
Galactoglucomannan oligosaccharide supplementation affects nutrient digestibility, fermentation end-product production, and large bowel microbiota of the dog.

A galactoglucomannan oligosaccharide (GGMO) obtained from fiberboard production was evaluated as a dietary supplement for dogs. The GGMO substrate contained increased concentrations of oligosaccharides containing mannose, xylose, and glucose, with the mannose component accounting for 35% of DM. Adult dogs assigned to a 6 × 6 Latin square design were fed 6 diets, each containing a different concentration of supplemental GGMO (0, 0.5, 1, 2, 4, and 8%) that replaced dietary cellulose. Total tract DM and OM apparent digestibilities increased (P < 0.001) linearly, whereas total tract CP apparent digestibility decreased (P < 0.001) linearly as dietary GGMO substrate concentration increased. Fecal concentrations of acetate, propionate, and total short-chain fatty acids increased (P ≤ 0.001) linearly, whereas butyrate concentration decreased (P ≤ 0.001) linearly with increasing dietary concentrations of GGMO. Fecal pH decreased (P ≤ 0.001) linearly as dietary GGMO substrate concentration increased, whereas fecal score increased quadratically (P ≤ 0.001). Fecal phenol (P ≤ 0.05) and indole (P ≤ 0.01) concentrations decreased linearly with GGMO supplementation. Fecal biogenic amine concentrations were not different among treatments except for phenylethylamine, which decreased (P < 0.001) linearly as dietary GGMO substrate concentration increased. Fecal microbial concentrations of Escherichia coli, Lactobacillus spp. , and Clostridium perfringens were not different among treatments. A quadratic increase (P ≤ 0.01) was noted for Bifidobacterium spp. as dietary GGMO substrate concentration increased. The data suggest positive nutritional properties of supplemental GGMO when incorporated in a good-quality dog food.