Preschool Children’s Cooperative Problem Solving during Play in Everyday Classroom Contexts: China and the US

There is value in studying young children’s cooperative problem solving (CPS) during play in different cultures since children in our society will continue to face problems that are not unique to a particular culture, but also relevant to people from other countries. Cognitive development theory and sociocultural theory contend that play contexts can support children in the construction of their knowledge through explorations with different play materials and engagement in social interactions with peers during CPS experiences. However, there is a lack of research studying children’s CPS during play in their everyday preschool classrooms, and particularly, cross-culturally. Therefore, this dissertation, that includes three manuscripts, was designed to investigate (a) preschool children’s different patterns of engagement in play and CPS in Chinese and US preschool classrooms and (b) their teachers’ beliefs about their roles and pedagogical decisions for supporting children’s CPS in particular settings in these two cultures. In the first manuscript, a systematic literature review was conducted framed by PRISR, and it was found that there is a lack of cross-cultural studies that have investigated (a) preschool children’s CPS during play in their everyday classroom contexts and (b) teachers’ roles in children’s development of CPS. These research gaps were addressed in the second and third manuscripts by conducting (a) a 10-month, ethnographic informed observational study in a Chinese kindergarten and a US preschool center that included (b) semi-structured, teacher interviews with the integration of the visual stimulated recall approach. The data and findings are presented, based on over 960 minutes of (a) 16, four- and five-year-old children’s video recordings, (b) six classroom teachers’ interview transcriptions from two early care and education centers, and (c) the researcher’s field notes and journal entries. Findings support that there were cultural and gender differences in children’s engagement in their types of play (constructive play, fantasy play, and rough-and-tumble play) and CPS (debating and mentoring). Further, teachers in both cultures showed similarities and differences, within and across the cultural contexts, in their beliefs and pedagogy regarding their image of the child, their role as teachers, and their arrangements of classroom environments

A Mixed Apocrine Gland Tumor with Metastases to the Bone and Bone Marrow in a Miniature Poodle

A 10-year-old female miniature poodle had a mass in its carpal joint of the left forelimb. The tumor was divided into small multiple lobules by delicate connective tissues, and necroses were found in some of the central lobules. In some connective stromal areas, chondroid and osteoid tissues were formed. The tumor cells were similar to the structure of apocrine gland epithelial cells with apical blebs resembling apocrine secretion and eosinophilic secretary materials within the luminal space, and spindle cells were sometimes found in the basal area of the glandular structure. In some areas, tumor cells invaded in the blood vessels, bone and bone marrow. Immunohistochemically, the tumor cells forming tubulo-acinar to solid structures were intensely positive for cytokeratin and keratin K8/K18, and the spindle cells were positive for vimentin and alpha-smooth muscle actin. This case was diagnosed as a malignant mixed apocrine gland tumor with metastases to the bone and bone marrow

Protective Efficacy of Vitamins C and E on p,p′-DDT-Induced Cytotoxicity via the ROS-Mediated Mitochondrial Pathway and NF-κB/FasL Pathway

Dichlorodiphenoxytrichloroethane (DDT) is a known persistent organic pollutant and liver damage toxicant. However, there has been little emphasis on the mechanism underlying liver damage toxicity of DDT and the relevant effective inhibitors. Hence, the present study was conducted to explore the protective effects of vitamin C (VC) and vitamin E (VE) on the cytotoxicity of DDT in HL-7702 cells and elaborate the specific molecular mechanisms. The results demonstrated that p,p′-DDT exposure at over 10 µM depleted cell viability of HL-7702 cells and led to cell apoptotic. p,p′-DDT treatment elevated the level of reactive oxygen species (ROS) generation, induced mitochondrial membrane potential, and released cytochrome c into the cytosol, with subsequent elevations of Bax and p53, along with suppression of Bcl-2. In addition, the activations of caspase-3 and -8 were triggered. Furthermore, p,p′-DDT promoted the expressions of NF-κB and FasL. When the cells were exposed to the NF-κB inhibitor (PDTC), the up-regulated expression of FasL was attenuated. Strikingly, these alterations caused by DDT treatment were prevented or reversed by the addition of VC or VE, and the protective effects of co-treatment with VC and VE were higher than the single supplement with p,p′-DDT. Taken together, these findings provide novel experimental evidences supporting that VC or/and VE could reduce p,p′-DDT-induced cytotoxicity of HL-7702 cells via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway

SIRT1-mediated downregulation of p27(Kip1) is essential for overcoming contact inhibition of Kaposi's sarcoma-associated herpesvirus transformed cells

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus associated with Kaposi's sarcoma (KS), a malignancy commonly found in AIDS patients. Despite intensive studies in the last two decades, the mechanism of KSHV-induced cellular transformation and tumorigenesis remains unclear. In this study, we found that the expression of SIRT1, a metabolic sensor, was upregulated in a variety of KSHV-infected cells. In a model of KSHV-induced cellular transformation, SIRT1 knockdown with shRNAs or knockout by CRISPR/Cas9 gene editing dramatically suppressed cell proliferation and colony formation in soft agar of KSHV-transformed cells by inducing cell cycle arrest and contact inhibition. SIRT1 knockdown or knockout induced the expression of cyclin-dependent kinase inhibitor 1B (p27(Kip1)). Consequently, p27 knockdown rescued the inhibitory effect of SIRT1 knockdown or knockout on cell proliferation and colony formation. Furthermore, treatment of KSHV-transformed cells with a SIRT1 inhibitor, nicotinamide (NAM), had the same effect as SIRT1 knockdown and knockout. NAM significantly inhibited cell proliferation in culture and colony formation in soft agar, and induced cell cycle arrest. Significantly, NAM inhibited the progression of tumors and extended the survival of mice in a KSHV-induced tumor model. Collectively, these results demonstrate that SIRT1 suppression of p27 is required for KSHV-induced tumorigenesis and identify a potential therapeutic target for KS.

Uterine Carcinosarcoma in a 2-year-old Female Wistar Hannover GALAS Rat

Carcinosarcomas are rare tumors in humans as well as rats and most commonly occur in the uterus. Recently, we observed a case of incidental carcinosarcoma of the uterus in a female Wistar Hannover GALAS [BrlHan:WIST@ Jcl (GALAS)] rat at 2 years of age. Histopathologically, the tumor was characterized by an admixture of malignant epithelial and nonepithelial elements. The carcinomatous components represented a type of endometrial carcinoma, consisting of glandular and solid proliferation of large-sized tumor cells. Prominent mitoses and tumor cell invasion were observed. The sarcomatous components were characterized by multifocal proliferation of severe atypical cells with cartilage matrix and were diagnosed as chondrosarcoma. Transitions between carcinomatous and sarcomatous components were observed, and many tumor cells in the solid lesion showed immunohistochemical reactivity with both cytokeratin and vimentin. Based on these findings, this tumor was diagnosed as a uterine carcinosarcoma. This is the first report of uterine carcinosarcoma in Wistar Hannover GALAS [BrlHan:WIST@Jcl (GALAS)] rats

Impact of self-reported Gastroesophageal reflux disease in subjects from COPDGene cohort

Abstract Background The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes. Methods Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD. Physician-diagnosed GERD was ascertained by questionnaire. Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD. We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models. Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs). To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score. Results GERD was reported by 29% of subjects with female predominance. Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs. 13.4.0%, p < 0.0001). Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs. 1.8, p < 0.0001), and poorer quality of life (QOL) scores (St. George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs. 34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs. 41.4, p < 0.0001). In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006). During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included. PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association. Conclusions In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up. These associations are maintained after controlling for PPI use. The PPI-exacerbations association could result from confounding-by-indication.http://deepblue.lib.umich.edu/bitstream/2027.42/109476/1/12931_2014_Article_1500.pd

Impact of self-reported Gastroesophageal reflux disease in subjects from COPDGene cohort

Abstract Background The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes. Methods Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD. Physician-diagnosed GERD was ascertained by questionnaire. Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD. We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models. Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs). To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score. Results GERD was reported by 29% of subjects with female predominance. Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs. 13.4.0%, p < 0.0001). Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs. 1.8, p < 0.0001), and poorer quality of life (QOL) scores (St. George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs. 34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs. 41.4, p < 0.0001). In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006). During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included. PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association. Conclusions In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up. These associations are maintained after controlling for PPI use. The PPI-exacerbations association could result from confounding-by-indication.http://deepblue.lib.umich.edu/bitstream/2027.42/134572/1/12931_2014_Article_1500.pd

A controlled statistical study to assess measurement variability as a function of test object position and configuration for automated surveillance in a multicenter longitudinal COPD study (SPIROMICS)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134827/1/mp7303.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134827/2/mp7303_am.pd

The Ubiquitin/Proteasome System Mediates Entry and Endosomal Trafficking of Kaposi's Sarcoma-Associated Herpesvirus in Endothelial Cells

Ubiquitination, a post-translational modification, mediates diverse cellular functions including endocytic transport of molecules. Kaposi's sarcoma-associated herpesvirus (KSHV), an enveloped herpesvirus, enters endothelial cells primarily through clathrin-mediated endocytosis. Whether ubiquitination and proteasome activity regulates KSHV entry and endocytosis remains unknown. We showed that inhibition of proteasome activity reduced KSHV entry into endothelial cells and intracellular trafficking to nuclei, thus preventing KSHV infection of the cells. Three-dimensional (3-D) analyses revealed accumulation of KSHV particles in a cytoplasmic compartment identified as EEA1+ endosomal vesicles upon proteasome inhibition. KSHV particles are colocalized with ubiquitin-binding proteins epsin and eps15. Furthermore, ubiquitination mediates internalization of both KSHV and one of its receptors integrin β1. KSHV particles are colocalized with activated forms of the E3 ligase c-Cbl. Knock-down of c-Cbl or inhibition of its phosphorylation reduced viral entry and intracellular trafficking, resulting in decreased KSHV infectivity. These results demonstrate that ubiquitination mediates internalization of both KSHV and one of its cognate receptors integrin β1, and identify c-Cbl as a potential E3 ligase that facilitates this process

Low Ca diet leads to increased Ca retention by changing the gut flora and ileal pH value in laying hens

Osteoporosis is a common degenerative metabolic bone disease in caged laying hens. Intensive egg production mobilizing large amounts of Ca from bone for eggshell formation, consequently leading to Ca deficiency, has been recognized as a critical factor causing osteoporosis in commercial laying hens. The aim of this study was to examine the effect of Ca deficiency on the function of the gut microbiota–bone axis and related egg production traits and bone health in laying hens. Twenty-four 48-week-old laying hens were fed a control diet (Control, 3.72%) or a low Ca diet (LC, 2.04%) for 60 d (n = 12). Compared to the Control hens, the LC hens had higher levels of alkaline phosphatase and tartrate resistant acid phosphatase (P < 0.05) with lower bone strength, eggshell thickness, and eggshell strength (P < 0.05). In addition, the LC hens had higher plasma estradiol concentrations, while having lower concentrations of interleukin-1 (IL-1) and IL-6. The LC hens also had a lower pH value in the ileum with an increased Ca retention. The principal co-ordinates analysis showed significantly separate cecal microbiota populations between the Control and LC hens. The Prevotellaceae_UCG-001, Subdoligranulum, Peptococcus, and Eubacterium_hallii_group (P < 0.05) were higher, while the CHKC1001 and Sutterella (P < 0.05) were lower at the genus level in the LC hens. In addition, Prevotellaceae_UCG-001, Subdoligranulum and Eubacterium_hallii_group had a negative correlation, while Sutterella was positively correlated with ileal pH values. The transcriptome analysis revealed that the low Ca diet caused 20 and 31 genes to be significantly up- and down-regulated, respectively. The gene expressions of cystic fibrosis transmembrane conductance regulator, solute carrier family 26 member 3 of the anion exchangers, and mitogen-activated protein kinase 12 of pro-inflammatory factors were lower in the LC birds, which was correlated with the lower ileal pH values. These results suggest that the hens with low Ca diet-induced osteoporosis have an increased intestinal Ca retention with a decreased ileal pH value, correlated with the changes in Prevotellaceae_UCG-001, Subdoligranulum, and Eubacterium_hallii_group of beneficial genera. The results provide insights for further understanding and preventing osteoporosis in laying hens