Challenging notions of gendered game play: teenagers playing `The Sims`

This paper challenges notions of gendered game playing practice implicit in much research into young women\u27s involvement with the computer gaming culture. It draws on a study of Australian teenagers playing The Sims Deluxe as part of an English curriculum unit and insights from feminist media studies to explore relationships between gender and game playing practices. Departing from a reliance on predetermined notions of &ldquo;gender&rdquo;, &ldquo;domestic space&rdquo;, and &ldquo;successful game play&rdquo;, it conceptualizes The Sims as a game in which the boundaries between gender and domestic space are disturbed. It argues that observing students\u27 constructions of gender and domestic space through the act of game play itself provides a more productive insight into the gendered dimensions of game play for educators wishing to work computer games such as The Sims into curriculum development.<br /

Efeito da monensina e do óleo de soja sobre os protozoários ciliados do rúmen e correlação dos protozoários com parâmetros da fermentação ruminal e digestivos.

Fazem parte dos objetivos do trabalho estudar as possíveis correlações entre a população de ciliados com alguns parâmetros de consumo, fermentação ruminal e digestão de nutrientes no rúmen, no intuito de gerar informações que possam resultar em estratégias alimentares que aumentem a eficiência na alimentação de ruminantes

Predictive energy equations for spinal muscular atrophy type I children

BACKGROUND: Knowledge on resting energy expenditure (REE) in spinal muscular atrophy type I (SMAI) is still limited. The lack of a population-specific REE equation has led to poor nutritional support and impairment of nutritional status. OBJECTIVE: To identify the best predictors of measured REE (mREE) among simple bedside parameters, to include these predictors in population-specific equations, and to compare such models with the common predictive equations. METHODS: Demographic, clinical, anthropometric, and treatment variables were examined as potential predictors of mREE by indirect calorimetry (IC) in 122 SMAI children consecutively enrolled in an ongoing longitudinal observational study. Parameters predicting REE were identified, and prespecified linear regression models adjusted for nusinersen treatment (discrete: 0 = no; 1 = yes) were used to develop predictive equations, separately in spontaneously breathing and mechanically ventilated patients. RESULTS: In na\uefve patients, the median (25th, 75th percentile) mREE was 480 (412, 575) compared with 394 (281, 554) kcal/d in spontaneously breathing and mechanically ventilated patients, respectively (P = 0.009).In nusinersen-treated patients, the median (25th, 75th percentile) mREE was 609 (592, 702) compared with 639 (479, 723) kcal/d in spontaneously breathing and mechanically ventilated patients, respectively (P = 0.949).Both in spontaneously breathing and mechanically ventilated patients, the best prediction of REE was obtained from 3 models, all using as predictors: 1 body size related measurement and nusinersen treatment status. Nusinersen treatment was correlated with higher REE both in spontaneously breathing and mechanically ventilated patients. The population-specific equations showed a lower interindividual variability of the bias than the other equation tested, however, they showed a high root mean squared error. CONCLUSIONS: We demonstrated that ventilatory status, nusinersen treatment, demographic, and anthropometric characteristics determine energy requirements in SMAI. Our SMAI-specific equations include variables available in clinical practice and were generally more accurate than previously published equations. At the individual level, however, IC is strongly recommended for assessing energy requirements. Further research is needed to externally validate these predictive equations

Open access resources for genome-wide association mapping in rice.

Increasing food production is essential to meet the demands of a growing human population, with its rising income levels and nutritional expectations. To address the demand, plant breeders seek new sources of genetic variation to enhance the productivity, sustainability and resilience of crop varieties. Here we launch a high-resolution, open-access research platform to facilitate genome-wide association mapping in rice, a staple food crop. The platform provides an immortal collection of diverse germplasm, a high-density single-nucleotide polymorphism data set tailored for gene discovery, well-documented analytical strategies, and a suite of bioinformatics resources to facilitate biological interpretation. Using grain length, we demonstrate the power and resolution of our new high-density rice array, the accompanying genotypic data set, and an expanded diversity panel for detecting major and minor effect QTLs and subpopulation-speci&#64257;c alleles, with immediate implications for rice improvement.Article number:10532

CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum

Purpose: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD). Methods: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function. Results: The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits. Conclusion: We significantly broaden the mutational and clinical spectrum of CTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.Peer reviewe

De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is the main pathology underlying steroid-resistant nephrotic syndrome (SRNS) and a leading cause of chronic kidney disease. Monogenic forms of pediatric SRNS are predominantly caused by recessive mutations, while the contribution of de novo variants (DNVs) to this trait is poorly understood. Using exome sequencing (ES) in a proband with FSGS/SRNS, developmental delay, and epilepsy, we discovered a nonsense DNV in TRIM8, which encodes the E3 ubiquitin ligase tripartite motif containing 8. To establish whether TRIM8 variants represent a cause of FSGS, we aggregated exome/genome-sequencing data for 2,501 pediatric FSGS/SRNS-affected individuals and 48,556 control subjects, detecting eight heterozygous TRIM8 truncating variants in affected subjects but none in control subjects (p = 3.28 × 10−11). In all six cases with available parental DNA, we demonstrated de novo inheritance (p = 2.21 × 10−15). Reverse phenotyping revealed neurodevelopmental disease in all eight families. We next analyzed ES from 9,067 individuals with epilepsy, yielding three additional families with truncating TRIM8 variants. Clinical review revealed FSGS in all. All TRIM8 variants cause protein truncation clustering within the last exon between residues 390 and 487 of the 551 amino acid protein, indicating a correlation between this syndrome and loss of the TRIM8 C-terminal region. Wild-type TRIM8 overexpressed in immortalized human podocytes and neuronal cells localized to nuclear bodies, while constructs harboring patient-specific variants mislocalized diffusely to the nucleoplasm. Co-localization studies demonstrated that Gemini and Cajal bodies frequently abut a TRIM8 nuclear body. Truncating TRIM8 DNVs cause a neuro-renal syndrome via aberrant TRIM8 localization, implicating nuclear bodies in FSGS and developmental brain disease

Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals

Purpose: Coffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort. Methods: Clinical symptoms for 41 novel and 24 previously published affected individuals were analyzed using the Human Phenotype Ontology. For genotype-phenotype correlations, molecular data were standardized and grouped into non-truncating and likely gene-disrupting (LGD) variants. Missense variant protein expression and BAF-subunit interactions were examined using 3D protein modeling, co-immunoprecipitation, and proximity-ligation assays. Results: Neurodevelopmental delay with intellectual disability, muscular hypotonia, and behavioral disorders were the major manifestations. Clinical hallmarks of BAFopathies were rare. Clinical presentation differed significantly, with LGD variants being predominantly inherited and associated with mildly reduced or normal cognitive development, whereas non-truncating variants were mostly de novo and presented with severe developmental delay. These distinct manifestations and non-truncating variant clustering in functional domains suggest different pathomechanisms. In vitro testing showed decreased protein expression for N-terminal missense variants similar to LGD. Conclusion: This study improved SMARCC2 variant classification and identified discernible SMARCC2-associated phenotypes for LGD and non-truncating variants, which were distinct from other BAFopathies. The pathomechanism of most non-truncating variants has yet to be investigated

A mature macrophage is a principal HIV-1 cellular reservoir in humanized mice after treatment with long acting antiretroviral therapy

BACKGROUND: Despite improved clinical outcomes seen following antiretroviral therapy (ART), resting CD4+ T cells continue to harbor latent human immunodeficiency virus type one (HIV-1). However, such cells are not likely the solitary viral reservoir and as such defining where and how others harbor virus is imperative for eradication measures. To such ends, we used HIV-1(ADA)-infected NOD.Cg-Prkdc (scid) Il2rg (tm1Wjl)/SzJ mice reconstituted with a human immune system to explore two long-acting ART regimens investigating their abilities to affect viral cell infection and latency. At 6 weeks of infection animals were divided into four groups. One received long-acting (LA) cabotegravir (CAB) and rilpivirine (RVP) (2ART), a second received LA CAB, lamivudine, abacavir and RVP (4ART), a third were left untreated and a fourth served as an uninfected control. After 4 weeks of LA ART treatment, blood, spleen and bone marrow (BM) cells were collected then phenotypically characterized. CD4+ T cell subsets, macrophages and hematopoietic progenitor cells were analyzed for HIV-1 nucleic acids by droplet digital PCR. RESULTS: Plasma viral loads were reduced by two log(10) or to undetectable levels in the 2 and 4ART regimens, respectively. Numbers and distributions of CD4+ memory and regulatory T cells, macrophages and hematopoietic progenitor cells were significantly altered by HIV-1 infection and by both ART regimens. ART reduced viral DNA and RNA in all cell and tissue compartments. While memory cells were the dominant T cell reservoir, integrated HIV-1 DNA was also detected in the BM and spleen macrophages in both regimen-treated mice. CONCLUSION: Despite vigorous ART regimens, HIV-1 DNA and RNA were easily detected in mature macrophages supporting their potential role as an infectious viral reservoir. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-017-0344-7) contains supplementary material, which is available to authorized users