166 research outputs found

    Visual Tools for Eliciting Connections and Cohesiveness in Mixed Methods Research

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    In this commentary, we offer a set of visual tools that can assist education researchers, especially those in the field of mathematics, in developing cohesiveness from a mixed methods perspective, commencing at a study’s research questions and literature review, through its data collection and analysis, and finally to its results. This expounds upon the ideas and methodological insights relating to research connections and structure presented by other scholars (e.g., Creswell, 2009; Heid & Blume, 2011; Mertens, 2010; Thanheiser, Ellis, & Herbel-Eisenmann, 2012). As faculty who work with graduate students in education, we have found that these visual tools help students elicit and maintain salient connections throughout the research process

    Coherence and enrichment across the middle and secondary levels: Four mathematically authentic learning experiences

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    This article discusses four mathematically rich settings with origins in the elementary, middle, and secondary school curricula. Depending on the questions asked and the connections made within each setting, the problem spaces allow the instructor to import tools leading to sophisticated extensions appropriate for college-level study. These topics include the Heaviside function, randomness, symmetry, modular arithmetic, the generalized Pythagorean Theorem, and the theory of groups. Given the potentially extensive ground covered by these settings, they serve to reward those students who are inherently curious while highlighting the coherence in the curriculum as one progresses through the grades. The mathematical experiences invite disciplinary and interdisciplinary connections and encourage discourse and productive struggle

    Multiple Aspects of ATP-Dependent Nucleosome Translocation by RSC and Mi-2 Are Directed by the Underlying DNA Sequence

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    Contains fulltext : 129351.pdf (publisher's version ) (Open Access)Background Chromosome structure, DNA metabolic processes and cell type identity can all be affected by changing the positions of nucleosomes along chromosomal DNA, a reaction that is catalysed by SNF2-type ATP-driven chromatin remodelers. Recently it was suggested that in vivo, more than 50% of the nucleosome positions can be predicted simply by DNA sequence, especially within promoter regions. This seemingly contrasts with remodeler induced nucleosome mobility. The ability of remodeling enzymes to mobilise nucleosomes over short DNA distances is well documented. However, the nucleosome translocation processivity along DNA remains elusive. Furthermore, it is unknown what determines the initial direction of movement and how new nucleosome positions are adopted. Methodology/Principal Findings We have used AFM imaging and high resolution PAGE of mononucleosomes on 600 and 2500 bp DNA molecules to analyze ATP-dependent nucleosome repositioning by native and recombinant SNF2-type enzymes. We report that the underlying DNA sequence can control the initial direction of translocation, translocation distance, as well as the new positions adopted by nucleosomes upon enzymatic mobilization. Within a strong nucleosomal positioning sequence both recombinant Drosophila Mi-2 (CHD-type) and native RSC from yeast (SWI/SNF-type) repositioned the nucleosome at 10 bp intervals, which are intrinsic to the positioning sequence. Furthermore, RSC-catalyzed nucleosome translocation was noticeably more efficient when beyond the influence of this sequence. Interestingly, under limiting ATP conditions RSC preferred to position the nucleosome with 20 bp intervals within the positioning sequence, suggesting that native RSC preferentially translocates nucleosomes with 15 to 25 bp DNA steps. Conclusions/Significance Nucleosome repositioning thus appears to be influenced by both remodeler intrinsic and DNA sequence specific properties that interplay to define ATPase-catalyzed repositioning. Here we propose a successive three-step framework consisting of initiation, translocation and release steps to describe SNF2-type enzyme mediated nucleosome translocation along DNA. This conceptual framework helps resolve the apparent paradox between the high abundance of ATP-dependent remodelers per nucleus and the relative success of sequence-based predictions of nucleosome positioning in vivo

    Bdnf impact on biological markers of depression—role of physical exercise and training

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    Depression is the most common and devastating psychiatric disorder in the world. Its symptoms, especially during the pandemic, are observed in all age groups. Exercise training (ET) is well known as a non-pharmacological strategy to alleviate clinical depression. The brain-derived neurotrophic factor (BDNF) is one of the biological factors whose expression and secretion are intensified in response to ET. BDNF is also secreted by contracted skeletal muscle that likely exerts para-, auto-and endocrine effects, supporting the crosstalk between skeletal muscle and other distant organs/tissues, such as the nervous system. This finding suggests that they communicate and work together to induce improvements on mood, cognition, and learning processes as BDNF is the main player in the neurogenesis, growth, and survival of neurons. Therefore, BDNF has been recognized as a therapeutic factor in clinical depression, especially in response to ET. The underlying mechanisms through which ET impacts depression are varied. The aim of this review was to provide information of the biological markers of depression such as monoamines, tryptophan, endocannabinoids, markers of inflammatory processes (oxidative stress and cytokines) stress and sex hormones and their relationship to BDNF. In addition, we reviewed the effects of ET on BNDF expression and how it impacts depression as well as the potential mechanisms mediating this process, providing a better understanding of underlying ET-related mechanisms in depression.Internal grant of University School of Physical Education. Project No. 503 62/05 Effectiveness of various therapeutic forms and their influence on nervous, muscular and vascular plasticity in patients after ischemic stroke”

    Association between the ACE I/D polymorphism and physical activity in Polish women

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    Angiotensin converting enzyme gene (ACE) is the most frequently investigated genetic marker in the context of genetic conditioning of athletic predispositions. However, the knowledge of ACE\u2019s potential modifying effect on changes in selected body traits achieved through a training programme is still limited. Therefore, we have decided to check whether selected body mass, body composition variables, oxygen uptake parameters as well as strength/speed parameters observed in physically active participants will be modulated by the ACE I/D polymorphism. The genotype distribution was examined in a group of 201 young healthy women measured for chosen traits before and after the completion of a 12-week moderate-intensive aerobic training programme. Our results revealed the significant genotype 7 training interactions for VEmax and power of countermovement jump, whereas training improvements were demonstrated for almost all parameters. In addition, main effects of the ACE I/D genotype on TGL, HDL, glucose and 10 m run were observed. A significant increase in VEmax was demonstrated for II and DD genotypes, but not for ID heterozygotes. The greatest gain in power of countermovement jump was observed in II homozygotes, although DD and ID were associated with a significant increase as well. Our study indicated that the polymorphism was associated with changes in VEmax and power of countermovement jump in response to a 12-week aerobic training programme in Caucasian women. However, more experimental studies are needed to establish the ACE gene 7 physical activity interaction

    LINT, a Novel dL(3)mbt-Containing Complex, Represses Malignant Brain Tumour Signature Genes

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    Mutations in the l(3)mbt tumour suppressor result in overproliferation of Drosophila larval brains. Recently, the derepression of different gene classes in l(3)mbt mutants was shown to be causal for transformation. However, the molecular mechanisms of dL(3)mbt-mediated gene repression are not understood. Here, we identify LINT, the major dL(3)mbt complex of Drosophila. LINT has three core subunits—dL(3)mbt, dCoREST, and dLint-1—and is expressed in cell lines, embryos, and larval brain. Using genome-wide ChIP–Seq analysis, we show that dLint-1 binds close to the TSS of tumour-relevant target genes. Depletion of the LINT core subunits results in derepression of these genes. By contrast, histone deacetylase, histone methylase, and histone demethylase activities are not required to maintain repression. Our results support a direct role of LINT in the repression of brain tumour-relevant target genes by restricting promoter access

    Stress-Induced PARP Activation Mediates Recruitment of Drosophila Mi-2 to Promote Heat Shock Gene Expression

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    Eukaryotic cells respond to genomic and environmental stresses, such as DNA damage and heat shock (HS), with the synthesis of poly-[ADP-ribose] (PAR) at specific chromatin regions, such as DNA breaks or HS genes, by PAR polymerases (PARP). Little is known about the role of this modification during cellular stress responses. We show here that the nucleosome remodeler dMi-2 is recruited to active HS genes in a PARP–dependent manner. dMi-2 binds PAR suggesting that this physical interaction is important for recruitment. Indeed, a dMi-2 mutant unable to bind PAR does not localise to active HS loci in vivo. We have identified several dMi-2 regions which bind PAR independently in vitro, including the chromodomains and regions near the N-terminus containing motifs rich in K and R residues. Moreover, upon HS gene activation, dMi-2 associates with nascent HS gene transcripts, and its catalytic activity is required for efficient transcription and co-transcriptional RNA processing. RNA and PAR compete for dMi-2 binding in vitro, suggesting a two step process for dMi-2 association with active HS genes: initial recruitment to the locus via PAR interaction, followed by binding to nascent RNA transcripts. We suggest that stress-induced chromatin PARylation serves to rapidly attract factors that are required for an efficient and timely transcriptional response

    Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

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    The aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive triple-negative breast cancer patients with brain metastases treated in the years 2003–2009 was performed. In 75 patients, immunohistochemistry was used as a surrogate of microarray in order to evaluate the expression of three basal markers: cytokeratin 5/6 (CK 5/6), EGFR/HER1 and c-KIT. The basal-like (ER/PgR/HER2-negative, CK5/6positive and/or HER1-positive) and non-basal-like (ER/PgR/HER2-negative, CK5/6-negative, HER1-negative) subsets were selected. Clinical features and survivals were compared in both groups. In the group of 111 triple-negative breast cancer patients, median DFS, OS and survival from brain metastases were 20, 29 and 4 months, respectively. In 75 patients who were evaluable for basal markers, median DFS, OS and survival from brain metastases were 18, 26 and 3.2 months, respectively. In the basal-like subtype, the survival rates were 15, 26 and 3 months, respectively, and in the non-basal-like subtypes, they were 20, 30 and 2.8 months, respectively. No statistically significant differences in survivals were detected between the basal-like and non-basal-like biological subtypes. Factors influencing survival from brain metastases were: Karnofsky performance status (KPS), the status of extracranial disease and age. Biological markers differentiating triple-negative group into basal-like and non-basal-like subtype (CK 5/6, HER1, c-KIT) had no influence on survival. In patients with triple-negative breast cancer and brain metastases, well-known clinical, but not molecular, features correlated with survival
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