The DNMT1 intrinsically disordered domain regulates genomic methylation during development.

The DNMT1 cytosine methyltransferase enzyme contains a large ∼300-aa intrinsically disordered domain (IDD) that we previously showed regulated DNA methylation patterns in mouse ES cells. Here we generated seven mouse lines with different mutations in the IDD. Homozygous mutant mice of five lines developed normally, with normal levels of methylation on both imprinted and nonimprinted DNA sequences.

Impact of Leishmania mexicana infection on dendritic cell signaling and functions.

Leishmania parasites have the ability to modify macrophage signaling pathways in order to survive and multiply within its mammalian host. They are also known to invade other cells including neutrophils, fibroblasts and dendritic cells (DCs). DCs have an important role in immunity as the link between innate and adaptive immunity, necessary for the development of an effective response; however, the impact of Leishmania mexicana infection on DCs has been poorly studied.

The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress.

The blood system is sustained by a pool of haematopoietic stem cells (HSCs) that are long-lived due to their capacity for self-renewal. A consequence of longevity is exposure to stress stimuli including reactive oxygen species (ROS), nutrient fluctuation and DNA damage. Damage that occurs within stressed HSCs must be tightly controlled to prevent either loss of function or the clonal persistence of oncogenic mutations that increase the risk of leukaemogenesis.

Functional dynamics of Foxp3⁺ regulatory T cells in mice and humans.

Forkhead box protein 3 (Foxp3)(+) regulatory T (Treg) cells are critical mediators for the establishment of self-tolerance and immune homeostasis and for the control of pathology in various inflammatory responses. While Foxp3(+) Treg cells often control immune responses in secondary lymphoid tissues, they must also traffic to and persist within non-lymphoid tissues, where they integrate various environmental cues to coordinate and adapt their effector acitvities in these sites. In recent years, our group has made use of several mouse models, including the non-obese diabetic model of type 1 diabetes, to characterize the factors, which impact the homeostasis, function, and reprogramming potential of Foxp3(+) Treg cells in situ.

Reduced lymphoid lineage priming promotes human hematopoietic stem cell expansion.

The hematopoietic system sustains regeneration throughout life by balancing self-renewal and differentiation. To stay poised for mature blood production, hematopoietic stem cells (HSCs) maintain low-level expression of lineage-associated genes, a process termed lineage priming. Here, we modulated expression levels of Inhibitor of DNA binding (ID) proteins to ask whether lineage priming affects self-renewal of human HSCs.

Environmental sensing and regulation of gene expression in CD4+ T cell subsets.

Foxp3(+) regulatory T (Treg) cells represent a major mechanism for the maintenance of self-tolerance and immune homeostasis in various inflammatory responses. To achieve this, Foxp3(+) Treg cells must integrate a spectrum of environmental stimuli to orchestrate the required pathways for their coordinated action in vivo. Transcriptional and post-transcriptional mechanisms of gene regulation enable T cells to respond to inflammatory events, by altering the nature, amounts and activities of specific proteins produced for their controlled and coordinated modulation of immunity.

Validity and applications of the Montreal cognitive assessment for the assessment of vascular cognitive impairment.

Cognitive impairment is common among patients with stroke or other cerebrovascular disease and influences long-term outcome, including occupational functioning. Recognition and monitoring of mild cognitive impairment is thus essential to good patient care. The Montreal Cognitive Assessment (MoCA) has been suggested as a brief screening test of vascular cognitive impairment.

The 16p13.3 (PDPK1) Genomic Gain in Prostate Cancer: A Potential Role in Disease Progression.

Background: Prostate cancer (PCa) is a leading cause of cancer death, and distinguishing aggressive from indolent tumors is a major challenge. Identification and characterization of genomic alterations associated with advanced disease can provide new markers of progression and better therapeutic approaches.

Methods: We performed fluorescence in situ hybridization to detect the copy number gain of chromosome 16p13.

Limitations for interpreting failure on individual subtests of the Montreal Cognitive Assessment.

Background: The Montreal Cognitive Assessment (MoCA) is sensitive to mild forms of cognitive impairment in geriatric populations and asks questions under the subheadings visuospatial/executive, naming, attention, language, abstraction, delayed recall, and orientation. This study examined the extent to which these subsets of MoCA items evaluate their intended cognitive domains.

Methods: Clinical data from 185 geriatric memory clinic outpatients who underwent cognitive screening and subsequent neuropsychological assessment were analyzed.

PTEN genomic deletion predicts prostate cancer recurrence and is associated with low AR expression and transcriptional activity.

Background: Prostate cancer (PCa), a leading cause of cancer death in North American men, displays a broad range of clinical outcome from relatively indolent to lethal metastatic disease. Several genomic alterations have been identified in PCa which may serve as predictors of progression. PTEN, (10q23.

RNA interference: Systemic RNAi SIDes with endosomes.

Systemic RNAi, the intercellular spreading of RNAi silencing, requires SID-1 and SID-3 to import silencing signals in Caenorhabditis elegans. How are these signals exported? SID-5, an endosome-associated protein, is a candidate for the job.

Site of allergic airway narrowing and the influence of exogenous surfactant in the Brown Norway rat.

Background: The parameters R(N) (newtonian resistance), G (tissue damping), and H (tissue elastance) of the constant phase model of respiratory mechanics provide information concerning the site of altered mechanical properties of the lung. The aims of this study were to compare the site of allergic airway narrowing implied from respiratory mechanics to a direct assessment by morphometry and to evaluate the effects of exogenous surfactant administration on the site and magnitude of airway narrowing.

Methods: We induced airway narrowing by ovalbumin sensitization and challenge and we tested the effects of a natural surfactant lacking surfactant proteins A and D (Infasurf®) on airway responses.

Proteasomal activity is required to initiate and to sustain translational activation of messenger RNA encoding the stem-loop-binding protein during meiotic maturation in mice.

Developmentally regulated translation plays a key role in controlling gene expression during oogenesis. In particular, numerous mRNA species are translationally repressed in growing oocytes and become translationally activated during meiotic maturation. While many studies have focused on a U-rich sequence, termed the cytoplasmic polyadenylation element (CPE), located in the 3'-untranslated region (UTR) and the CPE-binding protein (CPEB) 1, multiple mechanisms likely contribute to translational control in oocytes.

Measuring cognition in a geriatric outpatient clinic: Rasch analysis of the Montreal Cognitive Assessment.

Objective: To evaluate the psychometric properties of the Montreal Cognitive Assessment as a quantitative measure of cognitive ability.

Data Analyzed: A total of 222 cases extracted from a clinical database (57-91 years) of patients screened for cognitive impairment in outpatient geriatric assessment clinics.

Data Collected: Demographic information and individual item responses to Montreal Cognitive Assessment.

[The limited spectrum of pathogenic BRCA1 and BRCA2 mutations in the French Canadian breast and breast-ovarian cancer families, a founder population of Quebec, Canada].

The unique genetic demography of the French Canadian population of Quebec, Canada, has provided a means to study the contribution of BRCA1 and BRCA2, the breast-ovarian cancer susceptibility genes. Here we review BRCA1 and BRCA2 in the context of French Canadian cancer families, a well-characterized founder population known for its contributions to medical genetics. Pathogenic BRCA1 and BRCA2 mutations contribute to a significant proportion of hereditary breast and/or ovarian cancer families of French Canadian descent.