Site of breast cancer metastasis is independent of single nutrient levels.

Cancer metastasis is a major contributor to patient morbidity and mortality, yet the factors that determine the organs where cancers can metastasize are incompletely understood. In this study, we quantify the absolute levels of over 100 nutrients available across multiple tissues in mice and investigate how this relates to the ability of breast cancer cells to grow in different organs. We engineered breast cancer cells with broad metastatic potential to be auxotrophic for specific nutrients and assessed their ability to colonize different organs.

The effects of musical practice on the well-being, mental health and social support of student, amateur, and professional musicians in Canada during the COVID-19 pandemic.

This pan-Canadian study investigates the effects of musical practice on the well-being, mental health, and social support of Canadian musicians during the COVID-19 pandemic. Using a survey questionnaire, data was collected from 1,618 participants aged 14 and above during the first wave of the pandemic up to the first half of 2022. The survey included standardized questionnaires to self-assess well-being (WHO-5), mental health (MHC-SF), and social support (SPS-10 measures social support).

A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments.

Blocking the import of nutrients essential for cancer cell proliferation represents a therapeutic opportunity, but it is unclear which transporters to target. Here we report a CRISPR interference/activation screening platform to systematically interrogate the contribution of nutrient transporters to support cancer cell proliferation in environments ranging from standard culture media to tumours. We applied this platform to identify the transporters of amino acids in leukaemia cells and found that amino acid transport involves high bidirectional flux dependent on the microenvironment composition.

Bio-based surfactants derived from pectin.

Surfactants derived from renewable resources and synthesized using renewable feedstock and sustainable methods have become a major research focus over the past decade in the surfactant industry. This research presents an approach for rapidly converting readily available polysaccharides, like pectin derived from fruit waste, into safely biodegradable surface-active polymers. Commercially available pectin was modified with n-alkyl amines having different alkyl chain lengths using potassium carbonate as a catalyst.

Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer's disease mutations.

Disinhibition during early stages of Alzheimer's disease is postulated to cause network dysfunction and hyperexcitability leading to cognitive deficits. However, the underlying molecular mechanism remains unknown. Here we show that, in mouse lines carrying Alzheimer's disease-related mutations, a loss of neuronal membrane potassium-chloride cotransporter KCC2, responsible for maintaining the robustness of GABAA-mediated inhibition, occurs pre-symptomatically in the hippocampus and prefrontal cortex.

Online Group Music-Making in Community Concert Bands: Perspectives From Conductors and Older Amateur Musicians.

At the beginning of the pandemic, many music ensembles had to stop their activities due to the confinement. While some found creative ways to start making music again with the help of technologies, the transition from "real" rehearsals to "online" rehearsals was challenging, especially among older amateur musicians. The aim of this case study was to examine the effects of this transition on three community band conductors and three older amateur musicians.

Interactions with stromal cells promote a more oxidized cancer cell redox state in pancreatic tumors.

Access to electron acceptors supports oxidized biomass synthesis and can be limiting for cancer cell proliferation, but how cancer cells overcome this limitation in tumors is incompletely understood. Nontransformed cells in tumors can help cancer cells overcome metabolic limitations, particularly in pancreatic cancer, where pancreatic stellate cells (PSCs) promote cancer cell proliferation and tumor growth. However, whether PSCs affect the redox state of cancer cells is not known.

Expression Levels of Lamin A or C Are Critical to Nuclear Maturation, Functional Responses, and Gene Expression Profiles in Differentiating Mouse Neutrophils.

Neutrophils mediate critical innate immune responses by migrating to sites of infection or inflammation, phagocytosing microorganisms, and releasing an arsenal of antimicrobial agents, including reactive oxygen species. These functions are shared by other innate immune cell types, but an interesting feature of neutrophils is their hallmark lobulated nuclei. Although why this bizarre nuclear shape forms is still being elucidated, studies of two intermediate filament proteins that associate with the nuclear envelope, lamin A and C, indicate that expression levels of these proteins govern nuclear maturation.

Sex-Specific Retinal Anomalies Induced by Chronic Social Defeat Stress in Mice.

Major depressive disorder (MDD) is one of the most common consequences of chronic stress. Still, there is currently no reliable biomarker to detect individuals at risk to develop the disease. Recently, the retina emerged as an effective way to investigate psychiatric disorders using the electroretinogram (ERG).

Medical Assistance in Dying in patients with advanced cancer and their caregivers: a mixed methods longitudinal study protocol.

Background: The legal criteria for medical assistance in dying (MAiD) for adults with a grievous and irremediable medical condition were established in Canada in 2016. There has been concern that potentially reversible states of depression or demoralization may contribute to the desire for death (DD) and requests for MAiD. However, little is known about the emergence of the DD in patients, its impact on caregivers, and to what extent supportive care interventions affect the DD and requests for MAiD.

Methodological standards for qualitative and mixed methods patient centered outcomes research.

The Patient-Centered Outcomes Research Institute’s (PCORI) methodology standards for qualitative methods and mixed methods research help ensure that research studies are designed and conducted to generate the evidence needed to answer patients’ and clinicians’ questions about which methods work best, for whom, and under what circumstances. This set of standards focuses on factors pertinent to patient centered outcomes research, but it is also useful for providing guidance for other types of clinical research. The standards can be used to develop and evaluate proposals, conduct the research, and interpret findings.

Cell Type-Specific Intralocus Interactions Reveal Oligodendrocyte Mechanisms in MS.

Multiple sclerosis (MS) is an autoimmune disease characterized by attack on oligodendrocytes within the central nervous system (CNS). Despite widespread use of immunomodulatory therapies, patients may still face progressive disability because of failure of myelin regeneration and loss of neurons, suggesting additional cellular pathologies. Here, we describe a general approach for identifying specific cell types in which a disease allele exerts a pathogenic effect.

Characterization of neutrophils and macrophages from ex vivo-cultured murine bone marrow for morphologic maturation and functional responses by imaging flow cytometry.

Neutrophils and macrophages differentiate from common myeloid progenitors in the bone marrow, where they undergo nuclear morphologic changes during maturation. During this process, both cell types acquire critical innate immune functions that include phagocytosis of pathogens, and for neutrophils the release of nuclear material called nuclear extracellular traps (NETs). Primary cells used to study these functions are typically purified from mature mouse tissues, but bone marrow-derived ex vivo cultures provide more abundant numbers of progenitors and functionally mature cells.

FXR1P is a GSK3β substrate regulating mood and emotion processing.

Inhibition of glycogen synthase kinase 3β (GSK3β) is a shared action believed to be involved in the regulation of behavior by psychoactive drugs such as antipsychotics and mood stabilizers. However, little is known about the identity of the substrates through which GSK3β affects behavior. We identified fragile X mental retardation-related protein 1 (FXR1P), a RNA binding protein associated to genetic risk for schizophrenia, as a substrate for GSK3β.

Spatial intensity distribution analysis (SpIDA): a new tool for receptor tyrosine kinase activation and transactivation quantification.

This chapter presents a general approach for the application of spatial intensity distribution analysis (SpIDA) to pharmacodynamic quantification of receptor tyrosine kinase homodimerization in response to direct ligand activation or transactivation by G protein-coupled receptors. A custom graphical user interface developed for MATLAB is used to extract quantal brightness and receptor density information from intensity histograms calculated from single fluorescence microscopy images. This approach allows measurement of monomer/oligomer protein mixtures within subcellular compartments using conventional confocal laser scanning microscopy.

A role for cytosolic isocitrate dehydrogenase as a negative regulator of glucose signaling for insulin secretion in pancreatic ß-cells.

Cytosolic NADPH may act as one of the signals that couple glucose metabolism to insulin secretion in the pancreatic ß-cell. NADPH levels in the cytoplasm are largely controlled by the cytosolic isoforms of malic enzyme and isocitrate dehydrogenase (IDHc). Some studies have provided evidence for a role of malic enzyme in glucose-induced insulin secretion (GIIS) via pyruvate cycling, but the role of IDHc in ß-cell signaling is unsettled.

Perceived efficacy of e-cigarettes versus nicotine replacement therapy among successful e-cigarette users: a qualitative approach.

Background: Nicotine is widely recognized as an addictive psychoactive drug. Since most smokers are bio-behaviorally addicted, quitting can be very difficult and is often accompanied by withdrawal symptoms. Research indicates that nicotine replacement therapy (NRT) can double quit rates.

Quantification of receptor tyrosine kinase activation and transactivation by G-protein-coupled receptors using spatial intensity distribution analysis (SpIDA).

This chapter presents a general approach for the application of spatial intensity distribution analysis (SpIDA) to the pharmacodynamic quantification of receptor tyrosine kinase homodimerization in response to direct ligand activation or transactivation by G-protein-coupled receptors. Intensity histograms are generated from single fluorescence microscopy images. These histograms are then fit with Poissonian distributions to obtain density maps and quantal brightness values of the labeled proteins underlying the images.

Glucolipotoxicity alters lipid partitioning and causes mitochondrial dysfunction, cholesterol, and ceramide deposition and reactive oxygen species production in INS832/13 ss-cells.

Elevated glucose and saturated fatty acids synergize in inducing apoptosis in INS832/13 cells and in human islet cells. In order to gain insight into the molecular mechanism(s) of glucolipotoxicity (Gltox), gene profiling and metabolic analyses were performed in INS832/13 cells cultured at 5 or 20 mm glucose in the absence or presence of palmitate. Expression changes were observed for transcripts involved in mitochondrial, lipid, and glucose metabolism.

Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling.

Aims/hypothesis: The aim of this study was to determine the role of fatty acid signalling in islet beta cell compensation for insulin resistance in the Zucker fatty fa/fa (ZF) rat, a genetic model of severe obesity, hyperlipidaemia and insulin resistance that does not develop diabetes.

Materials And Methods: NEFA augmentation of insulin secretion and fatty acid metabolism were studied in isolated islets from ZF and Zucker lean (ZL) control rats.

Results: Exogenous palmitate markedly potentiated glucose-stimulated insulin secretion (GSIS) in ZF islets, allowing robust secretion at physiological glucose levels (5-8 mmol/l).

A role for the malonyl-CoA/long-chain acyl-CoA pathway of lipid signaling in the regulation of insulin secretion in response to both fuel and nonfuel stimuli.

The malonyl-CoA/long-chain acyl-CoA (LC-CoA) model of glucose-induced insulin secretion (GIIS) predicts that malonyl-CoA derived from glucose metabolism inhibits fatty acid oxidation, thereby increasing the availability of LC-CoA for lipid signaling to cellular processes involved in exocytosis. For directly testing the model, INSr3 cell clones overexpressing malonyl-CoA decarboxylase in the cytosol (MCDc) in a tetracycline regulatable manner were generated, and INS(832/13) and rat islets were infected with MCDc-expressing adenoviruses. MCD activity was increased more than fivefold, and the malonyl-CoA content was markedly diminished.

[Reactions of social workers in a mental health day center and the avoidance of institutionalization of individual defense mechanisms].

The author attempts to describe the different strengths that emerge from the role of the supervisor (clinic) in a community organization in relation to two aspects: the maintaining of the defining characteristics of the notion of "alternative" and the dynamic understanding of the social worker-user relationship. After a review of how a day centre operates, the author describes the individual and collective "defense mechanisms" that are used by social workers to alleviate the impact of the user's baffling behaviour on their personality. The author follows by showing that failure to use these defense mechanisms can lead to burnout for the social worker, while certain forms of collective defense mechanisms can prompt this alternative care system to institutionalize itself from within.

Dominantly inherited ataxias in Portugal.

We analysed the clinical features of 82 patients with dominantly inherited ataxia in a cohort survey. All patients fulfilled the diagnostic criteria for Machado-Joseph disease. The mean age of onset of symptoms was 39.

Linkage studies of Friedreich ataxia by means of blood-group and protein markers.

Friedreich ataxia (FA) is an autosomal recessive, neuro-degenerative disorder in which the pathogenetic mechanism remains unidentified despite extensive biochemical studies. Genetic-linkage studies provide an alternative approach to determining the basic defect. Linkage analysis between FA and 36 polymorphic-blood-group and protein markers has been carried out on three separate patient populations--16 families from the inbred Acadian population of Louisiana, 21 French-Canadian families from Quebec, and nine apparently unrelated British families--in an attempt to determine the chromosomal location of the disease mutation.