The mild hypothermia response (MHR) maintains organismal homeostasis during cold exposure and is thought to be critical for the neuroprotection documented with therapeutic hypothermia. To date, little is known about the transcriptional regulation of the MHR. We utilize a forward CRISPR-Cas9 mutagenesis screen to identify the histone lysine methyltransferase SMYD5 as a regulator of the MHR.
View Article and Find Full Text PDFIntroduction: The Mitf has been shown to regulate B cell activation and tolerance. However, the underlying B cell-specific mechanisms responsible, and those that distinguish Mitf from closely related Mitf/TFE (MiT) transcription factors Tfe3, Tfeb, and Tfec, remain obscure.
Methods: Two complementary mouse models of Mitf and MiT deficiency were used: the Mitf systemic loss-of-function mutation, and B-cell specific MiT family inactivation via transgenic expression of a trans-dominant negative (TDN) protein (TDN-B).
Background: Few individuals with alcohol use disorders receive treatment. Primary care has been suggested as an arena for early treatment for these disorders.
Aim: To evaluate whether the presence of a specialized addiction nurse can increase alcohol-related physician consultations in a primary care setting.
Long-finned pilot whales (Globicephala melas) are the most frequently stranded cetaceans in the world; however, the predominant drivers of these events are poorly understood. In this study the levels of persistent organic pollutants from pilot whales stranded in North-east Iceland were quantified and compared to historical data and physical parameters to investigate whether contaminant load may have influenced the physiological state of stranded individuals, how these loads fluctuate with sex and age group, and if this is consistent with the literature. Historical comparison was also carried out to discern how pollutant contamination has changed throughout the past few decades.
View Article and Find Full Text PDFThe mild hypothermia response (MHR) maintains organismal homeostasis during cold exposure and is thought to be critical for the neuroprotection documented with therapeutic hypothermia. To date, little is known about the transcriptional regulation of the MHR. We utilize a forward CRISPR-Cas9 mutagenesis screen to identify the histone lysine methyltransferase SMYD5 as a regulator of the MHR.
View Article and Find Full Text PDFGlobal climate change is causing abiotic shifts such as higher air and ocean temperatures, and disappearing sea ice in Arctic ecosystems. These changes influence Arctic-breeding seabird foraging ecology by altering prey availability and selection, affecting individual body condition, reproductive success, and exposure to contaminants such as mercury (Hg). The cumulative effects of alterations to foraging ecology and Hg exposure may interactively alter the secretion of key reproductive hormones such as prolactin (PRL), important for parental attachment to eggs and offspring and overall reproductive success.
View Article and Find Full Text PDFBackground: Increasing evidence shows that lifestyle interventions can improve the symptoms, quality of life (QoL), and even overall survival of patients with cancer. Digital therapeutics (DTx) can help implement behavioral modifications and empower patients through education, lifestyle support, and remote symptom monitoring.
Objective: We aimed to test the feasibility of a DTx program for patients with cancer, as measured by engagement, retention, and acceptability.
Monitoring cognitive workload has the potential to improve both the performance and fidelity of human decision making. However, previous efforts towards discriminating further than binary levels (e.g.
View Article and Find Full Text PDFThe aim was to assess the feasibility of an intervention to reduce stigma among primary care and community healthcare staff in Beijing, China through a contact-based education intervention. Participants were randomly assigned to: (i) "education only" group, a lecture-based education; or (ii) "education and contact" group, lectures plus contact with people with lived experience of mental illness. Each participant completed an assessment of mental health stigma related: knowledge (mental health knowledge schedule, MAKS); attitudes (mental illness: clinicians' attitudes scale, MICA-4); and behavior (reported and intended behavior scale, RIBS) before and after the intervention, with follow up at 1 month and 3 months after the intervention.
View Article and Find Full Text PDFThe microphthalmia-associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as a molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here, we show that MITF directly represses the expression of genes associated with the extracellular matrix (ECM) and focal adhesion pathways in human melanoma cells as well as of regulators of epithelial-to-mesenchymal transition (EMT) such as CDH2, thus affecting cell morphology and cell-matrix interactions.
View Article and Find Full Text PDFDespite the important role that monozygotic twins have played in genetics research, little is known about their genomic differences. Here we show that monozygotic twins differ on average by 5.2 early developmental mutations and that approximately 15% of monozygotic twins have a substantial number of these early developmental mutations specific to one of them.
View Article and Find Full Text PDFNumerous inflammatory skin disorders display a high prevalence of itch. The Mas-related G protein coupled receptor X2 (MRGPRX2) has been shown to modulate itch by inducing non-IgE-mediated mast cell degranulation and the release of endogenous inducers of pruritus. Various substances collectively known as basic secretagogues, which include inflammatory peptides and certain drugs, can trigger MRGPRX2 and thereby induce pseudo-allergic reactions characterized by histamine and protease release as well as inflammation.
View Article and Find Full Text PDFWaldenström's macroglobulinemia (WM) is a non-Hodgkin lymphoma, resulting in antibody-secreting lymphoplasmacytic cells in the bone marrow and pathologies resulting from high levels of monoclonal immunoglobulin M (IgM) in the blood. Despite the key role for BLIMP1 in plasma cell maturation and antibody secretion, its potential effect on WM cell biology has not yet been explored. Here we provide evidence of a crucial role for BLIMP1 in the survival of cells from WM cell line models and further demonstrate that BLIMP1 is necessary for the expression of the histone methyltransferase EZH2 in both WM and multiple myeloma cell lines.
View Article and Find Full Text PDFBackground: Itch is an unpleasant sensation that can be debilitating, especially if it is chronic and of non-histaminergic origin, as treatment options are limited. Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor that also has the ability to induce a burning, non-histaminergic pruritus when exogenously administered, by activating the endothelin A receptor (ETR) on primary afferents. ET-1 is released endogenously by several cell-types found in the skin, including macrophages and keratinocytes.
View Article and Find Full Text PDFHumpback whale songs associated with breeding behaviors are increasingly reported outside of traditional low latitude breeding grounds. Songs from a subarctic feeding ground during the winter were quantitatively characterized to investigate the structure and temporal changes of the songs at such an atypical location. Recordings were collected from 26.
View Article and Find Full Text PDFSubcutaneous formalin injections are used as a model for tissue injury-induced pain where formalin induces pain and inflammation indirectly by crosslinking proteins and directly through activation of the transient receptor potential A1 receptor on primary afferents. Activation of primary afferents leads to both central and peripheral release of neurotransmitters. Mast cells are found in close proximity to peripheral sensory nerve endings and express receptors for neurotransmitters released by the primary afferents, contributing to the neuro/immune interface.
View Article and Find Full Text PDFCardiovascular measures have been found to be sensitive to task onset and offset, but are less sensitive to adjacent levels of increasing cognitive workload. A potential confound in the literature is the disregard of individual differences in cardiovascular reactivity. In particular, the individuals' working memory capacity (WMC) is likely to play a role in cardiovascular reactivity to workload.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
February 2018
The role of calcitonin gene-related peptide (CGRP) in visceral and somatic nociception is incompletely understood. CGRPα is highly expressed in sensory neurons of dorsal root ganglia and particularly in neurons that also express the transient receptor potential cation channel subfamily V member 1 (Trpv1). Therefore, we investigated changes in visceral and somatic nociception following deletion of CGRPα from the Trpv1-Cre population using the Cre/lox system.
View Article and Find Full Text PDFIntroduction: Sexual violence against children is a hidden problem. Medical examination and evaluation is needed to search for possible injuries, exclude infections, procure legal evidence and ensure the child´s welfare. We assessed medical evaluations done at Landspitali University Hospital and in the Reykjavik Children's House, a specialized clinic for childhood abuse cases.
View Article and Find Full Text PDFAllergic reactions can in severe cases induce a state of circulatory shock referred to as anaphylaxis. Histamine, the primary mediator of this condition, is released from immune cells, and, therefore, anaphylaxis has so far been considered an immune system disorder. However, we here show that the glutamatergic receptor mGluR7, expressed on a subpopulation of both peripheral and spinal cord neurons, controls histamine-induced communication through calcium-dependent autoinhibition with implications for anaphylaxis.
View Article and Find Full Text PDFThe songs of the male humpback whales have traditionally been associated with breeding activities at low latitude breeding grounds during winter. This study provides the first detailed analysis of humpback whale songs recorded in the subarctic waters of Iceland using passive acoustic recorders. Recordings were collected during three winter seasons: 2008-2009, 2009-2010, and 2011 during which singing was detected in all seasons.
View Article and Find Full Text PDFGerm cells are the precursors to the gametes that carry genetic and epigenetic information between human generations and generate a new individual. Because germ cells are specified early during embryogenesis, at the time of embryo implantation, they are inaccessible for research. Our understanding of their biology has therefore developed slowly since their identification over one hundred years ago.
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