Consumers often cite cognitive improvements as reasons for making dietary changes or using dietary supplements, a motivation that if leveraged could greatly enhance public health. However, rarely is it considered whether standardized cognitive tests that are used in nutrition research are aligned to outcomes of interest to the consumer. This knowledge gap presents a challenge to the scientific substantiation of nutrition-based cognitive health benefits.
View Article and Find Full Text PDFThe myelinated white matter tracts of the central nervous system (CNS) are essential for fast transmission of electrical impulses and are often differentially affected in human neurodegenerative diseases across CNS region, age and sex. We hypothesize that this selective vulnerability is underpinned by physiological variation in white matter glia. Using single nucleus RNA sequencing of human post-mortem white matter samples from the brain, cerebellum and spinal cord and subsequent tissue-based validation we found substantial glial heterogeneity with tissue region: we identified region-specific oligodendrocyte precursor cells (OPCs) that retain developmental origin markers into adulthood, distinguishing them from mouse OPCs.
View Article and Find Full Text PDFObjectives: How Right Now (HRN) is an evidence-based, culturally responsive communication campaign developed to facilitate coping and resilience among US groups disproportionately affected by the COVID-19 pandemic. To inform the development of this campaign, we examined patterns in emotional health, stress, and coping strategies among HRN's audiences, focusing on differences among racial and ethnic groups.
Methods: We used a national probability panel, AmeriSpeak, to collect survey data from HRN's priority audience members in English and Spanish at 2 time points (May 2020 and May 2021).
The leucine-rich glioma-inactivated (LGI) family consists of four highly conserved paralogous genes, LGI1-4, that are highly expressed in mammalian central and/or peripheral nervous systems. LGI1 antibodies are detected in subjects with autoimmune limbic encephalitis and peripheral nerve hyperexcitability syndromes (PNHSs) such as Isaacs and Morvan syndromes. Pathogenic variations of LGI1 and LGI4 are associated with neurological disorders as disease traits including familial temporal lobe epilepsy and neurogenic arthrogryposis multiplex congenita 1 with myelin defects, respectively.
View Article and Find Full Text PDFEpithelial cells migrate across wounds to repair injured tissue. Leader cells at the front of migrating sheets often drive this process. However, it is unclear how leaders emerge from an apparently homogeneous epithelial cell population.
View Article and Find Full Text PDFAfter nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes significant clinical problems.
View Article and Find Full Text PDFRegeneration capacity is reduced as CNS axons mature. Using laser-mediated axotomy, proteomics and puromycin-based tagging of newly-synthesized proteins in a human embryonic stem cell-derived neuron culture system that allows isolation of axons from cell bodies, we show here that efficient regeneration in younger axons (d45 in culture) is associated with local axonal protein synthesis (local translation). Enhanced regeneration, promoted by co-culture with human glial precursor cells, is associated with increased axonal synthesis of proteins, including those constituting the translation machinery itself.
View Article and Find Full Text PDFTraumatology (Tallahass Fla)
January 2021
The How Right Now communication initiative (HRN) was developed to facilitate resilience amid the COVID-19 pandemic in the United States. HRN was designed as a conduit for promoting mental health and addressing feelings of grief, worry, and stress experienced during this time. This article provides an overview of the rapid, mixed-method, culturally responsive formative research process undertaken to inform the development of HRN.
View Article and Find Full Text PDFPurpose: Validation of transcranial direct current stimulation (tDCS) to treat obesity is hampered by evidence that participants can distinguish real from the traditional-control condition. Correctly guessing the real condition precludes knowing if it is neuromodulation or expectation that suppresses food craving and eating. Therefore, this study tested the putative efficacy of tDCS to the dorsolateral prefrontal cortex (DLPFC) to reduce food craving and eating when an alternative control condition was used that would be difficult to distinguish from the real condition.
View Article and Find Full Text PDFCell lineage reprogramming via transgene overexpression of key master regulatory transcription factors has been well documented. However, the poor efficiency and lack of fidelity of this approach is problematic. Synthetic transcription factors (sTFs)-built from the repurposed CRISPR/Cas9 system-can activate endogenous target genes to direct differentiation or trigger lineage reprogramming.
View Article and Find Full Text PDFTranscranial direct current stimulation (tDCS) is a neuromodulation technique with potential to treat eating disorders and obesity. As for any potential treatment, it is important to assess the degree to which expectation effects contribute to its reported efficacy. This study assessed the effect of tDCS on amount of food craving and eating while tightly controlling treatment expectation.
View Article and Find Full Text PDFSchwann cell c-Jun is implicated in adaptive and maladaptive functions in peripheral nerves. In injured nerves, this transcription factor promotes the repair Schwann cell phenotype and regeneration and promotes Schwann-cell-mediated neurotrophic support in models of peripheral neuropathies. However, c-Jun is associated with tumor formation in some systems, potentially suppresses myelin genes, and has been implicated in demyelinating neuropathies.
View Article and Find Full Text PDFJ Neurosci
September 2017
Cell competition is a quality control mechanism that eliminates unfit cells. How cells compete is poorly understood, but it is generally accepted that molecular exchange between cells signals elimination of unfit cells. Here we report an orthogonal mechanism of cell competition, whereby cells compete through mechanical insults.
View Article and Find Full Text PDFUnderstanding cells as integrated systems requires that we systematically decipher how single genes affect multiple biological processes and how processes are functionally linked. Here, we used multiprocess phenotypic profiling, combining high-resolution 3D confocal microscopy and multiparametric image analysis, to simultaneously survey the fission yeast genome with respect to three key cellular processes: cell shape, microtubule organization, and cell-cycle progression. We identify, validate, and functionally annotate 262 genes controlling specific aspects of those processes.
View Article and Find Full Text PDFThe ADAMTS proteinases are a family of secreted, matrix-associated enzymes that have diverse roles in the regulation of tissue organization and vascular homeostasis. Several of the 19 human family members have been identified as having either tumor promoting or suppressing roles. We previously demonstrated that decreased ADAMTS15 expression correlated with a worse clinical outcome in mammary carcinoma (e.
View Article and Find Full Text PDFWithin tissues, cells sense differences in fitness levels and this can lead to fitter cells eliminating less fit, albeit viable, cells via competitive cell interactions. The involvement of several cancer-related genes in this phenomenon has drawn attention to a potential connection between competitive cell interactions and cancer. Indeed, initial studies found that tumor-promoting genes can turn cells into 'supercompetitors', able to kill normal cells around them.
View Article and Find Full Text PDFEssays Biochem
December 2012
During cell competition fitter cells take over the tissue at the expense of viable, but less fit, cells, which are eliminated by induction of apoptosis or senescence. This probably acts as a quality-control mechanism to eliminate suboptimal cells and safeguard organ function. Several experimental conditions have been shown to trigger cell competition, including differential levels in ribosomal activity or in signalling pathway activation between cells, although it is unclear how those differences are sensed and translated into fitness levels.
View Article and Find Full Text PDFThe original notion that matrix metalloproteinases (MMPs) act as tumour and metastasis-promoting enzymes by clearing a path for tumour cells to invade and metastasize has been challenged in the last decade. It has become clear that MMPs are involved in numerous steps of tumour progression and metastasis, and hence are now considered to be multifaceted proteases. Moreover, more recent experimental evidence indicates that some members of the MMP family behave as tumour-suppressor enzymes and should therefore be regarded as anti-targets in cancer therapy.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2011
The human ADAMTS (a disintegrin and metalloproteinase with thrombospondin-like motifs) family of 19 secreted, multidomain proteolytic enzymes is involved in a wide range of biological processes including ECM assembly and degradation, hemostasis, organogenesis and the regulation of angiogenesis. Defects in certain family members give rise to inherited human genetic diseases, while aberrant expression of other ADAMTSs has been linked to the pathogenesis of arthritis and cancer. Several ADAMTSs act as tumor or metastasis suppressors whose functions are lost either by mutation or epigenetic silencing during tumor progression.
View Article and Find Full Text PDFMaspin is a member of the serine protease inhibitor (serpin) superfamily that lacks protease inhibitory ability, although displaying tumor metastasis-suppressing activity resulting from its influence on cell migration, invasion, proliferation, apoptosis, and adhesion. The molecular mechanisms of these actions of maspin are as yet undefined. Here, we sought to identify critical functional motifs by the expression of maspin with point mutations at sites potentially involved in protein-protein interactions: the G α-helix (G-helix), an internal salt bridge or the P1 position of the reactive center loop.
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