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Managing Male Ageing
Men are living longer today but many find that they do not have the energy or capability to enjoy this extra bit of life. Advancing age does not mean having to slow down because one is older. With knowledge, awareness and better care of his body, a man can extend his physical, mental and sexual capability and have so many more fulfilling and active years. Men and Health: Getting More Out of Life is about healthy aging in men; it is not a book about diseases. It examines the problems that affect a man's quality of life and how to deal with them. Covering general aspects of aging and andropause, sexual problems like erectile dysfunction, physical problems like urinary issues and common concerns like balding, weak bones, obesity, poor vision and hearing, as well as memory loss, it is a book with all the information men need to stay healthy and get more life out of their years.
eBook
Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids
Responding to the expansion of scientific knowledge about the roles of nutrients in human health, the Institute of Medicine has developed a new approach to establish Recommended Dietary Allowances (RDAs) and other nutrient reference values. The new title for these values Dietary Reference Intakes (DRIs), is the inclusive name being given to this new approach. These are quantitative estimates of nutrient intakes applicable to healthy individuals in the United States and Canada. This new book is part of a series of books presenting dietary reference values for the intakes of nutrients. It establishes recommendations for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. This book presents new approaches and findings which include the following:
The establishment of Estimated Energy Requirements at four levels of energy expenditure
Recommendations for levels of physical activity to decrease risk of chronic disease
The establishment of RDAs for dietary carbohydrate and protein
The development of the definitions of Dietary Fiber, Functional Fiber, and Total Fiber
The establishment of Adequate Intakes (AI) for Total Fiber
The establishment of AIs for linolenic and a-linolenic acids
Acceptable Macronutrient Distribution Ranges as a percent of energy intake for fat, carbohydrate, linolenic and a-linolenic acids, and protein
Research recommendations for information needed to advance understanding of macronutrient requirements and the adverse effects associated with intake of higher amounts
Also detailed are recommendations for both physical activity and energy expenditure to maintain health and decrease the risk of disease.
eBook
Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility
The gastrointestinal tract is the only internal organ to have evolved with its own independent nervous system, known as the enteric nervous system (ENS). This Review provides an update on advances that have been made in our understanding of how neurons within the ENS coordinate sensory and motor functions. Understanding this function is critical for determining how deficits in neurogenic motor patterns arise. Knowledge of how distension or chemical stimulation of the bowel evokes sensory responses in the ENS and central nervous system have progressed, including critical elements that underlie the mechanotransduction of distension-evoked colonic peristalsis. Contrary to original thought, evidence suggests that mucosal serotonin is not required for peristalsis or colonic migrating motor complexes, although it can modulate their characteristics. Chemosensory stimuli applied to the lumen can release substances from enteroendocrine cells, which could subsequently modulate ENS activity. Advances have been made in optogenetic technologies, such that specific neurochemical classes of enteric neurons can be stimulated. A major focus of this Review will be the latest advances in our understanding of how intrinsic sensory neurons in the ENS detect and respond to sensory stimuli and how these mechanisms differ from extrinsic sensory nerve endings in the gut that underlie the gut–brain axis.The enteric nervous system (ENS) is essential for life and controls the function of the gastrointestinal tract. Here, an overview of sensory transduction and neural circuits in the ENS is provided, yielding insights into the generation of gastrointestinal motility.
Journal Article
Motor learning promotes remyelination via new and surviving oligodendrocytes
Oligodendrocyte loss in neurological disease leaves axons vulnerable to damage and degeneration, and activity-dependent myelination may represent an endogenous mechanism to improve remyelination following injury. Here we report that, while learning a forelimb reach task transiently suppresses oligodendrogenesis, it subsequently increases oligodendrocyte precursor cell differentiation, oligodendrocyte generation and myelin sheath remodeling in the forelimb motor cortex. Immediately following demyelination, neurons exhibit hyperexcitability, learning is impaired and behavioral intervention provides no benefit to remyelination. However, partial remyelination restores neuronal and behavioral function, allowing learning to enhance oligodendrogenesis, remyelination of denuded axons and the ability of surviving oligodendrocytes to generate new myelin sheaths. Previously considered controversial, we show that sheath generation by mature oligodendrocytes is not only possible but also increases myelin pattern preservation following demyelination, thus presenting a new target for therapeutic interventions. Together, our findings demonstrate that precisely timed motor learning improves recovery from demyelinating injury via enhanced remyelination from new and surviving oligodendrocytes.Precisely timed motor learning promotes remyelination in the motor cortex by enhancing oligodendrogenesis and stimulating mature oligodendrocytes to generate new myelin, presenting mature oligodendrocytes as new targets in remyelinating therapies.
Journal Article
KDM5 histone demethylases repress immune response via suppression of STING
Cyclic GMP-AMP (cGAMP) synthase (cGAS) stimulator of interferon genes (STING) senses pathogen-derived or abnormal self-DNA in the cytosol and triggers an innate immune defense against microbial infection and cancer. STING agonists induce both innate and adaptive immune responses and are a new class of cancer immunotherapy agents tested in multiple clinical trials. However, STING is commonly silenced in cancer cells via unclear mechanisms, limiting the application of these agonists. Here, we report that the expression of STING is epigenetically suppressed by the histone H3K4 lysine demethylases KDM5B and KDM5C and is activated by the opposing H3K4 methyltransferases. The induction of STING expression by KDM5 blockade triggered a robust interferon response in a cytosolic DNA-dependent manner in breast cancer cells. This response resulted in resistance to infection by DNA and RNA viruses. In human tumors, KDM5B expression is inversely associated with STING expression in multiple cancer types, with the level of intratumoral CD8+ T cells, and with patient survival in cancers with a high level of cytosolic DNA, such as human papilloma virus (HPV)-positive head and neck cancer. These results demonstrate a novel epigenetic regulatory pathway of immune response and suggest that KDM5 demethylases are potential targets for antipathogen treatment and anticancer immunotherapy.
Journal Article
Investigating Age-related changes in fine motor control across different effectors and the impact of white matter integrity
Changes in fine motor control that eventually compromise dexterity accompany advanced age; however there is evidence that age-related decline in motor control may not be uniform across effectors. Particularly, the role of central mechanisms in effector-specific decline has not been examined but is relevant for placing age-related motor declines into the growing literature of age-related changes in brain function. We examined sub-maximal force control across three different effectors (fingers, lips, and tongue) in 18 young and 14 older adults. In parallel with the force variability measures we examined changes in white matter structural integrity in effector-specific pathways in the brain with diffusion tensor imaging (DTI). Motor pathways for each effector were identified by using an fMRI localizer task followed by tractography to identify the fiber tracts propagating to the midbrain. Increases in force control variability were found with age in all three effectors but the effectors showed different degrees of age-related variability. Motor control changes were accompanied by a decline in white matter structural integrity with age shown by measures of fractional anisotropy and radial diffusivity. The DTI metrics appear to mediate some of the age-related declines in motor control. Our findings indicate that the structural integrity of descending motor systems may play a significant role in age-related increases in motor performance variability, but that differential age-related declines in oral and manual effectors are not likely due to structural integrity of descending motor pathways in the brain.
•Oral and manual fine-motor performance of young and old adults were compared•Obtained DTI neural integrity measures specific to oral and manual effectors•Effector-specific age related declines in motor control were observed•Age-related motor control declines were correlated to changes in neuronal structure•White matter integrity did not predict differential decline among the effectors
Journal Article
Satellite cells, the engines of muscle repair
Satellite cells are a heterogeneous population of stem and progenitor cells with crucial roles in muscle repair and regeneration. Although paired-box 7 (PAX7) is necessary to maintain the undifferentiated stem cell state, a requirement for PAX7 in adult satellite cells was recently challenged and remains controversial.
Satellite cells are a heterogeneous population of stem and progenitor cells that are required for the growth, maintenance and regeneration of skeletal muscle. The transcription factors paired-box 3 (PAX3) and PAX7 have essential and overlapping roles in myogenesis. PAX3 acts to specify embryonic muscle precursors, whereas PAX7 enforces the satellite cell myogenic programme while maintaining the undifferentiated state. Recent experiments have suggested that PAX7 is dispensable in adult satellite cells. However, these findings are controversial, and the issue remains unresolved.
Journal Article
First spikes in ensembles of human tactile afferents code complex spatial fingertip events
It is generally assumed that primary sensory neurons transmit information by their firing rates. However, during natural object manipulations, tactile information from the fingertips is used faster than can be readily explained by rate codes. Here we show that the relative timing of the first impulses elicited in individual units of ensembles of afferents reliably conveys information about the direction of fingertip force and the shape of the surface contacting the fingertip. The sequence in which different afferents initially discharge in response to mechanical fingertip events provides information about these events faster than the fastest possible rate code and fast enough to account for the use of tactile signals in natural manipulation.
Journal Article