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Cold Spring Harbor Perspectives in Medicine

Arthur J Cheng, Nicolas Place, HÃ¥kan Westerblad
The contractile function of skeletal muscle declines during intense or prolonged physical exercise, that is, fatigue develops. Skeletal muscle fibers fatigue acutely during highly intense exercise when they have to rely on anaerobic metabolism. Early stages of fatigue involve impaired myofibrillar function, whereas decreased Ca(2+) release from the sarcoplasmic reticulum (SR) becomes more important in later stages. SR Ca(2+) release can also become reduced with more prolonged, lower intensity exercise, and it is then related to glycogen depletion...
April 21, 2017: Cold Spring Harbor Perspectives in Medicine
Leonela Amoasii, Eric N Olson, Rhonda Bassel-Duby
Exercise represents an energetic challenge to whole-body homeostasis. In skeletal muscle, exercise activates a variety of signaling pathways that culminate in the nucleus to regulate genes involved in metabolism and contractility; however, much remains to be learned about the transcriptional effectors of exercise. Mediator is a multiprotein complex that links signal-dependent transcription factors and other transcriptional regulators with the basal transcriptional machinery, thereby serving as a transcriptional "hub...
April 21, 2017: Cold Spring Harbor Perspectives in Medicine
Giovanna Distefano, Bret H Goodpaster
A substantial loss of muscle mass and strength (sarcopenia), a decreased regenerative capacity, and a compromised physical performance are hallmarks of aging skeletal muscle. These changes are typically accompanied by impaired muscle metabolism, including mitochondrial dysfunction and insulin resistance. A challenge in the field of muscle aging is to dissociate the effects of chronological aging per se on muscle characteristics from the secondary influence of lifestyle and disease processes. Remarkably, physical activity and exercise are well-established countermeasures against muscle aging, and have been shown to attenuate age-related decreases in muscle mass, strength, and regenerative capacity, and slow or prevent impairments in muscle metabolism...
April 21, 2017: Cold Spring Harbor Perspectives in Medicine
Daniel J Green, Kurt J Smith
Physical activity has profound impacts on the vasculature in humans. Acute exercise induces immediate changes in artery function, whereas repeated episodic bouts of exercise induce chronic functional adaptation and, ultimately, structural arterial remodeling. The nature of these changes in function and structure are dependent on the characteristics of the training load and may be modulated by other factors such as exercise-induced inflammation and oxidative stress. The clinical implications of these physiological adaptations are profound...
April 21, 2017: Cold Spring Harbor Perspectives in Medicine
Xiaojun Liu, Colin Platt, Anthony Rosenzweig
Noncoding microRNAs (miRNAs) have emerged as central regulators of cardiac biology, modulating cardiac development and the response to pathological stress in disease. Although less well developed, emerging evidence suggests miRNAs are likely also important in the heart's response to the physiological stress of exercise. Given the well-recognized cardiovascular benefits of exercise, elucidating the contribution of miRNAs to this response has the potential not only to reveal novel aspects of cardiovascular biology but also to identify new targets for therapeutic intervention that may complement those discovered through studies of diseased hearts...
April 7, 2017: Cold Spring Harbor Perspectives in Medicine
Carole A Long, Fidel Zavala
Evidence accumulated through the years clearly indicates that antiparasite immune responses can efficiently control malaria parasite infection at all development stages, and under certain circumstances they can prevent parasite infection. Translating these findings into vaccines or immunotherapeutic interventions has been difficult in part because of the extraordinary biological complexity of this parasite, which has several developmental stages expressing unique sets of stage-specific genes and multiple antigens, most of which are antigenically diverse...
April 7, 2017: Cold Spring Harbor Perspectives in Medicine
Christoph Hoffmann, Cora Weigert
Exercise stimulates the release of proteins with autocrine, paracrine, or endocrine functions produced in skeletal muscle, termed myokines. Based on the current state of knowledge, the major physiological function of myokines is to protect the functionality and to enhance the exercise capacity of skeletal muscle. Myokines control adaptive processes in skeletal muscle by acting as paracrine regulators of fuel oxidation, hypertrophy, angiogenesis, inflammatory processes, and regulation of the extracellular matrix...
April 7, 2017: Cold Spring Harbor Perspectives in Medicine
Daniel E Neafsey, Sarah K Volkman
The first reference genome assembly for the Plasmodium falciparum malaria parasite was completed over a decade ago, and the impact of this and other genomic resources on malaria research has been significant. Genomic resources for other malaria parasites are being established, even as P. falciparum continues to be the focus of development of new genomic methods and applications. Here we review the impact and applications of genomic data on malaria research, and discuss future needs and directions as genomic data generation becomes less expensive and more decentralized...
April 7, 2017: Cold Spring Harbor Perspectives in Medicine
Charles Dai, Hannelore Heemers, Nima Sharifi
The androgen-signaling axis plays a pivotal role in the pathogenesis of prostate cancer. Since the landmark discovery by Huggins and Hodges, gonadal depletion of androgens has remained a mainstay of therapy for advanced disease. However, progression to castration-resistant prostate cancer (CRPC) typically follows and is largely the result of restored androgen signaling. Efforts to understand the mechanisms behind CRPC have revealed new insights into dysregulated androgen signaling and intratumoral androgen synthesis, which has ultimately led to the development of several novel androgen receptor (AR)-directed therapies for CRPC...
April 7, 2017: Cold Spring Harbor Perspectives in Medicine
Peter A Humphrey
This review focuses on histopathological aspects of carcinoma of the prostate. A tissue diagnosis of adenocarcinoma is often essential for establishing a diagnosis of prostate cancer, and the foundation for a tissue diagnosis is currently light microscopic examination of hematoxylin and eosin (H&E)-stained tissue sections. Markers detected by immunohistochemistry on tissue sections can support a diagnosis of adenocarcinoma that is primary in the prostate gland or metastatic. Histological variants of carcinoma of the prostate are important for diagnostic recognition of cancer or as clinicopathologic entities that have prognostic and/or therapeutic significance...
April 7, 2017: Cold Spring Harbor Perspectives in Medicine
Sara N Mitchell, Flaminia Catteruccia
Vectorial capacity is a mathematical approximation of the efficiency of vector-borne disease transmission, measured as the number of new infections disseminated per case per day by an insect vector. Multiple elements of mosquito biology govern their vectorial capacity, including survival, population densities, feeding preferences, and vector competence. Intriguingly, biological pathways essential to mosquito reproductive fitness directly or indirectly influence a number of these elements. Here, we explore this complex interaction, focusing on how the interplay between mating and blood feeding in female Anopheles not only shapes their reproductive success but also influences their ability to sustain Plasmodium parasite development...
April 7, 2017: Cold Spring Harbor Perspectives in Medicine
Lauren Gerard Koch, Steven L Britton
Large-scale epidemiological studies show that low exercise capacity is the highest risk factor for all-cause morbidity and mortality relative to other conditions including diabetes, hypertension, and obesity. This led us to formulate the energy transfer hypothesis (ETH): Variation in capacity for energy transfer is the central mechanistic determinant of the divide between disease and health. As a test of this hypothesis, we predicted that two-way selective breeding of genetically heterogeneous rats for low and high intrinsic treadmill running capacity (a surrogate for energy transfer) would also produce rats that differ for disease risks...
April 7, 2017: Cold Spring Harbor Perspectives in Medicine
Weibo Zhang, Pamela Crotty Yelick
The craniofacial complex is composed of fundamental components such as blood vessels and nerves, and also a variety of specialized tissues such as craniofacial bones, cartilages, muscles, ligaments, and the highly specialized and unique organs, the teeth. Together, these structures provide many functions including speech, mastication, and aesthetics of the craniofacial complex. Craniofacial defects not only influence the structure and function of the jaws and face, but may also result in deleterious psychosocial issues, emphasizing the need for rapid and effective, precise, and aesthetic reconstruction of craniofacial tissues...
March 27, 2017: Cold Spring Harbor Perspectives in Medicine
Sashka Dimitrievska, Laura E Niklason
Over the past 40 years, remarkable advances have been made in our understanding of successful blood vessel regeneration, starting with the failures of early tissue-engineered vascular grafts designed using isolated components or molecules, such as collagen gels. The vascular tissue engineers are today better educated and have steered ongoing research developments toward clinical developments of more complete vascular grafts that replicate the multitude of specialized arterial aspects required for function.
March 27, 2017: Cold Spring Harbor Perspectives in Medicine
Johnny Lam, Esther J Lee, Elisa C Clark, Antonios G Mikos
An avenue of tremendous interest and need in health care encompasses the regeneration of bone and cartilage. Over the years, numerous tissue engineering strategies have contributed substantial progress toward the realization of clinically relevant therapies. Cell and tissue culture protocols, however, show many variations that make experimental results among different publications challenging to compare. This collection surveys prevalent cell sources, soluble factors, culture medium formulations, environmental factors, and genetic modification approaches in the literature...
March 27, 2017: Cold Spring Harbor Perspectives in Medicine
Nolan J Hoffman
The application of global "-omics" technologies to exercise has introduced new opportunities to map the complexity and interconnectedness of biological networks underlying the tissue-specific responses and systemic health benefits of exercise. This review will introduce major research tracks and recent advancements in this emerging field, as well as critical gaps in understanding the orchestration of molecular exercise dynamics that will benefit from unbiased omics investigations. Furthermore, significant research hurdles that need to be overcome to effectively fill these gaps related to data collection, computation, interpretation, and integration across omics applications will be discussed...
March 27, 2017: Cold Spring Harbor Perspectives in Medicine
Jennifer K Lee, Jarrett M Link, Jerry C Y Hu, Kyriacos A Athanasiou
Tissue engineering strives to create neotissues capable of restoring function. Scaffold-free technologies have emerged that can recapitulate native tissue function without the use of an exogenous scaffold. This review will survey, in particular, the self-assembling and self-organization processes as scaffold-free techniques. Characteristics and benefits of each process are described, and key examples of tissues created using these scaffold-free processes are examined to provide guidance for future tissue-engineering developments...
March 27, 2017: Cold Spring Harbor Perspectives in Medicine
Roger M Enoka, Jacques Duchateau
The force exerted by a muscle during a voluntary contraction depends on the number of motor units recruited for the action and the rates at which they discharge action potentials (rate coding). Over most of the operating range of a muscle, the nervous system controls muscle force by varying both motor unit recruitment and rate coding. Except at relatively low forces, however, the control of muscle force depends primarily on rate coding, especially during fast contractions. This review provides five examples of how the modulation of rate coding influences the force exerted by muscle during voluntary actions...
March 27, 2017: Cold Spring Harbor Perspectives in Medicine
Sean L McGee, Ken R Walder
An acute bout of exercise is sufficient to induce changes in skeletal muscle gene expression that are ultimately responsible for the adaptive responses to exercise. Although much research has described the intracellular signaling responses to exercise that are linked to transcriptional regulation, the epigenetic mechanisms involved are only just emerging. This review will provide an overview of epigenetic mechanisms and what is known in the context of exercise. Additionally, we will explore potential interactions between metabolism during exercise and epigenetic regulation, which serves as a framework for potential areas for future research...
March 20, 2017: Cold Spring Harbor Perspectives in Medicine
Andrew Trecartin, Tracy Grikscheit
The intestine shows extraordinary regenerative potential that might be harnessed to alleviate numerous morbid and lethal human diseases. The intestinal stem cells regenerate the epithelium every 5 days throughout an individual's lifetime. Understanding stem-cell signaling affords power to influence the niche environment for growing intestine. The manifold approaches to tissue engineering may be organized by variations of three basic components required for the transplantation and growth of stem/progenitor cells: (1) cell delivery materials or scaffolds; (2) donor cells including adult stem cells, induced pluripotent stem cells, and in vitro expansion of isolated or cocultured epithelial, smooth muscle, myofibroblasts, or nerve cells; and (3) environmental modulators or biopharmaceuticals...
March 20, 2017: Cold Spring Harbor Perspectives in Medicine
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