Accumulating evidence suggests that many classes of DNA repeats exhibit attributes that distinguish them from other genetic variants, including the fact that they are more liable to mutation; this ...enables them to mediate genetic plasticity. The expansion of tandem repeats, particularly of short tandem repeats, can cause a range of disorders (including Huntington disease, various ataxias, motor neuron disease, frontotemporal dementia, fragile X syndrome and other neurological disorders), and emerging data suggest that tandem repeat polymorphisms (TRPs) can also regulate gene expression in healthy individuals. TRPs in human genomes may also contribute to the missing heritability of polygenic disorders. A better understanding of tandem repeats and their associated repeatome, as well as their capacity for genetic plasticity via both germline and somatic mutations, is needed to transform our understanding of the role of TRPs in health and disease.
Climate change affects the range of pathogens and temperatures to which populations are exposed. This article reviews the nature of these changes and explores how efforts to mitigate climate change ...could be of value to the global community.
The global scale, interconnectedness, and economic intensity of contemporary human activity are historically unprecedented,
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as are many of the consequent environmental and social changes. These global changes fundamentally influence patterns of human health, international health care, and public health activities.
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They constitute a syndrome, not a set of separate changes, that reflects the interrelated pressures, stresses, and tensions arising from an overly large world population, the pervasive and increasingly systemic environmental impact of many economic activities, urbanization, the spread of consumerism, and the widening gap between rich and poor both within and between countries.
In recent decades, international connectivity has . . .
Post-activation potentiation (PAP) is a well-described phenomenon with a short half-life (~28 s) that enhances muscle force production at submaximal levels of calcium saturation (i.e., submaximal ...levels of muscle activation). It has been largely explained by an increased myosin light chain phosphorylation occurring in type II muscle fibers, and its effects have been quantified in humans by measuring muscle twitch force responses to a bout of muscular activity. However, enhancements in (sometimes maximal) voluntary force production detected several minutes after high-intensity muscle contractions are also observed, which are also most prominent in muscles with a high proportion of type II fibers. This effect has been considered to reflect PAP. Nonetheless, the time course of myosin light chain phosphorylation (underpinning “classic” PAP) rarely matches that of voluntary force enhancement and, unlike PAP, changes in muscle temperature, muscle/cellular water content, and muscle activation may at least partly underpin voluntary force enhancement; this enhancement has thus recently been called post-activation performance enhancement (PAPE) to distinguish it from “classical” PAP. In fact, since PAPE is often undetectable at time points where PAP is maximal (or substantial), some researchers have questioned whether PAP contributes to PAPE under most conditions
in vivo
in humans. Equally, minimal evidence has been presented that PAP is of significant practical importance in cases where multiple physiological processes have already been upregulated by a preceding, comprehensive, active muscle warm-up. Given that confusion exists with respect to the mechanisms leading to acute enhancement of both electrically evoked (twitch force; PAP) and voluntary (PAPE) muscle function in humans after acute muscle activity, the first purpose of the present narrative review is to recount the history of PAP/PAPE research to locate definitions and determine whether they are the same phenomena. To further investigate the possibility of these phenomena being distinct as well as to better understand their potential functional benefits, possible mechanisms underpinning their effects will be examined in detail. Finally, research design issues will be addressed which might contribute to confusion relating to PAP/PAPE effects, before the contexts in which these phenomena may (or may not) benefit voluntary muscle function are considered.
Although they existed more than a millennium apart, the great civilizations of New Kingdom Egypt (ca. 1548–1086 BCE) and Han dynasty China (206 BCE–220 CE) shared intriguing similarities. ...Both were centered around major, flood-prone rivers—the Nile and the Yellow River—and established complex hydraulic systems to manage their power. Both spread their territories across vast empires that were controlled through warfare and diplomacy and underwent periods of radical reform led by charismatic rulers—the “heretic king” Akhenaten and the vilified reformer Wang Mang. Universal justice was dispensed through courts, and each empire was administered by bureaucracies staffed by highly trained scribes who held special status. Egypt and China each developed elaborate conceptions of an afterlife world and created games of fate that facilitated access to these realms. This groundbreaking volume offers an innovative comparison of these two civilizations. Through a combination of textual, art historical, and archaeological analyses, Ancient Egypt and Early China reveals shared structural traits of each civilization as well as distinctive features.
Polyamines are evolutionarily ancient polycations derived from amino acids and are pervasive in all domains of life. They are essential for cell growth and proliferation in eukaryotes and are ...essential, important or dispensable for growth in bacteria. Polyamines present a useful scaffold to attach other moieties to, and are often incorporated into specialized metabolism. Life has evolved multiple pathways to synthesize polyamines, and structural variants of polyamines have evolved in bacteria, archaea and eukaryotes. Among the complex biosynthetic diversity, patterns of evolutionary reiteration can be distinguished, revealing evolutionary recycling of particular protein folds and enzyme chassis. The same enzyme activities have evolved from multiple protein folds, suggesting an inevitability of evolution of polyamine biosynthesis. This review discusses the different biosynthetic strategies used in life to produce diamines, triamines, tetra-amines and branched and long-chain polyamines. It also discusses the enzymes that incorporate polyamines into specialized metabolites and attempts to place polyamine biosynthesis in an evolutionary context.
Polyamines are primordial polycations found in most cells and perform different functions in different organisms. Although polyamines are mainly known for their essential roles in cell growth and ...proliferation, their functions range from a critical role in cellular translation in eukaryotes and archaea, to bacterial biofilm formation and specialized roles in natural product biosynthesis. At first glance, the diversity of polyamine structures in different organisms appears chaotic; however, biosynthetic flexibility and evolutionary and ecological processes largely explain this heterogeneity. In this review, I discuss the biosynthetic, evolutionary, and physiological processes that constrain or expand polyamine structural and functional diversity.
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