Circadian clocks - the fall and rise of physiology

Circadian clocks control the daily life of most light-sensitive organisms - from cyanobacteria to humans. Molecular processes generate cellular rhythmicity, and cellular clocks in animals coordinate rhythms through interaction (known as coupling). This hierarchy of clocks generates a complex, approximately 24-hour temporal programme that is synchronized with the rotation of the Earth. The circadian system ensures anticipation and adaptation to daily environmental changes, and functions on different levels - from gene expression to behaviour. Circadian research is a remarkable example of interdisciplinarity, unravelling the complex mechanisms that underlie a ubiquitous biological programme. Insights from this research will help to optimize medical diagnostics and therapy, as well as adjust social and biological timing on the individual level.     

Making waves: the rise and fall and rise of quantitative developmental biology

The tenth annual RIKEN Center for Developmental Biology symposium 'Quantitative Developmental Biology' held in March 2012 covered a range of topics from coat colour patterning to the mechanics of morphogenesis. The studies presented shared a common theme in which a combination of physical theory, quantitative analysis and experiment was used to understand a specific cellular process in development. This report highlights these innovative studies and the long-standing questions in developmental biology that they seek to answer.     

The fall and rise of US inequities in premature mortality: 1960-2002

Background

Debates exist as to whether, as overall population health improves, the absolute and relative magnitude of income- and race/ethnicity-related health disparities necessarily increase—or derease. We accordingly decided to test the hypothesis that health inequities widen—or shrink—in a context of declining mortality rates, by examining annual US mortality data over a 42 year period.

Methods and Findings

Using US county mortality data from 1960–2002 and county median family income data from the 1960–2000 decennial censuses, we analyzed the rates of premature mortality (deaths among persons under age 65) and infant death (deaths among persons under age 1) by quintiles of county median family income weighted by county population size. Between 1960 and 2002, as US premature mortality and infant death rates declined in all county income quintiles, socioeconomic and racial/ethnic inequities in premature mortality and infant death (both relative and absolute) shrank between 1966 and 1980, especially for US populations of color; thereafter, the relative health inequities widened and the absolute differences barely changed in magnitude. Had all persons experienced the same yearly age-specific premature mortality rates as the white population living in the highest income quintile, between 1960 and 2002, 14% of the white premature deaths and 30% of the premature deaths among populations of color would not have occurred.

Conclusions

The observed trends refute arguments that health inequities inevitably widen—or shrink—as population health improves. Instead, the magnitude of health inequalities can fall or rise; it is our job to understand why.     

Foxa2: the rise and fall of dopamine neurons

Understanding the development and maintenance of dopamine neurons is essential to establish novel stem cell therapies and animal models of Parkinson's disease. A recent PLoS Biology report (Kittappa et al., 2007) reveals that Foxa2 regulates dopamine neuron generation and differentiation, and that aging foxa2(+/-) mice spontaneously develop Parkinsonism.     

Homing endonuclease genes: the rise and fall and rise again of a selfish element

Homing endonuclease genes (HEGs) are selfish genetic elements that spread by first cleaving chromosomes that do not contain them and then getting copied across to the broken chromosome as a byproduct of the repair process. The success of this strategy will depend on the opportunities for homing--in other words, the frequency with which HEG(+) and HEG(-) chromosomes come into contact--which varies widely among host taxa. HEGs are also unusual in that the selection pressure for endonuclease function disappears if they become fixed in a population, which makes them susceptible to degeneration and imposes a need for regular horizontal transmission between species. HEGs will be selected to reduce the harm done to the host organism, and this is expected to influence the evolution of their sequence specificity and maturase functions. HEGs may also be domesticated by their hosts, and are currently being put to human uses.     

The evolution of germs and the evolution of disease: some British debates, 1870-1900

The germ theory of disease famously brought a new notion of specificity into concepts of disease. At the same time, the work of Pasteur, Koch and their colleagues was developed during the same decades as Charles Darwin's theories of evolutionary biology challenged traditional notions of the essentialism of biological species. This essay examines some of the ways in which Darwin's work was invoked by British doctors seeking to explain clinical or epidemiological anomalies, in which infectious diseases did not appear to breed true.     

The choroid plexus in the rise, fall and repair of the brain

The choroid plexuses (CPs) are involved in the most-basic aspects of neural function including maintaining the extracellular milieu of the brain by actively modulating chemical exchange between the CSF and brain parenchyma, surveying the chemical and immunological status of the brain, detoxifying the brain, secreting a nutritive "cocktail" of polypeptides and participating in repair processes following trauma. This diversity of functions may mean that even modest changes in the CP can have far-reaching effects. Indeed, changes in the anatomy and physiology of the CP have been linked to aging and several CNS diseases. It is also possible that replacing diseased or transplanting healthy CP might be useful for treating acute and chronic brain diseases. This review focuses on the wide-ranging and under-appreciated functions of the CP, alterations of these functions in aging and neurodegeneration, and recent demonstrations of the therapeutic potential of transplanted CP for neural trauma.     

The rise and fall of the mangrove forests in Maputo Bay, Mozambique

The change in area of mangrove forests since 1958 in Maputo Bay,Mozambique was studied. Around Maputo, a 44% reduction of the area was linkedtodifferences in accessibility, the areas closest to Maputo suffering most. Butsurprisingly, large expansions of mangrove forest were also observed. Thisincrease in area (+ 13%) was accompanied by an increase in tree cover from55 to 70%. The overall effect of mangrove forest reduction and growth resultedin a mean decrease of only 8%. The causes of the increase in mangrove area onInhaca island are discussed, and two possible factors are suggested: a changeinsedimentation and an increase in temperature. Sandbanks have increased atInhacaIsland, but no data are available for the other areas. An increase in sea andair temperature has also been noted by other authors and could explain thegrowth of the forests, which are situated at the southernmost limit of theirnormal distribution.     

Health and disease at a South Carolina plantation: 1840-1870

The analysis of 36 human skeletons (eight subadults, 13 males, 15 females) recovered during a cemetery relocation near Charleston, SC, provides data on health and disease for a 19th-century sample of Afro-Americans. The majority of the burials date from 1840-1870. Skeletal analysis verified some historical interpretations. Gender differential in mortality is evident with average age at death for males 35 and females 40 years. Females, besides living longer, had more missing and carious teeth but fewer abscesses. Both genders expressed childhood metabolic stress as indicated by linear enamel hypoplasias. Males, however, had a higher incidence (92%) than did females (70%). Age at occurrence was more widely distributed for females, but ages 2-4 were most critical for both genders. Postcranial indications of recovery from acute stress, Harris lines, occurred more frequently for males (45%) than for females (18%). Anemia, probably both genetic and acquired, was a significant health problem for both genders. Cribra orbitalia appeared in 35% of the adult crania, and 80% of the subadults had orbital lesions. Diplotic expansion of the cranial vault and infection were relatively common in the sample. Skeletal reaction to infections appeared in 69% of the males, 60% of the females, and 80% of the subadults. Skeletal changes associated with demanding physical labor were ubiquitous. The shoulder and hip were especially affected by degenerative changes, the cervical vertebrae frequently expressed osteophytosis, and males show a preponderance of Schmorl herniations and hypertrophy of the ulnar supinator crest. Skeletal trace elements indicate a relatively high exposure to lead, strontium concentrations indicative of a diet high in plant foods, and relatively low zinc and copper concentrations.     

The fall and rise of the Oblong woodsia in Britain

Summary

The vegetation of a small spoil heap at Jerah mine near Stirling was classified as species-rich acid grassland, an open barren-soil community with a high frequency of the moss Pohlia nutans, and a group which showed intermediate characteristics. Copper was present in the soil in potentially toxic concentrations and when the vegetation data were ordinated the axes showed highly significant correlations with soil copper and loss-on-ignition. The results suggest that copper is a major determinant of the spoil-heap vegetation, and contrast sharply with those reported for the Burn of Sorrow mine, a site with many superficial similarities.     

Modelling and the fall and rise of the handicap principle

The story of the fall and rise of Zahavi??s handicap principle is one of a battle between models. Early attempts at formal modeling produced negative results and, unsurprisingly, scepticism about the principle. A major change came in 1990 with Grafen??s production of coherent models of a handicap mechanism of honest signalling. This paper??s first claim is that acceptance of the principle, and its dissemination into other disciplines, has been driven principally by that, and subsequent modeling, rather than by empirical results. Secondly, there is a vast literature on biological signalling but few studies that make all of the observations necessary to diagnose the handicap mechanism. My final claim is that many of the applications of ??costly signalling theory?? in other disciplines are conceptually confused. Misinterpretations of what is meant by ??costly signalling?? are common. Demonstrating that a signal is costly is insufficient and is not always necessary in order to prove that, and explain why, a signal is honest. In addition to the biological modelling of signals, there is an economic literature on the same subject. The two run in parallel in the sense that they have had little mutual interaction. Additionally, it is the biological modelling that has been picked up, and often misapplied, by other disciplines.     

Genetics of melanoma progression: the rise and fall of cell senescence

There are many links between cell senescence and the genetics of melanoma, meaning both familial susceptibility and somatic–genetic changes in sporadic melanoma. For example, CDKN2A, the best‐known melanoma susceptibility gene, encodes two effectors of cell senescence, while other familial melanoma genes are related to telomeres and their maintenance. This article aimed to analyze our current knowledge of the genetic or epigenetic driver changes necessary to generate a cutaneous metastatic melanoma, the commonest order in which these occur, and the relation of these changes to the biology and pathology of melanoma progression. Emphasis is laid on the role of cell senescence and the escape from senescence leading to cellular immortality, the ability to divide indefinitely.