DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes

Recurrent chromosomal translocations underlie both haematopoietic and solid tumours. Their origin has been ascribed to selection of random rearrangements, targeted DNA damage, or frequent nuclear interactions between translocation partners; however, the relative contribution of each of these elements has not been measured directly or on a large scale. Here we examine the role of nuclear architecture and frequency of DNA damage in the genesis of chromosomal translocations by measuring these parameters simultaneously in cultured mouse B lymphocytes. In the absence of recurrent DNA damage, translocations between Igh or Myc and all other genes are directly related to their contact frequency. Conversely, translocations associated with recurrent site-directed DNA damage are proportional to the rate of DNA break formation, as measured by replication protein A accumulation at the site of damage. Thus, non-targeted rearrangements reflect nuclear organization whereas DNA break formation governs the location and frequency of recurrent translocations, including those driving B-cell malignancies.     

A spectrograph for exoplanet observations calibrated at the centimetre-per-second level

The best spectrographs are limited in stability by their calibration light source. Laser frequency combs are the ideal calibrators for astronomical spectrographs. They emit a spectrum of lines that are equally spaced in frequency and that are as accurate and stable as the atomic clock relative to which the comb is stabilized. Absolute calibration provides the radial velocity of an astronomical object relative to the observer (on Earth). For the detection of Earth-mass exoplanets in Earth-like orbits around solar-type stars, or of cosmic acceleration, the observable is a tiny velocity change of less than 10 cm s(-1), where the repeatability of the calibration--the variation in stability across observations--is important. Hitherto, only laboratory systems or spectrograph calibrations of limited performance have been demonstrated. Here we report the calibration of an astronomical spectrograph with a short-term Doppler shift repeatability of 2.5 cm s(-1), and use it to monitor the star HD 75289 and recompute the orbit of its planet. This repeatability should make it possible to detect Earth-like planets in the habitable zone of star or even to measure the cosmic acceleration directly.     

A large dust/ice ratio in the nucleus of comet 9P/Tempel 1

Comets spend most of their life in a low-temperature environment far from the Sun. They are therefore relatively unprocessed and maintain information about the formation conditions of the planetary system, but the structure and composition of their nuclei are poorly understood. Although in situ and remote measurements have derived the global properties of some cometary nuclei, little is known about their interiors. The Deep Impact mission shot a projectile into comet 9P/Tempel 1 in order to investigate its interior. Here we report the water vapour content (1.5 10(32) water molecules or 4.5 10(6) kg) and the cross-section of the dust (330 km2 assuming an albedo of 0.1) created by the impact. The corresponding dust/ice mass ratio is probably larger than one, suggesting that comets are 'icy dirtballs' rather than 'dirty snowballs' as commonly believed. High dust velocities (between 110 m s(-1) and 300 m s(-1)) imply acceleration in the comet's coma, probably by water molecules sublimated by solar radiation. We did not find evidence of enhanced activity of 9P/Tempel 1 in the days after the impact, suggesting that in general impacts of meteoroids are not the cause of cometary outbursts.     

Travelling waves in the occurrence of dengue haemorrhagic fever in Thailand

Dengue fever is a mosquito-borne virus that infects 50-100 million people each year. Of these infections, 200,000-500,000 occur as the severe, life-threatening form of the disease, dengue haemorrhagic fever (DHF). Large, unanticipated epidemics of DHF often overwhelm health systems. An understanding of the spatial-temporal pattern of DHF incidence would aid the allocation of resources to combat these epidemics. Here we examine the spatial-temporal dynamics of DHF incidence in a data set describing 850,000 infections occurring in 72 provinces of Thailand during the period 1983 to 1997. We use the method of empirical mode decomposition to show the existence of a spatial-temporal travelling wave in the incidence of DHF. We observe this wave in a three-year periodic component of variance, which is thought to reflect host-pathogen population dynamics. The wave emanates from Bangkok, the largest city in Thailand, moving radially at a speed of 148 km per month. This finding provides an important starting point for detecting and characterizing the key processes that contribute to the spatial-temporal dynamics of DHF in Thailand.     

In front of a mirror: visual displays may not be aggressive signals in nocturnal tree frogs

Some evidence indicates that in anuran amphibians, visual signalling can be important during social interactions such as territorial disputes among males, especially in diurnal species. The correct identification of a signal is not a trivial matter. A visual signal provides a visual cue during a social interaction, and to be effective it must elicit an immediate response in the receiver. We tested the hypothesis that visual displays in an agonistic context constitute aggressive signals, in three nocturnal species of Hylidae. We predicted that the production of visual displays would increase in the presence of a conspecific intruder male. Males of Hypsiboas raniceps, Dendropsophus nanus and Lysapsus limellum were submitted to two treatments: (1) Self Image, a reflection in a mirror, simulating the presence of an intruder; and (2) Control, a black rectangle covering the mirror. We observed three visual displays: vocal-sac display (inflate the vocal sac and maintain it inflated for some time), limb lifting (rapid up-and-down movements of one or more limbs), and toe/finger trembling (rapid up-and-down movements of one or more toes and/or fingers). This last display was observed only in H. raniceps males. Contrary to our hypothesis, the emission rates of all visual displays of the focal animals did not differ between treatments; and the behavioural response did not differ among species. Therefore, we suggest that these behaviours could not be used directly for communication in agonistic contexts, and may represent displacement activities (involuntary responses). Alternatively, an aggressive bimodal stimulus may be necessary to trigger a behavioural response by using visual signals during territory defence in these three species.     

Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study

Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14?years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.     

Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila

Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae), Caenorhabditis elegans and Drosophila melanogaster. Studies of the effects of genes on ageing are vulnerable to confounding effects of genetic background. Here we re-examined the reported effects of sirtuin overexpression on ageing and found that standardization of genetic background and the use of appropriate controls abolished the apparent effects in both C. elegans and Drosophila. In C. elegans, outcrossing of a line with high-level sir-2.1 overexpression abrogated the longevity increase, but did not abrogate sir-2.1 overexpression. Instead, longevity co-segregated with a second-site mutation affecting sensory neurons. Outcrossing of a line with low-copy-number sir-2.1 overexpression also abrogated longevity. A Drosophila strain with ubiquitous overexpression of dSir2 using the UAS-GAL4 system was long-lived relative to wild-type controls, as previously reported, but was not long-lived relative to the appropriate transgenic controls, and nor was a new line with stronger overexpression of dSir2. These findings underscore the importance of controlling for genetic background and for the mutagenic effects of transgene insertions in studies of genetic effects on lifespan. The life-extending effect of dietary restriction on ageing in Drosophila has also been reported to be dSir2 dependent. We found that dietary restriction increased fly lifespan independently of dSir2. Our findings do not rule out a role for sirtuins in determination of metazoan lifespan, but they do cast doubt on the robustness of the previously reported effects of sirtuins on lifespan in C. elegans and Drosophila.     

In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche

Stem cells reside in a specialized regulatory microenvironment or niche, where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity. The niche may also protect stem cells from environmental insults including cytotoxic chemotherapy and perhaps pathogenic immunity. The testis, hair follicle and placenta are all sites of residence for stem cells and are immune-suppressive environments, called immune-privileged sites, where multiple mechanisms cooperate to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression. We sought to determine if somatic stem-cell niches more broadly are immune-privileged sites by examining the haematopoietic stem/progenitor cell (HSPC) niche in the bone marrow, a site where immune reactivity exists. We observed persistence of HSPCs from allogeneic donor mice (allo-HSPCs) in non-irradiated recipient mice for 30?days without immunosuppression with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T (T(reg)) cells. High-resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with T(reg) cells that accumulated on the endosteal surface in the calvarial and trabecular bone marrow. T(reg) cells seem to participate in creating a localized zone where HSPCs reside and where T(reg) cells are necessary for allo-HSPC persistence. In addition to processes supporting stem-cell function, the niche will provide a relative sanctuary from immune attack.