Centenarians today: New insights on selection from the 5-COOP study

The number of oldest old grew tremendously over the past few decades. However, recent studies have disclosed that the pace of increase strongly varies among countries. The present study aims to specify the level of mortality selection among the nonagenarians and centenarians living currently in five low mortality countries, Denmark, France, Japan, Switzerland, and Sweden, part of the 5-Country Oldest Old Project (5-COOP). All data come from the Human Mortality Database, except for the number of centenarians living in Japan. We disclosed three levels of mortality selection, a milder level in Japan, a stronger level in Denmark and Sweden and an intermediary level in France and Switzerland. These divergences offer an opportunity to study the existence of a trade-off between the level of mortality selection and the functional health status of the oldest old survivors which will be seized by the 5-COOP project. © 2010 Jean-Marie Robine et al.published_or_final_versio

The nuclear cofactor receptor interacting protein-140 (RIP140) regulates the expression of genes involved in A beta generation

The receptor interacting protein-140 (RIP140) is a cofactor for several nuclear receptors and has been involved in the regulation of metabolic and inflammatory genes. We hypothesize that RIP140 may also affect Aβ generation because it modulates the activity of transcription factors previously implicated in amyloid precursor protein (APP) processing, such as peroxisome proliferator-activated receptor-γ (PPARγ). We found that the levels of RIP140 are reduced in Alzheimer's disease (AD) postmortem brains compared with healthy controls. In addition, in situ hybridization experiments revealed that RIP140 expression is enriched in the same brain areas involved in AD pathology, such as cortex and hippocampus. Furthermore, we provide evidence using cell lines and genetically modified mice that RIP140 is able to modulate the transcription of certain genes involved in AD pathology, such as β-APP cleaving enzyme (BACE1) and GSK3. Consequently, we found that RIP140 overexpression reduced the generation of Aβ in a neuroblastoma cell line by decreasing the transcription of β-APP cleaving enzyme via a PPARγ–dependent mechanism. The results of this study therefore provide molecular insights into common signaling pathways linking metabolic disease with AD

Resolving the human remains crisis in British archaeology

Human remains are a fundamental part of the archaeological record, offering unique insights into the lives of individuals and populations in the past. Like many archaeological materials human remains require distinctive and specialised methods of recovery, analysis and interpretation, while technological innovations and the accumulation of expertise have enabled archaeologists to extract ever greater amounts of information from assemblages of skeletal material. Alongside analyses of new finds, these advances have consistently thrown new light on existing collections of human remains in museums, universities and other institutions. Given the powerful emotional, social and religious meanings attached to the dead body, it is perhaps unsurprising that human remains pose a distinctive set of ethical questions for archaeologists. With the rise of indigenous rights movements and the emergence of post-colonial nations the acquisition and ownership of human remains became a divisive and politically loaded issue. It became increasingly clear that many human remains in museum collections around the world represented the traces of colonial exploitation and discredited pseudo-scientific theories of race. In the light of these debates and changing attitudes, some human remains were returned or repatriated to their communities of origin, a process which continues to this day. Recently a new set of challenges to the study of human remains has emerged from a rather unexpected direction: the British government revised its interpretation of nineteenth-century burial legislation in a way that would drastically curtail the ability of archaeologists to study human remains of any age excavated in England and Wales. This paper examines these extraordinary events and the legal, political and ethical questions that they raise

Genome sequence, population history, and pelage genetics of the endangered African wild dog (Lycaon pictus)

BACKGROUND: The African wild dog (Lycaon pictus) is an endangered sub-Saharan canid threatened by severe habitat fragmentation, human-wildlife conflict, and infectious disease. A highly specialized carnivore, it is distinguished by its social structure, dental morphology, absence of dewclaws, and colorful pelage. RESULTS: We sequenced the genomes of two individuals from populations representing two distinct ecological histories (Laikipia County, Kenya and KwaZulu-Natal Province, South Africa). We reconstructed population demographic histories for the two individuals and scanned the genomes for evidence of selection. CONCLUSIONS: We show that the African wild dog has undergone at least two effective population size reductions in the last one million years. We found evidence of Lycaon individual-specific regions of low diversity, suggestive of inbreeding or population-specific selection. Further research is needed to clarify whether these population reductions and low diversity regions are characteristic of the species as a whole. We documented positive selection on the Lycaon mitochondrial genome. Finally, we identified several candidate genes (ASIP, MITF, MLPH, PMEL) that may play a role in the characteristic Lycaon pelage

Hungry for change: the Sydney Food Fairness Alliance

The Sydney Food Fairness Alliance is one of a growing number of nascent food movements in Australia to have emerged out of concern for the country’s food future, as well as the deleterious effect the present food system is having on its citizens’ health and the continent’s fragile environment. The Alliance’s structure and activities clearly position it as a new social movement (NSM) engaged in collective action on a specific issue, in this instance, food security/justice, and operating outside the political sphere while aiming to influence and affect societal change. Food security as a human right lies at the heart of the Alliance’s philosophy, and equitable, sustainable food policies for New South Wales are a core focus of its advocacy work. The authors argue that the Alliance is a distinctive food movement in that it positions itself as an \u27umbrella\u27 organization representing a wide range of stakeholders in the food system. This chapter reflects on the values, achievements, issues of concern, strengths and weaknesses, and future of the Sydney Food Fairness Alliance. This resource is Chapter 8 in \u27Food Security in Australia: Challenges and Prospects for the Future\u27 published by Springer in 2013

The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals

Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of the epidermal growth factor-like family of growth factors. Although several studies indicate a role for RIP140 in breast cancer, its role in the development of the mammary gland is unclear. By using RIP140-null and RIP140 transgenic mice, we demonstrate that RIP140 is an essential factor for normal mammary gland development and that it functions by mediating oestrogen signalling. RIP140-null mice exhibit minimal ductal elongation with no side-branching, whereas RIP140-overexpressing mice show increased cell proliferation and ductal branching with age. Tissue recombination experiments demonstrate that RIP140 expression is required in both the mammary epithelial and stromal compartments for ductal elongation during puberty and that loss of RIP140 leads to a catastrophic loss of the mammary epithelium, whereas RIP140 overexpression augments the mammary basal cell population and shifts the progenitor/differentiated cell balance within the luminal cell compartment towards the progenitors. For the first time, we present a genome-wide global view of oestrogen receptor-α (ERα) binding events in the developing mammary gland, which unravels 881 ERα binding sites. Unbiased evaluation of several ERα binding sites for RIP140 co-occupancy reveals selectivity and demonstrates that RIP140 acts as a co-regulator with ERα to regulate directly the expression of amphiregulin (Areg), the progesterone receptor (Pgr) and signal transducer and activator of transcription 5a (Stat5a), factors that influence key mitogenic pathways that regulate normal mammary gland development

Stereotactically guided breast biopsy: a review

The aims of this review are to compare and contrast the available stereotactic equipment, and to describe the variety of needle types used and their affect on pathological results and subsequent patient management. Initial stereotactic devices were “added-on” to analogue mammography units and have been replaced by prone or ducubitus equipment using digital image acquisition. Biopsies use either 14-G core biopsy (CB) needles or vacuum-assisted biopsies (VAB). Vacuum-assisted biopsy systems consistently out-perform 14-G CB with reduced need for diagnostic or multi-treatment surgery. The false-negative rate is 8% for 14-G CB compared with 0.7% for VAB. There is a risk of underestimating the disease present for lesions of uncertain malignant potential (Cat B3) and suspicious of malignancy (Cat B4) results with 25% of patients with a B3 biopsy found to have cancer at subsequent surgery and 66% of those with a B4 biopsy. A CB diagnosis of in situ malignancy is upgraded to invasive disease at surgery in 15-36% of patients undergoing CB and of the order of 10% with VAB. A high degree of diagnostic accuracy and hence safe patient care can only be achieved by meticulous attention to technique and multi-disciplinary cooperation

Chiral Modulations in Curved Space I: Formalism

The goal of this paper is to present a formalism that allows to handle four-fermion effective theories at finite temperature and density in curved space. The formalism is based on the use of the effective action and zeta function regularization, supports the inclusion of inhomogeneous and anisotropic phases. One of the key points of the method is the use of a non-perturbative ansatz for the heat-kernel that returns the effective action in partially resummed form, providing a way to go beyond the approximations based on the Ginzburg-Landau expansion for the partition function. The effective action for the case of ultra-static Riemannian spacetimes with compact spatial section is discussed in general and a series representation, valid when the chemical potential satisfies a certain constraint, is derived. To see the formalism at work, we consider the case of static Einstein spaces at zero chemical potential. Although in this case we expect inhomogeneous phases to occur only as meta-stable states, the problem is complex enough and allows to illustrate how to implement numerical studies of inhomogeneous phases in curved space. Finally, we extend the formalism to include arbitrary chemical potentials and obtain the analytical continuation of the effective action in curved space.Comment: 22 pages, 3 figures; version to appear in JHE