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In 1946, a study began of all the babies born in one March week in England, Wales and Scotland, with a view to learning more about the social and economic costs of childbearing. Today the study is still going, and is one of the longest-running studies of human development in the world. The 1946 cohort has been followed into adulthood, so has allowed researchers to investigate how childhood health and lifetime social circumstances affect adult health and wealth. This week, the participants celebrate their 65th birthdays, the age at which many people in the United Kingdom retire. So now the National Survey of Health and Development has become a study of ageing. Helen Pearson talked to the surveys scientists and members of the 1946 cohort about the scientific immortality that their participation has given them, and looks at how priceless the accumulated data have become. Cover graphic: Oliver Munday.
Birth-cohort studies offer invaluable data on the links between childhood development and later life, but today's efforts could learn something from a pioneering project that turns 65 this week.
In 1946, scientists started tracking thousands of British children born during one cold March week. On their 65th birthday, the study members find themselves more scientifically valuable than ever before.
American Indians have had some unhappy interactions with scientists in the past. Now, America's tribal colleges are rapidly expanding their own research.
Two centuries on from the Luddite insurrection, David Edgerton celebrates today's most important opponents to new ideas, inventions and innovations: scientists.
The Athens-based orthodontist explains the art and science of reconstructing the heads of long-dead people from their skulls alone, including that of Myrtis — a young girl from more than 2,000 years ago, whose recreated face is our first glimpse of an ordinary ancient Greek.
Theory suggests that the accuracy of a decision often increases with the number of decision makers, a phenomenon exploited by betting agents, Internet search engines and stock markets. Fish also use this 'wisdom of the crowd' effect.
The idea of using ultracold atoms to simulate the behaviour of electrons in new kinds of quantum systems — from topological insulators to exotic superfluids and superconductors — is a step closer to becoming a reality. See Letterp.83
Protein folding is a high-stakes process, with cell dysfunction and death being the unforgiving penalties for failure. Work in bacteria hints that organisms manage this process beyond the boundaries of the cytoplasm — and even the cell.
The origin of the annelids is buried in distant evolutionary time. A molecular phylogeny resolves their deep family interrelationships and provides a picture of their 'urannelid' ancestor. See Letterp.95
A novel explanation for the long-term temperature record in Antarctic ice cores invokes local solar radiation as the driving agent. This proposal will prompt palaeoclimate scientists to pause and to go back to basics. See Letterp.91
Induced pluripotent stem cells have great therapeutic potential. But genomic and epigenomic analyses of these cells generated using current technology reveal abnormalities that may affect their safe use. See Articlesp.58, p.63 & p.68
Summer sea-ice extent in the Arctic has decreased greatly during recent decades. Simulations of twenty-first-century climate suggest that the ice can recover from artificially imposed ice-free summer conditions within a couple of years.
The protein Sae2 mediates the repair of double-strand breaks in DNA. It emerges that Sae2 activity is controlled by both its modification with acetyl groups and its degradation by the process of autophagy. See Articlep.74
Reprogramming of somatic cells to induced pluripotent stem (iPS) cells that can be differentiated into many cell types has great potential for personalized therapy. By comparing copy number variations of early- and intermediate-passage human iPS cells to their respective parental fibroblast cells and human embryonic stem (ES) cells, this study finds that a high mutation rate is associated with the reprogramming process. However, during moderate length culture, human iPS cells undergo a selection process leading to decreased mutation load of cells equivalent to that observed in human ES cells.
Reprogramming of somatic cells to induced pluripotent stem (iPS) cells that can be differentiated into many cell types has great potential for personalized therapy. This study finds that 22 human iPS cell lines that were reprogrammed using five different methods contain protein coding point mutations. Some mutations were pre existing in the somatic cells, others were new mutations that occurred during and after reprogramming. Therefore, it will be important to ensure iPS cell safety before clinical use.
Reprogramming of somatic cells to induce pluripotent cellular properties that closely resemble those of embryonic stem (ES) cells has important therapeutic potential. The first whole genome single-base resolution profiling of the DNA methylomes of several human ES cell, induced pluripotent stem cell (iPSC) and somatic progenitor lines shows that iPSCs are fundamentally distinct from ES cells, insofar as they manifest common, quantifiable epigenomic differences. These 'hotspots of aberrant reprogramming' might be potentially useful as diagnostic markers for incomplete iPSC reprogramming, for the characterization of the efficacy of different reprogramming techniques, and for screening the potential propagation of altered methylation states into derivative differentiated cells.
The presence of DNA lesions is a clear signal that initiates the DNA damage response; however, the mechanisms that attenuate this response when repair has occurred are less clear. Here, deacetylation of Sae2 by Rpd3 and Hda1 is shown to be required for it to act on Mre11. When the role of Sae2 in resection is completed, it is acetylated by Gcn5 and degraded through an autophagic pathway. This work highlights links between DNA damage signalling, acetylation of repair factors, and autophagy mediated degradation of these factors.
Direct observations over the past four centuries show that the number of sunspots observed on the Sun's surface varies periodically. After sunspot cycle 23, the Sun went into a prolonged minimum characterized by a very weak polar magnetic field and an unusually large number of days without sunspots. This study reports kinematic dynamo simulations which demonstrate that a fast meridional flow in the early half of a cycle, followed by a slower flow in the latter half, reproduces both characteristics of the minimum of sunspot cycle 23.
Spin–orbit coupling describes the interaction between a quantum particle's spin and its momentum, and is important for many areas of physics such as spintronics and topological insulators. However, in systems of ultracold neutral atoms, there is no coupling between the spin and the centre of mass motion of the atom. This study uses lasers to engineer such spin–orbit coupling in a neutral atomic Bose–Einstein condensate, the first time this has been achieved for any bosonic system. This should lead to the realization of topological insulators in fermionic neutral atom systems.
Simulations of interacting particles in classical systems generally involve the Metropolis algorithm. A quantum version of this approach has been hindered by the lack of a means to simulate the equilibrium and static properties of quantum systems. This study overcomes this problem. Its quantum version of the Metropolis algorithm could find widespread application in many body quantum physics, such as computing the binding energies of complex molecules or determining hadron masses in gauge theories.
According to the Milankovitch theory, glacial to interglacial climate variability — as recorded in Antarctica ice cores — is governed by summer insolation at high northern latitudes. It is now shown that accumulation of Antarctic snow is biased towards austral winter and may be explained simply by variations in local insolation, with no recourse to northern influences. Although not constituting a complete negative proof, the results show that the Antarctic ice core records do not, in themselves, provide sufficient support for the Milankovitch theory.
The annelids, or ringed worms, comprise one of the largest and most diverse animal phyla, and are found everywhere from garden soil to the deep sea. Their precise phylogeny has always been sketchy, but now, a new phylogenomic analysis unravels annelid evolution. Notable features include a division of most annelids into the Errantia and Sedentaria — a restitution for two groups based on classical morphology — showing how many details of anatomy and life history bear on the evolution of this important animal group.
This study describes a mechanotransduction pathway that links the body wall with the epidermis in Caenorhabditis elegans. The pathway involves the p21 activated kinase PAK 1, an adaptor GIT 1 and its partner PIX 1. Tension exerted by muscles or external pressure keeps GIT 1 on station at hemidesmosomes — the small rivet like bodies that attach epidermal cells to the underlying musculature — and stimulates PAK 1 through PIX 1 and Rac GTPase. The C. elegans hemidesmosome is more than a passive attachment structure, therefore, but a sensor that responds to tension by triggering signalling processes.
This is one of two papers demonstrating that in several cancer types including ovarian cancer and T-cell leukaemias, the apoptosis regulator MCL1 is targeted for degradation by the FBW7 tumour suppressor. This study finds that this mechanism can determine the response to drugs targeting BCL2 family apoptosis factors. Deletion or mutation of FBW7 found in cancer patients therefore can render tumours resistant to these therapies.
Different organisms use a variety of mechanisms to compensate for X chromosome dosage imbalance between the sexes. In Drosophila, the MSL complex increases transcription on the single X chromosome of males and is thought to regulate transcription elongation, although mechanistic details have been unclear. Here, a global run-on sequencing technique is used to reveal that the MSL complex seems to enhance transcription by facilitating the progression of RNA polymerase II across the bodies of active X linked genes. In this way, MSL can impose dosage compensation on diverse genes with a wide range of transcription levels along the X chromosome.
Misrepair of DNA double strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin and T-cell receptor loci has been implicated in the pathogenesis of lymphoid malignancies. Here, the RAG2 carboxy terminus is shown to be critical for maintaining genomic stability. Rag2c/c p53−/− mice, unlike Rag1c/c p53−/− and p53−/− mice, rapidly develop thymic lymphomas bearing complex chromosomal translocations, amplifications and deletions involving the Tcrα/δ and Igh loci. These results reveal a new 'genome guardian' role for RAG2 and suggest that similar 'end release/end persistence' mechanisms underlie genomic instability and lymphomagenesis in Rag2c/c p53−/− and Atm−/− mice.