Mean Motions in Ptolemy’s <Emphasis Type="Italic">Planetary Hypotheses</Emphasis>

In the Planetary Hypotheses, Ptolemy summarizes the planetary models that he discusses in great detail in the Almagest, but he changes the mean motions to account for more prolonged comparison of observations. He gives the mean motions in two different forms: first, in terms of ‘simple, unmixed’ periods and next, in terms of ‘particular, complex’ periods, which are approximations to linear combinations of the simple periods. As a consequence, all of the epoch values for the Moon and the planets are different at era Philip. This is in part a consequence of the changes in the mean motions and in part due to changes in Ptolemy’s time in the anomaly, but not the longitude or latitude, of the Moon, the mean longitude of Saturn and Jupiter, but not Mars, and the anomaly of Venus and Mercury, the former a large change, the latter a small one. The pattern of parameter changes we see suggests that the analyses that yielded the Planetary Hypotheses parameters were not the elegant trio analyses of the Almagest but some sort of serial determinations of the parameters based on sequences of independent observations.     

A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2

We report heterozygous mutations in the genes encoding either type I or type II transforming growth factor beta receptor in ten families with a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development. Despite evidence that receptors derived from selected mutated alleles cannot support TGFbeta signal propagation, cells derived from individuals heterozygous with respect to these mutations did not show altered kinetics of the acute phase response to administered ligand. Furthermore, tissues derived from affected individuals showed increased expression of both collagen and connective tissue growth factor, as well as nuclear enrichment of phosphorylated Smad2, indicative of increased TGFbeta signaling. These data definitively implicate perturbation of TGFbeta signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events.     

Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences

We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.     

Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding

The development and maintenance of an epithelium requires finely balanced rates of growth and cell death. However, the mechanical and biochemical mechanisms that ensure proper feedback control of tissue growth, which when deregulated contribute to tumorigenesis, are poorly understood. Here we use the fly notum as a model system to identify a novel process of crowding-induced cell delamination that balances growth to ensure the development of well-ordered cell packing. In crowded regions of the tissue, a proportion of cells undergo a serial loss of cell-cell junctions and a progressive loss of apical area, before being squeezed out by their neighbours. This path of delamination is recapitulated by a simple computational model of epithelial mechanics, in which stochastic cell loss relieves overcrowding as the system tends towards equilibrium. We show that this process of delamination is mechanistically distinct from apoptosis-mediated cell extrusion and precedes the first signs of cell death. Overall, this analysis reveals a simple mechanism that buffers epithelia against variations in growth. Because live-cell delamination constitutes a mechanistic link between epithelial hyperplasia and cell invasion, this is likely to have important implications for our understanding of the early stages of cancer development.     

Two levels of protection for the B cell genome during somatic hypermutation

Somatic hypermutation introduces point mutations into immunoglobulin genes in germinal centre B cells during an immune response. The reaction is initiated by cytosine deamination by the activation-induced deaminase (AID) and completed by error-prone processing of the resulting uracils by mismatch and base excision repair factors. Somatic hypermutation represents a threat to genome integrity and it is not known how the B cell genome is protected from the mutagenic effects of somatic hypermutation nor how often these protective mechanisms fail. Here we show, by extensive sequencing of murine B cell genes, that the genome is protected by two distinct mechanisms: selective targeting of AID and gene-specific, high-fidelity repair of AID-generated uracils. Numerous genes linked to B cell tumorigenesis, including Myc, Pim1, Pax5, Ocab (also called Pou2af1), H2afx, Rhoh and Ebf1, are deaminated by AID but escape acquisition of most mutations through the combined action of mismatch and base excision repair. However, approximately 25% of expressed genes analysed were not fully protected by either mechanism and accumulated mutations in germinal centre B cells. Our results demonstrate that AID acts broadly on the genome, with the ultimate distribution of mutations determined by a balance between high-fidelity and error-prone DNA repair.     

Greek angles from Babylonian numbers

Models of planetary motion as observed from Earth must account for two principal anomalies: the nonuniform speed of the planet as it circles the zodiac, and the correlation of the planet’s position with the position of the Sun. In the context of the geometrical models used by the Greeks, the practical difficulty is to somehow isolate the motion of the epicycle center on the deferent from the motion of the planet on its epicycle. One way to isolate the motion of the epicycle center is to determine the longitude and time of oppositions of the planet with the mean Sun. A Greek astronomer might have realized that the predictions of mean oppositions by Babylonian models could serve as useful proxies for real empirical observations. It is shown that a Greek astronomer with a reasonable understanding of Babylonian System A models for the outer planets and the Sun–Moon could have used those models to estimate approximate values for the eccentricity e and longitude of apogee A required for geometrical models. The same method would work for the inner planets if conjunctions were observable, but they are not, and the variation of the observable synodic events—first and last morning and evening visibilities—is dominated more by the motion of the planet in latitude than the nonuniform motion of the epicycle center.     

老龄健康影响因素的跨学科研究国际动态

本文从四方面综述并讨论老龄健康跨学科研究的国际新动态与进展:(1)发达国家高度重视和不断加强对老龄健康跨学科研究及其研究策略选择;(2)老龄健康的社会行为和环境影响因素研究;(3)老龄健康相关遗传基因研究;(4)社会行为、环境、遗传因素的交互作用对老龄健康影响研究.同时阐述国际上关于老龄健康跨学科研究的若干案例以及我国关于老龄健康影响因素调查和健康长寿候选基因研究方面取得的一些可喜进展与仍然十分薄弱的现状.最后对今后如何开展老龄健康的跨自然与社会科学综合交叉研究提出思考与展望,认为积极推进我国老龄健康跨学科研究势在必行,而我国学者可望为人类应对人口老化严峻挑战做出突出贡献.