A progeroid syndrome in mice is caused by defects in A-type lamins

Numerous studies of the underlying causes of ageing have been attempted by examining diseases associated with premature ageing, such as Werner's syndrome and Hutchinson-Gilford progeria syndrome (HGPS). HGPS is a rare genetic disorder resulting in phenotypes suggestive of accelerated ageing, including shortened stature, craniofacial disproportion, very thin skin, alopecia and osteoporosis, with death in the early teens predominantly due to atherosclerosis. However, recent reports suggest that developmental abnormalities may also be important in HGPS. Here we describe the derivation of mice carrying an autosomal recessive mutation in the lamin A gene (Lmna) encoding A-type lamins, major components of the nuclear lamina. Homozygous mice display defects consistent with HGPS, including a marked reduction in growth rate and death by 4 weeks of age. Pathologies in bone, muscle and skin are also consistent with progeria. The Lmna mutation resulted in nuclear morphology defects and decreased lifespan of homozygous fibroblasts, suggesting premature cell death. Here we present a mouse model for progeria that may elucidate mechanisms of ageing and development in certain tissue types, especially those developing from the mesenchymal cell lineage.     

A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans

Germline stem cells are defined by their unique ability to generate more of themselves as well as differentiated gametes. The molecular mechanisms controlling the decision between self-renewal and differentiation are central unsolved problems in developmental biology with potentially broad medical implications. In Caenorhabditis elegans, germline stem cells are controlled by the somatic distal tip cell. FBF-1 and FBF-2, two nearly identical proteins, which together are called FBF ('fem-3 mRNA binding factor'), were originally discovered as regulators of germline sex determination. Here we report that FBF also controls germline stem cells: in an fbf-1 fbf-2 double mutant, germline proliferation is initially normal, but stem cells are not maintained. We suggest that FBF controls germline stem cells, at least in part, by repressing gld-1, which itself promotes commitment to the meiotic cell cycle. FBF belongs to the PUF family ('Pumilio and FBF') of RNA-binding proteins. Pumilio controls germline stem cells in Drosophila females, and, in lower eukaryotes, PUF proteins promote continued mitoses. We suggest that regulation by PUF proteins may be an ancient and widespread mechanism for control of stem cells.     

A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans

Messenger RNA regulation is a critical mode of controlling gene expression. Regulation of mRNA stability and translation is linked to controls of poly(A) tail length. Poly(A) lengthening can stabilize and translationally activate mRNAs, whereas poly(A) removal can trigger degradation and translational repression. Germline granules (for example, polar granules in flies, P granules in worms) are ribonucleoprotein particles implicated in translational control. Here we report that the Caenorhabditis elegans gene gld-2, a regulator of mitosis/meiosis decision and other germline events, encodes the catalytic moiety of a cytoplasmic poly(A) polymerase (PAP) that is associated with P granules in early embryos. Importantly, the GLD-2 protein sequence has diverged substantially from that of conventional eukaryotic PAPs, and lacks a recognizable RRM (RNA recognition motif)-like domain. GLD-2 has little PAP activity on its own, but is stimulated in vitro by GLD-3. GLD-3 is also a developmental regulator, and belongs to the Bicaudal-C family of RNA binding proteins. We suggest that GLD-2 is the prototype for a class of regulatory cytoplasmic PAPs that are recruited to specific mRNAs by a binding partner, thereby targeting those mRNAs for polyadenylation and increased expression.     

Olfaction: scent-triggered navigation in honeybees

The honeybee, Apis mellifera, navigates rapidly and accurately to food sources that are often kilometres away. They achieve this by learning visual cues, such as the location and colour of nectar-bearing flowers, and chemical cues, such as the scent and the taste of the nectar. Here we train bees to visit differently scented sugar feeders placed at specific outdoor locations and find that they can be induced to visit the same locations simply by having the corresponding scent blown into the hive, even when the destinations no longer have the food or carry the scent. A familiar nectar scent can trigger specific memories of a route and therefore expedite navigation to the food source.     

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.     

The role of periostin in tissue remodeling across health and disease

Periostin, also termed osteoblast-specific factor 2, is a matricellular protein with known functions in osteology, tissue repair, oncology, cardiovascular and respiratory systems, and in various inflammatory settings. However, most of the research to date has been conducted in divergent and circumscribed areas meaning that the overall understanding of this intriguing molecule remains fragmented. Here, we integrate the available evidence on periostin expression, its normal role in development, and whether it plays a similar function during pathologic repair, regeneration, and disease in order to bring together the different research fields in which periostin investigations are ongoing. In spite of the seemingly disparate roles of periostin in health and disease, tissue remodeling as a response to insult/injury is emerging as a common functional denominator of this matricellular molecule. Periostin is transiently upregulated during cell fate changes, either physiologic or pathologic. Combining observations from various conditions, a common pattern of events can be suggested, including periostin localization during development, insult and injury, epithelial–mesenchymal transition, extracellular matrix restructuring, and remodeling. We propose mesenchymal remodeling as an overarching role for the matricellular protein periostin, across physiology and disease. Periostin may be seen as an important structural mediator, balancing appropriate versus inappropriate tissue adaption in response to insult/injury.     

奇异的航程：通过科幻影像学习科学 第二版

本书对一些神奇的问题（如：怎么判别日期？核裂变的重要性是什么？时间如何穿越星空？星际航行的可行性？）进行了描述，读者可从中得到令人深思的答复。书中用诸如《寂静的地球》《行星》《仙女座协变》及近年热播的《侏罗纪公园》《独立日》等科幻影片的片断为例进行讨论，给出了基本的物理学和生物学原理。