Mast cells promote homeostasis by limiting endothelin-1-induced toxicity

Endothelin-1 (ET-1) is a 21-amino-acid peptide, derived from vascular endothelial cells, with potent vasoconstrictor activity. ET-1 has been implicated in diverse physiological or pathological processes, including the vascular changes associated with sepsis. However, the factors that regulate ET-1-associated toxicity during bacterial infections, or in other settings, are not fully understood. Both the pathology associated with certain allergic and autoimmune disorders, and optimal host defence against bacterial and parasitic infections are mediated by mast cells. In vitro, mast cells can produce ET-1 (ref. 11), undergo ET-1-dependent and endothelin-A receptor (ET(A))-dependent activation, and release proteases that degrade ET-1 (ref. 14). Although the potential relationships between mast cells and the ET-1 system thus may be complex, the importance of interactions between ET-1 and mast cells in vivo is obscure. Here we show that ET(A)-dependent mast-cell activation can diminish both ET-1 levels and ET-1-induced pathology in vivo, and also can contribute to optimal survival during acute bacterial peritonitis. These findings identify a new biological function for mast cells: promotion of homeostasis by limiting the toxicity associated with an endogenous mediator.     

稻纵卷叶螟幼虫寄生性天敌的种群特征与多样性分析(英文)

水稻卷叶螟的田间种群包括三个种,即稻纵卷叶螟(Cnaphalocrocis medinalis),和 MarasmiaPatnalis,M.exigua。1989年雨季在菲律宾吕宋岛上两个点进行的试验共分别记录了15(内湖省)和12(中吕宋)个种的幼虫寄生性天敌,它们分别攻击寄主卵～幼虫、幼虫和幼虫～蛹期,这些寄生性天敌分属于外寄生或内寄生,单寄生或多寄生,这种生物学特征上的差异为寄生性天敌提供了降低寄主种群的广大的机会。进一步的调查显示,那些攻击低龄寄主的种类具有高繁殖力的小个体的特征,而攻击高龄寄主的种类具有较宽的寄主范围且常常发育历期较短。多数天敌寄生于2或3龄幼虫,将寄主杀死于5龄之前,优势种及寄生率随寄主密度和水稻的生长期不同而变化。 根据Hill(1972)的多样性序列指数分析指出,当以N_2为标准时,在内湖省的整个水稻生育期内始终仅有2—3个种为极优势种,其数据适于用几何或对数序列进行描述。两个点的寄生性天敌种群多样性(N_2)接近于常数3—4,均匀度(E_5)与寄主幼虫密度呈负相关。因此,幼虫的寄生作用可被认为是一个抑制并稳定水稻卷叶螟田间种群的关键因子。     

The break-up of heavy electrons at a quantum critical point

The point at absolute zero where matter becomes unstable to new forms of order is called a quantum critical point (QCP). The quantum fluctuations between order and disorder that develop at this point induce profound transformations in the finite temperature electronic properties of the material. Magnetic fields are ideal for tuning a material as close as possible to a QCP, where the most intense effects of criticality can be studied. A previous study on the heavy-electron material YbRh2Si2 found that near a field-induced QCP electrons move ever more slowly and scatter off one another with ever increasing probability, as indicated by a divergence to infinity of the electron effective mass and scattering cross-section. But these studies could not shed light on whether these properties were an artefact of the applied field, or a more general feature of field-free QCPs. Here we report that, when germanium-doped YbRh2Si2 is tuned away from a chemically induced QCP by magnetic fields, there is a universal behaviour in the temperature dependence of the specific heat and resistivity: the characteristic kinetic energy of electrons is directly proportional to the strength of the applied field. We infer that all ballistic motion of electrons vanishes at a QCP, forming a new class of conductor in which individual electrons decay into collective current-carrying motions of the electron fluid.     

Separate sodium and calcium spikes in the same axon

Aglantha digitale is a jellyfish (order Hydromedusae) capable of two distinct kinds of locomotion; 'slow' swimming which is generated endogenously and is used in fishing behaviour, and 'fast' swimming which is evoked by predators and serves for escape. Both forms of swimming are produced by contraction of the bell-shaped body wall and expulsion of a jet of water from an opening at the base of the animal. During slow swimming, the contractions are weak and the animal moves about 15 mm, roughly one body length, but during a fast swim there is a more violent contraction which can propel the animal five times as far. Both forms of contraction depend on impulses in the eight giant motor axons that synapse directly with the muscle sheet making up the inner surface of the body wall. We report here that the giant motor axons are able to mediate both kinds of activity because they can conduct two different sorts of impulse. Fast swimming requires a rapidly conducted Na+-dependent action potential whereas slow swimming depends on a low amplitude Ca2+ 'spike'. This is the first report of an axon capable of two kinds of impulse propagation and it provides a physiological function for low potential Ca2+ activation.     

Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination

A 'rescuable' plasmid containing globin gene sequences allowing recombination with homologous chromosomal sequences has enabled us to produce, score and clone mammalian cells with the plasmid integrated into the human beta-globin locus. The planned modification was achieved in about one per thousand transformed cells whether or not the target gene was expressed.     

Induction of proliferation or transformation of neuroretina cells by the mil and myc viral oncogenes

The genome of the avian retrovirus MH2 contains, in addition to the v-myc oncogene shared with three other avian retroviruses (MC29, CMII and OK-10), a second cell-derived oncogene, v-mil (refs 1-3). Like the three other viruses, which contain only v-myc, MH2 induces mainly liver and kidney carcinomas in fowl and transforms fibroblasts and macrophages in vitro. However, MH2 and MC29 differ in their biological properties when assayed on cultures of chicken embryo neuroretina (NR) cells. Indeed, NR cells, which normally do not multiply in vitro, are induced to proliferate and become transformed upon infection with MH2, whereas infection with MC29 has no apparent effect on these cells. To analyse the functions of the two oncogenes of MH2, we isolated spontaneous and in vitro-constructed mutants of this virus and investigated their effects on NR cell multiplication and transformation. We report here that expression of v-mil is sufficient to induce NR cell proliferation, although it does not result in cell transformation. In addition, viruses expressing only the v-myc oncogene fail to induce any detectable change in NR cells. However, cooperation of the two oncogenes is required to achieve transformation of NR cells by MH2.     

Extensive surface diversity of a commensal microorganism by multiple DNA inversions.

The dynamic interactions between a host and its intestinal microflora that lead to commensalism are unclear. Bacteria that colonize the intestinal tract do so despite the development of a specific immune response by the host. The mechanisms used by commensal organisms to circumvent this immune response have yet to be established. Here we demonstrate that the human colonic microorganism, Bacteroides fragilis, is able to modulate its surface antigenicity by producing at least eight distinct capsular polysaccharides-a number greater than any previously reported for a bacterium-and is able to regulate their expression in an on-off manner by the reversible inversion of DNA segments containing the promoters for their expression. This means of generating surface diversity allows the organism to exhibit a wide array of distinct surface polysaccharide combinations, and may have broad implications for how the predominant human colonic microorganisms, the Bacteroides species, maintain an ecological niche in the intestinal tract.     

c-Myc regulates mammalian body size by controlling cell number but not cell size.

Overexpression of the proto-oncogene c-myc has been implicated in the genesis of diverse human tumours. c-Myc seems to regulate diverse biological processes, but its role in tumorigenesis and normal physiology remains enigmatic. Here we report the generation of an allelic series of mice in which c-myc expression is incrementally reduced to zero. Fibroblasts from these mice show reduced proliferation and after complete loss of c-Myc function they exit the cell cycle. We show that Myc activity is not needed for cellular growth but does determine the percentage of activated T cells that re-enter the cell cycle. In vivo, reduction of c-Myc levels results in reduced body mass owing to multiorgan hypoplasia, in contrast to Drosophila c-myc mutants, which are smaller as a result of hypotrophy. We find that c-myc substitutes for c-myc in fibroblasts, indicating they have similar biological activities. This suggests there may be fundamental differences in the mechanisms by which mammals and insects control body size. We propose that in mammals c-Myc controls the decision to divide or not to divide and thereby functions as a crucial mediator of signals that determine organ and body size.