Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans

Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. Filamin A, encoded by the gene FLNA, is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers. We identified localized mutations in FLNA that conserve the reading frame and lead to a broad range of congenital malformations, affecting craniofacial structures, skeleton, brain, viscera and urogenital tract, in four X-linked human disorders: otopalatodigital syndrome types 1 (OPD1; OMIM 311300) and 2 (OPD2; OMIM 304120), frontometaphyseal dysplasia (FMD; OMIM 305620) and Melnick-Needles syndrome (MNS; OMIM 309350). Several mutations are recurrent, and all are clustered into four regions of the gene: the actin-binding domain and rod domain repeats 3, 10 and 14/15. Our findings contrast with previous observations that loss of function of FLNA is embryonic lethal in males but manifests in females as a localized neuronal migration disorder, called periventricular nodular heterotopia (PVNH; refs. 3-6). The patterns of mutation, X-chromosome inactivation and phenotypic manifestations in the newly described mutations indicate that they have gain-of-function effects, implicating filamin A in signaling pathways that mediate organogenesis in multiple systems during embryonic development.     

Morphological changes to Escherichia coli O157:H7, commensal E. coli and Salmonella spp in response to marginal growth conditions,with special reference to mildly stressing temperatures

Certain rod-shaped bacteria have been reported to form elongated filamentous cells when exposed to marginal growth conditions, including refrigeration temperatures. To expand upon these observations, the filamentation of commensal Escherichia coli, E. coli O157:H7 and Salmonella spp was investigated, following exposure to certain, mildly stressing, levels of temperature, pH or water activity (aw), with levels of cellular protein being monitored during cell elongation, in some experiments. Our studies indicated that cellular filamentation could be demonstrated in all 15 strains of the above organisms tested, following exposure to marginal conditions achieved by incubation at high or low temperatures, high or low pH values and low aw. The level of environmental stress causing filamentation tended to be specific to the particular organisms. For example, Salmonella spp formed filamentous cells at 44 degrees C, whereas E. coli strains, including O157, grew by binary fission at that temperature, but formed filamentous cells at 46 degrees C. In addition, plate count techniques to enumerate bacteria during filamentation, failed to reflect the increase in cell biomass that was occurring, whereas measurements of protein concentration demonstrated the increase quite strikingly. These findings have important implications for our understanding of the ability of food-borne pathogens to cause disease, since the infectious dose of a microorganism implicated in an outbreak of such disease is typically determined by a viable count method, which could underestimate the number of potential infectious units present in a food that had been stored in such a way as to provide marginal growth conditions.     

Evolutionary divergence in closely related populations of Mimulus guttatus (Scrophulariaceae)

The evolutionary divergence of five closely related populations of the yellow monkey flower. Mimulus guttatus was compared with the length of time the populations could have occupied the site and with the ability of the populations to intercross. Populations from the younger sites were found to be morphologically intermediate to populations from the older sites. Ability to intercross was not correlated with morphological divergence at this stage of evolution.       

Joseph H. M. Wedderburn and the structure theory of algebras

Archive for History of Exact Sciences -     

Invertebrate fauna of wastewater ponds in southeastern Idaho

Water column invertebrates were sampled with 3.8-L activity traps in 15 sewage, industrial, and radioactive wastewater ponds at the Idaho National Engineering Laboratory in southeastern Idaho. One collection was made per pond, per month, during all months the ponds were ice-free from June 1990 through July 1991. Arsenic, barium, boron, lead, selenium, and mercury were detected in ponds. Sewage ponds generally had higher nitrogen and phosphorus levels than industrial and radioactive ponds. Of the 30 aquatic invertebrate taxa collected, the most ubiquitous were Rotifera, Daphnidea, Eucopepdoa, Ostracoda, Acari, Baetidae, Corixidae, Notonectidiae, Dytiscidae, and Chironomidae. Activity trap samples from sewage ponds contained more Rotifere, Daphnidae, and Notonectide, whereas industrial ponds yielded more Chydoridae, Acari, and Baetidae. Numbers of Oligochaeta, Eucopepoda, Ostracoda, Corixidae, Dytiscidae, and Chironomidae collected were not significantly different between sewage and industrial ponds. Compared with natural systems, these ponds had fewer taxa, but a greater number of individuals of most taxa. The high number of invertebrates collected is attributed to the lack of fish in wastewater ponds and the high levels of nitrogen and phosphorus, particularly in sewage ponds.     

基因差异与不同药物反应

同种药物治疗同种疾病，不同的病人有不同的结果。很快，医生要先为病人做基国检测后再开处方。饱经折磨之后，一位深陷苦恼的年轻妇女拖着疲惫的身躯求助于医生。医生诊断为严重抑郁症后，安慰她道：“现在，我们能给你做个DNA检测，看看什么药对你最恰当。”他从她头上拔下一根头发，“等下午报告出来后我再开处方，你的病很快就会好。”她首次露出长久不见的充满希望的笑容。类似的情景，可能不要很久就会出现。从制药公司和生物技术公司看来，病人不久就能用上适合其本人基因组成的药品。今天的医生只会让这位年轻妇女去试用一种药品…