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31.
In 1905, Albert Einstein proposed that the forces that cause the random Brownian motion of a particle also underlie the resistance
to macroscopic motion when a force is applied. This insight, of a coupling between fluctuation (stochastic behavior) and responsiveness
(non-stochastic behavior), founded an important branch of physics. Here we argue that his insight may also be relevant for
understanding evolved biological systems, and we present a ‘fluctuation–response relationship’ for biology. The relationship
is consistent with the idea that biological systems are similarly canalized to stochastic, environmental, and genetic perturbations.
It is also supported by in silico evolution experiments, and by the observation that ‘noisy’ gene expression is often both
more responsive and more ‘evolvable’. More generally, we argue that in biology there is (and always has been) an important
role for macroscopic theory that considers the general behavior of systems without concern for their intimate molecular details. 相似文献
32.
van de Laar IM Oldenburg RA Pals G Roos-Hesselink JW de Graaf BM Verhagen JM Hoedemaekers YM Willemsen R Severijnen LA Venselaar H Vriend G Pattynama PM Collée M Majoor-Krakauer D Poldermans D Frohn-Mulder IM Micha D Timmermans J Hilhorst-Hofstee Y Bierma-Zeinstra SM Willems PJ Kros JM Oei EH Oostra BA Wessels MW Bertoli-Avella AM 《Nature genetics》2011,43(2):121-126
Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis. 相似文献
33.
Vitart V Rudan I Hayward C Gray NK Floyd J Palmer CN Knott SA Kolcic I Polasek O Graessler J Wilson JF Marinaki A Riches PL Shu X Janicijevic B Smolej-Narancic N Gorgoni B Morgan J Campbell S Biloglav Z Barac-Lauc L Pericic M Klaric IM Zgaga L Skaric-Juric T Wild SH Richardson WA Hohenstein P Kimber CH Tenesa A Donnelly LA Fairbanks LD Aringer M McKeigue PM Ralston SH Morris AD Rudan P Hastie ND Campbell H Wright AF 《Nature genetics》2008,40(4):437-442
Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes. 相似文献
34.
The Pristionchus pacificus genome provides a unique perspective on nematode lifestyle and parasitism
Dieterich C Clifton SW Schuster LN Chinwalla A Delehaunty K Dinkelacker I Fulton L Fulton R Godfrey J Minx P Mitreva M Roeseler W Tian H Witte H Yang SP Wilson RK Sommer RJ 《Nature genetics》2008,40(10):1193-1198
Here we present a draft genome sequence of the nematode Pristionchus pacificus, a species that is associated with beetles and is used as a model system in evolutionary biology. With 169 Mb and 23,500 predicted protein-coding genes, the P. pacificus genome is larger than those of Caenorhabditis elegans and the human parasite Brugia malayi. Compared to C. elegans, the P. pacificus genome has more genes encoding cytochrome P450 enzymes, glucosyltransferases, sulfotransferases and ABC transporters, many of which were experimentally validated. The P. pacificus genome contains genes encoding cellulase and diapausin, and cellulase activity is found in P. pacificus secretions, indicating that cellulases can be found in nematodes beyond plant parasites. The relatively higher number of detoxification and degradation enzymes in P. pacificus is consistent with its necromenic lifestyle and might represent a preadaptation for parasitism. Thus, comparative genomics analysis of three ecologically distinct nematodes offers a unique opportunity to investigate the association between genome structure and lifestyle. 相似文献
35.
The chromosomes of eukaryotic cells are separated from the cytoplasm by the nuclear envelope. The nuclear envelope includes two riveted membranes, plus embedded pore complexes that mediate nuclear import and export. In this sense, the nuclear envelope is truly a border zone. However, the envelope also links directly to chromosomes, and anchors two major infrastructures--the nuclear lamina and Tpr filaments--to the nuclear perimeter. Proteins of the nuclear envelope mediate a variety of fundamental activities, including DNA replication, gene expression and silencing, chromatin organization, cell division, apoptosis, sperm nuclear remodeling, the behavior of pronuclei, cell fate determination, nuclear migration and cell polarity. Furthermore, mutations in nuclear lamins and lamin-binding proteins cause tissue-specific inherited diseases. This special issue of Cell and Molecular Life Sciences is devoted to recent major advances in the characterization of nuclear envelope proteins and their roles. We offer here an overview of the topics covered in this issue of CMLS, and also discuss the emerging recognition that the nuclear envelope is an organelle critical for a wide range of genetic and developmental activity in multicellular organisms. 相似文献
36.
Horses damp the spring in their step. 总被引:6,自引:0,他引:6
The muscular work of galloping in horses is halved by storing and returning elastic strain energy in spring-like muscle-tendon units.These make the legs act like a child's pogo stick that is tuned to stretch and recoil at 2.5 strides per second. This mechanism is optimized by unique musculoskeletal adaptations: the digital flexor muscles have extremely short fibres and significant passive properties, whereas the tendons are very long and span several joints. Length change occurs by a stretching of the spring-like digital flexor tendons rather than through energetically expensive length changes in the muscle. Despite being apparently redundant for such a mechanism, the muscle fibres in the digital flexors are well developed. Here we show that the mechanical arrangement of the elastic leg permits it to vibrate at a higher frequency of 30-40 Hz that could cause fatigue damage to tendon and bone. Furthermore, we show that the digital flexor muscles have minimal ability to contribute to or regulate significantly the 2.5-Hz cycle of movement, but are ideally arranged to damp these high-frequency oscillations in the limb. 相似文献
37.
This paper presents a computer system reliability allocation method that is based on the theory of statistic and Markovian chain, which can be used to allocate reliability to subsystem, to hybrid system and software modules. A relevant supporting tool built by us is introduced. 相似文献
38.
39.
为了得到填料-高压微雾对组合式空调机组的降温效果,测试1台55 000m3/h风量的填料-高压微雾组合式空调机组.采用对比方法,将5种不同的测试的降温效果进行对比.实验数据表明,高压微雾和填料上采用三维布水相结合对空调机组的降温最为显著.从研究结果上看,高压微雾不仅是人们传统认识上的加湿器,还是一台良好的冷却器,能够对空气进行降温,满足一些场所降温的需要,具有广泛的应用范围. 相似文献
40.
Vegetation characteristics of 15 sagebrush community types identified on the Humboldt National Forest, northeastern Nevada, are described. A total of 218 plant species were found over the 372 relatively undisturbed rangeland communities sampled. The dominant plant families encountered were the Asteraceae (45 taxa), Poaceae (32 taxa), Scrophulariaceae (14 taxa), and the Fabaceae (12 taxa). Average annual dry weight production of the community types ranged from about 400 kg/ha/yr on types with Artemisia nova as the dominant sagebrush species to 1,200 kg/ha/yr on some A. tridentata ssp. vaseyana community types. A general increase in species richness and vegetation plus litter ground cover was observed within community types as the dominant sagebrush species changed from A. nova to A. arbuscula to A. longiloba to A. tridentata spp. tridentata to A. tridentata ssp. vaseyana . Major differences in plant species production and constancy exist between the sagebrush community types studied. 相似文献