Atypical base composition of foldback DNA

Summary Salmon, calf and human foldback DNAs all exhibited hypermethylation, reduced adenine plus thymine content and an excess of adenine over thymine when compared with their respective native DNAs. The only unusual feature of the base composition of wheat germ foldback DNA was the excess of thymine over adenine.This work was supported by grants from the Committee on Higher Degrees and Research Grants and the Department of Pathology, University of Hong Kong.This study was carried out in partial fulfillment of the requirements of the University of Hong Kong for the degree of Doctor of Philosophy.     

The effect of hog gastrin on gastric secretion in chronic gastric fistula rats

Résumé L'action de la gastrine de porc a été étudiée chez des rats mâles munis de fistules gastriques. La gastrine était injectée par voie s.c. à des doses de 1–2 ml: 1 ml équivalant à l'activité de 10 g de muqueuse de porc. Le volume de suc gastrique, le volume de suc gastrique par 100 g, l'acidité totale et le débit d'acide accusèrent une pointe dans la première h, alors que la concentration en acide atteignit son maximum vers la troisième h. Le débit de la pepsine diminua entre la troisième et la cinquième h et augmenta légèrement entre la cinquième et la sixième h.

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This research was supported in part by grants from the National Science Foundation (No. GB 6105) and from the AMA ERF, to J. H. T. — Dr.Robitscher of Ayerst Laboratories kindly supplied the ICI-50123.     

Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations

It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown. Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes--so-called sporadic or simplex families--we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported. Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD. Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected β-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics.     

The landscape of cancer genes and mutational processes in breast cancer

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.     

The diet of Australopithecus sediba

Specimens of Australopithecus sediba from the site of Malapa, South Africa (dating from approximately 2 million years (Myr) ago) present a mix of primitive and derived traits that align the taxon with other Australopithecus species and with early Homo. Although much of the available cranial and postcranial material of Au. sediba has been described, its feeding ecology has not been investigated. Here we present results from the first extraction of plant phytoliths from dental calculus of an early hominin. We also consider stable carbon isotope and dental microwear texture data for Au. sediba in light of new palaeoenvironmental evidence. The two individuals examined consumed an almost exclusive C(3) diet that probably included harder foods, and both dicotyledons (for example, tree leaves, fruits, wood and bark) and monocotyledons (for example, grasses and sedges). Like Ardipithecus ramidus (approximately 4.4 Myr ago) and modern savanna chimpanzees, Au. sediba consumed C(3) foods in preference to widely available C(4) resources. The inferred consumption of C(3) monocotyledons, and wood or bark, increases the known variety of early hominin foods. The overall dietary pattern of these two individuals contrasts with available data for other hominins in the region and elsewhere.     

A novel putative auxin carrier family regulates intracellular auxin homeostasis in plants

The phytohormone auxin acts as a prominent signal, providing, by its local accumulation or depletion in selected cells, a spatial and temporal reference for changes in the developmental program. The distribution of auxin depends on both auxin metabolism (biosynthesis, conjugation and degradation) and cellular auxin transport. We identified in silico a novel putative auxin transport facilitator family, called PIN-LIKES (PILS). Here we illustrate that PILS proteins are required for auxin-dependent regulation of plant growth by determining the cellular sensitivity to auxin. PILS proteins regulate intracellular auxin accumulation at the endoplasmic reticulum and thus auxin availability for nuclear auxin signalling. PILS activity affects the level of endogenous auxin indole-3-acetic acid (IAA), presumably via intracellular accumulation and metabolism. Our findings reveal that the transport machinery to compartmentalize auxin within the cell is of an unexpected molecular complexity and demonstrate this compartmentalization to be functionally important for a number of developmental processes.     

基于生存模型的沥青路面预防性养护经济性评价

为探索经济、有效的沥青路面养护方法,降低沥青路面的养护费用,对沥青路面的预防性养护进行了全寿命经济性评价.首先根据美国加利福尼亚州交通部门的路面观测数据,采用生存模型建立了沥青路面在裂缝类预防性养护情况下的全寿命周期的性能模型;进而,通过概率分析建立了路面的性能-成本模型,分析了不同破坏准则下预防性养护措施的经济性,并与矫正性修复措施的经济性进行了对比.结果表明,在沥青路面的寿命周期内,一直采用预防性养护的成本较采用矫正性修复的成本平均节约了27%,采用每两次矫正性修复间加入两次预防性养护的成本较一直使用矫正性修复的成本平均节约了17%.分析结果还表明,越早进行预防性养护,沥青路面的寿命周期成本越低.