A Molecular Switching Mechanism in Differentiation

Abstract. The selection of polarity in cells of the cambium in higher plants is a regulated process of development which results in horizontally or vertically oriented cells. A set of mathematical equations suggestive of this developmental dichotomy is given a new biologic interpretation. As a result, a molecular scheme capable of acting as a biochemical switch is suggested. The model features two structural protein monomers whose synthesis is controlled autogenously by feedback repression. The implications of this and similar mechanisms to other differentiating systems is discussed.     

The XcpR protein of Pseudomonas aeruginosa dimerizes via its N-terminus

Extracellular protein secretion by the main terminal branch of the general secretory pathway in Pseudomonas aeruginosa requires a secretion machinery comprising the products of at least 12 genes. One of the components of this machinery, the XcpR protein, belongs to a large family of related proteins distinguished by the presence of a highly conserved nucleotide binding domain (Walker box A). The XcpR protein is essential for the process of extracellular secretion and amino acid substitutions within the Walker A sequence result in inactive XcpR. The same mutations exert a dominant negative effect on protein secretion when expressed in wild-type bacteria. Transdominance of XcpR mutants suggests that this protein is involved in interactions with other components of the secretion machinery or that it functions as a multimer. In this study, the amino-terminal portion of the cI repressor protein of phage λ was used as a reporter of dimerization in Escherichia coli following fusion to full-length as well as a truncated form of XcpR. The cI–XcpR hybrid proteins were able to dimerize, as demonstrated by the immunity of bacteria expressing them to killing by λ phage. The full-length XcpR as well as several deletion mutants of XcpR were able to disrupt the dimerization of the chimeric cI–XcpR protein. The disruption of cI–XcpR dimers using the deletion mutants of XcpR, combined with the analysis of their dominant negative effects on protein secretion, was used to map the minimal dimerization domain of XcpR, which is located within an 85 amino acid region in its N-terminal domain. Taken together, the data presented in this paper suggest that the XcpR protein dimerizes via its N-terminus and that this dimerization is essential for extracellular protein secretion.     

Genome‐wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward‐related ventral striatum activity in African‐ and European‐Americans

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome‐wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European‐Americans (EA; 2927 cases) and 3132 African‐Americans (AA: 1315 cases) participating in the family‐based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h ² in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome‐wide significant (GWS; P < 5E‐08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion‐deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans‐ancestral meta‐analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward‐related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non‐European samples with distinct patterns of substance use may lead to the identification of novel ancestry‐specific genetic markers of risk.     

Proximity to seacoast: G. W. Field and the marine laboratory at Point Judith Pond,Rhode Island, 1896–1900

Conclusions By the time George Wilton Field concluded his work at the marine laboratory his initial scientific concerns had forced him directly into local politics. He pleaded with little success with the community of South Kingstown, and with no success with the town of Narragansett, to create and maintain a permanent breach:Is it not possible for the acute business sense and the broad philanthropy of the community to sweep aside petty, local, and personal jealousies which are now blocking practical progress for the establishment of a permanent breach at Point Judith Pond? It is truly criminal neglect which permits fifteen hundred acres of valuable water-farming area to lie practically idle and rapidly deteriorate with each passing year.... In the opinion of the writer the Point Judith Pond and those of similar type could be made the seat of oyster, clam, crab, herring, white perch, and striped bass fisheries.³⁰ In the summer of 1899 Field was invited to teach a summer course on echinoderms at the MBL in Woods Hole, and to conduct summer research in a laboratory of the U.S. Fish Commission, also located at Woods Hole. When the summer was over, he remained there. Whether he had intentions of returning to resume his position in Rhode Island is unclear. At this point all correspondence with the Agricultural Experiment Station ceases, and Field's last report is a brief statement in the annual report of the experiment station for 1900 wherein he laments the variety of experiments he has not been able to carry to conclusion, such as a study of the artificial fertilization of water analogous to the method of chemically fertilizing the land for crops.The correspondence reveals that the enthusiasm Field brought to Point Judith Pond in 1896 was gradually sapped by his own fragile health, by three years' exposure to the local politics surrounding the southern Rhode Island fishing industry, and by a college administration determined to remove the stench of his invertebrates. He sought a refuge in the sheltered world of pure research at the U.S. Fish Commission Laboratory, where he set out to investigate the Origin of Sex using, as his animal models, squid and toadfish.On November 14, 1899, the Board of Managers of the college ordered the director of the experiment station to dispose of the marine laboratory at Point Judith Pond.³¹ How long the laboratory at Buttonwood Point survived in the institutional memory of the University of Rhode Island is open to question. The current Graduate School of Oceanography, in the event, traces its history back to 1937, not 1896.Nevertheless, Field and his one-room marine station established a precedent of land-grant marine research that other state colleges would follow, including Rhode Island itself, which reestablished its marine station, this time permanently, at South Ferry in 1937. In his brief research career in Rhode Island, George Wilton Field had discovered the same coastal attributes that would lead later to the creation of one of the world's major marine research centers at the University of Rhode Island's Graduate School of Oceanography.And, in a measure of triumph for his work, little more than a year after Field left for Woods Hole and his laboratory was dismantled, the town of South Kingstown voted the funds necessary to begin the construction of a permanent breachway.³² Whether Field's scientific reasoning and the conclusions of his marine research played any part in finally deciding the thirty-year-old debate in the affirmative will probably never be known. What is evident is that Field had no patience for those who could not see the results of his research as clearly as he could himself.     

Charging up Battery Recycling Policies: Extended Producer Responsibility for Single‐Use Batteries in the European Union,Canada, and the United States

Extended producer responsibility (EPR) policies have proven effective at raising consumer awareness, expanding waste collection infrastructure, and shifting costs of end‐of‐life (EOL) management from municipalities to stewardship organizations. Yet, such policies have been less successful in advancing waste management programs that ensure a net environmental benefit. This article analyzes how EPR policies for single‐use batteries in the European Union (EU), Canada, and the United States address the environmental costs and benefits of EOL management. Considering these EPR policies is instructive, because single‐use batteries have high collection costs and are of relatively low economic value for waste processors. Without deliberate planning, the environmental burdens of collecting and recycling such batteries may exceed the benefits. This article considers how EPR policies for single‐use batteries integrate performance requirements such as collection rates, recycling efficiencies, and best available techniques. It argues that for such policies to be effective, they need to be extended to address waste collection practices, the life cycle consequences of EOL management, and the quality of recovered materials. Such strategies are relevant to EPR policies for other products with marginal secondary value, including some textiles, plastics, and other types of electronic waste.     

The effect of high temperature and high atmospheric CO2 on carbohydrate changes in bell pepper (Capsicum annuum) pollen in relation to its germination

Pollen viability and germination are known to be sensitive to high temperature (HT). However, the mode by which high temperature impairs pollen functioning is not yet clear. In the present study, we investigated the effect of high temperature on changes occurring in carbohydrate of bell pepper (Capsicum annuum L. cv. Mazurka) pollen in order to find possible relations between these changes and pollen germination under heat stress. When pepper plants were maintained under a moderate HT regime (32/26 degrees C, day/night) for 8 days before flowers have reached anthesis, pollen count at anthesis was similar to that found in plants grown under normal temperatures (NT 28/22 degrees C). However, the in vitro germination, carried out at 25 degrees C, of pollen from HT plants was greatly reduced. This effect matched the marked reduction in the number of seeds per fruit in the HT plants. Maintaining the plants at high air CO2 concentration (800 &mgr;mol mol-1 air) in both temperature treatments did not affect the in vitro germination of pollen from NT plants, but restored germination to near the normal level in pollen from HT plants. Under NT conditions, starch, which was negligible in pollen at meiosis (8 days before anthesis, A-8) started to accumulate at A-4 and continued to accumulate until A-2. From that stage until anthesis, starch was rapidly degraded. On the other hand, sucrose concentration rose from stage A-4 until anthesis. Acid invertase (EC 3.2.1.26) activity rose parallel with the increase of sucrose. In pollen from HT plants, sucrose and starch concentrations were significantly higher at A-1 pollen than in that of NT plants. Under high CO2 conditions, the sucrose concentration in the pollen of HT plants was reduced to levels similar to those in NT pollen. In accordance with the higher sucrose concentration in HT pollen, the acid invertase activity in these pollen grains was lower than in NT pollen. The results suggest that the higher concentrations of sucrose and starch in the pollen grains of HT plants may result from reduction in their metabolism under heat stress. Elevated CO2 concentration, presumably by increasing assimilate availability to the pollen grain, may alleviate the inhibition of sucrose and starch metabolism, thereby increasing their utilization for pollen germination under the HT stress. Acid invertase may have a regulatory role in this system.     

APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway

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