The ZERO: Zip-Tie Revolver

The Boise State University Microgravity Team has been challenged with designing a mechanical Zip-tie tool to be used during EVA missions on the ISS. NASA is looking for a new tool that will allow astronauts to fasten zip-ties to secure wires and hoses. This tool would need to have a number of zip-ties stored internally, be quickly reusable, and would need to be easily and safely operated by an astronaut in a single handed operation

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

Сельскохозяйственная кооперация Урала за 1926-27 хозяйственный год и за I квартал 1927-28 г.: материалы к III собранию уполномоченных Уралселькустсоюза

0|7|Общие условия и итоги работы с.-х. кооперации за отчетный период [c. 7]0|11|Направление и темп кооперирования [c. 11]0|13|Союзное строительство [c. 13]0|13|Социальный состав пайщиков и его регулирование [c. 13]0|16|Итоги перевыборной кампании [c. 16]0|17|Аппарат системы [c. 17]0|18|Направление и характер организационной работы системы [c. 18]0|19|Культработа [c. 19]0|20|Массовая работа [c. 20]0|20|Колхозное строительство [c. 20]0|22|Кредитная работа [c. 22]0|26|Торгово-посредническая деятельность [c. 26]0|30|Финансы [c. 30]0|33|Производственная деятельность [c. 33]0|34|Агрикультурная работа [c. 34]0|35|Кустарно-промысловая кооперация в системе сел.-хоз. кооперации [c. 35]0|38|Состояние и работа системы в I кв. 1927-28 г. [c. 38]0|39|Рост колхозного движения [c. 39]0|40|Товарооборот с.-х. кооперации [c. 40]0|41|Финансовое состояние системы [c. 41]0|41|Итоги и перспективы [c. 41]0|45|Таблицы [c. 45]1|45|Сельско-хозяйственная кооперация в 1926-28 году [c. 45]2|45|Организационное состояние [c. 45]3|46|Сеть кооперативов в районах деятельности союзов сельско-хоз. и куст. пром. кооперации Уралобласти по видам [c. 46]3|47|Число всех кооперативов и членов в них в районах деятельности отдельных союзов сел.-хоз. и куст.-пром. кооперации и процент кооперированности хозяйств по округам [c. 47]3|49|Социально-имущественный состав членов-пайщиков сел.-хоз. кредитных товариществ на 1 октября 1927 года [c. 49]3|50|Состав правлений и ревкомиссий низовой сети сельско-хозяйственной кооперации до и после перевыборов 1927-28 г. [c. 50]2|51|Финансовое состояние [c. 51]3|52|Сводные балансы по отдельным видам сельско-хозяйственных кооперативов на 1-Х-1926 г. и 1-Х-1927 г. [c. 52]3|53|Сводные балансы сельско-хозяйственных кредитных товариществ на 1 октября 1927 года по союзам [c. 53]3|54|Балансы (нетто) союзов сел.-хоз. куст.-пром. кооперации на 1 октября 26 г. и на 1 октября 27 г. [c. 54]3|56|Балансы Уралселькустсоюза на 1-Х-1926 г. и 1-Х-1927 года [c. 56]3|57|Использование фондов кооперирования бедноты в 1926-27 г. и создание таковых из прибылей 1926-27 г. по низовой сети [c. 57]2|59|Хозяйственная работа и ее результаты [c. 59]3|61|Оброт по продаже товаров отдельных звеньев сельско-хозяйственной кооперации по сортиментным группам за 1926-27 год [c. 61]3|62|Распределение торговых оборотов сель.-хоз, кредитных товариществ по контрагентам в 1926-27 г. [c. 62]3|63|Общеторговые расходы сел.-хоз. кредитных товариществ за 1926-27 год [c. 63]3|64|Доходы сельско-хозяйственных кредитных товариществ за 1926-1927 год [c. 64]3|65|Агрономические предприятия низовой сети сель.-хоз кооперации на 1-Х 1927 год [c. 65]3|66|Промышленные предприятия низовой сети сельско-хозяйственной кооперации на 1-Х-1927 г. [c. 66]3|67|Товарооборот союзов сельско-хозяйственной и кустарно-промысловой кооперации за 1926-27 год [c. 67]3|68|Покупка и продажа товаров по снабжению союзами с.-х. куст. промысл. кооперации с разбивкой на контрагентов в 1926-27 г. [c. 68]3|69|Покупка и продажа товаров по сбыту союзами сел.-хоз. куст. пром. кооперации с разбивкой на контрагентов в 1926-27 году [c. 69]3|70|Доходы и обще-торговые расходы союзов сел.-хоз. и куст.-пром. кооперации в 1926-1927 году [c. 70]3|71|Наложение на себестоимость товаров в 1927-28 году [c. 71]2|72|Сельско-хозяйственная кооперация в I квартале 1927-28 года [c. 72]3|73|Сеть кооперативов в районе деятельности окружных и районных союзов, входящих в систему областного союза сел.-хоз. кооперации на 1-Х-27 г. и 1-I-1928 г. [c. 73]3|74|Число всех кооперативов и членов в них по отдельным союзам и процент кооперированости хозяйств по округам [c. 74]3|75|Сводные балансы с.-хоз. кредитных товариществ на 1 октября 27 г. и 1 января 1928 г. [c. 75]3|76|Сводные балансы (нетто) 1-ти окружных и районных союзов сел.-хоз. кооперации на 1-Х-27 и 1-I -28 г. [c. 76]3|78|Балансы (нетто) Уралселькустсоюза на 1/I-27 г., 1/I-28 г. и 1-IV-28 г. [c. 78]3|80|Оборот по продаже товаров союзов сельско-хозяйственной кооперации за I кварта 1927-28 года [c. 80]3|81|Обще-торговые расходы союзов сел.-хоз. кооперации в I квартале 1927-28 года [c. 81]3|82|Товарооборот и обще-торговые расходы союзов сел.-хоз. кооперации [c. 82]2|83|Текущие кампании [c. 83]3|84|Паевая кампания [c. 84]3|85|Перевыборная кампания 1927-28 г. [c. 85]3|85|Общие перевыборные собрания членов пайщиков сел.-хоз. кооперации в 1927-1928 году [c. 85]3|86|Перевыборные собрания уполномоченных сельско-хозяйственных к-вово в 1917-28 году [c. 86]0|87|Пояснения к таблицам [c. 87]0|90|Оглавление [c. 90

Functional Analysis and Molecular Dynamics Simulation of LOX-1 K167N Polymorphism Reveal Alteration of Receptor Activity

The human lectin-like oxidized low density lipoprotein receptor 1 LOX-1, encoded by the ORL1 gene, is the major scavenger receptor for oxidized low density lipoprotein in endothelial cells. Here we report on the functional effects of a coding SNP, c.501G>C, which produces a single amino acid change (K>N at codon 167). Our study was aimed at elucidating whether the c.501G>C polymorphism changes the binding affinity of LOX-1 receptor altering its function. The presence of p.K167N mutation reduces ox-LDL binding and uptake. Ox-LDL activated extracellular signal-regulated kinases 1 and 2 (ERK 1/2) is inhibited. Furthermore, ox-LDL induced biosynthesis of LOX-1 receptors is dependent on the p.K167N variation. In human macrophages, derived from c.501G>C heterozygous individuals, the ox-LDL induced LOX-1 46 kDa band is markedly lower than in induced macrophages derived from c.501G>C controls. Investigation of p.K167N mutation through molecular dynamics simulation and electrostatic analysis suggests that the ox-LDL binding may be attributed to the coupling between the electrostatic potential distribution and the asymmetric flexibility of the basic spine residues. The N/N-LOX-1 mutant has either interrupted electrostatic potential and asymmetric fluctuations of the basic spine arginines

Structural and functional analysis of rare missense mutations in human chorionic gonadotrophin β-subunit

Heterodimeric hCG is one of the key hormones determining early pregnancy success. We have previously identified rare missense mutations in hCGβ genes with potential pathophysiological importance. The present study assessed the impact of these mutations on the structure and function of hCG by applying a combination of in silico (sequence and structure analysis, molecular dynamics) and in vitro (co-immunoprecipitation, immuno- and bioassays) approaches. The carrier status of each mutation was determined for 1086 North-Europeans [655 patients with recurrent miscarriage (RM)/431 healthy controls from Estonia, Finland and Denmark] using PCR-restriction fragment length polymorphism. The mutation CGB5 p.Val56Leu (rs72556325) was identified in a single heterozygous RM patient and caused a structural hindrance in the formation of the hCGα/β dimer. Although the amount of the mutant hCGβ assembled into secreted intact hCG was only 10% compared with the wild-type, a stronger signaling response was triggered upon binding to its receptor, thus compensating the effect of poor dimerization. The mutation CGB8 p.Pro73Arg (rs72556345) was found in five heterozygotes (three RM cases and two control individuals) and was inherited by two of seven studied live born children. The mutation caused ∼50% of secreted β-subunits to acquire an alternative conformation, but did not affect its biological activity. For the CGB8 p.Arg8Trp (rs72556341) substitution, the applied in vitro methods revealed no alterations in the assembly of intact hCG as also supported by an in silico analysis. In summary, the accumulated data indicate that only mutations with neutral or mild functional consequences might be tolerated in the major hCGβ genes CGB5 and CGB8

Classificatory Theory in Data-Intensive Science: The Case of Open Biomedical Ontologies

publication-status: Publishedtypes: ArticleThis is the author's version of a paper that was subsequently published in International Studies in the Philosophy of Science. Please cite the published version by following the DOI link.Knowledge-making practices in biology are being strongly affected by the availability of data on an unprecedented scale, the insistence on systemic approaches and growing reliance on bioinformatics and digital infrastructures. What role does theory play within data-intensive science, and what does that tell us about scientific theories in general? To answer these questions, I focus on Open Biomedical Ontologies, digital classification tools that have become crucial to sharing results across research contexts in the biological and biomedical sciences, and argue that they constitute an example of classificatory theory. This form of theorizing emerges from classification practices in conjunction with experimental know-how and expresses the knowledge underpinning the analysis and interpretation of data disseminated online.Economic and Social Research Council (ESRC)The British AcademyLeverhulme Trus

Binding Modes of Peptidomimetics Designed to Inhibit STAT3

STAT3 is a transcription factor that has been found to be constitutively activated in a number of human cancers. Dimerization of STAT3 via its SH2 domain and the subsequent translocation of the dimer to the nucleus leads to transcription of anti-apoptotic genes. Prevention of the dimerization is thus an attractive strategy for inhibiting the activity of STAT3. Phosphotyrosine-based peptidomimetic inhibitors, which mimic pTyr-Xaa-Yaa-Gln motif and have strong to weak binding affinities, have been previously investigated. It is well-known that structures of protein-inhibitor complexes are important for understanding the binding interactions and designing stronger inhibitors. Experimental structures of inhibitors bound to the SH2 domain of STAT3 are, however, unavailable. In this paper we describe a computational study that combined molecular docking and molecular dynamics to model structures of 12 peptidomimetic inhibitors bound to the SH2 domain of STAT3. A detailed analysis of the modeled structures was performed to evaluate the characteristics of the binding interactions. We also estimated the binding affinities of the inhibitors by combining MMPB/GBSA-based energies and entropic cost of binding. The estimated affinities correlate strongly with the experimentally obtained affinities. Modeling results show binding modes that are consistent with limited previous modeling studies on binding interactions involving the SH2 domain and phosphotyrosine(pTyr)-based inhibitors. We also discovered a stable novel binding mode that involves deformation of two loops of the SH2 domain that subsequently bury the C-terminal end of one of the stronger inhibitors. The novel binding mode could prove useful for developing more potent inhibitors aimed at preventing dimerization of cancer target protein STAT3

Protonation States of Remote Residues Affect Binding-Release Dynamics of the Ligand but not the Conformation of apo Ferric Binding Protein

We have studied the apo (Fe3+ free) form of periplasmic ferric binding protein (FbpA) under different conditions and we have monitored the changes in the binding and release dynamics of H2PO4- that acts as a synergistic anion in the presence of Fe3+. Our simulations predict a dissociation constant of 2.2$\pm$0.2 mM which is in remarkable agreement with the experimentally measured value of 2.3$\pm$0.3 mM under the same ionization strength and pH conditions. We apply perturbations relevant for changes in environmental conditions as (i) different values of ionic strength (IS), and (ii) protonation of a group of residues to mimic a different pH environment. Local perturbations are also studied by protonation or mutation of a site distal to the binding region that is known to mechanically manipulate the hinge-like motions of FbpA. We find that while the average conformation of the protein is intact in all simulations, the H2PO4- dynamics may be substantially altered by the changing conditions. In particular, the bound fraction which is 20$\%$ for the wild type system is increased to 50$\%$ with a D52A mutation/protonation and further to over 90$\%$ at the protonation conditions mimicking those at pH 5.5. The change in the dynamics is traced to the altered electrostatic distribution on the surface of the protein which in turn affects hydrogen bonding patterns at the active site. The observations are quantified by rigorous free energy calculations. Our results lend clues as to how the environment versus single residue perturbations may be utilized for regulation of binding modes in hFbpA systems in the absence of conformational changes.Comment: 26 pages, 4 figure