The expression of a recombinant glycolate dehydrogenase polyprotein in potato (Solanum tuberosum) plastids strongly enhances photosynthesis and tuber yield

We have increased the productivity and yield of potato (Solanum tuberosum) by developing a novel method to enhance photosynthetic carbon fixation based on expression of a polyprotein (DEFp) comprising all three subunits (D, E and F) of Escherichia coli glycolate dehydrogenase (GlcDH). The engineered polyprotein retained the functionality of the native GlcDH complex when expressed in E. coli and was able to complement mutants deficient for the D, E and F subunits. Transgenic plants accumulated DEFp in the plastids, and the recombinant protein was active in planta, reducing photorespiration and improving CO2 uptake with a significant impact on carbon metabolism. Transgenic lines with the highest DEFp levels and GlcDH activity produced significantly higher levels of glucose (5.8-fold), fructose (3.8-fold), sucrose (1.6-fold) and transitory starch (threefold), resulting in a substantial increase in shoot and leaf biomass. The higher carbohydrate levels produced in potato leaves were utilized by the sink capacity of the tubers, increasing the tuber yield by 2.3-fold. This novel approach therefore has the potential to increase the biomass and yield of diverse crops

What are the facilitating conditions that support teaching as inquiry (TaI) for secondary technology teachers who are middle leaders in greater Christchurch?

This study aims to propose ideal conditions for Technology teachers to develop effective philosophies enabling them to focus on activities that promote successful learning. This research examines how selected secondary Technology educators, exemplify aspects of Teaching as Inquiry (TaI) effective pedagogies, that support the generation and development of successful philosophies. By identifying five common traits or characteristics, this study enquires what it is they do that supports successful teacher philosophy, generating positive outcomes for learners. It explores how and why Technology teachers have developed this approach, how these traits are connected and inter-related to attitudes and the resulting dispositions they hold, and the philosophies they have developed. In the quest for sustainable conditions, enabling and inhibiting influences are also investigated. To be fully inclusive of all aspects influencing TaI practice, aspects outside the location of individual inquiry are explored: How individual TaI exists within school culture, faculty, senior administrative and management philosophies within systems where the teacher is employed, and how TaI practice exists within wider national policy. It explains how TaI in New Zealand, appears to flourish within a foundation of Culturally Responsive Pedagogies. It also suggests a simple re-consideration around the nature of individual learners, and how their needs to develop responsive and effective pedagogies, seeing a different ‘new construct, end-goal’ of future focussed schooling, could conflict with immediate current assessment, and compliance needs. This study concludes by suggesting a set of ideal facilitating conditions that together could enable the development of philosophies supporting the effective pedagogies of Teaching as Inquiry

Developing credit risk score using SAS programming

Объектом исследования являются данные о кредитоспособности заемщиков. Предмет исследования: модель кредитного риска и системный интерфейс (GUI). Цель проекта - разработать систему на основе модели кредитного риска с использованием программирования SAS, чтобы помочь банку в принятии решений, контролировать риск и выбирать более хороших заемщиков и удалять плохих заемщиков из банка.The object of the study is data on the creditworthiness of borrowers. The subject of the research the credit risk model and make a system interface (GUI). The objective of the project is to develop the system from credit risk model by using SAS programming to help the bank in decision-making, control the risk and choose more good borrowers and delete bad borrowers from the bank. In the research project, to learn how to develop credit scoring using SAS programming and create program calculate credit risk score using Python . As a result of the study, it is show that to improves the accuracy of the assessment of creditworthiness by using logistic regression (selection variables method, evaluation dataset). The conclusion is the program calculator is made

Heterogeneity of Myc expression in breast cancer exposes pharmacological vulnerabilities revealed through executable mechanistic modeling

Cells with higher levels of Myc proliferate more rapidly and supercompetitively eliminate neighboring cells. Nonetheless, tumor cells in aggressive breast cancers typically exhibit significant and stable heterogeneity in their Myc levels, which correlates with refractoriness to therapy and poor prognosis. This suggests that Myc heterogeneity confers some selective advantage on breast tumor growth and progression. To investigate this, we created a traceable MMTV-Wnt1-driven in vivo chimeric mammary tumor model comprising an admixture of low-Myc- and reversibly switchable high-Myc-expressing clones. We show that such tumors exhibit interclonal mutualism wherein cells with high-Myc expression facilitate tumor growth by promoting protumorigenic stroma yet concomitantly suppress Wnt expression, which renders them dependent for survival on paracrine Wnt provided by low-Myc-expressing clones. To identify any therapeutic vulnerabilities arising from such interdependency, we modeled Myc/Ras/p53/Wnt signaling cross talk as an executable network for low-Myc, for high-Myc clones, and for the 2 together. This executable mechanistic model replicated the observed interdependence of high-Myc and low-Myc clones and predicted a pharmacological vulnerability to coinhibition of COX2 and MEK. This was confirmed experimentally. Our study illustrates the power of executable models in elucidating mechanisms driving tumor heterogeneity and offers an innovative strategy for identifying combination therapies tailored to the oligoclonal landscape of heterogenous tumors

Rac1 Controls Both the Secretory Function of the Mammary Gland and Its Remodeling for Successive Gestations.

An important feature of the mammary gland is its ability to undergo repeated morphological changes during each reproductive cycle with profound tissue expansion in pregnancy and regression in involution. However, the mechanisms that determine the tissue's cyclic regenerative capacity remain elusive. We have now discovered that Cre-Lox ablation of Rac1 in mammary epithelia causes gross enlargement of the epithelial tree and defective alveolar regeneration in a second pregnancy. Architectural defects arise because loss of Rac1 disrupts clearance in involution following the first lactation. We show that Rac1 is crucial for mammary alveolar epithelia to switch from secretion to a phagocytic mode and rapidly remove dying neighbors. Moreover, Rac1 restricts the extrusion of dying cells into the lumen, thus promoting their eradication by live phagocytic neighbors while within the epithelium. Without Rac1, residual milk and cell corpses flood the ductal network, causing gross dilation, chronic inflammation, and defective future regeneration

LabCaS: Labeling calpain substrate cleavage sites from amino acid sequence using conditional random fields

The calpain family of Ca 2+ ‐dependent cysteine proteases plays a vital role in many important biological processes which is closely related with a variety of pathological states. Activated calpains selectively cleave relevant substrates at specific cleavage sites, yielding multiple fragments that can have different functions from the intact substrate protein. Until now, our knowledge about the calpain functions and their substrate cleavage mechanisms are limited because the experimental determination and validation on calpain binding are usually laborious and expensive. In this work, we aim to develop a new computational approach (LabCaS) for accurate prediction of the calpain substrate cleavage sites from amino acid sequences. To overcome the imbalance of negative and positive samples in the machine‐learning training which have been suffered by most of the former approaches when splitting sequences into short peptides, we designed a conditional random field algorithm that can label the potential cleavage sites directly from the entire sequences. By integrating the multiple amino acid features and those derived from sequences, LabCaS achieves an accurate recognition of the cleave sites for most calpain proteins. In a jackknife test on a set of 129 benchmark proteins, LabCaS generates an AUC score 0.862. The LabCaS program is freely available at: http://www.csbio.sjtu.edu.cn/bioinf/LabCaS . Proteins 2013. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97155/1/24217_ftp.pd

Исследование влияния солей лития на жизнеспособность бактерий E.coli

В работе исследовано влияние органических солей лития на жизнеспособность и метаболизм культуры E. coli. Установлено, что соли пирувата и сукцината лития не обладают токсичностью в концентрациях от 1,28 до 21,28 ммоль/л. Выявлено, что с увеличением концентрации сукцината и пирувата лития возрастает жизнеспособность культуры E. coli при культивировании на благоприятной и обеднённой питательных средах. Обнаружено, что добавление пирувата и сукцината лития влияет на биохимические процессы бактериальной клетки.The effect of organic lithium salts on the viability and metabolism of E. coli bacteria is investigated. It was found that the salts of lithium pyruvate and succinate do not have toxicity in concentrations from 1.28 to 21.28 mmol/l. It was found that lithium salts at the concentration of 12.77 and 21.28 mmol/l lead to growth increasing of E. coli bacteria in beef-extract broth and a physiological salt solution. It was found that the addition of lithium pyruvate and lithium succinate affects the biochemical processes of the bacterial cell

Stat3 controls cell death during mammary gland involution by regulating uptake of milk fat globules and lysosomal membrane permeabilization.

We have previously demonstrated that Stat3 regulates lysosomal-mediated programmed cell death (LM-PCD) during mouse mammary gland involution in vivo. However, the mechanism that controls the release of lysosomal cathepsins to initiate cell death in this context has not been elucidated. We show here that Stat3 regulates the formation of large lysosomal vacuoles that contain triglyceride. Furthermore, we demonstrate that milk fat globules (MFGs) are toxic to epithelial cells and that, when applied to purified lysosomes, the MFG hydrolysate oleic acid potently induces lysosomal leakiness. Additionally, uptake of secreted MFGs coated in butyrophilin 1A1 is diminished in Stat3-ablated mammary glands and loss of the phagocytosis bridging molecule MFG-E8 results in reduced leakage of cathepsins in vivo. We propose that Stat3 regulates LM-PCD in mouse mammary gland by switching cellular function from secretion to uptake of MFGs. Thereafter, perturbation of lysosomal vesicle membranes by high levels of free fatty acids results in controlled leakage of cathepsins culminating in cell death.This work was supported by a grant from the Medical Research Council programme grant no. MR/J001023/1 (T.J.S. and B. L-L.) and a Cancer Research UK Cambridge Cancer Centre PhD studentship (H.K.R.).This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb3043.html