Phosphatidylinositol (4,5)-bisphosphate turnover by INP51 regulates the cell wall integrity pathway in "Saccharomyces cerevisiae"

Signal transduction pathways are important for the cell to transduce external or internal stimuli where second messengers play an important role as mediators of the stimuli. One important group of second messengers are the phosphoinositide family present in organisms ranging from yeast to mammals. The dephosphorylation and phosphorylation cycle of the phosphatidylinositol species are thought to be important in signaling for recruitment or activation of proteins involved in vesicular transport and/or to control the organization of the actin cytoskeleton. In mammals, phosphatidylinositol (4,5)bisphosphate (PI(4,5)P2) signaling is essential and regulated by various kinases and phosphatases. In the model organism Saccharomyces cerevisiae PI(4,5)P2 signaling is also essential but the regulation remains unclear. My dissertation focuses on the regulation of PI(4,5)P2 signaling in Saccharomyces cerevisiae. The organization of the actin cytoskeleton in Saccharomyces cerevisiae is regulated by different proteins such as calmodulin, CMD1, and here I present data that CMD1 plays a role in the regulation of the only phosphatidylinositol 4-phosphate 5-kinase, MSS4, in Saccharomyces cerevisiae. CMD1 regulates MSS4 activity through an unknown mechanism and thereby controls the organization of the actin cytoskeleton. MSS4 and CMD1 do not physically interact but MSS4 seems to be part of a large molecular weight complex as shown by gel filtration chromatography. This complex could contain regulators of the MSS4 activity. The complex is not caused by dimerization of MSS4 since MSS4 does not interact with itself. Two pathways, the cell wall integrity pathway and TORC2 (target of rapamycin complex 2) signaling cascade are important for the organization of the actin cytoskeleton. Loss of TOR2 function results in a growth defect that can be suppressed by MSS4 overexpression. To further characterize the link between MSS4 and the TORC2 signaling pathway and the cell wall integrity pathway we looked for targets of PI(4,5)P2. The TORC2 pathway and the cell wall integrity pathway signal to the GEF ROM2, an activator of the small GTPase RHO1. In our study we identified ROM2 as a target of PI(4,5)P2 signaling. We observed that the ROM2 localization changes in an mss4 conditional mutant. This suggests that the proper localization needs PI(4,5)P2. This could be mediated by the putative PI(4,5)P2 binding pleckstrin homology (PH) domain of ROM2. To better understand the regulation of PI(4,5)P2 levels in Saccharomyces cerevisiae we focused on one of the PI(4,5)P2 5-phosphatases, INP51. Here we present evidence that INP51 is a new negative regulator of the cell wall integrity pathway as well as the TORC2 pathway. INP51 probably regulates these two pathways by the turnover of PI(4,5)P2 thereby inactivating the effector/s. The deletion of INP51 does not result in any phenotype, but when combined with mutations of the cell wall integrity pathway we observe synthetic interaction. INP51 together with the GTPase activating protein (GAP) SAC7, responsible for the negative regulation of RHO1, negatively regulates the cell wall integrity pathway during vegetative growth. One of the targets of cell wall integrity pathway, the cell wall component chitin, which is normally deposited at the bud end, bud neck and forms bud scars, is delocalized in the mother cell in the sac7 inp51 double deletion mutant. In addition, another downstream component of the cell wall integrity pathway, the MAP kinase MPK1, has increased phosphorylation and protein level in the sac7 inp51 double deletion mutant. This suggests that INP51 is important for the negative regulation of the cell wall integrity pathway. Furthermore, we show evidence that INP51 forms a complex with TAX4 or IRS4, with two EH-domain containing proteins, that positively regulates the activity of INP51 and in this manner negatively regulate the cell wall integrity pathway. The EH-domain is known to bind the NPF-motif. This motif is present in INP51 and is important for INP51 interaction with TAX4 or IRS4. The EH-NPF interaction is a conserved mechanism to build up protein networks. The interaction between an EH-domain containing protein and a PI(4,5)P2 5-phosphatase is conserved. This is demonstrated by the epidermal growth factor substrate EPS15 (EH) interaction with the PI(4,5)P2 5-phosphatase synaptojanin the mammalian orthologue of the Saccharomyces cerevisiae INP proteins. In summary, INP51 together with TAX4 and IRS4, forms complexes important for regulation of PI(4,5)P2 levels. The complexes are linked to the TORC2 signaling pathway and the cell wall integrity pathway, specifically regulating MPK1 activation and chitin biosynthesis. The work presented in this dissertation facilitates the development of a model of the complex regulation of PI(4,5)P2 signaling in Saccharomyces cerevisiae

Technical, Allocative, and Economic Efficiency in Swedish Dairy Farms: The Data Envelopment Analysis Versus the Stochastic Frontier Approach

Technical, allocative, and economic input efficiency scores were estimated for an unbalanced panel of Swedish dairy farms, using data envelopment analysis (DEA) and the stochastic frontier approach (SFA). By comparing the results it was concluded that when the entire dairy farm is studied the DEA is more appropriate to use since it does not require any particular parametric form to be chosen. The average DEA technical, allocative and economic efficiency indices were eventually found to be 0.77, 0.57, and 0.43 respectively. The influence of size on the efficiency scores was analyzed and significant evidence indicating a positive relationship between size and efficiency was found. Finally it was concluded that the main challenge facing the Swedish dairy farms is to enhance their cost minimizing skills.technical efficiency, allocative efficiency, economic efficiency, data envelopment analysis, stochastic frontier approach, Livestock Production/Industries, C14, C23, C24,

What is the Effect of Operational Managerial Practices on Dairy Farm Efficiency? Some Results from Sweden

The article aims to investigate how operational managerial practices can contribute to improved farm level efficiency at dairy farms. Operational managerial practices are defined as animal health, breeding, and feeding practices. The main contribution of the article is that it investigates aspects that can be adjusted every day to improve farm efficiency. Aspects describing each of the considered managerial practices are regressed on farm level data envelopment efficiency scores based on farm level data from Sweden. The results show that changes in breeding and feeding practices can lead to improved efficiency. Breeding exactly the number of heifers that is needed for replacement of the dairy cows negatively affects long-run technical efficiency. On the other hand, analyzing forage positively affects long-run allocative efficiency and analyzing fodder grain positively affects short-run economic efficiency. Feeding the cows hay instead of only silage, reduces long-run economic efficiency. No significant effects of animal health practices were found. These results suggest that the farms in the sample are homogeneous in terms of animal health practices and that inefficient farms cannot become more efficient by adapting to the animal health practices of more efficient farms.allocative efficiency, dairy farms, data envelopment analysis, economic efficiency, operational managerial practices, technical efficiency, tobit regression, Sweden, Livestock Production/Industries, Productivity Analysis,

How can Farmer Managerial Capacity Contribute to Improved Farm Performance? A Study of Dairy Farms in Sweden

This paper investigates how managerial capacity aspects influence efficiency of dairy farms in Sweden. Based on non-parametric methods, Tobit and logistic regressions, several managerial capacity aspects are found to influence long and short run input efficiency scores, but to influence output efficiency less. Examples of important aspects are: internal locus of control, positive profitability attitude, profitability perception and participation in study circles. Based on this, a way of supporting dairy farms to become more profitable is to organize educational and discussion clubs where the farmers learn from each other and form professional dairy farm advisors.dairy farms, data envelopment analysis, decision-making, efficiency, logistic regression, managerial capacity, Tobit Regression, Farm Management, Productivity Analysis,

Transferring custody from birth parents to foster parents - an ambiguous matter

In this study, we analyse 32 district court decisions regarding custody transfers from the birth parents to the foster parents in Sweden. When a child has been in foster care for three years, in order to enhance stability for child, the local social welfare committee considers a transferral of custody to the foster parents following an application to the district court. Although all but one of the decisions in our study favoured a custody transfer, the courts acknowledge different reasons for this. Specifically, there is vagueness about whether or not functioning contact between the child and birth parents is a hindrance in custody transfer. Our findings stress the need for clarification in the law regarding the criteria for custody transfer in order to reach a more unified judgment. Furthermore, the district courts do not sufficiently acknowledge children’s views, and we suggest that children and young people should be made more visible in the decision-making process

Interpretable Instance-Based Text Classification for Social Science Research Projects

In this study, two groups of respondents have evaluated explanations generated from an instance-based explanation method called WITE (Weighted Instance-based Text Explanations). One group consisted of 24 non-experts who answered a web survey about the words characterising the concepts of the classes and the other group consisted of three senior researchers and three respondents from a media house in Sweden who answered a questionnaire with open questions. The data used originates from one of the researchers’ project on media consumption in Sweden. The results from the non-experts indicate that WITE identified many words that corresponded to the human understanding but also included some insignificant or contrary words as important. In the results from the expert evaluation, there were indications that there is a risk that the explanations could persuade the users of the correctness of a prediction, even if it is incorrect. Consequently, the study indicates that an explanation method could be seen as a new actor which is able to persuade and interact with the humans and cause a change in the results of the classification of a text

Strengths and resilience of migrant women in transit: An analysis of the narratives of Central American women in irregular transit through Mexico towards the USA

This study departed from the idea that all people, including those hardest hit by adversity, have strengths and resiliencies. It posed the question on how a particularly vulnerable group, Central American migrant women in irregular transit through Mexico, used their strengths and resilience to reach the border with the USA. Past research has failed to address the issue of strengths and resilience in Central American migrant women, instead, much attention has been placed on the risks and vulnerabilities of this group. This research started from the strengths perspective and resilience theories to address the issue of skills and abilities of migrant women in transit through Mexico. Specifically, it was about discovering the women’s strengths, knowing how they used them to face and overcome the adversities of the journey and how they made sense of them. For this purpose, 10 narrative interviews were conducted in the Mexican border city of Tijuana, and microethnographic work was done with these women. The results of this research indicated that these migrant women are possessors of internal and external strengths; the first is related to their religious beliefs, courage, endurance and goal setting and the second with the support received from people, institutions, and their families. It was concluded that thanks to the combination of all these strengths, these women were able to successfully reach the border with the USA