Analysis of naturally occurring mutations in the human lipodystrophy protein seipin reveals multiple potential pathogenic mechanisms

Peer reviewedPublisher PD

Seipin oligomers can interact directly with AGPAT2 and lipin 1, physically scaffolding critical regulators of adipogenesis

This work was supported by a Merit Scholarship from the Islamic Development Bank (to M.M.U.T.), The Agency for Science, Technology and Research, Singapore (A*STAR) (M.F.M.S), the Medical Research Council (MRC) [NIRG GO800203 and Research Grant MR/L002620/1 (to J.J.R.), Program GrantG09000554 (to S.O.R)], The Wellcome Trust [078986/Z/06/Z (to S.O.R.)], the MRC Centre for Obesity and Related Metabolic Disorders (MRC-CORD) [GO600717] and the NIHR Comprehensive Biomedical Research Centre [CG50826].Peer reviewedPublisher PD

Detection of brain functional-connectivity difference in post-stroke patients using group-level covariance modeling

Functional brain connectivity, as revealed through distant correlations in the signals measured by functional Magnetic Resonance Imaging (fMRI), is a promising source of biomarkers of brain pathologies. However, establishing and using diagnostic markers requires probabilistic inter-subject comparisons. Principled comparison of functional-connectivity structures is still a challenging issue. We give a new matrix-variate probabilistic model suitable for inter-subject comparison of functional connectivity matrices on the manifold of Symmetric Positive Definite (SPD) matrices. We show that this model leads to a new algorithm for principled comparison of connectivity coefficients between pairs of regions. We apply this model to comparing separately post-stroke patients to a group of healthy controls. We find neurologically-relevant connection differences and show that our model is more sensitive that the standard procedure. To the best of our knowledge, these results are the first report of functional connectivity differences between a single-patient and a group and thus establish an important step toward using functional connectivity as a diagnostic tool

Impact of glucosinolate structure on the performance of the crucifer pest Phaedon cochleariae (F.)

Glucosinolates (GS) are sulfur-rich secondary metabolites found in the Brassicaceae and other related families of the order Brassicales. GS consist of structurally-related compounds with different side chains. To explore the possibility that various side chain confer divergent biological activities to individual GS, we have investigated the performance of the specialist pest beetle, Phaedon cochleariae (F.) on Arabidopsis thaliana L. mutants and Columbia wild-type (WT) which differ in the main group of GS. Plant lines of A. thaliana altered for the expression of MAM3, because of the introduction of an overexpression construct of MAM3 (mam3+) or containing double knockouts of CYP79B2 and CYP79B3 (cyp79B2-/cyp79B3-) were used for the study in comparison to the WT.A. thaliana genotypes differed in their GS profiles. The highest GS content was present in the WT followed by mam3+ and cyp79B2-/ cyp79B3-. A modified aliphatic GS content was detected for the mam3+ as compared to the WT lines. Furthermore, indolyl GS were completely absent in cyp79B2-/cyp79B3-. The percentage weight increase of larvae raised on each of the three plant genotypes was significant different. Larval performance was poorest on plants of cyp79B2-/cyp79B3- and best on WT, but there was no significant difference found in percentage weight increase on mam3+ and WT. There was no correlation between the weight increase of the larvae on genotypes and induced levels of aliphatic, indolyl, and total GS. However, the poor performance of beetle larvae on cyp79B2-/ cyp79B3-compared to WT and mam3+ might be explained by comparable high aliphatic GS levels of this mutant, a different induction of secondary metabolites, and the absence of indolyl GS. Basic knowledge about the relationship of GS structures and their insect pests may help in further resistance breeding of crucifer crops

A Case Study Analysis of the Kentucky Transportation Cabinet’s Design/Build Pilot Projects

The current economic climate has forced transportation agencies to evaluate opportunities to save money. One possible opportunity lies in Design/Build (DB) delivery. In 2006, with the approval of the Kentucky General Assembly, The Kentucky Transportation Cabinet selected ten projects to be developed through the Design/Build method. DB delivery offers many attainable advantages, the most notable being expedited delivery. The research described herein presents a case study of these DB pilot projects in order to capture lessons learned on the use of the DB delivery method on future projects. In order to determine which projects are suitable for DB delivery, a scorecard was developed based upon factors observed over the course of the DB pilot projects. Another important aspect of the DB pilot projects was their cost, it was believed their costs were much higher than a comparable design/bid/build (DBB) projects. However, after a thorough cost analysis, it was determined that the DB projects cost the Cabinet only an estimated three percent more than comparable DBB projects. The DB pilot projects have had mixed results. Several recommendations are provided that will assist agencies with DB project selection and successful management of DB projects

Institutional determinants of inward FDI: Evidence from Pakistan

FDI has been growing at a spectacular pace all over the world and emerging countries have been successful in attracting more FDI compared to developed countries. Institutional factors are becoming more important as determinants of inward FDI for emerging markets. However, research in this area is inadequate and also incosnsistent in terms of findings. In this paper, we have examined the institutional determinants of Pakistani FDI inflows and also examined the relative importance of those factors. The paper has found that certain institutional determinants such as size of the government, legal structure and strong property rights, freedom to trade and civil liberty have strong positive effect on FDI inflows. Among the institutional variables, regulation has been found to be most important to influence inward FDI flow to Pakistan. The paper has also found evidence that there was a structural break in FDI flows in Pakistan which coincides with market liberalization programme in early 1990s. This confirms the effectiveness of conducive institutional environment to attract foreign investment. Moreover, we have found that military government is more successful in attracting FDI compared to democratic government in Pakistan