Identification of a cellulose synthase-associated protein required for cellulose biosynthesis

Cellulose synthase-interactive protein 1 (CSI1) was identified in a two-hybrid screen for proteins that interact with cellulose synthase (CESA) isoforms involved in primary plant cell wall synthesis. CSI1 encodes a 2,150-amino acid protein that contains 10 predicted Armadillo repeats and a C2 domain. Mutations in CSI1 cause defective cell elongation in hypocotyls and roots and reduce cellulose content. CSI1 is associated with CESA complexes, and csi1 mutants affect the distribution and movement of CESA complexes in the plasma membrane

Genetic Interactions Between BOB1 And Multiple 26S Proteasome Subunits Suggest A Role For Proteostasis In Regulating Arabidopsis Development

Protein folding and degradation are both required for protein quality control, an essential cellular activity that underlies normal growth and development. We investigated how BOB1, an Arabidopsis thaliana small heat shock protein, maintains normal plant development. bob1 mutants exhibit organ polarity defects and have expanded domains of KNOX gene expression. Some of these phenotypes are ecotype specific suggesting that other genes function to modify them. Using a genetic approach we identified an interaction between BOB1 and FIL, a gene required for abaxial organ identity. We also performed an EMS enhancer screen using the bob1-3 allele to identify pathways that are sensitized by a loss of BOB1 function. This screen identified genetic, but not physical, interactions between BOB1 and the proteasome subunit RPT2a. Two other proteasome subunits, RPN1a and RPN8a, also interact genetically with BOB1. Both BOB1 and the BOB1-interacting proteasome subunits had previously been shown to interact genetically with the transcriptional enhancers AS1 and AS2, genes known to regulate both organ polarity and KNOX gene expression. Our results suggest a model in which BOB1 mediated protein folding and proteasome mediated protein degradation form a functional proteostasis module required for ensuring normal plant development

Prediction of immediate ventricular arrhythmias after coronary artery ligation

AbstractObjectives. Our aim was to test the hypothesis that increased beat to beat morphologic variations in the body surface electrocardiogram (ECG) are associated with fragmented diastolic electrical activity that appears after coronary artery ligation and to correlate the appearance of spontaneous ventricular fibrillation after coronary ligation with the magnitude of the ECG beat to beat variability.Background. Unstable and variably delayed electrical activation precedes the development of ventricular fibrillation in dogs with acute ischemia. Detection of these highly variable low amplitude signals from the body surface is currently impossible. We have developed a system designed to measure the degree of beat to beat variability of the ECG.Methods. With high fidelity electrocardiography, subtle beat to beat ECG morphologic variations were detected in epicardial and body surface electrograms and quantified as the variance of the ECG voltage at specific points of the cardiac cycle. The ratio of the variance at the QRS offset to that of the QRS onset (beat to beat variability index) was then calculated.Results. Ventricular fibrillation developed in 12 of 27 dogs after left anterior descending coronary artery ligation. In 7 of the 12 dogs it occurred immediately (<15 min) after ligation; in the other 5 it developed late (15 min) after ligation. Dogs with subsequently immediate ventricular fibrillation had a significantly higher beat to beat variability index than that of dogs with late or no ventricular fibrillation both before coronary ligation (4.7 ± 1.4 vs. 1.1 ± 0.2 and 0.8 ± 0.1, respectively, p < 0.001) and after ligation (6.4 ± 2.6, 1.0 ± 0.6 and 1.2 ± 0.6, respectively, p < 0.001). In dogs that developed ventricular fibrillation immediately after coronary ligation, the arrhythmia was preceded by fragmented diastolic electrical activity on the epicardial electrogram and a simultaneous increase in the beat to beat morphologic variability of the terminal portion of the body surface ECG QRS complex.Conclusions. Beat to beat QRS offset morphologic variations appear to be increased before and further increased after coronary artery ligation in dogs that develop ventricular fibrillation immediately after ligation. Increased beat to beat variability index may be associated with the presence of electrophysiologic instability and can predict early ventricular fibrillation

T cell receptor sequence clustering and antigen specificity

There has been increasing interest in the role of T cells and their involvement in cancer, autoimmune and infectious diseases. However, the nature of T cell receptor (TCR) epitope recognition at a repertoire level is not yet fully understood. Due to technological advances a plethora of TCR sequences from a variety of disease and treatment settings has become readily available. Current efforts in TCR specificity analysis focus on identifying characteristics in immune repertoires which can explain or predict disease outcome or progression, or can be used to monitor the efficacy of disease therapy. In this context, clustering of TCRs by sequence to reflect biological similarity, and especially to reflect antigen specificity have become of paramount importance. We review the main TCR sequence clustering methods and the different similarity measures they use, and discuss their performance and possible improvement. We aim to provide guidance for non-specialists who wish to use TCR repertoire sequencing for disease tracking, patient stratification or therapy prediction, and to provide a starting point for those aiming to develop novel techniques for TCR annotation through clustering

State Power and Economic Inefficiency : Explaining Political Failture in Africa

SUMMARY The problem of agricultural crisis in Africa has forced a review of the highly centralised and bureaucratised structures used to provide services to farmers since independence, and has resulted in a return to favour of decentralised market mechanisms. This article traces the historical evolution of the present system in the colonial period, and sets out the theoretical and political assumptions which lay behind its retention in the post?colonial period. It then attempts to account for current failures by examining the theoretical inconsistencies and actual conflicts of interest involved in the attempt to use these structures in the political, economic and social conditions prevailing in post?colonial Africa. It concludes by recommending a more flexible approach based upon the use of decentralised private and cooperative structures directly accountable to the farmers who use them. SOMMAIRE Le problème de la crise agricole en Afrique a forcé une révision des structures bureaucratìques et hautement centralisées, utilisées pour procurer des services aux fermiers depuis l'indépendance, ceci a eu pour résultat de plaider en faveur des mécanismes de marché décentralisées. Cet article trace révolution historique du système actuel dans la période coloniale, et présente les assomptions qui sont derrière son maintien dans la période post?coloniale. On tente ensuite d'expliquer les échecs récents en analysant les contradictions théoriques et les conflits d'intérêt actuels impliqués dans les tentatives d'utiliser ces structures sous des conditions politiques, économiques et sociales prévalant dans l'Afrique post?coloniale. L'article conclut en recommandant une approche plus flexible, basée sur l'utilisation de structures privées décentralisées et des structures coopératives imputables aux fermiers utilisateurs. RESUMEN El problema de la crisis agrícola en Africa ha forzado a una revisión de las estructuras altamente centralizadas y burocráticas utilizadas para proporcionar servicios a los agricultores, resultando en un retorno en favor de los mecanismos descentralizados del mercado. Este artículo describe la evolución histórica del sistema actual en el periodo colonial y establece las hipótesis teóricas y políticas que yacen por detrás de su persistencia en el periodo post?colonial. A continuación intenta explicar los fracasos actuales mediante el examen de las incoherencias teóricas y los conflictos de intereses involucrados en el propósito de utilizar estas estructuras en las condiciones políticas, sociales y económicas prevalecientes en Africa post?colonial. Concluye recomendando un enfoque más flexible basado en el uso de estructuras descentralizadas, tanto privadas como cooperativas, directamente responsables ante los granjeros que las utilizan

Modelling of regulatory factor and managerial impact assessment in the regional economy sectors: a case-study of the Kaliningrad region (Russia)

This article discusses the methodology of developing tools for assessing regulatory factors and managerial impacts on the regional economy and individual sectors and businesses. The potential of projection models is investigated, including balance models, convergence of regional and sectoral projection and compiling reliable and representative data sets capable of describing the current economic situation. An attempt was made to develop a series of models for several regional economies; to that end, the modelling of managerial and regulatory impact assessment was used in combination with the well-known value chain approach. In the interests of effective public administration, one of the requirements is to create sectoral model formats compatible with the regional projection models. Results of pilot modelling managerial and regulatory impacts on Kaliningrad region’s economies are presented through examples of agribusiness, transport, industry, tourism and recreation. Implementation of regulatory impact modelling in the framework of the suggested approach is proved for other regions. The main advantage of the developed models for the regional management is their ability to reduce uncertainty in decision-making due to obtaining estimates of the impact of the decisions on the changing situation and the conditions for the development of sectors and industries

SMAC mimetics promote NIK-dependent inhibition of CD4+ TH17 cell differentiation

Second mitochondria-derived activator of caspase (SMAC) mimetics (SMs) are selective antagonists of the inhibitor of apoptosis proteins (IAPs), which activate noncanonical NF-κB signaling and promote tumor cell death. Through gene expression analysis, we found that treatment of CD4+ T cells with SMs during T helper 17 (TH17) cell differentiation disrupted the balance between two antagonistic transcription factor modules. Moreover, proteomics analysis revealed that SMs altered the abundance of proteins associated with cell cycle, mitochondrial activity, and the balance between canonical and noncanonical NF-κB signaling. Whereas SMs inhibited interleukin-17 (IL-17) production and ameliorated TH17 cell–driven inflammation, they stimulated IL-22 secretion. Mechanistically, SM-mediated activation of NF-κB–inducing kinase (NIK) and the transcription factors RelB and p52 directly suppressed Il17a expression and IL-17A protein production, as well as the expression of a number of other immune genes. Induction of IL-22 production correlated with the NIK-dependent reduction in cMAF protein abundance and the enhanced activity of the aryl hydrocarbon receptor. Last, SMs also increased IL-9 and IL-13 production and, under competing conditions, favored the differentiation of naïve CD4+ T cells into TH2 cells rather than TH17 cells. These results demonstrate that SMs shape the gene expression and protein profiles of TH17 cells and inhibit TH17 cell–driven autoimmunity