The interaction of IQGAPs with calmodulin-like proteins

Since their identification over 15?years ago, the IQGAP (IQ-motif-containing GTPase-activating protein) family of proteins have been implicated in a wide range of cellular processes, including cytoskeletal reorganization, cell-cell adhesion, cytokinesis and apoptosis. These processes rely on protein-protein interactions, and understanding these (and how they influence one another) is critical in determining how the IQGAPs function. A key group of interactions is with calmodulin and the structurally related proteins myosin essential light chain and S100B. These interactions occur primarily through a series of IQ motifs, which are α-helical segments of the protein located towards the middle of the primary sequence. The three human IQGAP isoforms (IQGAP1, IQGAP2 and IQGAP3) all have four IQ motifs. However, these have different affinities for calmodulin, myosin light chain and S100B. Whereas all four IQ motifs of IQGAP1 interact with calmodulin in the presence of calcium, only the last two do so in the absence of calcium. IQ1 (the first IQ motif) interacts with the myosin essential light chain Mlc1sa and the first two undergo a calcium-dependent interaction with S100B. The significance of the interaction between Mlc1sa and IQGAP1 in mammals is unknown. However, a similar interaction involving the Saccharomyces cerevisiae IQGAP-like protein Iqg1p is involved in cytokinesis, leading to speculation that there may be a similar role in mammals.     

Increasing Accuracy and Throughput in Large-Scale Microsatellite Fingerprinting of Cacao Field Germplasm Collections

In this study we report on increasing the rate and accuracy of microsatellite fingerprinting of accessions in Theobroma cacao L. field germplasm collections with a medium-throughput capillary sequencing system. We examined the use of a reduced number of microsatellite loci to decrease the time and materials required for fingerprinting and determined the best available microsatellite loci for accurately separating accessions. A subset of nine informative loci that could separate sixty accessions into the same genetic groupings as a complete set of 37 loci was found. Stringent probability of identity values (i.e. chance of unique accession) was highly influenced (r?=??0.996; P?<?0.001) by the number of alleles utilised in the fingerprinting set but the composition of the primer set was more important when choosing discriminatory loci. DNA pooling to reduce the number of samples was also investigated. There was a relatively high level of mixture within plots (59% of 54 plots examined) of the field genebank, which opposed the use of a pooling strategy to fingerprint the multiple trees of an accession plot in the collection.     

Quantitative Study of the Effect of Tissue Microstructure on Contraction in a Computational Model of Rat Left Ventricle

Tissue microstructure, in particular the alignment of myocytes (fibre direction) and their lateral organisation into sheets, is fundamental to cardiac function. We studied the effect of microstructure on contraction in a computational model of rat left ventricular electromechanics. Different fibre models, globally rule-based or locally optimised to DT-MRI data, were compared, in order to understand whether a subject-specific fibre model would enhance the predictive power of our model with respect to the global ones. We also studied the impact of sheets on ventricular deformation by comparing: (a) a transversely isotropic versus an orthotropic material law and (b) a linear model with a bimodal model of sheet transmural variation. We estimated ejection fraction, wall thickening and base-to-apex shortening and compared them with measures from cine-MRI. We also evaluated Lagrangian strains as local metrics of cardiac deformation. Our results show that the subject-specific fibre model provides little improvement in the metric predictions with respect to global fibre models while material orthotropy allows closer agreement with measures than transverse isotropy. Nonetheless, the impact of sheets in our model is smaller than that of fibres. We conclude that further investigation of the modelling of sheet dynamics is necessary to fully understand the impact of tissue structure on cardiac deformation.     

Discovery and mapping of a new expressed sequence tag-single nucleotide polymorphism and simple sequence repeat panel for large-scale genetic studies and breeding of Theobroma cacao L

Theobroma cacao is an economically important tree of several tropical countries. Its genetic improvement is essential to provide protection against major diseases and improve chocolate quality. We discovered and mapped new expressed sequence tag-single nucleotide polymorphism (EST-SNP) and simple sequence repeat (SSR) markers and constructed a high-density genetic map. By screening 149 650 ESTs, 5246 SNPs were detected in silico, of which 1536 corresponded to genes with a putative function, while 851 had a clear polymorphic pattern across a collection of genetic resources. In addition, 409 new SSR markers were detected on the Criollo genome. Lastly, 681 new EST-SNPs and 163 new SSRs were added to the pre-existing 418 co-dominant markers to construct a large consensus genetic map. This high-density map and the set of new genetic markers identified in this study are a milestone in cocoa genomics and for marker-assisted breeding. The data are available at http://tropgenedb.cirad.fr.     

Microsatellite-aided detection of genetic redundancy improves management of the International Cocoa Genebank, Trinidad

Cacao (Theobroma cacao L.), the tree from which cocoa butter and chocolate is derived, is conserved in field genebanks. The largest of these ex situ collections in the public domain is the International Cocoa Genebank, Trinidad (ICG,T). Reduction of genetic redundancy is essential to improve the accuracy and efficiency of genebank management. This study examined the pedigree and genetic diversity in a subset of 387 accessions in this collection. Sibship reconstruction of this subset revealed 56 full-sib families nested within 189 half-sib families. Sixteen centers of interconnectivity were identified, which suggested a high level of genetic redundancy in the collection. Generally, consistent phylogenetic trees were obtained using different genetic distance measures. However, a principal coordinate analysis of the D _est differentiation measure elicited the best representation of accession group clustering, and we recommend this approach when probing fine-scale genetic differentiation among cacao accessions. The composite genetic diversity of 414 cacao accessions was contained in a core set of 59 unique accessions. These results have significant implications in the conservation of genetic resources of the ICG,T and other cacao genebanks. The approach developed in this study is recommended as a strategy to curators in guiding conservation management practices of cacao and other similar ex situ genebanks.     

Chaste: An Open Source C++ Library for Computational Physiology and Biology

Chaste — Cancer, Heart And Soft Tissue Environment — is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high-performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to ‘re-invent the wheel’ with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials.

This is a PLOS Computational Biology Software Article

     

Histiocytoid change in breast carcinoma: a report of 3 cases with an unusual cytomorphologic pattern of apocrine change

BACKGROUND: Breast carcinomas composed predominantly or exclusively of cells with foamy and/or granular cytoplasm have been termed histiocytoid breast carcinoma. CASES: Three cases of HBC had fine needle aspirates that were moderately cellular and composed of cells with abundant foamy and/or granular cytoplasm, arranged in loosely cohesive groups and dispersed singly. The cells showed subtle cytologic atypia, including nuclear hyperchromasia and slightly irregular nuclear outlines. Definitive cytologic diagnosis was not possible in the 3 cases, and they were reported as "suspicious for malignancy." Core biopsies of 2 cases showed a typical Indian file pattern of invasive lobular carcinoma, while the third case was composed of sheets of discohesive histiocytoid cells admixed with a prominent lymphoid infiltrate. All 3 cases were E-cadherin negative, confirming their lobular nature. CONCLUSION: HBC represents an unusual morphologic pattern of apocrine change that may be seen in lobular and ductal breast carcinomas. Recognition of these lesions is vital in that they may be mistaken for a variety of other entities composed of foamy/granular cells; some of those entities have vastly different implications for treatment and prognosis.