Fine needle aspiration (FNA) of synovial sarcoma—a comparative histological–cytological study of 15 cases, including immunohistochemical, electron microscopic and cytogenetic examination and DNA‐ploidy analysis

A retrospective study of 25 FNAs (11 aspirates from primary tumours and 14 from recurrencies and metastases) from 15 synovial sarcomas was performed. The cytological findings were correlated with the histopathology and the value of immunohistochemical and electron microscopic examination as well as DNA‐ploidy and cytogenetic analysis for diagnosis were assessed. A reproducible cellular pattern with a reliable diagnosis of spindle cell sarcoma was possible provided that the aspirates were cell rich. However, a true biphasic pattern indicative of synovial sarcoma was only seen in one of the 25 specimens. Electron microscopic examination of the aspirates was a valuable adjunctive diagnostic method, whereas immunocytochemistry and DNA‐ploidy analysis were not. Immunohistochemical, electron microscopic and cytogenetic analysis were all valuable ancillary methods when performed on surgical specimens. Malignant haemangiopericytoma and fibrosarcoma were the most important differential diagnoses in the FNA specimens.     

L2′ loop is critical for caspase‐7 active site formation

The active sites of caspases are composed of four mobile loops. A loop (L2) from one half of the dimer interacts with a loop (L2′) from the other half of the dimer to bind substrate. In an inactive form, the two L2′ loops form a cross‐dimer hydrogen‐bond network over the dimer interface. Although the L2′ loop has been implicated as playing a central role in the formation of the active‐site loop bundle, its precise role in catalysis has not been shown. A detailed understanding of the active and inactive conformations is essential to control the caspase function. We have interrogated the contributions of the residues in the L2′ loop to catalytic function and enzyme stability. In wild‐type and all mutants, active‐site binding results in substantial stabilization of the complex. One mutation, P214A, is significantly destabilized in the ligand‐free conformation, but is as stable as wild type when bound to substrate, indicating that caspase‐7 rests in different conformations in the absence and presence of substrate. Residues K212 and I213 in the L2′ loop are shown to be essential for substrate‐binding and thus proper catalytic function of the caspase. In the crystal structure of I213A, the void created by side‐chain deletion is compensated for by rearrangement of tyrosine 211 to fill the void, suggesting that the requirements of substrate‐binding are sufficiently strong to induce the active conformation. Thus, although the L2′ loop makes no direct contacts with substrate, it is essential for buttressing the substrate‐binding groove and is central to native catalytic efficiency.     

Centrosomes and cancer.

The centrosome functions as the major microtubule organizing center (MTOC) of the cell and as such it determines the number, polarity, and organization of interphase and mitotic microtubules. Cytoplasmic organization, cell polarity and the equal partition of chromosomes into daughter cells at the time of cell division are all dependent on the normal function of the centrosome and on its orderly duplication, once and only once, in each cell cycle. Malignant tumor cells show characteristic defects in cell and tissue architecture and in chromosome number that can be attributed to inappropriate centrosome behavior during tumor progression. In this review, we will summarize recent observations linking centrosome defects to disruption of normal cell and tissue organization and to chromosomal instability found in malignant tumors.     

Prothrombin structure: unanticipated features and opportunities

The structure of prothrombin has eluded investigators for decades but recent efforts have succeeded in revealing the architecture of this important clotting factor. Unanticipated features have emerged outlining the significant flexibility of the zymogen due to linker regions connecting the γ carboxyglutamic domain, kringles and protease domain. A new, structure-based framework helps in defining a molecular mechanism of prothrombin activation, rationalizes the severe bleeding phenotypes of several naturally occurring mutations and identifies targets for drug design.     

Complex Genetic Effects on Early Vegetative Development Shape Resource Allocation Differences Between Arabidopsis lyrata Populations

Costs of reproduction due to resource allocation trade-offs have long been recognized as key forces in life history evolution, but little is known about their functional or genetic basis. Arabidopsis lyrata, a perennial relative of the annual model plant A. thaliana with a wide climatic distribution, has populations that are strongly diverged in resource allocation. In this study, we evaluated the genetic and functional basis for variation in resource allocation in a reciprocal transplant experiment, using four A. lyrata populations and F₂ progeny from a cross between North Carolina (NC) and Norway parents, which had the most divergent resource allocation patterns. Local alleles at quantitative trait loci (QTL) at a North Carolina field site increased reproductive output while reducing vegetative growth. These QTL had little overlap with flowering date QTL. Structural equation models incorporating QTL genotypes and traits indicated that resource allocation differences result primarily from QTL effects on early vegetative growth patterns, with cascading effects on later vegetative and reproductive development. At a Norway field site, North Carolina alleles at some of the same QTL regions reduced survival and reproductive output components, but these effects were not associated with resource allocation trade-offs in the Norway environment. Our results indicate that resource allocation in perennial plants may involve important adaptive mechanisms largely independent of flowering time. Moreover, the contributions of resource allocation QTL to local adaptation appear to result from their effects on developmental timing and its interaction with environmental constraints, and not from simple models of reproductive costs.     

PDB-wide identification of physiological hetero-oligomeric assemblies based on conserved quaternary structure geometry

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100ps Molecular Dynamic Simulation of d(TATCACC)2

Abstract

A heptanucleotide sequence d(TATCACC)2 from OR3 region of bacteriophage X is considered sufficient for the recognition of Cro protein. We present here results on molecular dynamic simulations on this sequence for 100 ps in 0.02 ps interval. The simulations are done using computer program GROMOS. The conformational results are averaged over each ps. The IUPAC torsional parameters for 100 conformations are illustrated using a wheal and a dial systems. Several other stereochemical parameters such as H-bonding lengths and angles, sugar puckers, helix twist and roll angles as also distances between opposite strand phosphorus are depicted graphically. We find that there is rupture of terminal H-bonds. The bases are tilted and shifted away from the helix axis giving rise to bifurcated H-bonds. H- bonds are seen even in between different base pairs. The role of these dynamic structural changes in the recognition of OR3 operator by Cro protein is discussed in the paper.     

Studies on the Chitinolytic Enzymes of Black-koji Mold

It has been found that glycol chitin is a suitable substrate for the viscometric determination of chitinase activity, because the viscosity of its aqueous solution is not affected by the presence of added salt and the changes of pH, differing from chitosan acetate and carboxy-methyl chitin used by earlier workers. Using this substrate the viscometric activity is determined, basing on the observation that the time required to halve the viscosity of reaction mixture is inversely proportional to the amount of enzyme used.     

Kinetochore stretching-mediated rapid silencing of the spindle-assembly checkpoint required for failsafe chromosome segregation

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