A cytomorphological and immunohistochemical profile of aggressive B-cell lymphoma: high clinical impact of a cumulative immunohistochemical outcome predictor score

We analyzed morphological and immunohistochemical features in 174 aggressive B-cell lymphomas of nodal and extranodal origin. Morphological features included presence or absence of a follicular component and cytologic criteria according to the Kiel classification, whereas immunohistochemical studies included expression of CD10, BCL-2, BCL-6, IRF4/MUM1, HLA-DR, p53, Ki-67 and the assessment of plasmacytoid differentiation. Patients were treated with a CHOP-like regimen. While the presence or absence of either CD10, BCL-6 and IRF4/MUM1 reactivity or plasmacytoid differentiation did not identify particular cytomorphologic or site-specific subtypes, we found that expression of CD10 and BCL-6, and a low reactivity for IRF4/MUM1 were favourable prognostic indicators. In contrast, BCL-2 expression and presence of a monotypic cytoplasmic immunoglobulin expression was associated with an unfavourable prognosis in univariate analyses. Meta-analysis of these data resulted in the development of a cumulative immunohistochemical outcome predictor score (CIOPS) enabling the recognition of four distinct prognostic groups. Multivariate analysis proved this score to be independent of the international prognostic index. Such a cumulative immunohistochemical scoring approach might provide a valuable alternative in the recognition of defined risk types of aggressive B-cell lymphomas

Genome-Wide Transcriptomic Analysis of Intestinal Tissue to Assess the Impact of Nutrition and a Secondary Nematode Challenge in Lactating Rats

Gastrointestinal nematode infection is a major challenge to the health and welfare of mammals. Although mammals eventually acquire immunity to nematodes, this breaks down around parturition, which renders periparturient mammals susceptible to re-infection and an infection source for their offspring. Nutrient supplementation reduces the extent of periparturient parasitism, but the underlying mechanisms remain unclear. Here, we use a genome wide approach to assess the effects of protein supplementation on gene expression in the small intestine of periparturient rats following nematode re-infection.The use of a rat whole genome expression microarray (Affymetrix Gene 1.0ST) showed significant differential regulation of 91 genes in the small intestine of lactating rats, re-infected with Nippostrongylus brasiliensis compared to controls; affected functions included immune cell trafficking, cell-mediated responses and antigen presentation. Genes with a previously described role in immune response to nematodes, such as mast cell proteases, and intelectin, and others newly associated with nematode expulsion, such as anterior gradient homolog 2 were identified. Protein supplementation resulted in significant differential regulation of 64 genes; affected functions included protein synthesis, cellular function and maintenance. It increased cell metabolism, evident from the high number of non-coding RNA and the increased synthesis of ribosomal proteins. It regulated immune responses, through T-cell activation and proliferation. The up-regulation of transcription factor forkhead box P1 in unsupplemented, parasitised hosts may be indicative of a delayed immune response in these animals.This study provides the first evidence for nutritional regulation of genes related to immunity to nematodes at the site of parasitism, during expulsion. Additionally it reveals genes induced following secondary parasite challenge in lactating mammals, not previously associated with parasite expulsion. This work is a first step towards defining disease predisposition, identifying markers for nutritional imbalance and developing sustainable measures for parasite control in domestic mammals

A genome scan for milk production traits in dairy goats reveals two new mutations in <i>Dgat1</i> reducing milk fat content

The quantity of milk and milk fat and proteins are particularly important traits in dairy livestock. However, little is known about the regions of the genome that influence these traits in goats. We conducted a genome wide association study in French goats and identified 109 regions associated with dairy traits. For a major region on chromosome 14 closely associated with fat content, the Diacylglycerol O-Acyltransferase 1 (DGAT1) gene turned out to be a functional and positional candidate gene. The caprine reference sequence of this gene was completed and 29 polymorphisms were found in the gene sequence, including two novel exonic mutations: R251L and R396W, leading to substitutions in the protein sequence. The R251L mutation was found in the Saanen breed at a frequency of 3.5% and the R396W mutation both in the Saanen and Alpine breeds at a frequencies of 13% and 7% respectively. The R396W mutation explained 46% of the genetic variance of the trait, and the R251L mutation 6%. Both mutations were associated with a notable decrease in milk fat content. Their causality was then demonstrated by a functional test. These results provide new knowledge on the genetic basis of milk synthesis and will help improve the management of the French dairy goat breeding program

Investigation of Relative Micromotion at the Stem-Cement Interface in Total Hip Replacement

Abstract: Cemented total hip replacement has become a standard surgical technique to treat patients with osteoarthritis and osteonecrosis. The stem–cement interface experiences fretting wear in vivo due to low-amplitude oscillatory micromotion under physiological loading, and this wear is currently becoming important as a potential mechanism for the overall wear of cemented total hip replacements. However, the relative micromotion at the stem–cement interface has not been widely reported. In the present study, a new micromotion sensor is developed that is based on the deformation of a strain gauge, and this sensor is used to probe the migration of a polished Exeter stem within a Simplex P cement mantle through an in vitro wear simulation. It is demonstrated that the stem migration value generally increases with an increase in the number of loading cycles, with a gradual decrease of migration rate. Additionally, fretting wear is successfully replicated on the stem surface, and the micropores in the cement surface are considered to contribute to initiation and propagation of the fretting damage on the stem. This is confirmed by the observation that no evidence of fretting wear is detected on the stem where the surface is in contact with the pore-free areas on the cement. This study allows a deep insight into the micromotion at the stem–cement interface, and provides evidence highlighting the significance of the micropores in the cement surface in the generation of fretting wear on a polished femoral stem

Temperature and pressure dependencies of the crystal structure of the organic superconductor (TMTSF)

The crystal structure of (TMTSF)2ClO4 has been determined at (7 K, 1 bar) and at (7 K, 5 kbar) with a high accuracy. For the latter, low temperature and pressure were applied simultaneously using a X-ray diffraction instrumentation designed in our laboratory, these results are the first for molecular compounds. The effects of lowering the temperature are not the same as those produced by increasing the pressure. At (7 K, 1 bar) the anion ordering which occurs in this compound, and which is characterised by the appearance of $b^*/2$ superlattice reflections, is well observed. This anion ordering leads to the presence of two independent stacks of TMTSF cations which is the only case found in the Bechgaard salts family. The comparison of the low temperature crystal structures under atmospheric pressure and at 5 kbar shows that the centres of mass are nearly the same, independent of the pressure: the interchain interactions do not depend on the doubling of the unit cell. Under pressure, the ordering (0, 1/2, 0) does not occur at any temperature. These structural data are confirmed by the quantum chemical calculations which show that the difference in the site energy of the two independent cations is 100 meV

Dramatic anion size effect on structural and magnetic properties within a series of novel antiferromagnetic organometallic radical cation salts: [ Cp

Electrocrystallization of CH2Cl2 solutions of Cp2Mo(dmit), dmit2- = 2-thioxo-1,3-dithiole-4,5-dithiolate, in the presence of n-Bu4NX (X- = PF$_6^-$, AsF$_6^-$, SbF$_6^-$) affords the corresponding 1:1 cation radical salts [ Cp2Mo(dmit)$^{+\bullet}$] [ X-] . The three isostructural salts crystallize in the orthorhombic system, space group Cmcm. In the three salts, a second-order transition at a temperature T1, identified by EPR measurements and low-temperature X-ray Weissenberg photographs reveals also a splitting of some principal reflections and the twinned character of the crystals, whose room temperature structure may also be described in the monoclinic P21/m space group. The second order monoclinic $\rightarrow$ triclinic transition is associated with the apparition of a superlattice characterized by the critical wave vector ${\bf q}_1^{*}=(0,1/2,1/2)$ when expressed in the monoclinic system. A second transition at a lower temperature T2, of first order character, is observed only in the PF$_6^-$ salt. This triclinic $\rightarrow$ triclinic transition leads to a novel superlattice of wave vector ${\bf q}_2=(0,1/2,0)$ while the ${\bf q}_1^{*}$ superlattice is conserved down to 10 K in the AsF$_6^-$ and SbF$_6^-$ salts. Finally, a third transition to an antiferromagnetic ground state is observed for the three salts and investigated by static susceptibility measurements and Antiferromagnetic Resonance (AFMR) experiments. The detailed analysis of the AFMR rotation patterns confirms the twinned nature and the low temperature triclinic symmetry of the crystals as well as the peculiar behaviour of the PF$_6^-$ salt, when compared with the two other members of these novel series