Effects of unilateral motor cortex lesion on ipsilesional hand's reach and grasp performance in monkeys: relationship with recovery in the contralesional hand.

Manual dexterity, a prerogative of primates, is under the control of the corticospinal (CS) tract. Because 90-95% of CS axons decussate, it is assumed that this control is exerted essentially on the contralateral hand. Consistently, unilateral lesion of the hand representation in the motor cortex is followed by a complete loss of dexterity of the contralesional hand. During the months following lesion, spontaneous recovery of manual dexterity takes place to a highly variable extent across subjects, although largely incomplete. In the present study, we tested the hypothesis that after a significant postlesion period, manual performance in the ipsilesional hand is correlated with the extent of functional recovery in the contralesional hand. To this aim, ten adult macaque monkeys were subjected to permanent unilateral motor cortex lesion. Monkeys' manual performance was assessed for each hand during several months postlesion, using our standard behavioral test (modified Brinkman board task) that provides a quantitative measure of reach and grasp ability. The ipsilesional hand's performance was found to be significantly enhanced over the long term (100-300 days postlesion) in six of ten monkeys, with the six exhibiting the best, though incomplete, recovery of the contralesional hand. There was a statistically significant correlation (r = 0.932; P < 0.001) between performance in the ipsilesional hand after significant postlesion period and the extent of recovery of the contralesional hand. This observation is interpreted in terms of different possible mechanisms of recovery, dependent on the recruitment of motor areas in the lesioned and/or intact hemispheres.

Lentiviral gene transfer to the nonhuman primate brain.

Lentiviral vectors infect quiescent cells and allow for the delivery of genes to discrete brain regions. The present study assessed whether stable lentiviral gene transduction can be achieved in the monkey nigrostriatal system. Three young adult Rhesus monkeys received injections of a lentiviral vector encoding for the marker gene beta galatosidase (beta Gal). On one side of the brain, each monkey received multiple lentivirus injections into the caudate and putamen. On the opposite side, each animal received a single injection aimed at the substantia nigra. The first two monkeys were sacrificed 1 month postinjection, while the third monkey was sacrificed 3 months postinjection. Robust incorporation of the beta Gal gene was seen in the striatum of all three monkeys. Stereological counts revealed that 930,218; 1,192,359; and 1,501,217 cells in the striatum were beta Gal positive in monkeys 1 (n = 2) and 3 (n = 1) months later, respectively. Only the third monkey had an injection placed directly into the substantia nigra and 187,308 beta Gal-positive cells were identified in this animal. The injections induced only minor perivascular cuffing and there was no apparent inflammatory response resulting from the lentivirus injections. Double label experiments revealed that between 80 and 87% of the beta Gal-positive cells were neurons. These data indicate that robust transduction of striatal and nigral cells can occur in the nonhuman primate brain for up to 3 months. Studies are now ongoing testing the ability of lentivirus encoding for dopaminergic trophic factors to augment the nigrostriatal system in nonhuman primate models of Parkinson's disease.

Intestinal bacteria condition dendritic cells to promote IgA production.

Immunoglobulin (Ig) A represents the predominant antibody isotype produced at the intestinal mucosa, where it plays an important role in limiting the penetration of commensal intestinal bacteria and opportunistic pathogens. We show in mice that Peyer's Patch-derived dendritic cells (PP-DC) exhibit a specialized phenotype allowing the promotion of IgA production by B2 cells. This phenotype included increased expression of the retinaldehyde dehydrogenase 1 (RALDH1), inducible nitric oxide synthase (iNOS), B cell activating factor of the tumor necrosis family (BAFF), a proliferation-inducing ligand (APRIL), and receptors for the neuropeptide vasoactive intestinal peptide (VIP). The ability of PP-DC to promote anti-CD40 dependent IgA was partially dependent on retinoic acid (RA) and transforming growth factor (TGF)-beta, whilst BAFF and APRIL signaling were not required. Signals delivered by BAFF and APRIL were crucial for CD40 independent IgA production, although the contribution of B2 cells to this pathway was minimal. The unique ability of PP-DC to instruct naïve B cells to differentiate into IgA producing plasma cells was mainly imparted by the presence of intestinal commensal bacteria, and could be mimicked by the addition of LPS to the culture. These data indicate that exposure to pathogen-associated molecular patterns present on intestinal commensal bacteria condition DC to express a unique molecular footprint that in turn allows them to promote IgA production.

Selective absence of CD8+ TCRalpha beta+ intestinal epithelial cells in transgenic mice expressing beta2-microglobulin-associated ligands exclusively on thymic cortical epithelium.

Whereas interactions between the TCRalpha beta and self MHC:peptide complexes are clearly required for positive selection of mature CD4(+) and CD8(+) T cells during intrathymic development, the role of self or foreign ligands in maintaining the peripheral T cell repertoire is still controversial. In this report we have utilized keratin 14-beta2-microglobulin (K14-beta2m)-transgenic mice expressing beta2m-associated ligands exclusively on thymic cortical epithelial cells to address the possible influence of TCR:ligand interactions in peripheral CD8(+) T cell homeostasis. Our data indicate that CD8(+) T cells in peripheral lymphoid tissues are present in normal numbers in the absence of self MHC class I:peptide ligands. Surprisingly, however, steady state homeostasis of CD8(+) T cells in the intestinal epithelium is severely affected by the absence of beta2m-associated ligands. Indeed TCRalpha beta(+) IEL subsets expressing CD8alpha beta or CD8alpha alpha are both dramatically reduced in K14-beta2m mice, suggesting that the development, survival or expansion of CD8(+) IEL depends upon interaction of the TCR with MHC class I:peptide or other beta2m-associated ligands elsewhere than on thymic cortical epithelium. Collectively, our data reveal an unexpected difference in the regulation of CD8(+) T cell homeostasis by beta2m-associated ligands in the intestine as compared to peripheral lymphoid organs.

MP2RAGE, a self bias-field corrected sequence for improved segmentation and T-1-mapping at high field

The large spatial inhomogeneity in transmit B, field (B-1(+)) observable in human MR images at hi h static magnetic fields (B-0) severely impairs image quality. To overcome this effect in brain T-1-weighted images the, MPRAGE sequence was modified to generate two different images at different inversion times MP2RAGE By combining the two images in a novel fashion, it was possible to create T-1-weigthed images where the result image was free of proton density contrast, T-2* contrast, reception bias field, and, to first order transmit field inhomogeneity. MP2RAGE sequence parameters were optimized using Bloch equations to maximize contrast-to-noise ratio per unit of time between brain tissues and minimize the effect of B-1(+) variations through space. Images of high anatomical quality and excellent brain tissue differentiation suitable for applications such as segmentation and voxel-based morphometry were obtained at 3 and 7 T. From such T-1-weighted images, acquired within 12 min, high-resolution 3D T-1 maps were routinely calculated at 7 T with sub-millimeter voxel resolution (0.65-0.85 mm isotropic). T-1 maps were validated in phantom experiments. In humans, the T, values obtained at 7 T were 1.15 +/- 0.06 s for white matter (WM) and 1.92 +/- 0.16 s for grey matter (GM), in good agreement with literature values obtained at lower spatial resolution. At 3 T, where whole-brain acquisitions with 1 mm isotropic voxels were acquired in 8 min the T-1 values obtained (0.81 +/- 0.03 S for WM and 1.35 +/- 0.05 for GM) were once again found to be in very good agreement with values in the literature. (C) 2009 Elsevier Inc. All rights reserved.

Reduction of the hand representation in the ipsilateral primary motor cortex following unilateral section of the corticospinal tract at cervical level in monkeys.

BACKGROUND: After sub-total hemi-section of cervical cord at level C7/C8 in monkeys, the ipsilesional hand exhibited a paralysis for a couple of weeks, followed by incomplete recovery of manual dexterity, reaching a plateau after 40-50 days. Recently, we demonstrated that the level of the plateau was related to the size of the lesion and that progressive plastic changes of the motor map in the contralesional motor cortex, particularly the hand representation, took place following a comparable time course. The goal of the present study was to assess, in three macaque monkeys, whether the hand representation in the ipsilesional primary motor cortex (M1) was also affected by the cervical hemi-section.¦RESULTS: Unexpectedly, based on the minor contribution of the ipsilesional hemisphere to the transected corticospinal (CS) tract, a considerable reduction of the hand representation was also observed in the ipsilesional M1. Mapping control experiments ruled out the possibility that changes of motor maps are due to variability of the intracortical microstimulation mapping technique. The extent of the size reduction of the hand area was nearly as large as in the contralesional hemisphere in two of the three monkeys. In the third monkey, it represented a reduction by a factor of half the change observed in the contralesional hemisphere. Although the hand representation was modified in the ipsilesional hemisphere, such changes were not correlated with a contribution of this hemisphere to the incomplete recovery of the manual dexterity for the hand affected by the lesion, as demonstrated by reversible inactivation experiments (in contrast to the contralesional hemisphere). Moreover, despite the size reduction of M1 hand area in the ipsilesional hemisphere, no deficit of manual dexterity for the hand opposite to the cervical hemi-section was detected.¦CONCLUSION: After cervical hemi-section, the ipsilesional motor cortex exhibited substantial reduction of the hand representation, whose extent did not match the small number of axotomized CS neurons. We hypothesized that the paradoxical reduction of hand representation in the ipsilesional hemisphere is secondary to the changes taking place in the contralesional hemisphere, possibly corresponding to postural adjustments and/or re-establishing a balance between the two hemispheres.

Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.

Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤ 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

Lebenslauf und Regulation in Paarbeziehungen: Bestimmungsgründe der Ungleichheit familiarer Arbeitsteilung

On the basis of a recent survey of couples living together in Switzerland, classical and less classical explanatory factors of the un-equal division of family labour between the partners are explored. Resource-theoretical aspects are only modestly confirmed where-as the family cycle emerges as a strong con-dition that develops its effects concerning feminisation or equal distribution of family labour mainly through the female partner's occupational activity. An institutionalist ap-proach is proposed, based on the concept of sex-typed complementary master-statuses.

Cerebral extracellular lactate increase is predominantly nonischemic in patients with severe traumatic brain injury.

Growing evidence suggests that endogenous lactate is an important substrate for neurons. This study aimed to examine cerebral lactate metabolism and its relationship with brain perfusion in patients with severe traumatic brain injury (TBI). A prospective cohort of 24 patients with severe TBI monitored with cerebral microdialysis (CMD) and brain tissue oxygen tension (PbtO2) was studied. Brain lactate metabolism was assessed by quantification of elevated CMD lactate samples (>4 mmol/L); these were matched to CMD pyruvate and PbtO2 values and dichotomized as glycolytic (CMD pyruvate >119 μmol/L vs. low pyruvate) and hypoxic (PbtO2 <20 mm Hg vs. nonhypoxic). Using perfusion computed tomography (CT), brain perfusion was categorized as oligemic, normal, or hyperemic, and was compared with CMD and PbtO2 data. Samples with elevated CMD lactate were frequently observed (41±8%), and we found that brain lactate elevations were predominantly associated with glycolysis and normal PbtO2 (73±8%) rather than brain hypoxia (14±6%). Furthermore, glycolytic lactate was always associated with normal or hyperemic brain perfusion, whereas all episodes with hypoxic lactate were associated with diffuse oligemia. Our findings suggest predominant nonischemic cerebral extracellular lactate release after TBI and support the concept that lactate may be used as an energy substrate by the injured human brain.

Le Règne, Jésus et la Loi (Q 16,16-18)

(Résumé de l'ouvrage) Le Dieu qui juge : voilà un sujet de la théologie biblique qui n'est pas sans poser problème ! Le jugement est-il l'expression de la violence de Dieu ou d'un esprit vindicatif ? S'y manifeste-t-il une image choquante de Dieu, en particulier à une époque qui, à raison, se montre sensible à toute sorte de violence légitimée par des motifs religieux ? Les auteurs de ce volume, amis et collègues de Raymond Kuntzmann, professeur d'Ancien Testament à l'université Marc-Bloch de Strasbourg, ont abordé ce thème du jugement afin de faire apparaître la multitude d'aspects que revêt ce terme trop général. D'où le besoin d'examiner à frais nouveaux tout un ensemble de textes pour replacer le jugement dans tous ses contextes, tant historiques que théologiques. A y regarder ainsi de plus près, il résulte que l'idée de jugement est étroitement liée à celles de droit et de justice, valeurs dont Dieu s'avère être le garant ultime, et à celles de miséricorde et de salut. Et l'on suivra ici ses transformations remarquables au fil de l'évolution de la théologie biblique. Le présent volume, qui est consacré aux textes de l'Ancien Testament, est complété par un autre portant sur les textes du Nouveau Testament.