Magnetic phase separation in ordered alloys

We present a lattice model to study the equilibrium phase diagram of ordered alloys with one magnetic component that exhibits a low temperature phase separation between paramagnetic and ferromagnetic phases. The model is constructed from the experimental facts observed in Cu3-xAlMnx and it includes coupling between configurational and magnetic degrees of freedom that are appropriate for reproducing the low temperature miscibility gap. The essential ingredient for the occurrence of such a coexistence region is the development of ferromagnetic order induced by the long-range atomic order of the magnetic component. A comparative study of both mean-field and Monte Carlo solutions is presented. Moreover, the model may enable the study of the structure of ferromagnetic domains embedded in the nonmagnetic matrix. This is relevant in relation to phenomena such as magnetoresistance and paramagnetism

Cooperation between the transcription factors p63 and IRF6 is essential to prevent cleft palate in mice.

Cleft palate is a common congenital disorder that affects up to 1 in 2,500 live human births and results in considerable morbidity to affected individuals and their families. The etiology of cleft palate is complex, with both genetic and environmental factors implicated. Mutations in the transcription factor-encoding genes p63 and interferon regulatory factor 6 (IRF6) have individually been identified as causes of cleft palate; however, a relationship between the key transcription factors p63 and IRF6 has not been determined. Here, we used both mouse models and human primary keratinocytes from patients with cleft palate to demonstrate that IRF6 and p63 interact epistatically during development of the secondary palate. Mice simultaneously carrying a heterozygous deletion of p63 and the Irf6 knockin mutation R84C, which causes cleft palate in humans, displayed ectodermal abnormalities that led to cleft palate. Furthermore, we showed that p63 transactivated IRF6 by binding to an upstream enhancer element; genetic variation within this enhancer element is associated with increased susceptibility to cleft lip. Our findings therefore identify p63 as a key regulatory molecule during palate development and provide a mechanism for the cooperative role of p63 and IRF6 in orofacial development in mice and humans.

Promoter IV of the class II transactivator gene is essential for positive selection of CD4+ T cells.

Major histocompatibility complex class II (MHCII) expression is regulated by the transcriptional coactivator CIITA. Positive selection of CD4(+) T cells is abrogated in mice lacking one of the promoters (pIV) of the Mhc2ta gene. This is entirely due to the absence of MHCII expression in thymic epithelia, as demonstrated by bone marrow transfer experiments between wild-type and pIV(-/-) mice. Medullary thymic epithelial cells (mTECs) are also MHCII(-) in pIV(-/-) mice. Bone marrow-derived, professional antigen-presenting cells (APCs) retain normal MHCII expression in pIV(-/-) mice, including those believed to mediate negative selection in the thymic medulla. Endogenous retroviruses thus retain their ability to sustain negative selection of the residual CD4(+) thymocytes in pIV(-/-) mice. Interestingly, the passive acquisition of MHCII molecules by thymocytes is abrogated in pIV(-/-) mice. This identifies thymic epithelial cells as the source of this passive transfer. In peripheral lymphoid organs, the CD4(+) T-cell population of pIV(-/-) mice is quantitatively and qualitatively comparable to that of MHCII-deficient mice. It comprises a high proportion of CD1-restricted natural killer T cells, which results in a bias of the V beta repertoire of the residual CD4(+) T-cell population. We have also addressed the identity of the signal that sustains pIV expression in cortical epithelia. We found that the Jak/STAT pathways activated by the common gamma chain (CD132) or common beta chain (CDw131) cytokine receptors are not required for MHCII expression in thymic cortical epithelia.

Enhancing clinically-relevant shoulder function assessment using only essential movements.

Kinematic functional evaluation with body-worn sensors provides discriminative and responsive scores after shoulder surgery, but the optimal movements' combination has not yet been scientifically investigated. The aim of this study was the development of a simplified shoulder function kinematic score including only essential movements. The P Score, a seven-movement kinematic score developed on 31 healthy participants and 35 patients before surgery and at 3, 6 and 12 months after shoulder surgery, served as a reference.Principal component analysis and multiple regression were used to create simplified scoring models. The candidate models were compared to the reference score. ROC curve for shoulder pathology detection and correlations with clinical questionnaires were calculated.The B-B Score (hand to the Back and hand upwards as to change a Bulb) showed no difference to the P Score in time*score interaction (P > .05) and its relation with the reference score was highly linear (R(2) > .97). Absolute value of correlations with clinical questionnaires ranged from 0.51 to 0.77. Sensitivity was 97% and specificity 94%.The B-B and reference scores are equivalent for the measurement of group responses. The validated simplified scoring model presents practical advantages that facilitate the objective evaluation of shoulder function in clinical practice.

Perturbing Hele-Shaw flow with a small gap gradient

A controlled perturbation is introduced into the Saffman-Taylor flow problem by adding a gradient to the gap of a Hele-Shaw cell. The stability of the single-finger steady state was found to be strongly affected by such a perturbation. Compared with patterns in a standard Hele-Shaw cell, the single Saffman-Taylor finger was stabilized or destabilized according to the sign of the gap gradient. While a linear stability analysis shows that this perturbation should have a negligible effect on the early-stage pattern formation, the experimental data indicate that the characteristic length for the initial breakup of a flat interface has been changed by the perturbation.

Philo of Alexandria's De opificio mundi (LIII-LXI): discovering the essential features of Greek and Western Misogyny in a Platonising Jewish Text

The aim of this article is to show the Western centuries-old misogynist tradition from its origins in Greece by analysing a text by the allegorical interpreter of the Bible Philo of Alexandria, his De opifico mundi, which on many occasions is read by him from a Platonic point of view. The accurate analysis of the chapters devoted to the creation of the woman by God proves to what extent it is not possible to understand this text if one does not take into account a Greek philosophical tradition which was already centuries-old.

Involvement of gap junctional intercellular communication in the pathophysiology of inflammation

SUMMARY Inflammation has evolved as a mechanism to defend the body against invading microorganisms and to respond to injury. It requires the coordinated response of a large number of cell types from the whole organism in a time- and space-dependent fashion. This coordination involves several cell-cell communication mechanisms. Exchange of humoral mediators such as cytokines is a major one. Moreover, direct contact between cells happens and plays a primordial role, for example when macrophages present antigens to lymphocytes. Contact between endothelial cells and leucocytes occurs when the latter cross the blood vessel barrier and transmigrate to the inflammatory site. A particular way by which cells communicate with each other in the course of inflammation, which at this time starts to gain attention, is the intercellular communication mediated by gap junctions. Gap junctions are channels providing a direct pathway (i.e. without transit through the extracellular space) for the diffusion of small molecules between adjacent cells. This process is known as gap junctional intercellular communication (GJIC). The general aim of this thesis was to study a possible involvement of GJIC in the pathophysiology of inflammation. A first part of the work was dedicated to study the implication of GJIC in the modification of vascular endothelial function by inflammation. In a second part, we were interested in the possible role of GJIC in the transmigration of neutrophil polymorphonuclear leucocytes through the endothelium. The main positive finding of this work is that acute inflammation preferentially modulates the expression of connexin 40 (Cx40), a gap junction protein specifically expressed in vascular endothelium. The modulation could be towards overexpression (aortic endothelium of septic rats) or towards downregulation (acutely inflamed mouse lung). We put a lot of efforts in search of possible functions of these modulations, in two directions: a potential protective role of Cx40 increased expression against sepsis-induced endothelial dysfunction, and a facilitating role of Cx40 decreased expression in neutrophil transmigration. To pursue both directions, it seemed logical to study the impact of Cx40 deletion using knock-out mice. Concerning the potential protective role of Cx40 overexpression we encountered a roadblock as we observed, in the aorta, a Cx40 downregulation in wild type mouse whereas Cx40 was upregulated in the rat. Regarding the second direction and using an in vivo approach, we observed that pulmonary neutrophil transmigration was not affected by the genetic deletion of Cx40. In spite of their negative nature, these results are the very first ones regarding the potential implication of GJIC concerning leucocyte transmigration in vivo. Because this process involves such tight cell-cell physical contacts, the hypothesis for a role of GJIC remains attractive.

Effect of captopril on renal vascular tone in patients with essential hypertension.

1. The effect of acute inhibition of angiotensin-converting enzyme by captopril (50 mg) on renal haemodynamics and function was assessed in nine patients with essential hypertension on unrestricted sodium intake (n = 8) or low sodium diet (n = 1). 2. Captopril induced a rapid and significant decrease in arterial pressure, which was maximal within 60 min. 3. Effective renal plasma flow (ERPF) increased, glomerular filtration rate (GFR) did not change and filtration fraction (FF) decreased after captopril. No change in sodium excretion and a decrease in urinary potassium occurred. 4. In the patient on low sodium diet, captopril induced striking increases in GFR and ERPF (64 and 106% respectively). 5. The logarithm of baseline plasma renin activity was positvely correlated with the change in ERPF and negatively correlated with changes in FF and renal resistance. 6. The results indicate that in patients with essential hypertension angiotensin participates actively in the maintenance of renal vascular tone at the efferent arteriolar level. A possible influence of kinins remains to be defined.

Jonctions communicantes et sécrétion [Gap junctions and secretion]

The emergence of multicellular organisms has necessitated the development of mechanisms for interactions between adjacent and distant cells. A consistent feature of this network is the expression of gap junction channels between the secretory cells of all glands so far investigated in vertebrates. Here, we reviewed the distribution of the gap junctions proteins, named connexins, in a few mammalian glands, and discussed the recent evidence pointing to the participation of these proteins in the functioning of endocrine and exocrine cells. Specifically, available data indicate the importance of gap junctions for the proper control of glucose-induced insulin secretion. Understanding the functions of beta-cell connexins are crucial for the engineering of surrogate cells, which is necessary for implementation of a replacement cell therapy in diabetic patients.

Equilibrium and nonequilibrium gap-state distribution in amorphous silicon

A general and straightforward analytical expression for the defect-state-energy distribution of a-Si:H is obtained through a statistical-mechanical treatment of the hydrogen occupation for different sites. Broadening of available defect energy levels (defect pool) and their charge state, both in electronic equilibrium and nonequilibrium steady-state situations, are considered. The model gives quantitative results that reproduce different defect phenomena, such as the thermally activated spin density, the gap-state dependence on the Fermi level, and the intensity and temperature dependence of light-induced spin density. An interpretation of the Staebler-Wronski effect is proposed, based on the ''conversion'' of shallow charged centers to neutrals near the middle of the gap as a consequence of hydrogen redistribution.

Essential role of MALT1 protease activity in activated B cell-like diffuse large B-cell lymphoma.

A key element for the development of suitable anti-cancer drugs is the identification of cancer-specific enzymatic activities that can be therapeutically targeted. Mucosa-associated lymphoid tissue transformation protein 1 (MALT1) is a proto-oncogene that contributes to tumorigenesis in diffuse large B-cell lymphoma (DLBCL) of the activated B-cell (ABC) subtype, the least curable subtype of DLBCL. Recent data suggest that MALT1 has proteolytic activity, but it is unknown whether this activity is relevant for tumor growth. Here we report that MALT1 is constitutively active in DLBCL lines of the ABC but not the GCB subtype. Inhibition of the MALT1 proteolytic activity led to reduced expression of growth factors and apoptosis inhibitors, and specifically affected the growth and survival of ABC DLBCL lines. These results demonstrate a key role for the proteolytic activity of MALT1 in DLBCL of the ABC subtype, and provide a rationale for the development of pharmacological inhibitors of MALT1 in DLBCL therapy.

Dectin-1 is essential for reverse transcytosis of glycosylated SIgA-antigen complexes by intestinal M cells.

Intestinal microfold (M) cells possess a high transcytosis capacity and are able to transport a broad range of materials including particulate antigens, soluble macromolecules, and pathogens from the intestinal lumen to inductive sites of the mucosal immune system. M cells are also the primary pathway for delivery of secretory IgA (SIgA) to the gut-associated lymphoid tissue. However, although the consequences of SIgA uptake by M cells are now well known and described, the mechanisms whereby SIgA is selectively bound and taken up remain poorly understood. Here we first demonstrate that both the Cα1 region and glycosylation, more particularly sialic acid residues, are involved in M cell-mediated reverse transcytosis. Second, we found that SIgA is taken up by M cells via the Dectin-1 receptor, with the possible involvement of Siglec-5 acting as a co-receptor. Third, we establish that transcytosed SIgA is taken up by mucosal CX3CR1⁺ dendritic cells (DCs) via the DC-SIGN receptor. Fourth, we show that mucosal and systemic antibody responses against the HIV p24-SIgA complexes administered orally is strictly dependent on the expression of Dectin-1. Having deciphered the mechanisms leading to specific targeting of SIgA-based Ag complexes paves the way to the use of such a vehicle for mucosal vaccination against various infectious diseases.

Mapping the transcription start points of the Staphylococcus aureus eap, emp, and vwb promoters reveals a conserved octanucleotide sequence that is essential for expression of these genes.

Mapping the transcription start points of the eap, emp, and vwb promoters revealed a conserved octanucleotide sequence (COS). Deleting this sequence abolished the expression of eap, emp, and vwb. However, electrophoretic mobility shift assays gave no evidence that this sequence was a binding site for SarA or SaeR, known regulators of eap and emp.