TEMP/TDM et TEP/TDM en cardiologie : quel avenir ?

Over the recent years, clinical cardiology has witnessed a rapid evolution of multi-slice computed tomography (CT), starting with 4-slice CT developing into the current state of the heart 64-slice CT technology. This technology permits non-invasive visualization of the coronaries with high precision. CT coronary angiography will likely play an important role in the diagnosis of coronary artery disease. Because not all coronary stenoses detected by CT angiography are flow limiting, the stress myocardial perfusion imaging data complement the CT information. The integration of nuclear imaging (SPECT or PET) and CT data provides a potential opportunity to delineate the anatomic extent and the physiologic severity of coronary artery disease. The objective of this article is to provide a critical view of the relative strengths and weaknesses of myocardial perfusion imaging and CT coronary angiography, which we hope will help elucidate the potential role of these modalities in the diagnosis and management algorithms of patients with known or suspected coronary artery disease.     

Australopithecus afarensis : bipédie stricte ou associée à une composante arboricole ? Critiques et révision du matériel fémoral

Although much research has been carried out on Australopithecus afarensis locomotion, no consensus has yet been reached. Our new critic study on femoral material brings to the fore a strictly bipedal behaviour within this taxon. Our results are based on the pertinence of human anatomical characteristics among A. afarensis and on the absence of characteristics revealing arboreal displacement. These results have emerged from our different observation and interpretation of some preceding authors concerning the anatomy of these fossil hominids. It is important to underline that apomorphic characteristics of this species are difficult to interpret. They must not however be used to support the idea of arboreal displacement simply based on the fact of a no totally human morphe. We believe that present day humans do not necessarily reflect the earliest strict bipedal anatomic model. An the other hand, it appears that the disagreement between the two locomotor hypothesis for A. afarensis that are bipedalism and arboreal displacement, facing the possibility of bipedalism associated with negligible arboreal displacement, results more from an evolutionary fact than from a real scientific conflict.     

Impaired Synthesis of Erythropoietin,Glutamine Synthetase and Metallothionein in the Skin of NOD/SCID/γ<Stack><Subscript>c</Subscript><Superscript>null</Superscript></Stack> and Foxn1 nu/nu Mice with Misbalanced Production of MHC Class II Complex

Most skin pathologies are characterized by unbalanced synthesis of major histocompatability complex II (MHC-II) proteins. Healthy skin keratinocytes simultaneously produce large amounts of MHC-II and regeneration-supporting proteins, e.g. erythropoietin (EPO), EPO receptor (EPOR), glutamine synthetase (GS) and metallothionein (MT). To investigate the level of regeneration-supporting proteins in the skin during misbalanced production of MHC-II, skin sections from nonobese diabetic/severe combined immunodeficient (NOD/SCID)/γ_c^null and or Foxn1 nu/nu mice which are a priory known to under- and over-express MHC II, respectively, were used. Double immunofluorescence analysis of NOD/SCID/γ_c^null skin sections showed striking decrease in expression of MHC-II, EPO, GS and MT. In Foxn1 nu/nu mouse skin, GS was strongly expressed in epidermis and in hair follicles (HF), which lacked EPO. In nude mouse skin EPO and MHC-II were over-expressed in dermal fibroblasts and they were completely absent from cortex, channel, medulla and keratinocytes surrounding the HF, suggest a role for EPO in health and pathology of hair follicle. The level of expression of EPO and GS in both mutant mice was confirmed by results of Western blot analyses. Strong immunoresponsiveness of EPOR in the hair channels of NOD/SCID/γ_c^null mouse skin suggests increased requirements of skin cells for EPO and possible benefits of exogenous EPO application during disorders of immune system accompanied by loss MHC-II in skin cells.     

“RAF” neighborhood: Protein–protein interaction in the Raf/Mek/Erk pathway

The Raf/Mek/Erk signaling pathway, activated downstream of Ras primarily to promote proliferation, represents the best studied of the evolutionary conserved MAPK cascades. The investigation of the pathway has continued unabated since its discovery roughly 30 years ago. In the last decade, however, the identification of unexpected in vivo functions of pathway components, as well as the discovery of Raf mutations in human cancer, the ensuing quest for inhibitors, and the efforts to understand their mechanism of action, have boosted interest tremendously. From this large body of work, protein–protein interaction has emerged as a recurrent, crucial theme. This review focuses on the role of protein complexes in the regulation of the Raf/Mek/Erk pathway and in its cross-talk with other signaling cascades. Mapping these interactions and finding a way of exploiting them for therapeutic purposes is one of the challenges of future molecule-targeted therapy.     

L’art Paléolithique est-il un « art » ?: Réflexions autour d’une question d’actualité

During the last years, an international debate about the concept of “Palaeolithic art” has taken place. On one hand, several specialists have critiqued the use of the concept of “art” in naming the images created by Homo sapiens during the Palaeolithic era. They claim that the use of this term implies the projection of a modern category to a world - that of prehistoric humans - which is completely different from our own. On the other hand, some archaeologists consider that the term “Palaeolithic art” does not imply an anachronistic interpretation of prehistoric representations. In presenting the historical context, which has made such a discussion possible, we consider the causes and effects of this controversy. Firstly, we analyze the traditional interpretation, which considered Palaeolithic images as “works of art”. Secondly, we examine the connections, which can be found between the debate about “Palaeolithic art” and certain polemics, which have arisen from the history of art and anthropological frameworks. Thirdly, we consider the arguments utilized by those who are for and those who are against the term “Palaeolithic art”. Finally, we emphasize the importance of this debate to better understand the categories and the concepts, which determine the scientific practice.     

Nadaouiyeh – A Homo erectus in Acheulean context

The Middle East is apparently the most important passage for the dispersal of early hominins. Numerous archeological sites prove the existence of hominin populations in this region, but despite these rich cultural remains, hominin fossils are very rare. In 1996, a hominin left parietal was found in an Acheulean context. In addition, the faunal remains indicate a steppe environment. What does this single cranial fragment tell us? Based on new publications and in particular on recent finds, the value of isolated elements is discussed.     

Synthesis of N-tetra-O-acetyl-β-d-glucopyranosyl-N′-(4′,6′-diarylpyrimidin-2′-yl)thioureas

Some 2-amino-4,6-diarylpyrimidines 2 have been prepared from substituted benzylideneacetophenones and guanidine hydrochloride in the presence of alkali by conventional heating in alcoholic medium and microwave heating in solvent-free conditions. N-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl)-N′-(4′,6′-diarylpyrimidin-2′-yl)thioureas 4 have been synthesized by reaction of per-O-acetylated glucopyranosyl isothiocyanate 1 and substituted 2-amino-4,6-diarylpyrimidines 2. Two different methods have been used, namely, refluxing in anhydrous dioxane and solvent-free microwave-assisted coupling. The second procedure afforded higher yields in much shorter reaction times. The compounds 2 and 4 were tested for their antibacterial and antifungal activities in vitro against Staphylococcus epidermidis, Enterobacter aerogenes and Candida albicans by disc diffusion method.     

Targeting duplex DNA with DNA‐PNA chimeras? Physico‐chemical characterization of a triplex DNA‐PNA/DNA/DNA

Targeting double-stranded DNA with homopyrimidine PNAs results in strand displacement complexes PNA/DNA/PNA rather than PNA/DNA/DNA triplex structures. Not much is known about the binding properties of DNA-PNA chimeras. A 16-mer 5'-DNA-3'-p-(N)PNA(C) has been investigated for its ability to hybridize a complementary duplex DNA by DSC, CD, and molecular modeling studies. The obtained results showed the formation of a triplex structure having similar, if not slightly higher, stability compared to the same all-DNA complex.     

Expression and Developmental Regulation of the Cystine/Glutamate Exchanger (x<Stack><Subscript>c</Subscript><Superscript>−</Superscript></Stack>) in the Rat

The cystine/glutamate exchanger (antiporter x_c⁻) is a membrane transporter involved in the uptake of cystine, the rate-limiting amino acid in the synthesis of glutathione. Recent studies suggest that the antiporter plays a role in the slow oxidative excitotoxity and in the pathological effects of β-N-oxalylamino-l-alanine, the molecule responsible for neurolathyrism, a neurotoxic upper motor neuron disease. The mouse cystine/glutamate exchanger has been cloned and showed to be composed of two distinct proteins, one of which being a novel protein, named xCT, of 502 amino acids and 12 putative trans-membrane domains. We have generated and purified a polyclonal antibody to mouse xCT and studied its expression in rat brain and in different cultured cells (astrocytes, fibroblasts and neurons) using Western blot and immunocytochemical techniques. Expression of xCT was also studied in rat brain and muscle at different developmental stages. Parallel experiments were carried out with antibodies to the heavy chain of 4F2 surface antigen, the non-specific subunit of the antiporter x_c⁻. xCT antibody detected in all cell and tissue extracts a specific band of about 40 kDa. Subcellular fractionation demonstrated that xCT is concentrated mainly in the microsomal-mitochondrial fraction, in accord with its structure as transmembrane protein. Immunocytochemical analysis showed a strong staining in all cells examined, included neurons. Furthermore, both xCT and the heavy chain of 4F2 surface antigen increased in the brain during development, reaching the highest expression in adulthood. The study of the expression and developmental profile of xCT represents a first step towards a better characterization of its biochemical properties and function, which in turn may help to understand the relative contribution of the x_c⁻ antiporter in the pathogenesis of certain neurodegenerative diseases.     

免疫融合蛋白sFcεRIα/mIg(IgG2)的研制

哮喘、过敏性鼻炎、特应性皮炎及食物过敏等疾病为一类常见疾病,但存在治疗效果不佳,患者病程长等特点。IgE 分子是导致过敏性疾病的关键分子。抑制IgE分子与效应细胞膜表面FcεRI受体的结合可抑制过敏反应的发生。通过克隆FcεRI受体α亚基的cDNA与IgG2的稳定区铰链区、CH2和CH3的cDNA连接,以二聚化融合蛋白sFcεRIα/mIg(IgG2)的形式在CHO细胞中表达,达到提高sFcεRIα生物半衰期的目的。表达载体构建和初步的功能性试验等一系列研究证实,所表达的融合蛋白的分子量为170kDa,并与人IgE和鼠IgE有较好的结合活性。这些研究为该融合蛋白最终实现产业化打下良好基础。     

Simultaneous α/β spin-state selection for <Superscript>13</Superscript>C and <Superscript>15</Superscript>N from a time-shared HSQC-IPAP experiment

Two novel HSQC-IPAP approaches are proposed to achieve α/β spin-state editing simultaneously for ¹³C and ¹⁵N in a single NMR experiment. The pulse schemes are based on a time-shared (TS) 2D ¹H,¹³C/¹H,¹⁵N-HSQC correlation experiment that combines concatenated echo elements for simultaneous J(CH) and J(NH) coupling constants evolution, TS evolution of ¹³C and ¹⁵N chemical shifts in the indirect dimension and heteronuclear α/β-spin-state selection by means of the IPAP principle. Heteronuclear α/β-editing for all CH _n (n = 1–3) and NH _n (1–2) multiplicities can be achieved in the detected F2 dimension of a single TS-HSQC-F2-IPAP experiment. On the other hand, an alternative TS-HSQC-F1-IPAP experiment is also proposed to achieve α/β-editing in the indirect F1 dimension. Experimental and simulated data is provided to evaluate these principles in terms of sensitivity and performance simultaneously on backbone and side-chain CH, CH₂, CH₃, NH, and NH₂ spin systems in uniformly ¹³C/¹⁵N-labeled proteins and in small natural-abundance peptides.     

Murine diet/tissue and human brain tumorigenesis alter <Emphasis Type="Italic">Mthfr/MTHFR</Emphasis> 5′-end methylation

Polymorphisms and decreased activity of methylenetetrahydrofolate reductase (MTHFR) are linked to disease, including cancer. However, epigenetic regulation has not been thoroughly studied. Our goal was to generate DNA methylation profiles of murine/human MTHFR gene regions and examine methylation in brain and liver tumors. Pyrosequencing in four murine tissues revealed minimal DNA methylation in the CpG island. Higher methylation was seen in liver or intestine in the CpG island shore 5′ to the upstream translational start site or in another region 3′ to the downstream start site. In the latter region, there was negative correlation between expression and methylation. Three orthologous regions were investigated in human MTHFR, as well as a fourth region between the two translation start sites. We found significantly increased methylation in three regions (not the CpG island) in pediatric astrocytomas compared with control brain, with decreased expression in tumors. Methylation in hepatic carcinomas was also increased in the three regions compared with normal liver, but the difference was significant for only one CpG. This work, the first overview of the Mthfr/MTHFR epigenetic landscape, suggests regulation through methylation in some regions, demonstrates increased methylation/decreased expression in pediatric astrocytomas, and should serve as a resource for future epigenetic studies.     

Datation des travertins de Kocabaş par la méthode des nucléides cosmogéniques Al/Be

The archaic Homo erectus Kocaba? skullcap was discovered at Kocaba?, Denizli, Turkey in travertine formations over- and underlain by conglomerate formations. These units dated by the ²⁶Al/¹⁰Be cosmogenic nuclide method constrained the skullcap age between 1.0 and 1.6 Ma.     

Wnt/β-catenin/Tcf Signaling Pathway Activation in Malignant Progression of Rat Gliomas Induced by Transplacental <Emphasis Type="Italic">N-</Emphasis>Ethyl-<Emphasis Type="Italic">N-</Emphasis>Nitrosourea Exposure

Although Wnt/β-catenin/Tcf signaling pathway has been shown to be a crucial factor in the development of many cancers, little is known about its role in glioma malignancy. In the present study, we report the first evidence that Wnt/β-catenin/Tcf signaling pathway is constitutively activated in experimental gliomas induced by single transplacental dose of N-ethyl-N-nitrosourea (ENU). In the present study we analyzed ENU induced rat gliomas of different stages (P90, P135 and P180) for the expression of β-catenin, Lef1, Tcf4 and their targets c-Myc, N-Myc and cyclin D1. Western blot analysis revealed upregulation of β-catenin, Lef1, Tcf4, c-Myc, N-Myc and cyclin D1 in gliomas compared to controls and their levels were progressively increased from initial stage (P90) to progression stage (P180). In consistent with this, immunohistochemistry revealed the cytoplasmic and nuclear accumulation of β-catenin, and nuclear positivity was evident for Lef1, Tcf4, c-Myc, N-Myc and cyclin D1. Based on these results, we conclude that Wnt/β-catenin pathway may play a major role in the tumorigenesis and tumor progression in ENU induced rat gliomas.     

[Hg(μ-4,4′-bipy)(μ-AcO)(AcO)]n · n/2H2O, one-dimensional double-chain coordination polymer, syntheses, characterization, thermal, fluorescence, porous and structural studies

A new Hg^II coordination polymer with 4,4′-bipyridine and acetate anions, [Hg(μ-4,4′-bipy)(μ-AcO)(AcO)]_n · n/2H₂O (1), has been synthesized, characterized by elemental analysis, IR-, ¹H NMR-, ¹³C NMR spectroscopy and its structure determined by single-crystal X-ray diffraction. The thermal stability of compound 1 was studied by thermal gravimetric (TG) and differential thermal analyses (DTA). The structural studies of compound 1 show that the structure may be considered as a coordination polymer of mercury(II) consisting of linear double chains formed by a bridging 4,4′-bipy ligand and by connecting acetate-bridged centrosymmetric {Hg₂(OAc)₂}²⁺ nodes. Solid-state luminescent spectra of the ligand 4,4′-bipyridine and compound 1 indicate a fluorescent broad emission band with the maximum intensity at ca 468.2 and 446.4 nm upon excitation at 295 nm, respectively. The stability of porous network after removal of guest water molecules is not confirmed by X-ray powder diffraction.     

Improved accuracy in measuring one-bond and two-bond <Superscript>15</Superscript>N,<Superscript>13</Superscript>C<Superscript>α</Superscript> coupling constants in proteins by double-inphase/antiphase (DIPAP) spectroscopy

An extension to HN(CO-α/β-N,C^α-J)-TROSY (Permi and Annila in J Biomol NMR 16:221–227, 2000) is proposed that permits the simultaneous determination of the four coupling constants ¹ J _{N′(i)Cα(i)}, ² J _HN(i)Cα(i), ² J _{Cα(i−1)N′(i)}, and ³ J _{Cα(i−1)HN(i)} in ¹⁵N,¹³C-labeled proteins. Contrasting the original scheme, in which two separate subspectra exhibit the ² J _CαN′ coupling as inphase and antiphase splitting (IPAP), we here record four subspectra that exhibit all combinations of inphase and antiphase splittings possible with respect to both ² J _CαN′ and ¹ J _N′Cα (DIPAP). Complementary sign patterns in the different spectrum constituents overdetermine the coupling constants which can thus be extracted at higher accuracy than is possible with the original experiment. Fully exploiting data redundance, simultaneous 2D lineshape fitting of the E.COSY multiplet tilts in all four subspectra provides all coupling constants at ultimate precision. Cross-correlation and differential-relaxation effects were taken into account in the evaluation procedure. By applying a four-point Fourier transform, the set of spectra is reversibly interconverted between DIPAP and spin-state representations. Methods are exemplified using proteins of various size.     

Spin crossover behavior of a one-dimensional polymeric-chain compound {[Fe(abpt)2(μ-Ni(CN)4)]·xH2O}n (x = 0.5 → 0): Synthesis, spectral, thermal and magnetic properties

A one-dimensional polymeric-chain iron(II)-nickel(II) cyanido-bridged complex of the composition {[Fe(abpt)₂(μ-Ni(CN)₄)]·0.5H₂O}_n (1·0.5H₂O), where abpt = 4-amino-3,5-di-2-pyridyl-4H-1,2,4-triazole, was prepared and characterized by elemental and thermal analyses, FTIR and ⁵⁷Fe Mössbauer spectroscopies, and magnetic measurements. The incomplete spin crossover phenomenon was observed with approximately 12% of the frozen high-spin fraction at low temperatures and with the spin transition critical temperature above room temperature.