Thermal and optical properties of P3HT:PC70BM:ZnO nanoparticles composite films.

The results of studies on the influence of zinc oxide nanoparticles (ZnO-NPs) on the structural, thermal and optical properties of thin films of mixtures of phenyl-C71-butyric acid methyl ester (PCBM) with poly[3-hexylthiophene] (P3HT) of various molecular weights are described in this article. The structural properties of the layers of: polymers, mixtures of polymers with fullerenes and their composites with ZnO-NPs were investigated using X-ray diffraction. Whereas their glass transition temperature and optical parameters have been determined by temperature-dependent spectroscopic ellipsometry. The presence of ZnO-NPs was also visible in the images of the surface of the composite layers obtained using scanning electron microscopy. These blends and composite films have also been used as the active layer in bulk heterojunction photovoltaic structures. The molecular weight of P3HT (Mw = 65.2; 54.2 and 34.1 kDa) and the addition of nanoparticles affected the power conversion efficiency (PCE) of the obtained solar cells. The determined PCE was the highest for the device prepared from the blend of P3HT:PCBM with the polymer of the lowest molecular weight. However, solar cells with ZnO-NPs present in their active layer had lower efficiency, although the open-circuit voltage and fill factor of almost all devices had the same values whether they contained ZnO-NPs or not. It is worth noting that thermal studies carried out using temperature-dependent ellipsometry showed a significant effect of the presence of ZnO-NPs on the value of the glass transition temperature, which was higher for composite films than for films made of a polymer-fullerene blend alone.

Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases.

The group of chondrodysplasia with multiple dislocations includes several entities, characterized by short stature, dislocation of large joints, hand and/or vertebral anomalies. Other features, such as epiphyseal or metaphyseal changes, cleft palate, intellectual disability are also often part of the phenotype. In addition, several conditions with overlapping features are related to this group and broaden the spectrum. The majority of these disorders have been linked to pathogenic variants in genes encoding proteins implicated in the synthesis or sulfation of proteoglycans (PG). In a series of 30 patients with multiple dislocations, we have performed exome sequencing and subsequent targeted analysis of 15 genes, implicated in chondrodysplasia with multiple dislocations, and related conditions. We have identified causative pathogenic variants in 60% of patients (18/30); when a clinical diagnosis was suspected, this was molecularly confirmed in 53% of cases. Forty percent of patients remain without molecular etiology. Pathogenic variants in genes implicated in PG synthesis are of major importance in chondrodysplasia with multiple dislocations and related conditions. The combination of hand features, growth failure severity, radiological aspects of long bones and of vertebrae allowed discrimination among the different conditions. We propose key diagnostic clues to the clinician.

[Importance of preoperative and intraoperative imaging for operative strategies]. / Bedeutung der prä- und intraoperativen Bildgebung für die operative Strategie.

Recent advances in preoperative and postoperative imaging have an increasing influence on surgical decision-making and make more complex surgical interventions possible. This improves the possibilities for frequently occurring challenges and promoting improved functional and oncological outcome. This manuscript reviews the role of preoperative and intraoperative imaging in surgery. Various techniques are explained based on examples from hepatobiliary surgery and neurosurgery, in particular real-time procedures, such as the online use of augmented reality and in vivo fluorescence, as well as new and promising optical techniques including imaging of intrinsic signals and vibrational spectroscopy.

Uveal melanoma hepatic metastases mutation spectrum analysis using targeted next-generation sequencing of 400 cancer genes.

AIMS: Uveal melanoma (UM) is the most common malignant tumour of the eye. Diagnosis often occurs late in the course of disease, and prognosis is generally poor. Recently, recurrent somatic mutations were described, unravelling additional specific altered pathways in UM. Targeted next-generation sequencing (NGS) can now be applied to an accurate and fast identification of somatic mutations in cancer. The aim of the present study was to characterise the mutation pattern of five UM hepatic metastases with well-defined clinical and pathological features. METHODS: We analysed the UM mutation spectrum using targeted NGS on 409 cancer genes. RESULTS: Four previous reported genes were found to be recurrently mutated. All tumours presented mutually exclusive GNA11 or GNAQ missense mutations. BAP1 loss-of-function mutations were found in three UMs. SF3B1 missense mutations were found in the two UMs with no BAP1 mutations. We then searched for additional mutation targets. We identified the Arg505Cys mutation in the tumour suppressor FBXW7. The same mutation was previously described in different cancer types, and FBXW7 was recently reported to be mutated in UM exomes. CONCLUSIONS: Further studies are required to confirm FBXW7 implication in UM tumorigenesis. Elucidating the molecular mechanisms underlying UM tumorigenesis holds the promise for novel and effective targeted UM therapies.

[Identification of risk genes for myocardial infarction by genome wide association studies]. / Identifizierung von Risikogenen für den Herzinfarkt durch genomweite Assoziationsstudien.

Myocardial infarction (MI) shows a strong heritability. For a long time the identification of responsible genes has been rather unsuccessful. However, with the advent of genome wide association studies (GWAS) using DNA-array technology a number of significant loci for MI have been identified which were widely replicated. Interestingly, only a small fraction of the hitherto identified genes is also associated with classical risk factors for MI such as hypercholesterolemia or diabetes. Therefore it can be concluded that the MI risk mediated by the newly identified genes involves a number of novel pathophysiological mechanisms. This review summarizes the present state of knowledge in the field and tries to give a perspective on how these findings can be translated into clinical practice and further scientific discovery. Special consideration is given to the association of MI risk with genetic variants in the hemostatic system.

[Congestive heart failure is a common disease with complex inheritance--new perspectives through genome wide association studies]. / Die Herzinsuffizienz als komplexe genetische Erkrankung: Neue Perspektiven durch genomweite Assoziationsstudien.

Congestive heart failure can be defined as a complex syndrome comprising the end stage of multiple cardiovascular disorders. Genetics of congestive heart failure focused thus far mainly on rare familiar forms of hypertrophic or dilated cardiomyopathy. These are often caused by rare and deleterious mutations showing Mendelian inheritance conferred by genes encoding largely for structural proteins of the myocardium. However, from an epidemiological point of view, these rare familial forms play a minor role in the overall population. By far the most cases of congestive heart failure show a complex inheritance and phenotype. This review article will focus on congestive heart failure as a complex trait and will discuss the impact of new technology (genome wide association studies) on the elucidation of common genetic risk factors for congestive heart failure.

Mapping the bacterial cell architecture into the chromosome.

A genome is not a simple collection of genes. We propose here that it can be viewed as being organized as a 'celluloculus' similar to the homunculus of preformists, but pertaining to the category of programmes (or algorithms) rather than to that of architectures or structures: a significant correlation exists between the distribution of genes along the chromosome and the physical architecture of the cell. We review here data supporting this observation, stressing physical constraints operating on the cell's architecture and dynamics, and their consequences in terms of gene and genome structure. If such a correlation exists, it derives from some selection pressure: simple and general physical principles acting at the level of the cell structure are discussed. As a first case in point we see the piling up of planar modules as a stable, entropy-driven, architectural principle that could be at the root of the coupling between the architecture of the cell and the location of genes at specific places in the chromosome. We propose that the specific organization of certain genes whose products have a general tendency to form easily planar modules is a general motor for architectural organization in the bacterial cell. A second mechanism, operating at the transcription level, is described that could account for the efficient building up of complex structures. As an organizing principle we suggest that exploration by biological polymers of the vast space of possible conformation states is constrained by anchoring points. In particular, we suggest that transcription does not always allow the 5'-end of the transcript to go free and explore the many conformations available, but that, in many cases, it remains linked to the transcribing RNA polymerase complex in such a way that loops of RNA, rather than threads with a free end, explore the surrounding medium. In bacteria, extension of the loops throughout the cytoplasm would therefore be mediated by the de novo synthesis of ribosomes in growing cells. Termination of transcription and mRNA turnover would accordingly be expected to be controlled by sequence features at both the 3'- and 5'-ends of the molecule. These concepts are discussed taking into account in vitro analysis of genome sequences and experimental data about cell compartmentalization, mRNA folding and turnover, as well as known structural features of protein and membrane complexes.

Codon usage as a tool to predict the cellular location of eukaryotic ribosomal proteins and aminoacyl-tRNA synthetases.

In spite of many efforts, the prediction of the location of proteins in eukaryotic cells (cytoplasm, mitochondrion or chloroplast) is still far from straightforward. In some cases (e.g. ribosomal proteins and aminoacyl-tRNA synthetases) both the cytoplasmic proteins and their organellar counterparts are encoded by the nuclear genome. A factorial correspondence analysis of the codon usage in yeast and Caenorhabditis elegans shows that the codon usage of those nuclear genes encoding ribosomal proteins or aminoacyl-tRNA synthetases is markedly different, depending on the final location of the proteins (cytoplasmic or mitochondrial). As a consequence, the location of such proteins-whose sequences are now frequently determined by systematic genomic sequencing-can be easily and quickly predicted. A WWW interface has been developed, aimed at providing a user-friendly tool for codon usage pattern analysis. It is available from http://www.genetique.uvsq.fr/afc.html

Indigo: a World-Wide-Web review of genomes and gene functions.

The present article describes a genome database reviewing gene-related knowledge of two model bacteria, Bacillus subtilis and Escherichia coli. The database, Indigo, is open through the World-Wide Web (http://indigo.genetique.uvsq.fr). The concept used for organising the data, the concept of neighbourhood, allows one to explore the database content in an efficient although somewhat unusual way. Here, genes are related to each other by a variety of neighbourhoods, including proximity in the chromosome, phylogenetic kinship, participation in a common metabolic pathway, common presence in an article of the literature, or similar use of the genetic code. Several examples illustrate how this concept of neighbourhood permits one to review the available knowledge about a given gene or gene family, and elaborate unexpected, but revealing, analyses about gene functions.

Seven deaths in Darwin: case studies under the Rights of the Terminally Ill Act, Northern Territory, Australia.

BACKGROUND: During the 9 months between July, 1996, and March, 1997, the provision of euthanasia for the terminally ill was legal in the Northern Territory of Australia. Seven patients made formal use of the Rights of the Terminally Ill (ROTI) Act; four died under the Act. We report their clinical details and the decision-making process required by the Act. METHODS: We taped in-depth interviews with the general practitioner who provided euthanasia. Further information was available from public texts created by patients, the media, and the coroner. FINDINGS: All seven patients had cancer, most at advanced stages. Three were socially isolated. Symptoms of depression were common. Having met criteria of the Act, some patients deferred their decision for a time before proceeding with euthanasia. Medical opinions about the terminal nature of illness differed. INTERPRETATION: Provision of opinions about the terminal nature of illness and the mental health of the patient, as required by the ROTI Act, created problematic gatekeeping roles for the doctors involved.

Global analysis of genomic texts: the distribution of AGCT tetranucleotides in the Escherichia coli and Bacillus subtilis genomes predicts translational frameshifting and ribosomal hopping in several genes.

Present availability of the genomic text of bacteria allows assignment of biological known functions to many genes (typically, half of the genome's gene content). It is now time to try and predict new unexpected functions, using inductive procedures that allow correlating the content of the genomic text to possible biological functions. We show here that analysis of the genomes of Escherichia coli and Bacillus subtilis for the distribution of AGCT motifs predicts that genes exist for which the mRNA molecule can be translated as several different proteins synthesized after ribosomal frameshifting or hopping. Among these genes we found that several coded for the same function in E. coli and B. subtilis. We analyzed in depth the situation of the infB gene (experimentally known to specify synthesis of several proteins differing in their translation starts), the aceF/pdhC gene, the eno gene, and the rplI gene. In addition, genes specific to E. coli were also studied: ompA, ompFand tolA (predicting epigenetic variation that could help escape infection by phages or colicins).

Evolution of genes, evolution of species: the case of aminoacyl-tRNA synthetases.

All of the aminoacyl-tRNA synthetase (aaRS) sequences currently available in the data banks have been subjected to a systematic analysis aimed at finding gene duplications, genetic recombinations, and horizontal transfers. Evidence is provided for the occurrence (or probable occurrence) of such phenomena within this class of enzymes. In particular, it is suggested that the monomeric PheRS from the yeast mitochondrion is a chimera of the alpha and beta chains of the standard tetrameric protein. In addition, it is proposed that the dimeric and tetrameric forms of GlyRS are the result of a double and independent acquisition of the same specificity within two different subclasses of aaRS. The phylogenetic reconstructions of the evolutionary histories of the genes encoding aaRS are shown to be extremely diverse. While large segments of the population are consistent with the broad grouping into the three Woesian domains, some phylogenetic reconstructions do not place the Archae and the Eucarya as sister groups but, rather, show a gram-negative bacteria/eukaryote clustering. In addition, many individual genes pose difficulties that preclude any simple evolutionary scheme. Thus, aaRS's are clearly a paradigm of F. Jacob's "odd jobs of evolution" but, on the whole, do not call into question the evolutionary scenario originally proposed by Woese and subsequently refined by others.

Using codon usage to predict genes origin: is the Escherichia coli outer membrane a patchwork of products from different genomes?

Analysis of the codon usage of genes coding for the structural components of the outer membrane in Escherichia coli, is consistent with the requirement for high expression of these genes. Because porins (which constitute the major protein component of the outer membrane), and LPS (which constitute the major outermost constituent of the outer membrane), are synthesized from genes displaying widely different codon usage, it is possible to investigate the origin of the outer membrane. The analysis predicts that the outer membrane might originate from a genome other than the genome coding for the major part of the cell. Such a special origin would explain in structural terms, the likely lethality of porins if they were inadvertently inserted within the inner membrane, giving rise to the Gram-negative bacterial type, having an envelope comprising two membranes, instead of a single cytoplasmic membrane and a murein sacculus.

DEFPARAM: a program package for aligning elliptical sections of biological objects containing an n-fold symmetry.

A program package has been developed to align automatically images of biological objects containing an n-fold symmetry, and to remove the distortions induced on their circular shape by the microtomy. It uses an original procedure based on correlation techniques and replaces usual manual processing. Examples of direct averaging of transverse sections of biological objects are given to illustrate the program's capabilities.