Thyroid tumors: novel insights from proteomic studies

Several genomics-based techniques have been applied in the last decade to the molecular characterization of cancer, which has led to a variety of applications suitable for improved diagnosis, prognosis and prediction of outcome to treatment. Proteomics-based approaches have also been seen as crucial to the discovery of biomarkers for early diagnosis and prognosis of tumors, as well as for a better understanding of the molecular bases of cancer. Accordingly, proteomic techniques have been used extensively for a better molecular characterization of thyroid tumors. In this field, three main directions have been preceded: first, proteomic studies of model systems; second, proteomics of thyroid tumor specimens; and third, serum proteomics. In this review, we describe the most relevant results that have been obtained for tumors derived from thyroid follicular cells using various proteomic approaches.     

Melatonin and clinical application.

A review of the different publications dealing with melatonin in humans shows that this field has been very active in the last few years. Normative melatonin values have been defined. Various relationships between melatonin and other traits have been studied, such as sleep, circadian rhythm, surgical stress and anaesthesia. Age-related melatonin studies and melatonin during depression and other psychiatric disorders have been reviewed. Finally, some studies have been performed to use melatonin as a medication for sleep disturbance in depression, for jet-lag and as a skin protector for ultraviolet light.     

Fluorescent detection techniques for real-time multiplex strand specific detection of Bacillus anthracis using rapid PCR

Speed is a key area in our development of PCR assays for Bacillus anthracis. We believe that the strand specific detection of amplicons within 10 min is a realistic goal and that this will be achieved through fluorescent in-tube assays. We have used the Idaho LightCycler to study and develop candidate assays for B. anthracis. New strand specific fluorescent methods have been developed and a number of formats have been studied for speed and sensitivity. Internal controls have been developed as a method of improving our assay confidence. In this communication we will introduce the field of rapid PCR whilst discussing previous work in the areas described above, the development of our own rapid assay and a novel internal control system for B. anthracis. This work used PCR assays and hardware that are either commercially available, or have been previously described in open literature publications.     

Collection of anti-D immune plasma after labor. Apropos of 4370 plasmaphereses

4 370 plasmaphereses have been realized on women in the post delivery period for collection of immune anti-D plasma. 1.550 liters of such plasma have been collected and submitted to Cohn fractionation, leading to the preparation of about 100 000 vials of 100 micrograms. Thus, most of the Paris area needs for anti-D IgG have been covered for the past 13 years. Medico-legal aspects of blood donation at this particular period of a woman's life and proper motivations of these donors are underlined. Prospects for this type of blood collection are analyzed as a conclusion.     

A new set of DNA macrochips for the yeast Saccharomyces cerevisiae: features and uses.

The yeast Saccharomyces cerevisiae has been widely used for the implementation of DNA chip technologies. For this reason and due to the extensive use of this organism for basic and applied studies, yeast DNA chips are being used by many laboratories for expression or genomic analyses. While membrane arrays (macroarrays) offer several advantages, for many laboratories they are not affordable. Here we report that a cluster of four Spanish molecular-biology yeast laboratories, with relatively small budgets, have developed a complete set of probes for the genome of S. cerevisiae. These have been used to produce a new type of macroarray on a nylon surface. The macroarrays have been evaluated and protocols for their use have been optimized.     

ON THE OCCURRENCE IN ENGLAND OF THE PEAR FRUIT SAW-FLY, HOPLOCAMPA BEE VIS KLUG

Larvae of Hoplocampa brevis Klug., the Pear Fruit Saw-fly, have been found attacking pears in two gardens in Cambridge. In some continental countries this is a serious pest of pears; this is the first record of damage by this pest in England.
A preliminary study of the biology of this species has been made, and the egg, larval stages and cocoon have been briefly described.
The writer is indebted to Dr H. W. Miles for the identification of the saw-fly and for helpful criticism.     

THE MOLECULAR EVOLUTION OF PITUITARY HORMONES

1. The pituitary hormones can be divided into 4 families; within each the members are structurally related and have probably evolved from a common ancestor by a process of gene duplication and divergence. 2. Recent structural studies have revealed much about the evolution of proteins. The roles of point mutation, gene duplication and partial gene duplication in molecular evolution have been highlighted, and the nature of the evolutionary forces involved has been extensively debated. The information available about the evolution of proteins in general provides a background for consideration of pituitary hormone evolution. 3. The structure and function of the mammalian neurohypophysial hormones (oxytocin and vasopressin) has been studied in detail. Related (structurally similar) peptides have been found in the neurohypophyses of lower vertebrates and have been Characterized in many instances. Several schemes have been proposed for the evolution of these hormones. 4. The vasopressins of the pig and its relatives show a genetic polymorphism. The roles of neurohypophysial hormones in lower vertebrates are very varied and not fully understood. 5. The ACTHs and MSHs are members of a second family of pituitary hormones. They are polypeptides of moderate size. Studies on amino-acid sequences have been carried out for ACTHs and MSHs from several mammals. α-MSH is identical in all cases studied in detail, but β-MSH and ACTH vary to some extent. There is considerable sequence homology between the hormones in this family - indicating a common phylogenetic origin and several gene duplications. 6. Dogfish MSH is the only non-mammalian hormone of the ACTH-MSH family to have been studied in detail. Two MSHs have been isolated from this species; both resemble the a-MSH of mammals in amino-acid sequence. ACTH-like and MSH-like hormones exist in many other vertebrate groups, but have not been characterized fully. 7. Structure-function relationships have been widely studied in the ACTH-MSH family, and have some interesting evolutionary implications. Polymorphism of P-MSHs is found in some mammals. 8. A third family of protein hormones includes pituitary prolactin and growth hormone, and placental lactogen. These are proteins of moderate size which have been shown to be widely distributed among the vertebrates. Species specificity can be recognized with regard to biological, immunological and structural properties. 9. Amino-acid sequences have been determined for growth hormones and prolactins from several mammals. There is sequence homology between growth hormone and prolactin. Human placental lactogen closely resembles human growth hormone. A phylogenetic tree has been constructed for this protein family. Rates of evolution within the group are rather variable. 10. The fourth family of pituitary hormones (FSH, LH, TSH and some related placental hormones) are all glycoproteins and have a subunit structure. Extensive sequence studies have been carried out on the hormones from some mammals, and show that there is considerable homology between the various subunits. The α-subunits of human TSH, LH and HCG (and probably FSH) are very similar. The β-subunits are different, but homologous. Evolution of this family clearly took place by a series of gene duplications followed by gene divergence. Schemes whereby this could have occurred have been discussed. Related hormones occur in lower vertebrates, but have not been fully characterized. Some lower vertebrates may possess only one gonado-trophin. 11. The pituitary hormones provide an interesting range of evolutionary problems, and are useful models for the study of molecular evolution. The evolutionary processes involved in their diversification have been discussed, with particular reference to the co-evolution of hormones and their receptors. Neutral mutations and gene duplications may have played a role in providing co-existing variation of hormones and receptors. 12. A speculative model for the evolution of neurohypophysial hormones is proposed, as an example of how molecular evolution may have operated in this and other hormone groups. 13. Homologies have been proposed between the various families of pituitary hormones, and between pituitary proteins and other entero-secretory proteins. The pituitary protein hormones were probably elaborated from smaller molecules by a process of partial gene duplication.     

Some characteristics of new tissue-binding proteins for metabolites of vitamin D other than 1,25-dihydroxyvitamin D

Protein(s) have been found in a wide range of tissues which have a high affinity for 25-hydroxycholecalciferol. Of the tissues examined only erythrocytes do not have this protein. The properties of the protein have been examined and it has been found that the association constants range from 2 · 10⁹ to 5 · 10⁹ M⁻¹ and the sedimentation constants between 5.0 and 6.0 S. It was not possible to distinguish the proteins from the different tissues by their S values, mobility on gel electrophoresis or behaviour on ion-exchange chromatography. These techniques were all used, however, to show that the tissue 25-hydroxycholecalciferol binding protein is distinct from the main plasma binding protein for this steroid and from the intestinal 1,25-dihydroxycholecalciferol-binding protein. A protein has been found in the plasma of rachitic animals but not of normals, which is apparently indistinguishable from this new tissue 25-hydroxycholecalciferol-binding protein. The steroid specificity of this new binding protein has been shown to be dependent upon a C-25 hydroxyl group, and an intact conjugated double bond system. Possible functions for this protein have been briefly discussed.     

The non-monophyletic origin of the tRNA molecule

The hypothesis that the tRNA molecule may have originated from the assembly of two similar RNA hairpin structures is utilised to understand the evolutionary period in which this molecule originated. Consistent with the exon theory of genes is the observation that the introns in tRNA genes are found almost exclusively in the anticodon loop and "stitched together" the two halves of the molecule, which originally may have been simply two hairpin structures and which can still be observed in the three-dimensional structure of tRNAs. This theory therefore considers these hairpin structures as minigenes on which complex protein synthesis may have been achieved. This in turn leads to the belief that the organisation of the genetic code may have been determined by use of the hairpin structures but not the complete tRNA molecule. In view of this, it can be conjectured that tRNA molecules might have been assembled only after the establishment of the main phyletic lines. If this is all true, then the origin of the tRNA molecule might have been non-monophyletic, i.e. a tRNA specific for a certain amino acid might have been assembled in different phyletic lines with a second and different hairpin structure. This leads to the belief that tRNAs specific for different amino acids but belonging to the same phyletic line might have been more similar to one another than to tRNAs specific for the same amino acid but belonging to different phyletic lines. This prediction seems to be supported by phylogenetic analysis making major use of the bootstrap technique performed on the tRNA sequences and by analysis already existing in the literature which supports the non-monophyletic origin of the tRNA molecule. The main conclusion of this paper is that if the tRNA molecule was assembled in the main phyletic lines this would imply a still rapidly evolving translation apparatus which, in turn, seems to imply that the last universal common ancestor was a progenote.     

Upper lobe lobectomy and concomitant thoracoplasty in pulmonary tuberculosis. A preliminary report

In this, a preliminary report, the advantages and disadvantages of upper lobe lobectomy and concomitant thoracoplasty in tuberculosis have been summarized. There has been no undue increase in the operative hazard, there have been no complications, and the immediate results have been entirely satisfactory.Twenty-six patients were subjected to a combined operation (17 upper lobectomy-thoracoplasty and nine pneumonectomy-thoracoplasty) with one postoperative death. Indications for primary lobectomy have been discussed. The technique of resection and concomitant thoracoplasty has been briefly described.     

Structural and functional analysis of cloned DNA segments containing the replication and incompatibility regions of a miniplasmid derived from a copy number mutant of NR1.

A 1.45-megadalton segment of DNA cloned from a miniplasmid derived in vivo from a copy number mutant of the R plasmid NR1 has been shown to contain all functions essential for incompatibility and autonomous plasmid replication in Escherichia coli. Specific endonuclease cleavage sites within this DNA segment that localize functions required for replication have been mapped. A 0.45-megadalton fragment that specifies the FII incompatibility of NR1 has been identified within the replication region, and DNA fragments containing this incompatibility region, but lacking other functions required for replication, have been cloned.     

Identification of protein-coding regions in DNA sequences using a time-frequency filtering approach

Accurate identification of protein-coding regions (exons) in DNA sequences has been a challenging task in bioinformatics. Particularly the coding regions have a 3-base periodicity, which forms the basis of all exon identification methods. Many signal processing tools and techniques have been applied successfully for the identification task but still improvement in this direction is needed. In this paper, we have introduced a new promising model-independent time-frequency filtering technique based on S-transform for accurate identification of the coding regions. The S-transform is a powerful linear time-frequency representation useful for filtering in time-frequency domain. The potential of the proposed technique has been assessed through simulation study and the results obtained have been compared with the existing methods using standard datasets. The comparative study demonstrates that the proposed method outperforms its counterparts in identifying the coding regions.     

Try Tri again? Resolving species boundaries in the Lomatium triternatum (Apiaceae) complex

Species boundaries have traditionally been delimited by applying phenotypic characters to a morphological species concept. With an increased understanding of the complexities of speciation as a process, species concepts have proliferated while at the same time, the ability to gather greater numbers and types of molecular characters has expanded the means by which species can be delimited. Phylogenetic studies of molecular data provide an opportunity to identify reciprocally monophyletic groupsand have led to the identification of cryptic or nearly cryptic species in which subtle differences in phenotypes or ecological niches can be uncovered only after monophyletic groups have been identified. Here, we investigate evolutionary relationships among a group of species in the Lomatium triternatum complex using molecular phylogenetic analyses for all samples, and ecological parameters for two of the 38 species included in this study. The results indicate that there are more reciprocally monophyletic groups in this complex than had been estimated using phenotypic data alone. The ecological data show a clear differentiation for the one pair of sister species where ecological sampling was available, implying that divergence within this group may have resulted from environmental selection for soil preferences that have been strong enough to result in speciation.     

Upper Lobe Lobectomy and Concomitant Thoracoplasty in Pulmonary Tuberculosis—A Preliminary Report

In this, a preliminary report, the advantages and disadvantages of upper lobe lobectomy and concomitant thoracoplasty in tuberculosis have been summarized. There has been no undue increase in the operative hazard, there have been no complications, and the immediate results have been entirely satisfactory.Twenty-six patients were subjected to a combined operation (17 upper lobectomy-thoracoplasty and nine pneumonectomy-thoracoplasty) with one postoperative death.Indications for primary lobectomy have been discussed.The technique of resection and concomitant thoracoplasty has been briefly described.     

The Use of PC12 Cells for the Study of the Mechanism of Action of Neurotrophic Factors: Signal Transduction and Programmed Cell Death

The PC12 cell line is one of the most widely used of all neuronal cell lines. Over 2200 studies using PC12 cells have been published since the first in 1974. It is so widely used because it possesses properties that make it applicable to a wide variety of neurobiological problems. This article is a brief overview of some neurobiological issues that have been approached in recent years using the PC12 cell line and the properties of PC12 cells that have allowed their application to these problems. The intent is to provide an idea of the versatility of this line and of the types of studies that have successfully employed it. This may suggest potential approaches to solving problems in the readers own research. A major focus of this article is on the use of PC12 cells as a model for the study of neurotrophic factor signal transduction. PC12 cells have proved to be a particularly valuable model for this purpose and a significant fraction of studies using PC12 cells, particularly recent studies, have been directed toward this end.     

Leisure-time activities--its program and importance in the institutionalized protection of old people

This paper is a "report" or preliminary summation of a larger research project and paper. Leisure activities programs and their importance have not yet been systematically investigated in Croatian nursing homes, so this will contribute to a better understanding of this area of research. Through a ten year period of research study of 60 old people it has been shown that by the application of organized and suitable leisure activities we can prevent and redirect the measures so as to continually improve the life quality of old people living in nursing homes, regardless of their medical condition/place of residence. The topic of this paper is very popular in gerontological science. The research applied modern qualitative and quantitative methods of research in gerontology and therefore represents a novelty to the methodologically obsolete methods that have been in use in this country so far, which included polls and simplified quantitative processing of collected data. The results are useful for practical purposes because programs have been elaborated which will serve to improve the quality of leisure time and active life-planning in nursing homes. The foundations for further scientific research have been set with specific goals to focus on the certain aspects of the problems. In that sense, this paper invites all sorts of other challenging hypothesis to come out (e.g. the ratio of intellectual activities, active and passive types of activities etc.) and also opens the door for this kind of methodology in these types of research. This will help increase the number of such types of research as the qualitative methods of research have been disregarded in our country.     

Peptide crystal growth via sulfonate salt formation: The structure of bis-glycylglycine-1,5-naphthalenedisulfonate hydrate

Summary Continuing a line of investigations on methods for formation and growth of high-quality crystals of peptides, the glycylglycine sequence has been crystallized by evaporation methods as a salt with 1,5-naphthalenedisulfonic acid. The structure of the peptide is highly extended, and is conformationally quite similar to the structures which have been characterized for other zwitterionic and salt forms of this sequence. Thus, crystallization as a salt with this sulfonic acid has imposed no undue influence upon the molecular conformation. These results offer further indication that the preparation of peptide sulfonate salts, particularly with arene templates, may have broad general utility for crystallization of interesting sequences which until now have not been approachable in their zwitterionic forms.     

Validated numerical fluid simulation of a thin‐layer cascade photobioreactor in OpenFOAM

Recently, microalgae have been considered as a promising alternative for the production of biofuels from CO₂. For the efficient cultivation of these microalgae, several types of photobioreactors have been designed and Pilot scale photobioreactors have been used to assess the performance of these reactors. Therein the primarily investigated reactor type is the Raceway Pond. However, the less researched Thin‐Layer Cascade Photobioreactor (TLC) shows a high potential for efficient production processes. Unfortunately, for low‐value products like biofuels costs must be kept to a minimum for an economic operation. To facilitate this, 3D Computational Fluid Dynamic simulations can be employed to estimate performance of reactor variants e.g. with respect to power input and mixing. Since up to now little effort has been put into the modelling of TLC reactors, this report aims to present a simulation approach for these reactors types that allows simple adaptation to different geometric or operational boundary conditions. All models have been generated for a two‐phase mixture in OpenFOAM. To demonstrate its applicability, validation measurements with a physical unit have been performed and were compared to the simulation results. With errors in the order of 10 % a successful simulation of the reactor geometry could be proven.     

Biogeographical variation in the harvestman Mitopus morio (Opiliones, Arachnida)

The taxonomic status of three forms of the harvestman Mitopus morio in Britain have been examined. These have been identified by previous workers as a small, upland M, morio cinerascens , a larger, lowland M. morio morio , and a northern M. morio borealis. In this paper, the delimitation of trinomials has been found to be inappropriate for M. morio. since all three forms have been shown to lie at different points on a continuum of phenotypic variation within the species M. morio. It is suggested that this phenotypic variation is mediated by the variation in temperature regimes between different localities.     

Physical mapping identifies DXS265 as a useful genetic marker for carrier detection and prenatal diagnosis of X-linked agammaglobulinemia

The gene responsible for X-linked agammaglobulinemia (XLA) has not been identified; however, in the course of genetic linkage studies designed to map the locus more precisely, a number of closely linked polymorphic loci have been identified. These have proved to be useful in identifying carriers and in pre-natal diagnosis of this disease. The DXS178 locus was found to be closest to the XLA locus and has been the most usefully employed probe to date. Using physical mapping techniques, we have identified a previously cloned genetic marker, DXS265, as being situated within 5kb of DXS178. So far, we have found one family that is not informative for DXS178 but that is informative for DXS265; females in this family can now be offered the possibility of carrier determination and pre-natal diagnosis for this life-threatening disease.