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PubMed2001

Nucleic acid and polypeptide aptamers: a powerful approach to ligand discovery.

Nucleic acid ligands against important targets in infectious, malignant and vascular diseases are continually being discovered by the process of in vitro evolution. Promising methods are being developed for the exploitation of these aptamers in biosensors and other diagnostic devices. Ribosome and mRNA display methods for isolating polypeptide aptamers from highly complex libraries have been developed and have the potential to widen the target range and utility of in vitro evolved ligands.

Animals↗

PubMed2000

Novel fabrication of open-pore chitin matrixes.

A novel method has been developed to produce open-pore chitin matrixes. Chitin solutions were loaded with calcium carbonate (CaCO3) crystals and the mixture cast to form gels. The CaCO3-chitin gels were submerged in 1 N HCl solution to produce highly porous matrixes with good water vapor permeability, water uptake profile, and enhanced mechanical properties. The open-pore system is obtainable because CaCO3 loaded into the chitin gel reacts with 1 N HCl solution to produce gaseous carbon dioxide. Evolution of carbon dioxide during the reaction results in continuous pore structures from the matrix' bulk to surface. When the concentration of CaCO3 loaded into the chitin gel is controlled, defined homogeneous pores measuring 100-500 and 500-1000 microns, with porosities of approximately 76% and 81%, respectively, can be produced.

Calcium Carbonate↗

PubMed2003

Pathogenesis of DNA repair-deficient cancers: a statistical meta-analysis of putative Real Common Target genes.

DNA mismatch repair deficiency is observed in about 15% of human colorectal, gastric, and endometrial tumors and in lower frequencies in a minority of other tumors thereby causing insertion/deletion mutations at short repetitive sequences, recognized as microsatellite instability (MSI). Evolution of tumors, including those with MSI, is a continuous process of mutation and selection favoring neoplastic growth. Mutations in microsatellite-bearing genes that promote tumor cell growth in general (Real Common Target genes) are assumed to be the driving force during MSI carcinogenesis. Thus, microsatellite mutations in these genes should occur more frequently than mutations in microsatellite genes without contribution to malignancy (ByStander genes). So far, only a few Real Common Target genes have been identified by functional studies. Thus, comprehensive analysis of microsatellite mutations will provide important clues to the understanding of MSI-driven carcinogenesis. Here, we evaluated published mutation frequencies on 194 repeat tracts in 137 genes in MSI-H colorectal, endometrial, and gastric carcinomas and propose a statistical model that aims to identify Real Common Target genes. According to our model nine genes including BAX and TGFbetaRII were identified as Real Common Targets in colorectal cancer, one gene in gastric cancer, and three genes in endometrial cancer. Microsatellite mutations in five additional genes seem to be counterselected in gastrointestinal tumors. Overall, the general applicability, the capacity to unlimited data analysis, the inclusion of mutation data generated by different groups on different sets of tumors make this model a useful tool for predicting Real Common Target genes with specificity for MSI-H tumors of different organs, guiding subsequent functional studies to the most likely targets among numerous microsatellite harboring genes.

Base Pair Mismatch↗

PubMed2005

Oncolytic virotherapy: approaches to tumor targeting and enhancing antitumor effects.

The application of replicating viruses for the treatment of cancers represents a novel therapy that is distinct from traditional treatment modalities. It is apparent that the genetic changes that a virus produces within an infected cell in order to create an environment conducive to viral replication are often similar to the processes involved in cellular transformation. These include uncontrolled cellular proliferation, prevention of apoptosis, and resistance to host organism immune effector mechanisms. Deletions of viral genes involved in these processes have been exploited to produce viral mutants whose replication is selective for transformed cells. The use of tissue-specific transcriptional response or RNA stability elements to control the expression of critical viral genes has also resulted in targeted viruses. Work also is being undertaken to restrict or alter the tropism of viruses by altering their ability to infect certain cell types. Finally, the addition of exogenous genes can be used to increase the virus's lytic potential and/or bystander killing; to further induce the host's immune response against cancer cells; and/or to permit the controlled downregulation of viral replication if necessary. The combination of different tumor-targeting mutations in parallel with the expression of foreign genes has resulted in the evolution of second- and third-generation viruses that continue to become further distinct from their native parental strains. The movement of these viruses into the clinic has begun to demonstrate the potential of this approach in the treatment of cancers.

Apoptosis↗

PubMed2001

Plant biology in the future.

In the beginning of modern plant biology, plant biologists followed a simple model for their science. This model included important branches of plant biology known then. Of course, plants had to be identified and classified first. Thus, there was much work on taxonomy, genetics, and physiology. Ecology and evolution were approached implicitly, rather than explicitly, through paleobotany, taxonomy, morphology, and historical geography. However, the burgeoning explosion of knowledge and great advances in molecular biology, e.g., to the extent that genes for specific traits can be added (or deleted) at will, have created a revolution in the study of plants. Genomics in agriculture has made it possible to address many important issues in crop production by the identification and manipulation of genes in crop plants. The current model of plant study differs from the previous one in that it places greater emphasis on developmental controls and on evolution by differential fitness. In a rapidly changing environment, the current model also explicitly considers the phenotypic variation among individuals on which selection operates. These are calls for the unity of science. In fact, the proponents of "Complexity Theory" think there are common algorithms describing all levels of organization, from atoms all the way to the structure of the universe, and that when these are discovered, the issue of scaling will be greatly simplified! Plant biology must seriously contribute to, among other things, meeting the nutritional needs of the human population. This challenge constitutes a key part of the backdrop against which future evolution will occur. Genetic engineering technologies are and will continue to be an important component of agriculture; however, we must consider the evolutionary implications of these new technologies. Meeting these demands requires drastic changes in the undergraduate curriculum. Students of biology should be trained in molecular, cellular, organismal, and ecosystem biology, including all living organisms.

Environment↗

PubMed2002

Ribosome display: cell-free protein display technology.

Ribosome display is a cell-free system for the in vitro selection of proteins and peptides from large libraries. It uses the principle of coupling individual nascent proteins (phenotypes) to their corresponding mRNA (genotypes), through the formation of stable protein-ribosome-mRNA (PRM) complexes. This permits the simultaneous isolation of a functional nascent protein, through affinity for a ligand, together with the encoding mRNA, which is then converted and amplified as DNA for further manipulation, including repeated cycles or protein expression. Ribosome display has a number of advantages over cell-based systems such as phage display; in particular, it can display very large libraries without the restriction of bacterial transformation. It is also suitable for generating toxic, proteolytically sensitive and unstable proteins, and allows the incorporation of modified amino acids at defined positions. In combination with polymerase chain reaction (PCR)-based methods, mutations can be introduced efficiently into the selected DNA pool in subsequent cycles, leading to continuous DNA diversification and protein selection (in vitro protein evolution). Both prokaryotic and eukaryotic ribosome display systems have been developed and each has its own distinctive features. In this paper, ribosome display systems and their application in selection and evolution of proteins are reviewed.

Cell-Free System↗

PubMed2005

Update on pediatric vasculitis.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the recent research and progress made in the field of pediatric vasculitis. RECENT FINDINGS: Over the past year, researchers have described several polymorphisms in Henoch-Schonlein purpura and Kawasaki Disease as well as the association between various vasculitides and infections. International and multidisciplinary efforts in Kawasaki Disease have resulted in recommendations for its diagnosis, treatment, and long-term management to improve patient care and further increase global collaboration. Researchers are investigating the role of inflammation and its role in endothelial health and atherosclerosis. Treatment regimens continue to improve, with the use of different immunosuppressive medications; however, we continue to have incomplete treatment successes. SUMMARY: Vasculitides are rare conditions with significant morbidity and mortality whose prognosis has improved with newer diagnostic modalities and treatments; however, we continue to have insufficient knowledge of vasculitides and lack unambiguous diagnostic criteria. As technology continues to progress it is clear that a single cause of these diseases may be an oversimplification: the genetic makeup of individuals, as well as various environmental exposures, are of vital importance in the pathophysiology and evolution of disease processes, as well as response to therapy. Efforts should continue to improve international multicenter collaboration and interdisciplinary efforts to help solve this ever-growing puzzle.

Bacterial Infections↗

PubMed2006

Microsporidiosis: current status.

PURPOSE OF REVIEW: Microsporidiosis is an emerging and opportunistic infection associated with a wide range of clinical syndromes in humans. This review highlights the research on microsporidiosis in humans during the previous 2 years. RECENT FINDINGS: The reduced and compact microsporidian genome has generated much interest for better understanding the evolution of these parasites, and comparative molecular phylogenetic studies continue to support a relationship between the microsporidia and fungi. Through increased awareness and improved diagnostics, microsporidiosis has been identified in a broader range of human populations that, in addition to persons with HIV infection, includes travelers, children, organ transplant recipients, and the elderly. SUMMARY: Effective commercial therapies for Enterocytozoon bieneusi, the most common microsporidian species identified in humans, are still lacking, making the need to develop tissue culture and small animal models increasingly urgent. Environmental transport modeling and disinfection strategies are being addressed for improving water safety. Questions still exist about whether microsporidia infections remain persistent in asymptomatic immune-competent individuals, reactivate during conditions of immune compromise, or may be transmitted to others at risk, such as during pregnancy or through organ donation. Reliable serological diagnostic methods are needed to supplement polymerase chain reaction or histochemistry when spore shedding may be sporadic.

Animals↗

PubMed2002

Earth's biggest 'whodunnit': unravelling the clues in the case of the end-Permian mass extinction.

The mass extinction that occurred at the end of the Permian period, 250 million years ago, was the most devastating loss of life that Earth has ever experienced. It is estimated that ca. 96% of marine species were wiped out and land plants, reptiles, amphibians and insects also suffered. The causes of this catastrophic event are currently a topic of intense debate. The geological record points to significant environmental disturbances, for example, global warming and stagnation of ocean water. A key issue is whether the Earth's feedback mechanisms can become unstable on their own, or whether some forcing is required to precipitate a catastrophe of this magnitude. A prime suspect for pushing Earth's systems into a critical condition is massive end-Permian Siberian volcanism, which would have pumped large quantities of carbon dioxide and toxic gases into the atmosphere. Recently, it has been postulated that Earth was also the victim of a bolide impact at this time. If further research substantiates this claim, it raises some intriguing questions. The Cretaceous-Tertiary mass extinction, 65 million years ago, was contemporaneous with both an impact and massive volcanism. Are both types of calamity necessary to drive Earth to the brink of faunal cataclysm? We do not presently have enough pieces of the jigsaw to solve the mystery of the end-Permian extinction, but the forensic work continues.

Animals↗

PubMed1992

The insertion sequence IS200 fingerprints chromosomal genotypes and epidemiological relationships in Salmonella heidelberg.

In Salmonella heidelberg the copy number of the Salmonella-specific insertion element IS200 was found to vary from four to six. All strains tested contained at least one common insertion site which was serovar specific, and most strains contained three common sites. Concurrent analysis of plasmids indicated that all insertion sequence copies were chromosomally located, and also supported the equivalence of an IS200 fingerprint and clonality. Seven intra-serovar clonal lines were thereby identified. One of these was associated with human infections, including septicaemias. Another was associated with chicken as a host: all these strains also carried a unique plasmid of 23 MDa, which was typed as a member of the IncX group. The chromosomal fingerprint of a third clone showed it to be a descendant of the chicken line marked by a single IS200 transposition. One or two representatives of four other clonal lines were identified. These lines of S. heidelberg could be related by divergent evolution, and the most recent relatives conformed to a continuous branching process model of IS200 transposition. This insertion sequence provided a highly discriminatory molecular marker of the S. heidelberg chromosome, and two of the seven clonal lines so identified were associated with distinct clinical/epidemiological contexts.

Animals↗

PubMed2001

Anomalous two-state model for anomalous diffusion.

An anomalous two-state model (ATSM) with the anomalous long-tailed kinetics of transitions between states is proposed to describe the specific features of anomalous diffusion (AD) and AD-assisted transitions (ADAT) in the double-well potential. In the ATSM the system is assumed to undergo the conventional diffusion in both states but with different diffusion coefficients. The anomalous features of diffusion result from the modulation of the diffusion coefficient caused by transitions between ATSM states. The anomalous space-time evolution predicted by the ATSM is treated within the continuous time random walk theory. With the use of the proposed ATSM the transient behavior of the AD and the ADAT is analyzed in detail. We found a large variety of different (and sometimes peculiar) types of the space-time behavior of the free AD and ADAT. The free AD is found to be of subdiffusion or superdiffusion type for fairly long time depending on the relation between the parameters of the ATSM. The kinetics of the ADAT can be either conventional (exponential) or anomalous (of inverse power type) for different parameters of the model and time.

Journal Article↗

PubMed2005

A genetic and molecular profile of third chromosome centric heterochromatin in Drosophila melanogaster.

In this review, we combine the results of our published and unpublished work with the published results of other laboratories to provide an updated map of the centromeric heterochromatin of chromosome 3 in Drosophila melanogaster. To date, we can identify more than 20 genes (defined DNA sequences with well-characterized functions and (or) defined genetic complementation groups), including at least 16 essential loci. With the ongoing emergence of data from genetic, cytological, and genome sequencing studies, we anticipate continued, substantial progress towards understanding the function, structure, and evolution of centric heterochromatin.

Animals↗

PubMed1993

Variance components for statistical genetics: applications in medical research to characteristics related to human diseases and health.

RA Fisher introduced variance components in 1918. He synthesized Mendelian inheritance with Darwin's theory of evolution by showing that the genetic variance of a continuous trait could be decomposed into additive and non-additive components. The model can be extended to include environmental factors, interactions, covariation, and non-random mating. Identifiability depends critically on design. Methods of analysis include modelling the mean squares from a fixed effects analysis of variance, and covariance structure modelling, which can be extended to multivariate traits and has been used to study ordinal traits by reference to postulated, unmeasured, latent 'liabilities'. These methods operate on dependent observations within independent groups of the same size and structure, and therefore require balanced designs ('regular' pedigrees). A multivariate normal model handles data in its generic form, utilizes data efficiently from all members of pedigrees of unequal size or varying structure, accommodates individuals missing at random, and allows flexible modelling with tests of distributional assumptions and fit. Most analytical methods use least squares or maximum likelihood under normal theory. Robust methods, scale transformation, ascertainment, path diagrams and correlational path models (popular in behavioural genetics through addressing nonrandom mating and social interactions), 'heritability', and the contribution and limitations of statistical modelling to the 'nature-nurture' debate, are discussed.

Genetic Diseases, Inborn↗

PubMed2004

Cytotoxic chemotherapy in the home: a study of community nurses' attitudes and concerns.

Cytotoxic chemotherapy initiated in a hospital setting and continued in the home is an expanding service. The evolution of such a service received a boost with the publication of the NHS Cancer Plan (Department of Health (DH), 2000a) and the NHS Manual of Cancer Service Standards (DH, 2000b). The literature claims a range of benefits of such a service including enhanced standards of care and cost savings. Effective care depends on a number of key factors including assessment, management of risk and support, i.e. appropriate policies and the availability of adequate resources. This study among community nurses reveals a number of key findings including the incremental nature of the development of policy and practice, the general acceptance that changes in community practice are inevitable and welcome where the changes enhance the care of patients, and a level of concern about the availability of appropriate resources and structures necessary for safe and effective practice.

Antineoplastic Agents↗

PubMed1993

Evolution of maternal mood state and of the auditory and olfactory perception of their newborn: preliminary data.

The auditory and olfactory discrimination ability of mothers, in relation to stimuli from their newborn infants, was concomitantly measured in a sample of 12 mother-newborn dyads during the 1st week after the child's birth. Both types of discrimination ability had a parallel evolution from one day to the next. The performances continued to increase from day to day, except on the 4th and 7th days. These 2 days corresponded to times when the mothers were more depressed. Half of the mothers were more skilled in one sensorial skill than the other.

Adult↗

PubMed1998

[Obstructive sleep apnea syndrome in children].

The obstructive sleep apnoea syndrome (OSAS) in children is a clinical syndrome resulting from complete or partial obstruction of the upper respiratory tract during sleep. The pathogenesis is multifactorial; clear risk groups are children with anatomical anomalies of the upper airways, neurological abnormalities and genetic syndromes (including craniofacial syndromes). The clinical symptoms of OSAS in children vary. In partial obstructions, the most frequent forms, the patients may snore and have impaired respiration during sleep. Polysomnography contributes to definite confirmation and specification of the clinical diagnosis. Standard values should be interpreted with respect to age. Adenotonsillectomy is the most frequent treatment of children with OSAS. In persistent symptoms, continuous positive pressure therapy is often successful. The natural evolution and the long-term prognosis of OSAS in children are still unknown.

Adenoidectomy↗

PubMedDate not supplied

The pregnant adolescent--a group approach.

This paper has described the groups for pregnant teenagers developed in the Rochester Adolescent Maternity Project. One and one-half year's experience with these groups has allowed the authors time to begin their study of groups and to write a descriptive paper of their evolution. The groups' development goes on while the leaders continue their own theoretical study of groups at this writing. Groups for pregnant adolescents have ranged from group therapy sessions to structured groups where only didactic material is presented. The literature is somewhat limited in its discussion of types of groups and especially in describing group process. This paper differs from others in that both group structure and process, based on the group objectives, are discussed. Information on approaches beneficial to the adolescent have been included. The goals of the group are to help the teenagers work through the developmental tasks of adolescence and pregnancy and to prepare them for the labor, delivery, and initial parenthood experience. Group structure is based on the intent to engage teenagers in resolution of these tasks in order to be prepared at a variety of levels, i.e. cognitive, emotional, etc., for labor, delivery, and parenthood. Co-leadership of the groups and an unstructured format facilitate the movement of the group toward accomplishment of its objectives. Group content issues were explored and techniques developed to handle these issues were suggested. Included were the following: 1. Commitment to the group by the members is assisted by the structure set for the group and the leaders' active outreach to members. 2. Descriptions of emotions and thoughts are made in concrete rather than abstract terms because of the developmental status of the teenagers. 3. Expression of personal feelings, often difficult for teenagers, is aided by the use of a projective technique. 4. Transition from leader-oriented to group-directed discussion is made possible by the group leaders gradually changing their leadership from one of direct interaction to one of facilitating discussion. 5. Polarization of the group in a negative or positive direction is prevented through the use of a neutral group member or active intervention by the group leaders taking on a neltral role. 6. Control, an issue of pregnancy and adolescence, is dealt with on interactional, educational, and emotional levels. 7. Termination is determined by the stage of the group "work" and is identified and facilitated by the group leaders. Research questions needed to document the effectiveness of the group approach to the pregnant adolescent were addressed.

Adolescent↗

PubMed1981

A short time for an old hospital in Wales.

When a hospital is continually evolving one year brings no dramatic changes but evolution goes on. Stephen Halpern visited a long established hospital in Wales.

Hospital Bed Capacity, 300 to 499↗