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PubMed2005

Practical cancer genetics, genomics and proteomics.

Functional genomics is the science that defines the function of newly identified genes and translates this knowledge into related health and disease. Functional genomics is complex, involving multiple scientific disciplines including computational biology, genetics, physiology, structural biology, and molecular and cell biology. Due to its inherent complexity, the National Institutes of Health (NIH) has termed functional genomics "the science of collaboration." This paper will review microarray gene expression analysis, proteomics, and the impact of molecular medical genetics on medical care.

Gene Expression↗
PubMed2004

Siren call of metaphor: subverting the proper task of neuroscience.

Under the assumption that nervous systems form a distinct category among the objects in Nature, applying metaphors of psychological and behavioral science disciplines is flawed and invites confusion. Moreover, such practices obscure and detract from the primary task of Neurophysiology: to investigate the intrinsic properties of nervous systems, uncontaminated with concepts borrowed from other disciplines.

Animals↗
PubMed2005

New prospects for the management of renal bone disease.

The last decade has been a remarkably productive one in the field of bone biology. New insights into the maintenance of a normal bone microenvironment have led to significant advances in our understanding of many important skeletal disorders, including renal osteodystrophy. Novel targets for therapeutic manipulation have been exposed and encouraging progress made towards new treatments. In addition, just as clinical studies have alerted us to the potential hazards of vascular calcification, basic science has unearthed the intimate nature of the relationship between the previously separate disciplines of bone and vascular biology. The clinical nephrologist, however, may be forgiven a little cynicism at this point. If such progress has been made, why do the same proverbial difficulties confront us in day-to-day practice? Control of phosphate remains inadequate, despite a literature which constantly reaffirms its crucial importance, and parathyroid hyperplasia seems inevitable in many patients. Furthermore, even the satisfaction of successful control of serum parathyroid hormone concentration must now be tempered by disquiet regarding the skeletal and cardiovascular consequences of oversuppression. This review aims to provide an update of the latest developments in relevant skeletal research and to assess how recently acquired knowledge may improve clinical nephrological practice over the next five years.

Animals↗
PubMed2000

The impact of histochemistry--a historical perspective.

Histochemistry has a remarkable long-term impact on cell and tissue biology, embryology, and pathology and remains at the forefront of research in these disciplines. Histochemical techniques, and particularly immunohistochemical and in situ hybridization techniques, are now more widely used than ever and, in conjunction with new developments in microscopical imaging and analysis, will continue to have an important position in the life sciences and medicine. However, histochemistry is often mistakenly perceived as an archaic discipline, and its contributions to cell and molecular biology are not always given the credit it deserves.

Histocytochemistry↗
PubMed2005

Complex adaptive systems: concept analysis.

AIM: The aim of this paper is to explicate the concept of complex adaptive systems through an analysis that provides a description, antecedents, consequences, and a model case from the nursing and health care literature. BACKGROUND: Life is more than atoms and molecules--it is patterns of organization. Complexity science is the latest generation of systems thinking that investigates patterns and has emerged from the exploration of the subatomic world and quantum physics. A key component of complexity science is the concept of complex adaptive systems, and active research is found in many disciplines--from biology to economics to health care. However, the research and literature related to these appealing topics have generated confusion. A thorough explication of complex adaptive systems is needed. METHODS: A modified application of the methods recommended by Walker and Avant for concept analysis was used. FINDINGS: A complex adaptive system is a collection of individual agents with freedom to act in ways that are not always totally predictable and whose actions are interconnected. Examples include a colony of termites, the financial market, and a surgical team. It is often referred to as chaos theory, but the two are not the same. Chaos theory is actually a subset of complexity science. Complexity science offers a powerful new approach--beyond merely looking at clinical processes and the skills of healthcare professionals. CONCLUSION: The use of complex adaptive systems as a framework is increasing for a wide range of scientific applications, including nursing and healthcare management research. When nursing and other healthcare managers focus on increasing connections, diversity, and interactions they increase information flow and promote creative adaptation referred to as self-organization. Complexity science builds on the rich tradition in nursing that views patients and nursing care from a systems perspective.

Delivery of Health Care↗
PubMed2005

Edward B. Aveling: the people's Darwin.

By the late-19th century, evolutionary theory, known by most people as Darwinism, had earned a reputation as an atheistic theory that challenged religious orthodoxy. From recent historical work we now know a great deal about how those with religious convictions received Darwinian ideas, and the role that professional scientists played in styling and communicating 'Darwinism' to the wider public and between themselves. However, relatively little is known about how Darwinian ideas were received and used by avowedly irreligious groups, and how these groups set about communicating their own version of Darwinism to a public hungry for cheap and accessible science. The activities of the Secularist Edward Bibbins Aveling, a prolific popularizer of Darwinian ideas in the late-19th century, offer a unique insight into this relatively uncharted territory. His work helped to develop the polemic of popular irreligious groups and imbue Darwinism with overtly atheistic connotations; it also engendered unprecedented support for atheism from the general public, and challenged the monopoly that some professional scientists enjoyed over imparting serious scientific knowledge to them.

Biological Evolution↗
PubMed2004

Phosphate binding protein as the biorecognition element in a biosensor for phosphate.

This work explores the potential use of a member of the periplasmic family of binding proteins, the phosphate binding protein (PBP), as the biorecognition element in a sensing scheme for the detection of inorganic phosphate (Pi). The selectivity of this protein originates from its natural role which, in Escherichia coli, is to serve as the initial receptor for the highly specific translocation of Pi to the cytoplasm. The single polypeptide chain of PBP is folded into two similar domains connected by three short peptide linkages that serve as a hinge. The Pi binding site is located deep within the cleft between the two domains. In the presence of the ligand, the two globular domains engulf the former in a hinge-like manner. The resultant conformational change constitutes the basis of the sensor development. A mutant of PBP (MPBP), where an alanine was replaced by a cysteine residue, was prepared by site-directed mutagenesis using the polymerase chain reaction (PCR). The mutant was expressed, from plasmid pSD501, in the periplasmic space of E. coli and purified in a single chromatographic step on a perfusion anion-exchange column. Site-specific labeling was achieved by attaching the fluorophore, N-[2-(1-maleimidyl)ethyl]-7-(diethylamino)coumarin-3-carboxamide (MDCC), to the protein through the sulfhydryl group of the cysteine moiety. Steady-state fluorescence studies of the MPBP-MDCC conjugate showed a change in the intensity of the signal upon addition of Pi. Calibration curves for Pi were constructed by relating the intensity of the fluorescence signal with the amount of analyte present in the sample. The sensing system was first developed and optimized on a spectrofluorometer using ml volumes of sample. It was then adapted to be used on a microtiter plate arrangement with microliter sample volumes. The system's versatility was finally proven by developing a fiber optic fluorescence-based sensor for monitoring Pi. In all three cases the detection limits for the analyte were in the sub-microMolar range. It was also demonstrated that the sensing system was selective for phosphate over other structurally-similar anions, paving the way for the design and development of a new family of biosensors utilizing the specific binding properties of periplasmic proteins.

Amino Acid Substitution↗
PubMed2026

PanForest: predicting genes in genomes using random forests.

MOTIVATION: The presence or absence of some genes in a genome can influence whether other genes are likely to be present or absent. Understanding these gene co-occurrence and avoidance patterns reveals fundamental principles of genome organization, with applications ranging from evolutionary reconstruction to rational design of synthetic genomes. RESULTS: PanForest, presented here, uses random forest classifiers to predict the presence and absence of genes in genomes from the set of other genes present. Performance statistics output by PanForest reveal how predictable each gene's presence or absence is, based on the presence or absence of other genes in the genome. Further, PanForest produces statistics indicating the importance of each gene in predicting the presence or absence of each other gene. The PanForest software can run serially or in parallel, thereby facilitating the analysis of pangenomes at Network of Life scale.A pangenome of 12 741 accessory genes in 1000 Escherichia coli genomes was analysed in around 5 h using eight processors. To demonstrate PanForest's utility, we present a case study and show that certain genes associated with resistance to antimicrobial drugs reliably predict the presence or absence of other genes associated with resistance to the same drug. Further, we highlight several associations between those genes and others not known to be associated with antimicrobial resistance (AMR), or associated with resistance to other drugs. We envisage PanForest's use in studies from multiple disciplines concerning the dynamics of gene distributions in pangenomes ranging from biomedical science and synthetic biology to molecular ecology. AVAILABILITY AND IMPLEMENTATION: The software if freely available with a full manual and can be found with at www.github.com/alanbeavan/PanForest DOI: https://doi.org/10.5281/zenodo.17865482.

Software↗
PubMed1998

Status of current research on endometriosis.

Endometriosis, a benign gynecologic disorder, occurs in about 10% of women of reproductive age and in up to 50% of women with infertility. Endometriosis is defined as the presence of endometrial glandular and stromal cells outside their normal location in the uterus. Commonly affected areas in the abdominopelvic cavity include the ovaries, the cul-desac and other kinds of pelvic peritoneum, bowel and diaphragm. Rarely is it found in extraabdominal sites, including the pleura and pericardium. While it is not a malignant disorder, endometriosis exhibits cellular proliferation, cellular invasion and neoangiogenesis. The steroid hormone dependence of endometriosis is underscored by its appearance during the reproductive years. Furthermore, the progress of this enigmatic disease can be tempered by administration of antiestrogens, inhibitors of endogenous estradiol production, and hormonal and surgical castration. It is a disorder that markedly affects well-being and physical and emotional health in women. Research on the pathogenesis of endometriosis currently interfaces with four areas of basic research, including the fields of genetics, environmental science, cancer biology and immunology. Here we focus on current research in the latter two disciplines and their relevance to endometriosis research.

Cytokines↗
PubMed2003

Sphingolipids as therapeutics.

The sphingolipid field has made significant strides over the past 10 years: from identifying metabolites of the sphingomyelin pathway as second messengers to discerning the molecular biology and biophysics of these lipid-derived second messengers. Building upon this vast basic science literature, scientists from multiple disciplines have begun to translate manipulations of endogenous sphingolipid metabolites and targets into therapeutic initiatives. Multiple publications have reviewed the biochemistry [Biochemistry 40 (16) (2001) 4893 [1]; Environ. Health Perspect. 109 (Suppl. 2) (2001) 283 ], biophysics [J. Cell Physiol. 184 (3) (2000) 285; Trends Cell Biol. 10 (10) (2000) 408 ], molecular biology [Biochim. Biophys. Acta 1426 (2) (1999) 347 ], and physiology [J. Biol. Chem. 277 (29) (2002) 25851; J. Biol. Chem. 277 (29) (2002) 25847 ] of sphingolipid metabolites. The present review serves to document the emerging concept of sphingolipid metabolites as therapeutics with clear clinical potential.

Animals↗
PubMed2005

Advances in text analytics for drug discovery.

The automated extraction of biological and chemical information has improved over the past year, with advances in access to content, entity extraction of genes, chemicals, kinetic data and relationships, and algorithms for generating and testing hypotheses. As the systems for reading and understanding scientific literature grow more powerful, so must the infrastructure in which to assemble information. Advances in infrastructure systems are discussed in this review. Research efforts have flourished as a result of text analytics competitions that attract participants from various disciplines, from computer science to bioinformatics.

Animals↗
PubMed2004

Aids, race and the limits of science.

In the US, HIV is understood as the virus that causes AIDS, the root of a disease syndrome perceived to indicate an immune system that has ceased to function. These understandings reflect the unquestioned hegemony of Euro/American scientific knowledge, a hegemony that precludes alternative interpretations of life and death, health and disease. This paper argues that HIV/AIDS is more complicated than biomedicine allows, and that the "overmedicalization" of treatment and prevention efforts obscures the significant socio-cultural and political-economic realities that shape the global pandemic, including conceptions of race. The paper specifically focuses on the discourses of bio- and socio-pathology that link African diasporic communities around the globe, and which often seamlessly articulate with structural locations, producing a coherent narrative in which social and moral positions justify and substantiate one another. The analysis here occurs on both these levels: the discursive and the structural. If we are to understand the complex relationships that form the AIDS epidemic, the disciplinary lines imagined between scientific paradigms and the clinical focus on the individual body on one hand, and the social sciences and humanities disciplines on the other, must be breached. If what we call AIDS is a socio-cultural and political-economic phenomenon with biological manifestations, then it is essential that the insights of the social sciences and humanities be brought to bear on finding solutions to the epidemic.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Pharmacovigilance during the pre-approval phases: an evolving pharmaceutical industry model in response to ICH E2E, CIOMS VI, FDA and EMEA/CHMP risk-management guidelines.

Pharmacovigilance science has traditionally been a discipline focussed on the postmarketing or post-authorisation period, with due attention directed towards pre-clinical safety data, clinical trials and adverse events. As the biological sciences have evolved, pharmacovigilance has slowly shifted toward earlier, proactive consideration of risks and potential benefits of drugs in the pre- and peri-approval stages of drug development, leading to a maturing of drug safety risk management. Further advances in biology, pharmacology and improvements in computational applications to medicine have led to the development of more complex medicines previously unobtainable and have also permitted a more thorough assessment of risks and potential benefits even earlier in the development process. Elevated public concern with the safety of more sophisticated medicines, combined with new science, have led pharmaceutical innovators, regulators and healthcare professionals to collaborate to develop guidelines, which drive enhanced pharmacovigilance and safety risk management earlier in drug development. In this paper, we review international guidelines on pharmacovigilance planning applicable to the pre-approval phases of medicines development and provide author opinion on these guidelines' potential drug safety implications. We discuss the possible evolution of a pharmaceutical industry model to respond to these guidelines; a view on multidisciplinary safety management teams is provided to encourage refinement of safety-signal identification and risk assessment early in drug development and to communicate important safety concerns to internal research efforts, patients, investigators and regulators. We further describe these functions in the context of the complexities of vulnerable populations, including the example of medicines research for paediatric populations. We also discuss the special role of epidemiology in pre-approval drug development and the impact on epidemiological science of changes to the pharmacovigilance paradigm.

Adverse Drug Reaction Reporting Systems↗
PubMed1992

Is mental disease just brain disease? The limits to biological psychiatry.

As a process of rational enquiry into an empirical field, psychiatry must submit itself to the same discipline as other areas of science. Effectively, it must show that its fundamental premises are both internally and externally consistent, and that its methods of investigation satisfy prevailing criteria of scientific methodology. When psychoanalytic psychology (and hence all psychodynamic models) and behaviourism were analysed from these points of view, they were found wanting. To date, there has been little or no meta-analysis of the third great school of psychiatric theorizing, biological psychiatry. A preliminary analysis establishes sharp limits to the notion that biological psychiatry is the "wave of the future". Like psychoanalysis and behaviourism, it cannot form the basis of a general theory of psychiatry. Since it lacks an adequate theoretical framework, the inescapable conclusion is that psychiatry is nothing more than protoscience.

Attitude of Health Personnel↗
PubMed2006

Using literature and innovative assessments to ignite interest and cultivate critical thinking skills in an undergraduate neuroscience course.

Science education reform initiatives emphasize 1) the value of concepts over facts; 2) the benefits of open-ended, inquiry-based problem-solving rather than protocols leading to a single correct answer; and 3) the importance of a multidisciplinary approach to teaching that is not confined by departmental boundaries. Neuroscientists should be at the forefront of this movement by the very nature of the discipline we study. Neuroscience is a relatively new field that integrates diverse subjects (anatomy, physiology, pharmacology, molecular biology, computer science, and psychology) and experimental advances are constantly changing and expanding our understanding of brain function. How can we convey this excitement in the classroom? The project described in this article uses nonscientific literature to introduce a scientific topic of study. In addition, the multitask assignment requires the acquisition of content knowledge and the development of critical thinking skills. As students explore the topic from multiple perspectives, they recognize the interconnectedness of science and society and confront ethical and moral issues related to science. A comparison of exam scores, essay responses, engagement level, as well as students' own reflections, demonstrates that inclusion of the project does not sacrifice content knowledge, rather it enhances the overall learning process.

Adult↗
PubMed2005

A systems- and signal-oriented approach to intracellular dynamics.

A mathematical understanding of regulation, and, in particular, the role of feedback, has been central to the advance of the physical sciences and technology. In this article, the framework provided by systems biology is used to argue that the same can be true for molecular biology. In particular, and using basic modular methods of mathematical modelling which are standard in control theory, a set of dynamic models is developed for some illustrative cell signalling processes. These models, supported by recent experimental evidence, are used to argue that a control theoretical approach to the mechanisms of feedback in intracellular signalling is central to furthering our understanding of molecular communication. As a specific example, a MAPK (mitogen-activated protein kinase) signalling pathway is used to show how potential feedback mechanisms in the signalling process can be investigated in a simulated environment. Such 'what if' modelling/simulation studies have been an integral part of physical science research for many years. Using tools of control systems analysis, as embodied in the disciplines of systems biology, similar predictive modelling/simulation studies are now bearing fruit in cell signalling research.

Cells↗