The first decade of microbial genomics: what have we learned and where are we going next?

A report on the International Conference on Microbial Genomics, Halifax, Canada, 13-16 April 2005.     

Two Decades of Molecular Ecology: where are we and where are we heading?

The twentieth anniversary of the journal Molecular Ecology was celebrated with a symposium on the current state and the future directions of the field. The event, organized by Tim Vines and Loren Rieseberg, took place on the opening day of the First Joint Congress on Evolutionary Biology organized by the American Society of Naturalists (ASN), the Canadian Society for Ecology and Evolution (CSEE), the European Society for Evolutionary Biology (ESEB), the Society for the Study of Evolution (SSE) and the Society of Systematic Biologists (SSB) in Ottawa (Canada) from 6–10 July 2012. The get together of these five societies created a truly international and exciting “Evolution conference” and the ideal framework for the Molecular Ecology symposium. Its thirteen talks were grouped into the five different subject areas of the journal: Speciation and Hybridization; Landscape Genetics, Phylogeography and Conservation; Ecological Genomics and Molecular Adaptation; Kinship, Parentage and Behaviour; Ecological Interactions. Each session was followed by a panel discussion on the future direction of the subfield. That more than 300 colleagues registered for this special symposium illustrates the broad interest in, and appreciation of, molecular ecology – both the field and the journal.     

Recent insights into human bronchial proteomics – how are we progressing and what is next?

Introduction: The human respiratory system is highly prone to diseases and complications. Many lung diseases, including lung cancer (LC), tuberculosis (TB), and chronic obstructive pulmonary disease (COPD) have been among the most common causes of death worldwide. Cystic fibrosis (CF), the most common genetic disease in Caucasians, has adverse impacts on the lungs. Bronchial proteomics plays a significant role in understanding the underlying mechanisms and pathogenicity of lung diseases and provides insights for biomarker and therapeutic target discoveries.

Areas covered: We overview the recent achievements and discoveries in human bronchial proteomics by outlining how some of the different proteomic techniques/strategies are developed and applied in LC, TB, COPD, and CF. Also, the future roles of bronchial proteomics in predictive proteomics and precision medicine are discussed.

Expert commentary: Much progress has been made in bronchial proteomics. Owing to the advances in proteomics, we now have better ability to isolate proteins from desired cellular compartments, greater protein separation methods, more powerful protein detection technologies, and more sophisticated bioinformatic techniques. These all contributed to our further understanding of lung diseases and for biomarker and therapeutic target discoveries.     

Pim kinases in hematological malignancies: where are we now and where are we going?

The proviral insertion in murine (PIM) lymphoma proteins are a serine/threonine kinase family composed of three isoformes: Pim-1, Pim-2 and Pim-3. They play a critical role in the control of cell proliferation, survival, homing and migration. Recently, overexpression of Pim kinases has been reported in human tumors, mainly in hematologic malignancies. In vitro and in vivo studies have confirmed their oncogenic potential. Indeed, PIM kinases have shown to be involved in tumorgenesis, to enhance tumor growth and to induce chemo-resistance, which is why they have become an attractive therapeutic target for cancer therapy. Novel molecules inhibiting Pim kinases have been evaluated in preclinical studies, demonstrating to be effective and with a favorable toxicity profile. Given the promising results, some of these compounds are currently under investigation in clinical trials. Herein, we provide an overview of the biological activity of PIM-kinases, their role in hematologic malignancies and future therapeutic opportunities.     

Antibiotic use in animal agriculture: what have we learned and where are we going?

Antibiotics are enormously important for the humane and efficient production of food animals. These benefits are somewhat offset by the human and animal health antibiotic resistance risks posed by their use in animals. This article provides an overview of what we have learned about antibiotic resistance as an issue in animal agriculture and where that knowledge could lead us in the future. To preserve the effectiveness of antibiotics, more action is needed to ensure their prudent use, particularly in the case of antibiotic growth promoters and antibiotics deemed critically important for human and animal health.     

Leptin in farm animals: where are we and where can we go?

Fat affects meat quality, value and production efficiency as well as providing energy reserves for pregnancy and lactation in farm livestock. Leptin, the adipocyte product of the obese (ob) gene, was quickly seen as a predictor of body fat content in animals approaching slaughter and an aid to assessing reproductive readiness in females. Its participation in inflammation and immune responses that help animals survive infection and trauma has clear additional relevance to meat and milk production. Furthermore, almost a decade of discoveries of nucleotide polymorphisms in the leptin and leptin receptor genes has suggested useful applications relating to feed intake regulation, the efficiency of feed use, the composition of growth, the timing of puberty, mammogenesis and mammary gland function and fertility in cattle, pigs and poultry. The current review attempts to summarise where research has taken us in each of these aspects and speculates on where future research might lead.     

Neurochemical dementia diagnostics in Alzheimer's disease: where are we now and where are we going?

Neurochemical dementia diagnostics (NDD) is a routine laboratory tool used in the diagnostic process for patients with neurodegenerative disorders, such as Alzheimer's disease. Currently, two groups of biomarkers analyzed in the cerebrospinal fluid are considered - namely amyloid-β peptides and Tau proteins - along with the hyperphosphorylated forms of the latter (pTau). Current directions in the development of NDD include the following: search for novel biomarkers with improved analytical or diagnostic performance; optimization of the analysis of the biomarkers already available (e.g., by improved quality control and interlaboratory comparison of results); applications of novel technologies enabling better management of patient samples; and search for biomarkers in the blood. This article presents the state-of-the-art in the field of cerebrospinal fluid-based NDD, and also summarizes some of the hypotheses of how the future development of NDD tools might look.     

Structure and function of xanthine oxidoreductase: where are we now?

Xanthine oxidoreductase (XOR) is a complex molybdoflavoenzyme, present in milk and many other tissues, which has been studied for over 100 years. While it is generally recognized as a key enzyme in purine catabolism, its structural complexity and specialized tissue distribution suggest other functions that have never been fully identified. The publication, just over 20 years ago, of a hypothesis implicating XOR in ischemia-reperfusion injury focused research attention on the enzyme and its ability to generate reactive oxygen species (ROS). Since that time a great deal more information has been obtained concerning the tissue distribution, structure, and enzymology of XOR, particularly the human enzyme. XOR is subject to both pre- and post-translational control by a range of mechanisms in response to hormones, cytokines, and oxygen tension. Of special interest has been the finding that XOR can catalyze the reduction of nitrates and nitrites to nitric oxide (NO), acting as a source of both NO and peroxynitrite. The concept of a widely distributed and highly regulated enzyme capable of generating both ROS and NO is intriguing in both physiological and pathological contexts. The details of these recent findings, their pathophysiological implications, and the requirements for future research are addressed in this review.     

Teaching history-taking: where are we?

Knowledge in history-taking has increased rapidly over the last twenty years. Currently the principles to be taught include "conduct," "content," and "diagnostic reasoning." However, inattentiveness of medical schools, reluctance of busy faculty to be involved, and increasing enrollments have resulted in difficulties in teaching these skills. Studies have shown a beneficial short-term effect of teaching these materials on interview performance but it is unknown whether this effect is long-lasting. The methods for instruction include the bedside and videotape models utilizing the concept of the fifteen-minute interview technique, programmed instruction, patient instructors, and direct student feedback. Future research should focus on identifying strategies in diagnostic reasoning, developing graduated competency criteria for trainees at different levels of their education, refining methods to evaluate large numbers of students, measuring outcomes of effective training such as compliance, and comparing costs and effectiveness of various methods. In addition, there remains the need to establish an association of course directors.     

Oxidative stress and neurodegeneration: where are we now?

The brain and nervous system are prone to oxidative stress, and are inadequately equipped with antioxidant defense systems to prevent 'ongoing' oxidative damage, let alone the extra oxidative damage imposed by the neurodegenerative diseases. Indeed, increased oxidative damage, mitochondrial dysfunction, accumulation of oxidized aggregated proteins, inflammation, and defects in protein clearance constitute complex intertwined pathologies that conspire to kill neurons. After a long lag period, therapeutic and other interventions based on a knowledge of redox biology are on the horizon for at least some of the neurodegenerative diseases.     

Statin therapy and stroke prevention: what was known, what is new and what is next?

PURPOSE OF REVIEW: Randomized trials have shown that statins may reduce the risk of primary stroke. There is no evidence however that statins can reduce recurrent stroke incidence. RECENT FINDINGS: In the SPARCL trial, patients with a recent stroke or transient ischemic attack randomized to atorvastatin 80 mg/day had a significant 16% relative risk reduction of stroke, and a 35% reduction in major coronary events compared with placebo. This was obtained despite 25% of the placebo arm patients receiving a commercially-available statin outside of the trial. Post-hoc analysis used blinded LDL-cholesterol measurements as a marker of adherence to lipid-lowering therapy. Compared with the group with no change or an increase in LDL-cholesterol (the group adherent to placebo or not taking a statin), the group with over 50% reduction in LDL-cholesterol had a significant 31% reduction in stroke. The next step is to define whether achieving LDL-cholesterol below 70 mg/dl is better than a standard dose of statin (LDL around 100-110 mg/dl) in the secondary prevention of stroke. SUMMARY: Statins are effective in reducing both first-ever and recurrent stroke, and this effect seems driven by the extent of LDL-cholesterol lowering.     

Insurance and genetic testing: where are we now?

Basic research will spur development of genetic tests that are capable of presymptomatic prediction of disease, disability, and premature death in presently asymptomatic individuals. Concerns have been expressed about potential harms related to the use of genetic test results, especially loss of confidentiality, eugenics, and discrimination. Existing laws and administrative policies may not be sufficient to assure that genetic information is used fairly. To provide factual information and conceptual principles upon which sound social policy can be based, the Human Genome Initiative established an Ethical, Legal, and Social Issues Program. Among the first areas to be identified as a priority for study was insurance. This paper provides a review of life, health, and disability insurance systems, including basic principles, risk classification, and market and regulatory issues, and examines the potential impact of genetic information on the insurance industry.