Macroecological relationships between coral species�� traits and disease potential

Coral disease is a growing problem for reef corals and a primary driver of reef degradation. Incidences of coral disease on the Great Barrier Reef (GBR) are increasing; however, our understanding of differences among species in their potential for contracting disease is poor. In this study, we integrate observations of coral disease on the GBR from the primary literature as well as morphological, ecological and biogeographical traits of coral species that have been hypothesised to influence “disease potential.” Most of the examined traits influence species’ disease potential when considered alone. However, when all traits are analysed together, diversity of predators, geographical range size and characteristic local abundance are the primary predictors of disease potential. Biases associated with species’ local abundance and phylogeny are tested but do not overpower relationships. This large-scale macroecological evaluation of coral disease provides insights into species-level traits that drive disease susceptibility.     

Serial visual evoked potential recordings in Alzheimer's disease.

Primary presenile dementia slows the major positive component of the visual evoked potential to flash stimulation but does not affect the visual evoked potential to patterned stimulation. The progressive effect of Alzheimer''s disease was followed in a 58 year old woman over three and a half years from the development of the earliest symptoms to complete mental incapacity. The pattern reversal visual evoked potential remained normal, but the flash visual evoked potential gradually slowed from 129 ms in 1981 to 153 ms in 1984. The severity of the abnormality of the flash visual evoked potential thus reflected the severity of the dementia. Electroencephalography, computed tomography, and psychometric tests indicated generalised cortical disease, but the results were not specific to dementia. The combination of a slowed flash and normal pattern visual evoked potential seems to be specific to Alzheimer''s disease and supports the use of flash and pattern visual evoked potentials in routine diagnostic testing for this condition.     

Targets for neuroprotection in Parkinson's disease

Current therapies for Parkinson's disease significantly improve the quality of life for patients suffering from this neurodegenerative disease, yet none of the current therapies has been convincingly shown to slow or prevent the progression of disease. Much has been learned about the pathophysiology of Parkinson's disease in recent years, and these discoveries offer a variety of potential targets for protective therapy. Mechanisms implicated in the disease process include oxidative stress, mitochondrial dysfunction, protein aggregation and misfolding, inflammation, excitotoxicity, and apoptosis. At the same time, the involvement of these diverse processes makes modeling the disease and evaluation of potential treatments difficult. In addition, available clinical tools are limited in their ability to monitor the progression of the disease. In this review, we summarize the different pathogenic mechanisms implicated in Parkinson's disease and neuroprotective strategies targeting these mechanisms currently under clinical study or under preclinical development, with a view towards strategies that seem most promising.     

Endothelial progenitor cells: diagnostic and therapeutic considerations

Endothelial progenitor cells (EPCs) may be defined as adherent cells derived from peripheral blood- or bone marrow-derived mononuclear cells demonstrating acLDL uptake and isolectin-binding capacity. The number of circulating EPCs inversely correlates with the number of cardiovascular risk factors and is reduced in cardiovascular disease. This measurement may therefore serves as a surrogate marker for cardiovascular disease risk. EPC numbers can be modified by various means. However, the effectiveness of risk-factor modification on EPC number and function is currently unknown. Furthermore, EPCs may be used as a potential therapy for a variety of vascular disease states including ischaemia, restenosis and pulmonary hypertension. This review provides an update on multiple factors that affect EPC number as well as highlighting the potential use of EPCs as a novel marker of vascular dysfunction. Furthermore, potential gene- and/or EPC-based approaches to a number of vascular disease states are explored.     

Alcoholic liver disease: new insights into mechanisms and preventative strategies

Alcoholic liver disease has a known aetiology but a complex pathogenesis. It is an extremely common disease with a high mortality, but the reason why only a relatively small proportion of heavy drinkers progress to advanced disease remains elusive. Accumulating evidence points towards an elaborate interplay between metabolism, inflammation and immunity in the development of steatosis, hepatitis and fibrosis. These complex pathways leading to liver injury offer many potential susceptibility loci, as well as sites for potential therapeutic intervention.     

Olfactory Assays for Mouse Models of Neurodegenerative Disease

In many neurodegenerative diseases and particularly in Parkinson’s disease, deficits in olfaction are reported to occur early in the disease process and may be a useful behavioral marker for early detection. Earlier detection in neurodegenerative disease is a major goal in the field because this is when neuroprotective therapies have the best potential to be effective. Therefore, in preclinical studies testing novel neuroprotective strategies in rodent models of neurodegenerative disease, olfactory assessment could be highly useful in determining therapeutic potential of compounds and translation to the clinic. In the present study we describe a battery of olfactory assays that are useful in measuring olfactory function in mice. The tests presented in this study were chosen because they measure olfaction abilities in mice related to food odors, social odors, and non-social odors. These tests have proven useful in characterizing novel genetic mouse models of Parkinson’s disease as well as in testing potential disease-modifying therapies.     

Transgenic mouse models of Alzheimer's disease

Recent advances in the understanding of the genetic basis of Alzheimer's disease have enabled the production of transgenic mouse models of the disease. Utilizing both cDNA- and genomic-based approaches, these mouse models for Alzheimer's disease have already provided valuable insights into the pathogenesis of the disease and potential therapeutic interventions.     

Infantile Pompe disease on ERT: update on clinical presentation, musculoskeletal management, and exercise considerations

Enzyme replacement therapy (ERT) with alglucosidase alpha, approved by the FDA in 2006, has expanded possibilities for individuals with Pompe disease (glycogen storage disease type II, GSDII, or acid maltase deficiency). Children with infantile Pompe disease are surviving beyond infancy, some achieving independent walking and functional levels never before possible. Individuals with late-onset Pompe disease are experiencing motor and respiratory improvement and/or stabilization with slower progression of impairments. A new phenotype is emerging for those with infantile Pompe disease treated with ERT. This new phenotype appears to be distinct from the late-onset phenotype rather than a shift from infantile to late-onset phenotype that might be expected from a simple diminution of symptoms with ERT. Questions arise regarding the etiology of the distinct distribution of weakness in this new phenotype, with increasing questions regarding exercise and musculoskeletal management. Answers require an increased understanding of the muscle pathology in Pompe disease, how that muscle pathology may be impacted by ERT, and the potential impact of, and need for, other clinical interventions. This article reviews the current state of knowledge regarding the pathology of muscle involvement in Pompe disease and the potential change in muscle pathology with ERT; the newly emerging musculoskeletal and gross motor phenotype of infantile Pompe disease treated with ERT; updated recommendations regarding musculoskeletal management in Pompe disease, particularly in children now surviving longer with residual weakness impacting development and integrity of the musculoskeletal system; and the potential impact and role of exercise in infantile Pompe survivors treated with ERT.     

Prion protein scrapie and the normal cellular prion protein

Prions are infectious proteins and over the past few decades, some prions have become renowned for their causative role in several neurodegenerative diseases in animals and humans. Since their discovery, the mechanisms and mode of transmission and molecular structure of prions have begun to be established. There is, however, still much to be elucidated about prion diseases, including the development of potential therapeutic strategies for treatment. The significance of prion disease is discussed here, including the categories of human and animal prion diseases, disease transmission, disease progression and the development of symptoms and potential future strategies for treatment. Furthermore, the structure and function of the normal cellular prion protein (PrP^C) and its importance in not only in prion disease development, but also in diseases such as cancer and Alzheimer's disease will also be discussed.     

Network Propagation with Dual Flow for Gene Prioritization

Based on the hypothesis that the neighbors of disease genes trend to cause similar diseases, network-based methods for disease prediction have received increasing attention. Taking full advantage of network structure, the performance of global distance measurements is generally superior to local distance measurements. However, some problems exist in the global distance measurements. For example, global distance measurements may mistake non-disease hub proteins that have dense interactions with known disease proteins for potential disease proteins. To find a new method to avoid the aforementioned problem, we analyzed the differences between disease proteins and other proteins by using essential proteins (proteins encoded by essential genes) as references. We find that disease proteins are not well connected with essential proteins in the protein interaction networks. Based on this new finding, we proposed a novel strategy for gene prioritization based on protein interaction networks. We allocated positive flow to disease genes and negative flow to essential genes, and adopted network propagation for gene prioritization. Experimental results on 110 diseases verified the effectiveness and potential of the proposed method.     

Disease risk and inter‐institutional transfer of specimens in cooperative breeding programs: Herpes and the elephant species survival plans

Managers of cooperative breeding programs and re‐introduction projects are increasingly concerned with the risk of disease transmission when specimens are transferred among facilities or between facilities and the natural environment. We used data maintained in North American studbooks to estimate the potential risks of disease transmission by direct and indirect contact of specimens in the American Zoo and Aquarium Association’s Elephant Species Survival Plan. Histological evidence for a novel herpesvirus disease transmitted between and within elephant species housed in North American facilities prompted an examination of the scope of possible transmission routes within the captive population. We found that, compared with other species managed through Species Survival Plans, elephants experience relatively few transfers between zoos. Nevertheless, the number of direct contacts with other elephants born during the study period of 1983–1996 (excluding stillbirths) was much higher than we had anticipated (μ = 25 ± 27; N = 59) and the number of potential indirect contacts was surprisingly large (μ = 143 ± 92; N = 59). Although these high rates of potential contacts complicate exact identification of infection pathways for herpesvirus, we were able to propose potential routes of transmission for the histologically identified cases. Furthermore, the extraction of data from studbooks allowed us to readily identify other specimens that did not succumb to the disease despite similar exposure. Moreover, we were able to identify other possible cases to recommend for histological examination. Herein we reveal the possibilities of multiple disease transmission pathways and demonstrate how complex the patterns of transmission can be, confounded by the unknown latency of this novel herpesvirus. This emphasizes the need for zoo veterinarians and cooperative breeding programs to consider the full potential for disease transmission associated with each and every inter‐zoo transfer of specimens. Zoo Biol 20:89–101, 2001. © 2001 Wiley‐Liss, Inc.     

Redox proteomics identification of oxidatively modified proteins in Alzheimer's disease brain and in vivo and in vitro models of AD centered around Abeta(1-42)

Alzheimer's disease is a progressive neurodegenerative disease associated with loss of memory and cognition. One hallmark of AD is the accumulation of amyloid beta-peptide (Abeta), which invokes a cascade of oxidative damage to neurons that can eventually result in neuronal death. Several markers of oxidative stress have been identified in AD brain, thus providing greater understanding into potential mechanisms involved in the disease pathogenesis and progression. In the present article, we review the application of redox proteomics to the identification of oxidized proteins in AD brain and also our recent findings on amyloid beta-peptide (Abeta)-associated in vivo and in vitro models of AD. Our redox proteomics approach has made possible the identification of specifically oxidized proteins in Alzheimer's disease (AD) brain, providing for the first time evidence on how oxidative stress plays a crucial role in AD-related neurodegeneration. The information obtained has great potential to aid in determining the molecular pathogenesis in and detecting disease markers of AD, as well as identifying potential targets for drug therapy in AD. Application of redox proteomics to study cellular events, especially related to disease dysfunction, may provide an efficient tool to understand the main mechanisms involved in the pathogenesis and progression of oxidative stress-related neurodegenerative disorders.     

Parkinson disease drug screening based on the interaction between D2 dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis

Parkinson’s disease is the second most common neurodegenerative disease in the world. Beta-arrestin-2 has been reported to be an important protein involved in D₂ dopamine receptor desensitization, which is essential to Parkinson’s disease. Moreover, the potential value of pharmacological inactivation of G protein-coupled receptor kinase or arrestin in the treatment of patients with Parkinson’s disease has recently been shown. We studied the interaction between D₂ dopamine receptor and beta-arrestin-2 and the pharmacological regulation of chemical compounds on such interaction using capillary zone electrophoresis. The results from screening more than 40 compounds revealed three compounds that remarkably inhibit the beta-arrestin-2/D₂ dopamine receptor interaction among them. These compounds are promising therapies for Parkinson’s disease, and the method used in this study has great potential for application in large-scale drug screening and evaluation.     

Immunomodulatory benefits of cyclosporine A in inflammatory bowel disease

Etiopathogenesis of mucosal inflammation in inflammatory bowel disease remains a complex and enigmatic field; various factors (genetic, environmental and microbial) trigger an event that activates intestinal immune and nonimmune systems culminating in inflammation and tissue injury. Specifically, both innate and adaptive immune systems seem to play important roles in the pathophysiology of this disease. Cyclosporine A represents a macrolide immune modulator with primary inhibitory effects on T helper lymphocyte production of interleukin-2, and other cytokines leading to altered T-lymphocyte and B-lymphocyte function. The diversity of its therapeutic outcome reported in inflammatory bowel disease may be due to the intricate immuno-pathogenic profile of the disease and the variety of the applied dose-dependent courses of therapy. Cyclosporine A exerts additional actions on other components of the inflammatory infiltrate, including neutrophils and mast cells, thereby appearing to be a multi-dynamic therapeutic approach, although with potential drawbacks, that may be applied alone or combined with other immunomodulatory agents in inflammatory bowel disease patients. Because cyclosporine A induces apoptosis of T-lymphocytes responsible for perpetuation of the chronic inflammatory process in the disease with potential tumorigenic effect, it may exert a further inhibitory effect on cancer development in inflammatory bowel disease patients, and can be combined with other relative agents, such as rapamycin, which also promotes T-lymphocyte apoptosis. Therefore, recently established multifactorial action of cyclosporine A in relation to the pathogenesis of the disease can open new horizons for prospective, controlled trials in large cohorts, aiming to emphasize cyclosporine A's potential.     

Strategies to improve regenerative potential of mesenchymal stem cells

In the last few decades, stem cell-based therapies have gained attention worldwide for various diseases and disorders. Adult stem cells, particularly mesenchymal stem cells (MSCs), are preferred due to their significant regenerative potential in cellular therapies and are currently involved in hundreds of clinical trials. Although MSCs have high self-renewal as well as differentiation potential, such abilities are compromised with “advanced age” and “disease status” of the donor. Similarly, cell-based therapies require high cell number for clinical applications that often require in vitro expansion of cells. It is pertinent to note that aged individuals are the main segment of population for stem cell-based therapies, however; autologous use of stem cells for such patients (aged and diseased) does not seem to give optimal results due to their compromised potential. In vitro expansion to obtain large numbers of cells also negatively affects the regenerative potential of MSCs. It is therefore essential to improve the regenerative potential of stem cells compromised due to “in vitro expansion”, “donor age” and “donor disease status” for their successful autologous use. The current review has been organized to address the age and disease depleted function of resident adult stem cells, and the strategies to improve their potential. To combat the problem of decline in the regenerative potential of cells, this review focuses on the strategies that manipulate the cell environment such as hypoxia, heat shock, caloric restriction and preconditioning with different factors.     

Charcot-Marie-Tooth disease: emerging mechanisms and therapies

Charcot-Marie-Tooth disease is the most common inherited disorder of the peripheral nervous system. The disease is characterized by a progressive muscle weakness and atrophy, sensory loss, foot (and hand) deformities and steppage gait. While many of the genes associated with axonal CMT have been identified, to date it is unknown which mechanism(s) causes the disease. However, genetic findings indicate that the underlying mechanisms mainly converge to the axonal cytoskeleton. In this review, we will summarize the evidence for this pathogenic convergence. Furthermore, recent work with new transgenic mouse models has led to the identification of histone deacetylase 6 as a potential therapeutic target for inherited peripheral neuropathies. This enzyme deacetylates microtubules and plays a crucial role in the regulation of axonal transport. These findings offer new perspectives for a potential therapy to treat axonal Charcot-Marie-Tooth disease and other neurodegenerative disorders characterized by axonal transport defects.     

Biomarkers for Alzheimer disease in cerebrospinal fluid, urine, and blood

Alzheimer disease is the most common cause of dementia, yet its clinical diagnosis remains uncertain until an eventual postmortem histopathology examination. Currently, therapy for patients with Alzheimer disease only treats the symptoms; however, it is anticipated that new disease-modifying drugs will soon become available.Diagnostic tools for detecting Alzheimer disease at an incipient stage that can reliably differentiate the disease from other forms of dementia are of key importance for optimal treatment. Biomarkers have the potential to aid in a correct diagnosis, and great progress has been made in the discovery and development of potentially useful biomarkers in recent years. This includes single protein biomarkers in the cerebrospinal fluid, as well as multi-component biomarkers, and biomarkers based on gene expression. Novel biomarkers that use blood and urine, the more easily available clinical samples, are also being discovered and developed. The plethora of potential biomarkers currently being investigated may soon provide biomarkers that fulfill different functions, not only for diagnostic purposes but also for drug development and to follow disease progression.     

Selection of peptides for serological detection of equine infectious anemia

Equine infectious anemia caused by equine infectious anemia virus is an important disease due to its high severity and incidence in animals. We used a phage display library to isolate peptides that can be considered potential markers for equine infectious anemia diagnosis. We selected peptides using IgG purified from a pool comprised of 20 sera from animals naturally infected with equine infectious anemia virus. The diagnostic potential of these peptides was investigated by ELISA, Western blot and dot blot with purified IgG and serum samples. Based on the results, we chose a peptide mimetic for glycoprotein gp45 epitopes of equine infectious anemia virus, with potential for use as an antigen in indirect diagnostic assays. Synthesis of this peptide has possible applications for the development of new diagnostic tools for this disease.     

Consequences of non-intervention for infectious disease in African great apes

Infectious disease has recently joined poaching and habitat loss as a major threat to African apes. Both "naturally" occurring pathogens, such as Ebola and Simian Immunodeficiency Virus (SIV), and respiratory pathogens transmitted from humans, have been confirmed as important sources of mortality in wild gorillas and chimpanzees. While awareness of the threat has increased, interventions such as vaccination and treatment remain controversial. Here we explore both the risk of disease to African apes, and the status of potential responses. Through synthesis of published data, we summarize prior disease impact on African apes. We then use a simple demographic model to illustrate the resilience of a well-known gorilla population to disease, modeled on prior documented outbreaks. We found that the predicted recovery time for this specific gorilla population from a single outbreak ranged from 5 years for a low mortality (4%) respiratory outbreak, to 131 years for an Ebola outbreak that killed 96% of the population. This shows that mortality rates comparable to those recently reported for disease outbreaks in wild populations are not sustainable. This is particularly troubling given the rising pathogen risk created by increasing habituation of wild apes for tourism, and the growth of human populations surrounding protected areas. We assess potential future disease spillover risk in terms of vaccination rates amongst humans that may come into contact with wild apes, and the availability of vaccines against potentially threatening diseases. We discuss and evaluate non-interventionist responses such as limiting tourist access to apes, community health programs, and safety, logistic, and cost issues that constrain the potential of vaccination.