Junying Yuan: changing avenues without losing focus. Interview by Nicole LeBrasseur

An interest in neurodegenerative diseases drove Junying Yuan to study cell death as a graduate student at Harvard University. Now a full professor at the hallowed institute, Yuan is moved by the same interest in a new direction--the removal of misfolded proteins.     

NAC/MEA conjugate: a new potent antioxidant which increases the GSH level in various cell lines

I-152 is a prodrug of NAC and MEA with potent pro-GSH effects in human macrophages, astrocytes and lymphocytes. This molecule could be of interest in HIV infection in respect to its antioxidant and anti-HIV activities, but also in other diseases to counteract oxidative stress, that is, inflammation, cardiovascular diseases, and neurodegenerative diseases.     

鸡MHC与传染性疾病遗传抗性的相关性研究进展

鸡是我国主要的家禽品种,抗病分子育种在鸡的疾病尤其是传染病控制中有着重要地位,抗性基因选择是其技术关键。鸡主要组织相容性复合体(MHC)基因具有高度多态性,与多种传染性疾病抗性紧密相关,受到家禽育种专家的高度关注。文章介绍国外有关鸡MHC与传染性疾病抗性的相关性及抗性基因研究进展,并展望其在鸡抗病育种中的应用前景。     

Urinary proteomics: a tool to discover biomarkers of kidney diseases

There is intense interest in applying proteomics to urine analysis in order to promote a better understanding of kidney disease processes, develop new biomarkers for diagnosis and detect early factors that contribute to end-stage renal diseases. This interest creates numerous opportunities as well as challenges. To fulfill this task, proteomics requires, in its different stages of realization, various technological platforms with high sensitivity, high throughput and large automation ability. In this review, we will give an overview of promising proteomic methods that can be used for analyzing urinary proteome and detecting biomarkers for different kidney diseases. Furthermore, we will focus on the current status and future directions in investigating kidney diseases using urinary proteomics.     

Urinary proteomics: a tool to discover biomarkers of kidney diseases

There is intense interest in applying proteomics to urine analysis in order to promote a better understanding of kidney disease processes, develop new biomarkers for diagnosis and detect early factors that contribute to end–stage renal diseases. This interest creates numerous opportunities as well as challenges. To fulfill this task, proteomics requires, in its different stages of realization, various technological platforms with high sensitivity, high throughput and large automation ability. In this review, we will give an overview of promising proteomic methods that can be used for analyzing urinary proteome and detecting biomarkers for different kidney diseases. Furthermore, we will focus on the current status and future directions in investigating kidney diseases using urinary proteomics.     

Early mechanisms of amyloid fibril nucleation in model and disease-related proteins

Protein amyloid aggregation is a hallmark in neuropathologies and other diseases of tremendous impact such as Alzheimer’s or Parkinson’s diseases. During the last decade, it has become increasingly evident that neuronal death is mainly induced by proteinaceous oligomers rather than the mature amyloid fibrils. Therefore, the earliest molecular events occurring during the amyloid aggregation cascade represent a growing interest of study.Important breakthroughs have been achieved using experimental data from different proteins, used as models, as well as systems related to diseases. Here, we summarize the structural properties of amyloid oligomeric and fibrillar aggregates and review the recent advances on how biophysical techniques can be combined with quantitative kinetic analysis and theoretical models to study the detailed mechanism of oligomer formation and nucleation of fibrils.These insights into the mechanism of early oligomerization and amyloid nucleation are of relevant interest in drug discovery and in the design of preventive strategies against neurodegenerative diseases.     

Using genomic inbreeding coefficient estimates for homozygosity mapping of rare recessive traits: application to Taybi-Linder syndrome

The use of inbred patients whose exact genealogy may not be available is of primary interest in mapping genes involved in rare recessive diseases. We show here that this can be achieved by estimating inbreeding coefficients from the patients' genomic information and using these estimates to perform homozygosity mapping. We show the interest of the approach by mapping a gene for Taybi-Linder syndrome to chromosome 2q, with the use of a key patient with no genealogical information.     

Therapeutic potency of crocin in the treatment of inflammatory diseases: Current status and perspective

Crocin is the major component of saffron, which is used in phytomedicine for the treatment of several diseases including diabetes, fatty liver, depression, menstruation disorders, and, of special interest in this review, inflammatory diseases. Promising selective anti-inflammatory properties of this pharmacological active component have been observed in several studies. Saffron has been shown to exert anti-inflammatory properties against several inflammatory diseases and can be used as a novel therapeutic agent for the treatment of inflammatory diseases either alone or in combination with other standard anti-inflammatory agents. This review summarizes the protective role of saffron and its pharmacologically active constituents in the pathogenesis of inflammatory diseases including digestive diseases, dermatitis, asthma, atherosclerosis, and neurodegenerative diseases for a better understanding and hence a better management of these diseases.     

Varicella-like herpesvirus infections of nonhuman primates

At least three distinct herpesviruses cause varicella like exanthematous diseases among nonhuman primates. Spontaneous epizootics have resulted in high morbidity and mortality rates among Cercopithecus aethiops, Erythrocebus patas and Macaca species in research colonies. Mild infections have been observed in infant chimpanzees and a gorilla. This group of diseases is of interest not only because they are a threat to primate colonies, but also because their pathologic similarity to progressive human varicella makes them a potentially valuable animal model of this disease. The nonhuman primate varicella-like exanthematous diseases are reviewed and compared to varicella in man.     

Immunity to fungal infections

The topic of immunity to fungal infections is of interest to a wide range of disciplines, from microbiology to immunology. It is of particular interest in terms of therapy of HIV-infected individuals, and patients with cancer or individuals who have received transplants. Understanding the nature and function of the immune response to fungi is an exciting challenge that might set the stage for new approaches to the treatment of fungal diseases, from immunotherapy to vaccines. The past decade has witnessed the development of a wide range of new approaches to elucidate events that occur at the host-fungus interface.     

Antiprotozoal alkaloid principles of the plant family Amaryllidaceae

Protozoan-borne diseases are prominent amongst diseases caused by parasites. Given their alarming morbidity and mortality statistics, there is ever growing interest in new therapies against these diseases. Whilst synthetic drugs such as benznidazole and melarsoprol have had a profound influence on the clinical setup, there has been significant interest in the phytochemical platform to also deliver such drug candidates. The plant family Amaryllidaceae is recognizable for its isoquinoline alkaloids, which exhibit attractive molecular architectures and interesting biological properties. This survey focuses on the antiprotozoal activities of 73 of such substances described in 18 different species of the Amaryllidaceae. Of these, 2-O-acetyllycorine was identified as the most potent (IC₅₀ 0.15 μg/mL against Trypansoma brucei brucei). Also considered are structure-activity relationships which have served to modulate activities, as well as the plausible mechanisms that underpin these effects and afford insight to the Amaryllidaceae alkaloid antiprotozoal pharmacophore.     

Wound healing from a cellular stress response perspective

This meeting review highlights areas of mutual interest to investigators in the cellular stress response field and to those carrying out wound-healing research. Inflammation, perhaps the major unifying theme of this meeting, is an essential component of the adult wound response and understanding the control of inflammation is a common interest shared with researchers of the cellular stress response. The particular interest of the authors of this review is in chronic non-healing wounds that frequently occur in patients with major illnesses such as diabetes and diseases of the blood vessels. This orientation has undoubtedly influenced the selection of topics. It is fair to say that the authors were often surprised and certainly impressed with the overlapping interests and possibilities for collaboration among investigators of these two research areas.     

Analysis of symmetries in models of multi-strain infections

In mathematical studies of the dynamics of multi-strain diseases caused by antigenically diverse pathogens, there is a substantial interest in analytical insights. Using the example of a generic model of multi-strain diseases with cross-immunity between strains, we show that a significant understanding of the stability of steady states and possible dynamical behaviours can be achieved when the symmetry of interactions between strains is taken into account. Techniques of equivariant bifurcation theory allow one to identify the type of possible symmetry-breaking Hopf bifurcation, as well as to classify different periodic solutions in terms of their spatial and temporal symmetries. The approach is also illustrated on other models of multi-strain diseases, where the same methodology provides a systematic understanding of bifurcation scenarios and periodic behaviours. The results of the analysis are quite generic, and have wider implications for understanding the dynamics of a large class of models of multi-strain diseases.     

DNA vaccines: future strategies and relevance to intracellular pathogens

Increasing awareness of microbial threat has rekindled interest in the great potential of vaccines for controlling infectious diseases. The fact that diseases caused by intracellular pathogens cannot be overcome by chemotherapy alone has increased our interest in the generation of highly efficacious novel vaccines. Vaccines have proven their efficacy, as the immunoprotection they induce appears to be mediated by long-lived humoral immune responses. However, there are no consistently effective vaccines available against diseases such as tuberculosis and HIV, and other infections caused by intracellular pathogens, which are predominantly controlled by T lymphocytes. This review describes the T-cell populations and the type of immunity that should be activated by successful DNA vaccines against intracellular pathogens. It further discusses the parameters that need to be fulfilled by protective T-cell Ag. We then discuss future approaches for DNA vaccination against diseases in which cell-mediated immune responses are essential for providing protection.     

Emerging infectious disease: what are the relative roles of ecology and evolution?

The increasing threat of infectious diseases in humans has renewed interest in factors leading to the emergence of new diseases and the re-emergence of familiar diseases. Examples of seemingly novel diseases currently spreading in human populations include HIV, dengue hemorrhagic fever and Lyme disease; drug-resistant forms of well-known diseases such as tuberculosis are also increasing. The problem of disease emergence also extends to other animal and plant populations. In most current epidemics, ecological factors (e.g. migration, climate, agricultural practices) play a more significant role in disease emergence than evolutionary changes in pathogens or hosts. Evolutionary biologists and ecologists have much to offer to the development of strategies for the control of emerging diseases.     

Research on motor neuron diseases konzo and neurolathyrism: trends from 1990 to 2010

Konzo (caused by consumption of improperly processed cassava, Manihot esculenta) and neurolathyrism (caused by prolonged overconsumption of grass pea, Lathyrus sativus) are two distinct non-infectious upper motor neurone diseases with identical clinical symptoms of spastic paraparesis of the legs. They affect many thousands of people among the poor in the remote rural areas in the central and southern parts of Africa afflicting them with konzo in Ethiopia and in the Indian sub-continent with neurolathyrism. Both diseases are toxico-nutritional problems due to monotonous consumption of starchy cassava roots or protein-rich grass pea seeds as a staple, especially during drought and famine periods. Both foods contain toxic metabolites (cyanogenic glycosides in cassava and the neuro-excitatory amino acid β-ODAP in grass pea) that are blamed for theses diseases. The etiology is also linked to the deficiency in the essential sulfur amino acids that protect against oxidative stress. The two diseases are not considered reportable by the World Health Organization (WHO) and only estimated numbers can be found. This paper analyzes research performance and determines scientific interest in konzo and neurolathyrism. A literature search of over 21 years (from 1990 to 2010) shows that in terms of scientific publications there is little interest in these neglected motorneurone diseases konzo and neurolathyrism that paralyze the legs. Comparison is made with HTLV-1/TSP, an infectious disease occurring mainly in Latin America of which the clinical manifestation is similar to konzo and neurolathyrism and requires a differential diagnosis. Our findings emphasize the multidisciplinary nature of studies on these neglected diseases, which however have not really captured the attention of decision makers and project planners, especially when compared with the infectious HTLV-1/TSP. Konzo and neurolathyrism can be prevented by a balanced diet.     

Molecular mechanistic associations of human diseases

Background  

The study of relationships between human diseases provides new possibilities for biomedical research. Recent achievements on human genetic diseases have stimulated interest to derive methods to identify disease associations in order to gain further insight into the network of human diseases and to predict disease genes.     

Protein misfolding disorders and macroautophagy

A large group of diseases, termed protein misfolding disorders, share the common feature of the accumulation of misfolded proteins. The possibility of a common mechanism underlying either the pathogenesis or therapy for these diseases is appealing. Thus, there is great interest in the role of protein degradation via autophagy in such conditions where the protein is found in the cytoplasm. Here we review the growing evidence supporting a role for autophagic dysregulation as a contributing factor to protein accumulation and cellular toxicity in certain protein misfolding disorders and discuss the available evidence that upregulation of autophagy may be a valuable therapeutic strategy.     

Impact factor in AIDS and other infectious diseases.

The impact factor (IF) is the most accurate system currently available for objectively evaluating the scientific productivity of individual researchers and institutions. It represents the quality level of a periodical and, at the same time, is a convenient reference parameter for the researcher to use in choosing an appropriate journal before submitting his own work for consideration. From this standpoint, we conducted an analysis of periodicals with the highest IF, including those strictly related to infectious diseases and HIV/AIDS, specialty journals, and general medicine reviews. This was done in order to determine just how much of these journals' total 1998 production consisted of articles concerning HIV infection and AIDS. This examination, conducted through a search of the MEDLINE database, predictably revealed greater interest in the HIV/AIDS topic among journals with the highest IF that focus on infectious diseases, though the same interest revealed when examining specialty journals and general medicine periodicals was not negligible.     

Statins and Neuroprotection: Basic Pharmacology Needed

Statins are attracting great interest albeit with some controversy in treating certain neurodegenerative diseases such as Alzheimer disease, Parkinson disease, multiple sclerosis, ischemic stroke, and traumatic brain injury. Support for the use of statins has come from human studies and animal and cell models. Despite the intense level of interest, there is a deficiency in information on the basic pharmacokinetics and pharmacodynamics of statins in the brain. The purpose of this focused review is to examine what is known and the gaps in our knowledge on detectability of statin lactones and acids in the brain, membrane partitioning and active transport of statins across the blood–brain barrier, and statin effects on brain isoprenoid levels. Statins may be efficacious in treating certain neurodegenerative diseases. Having basic information on statin pharmacokinetics and pharmacodynamics in the brain would provide insight into specific drug targets and also provide the rationale for optimizing statins in terms of enhancing brain influx and inhibiting efflux.