Call for Papers Special Issue on “Biomarkers for Autoimmune Diseases”

正The journal Genomics ProteomicsBioinformatics(GPB)is now inviting submissions for a specialissue(to be published in April of 2015)on the topic of"Biomarkers for Autoimmune Diseases".Autoimmune diseases(AIDs)are the third most common category of disease after cancer and heart disease and affect more than 5%of the general population.AIDs result from a complex interaction of genetic and epigenetic     

Call for Papers Special Issue on “Biomarkers for Autoimmune Diseases”

正The journal Genomics ProteomicsBioinformatics(GPB)is now inviting submissions for a special issue(to be published in April of 2015)on the topic of"Biomarkers for Autoimmune Diseases".Autoimmune diseases(AIDs)are the third most common category of disease after cancer and heart disease and affect more than 5%of the general population.AIDs result from a complex interaction of genetic and epigenetic     

Call for Papers

正Special Issue on‘‘Biomarkers for Autoimmune Diseases’’The journal Genomics ProteomicsBioinformatics(GPB)is now inviting submissions for a special issue(to be published in April of 2015)on the topic of‘‘Biomarkers for Autoimmune Diseases’’.Autoimmune diseases(AIDs)are the third most common category of disease after cancer and heart disease and affect more than 5%of the general population.AIDs result     

Special Issue on “Biomarkers for Autoimmune Diseases”

<正>The journal Genomics ProteomicsBioinformatics(GPB)is now inviting submissions for a special issue(to be published in the summer of 2015)on the topic of‘‘Biomarkers for Autoimmune Diseases’’.Autoimmune diseases(AIDs)are the third most common category of disease after cancer and heart disease and affect more than 5%of the general population.AIDs result     

Special Issue on ＂Biomarkers for Diseases＂

The journal Genomics Proteomics ＆ Bioinformatics （GPB） is now inviting submissions for a special issue （to be published in June of 2015） on the topic of ＂Biomarkers for Diseases＂.
As an emerging index, disease biomarkers have demonstrated the potential application in diagnosis and prognosis. The detection of the disease indicators at molecular level, DNA, RNA, protein or metabolites, could gain highly sensitive and specific signals that truly reflect the pathological changes and fully facilitate diagnostic analysis at early phase with invasive mode. Revolution of high-throughput techniques, such as genome-sequencing and mass spectrometers, greatly promotes the discovery and application of the disease biomarkers. The existing disease biomarkers have covered nearly all the macromolecular categories as well as their variants and modifications, including predisposing genetic variations （such as SNPs）, mutations, epigenetic modifications, miRNAs, splice isoforms, abnormal proteins and autoantibodies. Although some biomarkers have been adopted in clinical practice, there are still great needs for studies on identifying new ones, understanding the existing ones and applying the well-studied ones in practice.     

One-carbon metabolism and breast cancer: an epidemiological perspective

One-carbon metabolism is a network of biological reactions that plays critical role in DNA methylation and DNA synthesis, and in turn, facilitates the cross-talk between genetic and epigenetic processes. Genetic polymorphisms and supplies of cofactors （e.g. folate, vitamins B） involved in this pathway have been shown to influence cancer risk and even survival. In this review, we summarized the epidemiological evidence for one-carbon metabolism, from both genetics and lifestyle aspects, in relation to breast cancer risk. We also discussed this pathway in relation to breast cancer survival and the modulation of one-carbon polymorphism in chemotherapy. Emerging evidence on modulation of DNA methylation by one-carbon metabolism suggests that disruption of epigenome might have been the underlying mechanism. More results are expected and will be translated to guidance to the general population for disease prevention as well as to clinicians for treatment and management of the disease.     

Pluripotent Stem Cells Models for Huntington＇s Disease： Prospects and Challenges

Pluripotent cellular models have shown great promise in the study of a number of neurological disorders.Several advantages of using a stem cell model include the potential for cells to derive disease relevant neuronal cell types,providing a system for researchers to monitor disease progression during neurogenesis,along with serving as a platform for drug discovery.A number of stem cell derived models have been employed to establish in vitro research models of Huntington’s disease that can be used to investigate cellular pathology and screen for drug and cell-based therapies.Although some progress has been made,there are a number of challenges and limitations that must be overcome before the true potential of this research strategy is achieved.In this article we review current stem cell models that have been reported,as well as discuss the issues that impair these studies.We also highlight the prospective application of Huntington’s disease stem cell models in the development of novel therapeutic strategies and advancement of personalized medicine.     

Biomimetic Leukocyte Adhesion： A Review of Microfluidic and Computational Approaches and Applications

Leukocyte rolling and adhesion are complex physiological processes that have received a great deal of attention over the past decade. Significant increases in the knowledge base related to how leukocytes adhere in shear flows have occurred as a result of the development of novel experimental and computational techniques. Micro- and nano-fabrication techniques have enabled the development of novel flow devices for studying leukocyte adhesion in simple and complex geometries. Improvements in computer technology have enabled simulations of complex flow processes to be developed. As a result of these advances in knowledge related to leukocyte adhesion, numerous novel devices have been developed that mimic the leukocyte rolling and adhesion process. Examples of these devices include cell separation and enrichment devices and targeted ultrasound contrast agents. Future advances related to leukocyte rolling and adhesion processes hold great promise for advancing our knowledge of disease processes as well as development of novel therapeutic devices.     

ABC transporters, neural stem cells and neurogenesis--a different perspective

Stem cells intrigue. They have the ability to divide exponentially, recreate the stem cell compartment, as well as create differentiated cells to generate tissues. Therefore, they should be natural candidates to provide a renewable source of cells for transplantation applied in regenerative medicine. Stem cells have the capacity to generate specific tissues or even whole organs like the blood, heart, or bones. A subgroup of stem cells, the neural stem cells （NSCs）, is characterized as a self-renewing population that generates neurons and glia of the developing brain. They can be isolated, genetically manipulated and differentiated in vitro and reintroduced into a developing, adult or a pathologically altered central nervous system. NSCs have been considered for use in cell replacement therapies in various neurodegenerative diseases such as Parkinson＇s disease and Alzheimer＇s disease. Characterization of genes with tightly controlled expression patterns during differentiation represents an approach to understanding the regulation of stem cell commitment. The regulation of stem cell biology by the ATP-binding cassette （ABC） transporters has emerged as an important new field of investigation. As a major focus of stem cell research is in the manipulation of cells to enable differentiation into a targeted cell population; in this review, we discuss recent literatures on ABC transporters and stem cells, and propose an integrated view on the role of the ABC transporters, especially ABCA2, ABCA3, ABCB 1 and ABCG2, in NSCs＇ proliferation, differentiation and regulation, along with comparisons to that in hematopoietic and other stem cells.     

The Involvement of Lipids in Alzheimer's Disease

It has been estimated that Alzheimer＇s disease （AD）, the most common form of dementia, will affect approximately 81 million individuals by 2040. To date, the actual cause and cascade of events in the progression of this disease have not been fully determined. Furthermore, there is currently no definitive blood test or simple diagnostic method for AD. Considerable efforts have been put into proteomic approaches to develop a diagnostic blood test, but to date these efforts have not been successful. More recently, there has been a stronger focus on lipidomic studies in the hope of increasing our understanding of the underlying mechanisms leading to AD and developing an AD blood test. It is well known that the strongest genetic risk factor for AD is the e4 variant of apolipoprotein E （APOE）. Evidence suggests that the ApoE protein, a major lipid transporter, plays a key role in the pathogenesis of AD, and its role in both normal and aberrant lipid metabolism warrants further extensive investigation. Here, we review ApoE-lipid interactions, as well as the roles that lipids may play in the pathogenesis of AD.     

Inflammatory bowel disease requires the interplay between innate and adaptive immune signals

Inflammatory bowl disease （IBD） is a type 1 T helper cell （Th1）-mediated autoimmune disease. Various studies have revealed that environmental pathogens also play a significant role in the initiation and progression of this disease. Interestingly, the pathogenesis of IBD has been shown to be related to nitric oxide （NO） released from innate immune cells. Although NO is known to be highly toxic to the gut epithelia, there is very little information about the regulation of NO production, One major question in the etiology of IBD is how Thl cells and pathogens interact in the induction of IBD. In present study, we focused on the regulation of NO. We show that macrophages require both interferon-γ, （IFN-γ）-mediated and TLR4-mediated signals for the production of NO, which causes inflammation in the intestine and subsequently IBD. Thus, IBD is the result of concerted actions of innate immune signals, such as the binding of LPS to TLR-4, and adaptive immune signals, such as IFN-γ produced by Thl cells.     

A multiplexer liquidchip technology for detecting single nucleotide polymorphisms from metabolism of anti-thrombotic drugs in dried blood spots on filter paper

A single nucleotide polymorphism （SNP） is the most fre quent type of variation in the genome. There are around 10 million SNPs that have been identified in the human genome [1]. Because SNPs are highly conserved throughout evolu tion and within a population, the map of SNPs serves as an excellent genotypic marker for research. The elucidation of SNP information will contribute to an individual＇s suscepti bility to disease and responsiveness to drug toxicity and medical intervention [2,3]. Nowadays, a variety of techni ques have been used to perform SNP genotyping, but these techniques required whole blood as the sample. Dried blood spot （DBS） specimens require less material and are substan tially more stable （several months at room temperature） than whole blood [4]. Thus, the simplicity of sample preparation, long time storage and convenient transport make DBS to be a costeffective and suitable alternative tool for collecting blood sample.     

Wnt signaling in the nervous system and in Alzheimer＇s disease

Wnts comprise a large family of proteins that have shown to be part of a signaling cascade that regulates several aspects of develop- ment including organogenesis, mid brain development as welt as stem cell proliferation. Wnt signaling pathway plays different roles in the development of neuronal circuits and also in the adult brain, where it regulates synaptic transmission and plasticity. It has been also implicated in various diseases including cancer and neurodegenerative diseases, reflecting its relevance in fundamental biological pro- cesses. This review summarizes the progress about Wnts function in mature nervous system with a focus on Alzheimer＇s disease （AD）. We discuss the prospects of modulating canonical and non-canonical Wnt signaling as a strategy for neuroprotection. This will include the potential of Wnts to： （i） act as potent regulators of hippocampai synapses and impact in learning and memory; （ii） regulate adult neurogenesis; and finally （iii） control AD pathogenesis.     

Screening landraces for additional sources of field resistance to cassava mosaic disease and green mite for integration into the cassava improvement program

Twelve cassava landraces were evaluated for sources of resistance genes to diseases and pests of major economic importance in Africa. The objective was to assess their levels of field resistance to mosaic disease （ACMD）, bacterial blight （CBB）, anthracnose （CAD）, and green mite （CGM）, compared to TMS30572, an elite cultivar widely adopted in Africa. Considerable genotypic variation was observed among cultivars for resistance to ACMD and CGM but not for CBB and CAD. The lowest mean incidence of 12% and severity of 1.8 on a scale of 1-5 for ACMD was recorded for Atu, a landrace with farmer acceptable qualities. In comparison, the improved cultivar, TMS 30572, had a mean disease incidence of 72% and a severity score of 2.8. Another landrace, MS-20 had the lowest CGM damage score （2.1） while TMS 30572 emerged as one of the susceptible cultivars with a damage score of 3. Additional sources of resistance to ACMD and CGM that may possibly be better than the popular improved cultivar, TMS 30572, were identified in this study. These could serve as novel sources of additional genes to complement existing resources for elite cassava breeding in Africa.     

A genetic adaptive pattern＊low hemoglobin concentration in the himalayan highlanders

Mean hemoglobin （Hb） concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders （Tibetans, Sherpas, and Ladakhis） was compared with lowlanders （Chinese Han, Indian Tamils） lived in the Himalayas, and European climbers during Everest expeditions as well as Andean natives. The results found that Hb concentration in Himalayan highlanders was systemically lower than those reported for Andean natives and lowland immigrants. These comparative data demonstrated that a healthy native population may successfully reside at high altitude without a significant elevation in Hb, and the lower Hb levels of Himalayan highlanders than those of migrated lowlanders and Andean natives are an example of favourable adaptation over the generations. In addition, excessive polycythemia has frequently been used as a marker of chronic mountain sickness （CMS）. Altitude populations who have a higher Hb concentration also have a higher incidence of CMS. The low Hb in Himalayans suggested as showing adaptation over many generations in Tibetan stock. Recent work in Tibet, suggested that Tibetans there may have adapted to high altitude as a result of evolutionary pressure selecting for genes which give an advantage at altitude. All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans. These data supported the hypothesis that Himalayan highlanders have evolved a genetically different erythropoietic response to chronic hypoxia by virtue of their much longer exposure to high altitude.     

Tetracycline-inducible Expression Systems： New Strategies and Practices in the Transgenic Mouse Modeling

To accurately analyze the function of transgene(s)of interest in transgenic mice,and togenerate credible transgenic animal models for multifarious human diseases to precisely mimic human dis-ease states,it is critical to tightly regulate gene expression in the animals in a conditional manner.The abilityto turn gene expression on or off in the restricted cells or tissues at specific time permits unprecedentedflexibility in dissecting gene functions in health and disease.Pioneering studies in conditional transgene ex-pression have brought about the development of a wide variety of controlled gene expression systems,whichmeet this criterion.Among them,the tetracycline-controlled expression systems(e.g.Tet-off system andTet-on system)have been used extensively in vitro and in vivo.In recent years,some strategies derived fromtetracycline-inducible system alone,as well as the combined use of Tet-based systems and Cre/lox P switch-ing gene expression system,have been newly developed to allow more flexibility for exploring gene functionsin health and disease,and produce credible transgenic animal models for various human diseases.In thisreview these newly developed strategies are discussed.     

Computational approaches to understanding protein aggregation in neurodegeneration

The generation of toxic non-native protein conformers has emerged as a unifying thread among disorders such as Alzheimer＇s disease, Parkinson＇s disease, and amyotrophic lateral sclerosis. Atomic-level detail regarding dynamical changes that facilitate protein aggre- gation, as well as the structural features of large-scale ordered aggregates and soluble non-native oligomers, would contribute signifi- cantly to current understanding of these complex phenomena and offer potential strategies for inhibiting formation of cytotoxic species. However, experimental limitations often preclude the acquisition of high-resolution structural and mechanistic information for aggregating systems. Computational methods, particularly those combine both aU-atom and coarse-grained simulations to cover a wide range of time and length scales, have thus emerged as crucial tools for investigating protein aggregation. Here we review the current state of computational methodology for the study of protein self-assembly, with a focus on the application of these methods toward understanding of protein aggregates in human neurodegenerative disorders.     

Critical thinking on amyloid-beta-targeted therapy: challenges and perspectives

Amyloid-beta(Aβ) plays a pivotal role in the pathogenesis of Alzheimer's disease(AD) and has been regarded as the main therapeutic target for AD. However, most of the Aβ-targeted clinical trials have not succeeded. Therefore, the Aβ-targeted therapeutic strategy on treating this complex disease needs to be re-evaluated. In this review, we analyzed the challenges and critical points of the current anti-Aβ therapeutic strategies. In addition to Aβ, multiple pathological events such as tau hyperphosphorylation, oxidative stress, and neuroinflammation, which are involved in AD pathogenesis and synergistically drive disease progression, could be important targets for AD treatment. Tertiary prevention strategies are needed for the successful management of AD due to its complex and dynamic pathogenesis. Systemic perspective addressing the disease pathogenesis within and outside the brain, as well as the multidomain intervention targeting risk factors and comorbidities, are important approaches for the therapeutic solutions of AD.     

Autoimmune Diseases in the Bioinformatics Paradigm

<正>Autoimmune diseases(AIDs)consist of a group of physiological disorders with highly diversified pathogenesis and clinical manifestations[1],which affect more than 5%of the population worldwide[2].So far,the etiology of the AIDs is still poorly understood,whereas it is generally believed that autoimmune disorder results from a complex interaction of genetic and epigenetic variations,as well as triggering environmental factors[3].Because of the varied phenotypes in different individuals of one AID and sometimes shared     

New findings showing how DNA methylation influences diseases

In 1975, Holliday and Pugh as well as Riggs independently hypothesized that DNA methylation in eukaryotes could act as a hereditary regulation mechanism that influences gene expression and cell differentiation. Interest in the study of epigenetic processes has been inspired by their reversibility as well as their potentially preventable or treatable consequences. Recently, we have begun to understand that the features of DNA methylation are not the same for all cells.Major differences have been found between differentiated cells and stem cells.Methylation influences various pathologies, and it is very important to improve the understanding of the pathogenic mechanisms. Epigenetic modifications may take place throughout life and have been related to cancer, brain aging, memory disturbances, changes in synaptic plasticity, and neurodegenerative diseases,such as Parkinson's disease and Huntington's disease. DNA methylation also has a very important role in tumor biology. Many oncogenes are activated by mutations in carcinogenesis. However, many genes with tumor-suppressor functions are "silenced" by the methylation of CpG sites in some of their regions.Moreover, the role of epigenetic alterations has been demonstrated in neurological diseases. In neuronal precursors, many genes associated with development and differentiation are silenced by CpG methylation. In addition,recent studies show that DNA methylation can also influence diseases that do not appear to be related to the environment, such as IgA nephropathy, thus affecting,the expression of some genes involved in the T-cell receptor signaling. In conclusion, DNA methylation provides a whole series of fundamental information for the cell to regulate gene expression, including how and when the genes are read, and it does not depend on the DNA sequence.