[PERSPECTIVES] Imaging in Tuberculosis
Despite many advances in both diagnosis and treatment, tuberculosis still remains one of commonest causes of morbidity and mortality from any infectious cause in the world. Although the overall incidence and mortality rate for tuberculosis has decreased over the years, timely and accurate diagnosis of tuberculosis is essential for the health of the patient as well as the public. For the diagnosis of tuberculosis, a high degree of clinical suspicion is required, and this becomes much more important in high-risk populations. Tuberculosis may masquerade as any disease; therefore, tissue and microbiological assessment is somet...
Source: Cold Spring Harbor perspectives in medicine - June 1, 2015 Category: Research Authors: Bomanji, J. B., Gupta, N., Gulati, P., Das, C. J. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Gene Therapy for the Retinal Degeneration of Usher Syndrome Caused by Mutations in MYO7A
Usher syndrome is a deaf-blindness disorder. One of the subtypes, Usher 1B, is caused by loss of function of the gene encoding the unconventional myosin, MYO7A. A variety of different viral-based delivery approaches have been tested for retinal gene therapy to prevent the blindness of Usher 1B, and a clinical trial based on one of these approaches has begun. This review evaluates the different approaches. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - June 1, 2015 Category: Research Authors: Lopes, V. S., Williams, D. S. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Genetic Modifiers and Oligogenic Inheritance
Despite remarkable progress in the identification of mutations that drive genetic disorders, progress in understanding the effect of genetic background on the penetrance and expressivity of causal alleles has been modest, in part because of the methodological challenges in identifying genetic modifiers. Nonetheless, the progressive discovery of modifier alleles has improved both our interpretative ability and our analytical tools to dissect such phenomena. In this review, we analyze the genetic properties and behaviors of modifiers as derived from studies in patient populations and model organisms and we highlight conceptu...
Source: Cold Spring Harbor perspectives in medicine - June 1, 2015 Category: Research Authors: Kousi, M., Katsanis, N. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] The Human Placental Methylome
This review provides an overview of the unique features of DNA methylation in the human placenta. We discuss the importance of understanding placental development, structure, and function in the interpretation of DNA methylation data. Examples are given of how DNA methylation is important in regulating placental-specific gene expression, including monoallelic expression and X-chromosome inactivation in the placenta. We also discuss studies of global DNA methylation changes in the context of placental pathology and environmental exposures. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: Robinson, W. P., Price, E. M. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Malformations of Cortical Development and Epilepsy
Malformations of cortical development (MCDs) are an important cause of epilepsy and an extremely interesting group of disorders from the perspective of brain development and its perturbations. Many new MCDs have been described in recent years as a result of improvements in imaging, genetic testing, and understanding of the effects of mutations on the ability of their protein products to correctly function within the molecular pathways by which the brain functions. In this review, most of the major MCDs are reviewed from a clinical, embryological, and genetic perspective. The most recent literature regarding clinical diagno...
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: Barkovich, A. J., Dobyns, W. B., Guerrini, R. Tags: Epilepsy: The Biology of a Spectrum Disorder PERSPECTIVES Source Type: research

[PERSPECTIVES] Hepatitis B Virus Genotypes and Variants
In conclusion, HBV genotypes and variants may serve as viral genetic markers to predict disease progression as well as help practicing physicians optimize individualized antiviral therapy in clinical practice. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: Lin, C.-L., Kao, J.-H. Tags: Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] Hepatitis B Virus Epidemiology
The epidemiology of hepatitis B virus (HBV) infection is geographically diverse, with population prevalence, age and mode of acquisition, and likelihood of progression to chronic infection mutually interdependent. The burden of chronic HBV infection is increasingly being recognized, with cirrhosis and liver cancer attributable to HBV continuing to increase. The outcomes of chronic HBV infection are affected by a range of factors, including viral genotype, the presence of coinfections with other blood-borne viruses, and the impact of other causes of liver disease. The increased recognition of HBV infection as a leading caus...
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: MacLachlan, J. H., Cowie, B. C. Tags: Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] The Impact of Myriad and Mayo: Will Advancements in the Biological Sciences Be Spurred or Disincentivized? (Or Was Biotech Patenting Not Complicated Enough?)
For years, purified and isolated naturally occurring biological substances of great medical importance—including genes—have been the subject of U.S. patents. Similarly, methods in which the detection of a biological substance (e.g., in a blood sample) dictates subsequent actions, as in disease diagnostics and treatment, have long enjoyed patent protection. However, two recent Supreme Court cases, Association for Molecular Pathology v. Myriad Genetics, Inc. (133 S. Ct. 2107) (2013) and Mayo Collaborative Services v. Prometheus Laboratories, Inc. (132 S. Ct. 1289) (2012), have shaken up the status quo of biotech ...
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: Gordon, J. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Patentability of Genes: A European Union Perspective
Unlike the position in the United States following the recent Supreme Court decision in Myriad, in the European Union naturally occurring genetic sequences, whether of human or other origin, remain patent-eligible. Here the basis for such eligibility in legislation and in case law is explained. The utility of a sequence must be disclosed as a condition of eligibility, and requirements outlined in European Patent Office (EPO) and U.K. case law are discussed. A claimed sequence must also satisfy requirements of novelty and inventive step, the latter being considered primarily using the tests of "obvious to try" and...
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: Cole, P. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] The Human Mycobiome
Fungi are fundamental to the human microbiome, the collection of microbes distributed across and within the body, and the microbiome has been shown, in total, to modify fundamental human physiology, including energy acquisition, vitamin-cofactor availability, xenobiotic metabolism, immune development and function, and even neurological development and behavior. Here, a comprehensive review of current knowledge about the mycobiome, the collective of fungi within the microbiome, highlights methods for its study, diversity between body sites, and dynamics during human development, health, and disease. Early-stage studies show...
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: Seed, P. C. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Antifungal Pharmacokinetics and Pharmacodynamics
Successful treatment of infectious diseases requires choice of the most suitable antimicrobial agent, comprising consideration of drug pharmacokinetics (PK), including penetration into infection site, pathogen susceptibility, optimal route of drug administration, drug dose, frequency of administration, duration of therapy, and drug toxicity. Antimicrobial pharmacokinetic/pharmacodynamic (PK/PD) studies consider these variables and have been useful in drug development, optimizing dosing regimens, determining susceptibility breakpoints, and limiting toxicity of antifungal therapy. Here the concepts of antifungal PK/PD studie...
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: Lepak, A. J., Andes, D. R. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Animal Models of Tuberculosis: Guinea Pigs
The progression of the disease that follows infection of guinea pigs with Mycobacterium tuberculosis displays many features of human tuberculosis (TB), and the guinea pig model of TB has been used for more than 100 years as a research tool to understand and describe disease mechanisms. Changes in the bacterial burden and pathology following infection can be readily monitored and used to evaluate the impact of TB interventions. Demonstration of the protective efficacy of vaccines in the low-dose aerosol guinea pig model is an important component of the preclinical data package for novel vaccines in development, and there is...
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: Clark, S., Hall, Y., Williams, A. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Tuberculosis Treatment and Drug Regimens
Tuberculosis is an airborne infectious disease treated with combination therapeutic regimens. Adherence to long-term antituberculosis therapy is crucial for maintaining adequate blood drug level. The emergence and spread of drug-resistant Mycobacterium tuberculosis strains are mainly favored by the inadequate medical management of the patients. The therapeutic approach for drug-resistant tuberculosis is cumbersome, because of the poor, expensive, less-effective, and toxic alternatives to the first-line drugs. New antituberculosis drugs (bedaquiline and delamanid) have been recently approved by the health authorities, but t...
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: Sotgiu, G., Centis, R., D'ambrosio, L., Migliori, G. B. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Gene Therapy of ABCA4-Associated Diseases
The ATP-binding cassette (ABC) transporter gene, ABCA4 (ABCR), was characterized in 1997 as the causal gene for autosomal recessive Stargardt disease (STGD1). Shortly thereafter several other phenotypes were associated with mutations in ABCA4, which now have collectively emerged as the most frequent cause of retinal degeneration phenotypes of Mendelian inheritance. ABCA4 functions as an important transporter (or "flippase") of vitamin A derivatives in the visual cycle. Several ways to alleviate the effects of the defective ABCA4 protein, which cause accumulation of 11-cis and all-trans-retinal in photoreceptors a...
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: Auricchio, A., Trapani, I., Allikmets, R. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Stem Cells as Tools for Studying the Genetics of Inherited Retinal Degenerations
The ability to provide early clinical intervention for inherited disorders is heavily dependent on knowledge of a patient’s disease-causing mutations and the resultant pathophysiologic mechanism(s). Without knowing a patient’s disease-causing gene, and how gene mutations alter the health and functionality of affected cells, it would be difficult to develop and deliver patient-specific molecular or small molecule therapies. Many believe that the field of stem cell biology holds the keys to the future development of disease-, patient-, and cell-specific therapies. In the case of the eye, which is susceptible to a...
Source: Cold Spring Harbor perspectives in medicine - May 1, 2015 Category: Research Authors: Wiley, L. A., Burnight, E. R., Mullins, R. F., Stone, E. M., Tucker, B. A. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] The Amniotic Fluid Transcriptome as a Guide to Understanding Fetal Disease
Numerous recent studies have shown the power of cell-free fetal RNA, obtained from amniotic fluid supernatant, to report on the development of the living fetus in real time. Examination of these transcripts on a genome-wide basis has led to new insights into the prenatal pathophysiology of multiple genetic, developmental, and environmental diseases. Each studied condition presents a unique, characteristic fetal transcriptome, which points to specific disrupted molecular pathways. These studies have also improved our knowledge of the normal development of the human fetus, revealing gestational age-related dynamic gene expre...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Zwemer, L. M., Bianchi, D. W. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] mTOR Signaling in Epilepsy: Insights from Malformations of Cortical Development
Over the past decade enhanced activation of the mammalian target of rapamycin (mTOR)-signaling cascade has been identified in focal malformations of cortical development (MCD) subtypes, which have been collectively referred to as "mTORopathies." Mutations in mTOR regulatory genes (e.g., TSC1, TSC2, AKT3, DEPDC5) have been associated with several focal MCD highly associated with epilepsy such as tuberous sclerosis complex (TSC), hemimegalencephaly (HME; brain malformation associated with dramatic enlargement of one brain hemisphere), and cortical dysplasia. mTOR plays important roles in the regulation of cell divi...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Crino, P. B. Tags: Epilepsy: The Biology of a Spectrum Disorder PERSPECTIVES Source Type: research

[PERSPECTIVES] Antiviral Therapies and Prospects for a Cure of Chronic Hepatitis B
Current therapies of chronic hepatitis B (CHB) remain limited to either pegylated interferon-α (Peg-IFN-α), or one of the five approved nucleoside analog (NA) treatments. Although viral suppression can be achieved in the majority of patients with high-barrier-to-resistance new-generation NAs (i.e., entecavir and tenofovir), HBsAg loss is achieved in only 10% of patients with both classes of drugs after a follow-up of 5 years. Attempts to improve the response by administering two different NAs or a combination of NA and Peg-IFN-α have been unsuccessful. Therefore, there is a renewed interest to investigate...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Zoulim, F., Durantel, D. Tags: Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] Animal Models and the Molecular Biology of Hepadnavirus Infection
Australian antigen, the envelope protein of hepatitis B virus (HBV), was discovered in 1967 as a prevalent serum antigen in hepatitis B patients. Early electron microscopy (EM) studies showed that this antigen was present in 22-nm particles in patient sera, which were believed to be incomplete virus. Complete virus, much less abundant than the 22-nm particles, was finally visualized in 1970. HBV was soon found to infect chimpanzees, gorillas, orangutans, gibbon apes, and, more recently, tree shrews (Tupaia belangeri) and cynomolgus macaques (Macaca fascicularis). This restricted host range placed limits on the kinds of stu...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Mason, W. S. Tags: Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] Mycobacterium tuberculosis Metabolism
Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances—in particular, the development of systems biology tools such as metabolomics—have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mec...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Warner, D. F. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Trade Secrets in Life Science and Pharmaceutical Companies
Trade secret protection arises under state common law and state statutes. In general, a trade secret is information that is not generally known to the public and is maintained as a secret, and it provides a competitive advantage or economic benefit to the trade secret holder. Trade secrets can be worth tens or hundreds of millions of dollars, and damage awards in trade secret litigation have been high; often, there is a lot at stake. Obtaining a trade secret through "improper means" is misappropriation. If the alleged trade secret, however, was developed independently, known publicly, or not maintained as a secre...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Nealey, T., Daignault, R. M., Cai, Y. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] What Is Your Reasonable Expectation of Success in Obtaining Pharmaceutical or Biotechnology Patents Having Nonobvious Claimed Inventions That the Courts Will Uphold? An Overview of Obviousness Court Decisions
This article explores the legal basis for establishing the nonobviousness of patent claims in the life sciences fields of technology drawn from the guidance provided in published decisions of the U.S. Patent and Trademark Office’s Patent Trial and Appeal Board, federal district courts, the Federal Circuit Court of Appeals, and the U.S. Supreme Court. Our analysis, although equally applicable to all disciplines and technologies, focuses primarily on decisions of greatest import affecting patents in the fields of pharmaceutical chemistry and biotechnology. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Pereira, D. J., Kunin, S. G. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Treatment Principles for the Management of Mold Infections
Survival rates among immunocompromised patients with invasive mold infections have markedly improved over the last decade with earlier diagnosis and new antifungal treatment options. Yet, increasing antifungal resistance, breakthrough infections with intrinsically resistant fungi, and potentially life-threatening adverse effects and drug interactions are becoming more problematic, especially with prolonged therapy. Evidence-based recommendations for treating invasive aspergillosis and mucormycosis provide excellent guidance on the initial workup and treatment of these molds, but they cannot address all of the key managemen...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Kontoyiannis, D. P., Lewis, R. E. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Human Fungal Pathogens of Mucorales and Entomophthorales
In recent years, we have seen an increase in the number of immunocompromised cohorts as a result of infections and/or medical conditions, which has resulted in an increased incidence of fungal infections. Although rare, the incidence of infections caused by fungi belonging to basal fungal lineages is also continuously increasing. Basal fungal lineages diverged at an early point during the evolution of the fungal lineage, in which, in a simplified four-phylum fungal kingdom, Zygomycota and Chytridiomycota belong to the basal fungi, distinguishing them from Ascomycota and Basidiomycota. Currently there are no known human inf...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Mendoza, L., Vilela, R., Voelz, K., Ibrahim, A. S., Voigt, K., Lee, S. C. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Clinical Immunology and Multiplex Biomarkers of Human Tuberculosis
The discovery of tuberculosis (TB) biomarkers is an important goal in current TB research, because the availability of such markers would have significant impact on TB prevention and treatment. Correlates of protection would greatly facilitate vaccine development and evaluation, whereas correlates of TB disease risk would facilitate early diagnosis and help installing early or preventive treatment. Currently, no such markers are available. This review describes several strategies that are currently being pursued to identify TB biomarkers and places these in a clinical context. The approaches discussed include both targeted...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Walzl, G., Haks, M. C., Joosten, S. A., Kleynhans, L., Ronacher, K., Ottenhoff, T. H. M. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Gene Therapy Using Stem Cells
This article explores the development of gene therapy and patient-derived stem cells for the purpose of restoring vision to individuals suffering from inherited retinal degenerations. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Burnight, E. R., Wiley, L. A., Mullins, R. F., Stone, E. M., Tucker, B. A. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Leber Congenital Amaurosis Caused by Mutations in RPGRIP1
Recessive null mutations in retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1) gene are the cause of LCA6 and account for 5% to 6% of the total patient population. RPGRIP1 has an essential role in the photoreceptor connecting cilia, and photoreceptors lacking RPGRIP1 are unable to maintain the light sensing outer segments. As a result, patients lose retinal functions at an early age but retain photoreceptors in the central retina well into adulthood thus holding out the prospect for gene augmentation therapies. Laboratory studies in animal models have demonstrated efficacy of gene therapy in slowing dise...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Li, T. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[CONCEPTS] Signal Transduction in Cancer
Cancer is driven by genetic and epigenetic alterations that allow cells to overproliferate and escape mechanisms that normally control their survival and migration. Many of these alterations map to signaling pathways that control cell growth and division, cell death, cell fate, and cell motility, and can be placed in the context of distortions of wider signaling networks that fuel cancer progression, such as changes in the tumor microenvironment, angiogenesis, and inflammation. Mutations that convert cellular proto-oncogenes to oncogenes can cause hyperactivation of these signaling pathways, whereas inactivation of tumor s...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2015 Category: Research Authors: Sever, R., Brugge, J. S. Tags: Signal Transduction CONCEPTS Source Type: research

[PERSPECTIVES] Genetic Considerations in Recurrent Pregnancy Loss
Human reproduction is remarkably inefficient; nearly 70% of human conceptions do not survive to live birth. Spontaneous fetal aneuploidy is the most common cause for spontaneous loss, particularly in the first trimester of pregnancy. Although losses owing to de novo fetal aneuploidy occur at similar frequencies among women with sporadic and recurrent losses, some couples with recurrent pregnancy loss have additional associated genetic factors and some have nongenetic etiologies. Genetic testing of the products of conception from couples experiencing two or more losses may aid in defining the underlying etiology and in coun...
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: Hyde, K. J., Schust, D. J. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Placental Extracellular Vesicles and Feto-Maternal Communication
The human placenta is an anatomically unique structure that extrudes a variety of extracellular vesicles into the maternal blood (including syncytial nuclear aggregates, microvesicles, and nanovesicles). Large quantities of extracellular vesicles are produced by the placenta in both healthy and diseased pregnancies. Since their first description more than 120 years ago, placental extracellular vesicles are only now being recognized as important carriers for proteins, lipids, and nucleic acids, which may play a crucial role in feto-maternal communication. Here, we summarize the current literature on the cargos of placental ...
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: Tong, M., Chamley, L. W. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Role of Astrocytes in Epilepsy
Astrocytes express ion channels, transmitter receptors, and transporters and, thus, are endowed with the machinery to sense and respond to neuronal activity. Recent studies have implicated that astrocytes play important roles in physiology, but these cells also emerge as crucial actors in epilepsy. Astrocytes are abundantly coupled through gap junctions allowing them to redistribute elevated K+ and transmitter concentrations from sites of enhanced neuronal activity. Investigation of specimens from patients with pharmacoresistant temporal lobe epilepsy and epilepsy models revealed alterations in expression, localization, an...
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: Coulter, D. A., Steinhauser, C. Tags: Epilepsy: The Biology of a Spectrum Disorder PERSPECTIVES Source Type: research

[PERSPECTIVES] Prevention of Hepatitis B
Hepatitis B virus (HBV) causes life-threatening liver disease. It is transmitted through a horizontal route or a mother-to-infant route, and the latter is the major route in endemic areas. Prevention of HBV infection by immunization is the best way to eliminate HBV-related diseases. The HBV vaccine is the first human vaccine using a viral antigen from infected persons, which is safe and effective. Either passive immunization by hepatitis B immunoglobulin (HBIG) or active immunization by HBV vaccine is effective, and a combination of both yields the best efficacy in preventing HBV infection. The impact of universal HBV immu...
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: Chang, M.-H., Chen, D.-S. Tags: Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] Patenting Stem Cell Technologies in Europe
European patent law as it applies to stem cell technologies is complex. The complexities have developed from different supranational sources of law during the last 50 years and from the various levels of exceptions to patentability embodied in the law. In relation to stem cells of human embryonic origin, the definition of a human embryo, although broad, is still in some respects unclear; and the definition of what constitutes the use of a human embryo for industrial or commercial purposes, which is excluded from patentability in Europe, is also remarkably broad. Further clarification is awaited from the courts and from the...
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: Sheard, A. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Licensing Biotech Intellectual Property in University-Industry Partnerships
Appropriate negotiation and drafting of license agreements are critical to successfully establishing and managing the expansive and complex relationships that are becoming more common between industry and universities. More often than not, the resulting licensing agreements become quite lengthy and complex, and the key principles become difficult to discern among all the details. This summary provides a short, nonexhaustive introduction to some of the essential components of these licenses with the intent of providing the non–licensing professional a better appreciation of some of the key commercial and legal terms f...
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: Drozdoff, V., Fairbairn, D. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Adaptive Immunity to Fungi
We describe recent insights in understanding the mammalian immune defenses that are deployed against pathogenic fungi. We focus on adaptive immunity to the major medically important fungi and emphasize three elements that coordinate the response: (1) dendritic cells and subsets that are mobilized against fungi in various anatomical compartments; (2) fungal molecular patterns and their corresponding receptors that signal responses and shape the differentiation of T-cell subsets and B cells; and, ultimately (3) the effector and regulatory mechanisms that eliminate these invaders while constraining collateral damage to vital ...
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: Verma, A., Wuthrich, M., Deepe, G., Klein, B. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Functional Profiling of Human Fungal Pathogen Genomes
Fungal infections are challenging to diagnose and often difficult to treat, with only a handful of drug classes existing. Understanding the molecular mechanisms by which pathogenic fungi cause human disease is imperative. Here, we discuss how the development and use of genome-scale genetic resources, such as whole-genome knockout collections, can address this unmet need. Using work in Saccharomcyes cerevisiae as a guide, studies of Cryptococcus neoformans and Candida albicans have shown how the challenges of large-scale gene deletion can be overcome, and how such collections can be effectively used to obtain insights into ...
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: Goranov, A. I., Madhani, H. D. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Animal Models of Tuberculosis: Zebrafish
This article will highlight the unique features of the zebrafish–Mycobacterium marinum infection model and its added value for tuberculosis research. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: van Leeuwen, L. M., van der Sar, A. M., Bitter, W. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Role of B Cells and Antibodies in Acquired Immunity against Mycobacterium tuberculosis
Accumulating evidence has documented a role for B cells and antibodies (Abs) in the immunity against Mycobacterium tuberculosis (Mtb). Passive transfer studies with monoclonal antibodies (mAbs) against mycobacterial antigens have shown protection against the tubercle bacillus. B cells and Abs are believed to contribute to an enhanced immune response against Mtb by modulating various immunological components in the infected host including the T-cell compartment. Nevertheless, the extent and contribution of B cells and Abs to protection against Mtb remains uncertain. In this article we summarize the most relevant findings su...
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: Achkar, J. M., Chan, J., Casadevall, A. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Gene Therapy for Choroideremia Using an Adeno-Associated Viral (AAV) Vector
Choroideremia is an outer retinal degeneration with a characteristic clinical appearance that was first described in the nineteenth century. The disorder begins with reduction of night vision and gradually progresses to blindness by middle age. The appearance of the fundus in sufferers is recognizable by the characteristic pale color caused by the loss of the outer retina, retinal-pigmented epithelium, and choroidal vessels, leading to exposure of the underlying sclera. Choroideremia shows X-linked recessive inheritance and the choroideremia gene (CHM) was one of the first to be identified by positional cloning in 1990. Su...
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: Barnard, A. R., Groppe, M., MacLaren, R. E. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Highly Penetrant Alleles in Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is a complex disease caused by a combination of genetic and environmental factors. Genome-wide association studies have identified several common genetic variants associated with AMD, which together account for 15%–65% of the heritability of AMD. Multiple hypotheses to clarify the unexplained portion of genetic variance have been proposed, such as gene–gene interactions, gene–environment interactions, structural variations, epigenetics, and rare variants. Several studies support a role for rare variants with large effect sizes in the pathogenesis of AMD. In this work...
Source: Cold Spring Harbor perspectives in medicine - March 2, 2015 Category: Research Authors: den Hollander, A. I., de Jong, E. K. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[ERRATUM] Cardiac Cell Lineages that Form the Heart
(Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Meilhac, S. M., Lescroart, F., Blanpain, C., Buckingham, M. E. Tags: ERRATUM Source Type: research

[PERSPECTIVES] Genomics of Preterm Birth
The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of ...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Swaggart, K. A., Pavlicev, M., Muglia, L. J. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Hepatocellular Carcinoma
The hepatitis B virus (HBV) is a widespread human pathogen that causes liver inflammation, cirrhosis, and hepatocellular carcinoma (HCC). Recent sequencing technologies have refined our knowledge of the genomic landscape and pathogenesis of HCC, but the mechanisms by which HBV exerts its oncogenic role remain controversial. In a prevailing view, inflammation, liver damage, and regeneration may foster the accumulation of genetic and epigenetic defects leading to cancer onset. However, a more direct and specific contribution of the virus is supported by clinical and biological observations. Among genetically heterogeneous HC...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Buendia, M.-A., Neuveut, C. Tags: Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[RETROSPECTIVE] Viral Hepatitis: Past and Future of HBV and HDV
Viral hepatitis is a significant disease afflicting hundreds of millions of people. Hepatitis-causing viruses initiate significant morbidity and mortality by establishing both acute and chronic infections, and several of these viruses are specifically associated with the development of hepatocellular carcinoma (HCC). Consequently, intense research efforts are focused on increasing our understanding of virus biology and on improving antiviral therapy. Even though viral hepatitis can be caused by several viruses from a range of virus families, the discovery of components of the hepatitis B virus (HBV) became a catalyst for t...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Thomas, E., Yoneda, M., Schiff, E. R. Tags: Hepatitis B and Delta Viruses RETROSPECTIVE Source Type: research

[PERSPECTIVES] Comparative Genomics of Mycobacteria: Some Answers, Yet More New Questions
Comparative genomic studies permit a genus-level perspective on the distinction between environmental mycobacteria and Mycobacterium tuberculosis, as well as a species-level assessment of genetic variability within M. tuberculosis. Both of these strata of evolutionary analysis serve to generate hypotheses regarding the genomic basis of M. tuberculosis virulence. In contrasting lessons from macroevolutionary study and microevolutionary study, one can form predictions about which segments of the genome are likely to be essential for or dispensable for the pathogenesis of tuberculosis. Although some of these predictions have ...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Behr, M. A. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Research Exemption/Experimental Use in the European Union: Patents Do Not Block the Progress of Science
In the public debate about patents, specifically in the area of biotechnology, the position has been taken that patents block the progress of science. As we demonstrate in this review, this is not the case in the European Union (EU). The national patent acts of the EU member states define research and experimental use exemptions from patent infringement that allow sufficient room for research activities to promote innovation. This review provides a comparative overview of the legal requirements and the extent and limitations of experimental use exemptions, including the so-called Bolar provision, in Germany, the United Kin...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Jaenichen, H.-R., Pitz, J. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Research Use Exemptions to Patent Infringement for Drug Discovery and Development in the United States
This article analyzes the history of these exemptions and how the courts have interpreted their scope and provides future perspectives on protecting research and development activities from liability. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Russo, A. A., Johnson, J. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Aspergillus fumigatus and Related Species
The genus Aspergillus contains etiologic agents of aspergillosis. The clinical manifestations of the disease range from allergic reaction to invasive pulmonary infection. Among the pathogenic aspergilli, Aspergillus fumigatus is most ubiquitous in the environment and is the major cause of the disease, followed by Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Aspergillus nidulans, and several species in the section Fumigati that morphologically resemble A. fumigatus. Patients that are at risk for acquiring aspergillosis are those with an altered immune system. Early diagnosis, species identification, and adequ...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Sugui, J. A., Kwon-Chung, K. J., Juvvadi, P. R., Latge, J.-P., Steinbach, W. J. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Fungal Morphogenesis
Morphogenesis in fungi is often induced by extracellular factors and executed by fungal genetic factors. Cell surface changes and alterations of the microenvironment often accompany morphogenetic changes in fungi. In this review, we will first discuss the general traits of yeast and hyphal morphotypes and how morphogenesis affects development and adaptation by fungi to their native niches, including host niches. Then we will focus on the molecular machinery responsible for the two most fundamental growth forms, yeast and hyphae. Last, we will describe how fungi incorporate exogenous environmental and host signals together ...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Lin, X., Alspaugh, J. A., Liu, H., Harris, S. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Mouse Model of Tuberculosis
The mouse provides a tool with which to probe the complex interaction between the mammalian immune system and the slow-growing, inflammatory, and persistent bacterium, Mycobacterium tuberculosis (Mtb). Simple mouse models using genetic deletion or antibody inhibition have identified causal connections between specific components of the immune response and survival upon challenge with Mtb, and these studies have corresponded with observations made in humans. To improve on current intervention strategies, it is essential that the complex interactions between the components of the immune response that mediate and regulate the...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Cooper, A. M. Tags: Tuberculosis PERSPECTIVES Source Type: research