[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

[PERSPECTIVES] Global Epidemiology of Tuberculosis
This article provides a short overview of sources of data to estimate TB disease burden; presents estimates of TB incidence, prevalence, and mortality in 2012 and an assessment of progress toward the 2015 targets for reductions in these indicators based on trends since 1990 and projections up to 2015; analyzes trends in TB notifications and in the implementation of the Stop TB Strategy; and considers prospects for elimination of TB after 2015. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Glaziou, P., Sismanidis, C., Floyd, K., Raviglione, M. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Gene Augmentation for X-Linked Retinitis Pigmentosa Caused by Mutations in RPGR
X-linked retinitis pigmentosa (XLRP) caused by mutations in the RPGR gene is a severe and early onset form of retinal degeneration, and no treatment is currently available. Recent evidence in two clinically relevant canine models shows that adeno-associated viral (AAV)-mediated RPGR gene transfer to rods and cones can prevent disease onset and rescue photoreceptors at early- and mid-stages of degeneration. There is thus a strong incentive for conducting long-term, preclinical efficacy and safety studies, while concomitantly pursuing the detailed phenotypic characterization of XLRP disease in patients that may benefit from ...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Beltran, W. A., Cideciyan, A. V., Lewin, A. S., Hauswirth, W. W., Jacobson, S. G., Aguirre, G. D. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Clinical Characteristics and Current Therapies for Inherited Retinal Degenerations
Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307–316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod–cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone–rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndro...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2015 Category: Research Authors: Sahel, J.-A., Marazova, K., Audo, I. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Wound Healing and Skin Regeneration
The skin is a complex organ consisting of the epidermis, dermis, and skin appendages, including the hair follicle and sebaceous gland. Wound healing in adult mammals results in scar formation without any skin appendages. Studies have reported remarkable examples of scarless healing in fetal skin and appendage regeneration in adult skin following the infliction of large wounds. The models used in these studies have offered a new platform for investigations of the cellular and molecular mechanisms underlying wound healing and skin regeneration in mammals. In this article, we will focus on the contribution of skin appendages ...
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Takeo, M., Lee, W., Ito, M. Tags: The Skin and Its Diseases PERSPECTIVES Source Type: research

[PERSPECTIVES] Pharmacologic Considerations in Use and Development of Antituberculosis Drugs
Rational development and deployment of antituberculosis drugs depend on a comprehensive understanding of the pharmacokinetics and pharmacodynamics that underlie their clinical behavior. Successful implementation of a pharmacokinetic–pharmacodynamic approach faces difficulties that, although not unique to tuberculosis as a therapeutic area, in combination pose a significant scientific challenge. In recent years, a multidisciplinary response combining new technological and analytical approaches has begun to directly address many of these issues, shedding light on some previously poorly understood aspects of drug distri...
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Davies, G. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Patentability of Self-Replicating Technologies
Patents provide an incentive to inventors, investors, and entrepreneurs to conduct research and development, especially in risky (i.e., unpredictable) fields of technology. This review discusses whether self-replicating technologies are patentable within the United States and the issues surrounding them. Self-replicating technologies discussed include plants, bacteria, and genetic technology and the historical legal precedents that have led to the current status of the patent law. To clearly understand these issues, the review also discusses various U.S. Supreme Court cases that, although not related to self-replicating te...
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Shear, R. H. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Decoding Gene Patents in Australia
Patents directed to naturally occurring genetic material, such as DNA, RNA, chromosomes, and genes, in an isolated or purified form have been granted in Australia for many years. This review provides scientists with a summary of the gene patent debate from an Australian perspective and specifically reviews how the various levels of the legal system as they apply to patents—the Australian Patent Office, Australian courts, and Australian government—have dealt with the issue of whether genetic material is proper subject matter for a patent. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Denley, A., Cherry, J. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Host Cell Invasion by Medically Important Fungi
To infect the host and cause disease, many medically important fungi invade normally nonphagocytic host cells, such as endothelial cells and epithelial cells. Host cell invasion is a two-step process consisting of adherence followed by invasion. There are two general mechanisms of host cell invasion, induced endocytosis and active penetration. Furthermore, fungi can traverse epithelial or endothelial cell barriers either by proteolytic degradation of intercellular tight junctions or via a Trojan horse mechanism in which they are transported by leukocytes. Although these mechanisms of host cell invasion have been best studi...
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Sheppard, D. C., Filler, S. G. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] The Spectrum of Fungi That Infects Humans
Few among the millions of fungal species fulfill four basic conditions necessary to infect humans: high temperature tolerance, ability to invade the human host, lysis and absorption of human tissue, and resistance to the human immune system. In previously healthy individuals, invasive fungal disease is rare because animals’ sophisticated immune systems evolved in constant response to fungal challenges. In contrast, fungal diseases occur frequently in immunocompromised patients. Paradoxically, successes of modern medicine have put increasing numbers of patients at risk for invasive fungal infections. Uncontrolled HIV ...
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Kohler, J. R., Casadevall, A., Perfect, J. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Toward a Unified Biosignature for Tuberculosis
Accurate and rapid diagnosis of active tuberculosis (TB) disease is still hampered by inadequate tools. Although current assays relying on single-marker readouts mostly display inadequate sensitivity and/or specificity, host-related multimarker signatures are especially poorly developed. As a consequence, research programs have been initiated to search for combinations of markers—so-called biosignatures with superior performance. Many such investigations harness high-throughput platforms to analyze the host response during infection and disease. A major challenge for these activities is the analysis of vast amounts o...
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Maertzdorf, J., Kaufmann, S. H. E., Weiner, J. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Leber Congenital Amaurosis Caused by Mutations in GUCY2D
This article will summarize clinical characterization of patients and proof of concept gene replacement studies in several animal models of GC1 deficiency, both of which have laid the groundwork for clinical application of a gene therapy for treatment of LCA1. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Boye, S. E. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, prov...
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Yonekawa, Y., Kim, I. K. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Natural and Sun-Induced Aging of Human Skin
With worldwide expansion of the aging population, research on age-related pathologies is receiving growing interest. In this review, we discuss current knowledge regarding the decline of skin structure and function induced by the passage of time (chronological aging) and chronic exposure to solar UV irradiation (photoaging). Nearly every aspect of skin biology is affected by aging. The self-renewing capability of the epidermis, which provides vital barrier function, is diminished with age. Vital thermoregulation function of eccrine sweat glands is also altered with age. The dermal collagenous extracellular matrix, which co...
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Rittie, L., Fisher, G. J. Tags: The Skin and Its Diseases PERSPECTIVES Source Type: research

[PERSPECTIVES] Personalized Genomes and Cardiovascular Disease
The emerging ability to obtain a personalized genome, that is, to perform whole-genome sequencing to determine the entirety of the DNA sequence in an individual patient’s chromosomes, holds out the promise of transforming patient care by allowing physicians to more accurately predict the risk of disease and to tailor therapy to that individual. Although no established applications of personalized genomics in cardiovascular medicine yet exist, there are at least two emerging applications that may ultimately become everyday practice. In the first application, DNA sequence variants that have been found to be associated ...
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Musunuru, K. Tags: The Biology of Heart Disease PERSPECTIVES Source Type: research

[PERSPECTIVES] Synthetic Chemically Modified mRNA (modRNA): Toward a New Technology Platform for Cardiovascular Biology and Medicine
Over the past two decades, a host of new molecular pathways have been uncovered that guide mammalian heart development and disease. The ability to genetically manipulate these pathways in vivo have largely been dependent on the generation of genetically engineered mouse model systems or the transfer of exogenous genes in a variety of DNA vectors (plasmid, adenoviral, adeno-associated viruses, antisense oligonucleotides, etc.). Recently, a new approach to manipulate the gene program of the adult mammalian heart has been reported that will quickly allow the high-efficiency expression of virtually any protein in the intact he...
Source: Cold Spring Harbor perspectives in medicine - January 5, 2015 Category: Research Authors: Chien, K. R., Zangi, L., Lui, K. O. Tags: The Biology of Heart Disease PERSPECTIVES Source Type: research

[PERSPECTIVES] Viral Hepatitis B: Clinical and Epidemiological Characteristics
It is now 50 years since the discovery of the hepatitis B virus (HBV), and, despite the availability of a prophylactic vaccine for more than 20 years, HBV infection remains a disease of significant global health burden. It is estimated that more than 240 million people are chronically infected with HBV and, therefore, are at risk for the development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). The risk of clinical complications has traditionally been higher in older males with hepatitis B e antigen (HBeAg)–positive disease, high-grade liver necroinflammation, and progressive fibrosis. Rec...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2014 Category: Research Authors: Burns, G. S., Thompson, A. J. Tags: Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] Diversity and Evolution of Mycobacterium tuberculosis: Moving to Whole-Genome-Based Approaches
Genotyping of clinical Mycobacterium tuberculosis complex (MTBC) strains has become a standard tool for epidemiological tracing and for the investigation of the local and global strain population structure. Of special importance is the analysis of the expansion of multidrug (MDR) and extensively drug-resistant (XDR) strains. Classical genotyping and, more recently, whole-genome sequencing have revealed that the strains of the MTBC are more diverse than previously anticipated. Globally, several phylogenetic lineages can be distinguished whose geographical distribution is markedly variable. Strains of particular (sub)lineage...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2014 Category: Research Authors: Niemann, S., Supply, P. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Patenting the Life Sciences at the European Patent Office
The European patent system is very much like those of the United States and other major countries. Patent applications can be filed as a first filing, as a priority application, or as a national phase of a Patent Cooperation Treaty application. The applications are searched, rigorously examined, and ultimately granted, with the time periods varying somewhat depending on the application type. The object of this article is to highlight some of the differences between the U.S. and European systems, particularly as they relate to life sciences. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - December 1, 2014 Category: Research Authors: Gates, C. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Pneumocystis
Since its initial misidentification as a trypanosome some 100 years ago, Pneumocystis has remained recalcitrant to study. Although we have learned much, we still do not have definitive answers to such basic questions as, where is the reservoir of infection, how does Pneumocystis reproduce, what is the mechanism of infection, and are there true species of Pneumocystis? The goal of this review is to provide the reader the most up to date information available about the biology of Pneumocystis and the disease it produces. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - December 1, 2014 Category: Research Authors: Gigliotti, F., Limper, A. H., Wright, T. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Metabolism in Fungal Pathogenesis
Fungal pathogens must assimilate local nutrients to establish an infection in their mammalian host. We focus on carbon, nitrogen, and micronutrient assimilation mechanisms, discussing how these influence host–fungus interactions during infection. We highlight several emerging trends based on the available data. First, the perturbation of carbon, nitrogen, or micronutrient assimilation attenuates fungal pathogenicity. Second, the contrasting evolutionary pressures exerted on facultative versus obligatory pathogens have led to contemporary pathogenic fungal species that display differing degrees of metabolic flexibilit...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2014 Category: Research Authors: Ene, I. V., Brunke, S., Brown, A. J. P., Hube, B. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Modeling Tuberculosis in Nonhuman Primates
Nonhuman primates have emerged as an excellent model of human tuberculosis, in large part because they recapitulate the full spectrum of infection outcome and pathology seen in humans. Several variables inherent to the nonhuman primate models of tuberculosis are discussed in this review, including the monkey species, Mycobacterium tuberculosis strains, and routes of infection, all of which can influence the model to be chosen for various studies. New technologies for studying the microbiology, immunology, and pathogenesis of tuberculosis in nonhuman primates have greatly expanded the capabilities of this model for basic an...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2014 Category: Research Authors: Scanga, C. A., Flynn, J. L. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Common and Rare Genetic Risk Factors for Glaucoma
In this report, we present a comprehensive overview of the genes and genomic regions contributing to inherited glaucoma. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - December 1, 2014 Category: Research Authors: Wang, R., Wiggs, J. L. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Genome-Wide Association Studies: Getting to Pathogenesis, the Role of Inflammation/Complement in Age-Related Macular Degeneration
This article explores the research efforts that brought about the discovery and characterization of the role of inflammatory and immune processes (specifically complement) in AMD. The focus herein is on the genetic evidence for the role of complement in AMD as supported specifically by genome-wide association (GWA) studies, which interrogate hundreds of thousands of variants across the genome in a hypothesis-free approach, and other genetic interrogation methods. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - December 1, 2014 Category: Research Authors: Cooke Bailey, J. N., Pericak-Vance, M. A., Haines, J. L. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Immunology and Skin in Health and Disease
The skin is a complex organ that, in addition to providing a strong barrier against external insults, serves as an arena for a wide variety of inflammatory processes, including immunity against infections, tumor immunity, autoimmunity, and allergy. A variety of cells collaborate to mount functional immune responses, which are initiated by resident populations and evolve through the recruitment of additional cell populations to the skin. Inflammatory responses are quite diverse, resulting in a wide range of signs and symptoms that depend on the initiating signals, characteristics of the infiltrating cell populations, and cy...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2014 Category: Research Authors: Richmond, J. M., Harris, J. E. Tags: The Skin and Its Diseases PERSPECTIVES Source Type: research

[PERSPECTIVES] Epidermal Polarity Genes in Health and Disease
This article will address the importance of polarizing processes and their molecular regulators in epidermal morphogenesis and homeostasis and discuss how alterations in polarity may contribute to skin disease. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - December 1, 2014 Category: Research Authors: Tellkamp, F., Vorhagen, S., Niessen, C. M. Tags: The Skin and Its Diseases PERSPECTIVES Source Type: research

[PERSPECTIVES] Next-Generation Models of Human Cardiogenesis via Genome Editing
Cardiogenesis is one of the earliest and most important steps during human development and is orchestrated by discrete families of heart progenitors, which build distinct regions of the fetal heart. For the past decade, a lineage map for the distinct subsets of progenitors that generate the embryonic mammalian heart has begun to lay a foundation for the development of new strategies for rebuilding the adult heart after injury, an unmet clinical need for the vast majority of patients with end-stage heart failure who are not heart transplant recipients. The studies also have implications for the root causes of congenital hea...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2014 Category: Research Authors: Lian, X., Xu, J., Li, J., Chien, K. R. Tags: The Biology of Heart Disease PERSPECTIVES Source Type: research

[BANBURY WHITE PAPER] Rhabdomyosarcoma: Current Challenges and Their Implications for Developing Therapies
Rhabdomyosarcoma (RMS) represents a rare, heterogeneous group of mesodermal malignancies with skeletal muscle differentiation. One major subgroup of RMS tumors (so-called "fusion-positive" tumors) carries exclusive chromosomal translocations that join the DNA-binding domain of the PAX3 or PAX7 gene to the transactivation domain of the FOXO1 (previously known as FKHR) gene. Fusion-negative RMS represents a heterogeneous spectrum of tumors with frequent RAS pathway activation. Overtly metastatic disease at diagnosis is more frequently found in individuals with fusion-positive than in those with fusion-negative tumo...
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Hettmer, S., Li, Z., Billin, A. N., Barr, F. G., Cornelison, D. D. W., Ehrlich, A. R., Guttridge, D. C., Hayes-Jordan, A., Helman, L. J., Houghton, P. J., Khan, J., Langenau, D. M., Linardic, C. M., Pal, R., Partridge, T. A., Pavlath, G. K., Rota, R., Sch Tags: BANBURY WHITE PAPER Source Type: research