[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

[PERSPECTIVES] Hepatitis D Virus Coinfection and Superinfection
HDV is a defective RNA pathogen requiring the simultaneous presence of HBV to complete its life cycle. Two major specific patterns of infection have been described: the coinfection with HDV and HBV of a susceptible, anti-HBs-negative individual, or the HDV superinfection of a chronic HBV carrier. Coinfection mostly leads to the eradication of both agents, whereas the majority of patients with HDV superinfection evolve to chronic HDV infection and hepatitis. Chronic HDV infection worsens the preexisting HBV-related liver damage. HDV-associated chronic liver disease (chronic hepatitis D) is characterized by necroinflammation...
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Negro, F. Tags: Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] Must an Inventor "Possess" an Invention to Patent It?
The requirements for patenting inventions relating to biotechnology have become increasingly strict and complicated in recent years. Despite early patent rulings that there is no need for an inventor to "reduce to practice" an invention, the courts are now ruling that an inventor must "possess" his or her invention before filing for patent. This review discusses what such "possession" may mean and describes decisions in which courts have found that an inventor has met or failed the possession test before filing for patent protection. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Woessner, W. D., Chadwick, R. A. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Antifungal Clinical Trials and Guidelines: What We Know and Do Not Know
This article will review some of the major advances, as well as significant challenges that remain in the management of invasive mycoses. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Pappas, P. G. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Fungal Vaccines and Immunotherapeutics
Concomitant with the increased prevalence of immunocompromised persons, invasive fungal infections have become considerably more frequent in the last 50 years. High mortality rates caused by invasive mycoses and high morbidity because of intractable mucosal infections have created an unmet need for innovative prophylactic and therapeutic strategies against fungal pathogens. Several immunotherapeutics and vaccines are in development to address this need, although one has yet to reach the clinic. This review focuses on past and current immunotherapeutic and vaccine strategies being tested to either prevent or treat fungal in...
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Santos, E., Levitz, S. M. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Manipulation of the Mononuclear Phagocyte System by Mycobacterium tuberculosis
Over the past 20 years, there has been an emerging appreciation about the role of the mononuclear phagocyte system (MPS) to control and eradicate pathogens. Likewise, there have been significant advances in dissecting the mechanisms involved in the microbial subversion of MPS cells, mainly affecting their differentiation and effector functions. Mycobacterium tuberculosis is a chronic bacterial pathogen that represents an enigma to the field because of its remarkable ability to thrive in humans. One reason is that M. tuberculosis renders a defective MPS compartment, which is perhaps the most ingenious strategy for survival ...
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Lugo-Villarino, G., Neyrolles, O. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Autophagy in Tuberculosis
Autophagy as an immune mechanism controls inflammation and acts as a cell-autonomous defense against intracellular microbes including Mycobacterium tuberculosis. An equally significant role of autophagy is its anti-inflammatory and tissue-sparing function. This combination of antimicrobial and anti-inflammatory actions prevents active disease in animal models. In human populations, genetic links between autophagy, inflammatory bowel disease, and susceptibility to tuberculosis provide further support to these combined roles of autophagy. The autophagic control of M. tuberculosis and prevention of progressive disease provide...
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Deretic, V. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Curing Color Blindness--Mice and Nonhuman Primates
It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates,...
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Neitz, M., Neitz, J. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Gene Therapy for PRPH2-Associated Ocular Disease: Challenges and Prospects
The peripherin-2 (PRPH2) gene encodes a photoreceptor-specific tetraspanin protein called peripherin-2/retinal degeneration slow (RDS), which is critical for the formation and maintenance of rod and cone outer segments. Over 90 different disease-causing mutations in PRPH2 have been identified, which cause a variety of forms of retinitis pigmentosa and macular degeneration. Given the disease burden associated with PRPH2 mutations, the gene has long been a focus for preclinical gene therapy studies. Adeno-associated viruses and compacted DNA nanoparticles carrying PRPH2 have been successfully used to mediate improvement in t...
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Conley, S. M., Naash, M. I. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease
Desmosomes are intercellular junctions that mediate cell–cell adhesion and anchor the intermediate filament network to the plasma membrane, providing mechanical resilience to tissues such as the epidermis and heart. In addition to their critical roles in adhesion, desmosomal proteins are emerging as mediators of cell signaling important for proper cell and tissue functions. In this review we highlight what is known about desmosomal proteins regulating adhesion and signaling in healthy skin—in morphogenesis, differentiation and homeostasis, wound healing, and protection against environmental damage. We also disc...
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Johnson, J. L., Najor, N. A., Green, K. J. Tags: The Skin and Its Diseases PERSPECTIVES Source Type: research

[PERSPECTIVES] Induced Pluripotent Stem Cells in Dermatology: Potentials, Advances, and Limitations
The discovery of methods for reprogramming adult somatic cells into induced pluripotent stem cells (iPSCs) has raised the possibility of producing truly personalized treatment options for numerous diseases. Similar to embryonic stem cells (ESCs), iPSCs can give rise to any cell type in the body and are amenable to genetic correction by homologous recombination. These ESC properties of iPSCs allow for the development of permanent corrective therapies for many currently incurable disorders, including inherited skin diseases, without using embryonic tissues or oocytes. Here, we review recent progress and limitations of iPSC r...
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Bilousova, G., Roop, D. R. Tags: The Skin and Its Diseases PERSPECTIVES Source Type: research

[PERSPECTIVES] How to Make a Heart Valve: From Embryonic Development to Bioengineering of Living Valve Substitutes
Cardiac valve disease is a significant cause of ill health and death worldwide, and valve replacement remains one of the most common cardiac interventions in high-income economies. Despite major advances in surgical treatment, long-term therapy remains inadequate because none of the current valve substitutes have the potential for remodeling, regeneration, and growth of native structures. Valve development is coordinated by a complex interplay of signaling pathways and environmental cues that cause disease when perturbed. Cardiac valves develop from endocardial cushions that become populated by valve precursor mesenchyme f...
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: MacGrogan, D., Luxan, G., Driessen-Mol, A., Bouten, C., Baaijens, F., de la Pompa, J. L. Tags: The Biology of Heart Disease PERSPECTIVES Source Type: research

[PERSPECTIVES] Genetic Networks Governing Heart Development
Animal genomes contain a code for construction of the body plan from a fertilized egg. Understanding how genome information is deciphered to create the complex multilayered regulatory systems that drive organismal development, and which become altered in disease, is one of the greatest challenges in the biological sciences. The development of methods that effectively represent and communicate the complexity inherent in gene regulatory networks remains a major barrier. This review introduces the philosophy of systems biology and discusses recent progress in understanding the development of the heart at a systems biology lev...
Source: Cold Spring Harbor perspectives in medicine - November 3, 2014 Category: Research Authors: Waardenberg, A. J., Ramialison, M., Bouveret, R., Harvey, R. P. Tags: The Biology of Heart Disease PERSPECTIVES Source Type: research