[PERSPECTIVES] The Impact of Myriad on the Future Development and Commercialization of DNA-Based Therapies and Diagnostics
One of the reasons that the United States is a leader in biotechnology is its strong and reliable patent system. However, the Supreme Court’s decision in Myriad potentially limits an inventor’s ability to protect her DNA-based inventions. Fortunately, with creativity, there are numerous ways in which to "claim around" Myriad, enabling inventors to fully protect their diagnostic or therapeutic inventions. Thus, under a proper reading of the holding, the potential negative effect of Myriad on the progress of biotechnology would be negligible. Unfortunately, the U.S. Patent and Trademark Office has promu...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2015 Category: Research Authors: Wales, M., Cartier, E. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Innate and Adaptive Cellular Immune Responses to Mycobacterium tuberculosis Infection
Host resistance to Mycobacterium tuberculosis (Mtb) infection requires the coordinated efforts of innate and adaptive immune cells. Diverse pulmonary myeloid cell populations respond to Mtb with unique contributions to both host-protective and potentially detrimental inflammation. Although multiple cell types of the adaptive immune system respond to Mtb infection, CD4 T cells are the principal antigen-specific cells responsible for containment of Mtb infection, but they can also be major contributors to disease during Mtb infection in several different settings. Here, we will discuss the role of different myeloid populatio...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2015 Category: Research Authors: Mayer-Barber, K. D., Barber, D. L. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Advances in Diagnostic Assays for Tuberculosis
Approximately one-third of the global burden of tuberculosis (TB) remains undiagnosed each year and the vast majority of cases of multidrug-resistant TB remain undetected. Many countries still place heavy reliance on outdated technologies that are blunt and ineffective tools for controlling this epidemic. However, during the past 10 years, there has been substantial progress within the TB diagnostics developmental pipeline. Old technologies have been reviewed and improved and new technologies have been developed and evaluated and are now being implemented. This review summarizes these developments and describes the current...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2015 Category: Research Authors: Lawn, S. D. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Past, Present, and Future of Healthy Life Expectancy
The success of the current biomedical paradigm based on a "disease model" may be limited in the future because of large number of comorbidities inflicting older people. In recent years, there has been growing empirical evidence, based on animal models, suggesting that the aging process could be delayed and that this process may lead to increases in life expectancy accompanied by improvements in health at older ages. In this review, we explore past, present, and future prospects of healthy life expectancy and examine whether increases in average length of life associated with delayed aging link with additional yea...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Beltran-Sanchez, H., Soneji, S., Crimmins, E. M. Tags: Aging PERSPECTIVES Source Type: research

[PERSPECTIVES] A Review of Secondary Photoreceptor Degenerations in Systemic Disease
Photoreceptor neuronal degenerations are common and incurable causes of human blindness with one in 2000 affected. Approximately, half of all patients are associated with known mutations in more than 200 disease genes. Most retinal degenerations are restricted to the retina (primary retinal degeneration) but photoreceptor degeneration can also be found in a wide variety of systemic and syndromic diseases. These are called secondary retinal degenerations. We review several well-known systemic diseases with retinal degenerations (RD). We discuss RD with hearing loss, RD with brain disease, and RD with musculoskeletal disease...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Mysore, N., Koenekoop, J., Li, S., Ren, H., Keser, V., Lopez-Solache, I., Koenekoop, R. K. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Biochemical Genetic Pathways that Modulate Aging in Multiple Species
The mechanisms underlying biological aging have been extensively studied in the past 20 years with the avail of mainly four model organisms: the budding yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, the fruitfly Drosophila melanogaster, and the domestic mouse Mus musculus. Extensive research in these four model organisms has identified a few conserved genetic pathways that affect longevity as well as metabolism and development. Here, we review how the mechanistic target of rapamycin (mTOR), sirtuins, adenosine monophosphate-activated protein kinase (AMPK), growth hormone/insulin-like growth factor 1 ...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Bitto, A., Wang, A. M., Bennett, C. F., Kaeberlein, M. Tags: Aging PERSPECTIVES Source Type: research

[PERSPECTIVES] Molecular Regulation of Parturition: The Role of the Decidual Clock
The timing of birth is a critical determinant of perinatal outcome. Despite intensive research, the molecular mechanisms responsible for the onset of labor both at term and preterm remain unclear. It is likely that a "parturition cascade" exists that triggers labor at term, that preterm labor results from mechanisms that either prematurely stimulate or short-circuit this cascade, and that these mechanisms involve the activation of proinflammatory pathways within the uterus. It has long been postulated that the fetoplacental unit is in control of the timing of birth through a "placental clock." We sugges...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Norwitz, E. R., Bonney, E. A., Snegovskikh, V. V., Williams, M. A., Phillippe, M., Park, J. S., Abrahams, V. M. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Molecular Regulation of Parturition: A Myometrial Perspective
The molecular mechanisms that maintain quiescence of the myometrium throughout most of pregnancy and promote its transformation to a highly coordinated contractile unit culminating in labor are complex and intertwined. During pregnancy, progesterone (P4) produced by the placenta and/or ovary serves a dominant role in maintaining myometrial quiescence by blocking proinflammatory response pathways and expression of so-called "contractile" genes. In the majority of placental mammals, increased uterine contractility near term is heralded by an increase in circulating estradiol-17β (E2) and/or increased estrogen ...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Renthal, N. E., Williams, K. C., Montalbano, A. P., Chen, C.-C., Gao, L., Mendelson, C. R. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Microcircuits in Epilepsy: Heterogeneity and Hub Cells in Network Synchronization
Epilepsy is a complex disorder involving neurological alterations that lead to the pathological development of spontaneous, recurrent seizures. For decades, seizures were thought to be largely repetitive, and had been examined at the macrocircuit level using electrophysiological recordings. However, research mapping the dynamics of large neuronal populations has revealed that seizures are not simply recurrent bursts of hypersynchrony. Instead, it is becoming clear that seizures involve a complex interplay of different neurons and circuits. Herein, we will review studies examining microcircuit changes that may underlie netw...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Bui, A., Kim, H. K., Maroso, M., Soltesz, I. Tags: Epilepsy: The Biology of a Spectrum Disorder PERSPECTIVES Source Type: research

[PERSPECTIVES] Single-Gene Determinants of Epilepsy Comorbidity
Common somatic conditions are bound to occur by chance in individuals with neurological disorders as prevalent as epilepsy, but when biological links underlying the comorbidity can be uncovered, the relationship may provide clues into the origin and mechanisms of both. The expanding list of monogenic epilepsies and their associated clinical features offer a remarkable opportunity to mine the epilepsy genome for coordinate neurodevelopmental phenotypes and examine their pathogenic mechanisms. Defined single-gene-linked epilepsy syndromes identified to date include all of the most frequently cited comorbidities, such as cogn...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Noebels, J. L. Tags: Epilepsy: The Biology of a Spectrum Disorder PERSPECTIVES Source Type: research

[PERSPECTIVES] Hepatitis D Virus Replication
This work reviews specific related aspects of hepatitis delta virus (HDV) reproduction, including virion structure, the RNA genome, the mode of genome replication, the delta antigens, and the assembly of HDV using the envelope proteins of its helper virus, hepatitis B virus (HBV). These topics are considered with perspectives ranging from a history of discovery through to still-unsolved problems. HDV evolution, virus entry, and associated pathogenic potential and treatment of infections are considered in other articles in this collection. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Taylor, J. M. Tags: The Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] Mouse Models of Hepatitis B Virus Pathogenesis
The host range of hepatitis B virus (HBV) is limited to humans and chimpanzees. As discussed in the literature, numerous studies in humans and chimpanzees have generated a great deal of information on the mechanisms that cause viral clearance, viral persistence, and disease pathogenesis during acute or chronic HBV infection. Relevant pathogenetic studies have also been performed in those few species representing natural hosts of hepadnaviruses that are related to HBV, such as the woodchuck hepatitis virus and the duck hepatitis virus. Further insight has been gained from multidisciplinary studies in transgenic or humanized...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Iannacone, M., Guidotti, L. G. Tags: The Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] Inventorship and Authorship
Ownership of a U.S. patent is based on inventorship. In the United States, an inventor is the owner of the claimed invention unless it is assigned to another entity. The correct naming of inventors is important, and the improper naming of inventors in a patent can be grounds for rendering the patent unenforceable. Each inventor must make an intellectual contribution, solely or jointly, to at least one element of a claim in the patent. This is in contrast to authorship of a research article, where authors may be named to acknowledge contribution to the reported research rather than an intellectual contribution. Thus, identi...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Konski, A. F., Wu, L. X. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Tuberculosis Comorbidity with Communicable and Noncommunicable Diseases
The 18th WHO Global Tuberculosis Annual Report indicates that there were an estimated 8.6 million incident cases of tuberculosis (TB) in 2012, which included 2.9 million women and 530,000 children. TB caused 1.3 million deaths including 320,000 human immunodeficiency virus (HIV)-infected people; three-quarters of deaths occurred in Africa and Southeast Asia. With one-third of the world’s population latently infected with Mycobacterium tuberculosis (Mtb), active TB disease is primarily associated with a break down in immune surveillance. This explains the strong link between active TB disease and other communicable di...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Bates, M., Marais, B. J., Zumla, A. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Diagnosis and Management of Latent Tuberculosis Infection
The post-2015 World Health Organization global tuberculosis strategy recognizes that elimination requires a focus on reducing the pool of latently infected individuals, an estimated 30% of the global population, from which future tuberculosis cases would be generated. Tackling latent tuberculosis infection requires the identification and treatment of asymptomatic individuals to reduce the risk of progression to active disease. Diagnosis of latent tuberculosis infection is based on the detection of an immune response to Mycobacterium tuberculosis antigens using either the tuberculin skin test or interferon- release assays. ...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2015 Category: Research Authors: Munoz, L., Stagg, H. R., Abubakar, I. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] DNA Damage, DNA Repair, Aging, and Neurodegeneration
Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Maynard, S., Fang, E. F., Scheibye-Knudsen, M., Croteau, D. L., Bohr, V. A. Tags: Aging PERSPECTIVES Source Type: research

[PERSPECTIVES] Molecular Mechanisms of Preeclampsia
Preeclampsia is a pregnancy-specific disease characterized by new onset hypertension and proteinuria after 20 wk of gestation. It is a leading cause of maternal and fetal morbidity and mortality worldwide. Exciting discoveries in the last decade have contributed to a better understanding of the molecular basis of this disease. Epidemiological, experimental, and therapeutic studies from several laboratories have provided compelling evidence that an antiangiogenic state owing to alterations in circulating angiogenic factors leads to preeclampsia. In this review, we highlight the role of key circulating antiangiogenic factors...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Hod, T., Cerdeira, A. S., Karumanchi, S. A. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Genome-Wide Sequencing for Prenatal Detection of Fetal Single-Gene Disorders
New sequencing methods capable of rapidly analyzing the genome at increasing resolution have transformed diagnosis of single-gene or oligogenic genetic disorders in pediatric and adult medicine. Targeted tests, consisting of disease-focused multigene panels and diagnostic exome sequencing to interrogate the sequence of the coding regions of nearly all genes, are now clinically offered when there is suspicion for an undiagnosed genetic disorder or cancer in children and adults. Implementation of diagnostic exome and genome sequencing tests on invasively and noninvasively obtained fetal DNA samples for prenatal genetic diagn...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Van den Veyver, I. B., Eng, C. M. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Epileptogenesis
Epileptogenesis is a chronic process that can be triggered by genetic or acquired factors, and that can continue long after epilepsy diagnosis. In 2015, epileptogenesis is not a treatment indication, and there are no therapies available in clinic to treat individuals at risk of epileptogenesis. However, thanks to active research, a large number of animal models have become available for search of molecular mechanisms of epileptogenesis. The first glimpses of treatment targets and biomarkers that could be developed to become useful in clinic are in sight. However, the heterogeneity of the epilepsy condition, and the dynamic...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Pitkanen, A., Lukasiuk, K., Dudek, F. E., Staley, K. J. Tags: Epilepsy: The Biology of a Spectrum Disorder PERSPECTIVES Source Type: research

[PERSPECTIVES] Mechanisms Responsible for Cognitive Impairment in Epilepsy
Epilepsy is often associated with cognitive and behavioral impairments that can have profound impact on the quality of life of patients. Although the mechanisms of cognitive impairment are not completely understood, we make an attempt to describe, from a systems perspective, how information processing is affected in epilepsy disorders. The aim of this review is to (1) define the nature of cognitive deficits associated with epilepsy, (2) review fundamental systems-level mechanisms underlying information processing, and (3) describe how information processing is dysfunctional in epilepsy and investigate the relative contribu...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Lenck-Santini, P.-P., Scott, R. C. Tags: Epilepsy: The Biology of a Spectrum Disorder PERSPECTIVES Source Type: research

[PERSPECTIVES] Therapy of Delta Hepatitis
Delta hepatitis is the less frequently encountered but most severe form of viral hepatitis. Acute delta hepatitis, as a result of coinfection with hepatitis B and hepatitis delta, is rare, but may lead to fulminant hepatitis, and no therapy exists for this form. Chronic delta hepatitis (CDH) mostly develops as a result of superinfection of a hepatitis B surface antigen (HBsAg) carrier with hepatitis delta virus (HDV). In general, HDV is the dominant virus. However, a dynamic shift of the dominant virus may occur with time in rare instances, and hepatitis B virus (HBV) may become the dominant virus, at which time nucleos(t)...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Yurdaydin, C., Idilman, R. Tags: The Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] Host-Directed Therapies for Tuberculosis
Host-directed therapies are a relatively new and promising approach to treatment of tuberculosis. Modulation of specific host immune pathways, including those that impact inflammation and immunopathology, can limit mycobacterial infection and pathology, both in cell culture and in animal models. This review explores a range of host pathways and drugs, some already approved for clinical use that have the potential to provide new adjunctive therapies for tuberculosis. Drugs targeting host processes may largely avoid the development of bacterial antibiotic resistance, a major public health concern for tuberculosis. However, t...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Tobin, D. M. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Mycobacterial Growth
In this work, we review progress made in understanding the molecular underpinnings of growth and division in mycobacteria, concentrating on work published since the last comprehensive review ( Hett and Rubin 2008). We have focused on exciting work making use of new time-lapse imaging technologies coupled with reporter-gene fusions and antimicrobial treatment to generate insights into how mycobacteria grow and divide in a heterogeneous manner. We try to reconcile the different observations reported, providing a model of how they might fit together. We also review the topic of mycobacterial spores, which has generated consid...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Uhia, I., Williams, K. J., Shahrezaei, V., Robertson, B. D. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Protecting Traditional Knowledge Related to Biological Resources: Is Scientific Research Going to Become More Bureaucratized?
For the past several decades, there has been a world debate on the need for protecting traditional knowledge. A global treaty appears to be a distant reality. Of more immediate concern are the steps taken by the global community to protect access to biological resources in the name of protecting traditional knowledge. The Indian experience with implementing the Convention on Biological Diversity has created substantial legal uncertainty in collaborative scientific research between Indians and foreigners apart from bureaucratizing the entire process of scientific research, especially with regard to filing of applications fo...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Reddy, P., Lakshmikumaran, M. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] The Patentability of Stem Cells in Australia
The potential therapeutic applications of stem cells are unlimited. However, the ongoing political and social debate surrounding the intellectual property and patenting considerations of stem cell research has led to the implementation of strict legislative regulations. In Australia the patent landscape surrounding stem cells has evolved considerably over the past 20 years. The Australian Patents Act 1990 includes a specific exclusion to the patentability of human beings and of biological processes for their generation. However, this exclusion has received no judicial consideration to date, and so its scope and potential i...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Petering, J., Cowin, P. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PROSPECTIVE] What Is Next for Retinal Gene Therapy?
The field of gene therapy for retinal blinding disorders is experiencing incredible momentum, justified by hopeful results in early stage clinical trials for inherited retinal degenerations. The premise of the use of the gene as a drug has come a long way, and may have found its niche in the treatment of retinal disease. Indeed, with only limited treatment options available for retinal indications, gene therapy has been proven feasible, safe, and effective and may lead to durable effects following a single injection. Here, we aim at putting into context the promise and potential, the technical, clinical, and economic bound...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Vandenberghe, L. H. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PROSPECTIVE Source Type: research

[PERSPECTIVES] Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa
Retinitis pigmentosa (RP) has a prevalence of approximately one in 4000; 25%–30% of these cases are autosomal dominant retinitis pigmentosa (adRP). Like other forms of inherited retinal disease, adRP is exceptionally heterogeneous. Mutations in more than 25 genes are known to cause adRP, more than 1000 mutations have been reported in these genes, clinical findings are highly variable, and there is considerable overlap with other types of inherited disease. Currently, it is possible to detect disease-causing mutations in 50%–75% of adRP families in select populations. Genetic diagnosis of adRP has advantages ove...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2015 Category: Research Authors: Daiger, S. P., Bowne, S. J., Sullivan, L. S. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] The Aging Heart
This article will provide an overview of the phenotypic changes of cardiac aging, the molecular mechanisms underlying these changes, and will present some of the recent advances in the development of interventions to delay or reverse cardiac aging. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: Chiao, Y. A., Rabinovitch, P. S. Tags: Aging PERSPECTIVES Source Type: research

[PERSPECTIVES] Protecting Trade Secrets in Canada
Patents in the life sciences industries are a key form of intellectual property (IP), particularly for products such as brand-name drugs and medical devices. However, trade secrets can also be a useful tool for many types of innovations. In appropriate cases, trade secrets can offer long-term protection of IP for a lower financial cost than patenting. This type of protection must be approached with caution as there is little room for error when protecting a trade secret. Strong agreements and scrupulous security can help to protect the secret. Once a trade secret is disclosed to the public, it cannot be restored as the own...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: Courage, N., Calzavara, J. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Noninvasive Prenatal Screening for Genetic Diseases Using Massively Parallel Sequencing of Maternal Plasma DNA
The identification of cell-free fetal DNA (cffDNA) in maternal plasma in 1997 heralded the most significant change in obstetric care for decades, with the advent of safer screening and diagnosis based on analysis of maternal blood. Here, we describe how the technological advances offered by next-generation sequencing have allowed for the development of a highly sensitive screening test for aneuploidies as well as definitive prenatal molecular diagnosis for some monogenic disorders. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: Chitty, L. S., Lo, Y. M. D. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] MicroRNA in Ovarian Biology and Disease
MicroRNAs (miRNAs) are posttranscriptional gene regulatory molecules that show regulated expression within ovarian tissue. Most research investigating miRNAs in the ovary has relied exclusively on in vitro analyses. In this review, we highlight those few studies in which investigators have illustrated an in vivo effect of miRNAs on ovarian function. We also provide a synopsis of how these small noncoding RNAs can impact ovarian disease. miRNAs have great potential as novel diagnostic biomarkers for the detection of ovarian disease and in the assisted reproductive technologies (ART) for selection of healthy viable oocytes a...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: McGinnis, L. K., Luense, L. J., Christenson, L. K. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Epilepsy: A Spectrum Disorder
Epilepsy, a disorder of unprovoked seizures is a multifaceted disease affecting individuals of all ages with a particular predilection for the very young and old. In addition to seizures, many patients often report cognitive and psychiatric problems associated with both the seizures themselves and its therapy. Epilepsy has numerous etiologies both idiopathic and acquired with a wide range of therapeutic responses. Despite numerous treatments available to control repetitive seizures including medications, diets, immunotherapy, surgery, and neuromodulatory devices, a large percentage of patients continue to suffer the conseq...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: Sirven, J. I. Tags: Epilepsy: The Biology of a Spectrum Disorder PERSPECTIVES Source Type: research

[PERSPECTIVES] Treatment of Liver Cancer
Primary liver cancer, mostly hepatocellular carcinoma, remains a difficult-to-treat cancer. Incidence of liver cancer varies geographically and parallels with the geographic prevalence of viral hepatitis. A number of staging systems have been developed, reflecting the heterogeneity of primary liver cancer, regional preferences, and regional variations in resectability or transplant eligibility. Multimodality treatments are available for this heterogeneous malignancy, and there are variations in the management recommendations for liver cancers across specialties and geographic regions. Novel treatment strategies have merged...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: Liu, C.-Y., Chen, K.-F., Chen, P.-J. Tags: The Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] Impact of America Invents Act on Biotech Intellectual Property
This article addresses changes that the AIA brings to U.S. patent law, keeping an eye toward issues relevant to biotech companies. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: Murphy, A., Stramiello, M., Stroud, J., Lewis, S., Irving, T. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Evolutionary Perspectives on Human Fungal Pathogens
Owing to their small size and paucity of phenotypic characters, progress in the evolutionary biology of microbes in general, and human pathogenic fungi in particular, has been linked to a series of advances in DNA sequencing over the past quarter century. Phylogenetics was the first area to benefit, with the achievement of a basic understanding of fungal phylogeny. Population genetics was the next advance, finding cryptic species everywhere, and recombination in species previously thought to be asexual. Comparative genomics saw the next advance, in which variation in gene content and changes in gene family size were found ...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: Taylor, J. W. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Immunity and Immunopathology in the Tuberculous Granuloma
Granulomas, organized aggregates of immune cells, are a defining feature of tuberculosis (TB). Granuloma formation is implicated in the pathogenesis of a variety of inflammatory disorders. However, the tuberculous granuloma has been assigned the role of a host protective structure which "walls-off" mycobacteria. Work conducted over the past decade has provided a more nuanced view of its role in pathogenesis. On the one hand, pathogenic mycobacteria accelerate and exploit granuloma formation for their expansion and dissemination by manipulating host immune responses to turn leukocyte recruitment and cell death pat...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: Pagan, A. J., Ramakrishnan, L. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Multidrug-Resistant Tuberculosis and Extensively Drug-Resistant Tuberculosis
The continuing spread of drug-resistant tuberculosis (TB) is one of the most urgent and difficult challenges facing global TB control. Patients who are infected with strains resistant to isoniazid and rifampicin, called multidrug-resistant (MDR) TB, are practically incurable by standard first-line treatment. In 2012, there were approximately 450,000 new cases and 170,000 deaths because of MDR-TB. Extensively drug-resistant (XDR) TB refers to MDR-TB strains that are resistant to fluoroquinolones and second-line injectable drugs. The main causes of the spread of resistant TB are weak medical systems, amplification of resista...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: Seung, K. J., Keshavjee, S., Rich, M. L. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] The Status of RPE65 Gene Therapy Trials: Safety and Efficacy
Several groups have reported the results of clinical trials of gene augmentation therapy for Leber congenital amaurosis (LCA) because of mutations in the RPE65 gene. These studies have used subretinal injection of adeno-associated virus (AAV) vectors to deliver the human RPE65 cDNA to the retinal pigment epithelial (RPE) cells of the treated eyes. In all of the studies reported to date, this approach has been shown to be both safe and effective. The successful clinical trials of gene augmentation therapy for retinal degeneration caused by mutations in the RPE65 gene sets the stage for broad application of gene therapy to t...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: Pierce, E. A., Bennett, J. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] RNA-Seq: Improving Our Understanding of Retinal Biology and Disease
Over the past several years, rapid technological advances have allowed for a dramatic increase in our knowledge and understanding of the transcriptional landscape, because of the ability to study gene expression in greater depth and with more detail than previously possible. To this end, RNA-Seq has quickly become one of the most widely used methods for studying transcriptomes of tissues and individual cells. Unlike previously favored analysis methods, RNA-Seq is extremely high-throughput, and is not dependent on an annotated transcriptome, laying the foundation for novel genetic discovery. Additionally, RNA-Seq derived tr...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2015 Category: Research Authors: Farkas, M. H., Au, E. D., Sousa, M. E., Pierce, E. A. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Confrontation, Consolidation, and Recognition: The Oocyte's Perspective on the Incoming Sperm
From the oocyte’s perspective, the incoming sperm poses a significant challenge. Despite (usually) arising from a male of the same species, the sperm is a "foreign" body that may carry with it additional, undesirable factors such as transposable elements (mainly retroposons) into the egg. These factors can arise either during spermatogenesis or while the sperm is moving through the epididymis or the female genital tract. Furthermore, in addition to the paternal genome, the sperm also carries its own complex repertoire of RNAs into the egg that includes mRNAs, lncRNAs, and sncRNAs. Last, the paternal genome ...
Source: Cold Spring Harbor perspectives in medicine - August 3, 2015 Category: Research Authors: Miller, D. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] The Function of TrophomiRs and Other MicroRNAs in the Human Placenta
In eutherian organisms, the placenta interfaces the fetal and maternal environments. Located at the placental villous surface, in direct contact with maternal blood, is the trophoblast layer, which mediates the crucial maternal–fetal exchange of gases, nutrients, and waste products, produces hormones that support the pregnancy, and provides immunologic defense. Discovery of microRNAs (miRNAs) and their role in development, differentiation, and homeostatic resilience has increased our understanding of genomic and epigenomic networks that regulate placental function. Moreover, unique miRNA species, which are expressed ...
Source: Cold Spring Harbor perspectives in medicine - August 3, 2015 Category: Research Authors: Sadovsky, Y., Mouillet, J.-F., Ouyang, Y., Bayer, A., Coyne, C. B. Tags: Molecular Approaches to Reproductive and Newborn Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Glutamatergic Mechanisms Associated with Seizures and Epilepsy
Epilepsy is broadly characterized by aberrant neuronal excitability. Glutamate is the predominant excitatory neurotransmitter in the adult mammalian brain; thus, much of past epilepsy research has attempted to understand the role of glutamate in seizures and epilepsy. Seizures induce elevations in extracellular glutamate, which then contribute to excitotoxic damage. Chronic seizures can alter neuronal and glial expression of glutamate receptors and uptake transporters, further contributing to epileptogenesis. Evidence points to a shared glutamate pathology for epilepsy and other central nervous system (CNS) disorders, incl...
Source: Cold Spring Harbor perspectives in medicine - August 3, 2015 Category: Research Authors: Barker-Haliski, M., White, H. S. Tags: Epilepsy: The Biology of a Spectrum Disorder PERSPECTIVES Source Type: research

[PERSPECTIVES] Immune Response in Hepatitis B Virus Infection
Hepatitis B virus (HBV) can replicate within hepatocytes without causing direct cell damage. The host immune response is, therefore, not only essential to control the spread of virus infection, but it is also responsible for the inflammatory events causing liver pathologies. In this review, we discuss how HBV deals with host immunity and how we can harness it to achieve virus control and suppress liver damage. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - August 3, 2015 Category: Research Authors: Tan, A., Koh, S., Bertoletti, A. Tags: The Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[PERSPECTIVES] Hepatitis B Virus and Hepatitis D Virus Entry, Species Specificity, and Tissue Tropism
Entry of hepatitis B (HBV) and hepatitis D viruses (HDV) into a host cell represents the initial step of infection. This process requires multiple steps, including the low-affinity attachment of the virus to the cell surface, followed by high-affinity attachment to specific receptor(s), and subsequent endocytosis-mediated internalization. Within the viral envelope, the preS1 region is involved in receptor binding. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as an entry receptor of HBV and HDV by affinity purification using a preS1 peptide. NTCP is mainly or exclusively expressed in t...
Source: Cold Spring Harbor perspectives in medicine - August 3, 2015 Category: Research Authors: Watashi, K., Wakita, T. Tags: The Hepatitis B and Delta Viruses PERSPECTIVES Source Type: research

[RETROSPECTIVE] Tuberculosis Drug Development: History and Evolution of the Mechanism-Based Paradigm
Modern tuberculosis (TB) chemotherapy is widely viewed as a crowning triumph of anti-infectives research. However, only one new TB drug has entered clinical practice in the past 40 years while drug resistance threatens to further destabilize the pandemic. Here, we review a brief history of TB drug development, focusing on the evolution of mechanism(s)-of-action studies and key conceptual barriers to rational, mechanism-based drugs. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - August 3, 2015 Category: Research Authors: Chakraborty, S., Rhee, K. Y. Tags: Tuberculosis RETROSPECTIVE Source Type: research

[PERSPECTIVES] The Mycobacterial Cell Wall--Peptidoglycan and Arabinogalactan
The mycobacterial bacillus is encompassed by a remarkably elaborate cell wall structure. The mycolyl-arabinogalactan-peptidoglycan (mAGP) complex is essential for the viability of Mycobacterium tuberculosis and maintains a robust basal structure supporting the upper "myco-membrane." M. tuberculosis peptidoglycan, although appearing to be unexceptional at first glance, contains a number of unique molecular subtleties that become particularly important as the TB-bacilli enters into nonreplicative growth during dormancy. Arabinogalactan, a highly branched polysaccharide, serves to connect peptidoglycan with the oute...
Source: Cold Spring Harbor perspectives in medicine - August 3, 2015 Category: Research Authors: Alderwick, L. J., Harrison, J., Lloyd, G. S., Birch, H. L. Tags: Tuberculosis PERSPECTIVES Source Type: research

[PERSPECTIVES] Inherent Anticipation in the Pharmaceutical and Biotechnology Industries
Pharmaceutical and biotech research often involves discovering new properties of, or new methods to use, existing compositions. The doctrine of inherent anticipation, however, prevents the issuance and/or validity of a patent for discoveries deemed to have been implicitly disclosed in the prior art. This can be a barrier to patent rights in these technologies. Inherent anticipation therefore creates uncertainty for patent protection in the pharmaceutical and biotech sciences. Despite this uncertainty, Federal Circuit jurisprudence provides guidance on the boundaries of the inherent anticipation doctrine. In view of the cas...
Source: Cold Spring Harbor perspectives in medicine - August 3, 2015 Category: Research Authors: Goldman, M., Evans, G., Zappia, A. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Introduction to Intellectual Property: A U.S. Perspective
This review introduces patents and trade secrets, the two mechanisms that U.S. law provides inventors to protect their inventions. These mechanisms are mutually exclusive: One demands disclosure and the other calls for concealment. Many biotechnology innovators opt for patents, which grant legal, time-limited monopolies to eligible inventions. To obtain a patent in the United States, an invention must be useful to the public and made or altered by the hand of man. It must then clear the hurdles of novelty and nonobviousness. If an invention can do that, obtaining a patent becomes a matter of form: Who qualifies as an inven...
Source: Cold Spring Harbor perspectives in medicine - August 3, 2015 Category: Research Authors: Murphy, A., Stramiello, M., Lewis, S., Irving, T. Tags: Intellectual Property in Molecular Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Thermally Dimorphic Human Fungal Pathogens--Polyphyletic Pathogens with a Convergent Pathogenicity Trait
Fungi are adept at changing their cell shape and developmental program in response to signals in their surroundings. Here we focus on a group of evolutionarily related fungal pathogens of humans known as the thermally dimorphic fungi. These organisms grow in a hyphal form in the environment but shift their morphology drastically within a mammalian host. Temperature is one of the main host signals that initiates their conversion to the "host" form and is sufficient in the laboratory to trigger establishment of this host-adapted developmental program. Here we discuss the major human pathogens in this group, which a...
Source: Cold Spring Harbor perspectives in medicine - August 3, 2015 Category: Research Authors: Sil, A., Andrianopoulos, A. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research

[PERSPECTIVES] Black Molds and Melanized Yeasts Pathogenic to Humans
A review is given of melanized fungi involved in human infection, including species forming budding cells and strictly filamentous representatives. Classically, they are known as "phaeoid" or "dematiaceous" fungi, and, today, agents are recognized to belong to seven orders of fungi, of which the Chaetothyriales and Pleosporales are the most important. Infections range from cutaneous or pulmonary colonization to systemic or disseminated invasion. Subcutaneous involvement, either primary or after dissemination, may lead to host tissue proliferation of dermis or epidermis. Particularly in the Chaetothyrial...
Source: Cold Spring Harbor perspectives in medicine - August 3, 2015 Category: Research Authors: Chowdhary, A., Perfect, J., de Hoog, G. S. Tags: Human Fungal Pathogens PERSPECTIVES Source Type: research