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Journal Cover F1000Research
  [SJR: 0.219]   [H-I: 3]   [4 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • Up in the air: Untethered Factors of Auxin Response [version 1; referees:
           5 approved]

    • Authors: Samantha K. Powers, Lucia C. Strader
      Abstract: As a prominent regulator of plant growth and development, the hormone auxin plays an essential role in controlling cell division and expansion. Auxin-responsive gene transcription is mediated through the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX (TIR1/AFB) pathway. Roles for TIR1/AFB pathway components in auxin response are understood best, but additional factors implicated in auxin responses require more study. The function of these factors, including S-Phase Kinase-Associated Protein 2A (SKP2A), SMALL AUXIN UP RNAs (SAURs), INDOLE 3-BUTYRIC ACID RESPONSE5 (IBR5), and AUXIN BINDING PROTEIN1 (ABP1), has remained largely obscure. Recent advances have begun to clarify roles for these factors in auxin response while also raising additional questions to be answered.
      PubDate: 2016-02-03T15:58:54Z
      DOI: 10.12688/f1000research.7492.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding hepatitis C [version 1; referees: 2

    • Authors: Florian Douam, Qiang Ding, Alexander Ploss
      Abstract: The past decade has seen tremendous progress in understanding hepatitis C virus (HCV) biology and its related disease, hepatitis C. Major advances in characterizing viral replication have led to the development of direct-acting anti-viral therapies that have considerably improved patient treatment outcome and can even cure chronic infection. However, the high cost of these treatments, their low barrier to viral resistance, and their inability to prevent HCV-induced liver cancer, along with the absence of an effective HCV vaccine, all underscore the need for continued efforts to understand the biology of this virus. Moreover, beyond informing therapies, enhanced knowledge of HCV biology is itself extremely valuable for understanding the biology of related viruses, such as dengue virus, which is becoming a growing global health concern. Major advances have been realized over the last few years in HCV biology and pathogenesis, such as the discovery of the envelope glycoprotein E2 core structure, the generation of the first mouse model with inheritable susceptibility to HCV, and the characterization of virus-host interactions that regulate viral replication or innate immunity. Here, we review the recent findings that have significantly advanced our understanding of HCV and highlight the major challenges that remain.
      PubDate: 2016-02-03T11:30:45Z
      DOI: 10.12688/f1000research.7354.1
      Issue No: Vol. 5 (2016)
  • Catalysts of plant cell wall loosening [version 1; referees: 2 approved]

    • Authors: Daniel J. Cosgrove
      Abstract: The growing cell wall in plants has conflicting requirements to be strong enough to withstand the high tensile forces generated by cell turgor pressure while selectively yielding to those forces to induce wall stress relaxation, leading to water uptake and polymer movements underlying cell wall expansion. In this article, I review emerging concepts of plant primary cell wall structure, the nature of wall extensibility and the action of expansins, family-9 and -12 endoglucanases, family-16 xyloglucan endotransglycosylase/hydrolase (XTH), and pectin methylesterases, and offer a critical assessment of their wall-loosening activity
      PubDate: 2016-01-29T16:00:30Z
      DOI: 10.12688/f1000research.7180.1
      Issue No: Vol. 5 (2016)
  • Recent Advances in the Diagnosis and Treatment of Clostridium Difficile
           Infection [version 1; referees: 3 approved]

    • Authors: Meera B. Avila, Nathaniel P. Avila, Andrew W. Dupont
      Abstract: Clostridium difficile infection (CDI) has become the most frequently reported health care-associated infection in the United States [1]. As the incidence of CDI rises, so too does the burden it produces on health care and society. In an attempt to decrease the burden of CDI and provide the best outcomes for patients affected by CDI, there have been many recent advancements in the understanding, diagnosis, and management of CDI. In this article, we review the current recommendations regarding CDI testing and treatment strategies.
      PubDate: 2016-01-29T15:21:54Z
      DOI: 10.12688/f1000research.7109.1
      Issue No: Vol. 5 (2016)
  • Dietary restriction with and without caloric restriction for healthy aging
           [version 1; referees: 3 approved]

    • Authors: Changhan Lee, Valter Longo
      Abstract: Caloric restriction is the most effective and reproducible dietary intervention known to regulate aging and increase the healthy lifespan in various model organisms, ranging from the unicellular yeast to worms, flies, rodents, and primates. However, caloric restriction, which in most cases entails a 20–40% reduction of food consumption relative to normal intake, is a severe intervention that results in both beneficial and detrimental effects. Specific types of chronic, intermittent, or periodic dietary restrictions without chronic caloric restriction have instead the potential to provide a significant healthspan increase while minimizing adverse effects. Improved periodic or targeted dietary restriction regimens that uncouple the challenge of food deprivation from the beneficial effects will allow a safe intervention feasible for a major portion of the population. Here we focus on healthspan interventions that are not chronic or do not require calorie restriction.
      PubDate: 2016-01-29T11:05:42Z
      DOI: 10.12688/f1000research.7136.1
      Issue No: Vol. 5 (2016)
  • The critical importance of the fetal hypothalamus-pituitary-adrenal axis
           [version 1; referees: 3 approved]

    • Authors: Charles E. Wood, Maureen Keller-Wood
      Abstract: The fetal hypothalamus-pituitary-adrenal (HPA) axis is at the center of mechanisms controlling fetal readiness for birth, survival after birth and, in several species, determination of the timing of birth. Stereotypical increases in fetal HPA axis activity at the end of gestation are critical for preparing the fetus for successful transition to postnatal life. The fundamental importance in fetal development of the endogenous activation of this endocrine axis at the end of gestation has led to the use of glucocorticoids for reducing neonatal morbidity in premature infants. However, the choice of dose and repetition of treatments has been controversial, raising the possibility that excess glucocorticoid might program an increased incidence of adult disease (e.g., coronary artery disease and diabetes). We make the argument that because of the critical importance of the fetal HPA axis and its interaction with the maternal HPA axis, dysregulation of cortisol plasma concentrations or inappropriate manipulation pharmacologically can have negative consequences at the beginning of extrauterine life and for decades thereafter.
      PubDate: 2016-01-28T16:41:38Z
      DOI: 10.12688/f1000research.7224.1
      Issue No: Vol. 5 (2016)
  • Podocytes [version 1; referees: 2 approved]

    • Authors: Jochen Reiser, Mehmet M. Altintas
      Abstract: Podocytes are highly specialized cells of the kidney glomerulus that wrap around capillaries and that neighbor cells of the Bowman’s capsule. When it comes to glomerular filtration, podocytes play an active role in preventing plasma proteins from entering the urinary ultrafiltrate by providing a barrier comprising filtration slits between foot processes, which in aggregate represent a dynamic network of cellular extensions. Foot processes interdigitate with foot processes from adjacent podocytes and form a network of narrow and rather uniform gaps. The fenestrated endothelial cells retain blood cells but permit passage of small solutes and an overlying basement membrane less permeable to macromolecules, in particular to albumin. The cytoskeletal dynamics and structural plasticity of podocytes as well as the signaling between each of these distinct layers are essential for an efficient glomerular filtration and thus for proper renal function. The genetic or acquired impairment of podocytes may lead to foot process effacement (podocyte fusion or retraction), a morphological hallmark of proteinuric renal diseases. Here, we briefly discuss aspects of a contemporary view of podocytes in glomerular filtration, the patterns of structural changes in podocytes associated with common glomerular diseases, and the current state of basic and clinical research.
      PubDate: 2016-01-28T12:23:48Z
      DOI: 10.12688/f1000research.7255.1
      Issue No: Vol. 5 (2016)
  • Advances in the endoscopic diagnosis and treatment of Barrett’s
           neoplasia [version 1; referees: 2 approved]

    • Authors: Fergus J.Q. Chedgy, Kesavan Kandiah, Sreedhari Thayalasekaran, Sharmila Subramaniam, Pradeep Bhandari
      Abstract: Barrett’s oesophagus is a well-recognised precursor of oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma is continuing to rise in the Western world with dismal survival rates. In recent years, efforts have been made to diagnose Barrett’s earlier and improve surveillance techniques in order to pick up cancerous changes earlier. Recent advances in endoscopic therapy for early Barrett’s cancers have shifted the paradigm away from oesophagectomy and have yielded excellent results.
      PubDate: 2016-01-28T10:22:15Z
      DOI: 10.12688/f1000research.6996.1
      Issue No: Vol. 5 (2016)
  • Improved Cardiovascular Disease Outcomes in Older Adults [version 1;
           referees: 3 approved]

    • Authors: Daniel E. Forman, Karen Alexander, Ralph G. Brindis, Anne B. Curtis, Mathew Maurer, Michael W. Rich, Laurence Sperling, Nanette K. Wenger
      Abstract: Longevity is increasing and the population of older adults is growing. The biology of aging is conducive to cardiovascular disease (CVD), such that prevalence of coronary artery disease, heart failure, valvular heart disease, arrhythmia and other disorders are increasing as more adults survive into old age.  Furthermore, CVD in older adults is distinctive, with management issues predictably complicated by multimorbidity, polypharmacy, frailty and other complexities of care that increase management risks (e.g., bleeding, falls, and rehospitalization) and uncertainty of outcomes.  In this review, state-of-the-art advances in heart failure, acute coronary syndromes, transcatheter aortic valve replacement, atrial fibrillation, amyloidosis, and CVD prevention are discussed.  Conceptual benefits of treatments are considered in relation to the challenges and ambiguities inherent in their application to older patients.
      PubDate: 2016-01-28T10:03:26Z
      DOI: 10.12688/f1000research.7088.1
      Issue No: Vol. 5 (2016)
  • Structural Mechanisms of Hexameric Helicase Loading, Assembly, and
           Unwinding [version 1; referees: 3 approved]

    • Authors: Michael A. Trakselis
      Abstract: Hexameric helicases control both the initiation and the elongation phase of DNA replication. The toroidal structure of these enzymes provides an inherent challenge in the opening and loading onto DNA at origins, as well as the conformational changes required to exclude one strand from the central channel and activate DNA unwinding. Recently, high-resolution structures have not only revealed the architecture of various hexameric helicases but also detailed the interactions of DNA within the central channel, as well as conformational changes that occur during loading. This structural information coupled with advanced biochemical reconstitutions and biophysical methods have transformed our understanding of the dynamics of both the helicase structure and the DNA interactions required for efficient unwinding at the replisome.
      PubDate: 2016-01-27T17:12:52Z
      DOI: 10.12688/f1000research.7509.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding Type 1 Diabetes [version 1; referees: 2

    • Authors: Gustaf Christoffersson, Teresa Rodriguez-Calvo, Matthias von Herrath
      Abstract: Type 1 diabetes is a multifactorial disease in which genetic and environmental factors play a key role. The triggering event is still obscure, and so are many of the immune events that follow. In this brief review, we discuss the possible role of potential environmental factors and which triggers are believed to have a role in the disease. In addition, as the disease evolves, beta cells are lost and this occurs in a very heterogeneous fashion. Our knowledge of how beta cell mass declines and our view of the disease’s pathogenesis are also debated. We highlight the major hallmarks of disease, among which are MHC-I (major histocompatibility complex class I) expression and insulitis. The dependence versus independence of antigen for the immune infiltrate is also discussed, as both the influence from bystander T cells and the formation of neo-epitopes through post-translational modifications are thought to influence the course of the disease. As human studies are proliferating, our understanding of the disease’s pathogenesis will increase exponentially. This article aims to shed light on some of the burning questions in type 1 diabetes research.
      PubDate: 2016-01-27T14:37:31Z
      DOI: 10.12688/f1000research.7356.1
      Issue No: Vol. 5 (2016)
  • Recent Understandings of Pet Allergies [version 1; referees: 2 approved]

    • Authors: Dennis Ownby, Christine Cole Johnson
      Abstract: Allergic reactions to pets have been recognized for at least a hundred years. Yet our understanding of the effects of all of the interactions between pet exposures and human immune responses continues to grow. Allergists, epidemiologists, and immunologists have spent years trying to better understand how exposures to pet allergens lead to allergic sensitization (the production of allergen-specific immunoglobulin class E [IgE] antibodies) and subsequent allergic disease. A major new development in this understanding is the recognition that pet exposures consist of not only allergen exposures but also changes in microbial exposures. Exposures to certain pet-associated microbes, especially in the neonatal period, appear to be able to dramatically alter how a child’s immune system develops and this in turn reduces the risk of allergic sensitization and disease. An exciting challenge in the next few years will be to see whether these changes can be developed into a realistic preventative strategy with the expectation of significantly reducing allergic disease, especially asthma.
      PubDate: 2016-01-27T10:46:53Z
      DOI: 10.12688/f1000research.7044.1
      Issue No: Vol. 5 (2016)
  • Sequence co-evolutionary information is a natural partner to
           minimally-frustrated models of biomolecular dynamics [version 1; referees:
           3 approved]

    • Authors: Jeffrey K Noel, Faruck Morcos, Jose N Onuchic
      Abstract: Experimentally derived structural constraints have been crucial to the implementation of computational models of biomolecular dynamics. For example, not only does crystallography provide essential starting points for molecular simulations but also high-resolution structures permit for parameterization of simplified models. Since the energy landscapes for proteins and other biomolecules have been shown to be minimally frustrated and therefore funneled, these structure-based models have played a major role in understanding the mechanisms governing folding and many functions of these systems. Structural information, however, may be limited in many interesting cases. Recently, the statistical analysis of residue co-evolution in families of protein sequences has provided a complementary method of discovering residue-residue contact interactions involved in functional configurations. These functional configurations are often transient and difficult to capture experimentally. Thus, co-evolutionary information can be merged with that available for experimentally characterized low free-energy structures, in order to more fully capture the true underlying biomolecular energy landscape.
      PubDate: 2016-01-26T16:33:42Z
      DOI: 10.12688/f1000research.7186.1
      Issue No: Vol. 5 (2016)
  • West Nile Virus Infection in the Central Nervous System [version 1;
           referees: 3 approved]

    • Authors: Evandro R. Winkelmann, Huanle Luo, Tian Wang
      Abstract: West Nile virus (WNV), a neurotropic single-stranded flavivirus has been the leading cause of arboviral encephalitis worldwide.  Up to 50% of WNV convalescent patients in the United States were reported to have long-term neurological sequelae.  Neither antiviral drugs nor vaccines are available for humans.  Animal models have been used to investigate WNV pathogenesis and host immune response in humans.  In this review, we will discuss recent findings from studies in animal models of WNV infection, and provide new insights on WNV pathogenesis and WNV-induced host immunity in the central nervous system.
      PubDate: 2016-01-26T16:05:43Z
      DOI: 10.12688/f1000research.7404.1
      Issue No: Vol. 5 (2016)
  • An update around the evidence base for the lower extremity ultrasound
           regional block technique [version 1; referees: 2 approved]

    • Authors: Andrea Fanelli, Daniela Ghisi, Rita Maria Melotti
      Abstract: Ultrasound guidance currently represents the gold standard for regional anesthesia. In particular for lower extremity blocks, despite the heterogeneity and the lack of large randomized controlled trials, current literature shows a modest improvement in block onset and quality compared with other localization techniques. This review aims to present the most recent findings on the application of ultrasound guidance for each single lower extremity approach.
      PubDate: 2016-01-26T14:06:00Z
      DOI: 10.12688/f1000research.7199.1
      Issue No: Vol. 5 (2016)
  • Renal Replacement Therapy [version 1; referees: 4 approved]

    • Authors: Zaccaria Ricci, Stefano Romagnoli, Claudio Ronco
      Abstract: During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients’ clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the “Tower of Babel” of critical care nephrology.
      PubDate: 2016-01-25T14:22:18Z
      DOI: 10.12688/f1000research.6935.1
      Issue No: Vol. 5 (2016)
  • The underactive bladder: detection and diagnosis [version 1; referees: 2

    • Authors: Nadir Osman, Altaf Mangera, Christopher Hillary, Richard Inman, Christopher Chapple
      Abstract: The inability to generate a voiding contraction sufficient to allow efficient bladder emptying within a reasonable time frame is a common problem seen in urological practice. Typically, the symptoms that arise are voiding symptoms, such as weak and slow urinary flow. These symptoms can cause considerable bother to patients and impact upon quality of life. The urodynamic finding of inadequate detrusor contraction has been termed detrusor underactivity (DUA). Although a definition is available for this entity, there are no widely accepted diagnostic criteria. Drawing parallels to detrusor overactivity and the overactive bladder, the symptoms arising from DUA have been referred to as the “underactive bladder” (UAB), while attempts to crystallize the definition of UAB are now ongoing. In this article, we review the contemporary literature pertaining to the epidemiology and etiopathogenesis of DUA as well as discuss the definitional aspects that are currently under consideration.
      PubDate: 2016-01-25T10:41:16Z
      DOI: 10.12688/f1000research.7344.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding urethral lichen sclerosus [version 1;
           referees: 3 approved]

    • Authors: Altaf Mangera, Nadir Osman, Christopher Chapple
      Abstract: Lichen sclerosus affecting the male genitalia is a poorly understood but potentially devastating condition. The natural history of the condition is beginning to be understood better with longer follow-up of patients. Recent long-term data suggest that circumcision for lichen sclerosus limited to the prepuce may not be curative as was once thought. In addition, surgical treatments should be followed up for longer periods as recurrences may occur after urethroplasty and perineal urethrostomy.
      PubDate: 2016-01-22T11:11:26Z
      DOI: 10.12688/f1000research.7120.1
      Issue No: Vol. 5 (2016)
  • Innovative Applications of Robotic Surgery: Renal Allograft and
           Autologous Transplantation [version 1; referees: 2 approved]

    • Authors: Jason Lee, Michael Ordon
      Abstract: Robotic surgery has enabled surgeons to offer more patients a minimally invasive surgical option in the management of their complex diseases. While renal transplantation is associated with significant improvements in quantity and quality of life for most end-stage renal disease (ESRD) patients, it is also not devoid of its surgical risks and potential morbidities. Robotic-assisted kidney transplantation is a recently described, innovative application of the robotic surgery platform, and early experiences suggest that it is associated with comparable graft function and lower rates of complications. Urinary tract obstruction, though less common than ESRD, can be a serious threat to renal function. Severe ureteric stricture disease can represent a clinically complex problem requiring major reconstructive surgery. Completely intra-corporeal robotic renal auto-transplantation is another innovative application of the robotic surgery platform and represents a significant advancement in urologic surgery. Initial reports of this procedure demonstrate safety, feasibility, and excellent renal function outcomes.
      PubDate: 2016-01-22T10:28:09Z
      DOI: 10.12688/f1000research.7343.1
      Issue No: Vol. 5 (2016)
  • Telomeres and telomerase as therapeutic targets to prevent and treat
           age-related diseases [version 1; referees: 4 approved]

    • Abstract: Telomeres, the protective ends of linear chromosomes, shorten throughout an individual’s lifetime. Telomere shortening is a hallmark of molecular aging and is associated with premature appearance of diseases associated with aging. Here, we discuss the role of telomere shortening as a direct cause for aging and age-related diseases. In particular, we draw attention to the fact that telomere length influences longevity. Furthermore, we discuss intrinsic and environmental factors that can impact on human telomere erosion. Finally, we highlight recent advances in telomerase-based therapeutic strategies for the treatment of diseases associated with extremely short telomeres owing to mutations in telomerase, as well as age-related diseases, and ultimately aging itself.
      PubDate: 2016-01-20T17:19:43Z
      DOI: 10.12688/f1000research.7020.1
      Issue No: Vol. 5 (2016)
  • Can follicular helper T cells be targeted to improve vaccine efficacy?
           [version 1; referees: 3 approved]

    • Authors: Michelle A. Linterman, Danika L. Hill
      Abstract: The success of most vaccines relies on the generation of antibodies to provide protection against subsequent infection; this in turn depends on a robust germinal centre (GC) response that culminates in the production of long-lived antibody-secreting plasma cells. The size and quality of the GC response are directed by a specialised subset of CD4+ T cells: T follicular helper (Tfh) cells. Tfh cells provide growth and differentiation signals to GC B cells and mediate positive selection of high-affinity B cell clones in the GC, thereby determining which B cells exit the GC as plasma cells and memory B cells. Because of their central role in the production of long-lasting humoral immunity, Tfh cells represent an interesting target for rational vaccine design.
      PubDate: 2016-01-20T17:04:34Z
      DOI: 10.12688/f1000research.7388.1
      Issue No: Vol. 5 (2016)
  • Chikungunya: epidemiology [version 1; referees: 2 approved]

    • Authors: Lyle R. Petersen, Ann M. Powers
      Abstract: Chikungunya virus is a mosquito-borne alphavirus that causes fever and debilitating joint pains in humans. Joint pains may last months or years. It is vectored primarily by the tropical and sub-tropical mosquito, Aedes aegypti, but is also found to be transmitted by Aedes albopictus, a mosquito species that can also be found in more temperate climates. In recent years, the virus has risen from relative obscurity to become a global public health menace affecting millions of persons throughout the tropical and sub-tropical world and, as such, has also become a frequent cause of travel-associated febrile illness. In this review, we discuss our current understanding of the biological and sociological underpinnings of its emergence and its future global outlook.
      PubDate: 2016-01-19T16:06:32Z
      DOI: 10.12688/f1000research.7171.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding dengue [version 1; referees: 3 approved]

    • Authors: Sophie Yacoub, Juthathip Mongkolsapaya, Gavin Screaton
      Abstract: Dengue is an emerging threat to billions of people worldwide. In the last 20 years, the incidence has increased four-fold and this trend appears to be continuing. Caused by one of four viral serotypes, dengue can present as a wide range of clinical phenotypes with the severe end of the spectrum being defined by a syndrome of capillary leak, coagulopathy, and organ impairment. The pathogenesis of severe disease is thought to be in part immune mediated, but the exact mechanisms remain to be defined. The current treatment of dengue relies on supportive measures with no licensed therapeutics available to date. There have been recent advances in our understanding of a number of areas of dengue research, of which the following will be discussed in this review: the drivers behind the global dengue pandemic, viral structure and epitope binding, risk factors for severe disease and its pathogenesis, as well as the findings of recent clinical trials including therapeutics and vaccines. We conclude with current and future dengue control measures and key areas for future research.
      PubDate: 2016-01-19T14:47:17Z
      DOI: 10.12688/f1000research.6233.1
      Issue No: Vol. 5 (2016)
  • The cardiac enigma: current conundrums in heart failure research [version
           1; referees: 3 approved]

    • Authors: Michael S. Kapiloff, Craig A. Emter
      Abstract: The prevalence of heart failure is expected to increase almost 50% in the next 15 years because of aging of the general population, an increased frequency of comorbidities, and an improved survival following cardiac events. Conventional treatments for heart failure have remained largely static over the past 20 years, illustrating the pressing need for the discovery of novel therapeutic agents for this patient population. Given the heterogeneous nature of heart failure, it is important to specifically define the cellular mechanisms in the heart that drive the patient’s symptoms, particularly when considering new treatment strategies. This report highlights the latest research efforts, as well as the possible pitfalls, in cardiac disease translational research and discusses future questions and considerations needed to advance the development of new heart failure therapies. In particular, we discuss cardiac remodeling and the translation of animal work to humans and how advancements in our understanding of these concepts relative to disease are central to new discoveries that can improve cardiovascular health.
      PubDate: 2016-01-18T12:09:00Z
      DOI: 10.12688/f1000research.7278.1
      Issue No: Vol. 5 (2016)
  • Prevention of Device-Related Healthcare-Associated Infections [version 1;
           referees: 2 approved]

    • Authors: Edward J. Septimus, Julia Moody
      Abstract: Healthcare-associated infections (HAIs) are a leading cause of morbidity and mortality in hospitalized patients. Up to 15% of patients develop an infection while hospitalized in the United States, which accounts for approximately 1.7 million HAIs, 99,000 deaths annually and over 10 billion dollars in costs per year. A significant percentage of HAIs are preventable using evidenced-based strategies. In terms of device-related HAIs it is estimated that 65-70% of catheter-line associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) are preventable. To prevent CLABSIs a bundle which includes hand hygiene prior to insertion and catheter manipulation, use of chlorhexidene alcohol for site preparation and maintenance, use of maximum barrier for catheter insertion, site selection, removing nonessential lines, disinfect catheter hubs before assessing line, and dressing changes are essential elements of basic practices. To prevent CAUTIs a bundle that includes hand hygiene for insertion and catheter or bag manipulation, inserting catheters for appropriate indications, insert using aseptic technique, remove catheters when no longer needed, maintain a close system keeping bag and tubing below the bladder are the key components of basic practices.
      PubDate: 2016-01-14T15:55:30Z
      DOI: 10.12688/f1000research.7493.1
      Issue No: Vol. 5 (2016)
  • Implications of circadian rhythm and stress in addiction vulnerability
           [version 1; referees: 2 approved]

    • Authors: Darius Becker-Krail, Colleen McClung
      Abstract: In the face of chronic stress, some individuals can maintain normal function while others go on to develop mental illness. Addiction, affecting one in every twelve people in America, is a substance use disorder long associated with stressful life events and disruptions in the sleep/wake cycle. The circadian and stress response systems have evolved to afford adaptability to environmental changes and allow for maintenance of functional stability, or homeostasis. This mini-review will discuss how circadian rhythms and stress individually affect drug response, affect each other, and how their interactions may regulate reward-related behavior. In particular, we will focus on the interactions between the circadian clock and the regulation of glucocorticoids by the hypothalamic-pituitary-adrenal (HPA) axis. Determining how these two systems act on dopaminergic reward circuitry may not only reveal the basis for vulnerability to addiction, but may also illuminate potential therapeutic targets for future investigation.
      PubDate: 2016-01-13T10:23:17Z
      DOI: 10.12688/f1000research.7608.1
      Issue No: Vol. 5 (2016)
  • Perioperative sleep apnea: a real problem or did we invent a new
           disease' [version 1; referees: 2 approved]

    • Authors: Sebastian Zaremba, James E. Mojica, Matthias Eikermann
      Abstract: Depending on the subpopulation, obstructive sleep apnea (OSA) can affect more than 75% of surgical patients. An increasing body of evidence supports the association between OSA  and perioperative complications, but some data indicate important perioperative outcomes do not differ between patients with and without OSA. In this review we will provide an overview of the pathophysiology of sleep apnea and the risk factors for perioperative complications related to sleep apnea. We also discuss a clinical algorithm for the identification and management of OSA patients facing surgery.
      PubDate: 2016-01-11T16:06:37Z
      DOI: 10.12688/f1000research.7218.1
      Issue No: Vol. 5 (2016)
  • Harnessing the protective potential of HIV-1 neutralizing antibodies
           [version 1; referees: 2 approved]

    • Authors: S Abigail Smith, Cynthia A Derdeyn
      Abstract: Recent biological, structural, and technical advances are converging within the HIV-1 vaccine field to harness the power of antibodies for prevention and therapy. Numerous monoclonal antibodies with broad neutralizing activity against diverse HIV-1 isolates have now been identified, revealing at least five sites of vulnerability on the envelope (Env) glycoproteins. While there are practical and technological barriers blocking a clear path from broadly neutralizing antibodies (bNAb) to a protective vaccine, this is not a dead end. Scientists are revisiting old approaches with new technology, cutting new trails through unexplored territory, and paving new roads in the hopes of preventing HIV-1 infection. Other promising avenues to capitalize on the power of bNAbs are also being pursued, such as passive antibody immunotherapy and gene therapy approaches. Moreover, non-neutralizing antibodies have inhibitory activities that could have protective potential, alone or in combination with bNAbs. With a new generation of bNAbs, and a clinical trial that associated antibodies with reduced acquisition, the field is closer than ever to developing strategies to use antibodies against HIV-1.
      PubDate: 2016-01-05T16:42:22Z
      DOI: 10.12688/f1000research.7254.1
      Issue No: Vol. 5 (2016)
  • A pocket guide to electronic laboratory notebooks in the academic life
           sciences [version 1; referees: 3 approved]

    • Authors: Ulrich Dirnagl, Ingo Przesdzing
      Abstract: Every professional doing active research in the life sciences is required to keep a laboratory notebook. However, while science has changed dramatically over the last centuries, laboratory notebooks have remained essentially unchanged since pre-modern science. We argue that the implementation of electronic laboratory notebooks (eLN) in academic research is overdue, and we provide researchers and their institutions with the background and practical knowledge to select and initiate the implementation of an eLN in their laboratories. In addition, we present data from surveying biomedical researchers and technicians regarding which hypothetical features and functionalities they hope to see implemented in an eLN, and which ones they regard as less important. We also present data on acceptance and satisfaction of those who have recently switched from paper laboratory notebook to an eLN.  We thus provide answers to the following questions: What does an electronic laboratory notebook afford a biomedical researcher, what does it require, and how should one go about implementing it'
      PubDate: 2016-01-04T11:07:27Z
      DOI: 10.12688/f1000research.7628.1
      Issue No: Vol. 5 (2016)
  • A three-dimensional model of the human blood-brain barrier to analyse the
           transport of nanoparticles and astrocyte/endothelial interactions [version
           2; referees: 2 approved]

    • Authors: Peddagangannagari Sreekanthreddy, Radka Gromnicova, Heather Davies, James Phillips, Ignacio A. Romero, David Male
      Abstract: The aim of this study was to develop a three-dimensional (3D) model of the human blood-brain barrier in vitro, which mimics the cellular architecture of the CNS and could be used to analyse the delivery of nanoparticles to cells of the CNS. The model includes human astrocytes set in a collagen gel, which is overlaid by a monolayer of human brain endothelium (hCMEC/D3 cell line). The model was characterised by transmission electron microscopy (TEM), immunofluorescence microscopy and flow cytometry. A collagenase digestion method could recover the two cell types separately at 92-96% purity.  Astrocytes grown in the gel matrix do not divide and they have reduced expression of aquaporin-4 and the endothelin receptor, type B compared to two-dimensional cultures, but maintain their expression of glial fibrillary acidic protein. The effects of conditioned media from these astrocytes on the barrier phenotype of the endothelium was compared with media from astrocytes grown conventionally on a two-dimensional (2D) substratum. Both induce the expression of tight junction proteins zonula occludens-1 and claudin-5 in hCMEC/D3 cells, but there was no difference between the induced expression levels by the two media. The model has been used to assess the transport of glucose-coated 4nm gold nanoparticles and for leukocyte migration. TEM was used to trace and quantitate the movement of the nanoparticles across the endothelium and into the astrocytes. This blood-brain barrier model is very suitable for assessing delivery of nanoparticles and larger biomolecules to cells of the CNS, following transport across the endothelium.
      PubDate: 2016-01-21T14:58:41Z
      DOI: 10.12688/f1000research.7142.2
      Issue No: Vol. 4 (2016)
  • The Dutch Techcentre for Life Sciences: Enabling data-intensive life
           science research in the Netherlands [version 2; referees: 1 approved, 2
           approved with reservations]

    • Authors: Lars Eijssen, Chris Evelo, Ruben Kok, Barend Mons, Rob Hooft, and the other founding members of DTL Data (see Acknowledgements)
      Abstract: We describe the Data programme of the Dutch Techcentre for Life Sciences (DTL, DTL is a new national organisation in scientific research that facilitates life scientists with technologies and technological expertise in an era where new projects often are data-intensive, multi-disciplinary, and multi-site. It is run as a lean not-for-profit organisation with research organisations (both academic and industrial) as paying members. The small staff of the organisation undertakes a variety of tasks that are necessary to perform or support modern academic research, but that are not easily undertaken in a purely academic setting. DTL Data takes care of such tasks related to data stewardship, facilitating exchange of knowledge and expertise, and brokering access to e-infrastructure. DTL also represents the Netherlands in ELIXIR, the European infrastructure for life science data. The organisation is still being fine-tuned and this will continue over time, as it is crucial for this kind of organisation to adapt to a constantly changing environment. However, already being underway for several years, our experiences can benefit researchers in other fields or other countries setting up similar initiatives.
      PubDate: 2016-01-06T15:12:28Z
      DOI: 10.12688/f1000research.6009.2
      Issue No: Vol. 4 (2016)
  • Is MTHFD1 polymorphism rs 2236225 (c.1958G>A) associated with the
           susceptibility of NSCL/P' A systematic review and meta-analysis
           [version 2; referees: 2 approved]

    • Authors: Huaxiang Zhao, Jieni Zhang, Mengqi Zhang, Feng Deng, Leilei Zheng, Hui Zheng, Feng Chen, Jiuxiang Lin
      Abstract: Aims: To investigate the association between the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) polymorphism rs 2236225 (c.1958G>A) and susceptibility to non-syndromic cleft of the lip and/or palate (NSCL/P). Methods: An extensive literature review has been conducted using PubMed, Web of Science, Cochrane Library, Google Scholar, the China National Knowledge Infrastructure (CNKI), and Wanfang Database for eligible researches. The terms for searching were “cleft lip OR cleft palate OR CLP OR CL/P OR oral facial cleft OR OFC” AND “methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 OR methenyltetrahydrofolate cyclohydrolase formyltetrahydrofolate synthetase OR MTHFD1 OR MTHFD”. Two independent researchers screened, evaluated and extracted the data of included studies. The pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated by random effects model under five gene models. Subgroup, sensitivity analysis and publication bias were also assessed. Results: Ten case-control studies have been included in the systematic review and eight studies have been considered for the meta-analysis. Overall, the MTHFD1 polymorphism rs2236225 and the risk of NSCL/P showed pooled OR (95% CI) of 1.02 (0.86-1.21) under allelic model. A higher degree of heterogeneity was observed in Asian countries (I2 = 75.6%) compared to non-Asian countries (I2 = 48.9%). Similar consequence appeared in the subgroup of children (I2 = 78.6%) compared with that of mothers (I2 = 0.0%). There was no significant difference in the publication bias by the Begg’s funnel plot (P = 0.711) and Egger’s regression test (P = 0.746). Conclusion: Our assessment suggested there was no significant association between the MTHFD1 polymorphism rs 2236225 (c.1958G>A) and the susceptibility to NSCL/P. Further investigations using a large sample size and a more advanced technique should be adopted to reach a more precise conclusion in the future.
      PubDate: 2016-01-06T10:52:08Z
      DOI: 10.12688/f1000research.6425.2
      Issue No: Vol. 4 (2016)
  • Differential analyses for RNA-seq: transcript-level estimates improve
           gene-level inferences [version 1; referees: 2 approved]

    • Authors: Charlotte Soneson, Michael I. Love, Mark D. Robinson
      Abstract: High-throughput sequencing of cDNA (RNA-seq) is used extensively to characterize the transcriptome of cells. Many transcriptomic studies aim at comparing either abundance levels or the transcriptome composition between given conditions, and as a first step, the sequencing reads must be used as the basis for abundance quantification of transcriptomic features of interest, such as genes or transcripts. Several different quantification approaches have been proposed, ranging from simple counting of reads that overlap given genomic regions to more complex estimation of underlying transcript abundances. In this paper, we show that gene-level abundance estimates and statistical inference offer advantages over transcript-level analyses, in terms of performance and interpretability. We also illustrate that while the presence of differential isoform usage can lead to inflated false discovery rates in differential expression analyses on simple count matrices and transcript-level abundance estimates improve the performance in simulated data, the difference is relatively minor in several real data sets. Finally, we provide an R package (tximport) to help users integrate transcript-level abundance estimates from common quantification pipelines into count-based statistical inference engines.
      PubDate: 2015-12-30T14:31:20Z
      DOI: 10.12688/f1000research.7563.1
      Issue No: Vol. 4 (2015)
  • CausalTrail: Testing hypothesis using causal Bayesian networks [version 1;
           referees: 2 approved]

    • Abstract: Summary Causal Bayesian Networks are a special class of Bayesian networks in which the hierarchy directly encodes the causal relationships between the variables. This allows to compute the effect of interventions, which are external changes to the system, caused by e.g. gene knockouts or an administered drug. Whereas numerous packages for constructing causal Bayesian networks are available, hardly any program targeted at downstream analysis exists. In this paper we present CausalTrail, a tool for performing reasoning on causal Bayesian networks using the do-calculus. CausalTrail's features include multiple data import methods, a flexible query language for formulating hypotheses, as well as an intuitive graphical user interface. The program is able to account for missing data and thus can be readily applied in multi-omics settings where it is common that not all measurements are performed for all samples. Availability and Implementation CausalTrail is implemented in C++ using the Boost and Qt5 libraries. It can be obtained from
      PubDate: 2015-12-30T12:00:50Z
      DOI: 10.12688/f1000research.7647.1
      Issue No: Vol. 4 (2015)
  • Transcriptome sequencing revealed differences in the response of renal
           cancer cells to hypoxia and CoCl2 treatment [version 1; referees: 2

    • Authors: Nadezhda Zhigalova, Artem Artemov, Alexander Mazur, Egor Prokhortchouk
      Abstract: Human cancer cells are subjected to hypoxic conditions in many tumours. Hypoxia causes alterations in the glycolytic pathway activation through stabilization of hypoxia-inducible factor 1. Currently, two approaches are commonly used to model hypoxia: an alternative to generating low-oxygen conditions in an incubator, cells can be treated with CoCl2. We performed RNA-seq experiments to study transcriptomes of human Caki-1 cells under real hypoxia and after CoCl2 treatment. Despite causing transcriptional changes of a much higher order of magnitude for the genes in the hypoxia regulation pathway, CoCl2 treatment fails to induce alterations in the glycolysis / gluconeogenesis pathway. Moreover, CoCl2 caused aberrant activation of other oxidoreductases in glycine, serine and threonine metabolism pathways.
      PubDate: 2015-12-30T10:38:35Z
      DOI: 10.12688/f1000research.7571.1
      Issue No: Vol. 4 (2015)
  • New tools for a new age: An evolution or revolution in higher
           education' [version 1; referees: 2 approved]

    • Authors: Roslyn Gleadow, Melissa Honeydew, Allie Ford, Bronwyn Isaac, Kirsti Abbott
      Abstract: In this paper we describe how digital technologies can be used to enhance collaboration and student engagement in a large, multicampus undergraduate science unit. Four innovations developed and implemented over a period of eight years are described: use of electronic whiteboards, on-line discussion forums, social media and blogs. In showing the intermediate steps in the evolution of the use of digital and communication technologies, we demonstrate that to be effective, good educational principles are paramount.
      PubDate: 2015-12-23T12:03:23Z
      DOI: 10.12688/f1000research.7533.1
      Issue No: Vol. 4 (2015)
  • Case Report: Postpartum hemorrhage associated with Dengue with warning
           signs in a term pregnancy and delivery [version 1; referees: 2 approved, 1
           not approved]

    • Authors: Le Phi Hung, Tran Diem Nghi, Nguyen Hoang Anh, Mai Van Hieu, Nguyen Thien Luan, Nguyen Phuoc Long, Than Trong Thach
      Abstract: Background: Dengue infection during peripartum period, although rare in endemic regions, has challenged clinicians regarding its management, especially if a parturient woman experiences postpartum hemorrhage due to a classical risk factor of maternal bleeding. Case: A full-term pregnant Vietnamese woman was diagnosed with polyhydramnios and Dengue with warning signs (DWS). She was administered platelet transfusion prior to delivery and then gave birth to a healthy newborn. After active management of the third stage of labor, the patient suffered a postpartum hemorrhage which was caused by uterine atony and accompanied with thrombocytopenia. Therefore, we decided to administer uterotonic drugs and additionally transfuse platelets. Conclusion: We describe a case of postpartum hemorrhage caused by uterine atony and coinciding with Dengue infection during delivery period, which is a rare clinical entity. With timely detection and management, the patient was finally discharged without complications.
      PubDate: 2015-12-21T14:48:16Z
      DOI: 10.12688/f1000research.7589.1
      Issue No: Vol. 4 (2015)
  • Pilot experience with opebacan/rBPI21 in myeloablative hematopoietic cell
           transplantation [version 1; referees: 2 approved]

    • Authors: Eva Guinan, David E Avigan, Robert J Soiffer, Nancy J Bunin, Lisa L Brennan, Ilana Bergelson, Spencer Brightman, Al Ozonoff, Patrick J Scannon, Ofer Levy
      Abstract: Bacterial infection and inflammation contribute significantly to the morbidity and mortality of myeloablative allogeneic hematopoietic cell transplantation (HCT). Endotoxin, a component of the outer membrane of Gram-negative bacteria, is a potent inflammatory stimulus in humans. Bactericidal/permeability increasing protein (BPI), a constituent of human neutrophil granules, binds endotoxin thereby precluding endotoxin-induced inflammation and also has direct anti-infective properties against bacteria. As a consequence of myeloablative therapy used in preparation for hematopoietic cell infusion, patients experience gastrointestinal leak of bacteria and bacterial toxins into the systemic circulation and a period of inflammatory cytokine elevation associated with subsequent regimen-related toxicities.  Patients frequently become endotoxemic and febrile as well as BPI-deficient due to sustained neutropenia. To examine whether enhancing endotoxin-neutralizing and anti-infective activity by exogenous administration of a recombinant N-terminal fragment of BPI (rBPI21, generic name opebacan) might ameliorate regimen-related toxicities including infection, we recruited patients scheduled to undergo myeloablative HCT to participate in a proof-of-concept prospective phase I/II trial. After the HCT preparative regimen was completed, opebacan was initiated 18-36 hours prior to administration of allogeneic hematopoietic stem cells (defined as Day 0) and continued for 72 hours. The trial was to have included escalation of rBPI21 dose and duration but was stopped prematurely due to lack of further drug availability.  Therefore, to better understand the clinical course of opebacan-treated patients (n=6), we compared their outcomes with a comparable cohort meeting the same eligibility criteria and enrolled in a non-interventional myeloablative HCT observational study (n = 35).  Opebacan-treated participants had earlier platelet engraftment (p=0.005), mirroring beneficial effects of rBPI21 previously observed in irradiated mice, fewer documented infections (p=0.03) and appeared less likely to experience significant regimen-related toxicities (p=0.05). This small pilot experience supports the potential utility of rBPI21 in ameliorating HCT-related morbidity and merits further exploration.
      PubDate: 2015-12-21T12:32:21Z
      DOI: 10.12688/f1000research.7558.1
      Issue No: Vol. 4 (2015)
  • Case Report: A case report of unstable Hangman fracture in a eighty year
           old male [version 2; referees: 2 approved, 1 not approved]

    • Authors: Sunil Munakomi, Binod Bhattarai
      Abstract: Herein we discuss a rare variant of hangman’s fracture in an eighty year old male with good Karnofsky performance score. We performed X-ray and magnetic resonance imaging (MRI) of the cervical spine to confirm the diagnosis. The patient was placed on a gentle cervical traction which showed good reduction. Despite being on a resource limited setup,  we performed posterior occipitocervical fusion with bone graft fusion followed by early mobilization. A postoperative scan showed good reduction and purchase of the screws. This case highlights the importance of choosing the correct therapeutic attitude for the management of the geriatric population especially in those who do not have any significant co-morbid conditions.
      PubDate: 2015-12-17T12:58:38Z
      DOI: 10.12688/f1000research.6799.2
      Issue No: Vol. 4 (2015)
  • Variable effects of nicotine, anabasine, and their interactions on
           parasitized bumble bees [version 2; referees: 2 approved]

    • Authors: Lukas P. Thorburn, Lynn S. Adler, Rebecca E. Irwin, Evan C. Palmer-Young
      Abstract: Secondary metabolites in floral nectar have been shown to reduce parasite load in two common bumble bee species. Previous studies on the effects of nectar secondary metabolites on parasitized bees have focused on single compounds in isolation; however, in nature, bees are simultaneously exposed to multiple compounds. We tested for interactions between the effects of two alkaloids found in the nectar of Nicotiana spp. plants, nicotine and anabasine, on parasite load and mortality in bumble bees (Bombus impatiens) infected with the intestinal parasite Crithidia bombi. Adult worker bees inoculated with C. bombi were fed nicotine and anabasine diet treatments in a factorial design, resulting in four nectar treatment combinations:  2 ppm nicotine, 5 ppm anabasine, 2ppm nicotine and 5 ppm anabasine together, or a control alkaloid-free solution. We conducted the experiment twice: first, with bees incubated under variable environmental conditions (‘Variable’; temperatures varied from 10-35°C with ambient lighting); and second, under carefully controlled environmental conditions (‘Stable’; 27°C incubator, constant darkness). In ‘Variable’, each alkaloid alone significantly decreased parasite loads, but this effect was not realized with the alkaloids in combination, suggesting an antagonistic interaction. Nicotine but not anabasine significantly increased mortality, and the two compounds had no interactive effects on mortality. In ‘Stable’, nicotine significantly increased parasite loads, the opposite of its effect in ‘Variable’. While not significant, the relationship between anabasine and parasite loads was also positive. Interactive effects between the two alkaloids on parasite load were non-significant, but the pattern of antagonistic interaction was similar to that in the variable experiment. Neither alkaloid, nor their interaction, significantly affected mortality under controlled conditions. Our results do not indicate synergy between Nicotiana nectar alkaloids; however, they do suggest a complex interaction between secondary metabolites, parasites, and environmental variables, in which secondary metabolites can be either toxic or medicinal depending on context.
      PubDate: 2015-12-16T14:27:18Z
      DOI: 10.12688/f1000research.6870.2
      Issue No: Vol. 4 (2015)
  • BioShaDock: a community driven bioinformatics shared Docker-based tools
           registry [version 1; referees: 2 approved]

    • Abstract: Linux container technologies, as represented by Docker, provide an alternative to complex and time-consuming installation processes needed for scientific software. The ease of deployment and the process isolation they enable, as well as the reproducibility they permit across environments and versions, are among the qualities that make them interesting candidates for the construction of bioinformatic infrastructures, at any scale from single workstations to high throughput computing architectures. The Docker Hub is a public registry which can be used to distribute bioinformatic software as Docker images. However, its lack of curation and its genericity make it difficult for a bioinformatics user to find the most appropriate images needed. BioShaDock is a bioinformatics-focused Docker registry, which provides a local and fully controlled environment to build and publish bioinformatic software as portable Docker images. It provides a number of improvements over the base Docker registry on authentication and permissions management, that enable its integration in existing bioinformatic infrastructures such as computing platforms. The metadata associated with the registered images are domain-centric, including for instance concepts defined in the EDAM ontology, a shared and structured vocabulary of commonly used terms in bioinformatics. The registry also includes user defined tags to facilitate its discovery, as well as a link to the tool description in the ELIXIR registry if it already exists. If it does not, the BioShaDock registry will synchronize with the registry to create a new description in the Elixir registry, based on the BioShaDock entry metadata. This link will help users get more information on the tool such as its EDAM operations, input and output types. This allows integration with the ELIXIR Tools and Data Services Registry, thus providing the appropriate visibility of such images to the bioinformatics community.
      PubDate: 2015-12-14T15:33:28Z
      DOI: 10.12688/f1000research.7536.1
      Issue No: Vol. 4 (2015)
  • The representation of research in the national curriculum and secondary
           school pupils’ perceptions of research, its function, usefulness and
           value to their lives [version 1; referees: 2 approved]

    • Authors: Kay Yeoman, Laura Bowater, Elena Nardi
      Abstract: Young people’s views on research, how it’s conducted and whether it’s important, influences the decisions they make about their further studies and career choices. We investigate how research is represented within the English national curriculum and the examination boards because we recognise that what is being taught influences secondary pupil views on research.  We use questionnaire data to focus particularly on pupil perceptions of research in the sciences and the scientific method. The questionnaire was a 25-item Likert Scale (1-5) distributed to seven collaborating schools. We received 2634 returns from pupils across key stages 3, 4 and 5. We also asked teachers to complete the questionnaire to reflect how they thought their pupils would respond. We received 54 teacher responses. Statistically significant differences in the responses were identified through a chi-square test on SPSS and the interpretive part of our analysis considers how the term ‘research’ appears in the national curriculum for England and Wales and the three main English exam boards. The main theoretical construct that informs our analysis is Angela Brew’s 4-tier descriptor of perceptions of research (domino, trading, layer, journey). We use this framework to map the national curriculum for Science in England to establish the when, what and how research is presented to school pupils in England and Wales. We highlight and discuss certain pupil views on: research as involving the identification of a research question; research as a means to confirm one’s own opinion; research as involving the generation of new knowledge and the collection of new data, such as interviews and questionnaires as well as laboratory work, field trips and library searches. We also discuss pupils’ statements of confidence in their ability to do research, school experiences of research, perceptions of difficulty and importance of research to future career choice.
      PubDate: 2015-12-14T11:41:50Z
      DOI: 10.12688/f1000research.7449.1
      Issue No: Vol. 4 (2015)
  • Case Report: Genetic analysis and anesthetic management of a child with
           Niemann-Pick disease Type A [version 1; referees: 2 approved]

    • Authors: Priti G. Dalal, Melissa Coleman, Meagan Horst, Dorothy Rocourt, Roger L. Ladda, Piotr K. Janicki
      Abstract: A 14-month-old child, recently diagnosed with Niemann-Pick disease type A, presented for a laparoscopic placement of a gastrostomy tube under general anesthesia. The disease was confirmed and further characterized by genetic testing, which revealed evidence of the presence of two known pathogenic mutations in the SMPD1 gene, and enzyme studies showed a corresponding very low level of enzymatic activity of acidic sphingomyelinase. The anesthetic management involved strategies to manage an anticipated difficult intubation and avoid post-operative ventilation.
      PubDate: 2015-12-10T15:52:38Z
      DOI: 10.12688/f1000research.7470.1
      Issue No: Vol. 4 (2015)
  • Optical characterization of epidermal cells and their
           relationship to DNA recovery from touch samples [version 1; referees:
           2 approved]

    • Authors: Cristina E. Stanciu, M. Katherine Philpott, Ye Jin Kwon, Eduardo E. Bustamante, Christopher J. Ehrhardt
      Abstract: The goal of this study was to investigate the relative contributions of different cellular and genetic components to biological samples created by touch or contact with a surface – one of the most challenging forms of forensic evidence. Touch samples were generated by having individuals hold an object for five minutes and analyzed for quantity of intact epidermal cells, extracellular DNA, and DNA from pelleted cell material after elution from the collection swab. Comparisons were made between samples where individuals had washed their hands immediately prior to handling and those where hand washing was not controlled. The vast majority (84-100%) of DNA detected in these touch samples was extracellular and was uncorrelated to the number of epidermal cells detected. Although little to no extracellular or cell pellet-associated DNA was detected when individuals washed their hands prior to substrate handling, we found that a significant number of epidermal cells (between ~5x103 and ~1x105) could still be recovered from these samples, suggesting that other types of biological information may be present even when no amplifiable nuclear DNA is present. These results help to elucidate the biological context for touch samples and characterize factors that may contribute to patterns of transfer and persistence of genetic material in forensic evidence.
      PubDate: 2015-11-26T16:46:23Z
      DOI: 10.12688/f1000research.7385.1
      Issue No: Vol. 4 (2015)
  • A DNA extraction protocol for improved DNA yield from individual
           mosquitoes [version 1; referees: 2 approved]

    • Authors: Catelyn C. Nieman, Youki Yamasaki, Travis C. Collier, Yoosook Lee
      Abstract: Typical DNA extraction protocols from commercially available kits provide an adequate amount of DNA from a single individual mosquito sufficient for PCR-based assays. However, next-generation sequencing applications and high-throughput SNP genotyping assays exposed the limitation of DNA quantity one usually gets from a single individual mosquito. Whole genome amplification could alleviate the issue but it also creates bias in genome representation. While trying to find alternative DNA extraction protocols for improved DNA yield, we found that a combination of the tissue lysis protocol from Life Technologies and the DNA extraction protocol from Qiagen yielded a higher DNA amount than the protocol using the Qiagen or Life Technologies kit only. We have not rigorously tested all the possible combinations of extraction protocols; we also only tested this on mosquito samples. Therefore, our finding should be noted as a suggestion for improving people’s own DNA extraction protocols and not as an advertisement of a commercially available product.
      PubDate: 2015-11-20T16:53:22Z
      DOI: 10.12688/f1000research.7413.1
      Issue No: Vol. 4 (2015)
  • YeATS - a tool suite for analyzing RNA-seq derived transcriptome
           identifies a highly transcribed putative extensin in heartwood/sapwood
           transition zone in black walnut [version 2; referees: 2 approved]

    • Abstract: The transcriptome provides a functional footprint of the genome by enumerating the molecular components of cells and tissues. The field of transcript discovery has been revolutionized through high-throughput mRNA sequencing (RNA-seq). Here, we present a methodology that replicates and improves existing methodologies, and implements a workflow for error estimation and correction followed by genome annotation and transcript abundance estimation for RNA-seq derived transcriptome sequences (YeATS - Yet Another Tool Suite for analyzing RNA-seq derived transcriptome). A unique feature of YeATS is the upfront determination of the errors in the sequencing or transcript assembly process by analyzing open reading frames of transcripts. YeATS identifies transcripts that have not been merged, result in broken open reading frames or contain long repeats as erroneous transcripts. We present the YeATS workflow using a representative sample of the transcriptome from the tissue at the heartwood/sapwood transition zone in black walnut. A novel feature of the transcriptome that emerged from our analysis was the identification of a highly abundant transcript that had no known homologous genes (GenBank accession: KT023102). The amino acid composition of the longest open reading frame of this gene classifies this as a putative extensin. Also, we corroborated the transcriptional abundance of proline-rich proteins, dehydrins, senescence-associated proteins, and the DNAJ family of chaperone proteins. Thus, YeATS presents a workflow for analyzing RNA-seq data with several innovative features that differentiate it from existing software.
      PubDate: 2015-11-06T15:36:36Z
      DOI: 10.12688/f1000research.6617.2
      Issue No: Vol. 4 (2015)
  • Predictors of psychiatric rehospitalization among elderly patients
           [version 1; referees: 2 approved]

    • Authors: Chun Yin Terry Wong
      Abstract: The population of Hong Kong and the proportion of elderly people have been increasing rapidly. The aim of this retrospective cohort study is to determine predictive factors for psychiatric rehospitalization within 2 years among elderly patients who were discharged from psychiatric wards, in attempt to reduce their rehospitalization rate and to reintegrate them into the community. Patients aged 65 and over, who were discharged from psychiatric wards of Pamela Youde Nethersole Eastern Hospital from 1 March 2010 to 29 February 2012, were identified. Rehospitalization within 2 years after discharge was the primary outcome measure, and the time to rehospitalization was measured as the secondary outcome. Patients were subgrouped into readmitted and non-readmitted groups. Logistic regression and Cox regression analyses were applied to the potential predictive factors with odds ratios and hazard ratios obtained, respectively, for the significant findings. Kaplan-Meier survival curves were plotted for graphical representation of the study results in survival analysis. 368 individuals satisfying the study criteria were identified. The same four factors were shown to be significantly associated with rehospitalization in both multiple logistic regression and Cox regression survival analysis. Referral to other psychiatric disciplines upon discharge (p< 0.001, OR=0.325, HR=0.405) was associated with a lower rehospitalization risk and correlated to a longer time to rehospitalization. History of suicidal behaviors (p< 0.001, OR=4.906, HR=3.161), history of violent behaviors (p< 0.001, OR=5.443, HR=3.935) and greater number of previous psychiatric admissions (p< 0.001, OR=1.250, HR=1.121)  were associated with a higher rehospitalization risk and predicted earlier rehospitalization. The rehospitalization rate of elderly patients was 5.2% at 1 month, 9.5% at 3 months, 15.0% at 6 months, 17.1% at 1 year, 18.8% at 1.5 year and 20.9% at 2 years.
      PubDate: 2015-09-30T10:46:06Z
      DOI: 10.12688/f1000research.7135.1
      Issue No: Vol. 4 (2015)
  • How to avoid pitfalls in antibody use [version 1; referees: 2 approved]

    • Authors: Diana Pauly, Katja Hanack
      Abstract: Antibody use is ubiquitous in the biomedical sciences. However, determining best research practices has not been trivial. Many commercially available antibodies and antibody-conjugates are poorly characterized and lack proper validation. Uncritical application of such useless tools has contributed to the reproducibility crisis in biomedical research. Despite early initiatives such as MIAPAR or PSI-PAR, a best practice guideline for antibody characterization is still not in prospect. Here, we analyze 24 antibody-related databases and compare their content with regard to validation aspects and coverage. We also provide a flowchart for end-users with all necessary steps to facilitate finding and choosing specific and sensitive antibodies for their experiments. Based on a growing demand for better and standardized validation procedures and characterization guidelines for antibody molecules we have summarized our findings in a five-point plan. We intend to keep the discussion alive and hope that properly used antibodies will remain as central to biomedicine as they are today.
      PubDate: 2015-09-07T15:09:41Z
      DOI: 10.12688/f1000research.6894.1
      Issue No: Vol. 4 (2015)
  • High Frequency Haplotypes are Expected Events, not Historical Figures
           [version 1; referees: 1 approved, 2 approved with reservations]

    • Authors: Elsa G. Guillot, Murray P. Cox
      Abstract: Cultural transmission of reproductive success states that successful men have more children and pass this raised fecundity to their offspring. Balaresque and colleagues found high frequency haplotypes in a Central Asian Y chromosome dataset, which they attribute to cultural transmission of reproductive success by prominent historical men, including Genghis Khan. Using coalescent simulation, we show that these high frequency haplotypes are consistent with a neutral model, where they commonly appear simply by chance. Hence, explanations invoking cultural transmission of reproductive success are statistically unnecessary.
      PubDate: 2015-09-04T14:27:50Z
      DOI: 10.12688/f1000research.7023.1
      Issue No: Vol. 4 (2015)
  • Double-Blinding and Bias in Medication and Cognitive-Behavioral Therapy
           Trials for Major Depressive Disorder [version 1; referees: 2 approved]

    • Authors: Douglas Berger
      Abstract: While double-blinding is a crucial aspect of study design in an interventional clinical trial of medication for a disorder with subjective endpoints such as major depressive disorder, psychotherapy clinical trials, particularly cognitive-behavioral therapy trials, cannot be double-blinded. This paper highlights the evidence-based medicine problem of double-blinding in the outcome research of a psychotherapy and opines that psychotherapy clinical trials should be called, “partially-controlled clinical data” because they are not double-blinded. The implications for practice are, 1. For practitioners to be clear with patients the level of rigor to which interventions have been studied, 2. For authors of psychotherapy outcome studies to be clear that the problem in the inability to blind a psychotherapy trial severely restricts the validity of any conclusions that can be drawn, and 3. To petition National Health Insurance plans to use caution in approving interventions studied without double-blinded confirmatory trials as they may lead patients to avoid other treatments shown to be effective in double-blinded trials.
      PubDate: 2015-08-27T15:15:44Z
      DOI: 10.12688/f1000research.6953.1
      Issue No: Vol. 4 (2015)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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