Showing papers by "University of Kentucky published in 2013"
TL;DR: High-throughput sequencing of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease showed that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.
Abstract: Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R. We identified >25,000 distinct RNA species in human fibroblasts that contained non-colinear exons (a "backsplice") and were reproducibly enriched by exonuclease degradation of linear RNA. These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo. In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by >10-fold. By conservative estimate, we identified ecircRNAs from 14.4% of actively transcribed genes in human fibroblasts. Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs. Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice. Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes. Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs. Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats. These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.
3,310 citations
Columbia University1, Cambridge University Hospitals NHS Foundation Trust2, University of Wisconsin-Madison3, McGill University4, University of Sheffield5, University of Kentucky6, French Institute of Health and Medical Research7, University of Washington8, Creighton University9, University of Arkansas for Medical Sciences10
TL;DR: The key revisions include omission of terminology used before 1987, recommendations regarding the parameters and technical information that should be included in all histomorphometry articles, recommendations on how to handle dynamic parameters of bone formation in settings of low bone turnover, and updating of references.
Abstract: Before publication of the original version of this report in 1987, practitioners of bone histomorphometry communicated with each other in a variety of arcane languages, which in general were unintelligible to those outside the field. The need for standardization of nomenclature had been recognized for many years,(1) during which there had been much talk but no action. To satisfy this need, B Lawrence Riggs (ASBMR President, 1985 to 1986) asked A Michael Parfitt to convene an ASBMR committee to develop a new and unified system of terminology, suitable for adoption by the Journal of Bone and Mineral Research (JBMR) as part of its Instructions to Authors. The resulting recommendations were published in 1987(2) and were quickly adopted not only by JBMR but also by all respected journals in the bone field. The recommendations improved markedly the ability of histomorphometrists to communicate with each other and with nonhistomorphometrists, leading to a broader understanding and appreciation of histomorphometric data.
In 2012, 25 years after the development of the standardized nomenclature system, Thomas L Clemens (Editor in Chief of JBMR) felt that it was time to revise and update the recommendations. The original committee was reconvened by David W Dempster, who appointed one new member, Juliet E Compston. The original document was circulated to the committee members and was extensively revised according to their current recommendations. The key revisions include omission of terminology used before 1987, recommendations regarding the parameters and technical information that should be included in all histomorphometry articles, recommendations on how to handle dynamic parameters of bone formation in settings of low bone turnover, and updating of references.
2,035 citations
TL;DR: Developing UV-protective approaches based on a detailed understanding of molecular events that occur after UV exposure, focusing particularly on epidermal melanization and the role of the MC1R in genome maintenance are targeted.
Abstract: UV radiation (UV) is classified as a "complete carcinogen" because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV also benefits human health by mediating natural synthesis of vitamin D and endorphins in the skin, therefore UV has complex and mixed effects on human health. Nonetheless, excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and molecularly linked to the three most common types of skin cancer, basal cell carcinoma, squamous cell carcinoma and malignant melanoma, which together affect more than a million Americans annually. Genetic factors also influence risk of UV-mediated skin disease. Polymorphisms of the melanocortin 1 receptor (MC1R) gene, in particular, correlate with fairness of skin, UV sensitivity, and enhanced cancer risk. We are interested in developing UV-protective approaches based on a detailed understanding of molecular events that occur after UV exposure, focusing particularly on epidermal melanization and the role of the MC1R in genome maintenance.
1,240 citations
TL;DR: The expert group defined bruxism as a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible and proposed a diagnostic grading system of 'possible', 'probable' and 'definite' sleep or awake bruXism.
Abstract: To date, there is no consensus about the definition and diagnostic grading of bruxism. A written consensus discussion was held among an international group of bruxism experts as to formulate a definition of bruxism and to suggest a grading system for its operationalisation. The expert group defined bruxism as a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. Bruxism has two distinct circadian manifestations: it can occur during sleep (indicated as sleep bruxism) or during wakefulness (indicated as awake bruxism). For the operationalisation of this definition, the expert group proposes a diagnostic grading system of 'possible', 'probable' and 'definite' sleep or awake bruxism. The proposed definition and grading system are suggested for clinical and research purposes in all relevant dental and medical domains.
821 citations
University of Pittsburgh1, University of California, Irvine2, University of California, Berkeley3, University of California, Santa Cruz4, University of California, San Diego5, Alfred P. Sloan Foundation6, Harvard University7, Max Planck Society8, Lawrence Berkeley National Laboratory9, University of Arizona10, University of Kentucky11, California Institute of Technology12, Goddard Space Flight Center13, Space Telescope Science Institute14, University of Southern California15, University of Washington16, Academia Sinica17, Sonoma State University18, Liverpool John Moores University19
TL;DR: The DEEP2 Galaxy Redshift Survey (DEEP2) as discussed by the authors is the largest high-precision redshift survey of galaxies at z ~ 1 completed to date, covering an area of 2.8 deg^2 divided into four separate fields observed to a limiting apparent magnitude of R_(AB) = 24.1.
Abstract: We describe the design and data analysis of the DEEP2 Galaxy Redshift Survey, the densest and largest high-precision redshift survey of galaxies at z ~ 1 completed to date. The survey was designed to conduct a comprehensive census of massive galaxies, their properties, environments, and large-scale structure down to absolute magnitude M_B = −20 at z ~ 1 via ~90 nights of observation on the Keck telescope. The survey covers an area of 2.8 deg^2 divided into four separate fields observed to a limiting apparent magnitude of R_(AB) = 24.1. Objects with z ≾0.7 are readily identifiable using BRI photometry and rejected in three of the four DEEP2 fields, allowing galaxies with z > 0.7 to be targeted ~2.5 times more efficiently than in a purely magnitude-limited sample. Approximately 60% of eligible targets are chosen for spectroscopy, yielding nearly 53,000 spectra and more than 38,000 reliable redshift measurements. Most of the targets that fail to yield secure redshifts are blue objects that lie beyond z ~ 1.45, where the [O ii] 3727 A doublet lies in the infrared. The DEIMOS 1200 line mm^(−1) grating used for the survey delivers high spectral resolution (R ~ 6000), accurate and secure redshifts, and unique internal kinematic information. Extensive ancillary data are available in the DEEP2 fields, particularly in the Extended Groth Strip, which has evolved into one of the richest multiwavelength regions on the sky. This paper is intended as a handbook for users of the DEEP2 Data Release 4, which includes all DEEP2 spectra and redshifts, as well as for the DEEP2 DEIMOS data reduction pipelines. Extensive details are provided on object selection, mask design, biases in target selection and redshift measurements, the spec2d two-dimensional data-reduction pipeline, the spec1d automated redshift pipeline, and the zspec visual redshift verification process, along with examples of instrumental signatures or other artifacts that in some cases remain after data reduction. Redshift errors and catastrophic failure rates are assessed through more than 2000 objects with duplicate observations. Sky subtraction is essentially photon-limited even under bright OH sky lines; we describe the strategies that permitted this, based on high image stability, accurate wavelength solutions, and powerful B-spline modeling methods. We also investigate the impact of targets that appear to be single objects in ground-based targeting imaging but prove to be composite in Hubble Space Telescope data; they constitute several percent of targets at z ~ 1, approaching ~5%–10% at z > 1.5. Summary data are given that demonstrate the superiority of DEEP2 over other deep high-precision redshift surveys at z ~ 1 in terms of redshift accuracy, sample number density, and amount of spectral information. We also provide an overview of the scientific highlights of the DEEP2 survey thus far.
776 citations
TL;DR: Iron deficiency anemia (IDA) is the most common anemia syndrome encountered in clinical medicine, and in a recent review of healthy individuals in the US military, IDA had an incidence of 3.4 per 10,000 patient-years in men but 29.5 in women.
Abstract: Iron is an essential mineral for oxygen transport and energy production. Increased requirements, as with pregnancy, or inadequate dietary intake of iron may lead to varying degrees of depletion. If iron depletion is severe, iron deficiency anemia (IDA) occurs. By World Health Organization standards, anemia during pregnancy is a hemoglobin (Hb) concentration ≤13.0 g/dl, and by this definition anemia may complicate over 50% of all gestations in the United States.1 Of pregnant women with an abnormally low Hb concentration and packed cell volume (PCV), 75–85% have IDA.2 Indeed, some degree of iron depletion appears to be almost universal during pregnancy. The problem is compounded by multiple gestations, successive pregnancies (<2–3 years apart), adolescent pregnancy, chronic blood loss, intravascular hemolysis, and poor iron absorption associated with certain medical conditions.
750 citations
Arizona State University1, Pace University2, Texas State University3, DePaul University4, Universidad del Norte, Colombia5, University of Kentucky6, Washington State University7, Oklahoma State University–Stillwater8, Northern Illinois University9, Japan Advanced Institute of Science and Technology10, Rutgers University11
TL;DR: In this article, the authors present a research agenda for the emerging area of transformative service research, which lies at the intersection of service research and consumer research and focuses on well-being outcomes related to service and services.
672 citations
TL;DR: Emerging evidences indicate that Snail causes a metabolic reprogramming, bestows tumor cells with cancer stem cell-like traits, and additionally, promotes drug resistance, tumor recurrence and metastasis.
Abstract: Epithelial-mesenchymal transition (EMT) is a highly conserved process in which polarized, immobile epithelial cells lose tight junctions, associated adherence, and become migratory mesenchymal cells. Several transcription factors, including the Snail/Slug family, Twist, δEF1/ZEB1, SIP1/ZEB2 and E12/E47 respond to microenvironmental stimuli and function as molecular switches for the EMT program. Snail is a zinc-finger transcriptional repressor controlling EMT during embryogenesis and tumor progression. Through its N-terminal SNAG domain, Snail interacts with several corepressors and epigenetic remodeling complexes to repress specific target genes, such as the E-cadherin gene (CDH1). An integrated and complex signaling network, including the RTKs, TGF-β, Notch, Wnt, TNF-α, and BMPs pathways, activates Snail, thereby inducing EMT. Snail expression correlates with the tumor grade, nodal metastasis of many types of tumor and predicts a poor outcome in patients with metastatic cancer. Emerging evidences indicate that Snail causes a metabolic reprogramming, bestows tumor cells with cancer stem cell-like traits, and additionally, promotes drug resistance, tumor recurrence and metastasis. Despite many new and exciting developments, several challenges remain to be addressed in order to understand more thoroughly the role of Snail in metastasis. Additional investigations are required to disclose the contribution of microenvironmental factors on tumor progression. This information will lead to a comprehensive understanding of Snail in cancer and will provide us with novel approaches for preventing and treating metastatic cancers.
651 citations
TL;DR: Rubin and Ruggiero as discussed by the authors pointed out that measures designed for older media are used to capture gratifications from newer media, and that gratifications are conceptualized and operationalized too broadly (e.g., information-seeking), thus missing the nuanced gratifications obtained from modern media.
Abstract: This article responds to recent calls for conceptual and methodological refinement, issued by uses-and-gratifications scholars (Rubin, 2009; Ruggiero, 2000), for studying emergent media. Noting that studies on the uses of the Internet have generated a list of gratifications that are remarkably similar to those obtained from older media, it identifies two measurement artifacts—(1) measures designed for older media are used to capture gratifications from newer media; and (2) gratifications are conceptualized and operationalized too broadly (e.g., information-seeking), thus missing the nuanced gratifications obtained from newer media. It challenges the notion that all gratifications are borne out of innate needs, and proposes that affordances of media technology can shape user needs, giving rise to new and distinctive gratifications. A sample of new gratifications and potential measures for those are provided.
633 citations
TL;DR: This study indicates that the loss of FBP1 is a critical oncogenic event in EMT and BLBC.
630 citations
TL;DR: In this article, the state-of-the-art in predictive performance models for machining operations is presented, and a critical assessment of the relevant modelling techniques and their applicability and/or limitations for the prediction of the complex machining operation performed in industry.
University of Washington1, Virginia Mason Medical Center2, Broad Institute3, Agency for Science, Technology and Research4, University of Konstanz5, Université de Montréal6, University of Oregon7, Federal University of Pará8, Harvard University9, University of Utah10, École normale supérieure de Lyon11, University of Kentucky12, Rhodes University13, University of Trieste14, Wellcome Trust Sanger Institute15, Marche Polytechnic University16, University of Liège17, Victoria University, Australia18, University of Hamburg19, University of South Florida20, University of the Western Cape21, Woods Hole Oceanographic Institution22, University of Oxford23, Leipzig University24, Keio University25, Johns Hopkins University26, University of Tennessee Health Science Center27, Graduate University for Advanced Studies28, National Institute of Genetics29, University of Chicago30, University of Würzburg31, Uppsala University32
TL;DR: Through a phylogenomic analysis, it is concluded that the lungfish, and not the coelacanth, is the closest living relative of tetrapods.
Abstract: The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
University of Toledo1, University College Dublin2, Indiana University3, Qatar Airways4, The Chinese University of Hong Kong5, University of Virginia6, University of Sydney7, University of Delaware8, University of Kentucky9, Radboud University Nijmegen Medical Centre10, University of Queensland11, University of North Carolina at Chapel Hill12
TL;DR: There is a need to provide standards for patient/participant selection criteria in research focused on CAI, with justifications using the best available evidence.
Abstract: While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalise this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient.
University of California, Santa Cruz1, University of Massachusetts Amherst2, Space Telescope Science Institute3, Harvard University4, Los Alamos National Laboratory5, INAF6, Johns Hopkins University7, University of Kentucky8, Colby College9, Max Planck Society10, University of California, Irvine11, University of Edinburgh12, Goddard Space Flight Center13, Rutgers University14, Carnegie Learning15, Purdue University16, University of California, Riverside17, University of Pittsburgh18
TL;DR: In this article, the authors presented a CANDELS/GOODS-S multi-wavelength catalog based on source detection in the WFC3 F160W band, which contains 34,930 sources with the representative 50% completeness reaching 25.9, 26.6, and 28.1?AB.
Abstract: We present a UV to mid-infrared multi-wavelength catalog in the CANDELS/GOODS-S field, combining the newly obtained CANDELS HST/WFC3 F105W, F125W, and F160W data with existing public data. The catalog is based on source detection in the WFC3 F160W band. The F160W mosaic includes the data from CANDELS deep and wide observations as well as previous ERS and HUDF09 programs. The mosaic reaches a 5? limiting depth (within an aperture of radius 0.''17) of 27.4, 28.2, and 29.7?AB for CANDELS wide, deep, and HUDF regions, respectively. The catalog contains 34,930 sources with the representative 50% completeness reaching 25.9, 26.6, and 28.1?AB in the F160W band for the three regions. In addition to WFC3 bands, the catalog also includes data from UV (U band from both CTIO/MOSAIC and VLT/VIMOS), optical (HST/ACS F435W, F606W, F775W, F814W, and F850LP), and infrared (HST/WFC3 F098M, VLT/ISAAC Ks, VLT/HAWK-I Ks, and Spitzer/IRAC 3.6, 4.5, 5.8, 8.0 ?m) observations. The catalog is validated via stellar colors, comparison with other published catalogs, zero-point offsets determined from the best-fit templates of the spectral energy distribution of spectroscopically observed objects, and the accuracy of photometric redshifts. The catalog is able to detect unreddened star-forming (passive) galaxies with stellar mass of 1010 M ? at a 50% completeness level to z ~ 3.4 (2.8), 4.6 (3.2), and 7.0 (4.2) in the three regions. As an example of application, the catalog is used to select both star-forming and passive galaxies at z ~ 2-4 via the Balmer break. It is also used to study the color-magnitude diagram of galaxies at 0 < z < 4.
Icahn School of Medicine at Mount Sinai1, University of London2, Columbia University Medical Center3, Charité4, University of Minnesota5, University of Missouri–Kansas City6, Geisinger Medical Center7, MedStar Washington Hospital Center8, Duke University9, George Washington University10, Harvard University11, Vita-Salute San Raffaele University12, University of Kentucky13
TL;DR: This study enrolled 5031 patients undergoing PCI with stent implantation in 15 clinical sites in the USA and Europe between July 1, 2009, and Dec 2, 2010 and examined the effect of DAPT cessation on major adverse events (MACE) and found those who discontinued had lower MACE risk.
TL;DR: A consensus statement was developed employing clinical, imaging, pathologic, and virologic evidence in support of the diagnosis of progressive multifocal leukoencephalopathy (PML) as mentioned in this paper.
Abstract: Objective: To establish criteria for the diagnosis of progressive multifocal leukoencephalopathy (PML). Methods: We reviewed available literature to identify various diagnostic criteria employed. Several search strategies employing the terms “progressive multifocal leukoencephalopathy” with or without “JC virus” were performed with PubMed, SCOPUS, and EMBASE search engines. The articles were reviewed by a committee of individuals with expertise in the disorder in order to determine the most useful applicable criteria. Results: A consensus statement was developed employing clinical, imaging, pathologic, and virologic evidence in support of the diagnosis of PML. Two separate pathways, histopathologic and clinical, for PML diagnosis are proposed. Diagnostic classification includes certain, probable, possible, and not PML. Conclusion: Definitive diagnosis of PML requires neuropathologic demonstration of the typical histopathologic triad (demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei) coupled with the techniques to show the presence of JC virus. The presence of clinical and imaging manifestations consistent with the diagnosis and not better explained by other disorders coupled with the demonstration of JC virus by PCR in CSF is also considered diagnostic. Algorithms for establishing the diagnosis have been recommended.
TL;DR: Interventions that used an individualized or decreasing frequency of messages over the course of the intervention were more successful than interventions that used a fixed message frequency and message tailoring and personalization were significantly associated with greater intervention efficacy.
TL;DR: It is shown that an epigenetic histone mark, H3K36me3, is required in vivo to recruit the mismatch recognition protein hMutSα onto chromatin through direct interactions with the hMSH6 PWWP domain.
TL;DR: Analysis of participant/descriptive, intervention, and methodological moderators shed some light on factors that may be important to the success of tailored interventions and provided further support for the differential benefits of tailored web-based interventions over nontailed approaches.
Abstract: Web-based tailored intervention programs show considerable promise in effecting health-promoting behaviors and improving health outcomes across a variety of medical conditions and patient populations. This meta-analysis compares the effects of tailored versus nontailored web-based interventions on health behaviors and explores the influence of key moderators on treatment outcomes. Forty experimental and quasi-experimental studies (N =20,180) met criteria for inclusion and were analyzed using meta-analytic procedures. The findings indicated that web-based tailored interventions effected significantly greater improvement in health outcomes as compared with control conditions both at posttesting, d =.139 (95% CI = .111, .166, p <.001, k =40) and at follow-up, d =.158 (95% CI = .124, .192, p <.001, k =21). The authors found no evidence of publication bias. These results provided further support for the differential benefits of tailored web-based interventions over nontailored approaches. Analysis of participa...
TL;DR: This discovery and validation of a balanced and high-potency dual incretin agonist enables a more physiological approach to management of diseases associated with impaired glucose tolerance and represents a new class of drug candidates for the treatment of metabolic diseases.
Abstract: We report the discovery and translational therapeutic efficacy of a peptide with potent, balanced co-agonism at both of the receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This unimolecular dual incretin is derived from an intermixed sequence of GLP-1 and GIP, and demonstrated enhanced antihyperglycemic and insulinotropic efficacy relative to selective GLP-1 agonists. Notably, this superior efficacy translated across rodent models of obesity and diabetes, including db/db mice and ZDF rats, to primates (cynomolgus monkeys and humans). Furthermore, this co-agonist exhibited synergism in reducing fat mass in obese rodents, whereas a selective GIP agonist demonstrated negligible weight-lowering efficacy. The unimolecular dual incretins corrected two causal mechanisms of diabesity, adiposity-induced insulin resistance and pancreatic insulin deficiency, more effectively than did selective mono-agonists. The duration of action of the unimolecular dual incretins was refined through site-specific lipidation or PEGylation to support less frequent administration. These peptides provide comparable pharmacology to the native peptides and enhanced efficacy relative to similarly modified selective GLP-1 agonists. The pharmacokinetic enhancement lessened peak drug exposure and, in combination with less dependence on GLP-1-mediated pharmacology, avoided the adverse gastrointestinal effects that typify selective GLP-1-based agonists. This discovery and validation of a balanced and high-potency dual incretin agonist enables a more physiological approach to management of diseases associated with impaired glucose tolerance.
Journal Article•
TL;DR: Cloud as discussed by the authors models the ionization, chemical, and thermal state of material that may be exposed to an external radiation field or other source of heating, and predicts observables such as emission and absorption spectra.
Abstract: This is a summary of the 2013 release of the plasma simulation code Cloudy. Cloudy models the ionization, chemical, and thermal state of material that may be exposed to an external radiation field or other source of heating, and predicts observables such as emission and absorption spectra. It works in terms of elementary processes, so is not limited to any particular temperature or density regime. This paper summarizes advances made since the last major review in 1998. Much of the recent development has emphasized dusty molecular environments, improvements to the ionization/chemistry solvers, and how atomic and molecular data are used. We present two types of simulations to demonstrate the capability of the code. We consider a molecular cloud irradiated by an X-ray source such as an active nucleus and show how treating EUV recombination lines and the full SED affects the observed spectrum. A second example illustrates the very wide range of particle and radiation density that can be considered.
Stanford University1, Memorial Sloan Kettering Cancer Center2, University of Kentucky3, Ohio State University4, Harvard University5, University of Wisconsin-Madison6, National Institutes of Health7, Icahn School of Medicine at Mount Sinai8, Vanderbilt University9, University of Pennsylvania10, University of South Florida11
TL;DR: A set of consensus tables intended to complement the North American Neuroendocrine Tumor Society guidelines and serve as a quick, accessible reference for the practicing physician are presented.
Abstract: Neuroendocrine tumors are a heterogeneous group of tumors originating in various anatomic locations. The management of this disease poses a significant challenge because of the heterogeneous clinical presentations and varying degrees of aggressiveness. The recent completion of several phase 3 trials, including those evaluating octreotide, sunitinib, and everolimus, demonstrate that rigorous evaluation of novel agents in this disease is possible and can lead to practice-changing outcomes. Nevertheless, there are many aspects to the treatment of neuroendocrine tumors that remain unclear and controversial. The North American Neuroendocrine Tumor Society published a set of consensus guidelines in 2010, which provided an overview for the treatment of patients with these malignancies. Here, we present a set of consensus tables intended to complement these guidelines and serve as a quick, accessible reference for the practicing physician.
TL;DR: The evolutionary events that gave rise to the tracheophytes are examined, followed by analysis of the genetic and hormonal networks that cooperate to orchestrate vascular development in the gymnosperms and angiosperms, in a comprehensive picture of the state-of-the-art in the area of plant vascular biology.
Abstract: The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology, in general, through its role in facilitating the development of plants with increased stature, photosynthetic output, and ability to colonize a greatly expanded range of environmental habitats. Recently, considerable progress has been made in terms of our understanding of the developmental and physiological programs involved in the formation and function of the plant vascular system. In this review, we first examine the evolutionary events that gave rise to the tracheophytes, followed by analysis of the genetic and hormonal networks that cooperate to orchestrate vascular development in the gymnosperms and angiosperms. The two essential functions performed by the vascular system, namely the delivery of resources (water, essential mineral nutrients, sugars and amino acids) to the various plant organs and provision of mechanical support are next discussed. Here, we focus on critical questions relating to structural and physiological properties controlling the delivery of material through the xylem and phloem. Recent discoveries into the role of the vascular system as an effective long-distance communication system are next assessed in terms of the coordination of developmental, physiological and defense-related processes, at the whole-plant level. A concerted effort has been made to integrate all these new findings into a comprehensive picture of the state-of-the-art in the area of plant vascular biology. Finally, areas important for future research are highlighted in terms of their likely contribution both to basic knowledge and applications to primary industry.
TL;DR: O-GlcNAc modification of CaMKII is a novel signalling event in pathways that may contribute critically to cardiac and neuronal pathophysiology in diabetes and other diseases.
Abstract: Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is an enzyme with important regulatory functions in the heart and brain, and its chronic activation can be pathological. CaMKII activation is seen in heart failure, and can directly induce pathological changes in ion channels, Ca(2+) handling and gene transcription. Here, in human, rat and mouse, we identify a novel mechanism linking CaMKII and hyperglycaemic signalling in diabetes mellitus, which is a key risk factor for heart and neurodegenerative diseases. Acute hyperglycaemia causes covalent modification of CaMKII by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAc modification of CaMKII at Ser 279 activates CaMKII autonomously, creating molecular memory even after Ca(2+) concentration declines. O-GlcNAc-modified CaMKII is increased in the heart and brain of diabetic humans and rats. In cardiomyocytes, increased glucose concentration significantly enhances CaMKII-dependent activation of spontaneous sarcoplasmic reticulum Ca(2+) release events that can contribute to cardiac mechanical dysfunction and arrhythmias. These effects were prevented by pharmacological inhibition of O-GlcNAc signalling or genetic ablation of CaMKIIδ. In intact perfused hearts, arrhythmias were aggravated by increased glucose concentration through O-GlcNAc- and CaMKII-dependent pathways. In diabetic animals, acute blockade of O-GlcNAc inhibited arrhythmogenesis. Thus, O-GlcNAc modification of CaMKII is a novel signalling event in pathways that may contribute critically to cardiac and neuronal pathophysiology in diabetes and other diseases.
TL;DR: The diverse immune cell types, inflammatory activators and pathways that are involved in AMD pathogenesis are outlined and the future of inflammation-directed therapeutics to treat AMD in the growing aged population is discussed.
Abstract: Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population.
TL;DR: In this article, the authors evaluated the performance of dynamic panel models on corporate finance data, in which the dependent variable may be clustered or censored and independent variables may be missing, correlated with one another, or endogenous.
TL;DR: An overview of the current research in meat color and how the findings are applied in the meat industry is provided to help engineer innovative processing strategies to minimize meat discoloration-induced revenue loss to the agricultural economy.
Abstract: Consumers rely heavily on fresh meat color as an indicator of wholesomeness at the point of sale, whereas cooked color is exploited as an indicator of doneness at the point of consumption. Deviations from the bright cherry-red color of fresh meat lead to product rejection and revenue loss. Myoglobin is the sarcoplasmic heme protein primarily responsible for the meat color, and the chemistry of myoglobin is species specific. The mechanistic interactions between myoglobin and multiple extrinsic and intrinsic factors govern the color of raw as well as cooked meats. The objective of this review is to provide an overview of the current research in meat color and how the findings are applied in the meat industry. Characterizing the fundamental basis of myoglobin's interactions with biomolecules in postmortem skeletal muscles is necessary to interpret the chemistry of meat color phenomena and to engineer innovative processing strategies to minimize meat discoloration-induced revenue loss to the agricultural economy.
TL;DR: NAFLD fibrosis score appears to be the best indicator of patients at risk, based on HRs, for liver-related complications or death in patients with nonalcoholic fatty liver disease.
TL;DR: The signatures of oxidatively modified brain proteins, identified using redox proteomics approaches, during the progression of AD are discussed, with the notion that methionine present at 35 position of Aβ is critical to Aβ-induced oxidative stress and neurotoxicity.
Abstract: Significance: Alzheimer disease (AD) is an age-related neurodegenerative disease. AD is characterized by progressive cognitive impairment. One of the main histopathological hallmarks of AD brain is the presence of senile plaques (SPs) and another is elevated oxidative stress. The main component of SPs is amyloid beta-peptide (Aβ) that is derived from the proteolytic cleavage of amyloid precursor protein. Recent Advances: Recent studies are consistent with the notion that methionine present at 35 position of Aβ is critical to Aβ-induced oxidative stress and neurotoxicity. Further, we also discuss the signatures of oxidatively modified brain proteins, identified using redox proteomics approaches, during the progression of AD. Critical Issues: The exact relationships of the specifically oxidatively modified proteins in AD pathogenesis require additional investigation. Future Directions: Further studies are needed to address whether the therapies directed toward brain oxidative stress and oxidatively...
TL;DR: The soil microbial diversity that once existed in this biome was reconstructed by analyzing relict prairie soils and found that the biogeographical patterns were largely driven by changes in the relative abundance of Verrucomicrobia, a poorly studied bacterial phylum that appears to dominate many prairies.
Abstract: Native tallgrass prairie once dominated much of the midwestern United States, but this biome and the soil microbial diversity that once sustained this highly productive system have been almost completely eradicated by decades of agricultural practices. We reconstructed the soil microbial diversity that once existed in this biome by analyzing relict prairie soils and found that the biogeographical patterns were largely driven by changes in the relative abundance of Verrucomicrobia, a poorly studied bacterial phylum that appears to dominate many prairie soils. Shotgun metagenomic data suggested that these spatial patterns were associated with strong shifts in carbon dynamics. We show that metagenomic approaches can be used to reconstruct below-ground biogeochemical and diversity gradients in endangered ecosystems; such information could be used to improve restoration efforts, given that even small changes in below-ground microbial diversity can have important impacts on ecosystem processes.