Extracellular Matrix Alterations and Deposit Formation in AMD.

Age related macular degeneration (AMD) is the primary cause of vision loss in the western world (Friedman et al., Arch Ophthalmol 122:564-572, 2004). The first clinical indication of AMD is the presence of drusen.

Formation of Soluble Mercury Oxide Coatings: Transformation of Elemental Mercury in Soils.

The impact of mercury (Hg) on human and ecological health has been known for decades. Although a treaty signed in 2013 by 147 nations regulates future large-scale mercury emissions, legacy Hg contamination exists worldwide and small-scale releases will continue. The fate of elemental mercury, Hg(0), lost to the subsurface and its potential chemical transformation that can lead to changes in speciation and mobility are poorly understood.

Ketocarotenoid Production in Soybean Seeds through Metabolic Engineering.

The pink or red ketocarotenoids, canthaxanthin and astaxanthin, are used as feed additives in the poultry and aquaculture industries as a source of egg yolk and flesh pigmentation, as farmed animals do not have access to the carotenoid sources of their wild counterparts. Because soybean is already an important component in animal feed, production of these carotenoids in soybean could be a cost-effective means of delivery. In order to characterize the ability of soybean seed to produce carotenoids, soybean cv.

Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas.

A phase 1 study with carfilzomib and vorinostat was conducted in 20 B-cell lymphoma patients. Vorinostat was given orally twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 followed by carfilzomib (given as a 30-min infusion) on days 1, 2, 8, 9, 15, and 16. A treatment cycle was 28 days.

A local complement response by RPE causes early-stage macular degeneration.

Inherited and age-related macular degenerations (AMDs) are important causes of vision loss. An early hallmark of these disorders is the formation of sub-retinal pigment epithelium (RPE) basal deposits. A role for the complement system in MDs was suggested by genetic association studies, but direct functional connections between alterations in the complement system and the pathogenesis of MD remain to be defined.

Reference-free removal of EEG-fMRI ballistocardiogram artifacts with harmonic regression.

Combining electroencephalogram (EEG) recording and functional magnetic resonance imaging (fMRI) offers the potential for imaging brain activity with high spatial and temporal resolution. This potential remains limited by the significant ballistocardiogram (BCG) artifacts induced in the EEG by cardiac pulsation-related head movement within the magnetic field. We model the BCG artifact using a harmonic basis, pose the artifact removal problem as a local harmonic regression analysis, and develop an efficient maximum likelihood algorithm to estimate and remove BCG artifacts.

The Impact of a Shortage of Pharmacy-Prepared Ephedrine Syringes on Intraoperative Medication Use.

Background: Anesthesia-related medication shortages have become increasingly common in the United States. We tested whether a local shortage of pharmacy-prepared ephedrine syringes, replaced by provider-prepared ephedrine, was associated with provider-level changes in ephedrine and phenylephrine use and patient-level changes in intraoperative hemodynamics.

Methods: Consecutive patients undergoing general and orthopedic surgery at a tertiary care center were included 1 month before and 1 month after the start of the pharmacy-prepared ephedrine syringe shortage.

The Structure of an Oxalate Oxidoreductase Provides Insight into Microbial 2-Oxoacid Metabolism.

Thiamine pyrophosphate (TPP), a derivative of vitamin B1, is a versatile and ubiquitous cofactor. When coupled with [4Fe-4S] clusters in microbial 2-oxoacid:ferredoxin oxidoreductases (OFORs), TPP is involved in catalyzing low-potential redox reactions that are important for the synthesis of key metabolites and the reduction of N2, H(+), and CO2. We have determined the high-resolution (2.

In situ remediation technologies for mercury-contaminated soil.

Mercury from anthropogenic activities is a pollutant that poses significant risks to humans and the environment. In soils, mercury remediation can be technically challenging and costly, depending on the subsurface mercury distribution, the types of mercury species, and the regulatory requirements. This paper introduces the chemistry of mercury and its implications for in situ mercury remediation, which is followed by a detailed discussion of several in situ Hg remediation technologies in terms of applicability, cost, advantages, and disadvantages.

RNA-Seq: Improving Our Understanding of Retinal Biology and Disease.

Over the past several years, rapid technological advances have allowed for a dramatic increase in our knowledge and understanding of the transcriptional landscape, because of the ability to study gene expression in greater depth and with more detail than previously possible. To this end, RNA-Seq has quickly become one of the most widely used methods for studying transcriptomes of tissues and individual cells. Unlike previously favored analysis methods, RNA-Seq is extremely high-throughput, and is not dependent on an annotated transcriptome, laying the foundation for novel genetic discovery.

The human burst suppression electroencephalogram of deep hypothermia.

Objective: Deep hypothermia induces 'burst suppression' (BS), an electroencephalogram pattern with low-voltage 'suppressions' alternating with high-voltage 'bursts'. Current understanding of BS comes mainly from anesthesia studies, while hypothermia-induced BS has received little study. We set out to investigate the electroencephalogram changes induced by cooling the human brain through increasing depths of BS through isoelectricity.

The Status of RPE65 Gene Therapy Trials: Safety and Efficacy.

Several groups have reported the results of clinical trials of gene augmentation therapy for Leber congenital amaurosis (LCA) because of mutations in the RPE65 gene. These studies have used subretinal injection of adeno-associated virus (AAV) vectors to deliver the human RPE65 cDNA to the retinal pigment epithelial (RPE) cells of the treated eyes. In all of the studies reported to date, this approach has been shown to be both safe and effective.

Targeted exon sequencing in Usher syndrome type I.

Purpose: Patients with Usher syndrome type I (USH1) have retinitis pigmentosa, profound congenital hearing loss, and vestibular ataxia. This syndrome is currently thought to be associated with at least six genes, which are encoded by over 180 exons. Here, we present the use of state-of-the-art techniques in the molecular diagnosis of a cohort of 47 USH1 probands.

Transcriptional analysis of South African cassava mosaic virus-infected susceptible and tolerant landraces of cassava highlights differences in resistance, basal defense and cell wall associated genes during infection.

Background: Cassava mosaic disease is caused by several distinct geminivirus species, including South African cassava mosaic virus-[South Africa:99] (SACMV). To date, there is limited gene regulation information on viral stress responses in cassava, and global transcriptome profiling in SACMV-infected cassava represents an important step towards understanding natural host responses to plant geminiviruses.

Results: A RNA-seq time course (12, 32 and 67 dpi) study, monitoring gene expression in SACMV-challenged susceptible (T200) and tolerant (TME3) cassava landraces, was performed using the Applied Biosystems (ABI) SOLiD next-generation sequencing platform.

Panel-based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible, and more sensitive for variant detection, than exome sequencing.

Purpose: Next-generation sequencing-based methods are being adopted broadly for genetic diagnostic testing, but the performance characteristics of these techniques with regard to test accuracy and reproducibility have not been fully defined.

Methods: We developed a targeted enrichment and next-generation sequencing approach for genetic diagnostic testing of patients with inherited eye disorders, including inherited retinal degenerations, optic atrophy, and glaucoma. In preparation for providing this genetic eye disease (GEDi) test on a CLIA-certified basis, we performed experiments to measure the sensitivity, specificity, and reproducibility, as well as the clinical sensitivity, of the test.

Systemic diseases associated with retinal dystrophies.

Inherited retinal degeneration (IRD) may occur in isolation or as part of a multi-systemic condition. Ocular manifestations may be the presenting symptom of a syndromic disease and can include retinitis pigmentosa, cone-rod dystrophy, or maculopathy. Alternatively, patients affected with syndromic disease may already have other systemic manifestations at the time retinal disease is diagnosed.

Competitive incorporation of perrhenate and nitrate into sodalite.

Nuclear waste storage tanks at the Hanford site in southeastern Washington have released highly alkaline solutions, containing radioactive and other contaminants, into subsurface sediments. When this waste reacts with subsurface sediments, feldspathoid minerals (sodalite, cancrinite) can form, sequestering pertechnetate (99TcO4-) and other ions. This study investigates the potential for incorporation of perrhenate (ReO4-), a chemical surrogate for 99TcO4-, into mixed perrhenate/nitrate (ReO4-/NO3-) sodalite.

Anesthesia and increased hypercarbic drive impair the coordination between breathing and swallowing.

Background: Coordination between breathing and swallowing helps prevent aspiration of foreign material into the respiratory tract. The authors examined the effects of anesthesia and hypercapnia on swallowing-breathing coordination.

Methods: In a randomized controlled crossover study, general anesthesia with propofol or sevoflurane was titrated using an up-down method to identify the threshold for suppression of the motor response to electrical stimulation of the forearm.

TNF-receptor inhibitor therapy for the treatment of children with idiopathic pneumonia syndrome. A joint Pediatric Blood and Marrow Transplant Consortium and Children's Oncology Group Study (ASCT0521).

Idiopathic pneumonia syndrome (IPS) is an acute, noninfectious lung disorder associated with high morbidity and mortality after hematopoietic cell transplantation. Previous studies have suggested a role for TNFα in the pathogenesis of IPS. We report a multicenter phase II trial investigating a soluble TNF-binding protein, etanercept (Enbrel, Amgen, Thousand Oaks, CA), for the treatment of pediatric patients with IPS.

A comparison of propofol- and dexmedetomidine-induced electroencephalogram dynamics using spectral and coherence analysis.

Background: Electroencephalogram patterns observed during sedation with dexmedetomidine appear similar to those observed during general anesthesia with propofol. This is evident with the occurrence of slow (0.1 to 1 Hz), delta (1 to 4 Hz), propofol-induced alpha (8 to 12 Hz), and dexmedetomidine-induced spindle (12 to 16 Hz) oscillations.

Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl syndrome.

Primary cilia are sensory organelles present on most mammalian cells. The assembly and maintenance of primary cilia are facilitated by intraflagellar transport (IFT), a bidirectional protein trafficking along the cilium. Mutations in genes coding for IFT components have been associated with a group of diseases called ciliopathies.

TMEM14C is required for erythroid mitochondrial heme metabolism.

The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells.

Mutations in pre-mRNA processing factors 3, 8, and 31 cause dysfunction of the retinal pigment epithelium.

Mutations in the ubiquitously expressed pre-mRNA processing factors 3, 8, and 31 (PRPF3, PRPF8, and PRPF31) cause nonsyndromic dominant retinitis pigmentosa in humans, an inherited retinal degeneration. It is unclear what mechanisms, or which cell types of the retina, are affected. Transgenic mice with the human mutations in these genes display late-onset morphological changes in the retinal pigment epithelium (RPE).

A murine RP1 missense mutation causes protein mislocalization and slowly progressive photoreceptor degeneration.

Mutations in the RP1 gene can cause retinitis pigmentosa. We identified a spontaneous L66P mutation caused by two adjacent point mutations in the Rp1 gene in a colony of C57BL/6J mice. Mice homozygous for the L66P mutation exhibited slow, progressive photoreceptor degeneration throughout their lifespan.