ABSTRACT
There remains continued interest in improving the advanced water oxidation process [e.g., ultraviolet (UV)/hydrogen peroxide (H2O2)] for more efficient and environmentally friendly wastewater treatment. Here, we report the design, fabrication, and performance of graphene oxide (GO, on top)/nickel-doped iron oxyhydroxide (Ni:FeOOH, shell)/silicon nanowires (SiNWs, core) as a new multifunctional photocatalyst for the degradation of common pollutants like polystyrene and methylene blue through enhancing the hydroxyl radical (â¢OH) production rate of the UV/H2O2 system. The photocatalyst combines the advantages of a large surface area and light absorption characteristics of SiNWs with heterogeneous photo-Fenton active Ni:FeOOH and photocatalytically active/charge separator GO. In addition, the built-in electric field of GO/Ni:FeOOH/SiNWs facilitates the charge separation of electrons to GO and holes to Ni:FeOOH, thus boosting the photocatalytic performance. Our photocatalyst increases the â¢OH yield by 5.7 times compared with that of a blank H2O2 solution sample and also extends the light absorption spectrum to include visible light irradiation.
ABSTRACT
The ATPase SecA is an essential component of the bacterial Sec machinery, which transports proteins across the cytoplasmic membrane. Most SecA proteins contain a long C-terminal tail (CTT). In Escherichia coli, the CTT contains a structurally flexible linker domain and a small metal-binding domain (MBD). The MBD coordinates zinc via a conserved cysteine-containing motif and binds to SecB and ribosomes. In this study, we screened a high-density transposon library for mutants that affect the susceptibility of E. coli to sodium azide, which inhibits SecA-mediated translocation. Results from sequencing this library suggested that mutations removing the CTT make E. coli less susceptible to sodium azide at subinhibitory concentrations. Copurification experiments suggested that the MBD binds to iron and that azide disrupts iron binding. Azide also disrupted binding of SecA to membranes. Two other E. coli proteins that contain SecA-like MBDs, YecA and YchJ, also copurified with iron, and NMR spectroscopy experiments indicated that YecA binds iron via its MBD. Competition experiments and equilibrium binding measurements indicated that the SecA MBD binds preferentially to iron and that a conserved serine is required for this specificity. Finally, structural modeling suggested a plausible model for the octahedral coordination of iron. Taken together, our results suggest that SecA-like MBDs likely bind to iron in vivo.
Subject(s)
Escherichia coli K12/metabolism , Escherichia coli Proteins/metabolism , Iron/metabolism , SecA Proteins/metabolism , Escherichia coli K12/genetics , Escherichia coli Proteins/genetics , Mutation , Protein Binding , Protein Domains , SecA Proteins/genetics , Sodium Azide/pharmacologyABSTRACT
The widely prescribed pharmaceutical metformin and its main metabolite, guanylurea, are currently two of the most common contaminants in surface and wastewater. Guanylurea often accumulates and is poorly, if at all, biodegraded in wastewater treatment plants. This study describes Pseudomonas mendocina strain GU, isolated from a municipal wastewater treatment plant, using guanylurea as its sole nitrogen source. The genome was sequenced with 36-fold coverage and mined to identify guanylurea degradation genes. The gene encoding the enzyme initiating guanylurea metabolism was expressed, and the enzyme was purified and characterized. Guanylurea hydrolase, a newly described enzyme, was shown to transform guanylurea to one equivalent (each) of ammonia and guanidine. Guanidine also supports growth as a sole nitrogen source. Cell yields from growth on limiting concentrations of guanylurea revealed that metabolism releases all four nitrogen atoms. Genes encoding complete metabolic transformation were identified bioinformatically, defining the pathway as follows: guanylurea to guanidine to carboxyguanidine to allophanate to ammonia and carbon dioxide. The first enzyme, guanylurea hydrolase, is a member of the isochorismatase-like hydrolase protein family, which includes biuret hydrolase and triuret hydrolase. Although homologs, the three enzymes show distinct substrate specificities. Pairwise sequence comparisons and the use of sequence similarity networks allowed fine structure discrimination between the three homologous enzymes and provided insights into the evolutionary origins of guanylurea hydrolase.IMPORTANCE Metformin is a pharmaceutical most prescribed for type 2 diabetes and is now being examined for potential benefits to COVID-19 patients. People taking the drug pass it largely unchanged, and it subsequently enters wastewater treatment plants. Metformin has been known to be metabolized to guanylurea. The levels of guanylurea often exceed that of metformin, leading to the former being considered a "dead-end" metabolite. Metformin and guanylurea are water pollutants of emerging concern, as they persist to reach nontarget aquatic life and humans, the latter if it remains in treated water. The present study has identified a Pseudomonas mendocina strain that completely degrades guanylurea. The genome was sequenced, and the genes involved in guanylurea metabolism were identified in three widely separated genomic regions. This knowledge advances the idea that guanylurea is not a dead-end product and will allow for bioinformatic identification of the relevant genes in wastewater treatment plant microbiomes and other environments subjected to metagenomic sequencing.
Subject(s)
Bacterial Proteins/metabolism , Guanidine/analogs & derivatives , Hydrolases/metabolism , Metabolic Networks and Pathways , Metformin/metabolism , Urea/analogs & derivatives , Water Pollutants, Chemical/metabolism , Ammonia/metabolism , Bacterial Proteins/genetics , Biodegradation, Environmental , Biomineralization , Genome, Bacterial/genetics , Guanidine/metabolism , Hydrolases/genetics , Multigene Family , Pseudomonas mendocina/genetics , Pseudomonas mendocina/isolation & purification , Pseudomonas mendocina/metabolism , Substrate Specificity , Urea/metabolism , Wastewater/microbiologyABSTRACT
We report a coherent terahertz (THz) imaging system that utilises a quantum cascade laser (QCL) operating in pulsed-mode as both the source and detector. The realisation of a short-pulsed THz QCL feedback interferometer permits both high peak powers and improved thermal efficiency, which enables the cryogen-free operation of the system. In this work, we demonstrated pulsed-mode swept-frequency laser feedback interferometry experimentally. Our interferometric detection scheme not only permits the simultaneous creation of both amplitude and phase images, but inherently suppresses unwanted background radiation. We demonstrate that the proposed system utilising microsecond pulses has the potential to achieve 0.25 mega-pixel per second acquisition rates, paving the pathway to video frame rate THz imaging.
ABSTRACT
Endothelin signaling is essential for neural crest development, and dysregulated Endothelin signaling is associated with several neural crest-related disorders, including Waardenburg and other syndromes. However, despite the crucial roles of this pathway in neural crest development and disease, the transcriptional effectors directly activated by Endothelin signaling during neural crest development remain incompletely elucidated. Here, we establish that the MADS box transcription factor MEF2C is an immediate downstream transcriptional target and effector of Endothelin signaling in the neural crest. We show that Endothelin signaling activates Mef2c expression in the neural crest through a conserved enhancer in the Mef2c locus and that CRISPR-mediated deletion of this Mef2c neural crest enhancer from the mouse genome abolishes Endothelin induction of Mef2c expression. Moreover, we demonstrate that Endothelin signaling activates neural crest expression of Mef2c by de-repressing MEF2C activity through a Calmodulin-CamKII-histone deacetylase signaling cascade. Thus, these findings identify a MEF2C-dependent, positive-feedback mechanism for Endothelin induction and establish MEF2C as an immediate transcriptional effector and target of Endothelin signaling in the neural crest.
Subject(s)
Endothelins/metabolism , Feedback, Physiological/physiology , Gene Expression Regulation, Developmental/physiology , Neural Crest/physiology , Signal Transduction/physiology , Animals , Galactosides , In Situ Hybridization , Indoles , MEF2 Transcription Factors/metabolism , Mice , Mice, Transgenic , Neural Crest/metabolism , beta-GalactosidaseABSTRACT
This paper is based on a literature review from 2011 to 2016. The paper is divided into two main sections. The first section relates to technical advances in fetal imaging techniques, including fetal motion compensation, imaging at 3.0 T, 3-D T2-weighted MRI, susceptibility-weighted imaging, computed tomography, morphometric analysis, diffusion tensor imaging, spectroscopy and fetal behavioral assessment. The second section relates to clinical updates, including cerebral lamination, migrational anomalies, midline anomalies, neural tube defects, posterior fossa anomalies, sulcation/gyration and hypoxic-ischemic insults.
Subject(s)
Central Nervous System Diseases/diagnostic imaging , Fetal Diseases/diagnostic imaging , Fetus/diagnostic imaging , Nervous System Malformations/diagnostic imaging , Neuroimaging/trends , Female , Humans , PregnancyABSTRACT
Pediatric lumbar puncture can be challenging or unsuccessful for several reasons. At the same time, the excellent sonographic window into the pediatric spine provides a distinct opportunity for ultrasound-guided lumbar puncture. Minimal cerebrospinal fluid and thecal displacement by subdural or epidural hematomas are common after failed clinical attempts. Ultrasound is useful for determining a safe infraconal level for subarachnoid access. Real-time guidance increases not only the success rate but also the safety of diagnostic lumbar puncture and injections for chemotherapy and myelography. In this article, we discuss clinical and technical factors for ultrasound-guided pediatric lumbar puncture.
Subject(s)
Spinal Puncture/methods , Ultrasonography, Interventional , Child , Child, Preschool , Female , Hematoma, Epidural, Cranial/etiology , Humans , Infant , Infant, Newborn , Injections, Spinal , Male , Patient Positioning , Risk Factors , Spinal Cord Injuries/etiology , Spinal Puncture/adverse effectsABSTRACT
Endothelin-converting enzyme-1 (Ece-1), a crucial component of the Endothelin signaling pathway, is required for embryonic development and is an important regulator of vascular tone, yet the transcriptional regulation of the ECE1 gene has remained largely unknown. Here, we define the activity and regulation of an enhancer from the human ECE1 locus in vivo. The enhancer identified here becomes active in endothelial progenitor cells shortly after their initial specification and is dependent on a conserved FOX:ETS motif, a composite binding site for Forkhead transcription factors and the Ets transcription factor Etv2, for activity in vivo. The ECE1 FOX:ETS motif is bound and cooperatively activated by FoxC2 and Etv2, but unlike other described FOX:ETS-dependent enhancers, ECE1 enhancer activity becomes restricted to arterial endothelium and endocardium by embryonic day 9.5 in transgenic mouse embryos. The ECE1 endothelial enhancer also contains an evolutionarily-conserved, consensus SOX binding site, which is required for activity in transgenic mouse embryos. Importantly, the ECE1 SOX site is bound and activated by Sox17, a transcription factor involved in endothelial cell differentiation and an important regulator of arterial identity. Moreover, the ECE1 enhancer is cooperatively activated by the combinatorial action of FoxC2, Etv2, and Sox17. Although Sox17 is required for arterial identity, few direct transcriptional targets have been identified in endothelial cells. Thus, this work has important implications for our understanding of endothelial specification and arterial subspecification.
Subject(s)
Aspartic Acid Endopeptidases/metabolism , Endocardium/embryology , Endothelium, Vascular/embryology , Forkhead Transcription Factors/metabolism , Metalloendopeptidases/metabolism , SOXF Transcription Factors/metabolism , Transcription Factors/metabolism , Animals , Aspartic Acid Endopeptidases/genetics , Cloning, Molecular , DNA Primers/genetics , Electrophoretic Mobility Shift Assay , Endocardium/metabolism , Endothelin-Converting Enzymes , Endothelium, Vascular/metabolism , Enhancer Elements, Genetic/genetics , Fluorescent Antibody Technique , Galactosides , Humans , Indoles , Metalloendopeptidases/genetics , Mice , Mice, Transgenic , Mutagenesis , SOX Transcription Factors/metabolismABSTRACT
Coordinated contraction of the heart is essential for survival and is regulated by the cardiac conduction system. Contraction of ventricular myocytes is controlled by the terminal part of the conduction system known as the Purkinje fiber network. Lineage analyses in chickens and mice have established that the Purkinje fibers of the peripheral ventricular conduction system arise from working myocytes during cardiac development. It has been proposed, based primarily on gain-of-function studies, that Endothelin signaling is responsible for myocyte-to-Purkinje fiber transdifferentiation during avian heart development. However, the role of Endothelin signaling in mammalian conduction system development is less clear, and the development of the cardiac conduction system in mice lacking Endothelin signaling has not been previously addressed. Here, we assessed the specification of the cardiac conduction system in mouse embryos lacking all Endothelin signaling. We found that mouse embryos that were homozygous null for both ednra and ednrb, the genes encoding the two Endothelin receptors in mice, were born at predicted Mendelian frequency and had normal specification of the cardiac conduction system and apparently normal electrocardiograms with normal QRS intervals. In addition, we found that ednra expression within the heart was restricted to the myocardium while ednrb expression in the heart was restricted to the endocardium and coronary endothelium. By establishing that ednra and ednrb are expressed in distinct compartments within the developing mammalian heart and that Endothelin signaling is dispensable for specification and function of the cardiac conduction system, this work has important implications for our understanding of mammalian cardiac development.
Subject(s)
Endothelins/metabolism , Myocardial Contraction/physiology , Purkinje Fibers/embryology , Receptors, Endothelin/genetics , Animals , Cell Differentiation , Cell Transdifferentiation , Connexin 43/biosynthesis , Connexins/biosynthesis , Endocardium/metabolism , Endothelium/metabolism , Gene Expression Regulation, Developmental , Mice , Mice, Knockout , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Organogenesis , Purkinje Fibers/physiology , Receptors, Endothelin/biosynthesis , Signal Transduction , Gap Junction alpha-5 ProteinABSTRACT
The demand for methods and technologies capable of rapid, inexpensive and continuous monitoring of health status or exposure to environmental pollutants persists. In this work, the development of novel surface-enhanced Raman spectroscopy (SERS) substrates from metal-coated silk fabric, known as zari, presents the potential for SERS substrates to be incorporated into clothing and other textiles for the routine monitoring of important analytes, such as disease biomarkers or environmental pollutants. Characterization of the zari fabric was completed using scanning electron microscopy, energy dispersive X-ray analysis and Raman spectroscopy. Silver nanoparticles (AgNPs) were prepared, characterized by transmission electron microscopy and UV-vis spectroscopy, and used to treat fabric samples by incubation, drop-coating and in situ synthesis. The quality of the treated fabric was evaluated by collecting the SERS signal of 4,4'-bipyridine on these substrates. When AgNPs were drop-coated on the fabric, sensitive and reproducible substrates were obtained. Adenine was selected as a second probe molecule, because it dominates the SERS signal of DNA, which is an important class of disease biomarker, particularly for pathogens such as Plasmodium spp. and Mycobacterium tuberculosis. Excellent signal enhancement could be achieved on these affordable substrates, suggesting that the developed fabric chips have the potential for expanding the use of SERS as a diagnostic and environmental monitoring tool for application in wearable sensor technologies.
Subject(s)
DNA, Bacterial/analysis , Metal Nanoparticles/chemistry , Silk/analysis , Silver/chemistry , Spectrum Analysis, Raman/methods , Textiles/analysis , Environmental Pollutants/analysis , Microscopy, Electron, Scanning/methods , Microscopy, Electron, Transmission/methods , Pyridines/chemistry , Silk/chemistry , Silk/economics , Surface PropertiesABSTRACT
OBJECT The objective of this study was to provide a technique that could be used in the preoperative period to facilitate the surgical exploration of peripheral nerve pathology. METHODS The authors describe a technique in which 1) ultrasonography is used in the immediate preoperative period to identify target peripheral nerves, 2) an ultrasound-guided needle electrode is used to stimulate peripheral nerves to confirm their position, and then 3) a methylene blue (MB) injection is performed to mark the peripheral nerve pathology to facilitate surgical exploration. RESULTS A cohort of 13 patients with varying indications for peripheral nerve surgery is presented in which ultrasound guidance, stimulation, and MB were used to localize and create a road map for surgeries. CONCLUSIONS Preoperative ultrasound-guided MB administration is a promising technique that peripheral nerve surgeons could use to plan and execute surgery.
Subject(s)
Methylene Blue/metabolism , Neurosurgical Procedures/methods , Peripheral Nervous System Diseases/diagnostic imaging , Peripheral Nervous System Diseases/surgery , Ultrasonography, Interventional/methods , Adult , Cohort Studies , Female , Humans , Injections, Intradermal , Magnetic Resonance Imaging , Male , Methylene Blue/administration & dosage , Middle Aged , Neurosurgical Procedures/standards , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/metabolismABSTRACT
Previous literature has consistently discussed reoccurring issues with conducting research in the gay and lesbian community and, for the purposes of this article, particularly the older lesbian community. Issues with sampling, including gaining access, ethical considerations, and conceptual definitions are ongoing struggles repeated within the literature. This article provides the experience of a research team in conducting such research and presents the viable solutions and ongoing barriers, as well as newer considerations that future research must take into account. In addition, this article provides the viewpoint of 189 older lesbians on the future research needs within their community.
Subject(s)
Homosexuality, Female , Research , Aged , Ethics, Research , Female , Health Services Needs and Demand , Homosexuality, Female/psychology , Humans , Racial Groups/psychology , Research Design , Sampling Studies , Social Work , Surveys and QuestionnairesABSTRACT
We synthesized and characterized two isomeric microporous hydrocarbon ladder polymers from catalytic arene norbornene annulation (CANAL) of regioisomeric bis-norbornene fused spirobifluorenes, where the ladder chains are connected either through the same fluorene unit or across two different fluorene units in spirobifluorene. This pair of isomeric polymers was used to investigate the effect of ladder macromolecular structures on the microporosity and transport properties. Both polymers form mechanically intact films with thermal stability up to 480 °C and relatively high BET surface areas. The polymer formed from 2,7-dibromospirobifluorene showed higher BET surface area and higher gas permeability than the polymer from 2,2'-dibromospirobifluorene despite similar intersegmental spacing as indicated by X-ray scattering. The aging behavior for both polymers followed the same trend as the previously reported CANAL-fluorene polymers, with dramatically increased permselectivities over time, resulting in gas separation performance above the 2008 upper bounds for H2/CH4 and O2/N2.
ABSTRACT
Potent partnerships among researchers, policymakers, and community members have potential to produce positive changes in communities on a range of topics, including behavioral health. The paper provides a brief illustrative review of such partnerships and then describes the development and evolution of one partnership in particular in Virginia. The origin of the partnership is traced, along with its founding vision, mission, and values. Some of its several projects are described, including (a) needs assessment for implementation of evidence-based programs (EBPs) pursuant to the Family First Prevention Services Act; (b) statewide fidelity monitoring of key EBPs; and (c) projects to synergize state investments in specific EBPs, like multisystemic therapy, functional family therapy, and high fidelity wraparound. The paper concludes with some themes around which the center has evolved to serve the state and its citizens more effectively.
Subject(s)
Policy , PsychiatryABSTRACT
OBJECTIVE: To evaluate the utility of digital mammography in detecting asymptomatic malignancy in autologous flap reconstructions after mastectomy. METHODS: A retrospective database review identified all mammograms performed on asymptomatic patients with flap reconstructions over a 9-year period (1/1/2009 to 12/31/2017). A negative examination was defined as BI-RADS 1 or 2 and a positive examination was defined as BI-RADS 0, 4, or 5 assigned to the mastectomy side. Malignant outcomes were determined by pathology results. Interval cancers, or false negatives, were defined as locoregional malignant diagnosis within one year of a negative mammogram. Sensitivity, specificity, predictive values, abnormal interpretation rate, and cancer detection rate were calculated. RESULTS: 626 mammograms of asymptomatic flap reconstructions were performed in 183 patients. The most common flap type was TRAM (83.5 %, 523/626) and DIEP (13.4 %, 84/626). Most exams (98.2 %, 615/626) were negative, assessed as BI-RADS 1 or 2, with no interval cancers at follow-up. Eleven exams (1.8 %, 11/626) were positive, assessed as BI-RADS 0, 4, or 5. After diagnostic work-up of all BI-RADS 0 exams, 9 cases had a final recommendation for biopsy of which 3 were malignant. Mammography yielded a cancer detection rate of 0.5 % (3/626), abnormal interpretation rate of 1.8 % (11/626), NPV of 100 % (615/615), overall PPV of 27.3 % (3/11), PPV2 (positive predictive value of a biopsy recommendation) of 33.3 % (3/9), sensitivity of 100 % (3/3), and specificity of 98.7 % (615/623). CONCLUSION: Digital mammography of asymptomatic autologous flap reconstructions after mastectomy demonstrated high sensitivity and low abnormal interpretation rate. Cancer detection rate was comparable to current national benchmarks for mammographic screening in the general U.S. population without mastectomy.
Subject(s)
Breast Neoplasms , Mammaplasty , Humans , Female , Mastectomy , Retrospective Studies , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/surgery , Mammography/methods , Sensitivity and SpecificityABSTRACT
OBJECTIVE: The orbit contains structures from which a wide spectrum of disease can arise. This article focuses on orbital anatomy and a simple compartmental approach to evaluating the orbit on diagnostic imaging. The characteristic findings of key fetal structural diseases and a wide spectrum of pediatric orbital disorders, including inflammatory disorders and developmental lesions, and the differential diagnosis of benign versus malignant masses will be discussed. CONCLUSION: Orbital abnormalities in fetuses may be recognized using ultrasound and MRI. Anophthalmia, hypertelorism, and hypotelorism either may be part of a genetic syndrome or may be related to a developmental abnormality of the fetal skull. In the pediatric population, cross-sectional imaging with CT and MRI offers a means to assess which compartments of the orbit are affected. Aggressive masses have characteristic features and must be evaluated for intracranial extension.
Subject(s)
Diagnostic Imaging , Orbit/abnormalities , Orbital Diseases/diagnosis , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Orbit/anatomy & histology , PregnancyABSTRACT
An increased level of uric acid in urine and plasma is indicative of the development of preeclampsia, a hypertensive disorder that can occur during pregnancy. The preliminary steps towards developing a rapid tool for early diagnosis of preeclampsia using electrochemical SERS (E-SERS) for the detection of uric acid in urine are presented herein. Characterization of the uric acid species was completed using cyclic voltammetry, UV spectroscopy, Raman spectroscopy and electrochemical surface-enhanced Raman spectroscopy (E-SERS). E-SERS was capable of easily detecting uric acid directly at concentrations <1 mM in urine simulant, without the need for costly enzymes and bulky equipment, and thus demonstrates promise as a rapid point-of-care diagnostic tool for detection of early onset preeclampsia in developing nation settings.
Subject(s)
Electrochemical Techniques , Pre-Eclampsia/diagnosis , Spectrum Analysis, Raman , Uric Acid/urine , Female , Humans , Metal Nanoparticles/chemistry , Pregnancy , Silver/chemistryABSTRACT
Two cases involving toddlers who presented with limb length shortening and radiological findings consistent with growth plate arrest are presented. Both cases had been cared for in the neonatal intensive care unit because of extreme prematurity, and both cases had a femoral arterial line inserted on the side of the body with the short limb. This complication has not been previously described in the preterm population.
Les auteurs présentent deux cas de tout-petits qui ont consulté en raison du raccourcissement d'un membre et dont les observations radiologiques concordaient avec un arrêt de croissance du cartilage de conjugaison. Les deux cas ont été soignés à l'unité de soins intensifs néonatals en raison d'une extrême prématurité et se sont fait insérer un cathéter de l'artère fémorale du côté du membre plus court. Cette complication n'a jamais été décrite dans la population de prématurés.
ABSTRACT
COVID-19 is associated with serious cardiovascular complications, with incompletely understood mechanism(s). Pericytes have key functions in supporting endothelial cells and maintaining vascular integrity. We demonstrate that human cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. Viral entry into pericytes is mediated by endosomal proteases, and infection leads to up-regulation of inflammatory markers, vasoactive mediators, and nuclear factor kappa-B-dependent cell death. Furthermore, we present evidence of cardiac pericyte infection in COVID-19 myocarditis patients. These data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a role for pericyte infection in COVID-19.