bluuebunny/crossref_metadata_2025 huggingface dataset:
Acne Vulgaris and its Association with Ocular Dryness - A Randomised Hospital Based Study
Authors: Das Sujit , Verma Sanjeev , Pradeep B.
Published: May 2020

Background:

Dry eye is a multi factorial disease of the tears and ocular surface. Both acne vulgaris and mebomian glands are influenced by androgenic hormone and there is a strong correlation found between acne vulgaris and evaporative type of ocular dryness in the present study.

Aim of the study:

To identify the prevalence of dryness in patients of acne vulgaris

Study design:

A randomised hospital based study over a period of 3 years

Methods & materials:

All patients between 13-30 years of age with acne vulgaris both inflammatory and non inflammatory were screened randomly for dry eye using Schirmer's test, tear film breakup time (TBUT), tear film height, presence of conjunctival injection, punctate epithelial erosions (PEE) on flourescein stain. Meibomian gland dysfunction (MGD) was used to diagnose dry eye.

Results:

Out of 200 patients male were [n=106] predominated and mostly in the age group of 21-25 years. After 3 months of treatment there was marked improvement in tear film break up time [TBUT] and Schirmer's test. Only 74 cases (37%) had punctate epitheleal lesions and 36% cases had associated mebomian gland dysfunction.

Conclusions:

Both acne vulgaris and mebomian glands are influenced by androgenic hormone and there is strong correlation between acne vulgaris and ocular dryness.
Macular Dystrophy in a Post LASIK Patient
Authors: Vatsa Sanjana , Sood Shana
Published: May 2020

LASIK (Laser Assisted Insitu keratomileusis) is the most commonly performed refractive surgery worldwide. A detailed pre operative and post operative evaluation of the anterior and posterior segment is a must. A 35 year old male patient with a history of LASIK surgery done 13 years back presented to us with complaint of painless, progressive diminution of vision in both eyes from past 2 years. Dilated retinal examination showed bulls eye maculopathy in both eyes. Macular OCT showed gross reduction in central foveal thickness. ERG showed marked reduction in photopic responses suggestive of a cone dystrophy. Treatment aims at alleviating the symptoms and use of low vision aids. Genetic counselling may be of benefit for affected individuals and their families.
Type-II Lepra Reaction and Granulomatous Uveitis – An Unusual Presentation
Authors: Das Sujit , Pradeep B. , Ojha Pushpanjali
Published: May 2020

We describe a case of young male who presented with lepra reaction with multiple macula-papular rash over face, forehead, ear lobules with peripheral neuropathy (Ulnar nerve thickening) and bilateral granulomatous uveitis. Slit skin smear was negative but skin nodular biopsy showed multiple discreet deeper dermis noncaseating well formed epitheloid cell granulomas with multinucleated giant cells intermixed with lymphocytes. Fite Faraco stain was negative suggestive of lepra reaction. Patient responded well with topical steroid and cycloplegic drops with disappearance of iris nodules. Systemic steroid was given for 12 weeks with gradual tapering to control lepra reaction and to prevent further ocular morbidity. Since ocular involvement can be seen even after completion of anti-leprosy treatment, the need for screening and periodic eye examination of the patient should be emphasized, for early identification of potentially sight-threatening lesions which can be easily treated. An ophthalmologist and a trained leprologist should preferably be included in the treatment of Hansen disease with ocular manifestations.
Secondary Fungal Infection in Viral Keratitis
Authors: Potti Sudhakar , Darla Santha Kumari , Sakare Eswar Rao
Published: May 2020

Purpose:

To report incidence of secondary fungal infection in herpes simplex keratitis.

Case Summary:

Two patients of recurrent viral keratitis who were on systemic antivirals and topical steroids presented with worsening symptoms and decreased vision with epithelial defect and pigmented stromal infiltrate. Corneal scrapings were done. Fungal hyphae were seen on smears and growth on culture. Steroid therapy was stopped, systemic antivirals continued and antifungal therapy was started.

Conclusion:

Secondary infection has to be considered, when herpes keratitis worsens on treatment. We should be aware of uncommon manifestations of keratitis.
c
‐Charts
Authors: Morais Manuel C. , Knoth Sven
Published: May 2020

Each specification that is not satisfied by a unit of a product is considered a defect, a demerit, or, more generally, a
nonconformity
. ‐chart is the term used in quality control for a chart in which the count of nonconformities in each of a sequence of samples of constant size is plotted against the serial number of the sample. We describe the ‐chart with 3‐ control limits, provide examples using R (programming language), and discuss a technique to mitigate its poor performance.
Bayesian Methods in Brain Networks
Authors: Durante Daniele , Guindani Michele
Published: May 2020

The recent developments in resonance imaging technologies have allowed growing access to a wide variety of complex information on brain functioning. Regardless of the several types of data modalities which are now available, a fundamental interest in the neurosciences is in conducting inference on brain networks. In this article, we discuss statistical methods for brain networks with a specific focus on the Bayesian approach. Due to its ability to allow careful uncertainty quantification, borrowing of information, and inclusion of experts knowledge, the Bayesian paradigm can provide a particularly effective tool in the neuroscience studies.
Data Validation
Authors: van der Loo Mark P.J. , de Jonge Edwin
Published: May 2020

Data validation is the activity where one decides whether or not a particular data set is fit for a given purpose. Formalizing the requirements that drive this decision process allows for unambiguous communication of the requirements, automation of the decision process, and opens up ways to maintain and investigate the decision process itself. The purpose of this article is to formalize the definition of data validation and to demonstrate some of the properties that can be derived from this definition. In particular, it is shown how a formal view of the concept permits a classification of data quality requirements, allowing them to be ordered in increasing levels of complexity. Some subtleties arising from combining possibly many such requirements are pointed out as well.
Risk to sustainability of pest management tools in peanut
Authors: Jordan David L. , Dunne Jeffrey , Stalker H. Thomas , Shew Barbara B. , Brandenburg Rick L. , Anco Dan , Mehl Hillary , Taylor Sally , Balota Maria
Published: May 2020

A diversity of pests can adversely affect peanut (Arachis hypogaea L.) yield, quality, and financial return. Farmers rely heavily on applied chemicals to suppress many of the economically important pests present in peanut. The effectiveness of this approach to pest management may not be sustainable, however, due to evolved resistance in pests to chemicals, reluctance of basic chemical manufacturers to invest in product development because of the relatively small market for peanut compared with other crops, cost to initially register or re‐register chemicals, and the desire for peanut buyers and processors to capture international markets that may have varying agrochemical residue restrictions for peanut. Heavy reliance on chemical control could leave peanut production systems vulnerable to yield loss; thus, a more concerted research effort is needed to increase the number and availability of nonchemical tools that protect peanut from pests in order to ensure long‐term sustainability of peanut production systems.
Magnetic carbon nanotube as a highly stable support for the heterogenization of InCl3 and its application in the synthesis of isochromeno[4,3‐c]pyrazole‐5(1H)‐one derivatives
Authors: Akbarzadeh Parisa , Koukabi Nadiya
Published: May 2020

In the present study, a novel magnetically retrievable catalytic system involving indium nanoparticles on magnetic carbon nanotube (Fe3O4‐CNT‐In) was synthesized and characterized using various techniques, such as Fourier transform‐infrared, thermogravimetric analysis, energy‐dispersive X‐ray analysis, vibrating‐sample magnetometry1, X‐ray diffraction, field emission‐scanning electron microscopy and inductively coupled plasma‐optical emission spectrometry. The catalytic activity of the synthesized nanocatalyst was evaluated in green synthesis of isochromeno[4,3‐c]pyrazole‐5(1H)‐one derivatives from the reaction of ninhydrin and arylhydrazones under solvent‐free conditions. The catalyst was magnetically separated from the reaction mixture using an external magnet and recovered for five cycles without an appreciable decrease in its catalytic efficiency. Performing the reactions in environmentally friendly and affordable conditions, the low catalyst percentage, high yield of products, short reaction times, large substrate scope and easy work‐up are the merits of this protocol. Furthermore, four of the synthesized isochromeno[4,3‐c]pyrazole‐5(1H)‐one derivatives are also new.
The search for enhanced dielectric strength of polymer‐based dielectrics: A focused review on polymer nanocomposites
Authors: Tan Daniel Q.
Published: May 2020

This report traces the leading scientific endeavors to enhance the dielectric strength of polymer dielectrics for energy storage and electrical insulation applications. Remarkable progress has occurred over the past 15 years through nanodielectric engineering involving inorganic nanofillers, coatings, and polymer matrices. This article highlights the challenges of dielectric polymers primarily toward capacitors and cable/wire insulation. It also summarizes several major technical approaches to enhance the dielectric strength of polymers and nanocomposites, including nanoparticle incorporation in polymers, filler‐polymer interface engineering, and film surface coating. More attention is directed to interface contributions, including rational design of core‐shell structures, use of low‐dimensional fillers and thermally conducting fillers, and inorganic surface coating of polymer films. These efforts demonstrated the enhancement in dielectric strength by 40–160% when controlling the fillers below 5 wt% in polyvinylidenedifluoride (PVDF) composites. This article also discussed the possible dielectric mechanisms and the positive role of interfaces against charge transport traps for attaining higher breakdown strength. The investigation of low‐dimensional filler/coating materials of high thermal conductivity can be key scientific subjects for future research.
Low‐Frequency Magnetic Fields in Cars and Office Premises and the Geomagnetic Field Variations
Authors: Sarimov Ruslan , Binhi Vladimir
Published: May 2020

In this study, we measured and analyzed the spectral characteristics of a low‐frequency magnetic field (MF) inside several gasoline‐powered cars while driving on busy city roads. The spectra obtained upon measurements in the interior of the cars are compared with those measured in office locations at different times of the day and with different disturbances of the geomagnetic field (k‐index of disturbance 2–8). The power spectral density of the electromagnetic field in cars moving on busy roads in the frequency range of 10−3–102 Hz is one to three orders of magnitude higher than that in urban offices. This raises a question regarding the possible influence of these MFs on the psychophysiological state of drivers. In turn, in the daytime, the MF power in the range from 10−3 to 1 Hz inside the locations is three times higher compared with the power of a strong geomagnetic storm. Despite such an overwhelming magnetic background, geomagnetic storms affect various organisms. The nonspecific effect of magnetic storms is supposed to be associated with relatively long (lasting several hours or more [frequency range of 10−4−10−5 Hz]) periods of enhancement or weakening of the local geomagnetic field. In this range, especially at night, the power spectral density of geomagnetic disturbances is comparable to and can even exceed the power density of urban MFs. © 2020 Bioelectromagnetics Society.
Cu2+‐selective naked‐eye ‘off–on' fluorescent probe with multisignals: chromaticity, fluorescence, electrochemistry
Authors: Xu Xiuling , Zhang Xiaoli , Cao Cuilan , Zheng Bingbing , Deng Hongxia , Shuai Qi
Published: May 2020

In this study, a rhodamine–acetylferrocene conjugate of RBFc was synthesized and then characterized using spectroscopy and single‐crystal analysis. The chemosensor RBFc exhibited a marked colour change from colourless to pink after binding to Cu2+ ions. Importantly, under the presence of the other competing cations in aqueous solution, only Cu2+ ions caused spirolactam ring opening in rhodamine B in RBFc, resulting in an enhanced absorbance of ultraviolet light spectra and fluorescence spectra, as well as obvious shifts in cyclic voltammetry curves and differential pulsed voltammetry curves. The novel probe described in this manuscript provides an attractive approach for detecting Cu2+ in the presence of other multisignals.
The Effect of Container Surface Passivation on Aggregation of Intravenous Immunoglobulin Induced by Mechanical Shock
Authors: Movafaghi Sanli , Wu Hao , Francino Urdániz Irene M. , Bull David S. , Kelly Mary D. , Randolph Theodore W. , Goodwin Andrew P.
Published: May 2020

Aggregation of therapeutic proteins can result from a number of stress conditions encountered during their manufacture, transportation, and storage. This work shows the effects of two interrelated sources of protein aggregation: the chemistry and structure of the surface of the container in which the protein is stored, and mechanical shocks that may result from handling of the formulation. How different mechanical stress conditions (dropping, tumbling, and agitation) and container surface passivation affect the stability of solutions of intravenous immunoglobulin are investigated. Application of mechanical shock causes cavitation to occur in the protein solution, followed by bubble collapse and the formation of high‐velocity fluid microjets that impinged on container surfaces, leading to particle formation. Cavitation was observed after dropping of vials from heights as low as 5 cm, but polyethylene glycol (PEG) grafting provided temporary protection against drop‐induced cavitation. PEG treatment of the vial surface reduced the formation of protein aggregates after repeated dropping events, most likely by reducing protein adsorption to container surfaces. These studies enable the development of new coatings and surface chemistries that can reduce the particulate formation induced by surface adsorption and/or mechanical shock.
Development of orthogonal T7 expression system in Klebsiella pneumoniae
Authors: Zhao Peng , Ren Minrui , Ge Xizhen , Tian Pingfang , Tan Tianwei
Published: May 2020

Most expression systems are tailored for model organisms rather than nonmodel organisms. However, heterologous gene expression in model organisms constrains the innate advantages of original strain carrying gene of interest. In this study, T7 expression system was developed in nonmodel bacterium Klebsiella pneumoniae for production of chemicals. First, we engineered a recombinant K. pneumoniae strain harboring two vectors. One vector was used to express T7 RNA polymerase (T7 RNAP) which would drive the expression of egfp in the other vector. This recombinant strain demonstrated 15.73‐fold of fluorescence relative to wild‐type K. pneumoniae and showed similar level of fluorescence to recombinant Escherichia coli overexpressing egfp. When egfp was replaced by puuC, an endogenous aldehyde dehydrogenase catalyzing 3‐hydroxypropionic acid (3‐HP) biosynthesis in K. pneumoniae, the recombinant strain coexpressing T7 RNAP and PuuC showed high‐level PuuC expression. In shake‐flask cultivation, this recombinant strain produced 1.72 g/L 3‐HP in 24 hr, which was 3.24 times that of wild‐type K. pneumoniae (0.53 g/L). To mitigate plasmid burden, the vector expressing T7 RNAP was eliminated, but the T7 RNAP expression cassette was integrated into K. pneumoniae genome. The resulting strain harboring only PuuC expression vector produced 2.44 g/L 3‐HP in 24 hr under shake‐flask conditions, which was 1.46 times that of the strain harboring both T7 RNAP and PuuC expression vectors. In bioreactor cultivation, this strain generated 67.59 g/L 3‐HP and did not show significantly halted growth. Overall, these results indicate that the engineered T7 expression system functioned efficiently in K. pneumoniae. This study provides a paradigm for the development of T7 expression system in prokaryotes.
Enhancing plasmid transformation efficiency and enabling CRISPR‐Cas9/Cpf1‐based genome editing in Clostridium tyrobutyricum
Authors: Zhang Jie , Hong Wei , Guo Liang , Wang Yifen , Wang Yi
Published: May 2020

Clostridium tyrobutyricum ATCC 25755 is known as a natural hyper‐butyrate producer with great potentials as an excellent platform to be engineered for valuable biochemical production from renewable resources. However, limited transformation efficiency and the lack of genetic manipulation tools have hampered the broader applications of this micro‐organism. In this study, the effects of Type I restriction‐modification system and native plasmid on conjugation efficiency of C. tyrobutyricum were investigated through gene deletion. The deletion of Type I restriction endonuclease resulted in a 3.7‐fold increase in conjugation efficiency, while the additional elimination of the native plasmid further enhanced conjugation efficiency to 6.05 ± 0.75 × 103 CFU/ml‐donor, which was 15.3‐fold higher than the wild‐type strain. Fermentation results indicated that the deletion of those two genetic elements did not significantly influence the end‐products production in the resultant mutant ΔRMIΔNP. Thanks to the increased conjugation efficiency, the CRISPR‐Cas9/Cpf1 systems, which previously could not be implemented in C. tyrobutyricum, were successfully employed for genome editing in ΔRMIΔNP with an efficiency of 12.5–25%. Altogether, approaches we developed herein offer valuable guidance for establishing efficient DNA transformation methods in nonmodel micro‐organisms. The ΔRMIΔNP mutant can serve as a great chassis to be engineered for diverse valuable biofuel and biochemical production.
Microbial production of 4‐amino‐1‐butanol, a four‐carbon amino alcohol
Authors: Prabowo Cindy Pricilia Surya , Shin Jae Ho , Cho Jae Sung , Chae Tong Un , Lee Sang Yup
Published: May 2020

4‐Amino‐1‐butanol (4AB) serves as an important intermediate compound for drugs and a precursor of biodegradable polymers used for gene delivery. Here, we report for the first time the fermentative production of 4AB from glucose by metabolically engineered Corynebacterium glutamicum harboring a newly designed pathway comprising a putrescine (PUT) aminotransferase (encoded by ygjG) and an aldehyde dehydrogenase (encoded by yqhD) from Escherichia coli, which convert PUT to 4AB. Application of several metabolic engineering strategies such as fine‐tuning the expression levels of ygjG and yqhD, eliminating competing pathways, and optimizing culture condition further improved 4AB production. Fed‐batch culture of the final metabolically engineered C. glutamicum strain produced 24.7 g/L of 4AB. The strategies reported here should be useful for the microbial production of primary amino alcohols from renewable resources.
Visual rating versus volumetry of regional brain atrophy and longitudinal changes over a 5‐year period in an elderly population
Authors: Velickaite Vilma , Ferreira Daniel , Lind Lars , Ahlström Håkan , Kilander Lena , Westman Erik , Larsson Elna‐Marie
Published: May 2020

Introduction

The purpose of our study was to compare visual rating and volumetry of brain atrophy in an elderly population over a 5‐year period and compare findings with cognitive test results.

Materials and Methods

Two hundred and one subjects were examined with magnetic resonance imaging (MRI) of the brain. Visual rating and volumetry were performed in all subjects at ages 75 and 80. Cognitive function at both time points was assessed with the Mini‐Mental State Examination (MMSE) and Trail Making Tests A and B (TMT‐A and TMT‐B). Changes in visual rating and volumetry were compared with changes in cognitive test.

Results

A correlation was found between visual rating of medial temporal lobe atrophy (MTA) and hippocampal volumetry at both time points (rs = −.42 and rs = −.49, p < .001, respectively). The correlation between visual rating of posterior atrophy (PA); frontal atrophy (F‐GCA) and volumetry of these brain regions was significant only at age 80 (rs = −.16, p = .02 for PA and rpb = .19, p = .006 for F‐GCA). Visual rating showed only a minimal progression of regional atrophy at age 80, whereas volumetry showed 2%–5% decrease in volume depending on brain region. Performance in the MMSE, TMT‐A, and TMT‐B was virtually unchanged between ages 75 and 80.

Conclusion

We found a mild age‐associated decrease in regional brain volumes in this healthy cohort with well‐preserved cognitive functions. Visual assessment may not be sufficient for detecting mild progression of brain atrophy due to normal aging, whereas volumetry is more sensitive to capture these subtle changes.
Pfeiffer Syndrome type 2; A case report of cranio‐orbitofaciostenosis with bilateral choanal atresia at Muhimbili National Hospital, Tanzania
Authors: Amiji Insiyah , Kalezi Zawadi E. , Abdulshakoor Ashfaq , Tarimo Janet F. , Leiya Raymond , Zuechner Antke , Naburi Helga E. , Massawe Augustine , Manji Karim P.
Published: May 2020

Pfeiffer syndrome is a rare genetic disorder with heterogenous phenotype and prognosis. Due to its diverse clinical presentation, it can easily be misdiagnosed. Where genetic testing still remains a challenge, antenatal sonogram can aid in early diagnosis. The cranioorbito‐faciostenosis demands aggressive management to permit survival instead of uniform early demise.
Synthesis Gas Conversion to Lower Olefins over ZnCr‐SAPO‐34 Catalysts: Role of ZnO−ZnCr2O4 Interface
Authors: Wang Xiaoyue , Cao Ruiwen , Chen Kuo , Si Congcong , Ban Hongyan , Zhang Peng , Meng Fanhui , Jia Litao , Mi Jie , Li Zhong , Li Congming
Published: May 2020

This work reports that the ZnO−ZnCr2O4 interface was constructed by tailoring the Zn/Cr ratio and the role of ZnO−ZnCr2O4 interface in activating CO molecule for the synthesis of lower olefins over a tandem catalyst was studied. A lower olefins selectivity of 71 % at a CO conversion of 34 % was achieving on Zn1Cr1&SAPO‐34. The presence of ZnO−ZnCr2O4 interface effectively reduces the activation energy of CO hydrogenation (from 51.8 kJ/mol to 33.6 kJ/mol) and subsequently leading to the triple increase of intrinsic activity. In situ DRIFTS and XPS studies demonstrate that the better catalytic activities of Zn1Cr1 catalyst are related to the presence of ZnO−ZnCr2O4 interface, which provides more oxygen vacancy sites for CO adsorption and activation. In this sense, the Zn1Cr1 catalyst with ZnO−ZnCr2O4 interface is more active than the simple physical mixture of ZnO and Cr2O3 catalyst separately and Zn1Cr2 catalyst. This work provides fundamental insights for a rational design of Zn−Cr based catalysts and even other heterogeneous catalysts by constructing oxide‐oxide interface.
Cu Anchored Ti2NO2 as High Performance Electrocatalyst for Oxygen Evolution Reaction: A Density Functional Theory Study
Authors: Chen Zhiguo , Fan Xiaoli , Shen Zihan , Ruan Xiaopeng , Wang Lan , Zeng Hanghang , Wang Jiahui , An Yurong , Hu Yan
Published: May 2020

MXenes have attracted great attention in the fields of energy conversion and catalysis, and have proved to be an effective supporting material for single atom catalysts (SACs). In the present study, we investigated the catalytic activity of a series mono‐atomic transition‐metal atoms supported by MXenes M2NO2 for oxygen evolution reaction (OER) via first principle calculation. Particularly, single atom Cu site on Ti2NO2 having the lowest overpotentials of 0.24 V and bonding with the reaction intermediates moderately, is the most active SAC for OER. Energetically, Cu atom prefers to be mono‐atomically anchored on Ti2NO2 instead of aggregating. Plus, Cu anchoring enhance the electronic states around Fermi level. Additionally, ab‐initio molecular dynamics simulations show that Cu atom is anchored on Ti2NO2, stable and isolatable at 300 K. Studies on the small molecule adsorption on Cu‐Ti2NO2 further prove the potential applications of Cu−Ti2NO2 as active SACs for OER. Our results broaden the perception of MXenes and guide the exploration of non‐noble metal based OER electrocatalysts.
Graphitic carbon nitride (g‐C3N4)‐based nanosized heteroarrays: Promising materials for photoelectrochemical water splitting
Authors: Wang Liqun , Si Wenping , Tong Yueyu , Hou Feng , Pergolesi Daniele , Hou Jungang , Lippert Thomas , Dou Shi Xue , Liang Ji
Published: May 2020

Photoelectrochemical (PEC) water splitting is recognized as a sustainable strategy for hydrogen generation due to its abundant hydrogen source, utilization of inexhaustible solar energy, high‐purity product, and environment‐friendly process. To actualize a practical PEC water splitting, it is paramount to develop efficient, stable, safe, and low‐cost photoelectrode materials. Recently, graphitic carbon nitride (g‐C3N4) has aroused a great interest in the new generation photoelectrode materials because of its unique features, such as suitable band structure for water splitting, a certain range of visible light absorption, nontoxicity, and good stability. Some inherent defects of g‐C3N4, however, seriously impair further improvement on PEC performance, including low electronic conductivity, high recombination rate of photogenerated charges, and limited visible light absorption at long wavelength range. Construction of g‐C3N4‐based nanosized heteroarrays as photoelectrodes has been regarded as a promising strategy to circumvent these inherent limitations and achieve the high‐performance PEC water splitting due to the accelerated exciton separation and the reduced combination of photogenerated electrons/holes. Herein, we summarize in detail the latest progress of g‐C3N4‐based nanosized heteroarrays in PEC water‐splitting photoelectrodes. Firstly, the unique advantages of this type of photoelectrodes, including the highly ordered nanoarray architectures and the heterojunctions, are highlighted. Then, different g‐C3N4‐based nanosized heteroarrays are comprehensively discussed, in terms of their fabrication methods, PEC capacities, and mechanisms, etc. To conclude, the key challenges and possible solutions for future development on g‐C3N4‐based nanosized heteroarray photoelectrodes are discussed.
Addressing cost‐related nonadherence to oral anticancer medications through health policy reform: Challenges and opportunities
Authors: Jazowski Shelley A. , Dusetzina Stacie B.
Published: May 2020

In this editorial, the authors discuss several of Dean et al's proposed interventions aimed at payers and the pharmaceutical supply chain and highlight the challenges and opportunities for improving patient access to oral anticancer medications through system reform. This editorial focuses on payers and the pharmaceutical supply chain because these systems set prices and reimbursement in the United States and are directly responsible for cost‐related barriers that influence the accessibility and affordability of prescription medications.
Proximity‐CLIP and Expedited Non‐Radioactive Library Preparation of Small RNA Footprints for Next‐Generation Sequencing
Authors: Anastasakis Dimitrios , Benhalevy Daniel , Hafner Markus
Published: May 2020

During the course of their life cycle, most RNAs move between several cellular environments where they associate with different RNA binding proteins (RBPs). Reciprocally, a significant portion of RBPs reside in more than a single cellular compartment, where they can interact with discrete RNAs and even exert distinct biological roles. Proximity‐CLIP combines proximity biotinylation of proteins with photoactivatable ribonucleoside‐enhanced protein‐RNA crosslinking to simultaneously profile the proteome, including RBPs and the RBP‐bound transcriptome, in any given subcellular compartment. Here we provide a detailed experimental protocol for Proximity‐CLIP along with a simplified non‐radioactive, small‐RNA cDNA library preparation protocol. Published 2020 U.S. Government.

Basic Protocol 1: Cell culture, 4SU labeling, proximity biotinylation, and crosslinking

Basic Protocol 2: Cell extraction, streptavidin affinity purification, and on‐beads trypsinization

Basic Protocol 3: RNA footprints cDNA library preparation

Support Protocol: Preparation of RNA‐seq libraries from intact RNA
Production of Digoxigenin‐Labeled Riboprobes for In Situ Hybridization Experiments
Authors: Barratt Kristen S. , Arkell Ruth M.
Published: May 2020

Experiments that visualize gene expression in intact tissues or organisms are fundamental to studies of gene function. These experiments, called in situ hybridization, require the production of a riboprobe, which is a labeled antisense RNA corresponding to a particular gene. The most commonly used system for visualizing gene expression via in situ hybridization is the incorporation of a digoxigenin label into an in vitro−transcribed RNA probe. After hybridization of the riboprobe to a target mRNA, its location can be detected via a high‐affinity α‐digoxigenin antibody conjugated to an alkaline‐phosphatase enzyme. The article describes the design and production of digoxigenin‐labeled riboprobes transcribed in vitro from template DNA (either plasmid or PCR amplicon). These riboprobes are suitable for use in tissue and whole‐mount in situ hybridization protocols. © 2020 by John Wiley & Sons, Inc.

Basic Protocol 1: Plasmid‐derived riboprobes

Alternate Protocol: PCR‐derived riboprobes

Basic Protocol 2: Riboprobe synthesis with DIG label
Serum concentrations, pharmacokinetic/pharmacodynamic modeling, and effects of dexamethasone on inflammatory mediators following intravenous and oral administration to exercised horses
Authors: Knych Heather K. , Weiner Daniel , Arthur Rick M. , Baden Russell , McKemie Daniel S. , Kass Philip H.
Published: May 2020

Corticosteroids are potent anti‐inflammatory drugs and as such are commonly administered to performance and racehorses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics and effects on cortisol and inflammatory mediator concentrations, following intravenous and oral administration to 12 exercised horses. Horses received an intravenous administration of 40 mg of dexamethasone sodium phosphate and 20 mg of dexamethasone tablets with a 4 week washout in between administrations. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Whole blood samples were collected at various time points and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. The concentrations of dexamethasone and eicosanoids were measured using LC–MS/MS and the concentrations from both routes of administration fit simultaneously using a three‐compartment pharmacokinetic model. A turnover model with inhibition of Kin gave an adequate fit to the dexamethasone‐cortisol PKPD data. Serum and urine dexamethasone concentrations were at the limit of quantitation at 96 and 48 hours post administration, respectively. The volume of distribution, systemic clearance, and terminal half‐life was 0.907 L/kg, 7.89 mL/h/kg, and 1.34 h, respectively. The IC50 for cortisol suppression was 0.007 ng/mL. Stimulation of dexamethasone treated blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of inflammatory biomarker production for a prolonged period of time post drug administration. The results of this study suggest that dexamethasone has a prolonged anti‐inflammatory effect following intravenous or oral administration to horses.
Functional significance of phylogeographic structure in a toxic benthic marine microbial eukaryote over a latitudinal gradient along the East Australian Current
Authors: Verma Arjun , Hughes David J. , Harwood D. Tim , Suggett David J. , Ralph Peter J. , Murray Shauna A.
Published: May 2020

Genetic diversity in marine microbial eukaryotic populations (protists) drives their ecological success by enabling diverse phenotypes to respond rapidly to changing environmental conditions. Despite enormous population sizes and lack of barriers to gene flow, genetic differentiation that is associated with geographic distance, currents, and environmental gradients has been reported from planktonic protists. However, for benthic protists, which have reduced dispersal opportunities, phylogeography and its phenotypic significance are little known. In recent years, the East Australian Current (EAC) has intensified its southward flow, associated with the tropicalization of temperate waters. Benthic harmful algal species have been increasingly found in south‐eastern Australia. Yet little is known about the potential of these species to adapt or extend their range in relation to changing conditions. Here, we examine genetic diversity and functional niche divergence in a toxic benthic dinoflagellate, Ostreopsis cf. siamensis, along a 1,500 km north–south gradient in southeastern Australia. Sixty‐eight strains were established from eight sampling sites. The study revealed long‐standing genetic diversity among strains established from the northern‐most sites, along with large phenotypic variation in observed physiological traits such as growth rates, cell volume, production of palytoxin‐like compounds, and photophysiological parameters. Strains from the southern populations were more uniform in both genetic and functional traits, and have possibly colonized their habitats more recently. Our study reports significant genetic and functional trait variability in a benthic harmful algal species, indicative of high adaptability, and a possible climate‐driven range extension. The observed high trait variation may facilitate development of harmful algal blooms under dynamic coastal environmental conditions.
Prevention and treatment of COVID‐19 disease by controlled modulation of innate immunity
Authors: Schijns Virgil , Lavelle Ed C.
Published: May 2020

The recent outbreak of coronavirus disease 2019 (COVID‐19), triggered by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) poses an enormous threat to global public health and economies. Human coronaviruses normally cause no or mild respiratory disease but in the past two decades, potentially fatal coronavirus infections have emerged, causing respiratory tract illnesses such as pneumonia and bronchitis. These include severe acute respiratory syndrome coronavirus (SARS‐CoV), followed by the Middle East respiratory syndrome coronavirus (MERS‐CoV), and recently the SARS‐CoV‐2 coronavirus outbreak that emerged in Wuhan, China, in December 2019. Currently, most COVID‐19 patients receive traditional supportive care including breathing assistance. To halt the ongoing spread of the pandemic SARS‐CoV‐2 coronavirus and rescue individual patients, established drugs and new therapies are under evaluation. Since it will be some time until a safe and effective vaccine will be available, the immediate priority is to harness innate immunity to accelerate early antiviral immune responses. Second, since excessive inflammation is a major cause of pathology, targeted anti‐inflammatory responses are being evaluated to reduce inflammation‐induced damage to the respiratory tract and cytokine storms. Here, we highlight prominent immunotherapies at various stages of development that aim for augmented anti‐coronavirus immunity and reduction of pathological inflammation.
Dynamic pH barrage junction focusing of amino acids, peptides, and digested monoclonal antibodies in capillary electrophoresis–mass spectrometry
Authors: Wang Lingyu , Cheng Jianhui , McNutt Julie E. , Morin Gregg B. , Chen David D. Y.
Published: May 2020

Dynamic pH barrage junction focusing in CE enables effective signal enhancement, quantitative capture efficiencies, and straightforward optimization. The method is a technical variant of dynamic pH junction focusing. CE separation with dynamic pH barrage junction focusing is compatible with both optical and mass spectrometric detection. We developed a CE–MS/MS method using hydrophilic polyethyleneimine‐coated capillaries and validated it for the qualitative analysis of amino acids, peptides, and tryptic peptides of digested monoclonal antibodies. The S/N of extracted ion electropherograms of zwitterionic analytes were enhanced by approximately two orders of magnitude with a tradeoff of a shortened separation window. Online focusing improved the MS signal intensity of a diluted antibody digest, enabling more precursor ions to be analyzed with subsequent tandem mass spectrometric identification. It also broadened the concentration range of protein digest samples for which adequate sequence coverage data can be obtained. With only 0.9 ng of digested infliximab sample loaded into the capillary, 76% and 100% sequence coverage was realized for antibody heavy and light chains, respectively, after online focusing. Full coverage was achieved with 9 ng of injected digest.
Resistance of salt marsh substrates to near‐instantaneous hydrodynamic forcing
Authors: Brooks Helen , Möller Iris , Carr Simon , Chirol Clementine , Christie Elizabeth , Evans Ben , Spencer Kate L. , Spencer Tom , Royse Katherine
Published: May 2020

Salt marshes deliver vital ecosystem services by providing habitats, storing pollutants and atmospheric carbon, and reducing flood and erosion risk in the coastal hinterland. Net losses in salt marsh areas, both modelled globally and measured regionally, are therefore of concern. Amongst other controls, the persistence of salt marshes in any one location depends on the ability of their substrates to resist hydrodynamic forcing at the marsh front, along creek margins and on the vegetated surface. Where relative sea level is rising, marsh elevation must keep pace with sea‐level rise and landward expansion may be required to compensate for areal loss at exposed margins. This paper reviews current understanding of marsh substrate resistance to the near‐instantaneous (seconds to hours) forcing induced by hydrodynamic processes. It outlines how variability in substrate properties may affect marsh substrate stability, explores current understanding of the interactions between substrate properties and erosion processes, and how the cumulative impact of these interactions may affect marsh stability over annual to decadal timescales.

Whilst important advances have been made in understanding how specific soil properties affect near‐instantaneous marsh substrate stability, less is known about how these properties interact and alter bulk substrate resistance to hydrodynamic forcing. Future research requires a more systematic approach to quantifying biological and sedimentological marsh substrate properties. These properties must then be linked to specific observable erosion processes, particularly at the marsh front and along creek banks. A better understanding of the intrinsic dynamics and processes acting on, and within, salt marsh substrates will facilitate improved prediction of marsh evolution under future hydrodynamic forcing scenarios. Notwithstanding the additional complications that arise from morphodynamic feedbacks, this would allow us to more accurately model the future potential protection from flooding and erosion afforded by marshes, while also increasing the effectiveness of salt marsh restoration and recreation schemes. © 2020 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd
Repeated administration of a flavonoid‐based formulated extract from citrus peels significantly reduces peripheral inflammation‐induced pain in the rat
Authors: Iannitti Tommaso , Di Cerbo Alessandro , Loschi Anna Rita , Rea Stefano , Suzawa Michiko , Morales‐Medina Julio César
Published: May 2020

Depression‐related disorders are the first cause of disability worldwide according to the World Health Organization, and there is limited availability of effective antidepressant medications without side effects. Similarly, pain management is a public health concern particularly due to the increase in use of opioid medications, which have a significant side effect profile. Flavonoids can modulate numerous physiological functions including emotional and anti‐nociceptive processes. Gold lotion (GL) is a natural product based on the extract of six citrus peels rich in flavonoids (0.45 mg/ml) with numerous reported biological activities. In the present study, we investigated the effect of repeated administration of GL in a battery of behavioral tests, including the open field test (OFT), forced swim test (FST), and von Frey test (vFT), in rats. While the OFT measured anxiolytic‐related effects, the FST evaluated depression‐related behavior. The vFT evaluated mechanical allodynia in two rat models of peripheral inflammation induced by carrageenan or complete Freund's adjuvant (CFA) administration. Treatment with GL reduced mechanical allodynia after either carrageenan or CFA administration. On the other hand, repeated GL administration did not modulate any behavior evaluated by OFT or FST. Consumption of GL inhibits behavioral signs of inflammatory pain. Therefore, GL may be a valuable analgesic product to be used for inflammatory pain.
Year around distilled water production, energy, and economic analysis of solar stills—A comparative study
Authors: Muthu Manokar A. , Vimala M. , Prince Winston D. , Rajendran D. R. , Sathyamurthy Ravishankar , Kabeel A. E.
Published: May 2020

In this paper, a year around energy efficiency (EnE) and economic analysis of single slope solar still (SSSS), the single slope solar still with glass cooling (SSSSGC), the single slope solar still with basin heating (SSSSBH), and the single slope solar still with glass cooling and basin heating (SSSSGCBH) was carried out based on the distilled water production. The annual yield production from the SSSS, SSSSGC, SSSSBH, and SSSSGCBH were 476.16, 637.44, 970.24, and 1167.36 kg, respectively. The yearly yield produced from the SSSSBH and SSSSGCBH was increased by 50.92% and 59.21%, respectively, as compared with the SSSS. Moreover, the annual EnE of the SSSSGCBH was 28.75%. However, the EnE of the SSSS was 11.73%. Also, freshwater making cost is found to be 18.9, 24.9, 37.9, and 45.6 Rs/day for the SSSS, SSSSGC, SSSSBH, and SSSSGCBH, respectively, if the buying cost of freshwater is Rs 10.
Dehydroascorbic acid, the oxidized form of vitamin C, improves renal histology and function in old mice
Authors: Forman Katherine , Martínez Fernando , Cifuentes Manuel , Fernández Marcos , Bertinat Romina , Torres Pablo , Salazar Katterine , Godoy Alejandro , Nualart Francisco
Published: May 2020

Oxidative stress and inflammation are crucial factors that increase with age. In the progression of multiple age‐related diseases, antioxidants and bioactive compounds have been recognized as useful antiaging agents. Oxidized or reduced vitamin C exerts different actions on tissues and has different metabolism and uptake. In this study, we analyzed the antiaging effect of vitamin C, both oxidized and reduced forms, in renal aging using laser microdissection, quantitative reverse‐transcription polymerase chain reaction, and immunohistochemical analyses. In the kidneys of old SAM mice (10 months of age), a model of accelerated senescence, vitamin C, especially in the oxidized form (dehydroascorbic acid [DHA]) improves renal histology and function. Serum creatinine levels and microalbuminuria also decrease after treatment with a decline in azotemia. In addition, sodium‐vitamin C cotransporter isoform 1 levels, which were increased during aging, are normalized. In contrast, the pattern of glucose transporter 1 expression is not affected by aging or vitamin C treatment. We conclude that oxidized and reduced vitamin C are potent antiaging therapies and that DHA reverses the kidney damage observed in senescence‐accelerated prone mouse 8 to a greater degree.
Induced pluripotent stem cells (iPSCs) as game‐changing tools in the treatment of neurodegenerative disease: Mirage or reality?
Authors: Yousefi Niloufar , Abdollahii Shahla , Kouhbanani Mohammad Amin Jadidi , Hassanzadeh Ali
Published: May 2020

Based on investigations, there exist tight correlations between neurodegenerative diseases' incidence and progression and aberrant protein aggregreferates in nervous tissue. However, the pathology of these diseases is not well known, leading to an inability to find an appropriate therapeutic approach to delay occurrence or slow many neurodegenerative diseases' development. The accessibility of induced pluripotent stem cells (iPSCs) in mimicking the phenotypes of various late‐onset neurodegenerative diseases presents a novel strategy for in vitro disease modeling. The iPSCs provide a valuable and well‐identified resource to clarify neurodegenerative disease mechanisms, as well as prepare a promising human stem cell platform for drug screening. Undoubtedly, neurodegenerative disease modeling using iPSCs has established innovative opportunities for both mechanistic types of research and recognition of novel disease treatments. Most important, the iPSCs have been considered as a novel autologous cell origin for cell‐based therapy of neurodegenerative diseases following differentiation to varied types of neural lineage cells (e.g. GABAergic neurons, dopamine neurons, cortical neurons, and motor neurons). In this review, we summarize iPSC‐based disease modeling in neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease. Moreover, we discuss the efficacy of cell‐replacement therapies for neurodegenerative disease.
LINC01121 induced intervertebral disc degeneration via modulating miR‐150‐5p/MMP16 axis
Authors: Chen Xin , Li Zheng , Xu Derong , Li Shugang
Published: May 2020

Background

Growing evidence indicates that Long noncoding RNAs contribute to cell differentiation, invasion, metabolism, proliferation and metastasis. However, the potential role of LINC01121 in progression of intervertebral disc degeneration (IDD) remains unclear.

Methods

LINC01121, matrix metalloprotease (MMP)‐16 and miR‐150‐5p expression was determined by a quantitative‐reverse transcriptase‐polymerase chain reaction assay. Inflammatory cytokines level was measured by an enzyme‐linked immunosorbent assay and cell counting kit‐8 analysis was used to assess cell proliferation. MMP‐16‐specific binding with miR‐150‐5p was verified with a luciferase reporter assay.

Results

We noted that interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α treatment enhanced LINC01121 and MMP‐16 expression in nucleus pulposus (NP) cells. LINC01121 was higher in IDD specimens compared to that in control specimens. Higher expression of LINC01121 was correlated with disc degeneration degree. Ectopic expression of LINC01121 enhanced cell proliferation and promoted ki‐67, MMP‐3 and ADAMTS5 expression and also suppressed collagen II expression in NP cells. We observed that overexpression of LINC01121 increased the secretion of three inflammatory cytokines, including IL‐6, TNF‐α and IL‐1β. We found that ectopic expression of LINC01121 decreased the miR‐150‐5p level in NP cells. Luciferase reporter data confirmed that MMP‐16 was one direct target of miR‐150‐5p. Overexpression of miR‐150‐5p inhibited MMP‐16 level and elevated the expression of LINC01121 enhanced MMP‐16 level. We also found that MMP‐16 was up‐regulated in IDD specimens compared to that in control specimens. Higher expression of MMP‐16 was correlated with disc degeneration degree. Interestingly, MMP‐16 expression was positively related to LINC01121 in IDD specimens. Finally, overexpression of LINC01121 regulated cell growth, extracellular matrix degradation and inflammatory cytokine secretion via modulating MMP‐16.

Conclusions

our data suggested LINC01121 may be a new therapeutic target for IDD.