bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional outcome of traumatic spinopelvic instabilities treated with lumbopelvic fixation
Authors: Yilmaz Emre , Hoffmann Martin F. , von Glinski Alexander , Kruppa Christiane , Hamsen Uwe , Schmidt Cameron K. , Oernek Ahmet , Koenigshausen Matthias , Dudda Marcel , Schildhauer Thomas A.
Published: September 2020

The aim of this study was to assess the functional outcome after lumbopelvic fixation (LPF) using the SMFA (short musculoskeletal functional assessment) score and discuss the results in the context of the existing literature. The last consecutive 50 patients who underwent a LPF from January 1st 2011 to December 31st 2014 were identified and administered the SMFA-questionnaire. Inclusion criteria were: (1) patient underwent LPF at our institution, (2) complete medical records, (3) minimum follow-up of 12 months. Out of the 50 recipients, 22 questionnaires were returned. Five questionnaires were incomplete and therefore seventeen were included for analysis. The mean age was 60.3 years (32–86 years; 9m/8f) and the follow-up averaged 26.9 months (14–48 months). Six patients (35.3%) suffered from a low-energy trauma and 11 patients (64.7%) suffered a high-energy trauma. Patients in the low-energy group were significantly older compared to patients in the high-energy group (72.2 vs. 53.8 years; p = 0.030). Five patients (29.4%) suffered from multiple injuries. Compared to patients with low-energy trauma, patients suffering from high-energy trauma showed significantly lower scores in “daily activities” (89.6 vs. 57.1; p = 0.031), “mobility” (84.7 vs. 45.5; p = 0.015) and “function” (74.9 vs. 43.4; p = 0.020). Our results suggest that patients with older age and those with concomitant injuries show a greater impairment according to the SMFA score. Even though mostly favorable functional outcomes were reported throughout the literature, patients still show some level of impairment and do not reach normative data at final follow-up.
All-optical charging and charge transport in quantum dots
Authors: Hastrup Jacob , Leandro Lorenzo , Akopian Nika
Published: September 2020

Optically active quantum dots are one of the promising candidates for fundamental building blocks in quantum technology. Many practical applications would comprise of multiple coupled quantum dots, each of which must be individually chargeable. However, the most advanced demonstrations are limited to devices with only a single dot, and individual charging has neither been demonstrated nor proposed for an array of optically active quantum dots. Here we propose and numerically demonstrate a method for controlled charging of multiple quantum dots and charge transport between the dots. We show that our method can be implemented in realistic structures with fidelities greater than 99.9%. The scheme is based on all-optical resonant manipulation of charges in an array of quantum dots formed by a type-II band alignment, such as crystal-phase quantum dots in nanowires. Our work opens new practical avenues for realizations of advanced quantum photonic devices, for instance, solid-state quantum registers with a photonic interface.
IRF2 maintains the stemness of colonic stem cells by limiting physiological stress from interferon
Authors: Minamide Kana , Sato Taku , Nakanishi Yusuke , Ohno Hiroshi , Kato Tamotsu , Asano Jumpei , Ohteki Toshiaki
Published: September 2020

The physiological stresses that diminish tissue stem-cell characteristics remain largely unknown. We previously reported that type I interferon (IFN), which is essential for host antiviral responses, is a physiological stressor for hematopoietic stem cells (HSCs) and small intestinal stem cells (ISCs) and that interferon regulatory factor-2 (IRF2), which attenuates IFN signaling, maintains their stemness. Here, using a dextran sodium sulfate (DSS)-induced colitis model, we explore the role of IRF2 in maintaining colonic epithelial stem cells (CoSCs). In mice with a conditional Irf2 deletion in the intestinal epithelium (hereafter Irf2ΔIEC mice), both the number and the organoid-forming potential of CoSCs were markedly reduced. Consistent with this finding, the ability of Irf2ΔIEC mice to regenerate colon epithelium after inducing colitis was severely impaired, independently of microbial dysbiosis. Mechanistically, CoSCs differentiated prematurely into transit-amplifying (TA) cells in Irf2ΔIEC mice, which might explain their low CoSC counts. A similar phenotype was induced in wild-type mice by repeated injections of low doses of poly(I:C), which induces type I IFN. Collectively, we demonstrated that chronic IFN signaling physiologically stresses CoSCs. This study provides new insight into the development of colitis and molecular mechanisms that maintain functional CoSCs throughout life.
Transcriptional analysis of cleft palate in TGFβ3 mutant mice
Authors: Liu J. , Chanumolu S. K. , White K. M. , Albahrani M. , Otu H. H. , Nawshad A.
Published: September 2020

Cleft palate (CP) is one of the most common craniofacial birth defects, impacting about 1 in 800 births in the USA. Tgf-β3 plays a critical role in regulating murine palate development, andTgf-β3null mutants develop cleft palate with 100% penetrance. In this study, we compared global palatal transcriptomes of wild type (WT) andTgf-β3−/− homozygous (HM) mouse embryos at the crucial palatogenesis stages of E14.5, and E16.5, using RNA-seq data. We found 1,809 and 2,127 differentially expressed genes at E16.5 vs. E14.5 in the WT and HM groups, respectively (adjustedp < 0.05; |fold change|> 2.0). We focused on the genes that were uniquely up/downregulated in WT or HM at E16.5 vs. E14.5 to identify genes associated with CP. Systems biology analysis relating to cell behaviors and function of WT and HM specific genes identified functional non-Smad pathways and preference of apoptosis to epithelial-mesenchymal transition. We identified 24 HM specific and 11 WT specific genes that are CP-related and/or involved in Tgf-β3 signaling. We validated the expression of 29 of the 35 genes using qRT-PCR and the trend of mRNA expression is similar to that of RNA-seq data . Our results enrich our understanding of genes associated with CP that are directly or indirectly regulated via TGF-β.
Plant growth promoting rhizobacteria isolated from halophytes and drought-tolerant plants: genomic characterisation and exploration of phyto-beneficial traits
Authors: Leontidou Kleopatra , Genitsaris Savvas , Papadopoulou Anastasia , Kamou Nathalie , Bosmali Irene , Matsi Theodora , Madesis Panagiotis , Vokou Despoina , Karamanoli Katerina , Mellidou Ifigeneia
Published: September 2020

Plant growth promoting rhizobacteria (PGPR) are able to provide cross-protection against multiple stress factors and facilitate growth of their plant symbionts in many ways. The aim of this study was to isolate and characterize rhizobacterial strains under natural conditions, associated with naturally occurring representatives of wild plant species and a local tomato cultivar, growing in differently stressed Mediterranean ecosystems. A total of 85 morphologically different rhizospheric strains were isolated; twenty-five exhibited multiple in vitro PGP-associated traits, including phosphate solubilization, indole-3-acetic acid production, and 1-aminocyclopropane-1-carboxylate deaminase activity. Whole genome analysis was applied to eight selected strains for their PGP potential and assigned seven strains to Gammaproteobacteria, and one to Bacteroidetes. The genomes harboured numerous genes involved in plant growth promotion and stress regulation. They also support the notion that the presence of gene clusters with potential PGP functions is affirmative but not necessary for a strain to promote plant growth under abiotic stress conditions. The selected strains were further tested for their ability to stimulate growth under stress. This initial screening led to the identification of some strains as potential PGPR for increasing crop production in a sustainable manner.
Caffeine as a promotor of sexual development in sterile Queensland fruit fly males
Authors: Adnan Saleh Mohammad , Farhana Iffat , Park Soo Jean , Rempoulakis Polychronis , Taylor Phillip W.
Published: September 2020

Sterile insect technique (SIT) is an environmentally benign pest management technique that involves releasing millions of sterile insects to suppress reproduction of pest populations. Many fruit flies, including Queensland fruit fly (Bactrocera tryoni Froggatt, ‘Q-fly’), have long adult maturation periods such that pre-maturation mortality can greatly reduce abundance of sexually active sterile males and impede SIT efficacy. Q-fly is the most difficult and costly challenge to market access for Australia’s horticulture industries, and has been targeted for intensive use of SIT program. We here demonstrate potential of pre-release caffeine supplements as a novel means to accelerate sexual maturation in male Q-fly. In mating trials, analytical caffeine was very effective at accelerating sexual maturation, while no positive effects of caffeine-containing instant coffee or guarana supplements were detected. In parallel, development of testes and ejaculatory apodemes was accelerated in males provided analytical caffeine but not instant coffee or guarana. High doses of guarana and instant coffee reduced longevity while even the highest doses of analytical caffeine did not affect longevity. Pre-release caffeine supplements promote sexual maturation in Q-flies, and similar benefits are expected in other fruit flies having long adult maturation periods.
The potential of gypsum speleothems for paleoclimatology: application to the Iberian Roman Humid Period
Authors: Gázquez Fernando , Bauska Thomas K. , Comas-Bru Laia , Ghaleb Bassam , Calaforra José-María , Hodell David A.
Published: September 2020

Carbonate cave deposits (speleothems) have been used widely for paleoclimate reconstructions; however, few studies have examined the utility of other speleothem-forming minerals for this purpose. Here we demonstrate for the first time that stable isotopes (δ17O, δ18O and δD) of structurally-bound gypsum (CaSO4·2H2O) hydration water (GHW) can be used to infer paleoclimate. Specifically, we used a 63 cm-long gypsum stalactite from Sima Blanca Cave to reconstruct the climate history of SE Spain from ~ 800 BCE to ~ 800 CE. The gypsum stalactite indicates wet conditions in the cave and humid climate from ~ 200 BCE to 100 CE, at the time of the Roman Empire apogee in Hispania. From ~ 100 CE to ~ 600 CE, evaporation in the cave increased in response to regional aridification that peaked at ~ 500–600 CE, roughly coinciding with the transition between the Iberian Roman Humid Period and the Migration Period. Our record agrees with most Mediterranean and Iberian paleoclimate archives, demonstrating that stable isotopes of GHW in subaerial gypsum speleothems are a useful tool for paleoclimate reconstructions.
Behavioral effects of SGK1 knockout in VTA and dopamine neurons
Authors: Doyle Marie A. , Stark Ali R. , Fejes-Tóth Geza , Náray-Fejes-Tóth Aniko , Mazei-Robison Michelle S.
Published: September 2020

Drugs of abuse cause significant neuroadaptations within the ventral tegmental area (VTA), with alterations in gene expression tied to changes in reward behavior. Serum- and glucocorticoid-inducible kinase 1 (SGK1) transcription, catalytic activity, and phosphorylation are upregulated in the VTA by chronic cocaine or morphine treatment, positioning SGK1 as a critical mediator of reward behavior. Using transgenic mouse models, we investigated the effect of SGK1 knockout in the VTA and in dopamine (DA) neurons to evaluate the necessity of protein expression for natural and drug reward behaviors. SGK1 knockdown in the VTA did not impact reward behaviors. Given VTA cellular heterogeneity, we also investigated a DA neuron-specific SGK1 knockout (KO). DA SGK1 KO significantly decreased body weight of adult mice as well as increased general locomotor activity; however, reward behaviors were similarly unaltered. Given that SGK1 mutants virally overexpressed in the VTA are capable of altering drug-associated behavior, our current results suggest that changes in SGK1 protein signaling may be distinct from expression. This work yields novel information on the impact of SGK1 deletion, critical for understanding the role of SGK1 signaling in the central nervous system and evaluating SGK1 as a potential therapeutic target for treatment of substance use disorders.
Parallel assessment of albuminuria and plasma sTNFR1 in people with type 2 diabetes and advanced chronic kidney disease provides accurate prognostication of the risks of renal decline and death
Authors: Martin William P. , Tuohy Colm , Doody Alison , Jackson Sabrina , Canavan Ronan J. , Slattery David , Twomey Patrick J. , McKenna Malachi J. , le Roux Carel W. , Docherty Neil G.
Published: September 2020

Identification of people with diabetes and chronic kidney disease at high-risk of early mortality is a priority to guide intensification of therapy. We aimed to investigate the complementary prognostic value of baseline urine albumin-to-creatinine ratio (uACR) and plasma soluble tumour necrosis factor receptor-1 (sTNFR1) with respect to early mortality and renal functional decline in a population with type 2 diabetes and advanced chronic kidney disease. We measured plasma sTNFR1 in people with type 2 diabetes (HbA1c ≥ 48 mmol/mol) at 2 hospital sites in Dublin between October 15th, 2014 and July 17th, 2015. In a subgroup of patients with advanced chronic kidney disease at baseline (estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/BSA) (n = 118), we collected clinical and longitudinal laboratory data to investigate relationships between sTNFR1 and renal and mortality endpoints by multivariable linear mixed-effects models and Cox proportional hazards regression models. The cohort was 64% male and 97% Caucasian. Mean age was 74 years, with a median type 2 diabetes duration of 16 years. Mean CKD-EPI eGFR was 42 mL/min/BSA and median [IQR] uACR was 3 [11] mg/mmol. Twenty-three (39%) people in quartiles 3 and 4 for plasma sTNFR1 died over 4-year follow-up. After adjustment for clinical variables, annual CKD-EPI eGFR decreased by − 0.56 mL/min/BSA/year for each logarithm unit increase in baseline uACR, corresponding to an annual loss of renal function of 3% per year. Furthermore, elevated uACR, but not sTNFR1, increased the risk of ≥ 40% decline in CKD-EPI eGFR (HR 1.5, p = 0.001) and doubling of serum creatinine (HR 2.0, p < 0.001). Plasma sTNFR1 did not predict a more negative trajectory in eGFR slope. However, for those people in quartiles 3 and 4 for plasma sTNFR1, an increased risk of incident mortality was detected (HR 4.9, p = 0.02). No such association was detected for uACR. In this elderly cohort of patients with type 2 diabetes and chronic kidney disease, sTNFR1 predicted short-to-medium term mortality risk but not risk of progressive renal functional decline. In contrast, parallel assessment of uACR predicted renal functional decline but not mortality, highlighting the complementary prognostic information provided by both parameters.
Tyrosine kinase inhibitor neratinib attenuates liver fibrosis by targeting activated hepatic stellate cells
Authors: Park Yong Joo , An Hyoung-Tae , Park Jong-Sung , Park Ogyi , Duh Alexander J. , Kim Kwangmeyung , Chung Kyu Hyuck , Lee Kang Choon , Oh Yumin , Lee Seulki
Published: September 2020

Liver fibrosis, a common outcome of chronic liver disease characterized by excessive accumulation of extracellular matrix (ECM), is a leading cause of mortality worldwide. The tyrosine kinase inhibitor neratinib is a human epidermal growth factor receptor 2 (HER2) inhibitor approved by the FDA for HER2-positive breast cancer treatment; however, it has not yet been evaluated for liver fibrosis treatment. We elucidated the anti-fibrotic effects of neratinib in hepatic stellate cells (HSCs) and in vivo models of CCl4-induced liver fibrosis. HSC activation is a key step in liver fibrogenesis and has a crucial role in collagen deposition, as it is primarily responsible for excessive ECM production. The effect of neratinib on HSC was evaluated in transforming growth factor (TGF-β)-incubated LX-2 cells and culture-activated primary human HSCs. In vivo study results indicated that neratinib inhibited the inflammatory response, HSC differentiation, and collagen accumulation induced by CCl4. Moreover, the anti-fibrotic effects of neratinib were not associated with the HER2 signaling pathways. Neratinib inhibited FGF2 expression in activated HSCs and serum FGF2 level in the model, suggesting that neratinib possessed therapeutic potency against liver fibrosis and the potential for application against other fibrotic diseases.
Differentiation of Cyanthillium cinereum, a smoking cessation herb, from its adulterant Emilia sonchifolia using macroscopic and microscopic examination, HPTLC profiles and DNA barcodes
Authors: Thongkhao Kannika , Pongkittiphan Veerachai , Phadungcharoen Thatree , Tungphatthong Chayapol , Urumarudappa Santhosh Kumar J. , Pengsuparp Thitima , Sutanthavibul Narueporn , Wiwatcharakornkul Worakorn , Kengtong Surapong , Sukrong Suchada
Published: September 2020

Cyanthillium cinereum (L.) H.Rob. is one of the most popular herbal smoking cessation aids currently used in Thailand, and its adulteration with Emilia sonchifolia (L.) DC. is often found in the herbal market. Therefore, the quality of the raw material must be considered. This work aimed to integrate macro- and microscopic, chemical and genetic authentication strategies to differentiate C. cinereum raw material from its adulterant. Different morphological features between C. cinereum and E. sonchifolia were simply recognized at the leaf base. For microscopic characteristics, trichome and pappus features were different between the two plants. HPTLC profiles showed a distinct band that could be used to unambiguously differentiate C. cinereum from E. sonchifolia. Four triterpenoid compounds, β-amyrin, taraxasterol, lupeol, and betulin, were identified from the distinct HPTLC band of C. cinereum. The use of core DNA barcode regions; rbcL, matK, ITS and psbA-trnH provided species-level resolution to differentiate the two plants. Taken together, the integration of macroscopic and microscopic characterization, phytochemical analysis by HPTLC and DNA barcoding distinguished C. cinereum from E. sonchifolia. The signatures of C. cinereum obtained here can help manufacturers to increase the quality control of C. cinereum raw material in commercialized smoking cessation products.
Characterization of capacitive electromyography biomedical sensor insulated with porous medical bandages
Authors: Ng Charn Loong , Reaz Mamun Bin Ibne , Crespo Maria Liz , Cicuttin Andres , Chowdhury Muhammad Enamul Hoque
Published: September 2020

A capacitive electromyography (cEMG) biomedical sensor measures the EMG signal from human body through capacitive coupling methodology. It has the flexibility to be insulated by different types of materials. Each type of insulator will yield a unique skin–electrode capacitance which determine the performance of a cEMG biomedical sensor. Most of the insulator being explored are solid and non-breathable which cause perspiration in a long-term EMG measurement process. This research aims to explore the porous medical bandages such as micropore, gauze, and crepe bandage to be used as an insulator of a cEMG biomedical sensor. These materials are breathable and hypoallergenic. Their unique properties and characteristics have been reviewed respectively. A 50 Hz digital notch filter was developed and implemented in the EMG measurement system design to further enhance the performance of these porous medical bandage insulated cEMG biomedical sensors. A series of experimental verifications such as noise floor characterization, EMG signals measurement, and performance correlation were done on all these sensors. The micropore insulated cEMG biomedical sensor yielded the lowest noise floor amplitude of 2.44 mV and achieved the highest correlation coefficient result in comparison with the EMG signals captured by the conventional wet contact electrode.
Analysis of tear film spatial instability for pediatric myopia under treatment
Authors: Cho Wan-Hua , Fang Po-Chiung , Yu Hun-Ju , Lin Pei-Wen , Huang Hsiu-Mei , Kuo Ming-Tse
Published: September 2020

In Taiwan, the prevalence of myopia in children between 6 and 18 years old is over 80%, and high myopia accounts for over 20%, which turned out to be in the leading place worldwide. Orthokeratology and low-dose atropine are proven treatments to reduce myopia progression, though the potential corneal disturbances remain an issue in young populations. The alteration of the tear film is widely discussed but there is no consensus to date, so we aim to investigate the tear film spatial instability in children with myopia control using atropine or orthokeratology. Thirty-eight treatment-naïve participants and 126 myopic children under treatments were enrolled. The ocular surface homeostasis, spatial distribution of tear break-up, and high-order aberrations (HOAs) of the corneal surface were assessed. We found out that myopic children treated with either atropine or orthokeratology showed ocular surface homeostasis similar to that in treatment-naïve children. Nevertheless, children treated with orthokeratology presented higher HOAs (p < 0.00001) and a tendency of the first tear break-up zone at the inner half of the cornea (p = 0.04). This unique spatial instability of the tear film associated with myopia treatment might provide a more focused way of monitoring the pediatric tear film instability.
ODiNPred: comprehensive prediction of protein order and disorder
Authors: Dass Rupashree , Mulder Frans A. A. , Nielsen Jakob Toudahl
Published: September 2020

Structural disorder is widespread in eukaryotic proteins and is vital for their function in diverse biological processes. It is therefore highly desirable to be able to predict the degree of order and disorder from amino acid sequence. It is, however, notoriously difficult to predict the degree of local flexibility within structured domains and the presence and nuances of localized rigidity within intrinsically disordered regions. To identify such instances, we used the CheZOD database, which encompasses accurate, balanced, and continuous-valued quantification of protein (dis)order at amino acid resolution based on NMR chemical shifts. To computationally forecast the spectrum of protein disorder in the most comprehensive manner possible, we constructed the sequence-based protein order/disorder predictor ODiNPred, trained on an expanded version of CheZOD. ODiNPred applies a deep neural network comprising 157 unique sequence features to 1325 protein sequences together with the experimental NMR chemical shift data. Cross-validation for 117 protein sequences shows that ODiNPred better predicts the continuous variation in order along the protein sequence, suggesting that contemporary predictors are limited by the quality of training data. The inclusion of evolutionary features reduces the performance gap between ODiNPred and its peers, but analysis shows that it retains greater accuracy for the more challenging prediction of intermediate disorder.
Effects of finish rolling temperature and yield ratio on variations in yield strength after pipe-forming of API-X65 line-pipe steels
Authors: Kim Dae Woong , Kim Wan-Keun , Bae Jin-ho , Choi Won-Doo , Sohn Seok Su , Lee Sunghak
Published: September 2020

Flattened plates often show the lower or higher yield strength than initial leveled plates because tensile and compressive strains are repeatedly experienced at outer and inner walls during the pipe-forming and flattening, but reasons for the yield-strength variation after the pipe-forming are not sufficiently verified yet. In this study, ten line-pipe steels were fabricated by controlling alloying elements and finish rolling temperatures (FRTs), and the yield strength of pipe-flattened steel plates was predicted by using cyclic simulation tests, based on competing contributions of Bauschinger effect (BE) and strain hardening (SH) effect quantified from yield drop (YD) and yield rise (YR) parameters, respectively. High-FRT-treated steels (H steels) showed the lower BE and the higher SH than low-FRT-treated steels (L steels), thereby resulting in the smaller yield-strength reduction. This lower BE in the H steels was caused by the lower total boundary density, while the higher SH was caused by the higher fraction of granular bainite. According to the SH analyses between the YR parameters obtained from cyclic simulation tests and the yield ratios obtained from ordinary tensile tests, the decrease in yield-strength reduction with decreasing yield ratio was not attributed to the increase in ordinary tensile SH but to the increase in YR parameter.
Temperature sensitivity differs between heart and red muscle mitochondria in mahi-mahi (Coryphaena hippurus)
Authors: Lau Gigi Y. , Cox Georgina K. , Stieglitz John D. , Benetti Daniel D. , Grosell Martin
Published: September 2020

Maintaining energy balance over a wide range of temperatures is critical for an active pelagic fish species such as the mahi-mahi (Coryphaena hippurus), which can experience rapid changes in temperature during vertical migrations. Due to the profound effect of temperature on mitochondrial function, this study was designed to investigate the effects of temperature on mitochondrial respiration in permeabilized heart and red skeletal muscle (RM) fibres isolated from mahi-mahi. As RM is thought to be more anatomically isolated from rapid ambient temperature changes compared to the myocardium, it was hypothesized that heart mitochondria would be more tolerant of temperature changes through a greater ability to match respiratory capacity to an increase in temperature and to maintain coupling, when compared to RM mitochondria. Results show that heart fibres were more temperature sensitive and increased respiration rate with temperature increases to a greater degree than RM. Respiratory coupling ratios at the three assay temperatures (20, 26, and 30 °C), revealed that heart mitochondria were less coupled at a lower temperature (26 °C) compared to RM mitochondria (30 °C). In response to an in vitro acute temperature challenge, both tissues showed irreversible effects, where both heart and RM increased uncoupling whether the assay temperature was acutely changed from 20 to 30 °C or 30 to 20 °C. The findings from this study indicate that mahi-mahi heart mitochondria were more temperature sensitive compared to those from RM.
Rapid, precise quantification of large DNA excisions and inversions by ddPCR
Authors: Watry Hannah L. , Feliciano Carissa M. , Gjoni Ketrin , Takahashi Gou , Miyaoka Yuichiro , Conklin Bruce R. , Judge Luke M.
Published: September 2020

The excision of genomic sequences using paired CRISPR-Cas nucleases is a powerful tool to study gene function, create disease models and holds promise for therapeutic gene editing. However, our understanding of the factors that favor efficient excision is limited by the lack of a rapid, accurate measurement of DNA excision outcomes that is free of amplification bias. Here, we introduce ddXR (droplet digital PCR eXcision Reporter), a method that enables the accurate and sensitive detection of excisions and inversions independent of length. The method can be completed in a few hours without the need for next-generation sequencing. The ddXR method uncovered unexpectedly high rates of large (> 20 kb) excisions and inversions, while also revealing a surprisingly low dependence on linear distance, up to 170 kb. We further modified the method to measure precise repair of excision junctions and allele-specific excision, with important implications for disease modeling and therapeutic gene editing.
Case studies of clinical hemodialysis membranes: influences of membrane morphology and biocompatibility on uremic blood-membrane interactions and inflammatory biomarkers
Authors: Westphalen Heloisa , Saadati Shaghayegh , Eduok Ubong , Abdelrasoul Amira , Shoker Ahmed , Choi Phillip , Doan Huu , Ein-Mozaffari Farhad
Published: September 2020

End stage renal disease (ESRD) patients depend on hemodialysis (HD) as a life-sustaining treatment, but HD membrane properties play a critical role in blood activation during HD and can lead to severe patient outcomes. This study reports on a series of investigations on the common clinical HD membranes available in Canadian hospitals to explore the key reasons behind their susceptibility to blood activation and unstable cytokine. Clinical HD membranes composed of cellulose triacetate (CTA) and polyvinylpyrrolidone: polyarylethersulfone (PAES: PVP) were thoroughly characterized in terms of morphology and chemical composition. Membrane-surface interactions with uremic blood samples after HD treatment were probed using Fourier Transform Infra-Red (FTIR) and Raman spectroscopic techniques in order to understand changes in chemistry on membrane fibers. In addition, as part of this innovative study, we utilized Molecular Modeling Docking to examine the interactions of human blood proteins and membrane models to gain an in-depth understanding of functional group types responsible for perceived interactions. In-vitro adsorption of fibrinogen on different clinical HD membranes was compared at similar clinical operating conditions. Samples were collected from dialysis patients to ascertain the extent of inflammatory biomarkers released, before, during (30 and 90 min) and after dialysis (4 h). Collected blood samples were analyzed using Luminex assays for the inflammatory biomarkers of Serpin/Antithrombin-III, Properdin, C5a, 1L-1α, 1L-1β, TNF-α, IL6, and vWF. We have likewise incubated uremic blood in vitro with the two membrane materials to determine the impact that membrane materials pose in favor of activation away from the hydrodynamics influences. The results of our morphological, chemical, spectroscopic, and in vitro incubation analyses indicate that CTA membranes have a smoother surface and higher biocompatibility than PAES: PVP membranes, however, it has smaller pore size distribution, which results in poor clearance of a broad spectrum of uremic toxins. However, the rougher surface and greater hydrophilicity of PAES: PVP membranes increases red blood cell rupture at the membrane surface, which promotes protein adsorption and biochemical cascade reactions. Molecular docking studies indicate sulfone functional groups play an important role in the adsorption of proteins and receptors. PAES: PVP membranes result in slower but greater adsorption of fibrinogen, but are more likely to experience reversible and irreversible fouling as well as backfiltration. Our major finding is that a single dialysis session, even with a more biocompatible membrane such as CTA, increases the levels of complement and inflammation factors, but to a milder extent than dialysis with a PAES membrane.
Asymmetry analysis of optical coherence tomography angiography macular perfusion density measurements in preperimetric and perimetric glaucoma
Authors: Chang Pei-Yao , Wang Jiun-Yi , Wang Jia-Kang , Yeh Shih-Cheng , Chang Shu-Wen
Published: September 2020

Macular retinal layer thickness asymmetry indices, particularly for the ganglion cell layer, are promising early indicators of glaucomatous damage. We evaluated macular perfusion density asymmetry (MPDA) among normal, preperimetric glaucoma (PPG), and perimetric glaucoma (PG) eyes, and we tested the performance of MPDA in differentiating between control and glaucoma eyes with or without visual field (VF) defects. In this study, 116 eyes (39 normal, 27 PPG, and 50 PG eyes) with optical coherence tomography angiography images of the macula were analysed. No significant difference was found in outer and inner MPDA between the control and PPG groups. However, outer MPDA was significantly higher in the PG group than in the PPG group (p = 0.009). Asymmetry of perfusion density and structural parameters was compared; no significant difference was found between controls and glaucoma patients. Outer MPDA had significantly higher discrimination ability between PPG and PG than did macular ganglion cell layer–inner plexiform layer thickness asymmetry (p = 0.039). In conclusion, the discriminant capability of MPDA for discriminating between glaucoma patients with and without VF defects is significantly higher than that of structural asymmetry. MPDA may be helpful in monitoring glaucoma progression in clinical practice.
Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer’s disease model
Authors: Fernandez-Valenzuela Juan Jose , Sanchez-Varo Raquel , Muñoz-Castro Clara , De Castro Vanessa , Sanchez-Mejias Elisabeth , Navarro Victoria , Jimenez Sebastian , Nuñez-Diaz Cristina , Gomez-Arboledas Angela , Moreno-Gonzalez Ines , Vizuete Marisa , Davila Jose Carlos , Vitorica Javier , Gutierrez Antonia
Published: September 2020

In Alzheimer’s disease (AD), and other tauopathies, microtubule destabilization compromises axonal and synaptic integrity contributing to neurodegeneration. These diseases are characterized by the intracellular accumulation of hyperphosphorylated tau leading to neurofibrillary pathology. AD brains also accumulate amyloid-beta (Aβ) deposits. However, the effect of microtubule stabilizing agents on Aβ pathology has not been assessed so far. Here we have evaluated the impact of the brain-penetrant microtubule-stabilizing agent Epothilone D (EpoD) in an amyloidogenic model of AD. Three-month-old APP/PS1 mice, before the pathology onset, were weekly injected with EpoD for 3 months. Treated mice showed significant decrease in the phospho-tau levels and, more interesting, in the intracellular and extracellular hippocampal Aβ accumulation, including the soluble oligomeric forms. Moreover, a significant cognitive improvement and amelioration of the synaptic and neuritic pathology was found. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation. Therefore, our results suggested that EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Aβ levels and promoting neuronal and cognitive protection. These results underline the existence of a crosstalk between cytoskeleton pathology and the two major AD protein lesions. Therefore, microtubule stabilizers could be considered therapeutic agents to slow the progression of both tau and Aβ pathology.
A novel nudivirus infecting the invasive demon shrimp Dikerogammarus haemobaphes (Amphipoda)
Authors: Allain Thomas W. , Stentiford Grant D. , Bass David , Behringer Donald C. , Bojko Jamie
Published: September 2020

The Nudiviridae are a family of large double-stranded DNA viruses that infects the cells of the gut in invertebrates, including insects and crustaceans. The phylogenetic range of the family has recently been enhanced via the description of viruses infecting penaeid shrimp, crangonid shrimp, homarid lobsters and portunid crabs. Here we extend this by presenting the genome of another nudivirus infecting the amphipod Dikerogammarus haemobaphes. The virus, which infects cells of the host hepatopancreas, has a circular genome of 119,754 bp in length, and encodes a predicted 106 open reading frames. This novel virus encodes all the conserved nudiviral genes (sharing 57 gene homologues with other crustacean-infecting nudiviruses) but appears to lack the p6.9 gene. Phylogenetic analysis revealed that this virus branches before the other crustacean-infecting nudiviruses and shares low levels of gene/protein similarity to the Gammanudivirus genus. Comparison of gene synteny from known crustacean-infecting nudiviruses reveals conservation between Homarus gammarus nudivirus and Penaeus monodon nudivirus; however, three genomic rearrangements in this novel amphipod virus appear to break the gene synteny between this and the ones infecting lobsters and penaeid shrimp. We explore the evolutionary history and systematics of this novel virus, suggesting that it be included in the novel Epsilonnudivirus genus (Nudiviridae).
Assessment of airborne particles and bioaerosols concentrations in a waste recycling environment in Brazil
Authors: Wikuats Caroline Fernanda Hei , Duarte Eduardo Henrique , Prates Kátia Valéria Marques Cardoso , Janiaski Laura Lahr Lourenço , de Oliveira Gabriel Bárbara , da Cunha Molina Alex , Martins Leila Droprinchinski
Published: September 2020

This study aims to assess the concentrations of size-fractioned particle mass (PM1.0, PM2.5, PM4.0, PM10) and number (PNC0.3, PNC0.5, PNC1.0, PNC2.5), bacteria, and fungi in a Materials Recycling Facility (MRF) in Brazil. The measurements were performed inside the waste processing shed (P1) and in the outdoor environment (P2) during working days in winter and spring of 2017, and summer of 2019. A total of 2,400 min of PM, 1,440 min of PNC, and 216 samples of bioaerosols were collected in the morning and afternoon. P1 has the strongest air contamination with mean values of 475.5 ± 563.7 µg m−3 for PM10, 58.6 ± 36.0 cm−3 for PNC0.3, 1,088.8 ± 825.2 colony-forming units per cubic meter (CFU m−3) for bacteria, and 2,738.3 ± 1,381.3 CFU m−3 for fungi. The indoor/outdoor ratios indicated the large influence of indoor sources due to the activities performed inside P1 that promote the generation and resuspension of pollutants. Gram-positive bacteria dominated with 58.6% of indoor samples. Overall, our results show a critical indoor air quality situation in a Brazilian MRF, which may cause several health risks for waste pickers. Finally, we call attention to the lack of occupational exposure limits for bioaerosols in industrial workplaces and mainly in MRFs.
Corneal topography in keratoconus evaluated more than 30 years after penetrating keratoplasty: a Fourier harmonic analysis
Authors: Ono Takashi , Kawasaki Yuki , Chen Lily Wei , Toyono Tetsuya , Shirakawa Rika , Yoshida Junko , Aihara Makoto , Miyai Takashi
Published: September 2020

The aim of this observational study was to examine the characteristics of anterior and posterior corneal topography in keratoconic eyes more than 30 years after penetrating keratoplasty (PK). Patients who maintained clear grafts for more than 30 years after PK were included and divided into the keratoconus (KC) group or other diseases (Others) group, based on the primary indication. Twenty-six eyes of 26 patients were included. The KC group and the Others group included 14 eyes and 12 eyes, respectively. The KC group participants were younger at the time of surgery (P = 0.03). No differences were found in best-spectacle-corrected visual acuity, keratometric power, and central-corneal-thickness. Based on corneal topography using Fourier harmonic analyses, regular astigmatism in the anterior cornea was significantly larger (P = 0.047) and the spherical component in the posterior cornea was significantly lower (P = 0.01) in the KC group. The area under the receiver operating characteristic curve of the spherical component, regular astigmatism, asymmetry component, and higher-order irregularity were 66.07%, 63.10%, 57.14%, and 59.23%, respectively, in the anterior cornea and 80.65%, 52.98%, 63.10%, and 63.99%, respectively, in the posterior cornea. Our results suggested that Fourier harmonic analysis of corneal topography could be useful for patients with KC long after PK.
Polyphenols profile of pomegranate leaves and their role in green synthesis of silver nanoparticles
Authors: Swilam Noha , Nematallah Khaled A.
Published: September 2020

The current study reports on polyphenols profile of pomegranate leaves (PL) Punica granatum grown in Egypt and exhibiting their role in development of an eco-friendly method of green synthesis of silver nanoparticles (AgNPs). PL aqueous alcohol extract was fractionated, the major phenolic compound was isolated from the polyphenols rich fraction (ethyl acetate fraction) and identified by conventional and spectroscopic methods of analysis as ellagic acid. Furthermore, the fraction was standardized and analysed using UPLC-PDA-UV and LC–MS-MS techniques revealing tentative identification of 23 polyphenolic compounds, quantifying ellagic acid as 43.14 ± 0.57 μg/mg of the fraction. AgNPs were successfully synthesized with the aid of polyphenols rich fraction. This is the first report revealing the systematic optimization of the green synthesis process using various independent variables. AgNPs were characterized by adopting UV–Vis spectroscopy, FTIR, XRD, and SEM, which revealed strong SPR band within average of λ max 425 nm and polygonal shaped nanoparticles of 26.22 nm size, respectively. The antimicrobial efficacies of AgNPs and polyphenols rich fraction were tested against Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus, and Sarcina lutea), Gram-negative bacteria (Salmonella paratyphi, Escherichia coli, and Pseudomonas aeruginosa) and fungi (Candida albicans). AgNPs showed a concentration-dependent activity against all the tested microorganisms.
The synergistic interaction of thermal stress coupled with overstocking strongly modulates the transcriptomic activity and immune capacity of rainbow trout (Oncorhynchus mykiss)
Authors: Rebl Alexander , Korytář Tomáš , Borchel Andreas , Bochert Ralf , Strzelczyk Joanna Ewa , Goldammer Tom , Verleih Marieke
Published: September 2020

The objective of the present study is to identify and evaluate informative indicators for the welfare of rainbow trout exposed to (A) a water temperature of 27 °C and (B) a stocking density of 100 kg/m3combined with a temperature of 27 °C. The spleen-somatic and condition index, haematocrit and the concentrations of haemoglobin, plasma cortisol and glucose revealed non-significant differences between the two stress groups and the reference group 8 days after the onset of the experiments. The transcript abundance of almost 1,500 genes was modulated at least twofold in in the spleen of rainbow trout exposed to a critical temperature alone or a critical temperature combined with crowding as compared to the reference fish. The number of differentially expressed genes was four times higher in trout that were simultaneously challenged with high temperature and crowding, compared to trout challenged with high temperature alone. Based on these sets of differentially expressed genes, we identified unique and common tissue- and stress type-specific pathways. Furthermore, our subsequent immunologic analyses revealed reduced bactericidal and inflammatory activity and a significantly altered blood-cell composition in challenged versus non-challenged rainbow trout. Altogether, our data demonstrate that heat and overstocking exert synergistic effects on the rainbow trout’s physiology, especially on the immune system.
Identifying metastasis-initiating miRNA-target regulations of colorectal cancer from expressional changes in primary tumors
Authors: Lee Jongmin , Hong Hye Kyung , Peng Sheng-Bin , Kim Tae Won , Lee Woo Yong , Yun Seong Hyun , Kim Hee Cheol , Liu Jiangang , Ebert Philip J. , Aggarwal Amit , Jung Sungwon , Cho Yong Beom
Published: September 2020

Colorectal cancer (CRC) is prevalent with high mortality, with liver metastasis contributing as a major factor that worsens the survival of patients. The roles of miRNAs in CRC have been elucidated, subsequent to recent studies that suggest the involvement of miRNAs in cancer biology. In this study, we compare the miRNA and gene expression profiles of primary tumors between two groups of patients (with and without liver metastasis) to identify the metastasis-initiating microRNA-target gene regulations. Analysis from 33 patients with metastasis and 14 patients without metastasis revealed that 17 miRNAs and their 198 predicted target genes are differentially expressed, where the target genes showed association with cancer progression and metastasis with statistical significance. In order to evaluate the clinical implications of the findings, we classified CRC patients of independent data into two groups based on the identified miRNA-target regulations, where one group was closer to primary tumors with metastasis than the other group. The comparison of survival showed statistically significant difference, thereby implying the roles of the identified miRNA-target regulations in cancer progression and metastasis. The identification of metastasis-initiating miRNA-target regulations in this study will lead to better understanding of the roles of miRNAs in CRC progression.
Effects of introducing eels on the yields and availability of fertilizer nitrogen in an integrated rice–crayfish system
Authors: Lv Weiwei , Yuan Quan , Lv Weiguang , Zhou Wenzong
Published: September 2020

Recently, many new rice–fish co-culture models have been developed to increase economic and ecological benefits. In this study, we added eels (Monopterus albus) to a rice–crayfish system and conducted a 3-year field investigation to compare the yields and availability of fertilizer N among groups with a low density of eels, high density of eels and no eels. We performed a mesocosm experiment and used an isotope tracer technique to detect the fate of fertilizer N. The results showed that the rice yields significantly improved after the introduction of the eels. However, the introduction of a high density of eels significantly limited the crayfish yield, increased water N and N2O emissions and decreased soil N content. The mesocosm experiment suggested that the use efficiency of fertilizer N was significantly increased after the introduction of the eels. The fertilizer N used by rice was significantly higher in rice–crayfish–eel system than in rice–crayfish system. This study indicated that the introduction of eels may be a good practice for improving yields and availability of fertilizer N in a rice–crayfish system.
Oxidation and electrical properties of chromium–iron alloys in a corrosive molten electrolyte environment
Authors: Esmaily M. , Mortazavi A. N. , Birbilis N. , Allanore A.
Published: September 2020

Chromium–iron (CrFe) binary alloys have recently been proposed to serve as the “inert” anode for molten oxide electrolysis (MOE). Herein, the effects of anodic polarization on physical and functional properties of CrFe anodes in the corrosive environment of MOE are studied via empirical observations and theoretical calculations. The findings indicate that the alloys form an inner chromia–alumina solid-solution covered by an MgCr2O4 spinel layer. A survey into the electrical properties of the detected oxides suggests that the layered oxide scale function as an efficient conductor of electricity at elevated temperature. The formation mechanism of the oxides is also investigated.
Mating and blood-feeding induce transcriptome changes in the spermathecae of the yellow fever mosquito Aedes aegypti
Authors: Camargo Carolina , Ahmed-Braimah Yasir H. , Amaro I. Alexandra , Harrington Laura C. , Wolfner Mariana F. , Avila Frank W.
Published: September 2020

Aedes aegyptimosquitoes are the primary vectors of numerous viruses that impact human health. As manipulation of reproduction has been proposed to suppress mosquito populations, elucidation of biological processes that enable males and females to successfully reproduce is necessary. One essential process is female sperm storage in specialized structures called spermathecae.Aedes aegyptifemales typically mate once, requiring them to maintain sperm viably to fertilize eggs they lay over their lifetime. Spermathecal gene products are required forDrosophilasperm storage and sperm viability, and a spermathecal-derived heme peroxidase is required for long-termAnopheles gambiaefertility. Products of theAe. aegyptispermathecae, and their response to mating, are largely unknown. Further, although female blood-feeding is essential for anautogenous mosquito reproduction, the transcriptional response to blood-ingestion remains undefined in any reproductive tissue. We conducted an RNAseq analysis of spermathecae from unfed virgins,mated only, and mated and blood-fed females at 6, 24, and 72 h post-mating and identified significant differentially expressed genes in each group at each timepoint. A blood-meal following mating induced a greater transcriptional response in the spermathecae than mating alone. This study provides the first view of elicited mRNA changes in the spermathecae by a blood-meal in mated females.