bluuebunny/crossref_metadata_2025 huggingface dataset:
High-performance chemical- and light-inducible recombinases in mammalian cells and mice
Authors: Weinberg Benjamin H. , Cho Jang Hwan , Agarwal Yash , Pham N. T. Hang , Caraballo Leidy D. , Walkosz Maciej , Ortega Charina , Trexler Micaela , Tague Nathan , Law Billy , Benman William K. J. , Letendre Justin , Beal Jacob , Wong Wilson W.
Published: October 2019

Site-specific DNA recombinases are important genome engineering tools. Chemical- and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, inducible recombinases are scarce due to the challenge of engineering high performance systems, thus constraining the sophistication of genetic circuits and animal models that can be created. Here we present a library of >20 orthogonal inducible split recombinases that can be activated by small molecules, light and temperature in mammalian cells and mice. Furthermore, we engineer inducible split Cre systems with better performance than existing systems. Using our orthogonal inducible recombinases, we create a genetic switchboard that can independently regulate the expression of 3 different cytokines in the same cell, a tripartite inducible Flp, and a 4-input AND gate. We quantitatively characterize the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs. This library expands capabilities for multiplexed mammalian gene expression control.
Prophages and satellite prophages are widespread in Streptococcus and may play a role in pneumococcal pathogenesis
Authors: Rezaei Javan Reza , Ramos-Sevillano Elisa , Akter Asma , Brown Jeremy , Brueggemann Angela B.
Published: October 2019

Prophages (viral genomes integrated within a host bacterial genome) can confer various phenotypic traits to their hosts, such as enhanced pathogenicity. Here we analyse >1300 genomes of 70 different Streptococcus species and identify nearly 800 prophages and satellite prophages (prophages that do not encode their own structural components but rely on the bacterial host and another helper prophage for survival). We show that prophages and satellite prophages are widely distributed among streptococci in a structured manner, and constitute two distinct entities with little effective genetic exchange between them. Cross-species transmission of prophages is not uncommon. Furthermore, a satellite prophage is associated with virulence in a mouse model of Streptococcus pneumoniae infection. Our findings highlight the potential importance of prophages in streptococcal biology and pathogenesis.
Quantifying the polygenic contribution to variable expressivity in eleven rare genetic disorders
Authors: Oetjens M. T. , Kelly M. A. , Sturm A. C. , Martin C. L. , Ledbetter D. H.
Published: October 2019

Rare genetic disorders (RGDs) often exhibit significant clinical variability among affected individuals, a disease characteristic termed variable expressivity. Recently, the aggregate effect of common variation, quantified as polygenic scores (PGSs), has emerged as an effective tool for predictions of disease risk and trait variation in the general population. Here, we measure the effect of PGSs on 11 RGDs including four sex-chromosome aneuploidies (47,XXX; 47,XXY; 47,XYY; 45,X) that affect height; two copy-number variant (CNV) disorders (16p11.2 deletions and duplications) and a Mendelian disease (melanocortin 4 receptor deficiency (MC4R)) that affect BMI; and two Mendelian diseases affecting cholesterol: familial hypercholesterolemia (FH;LDLRandAPOB) and familial hypobetalipoproteinemia (FHBL;PCSK9andAPOB). Our results demonstrate that common, polygenic factors of relevant complex traits frequently contribute to variable expressivity of RGDs and that PGSs may be a useful metric for predicting clinical severity in affected individuals and for risk stratification.
The geometry of masking in neural populations
Authors: Ringach Dario L.
Published: October 2019

The normalization model provides an elegant account of contextual modulation in individual neurons of primary visual cortex. Understanding the implications of normalization at the population level is hindered by the heterogeneity of cortical neurons, which differ in the composition of their normalization pools and semi-saturation constants. Here we introduce a geometric approach to investigate contextual modulation in neural populations and study how the representation of stimulus orientation is transformed by the presence of a mask. We find that population responses can be embedded in a low-dimensional space and that an affine transform can account for the effects of masking. The geometric analysis further reveals a link between changes in discriminability and bias induced by the mask. We propose the geometric approach can yield new insights into the image processing computations taking place in early visual cortex at the population level while coping with the heterogeneity of single cell behavior.
Author Correction: Identification and Characterization of USP7 Targets in Cancer Cells
Authors: Georges Anna , Marcon Edyta , Greenblatt Jack , Frappier Lori
Published: October 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Acid selective pro-dye for cellular compartments
Authors: Czaplińska Barbara , Malarz Katarzyna , Mrozek-Wilczkiewicz Anna , Musiol Robert
Published: October 2019

A novel pro-dye approach for the acid-selective staining of the subcellular compartments for better permeability and selectivity was applied. The designed sensor has suitable physicochemical properties such as a large Stokes shift and a long-lived intracellular fluorescence. The Schiff base fragment was used for the acid-sensitive release of a fluorophore without affecting the overall stability of the biological systems. Due to the presence of an imine bond in its structure and its unique fluorescent properties, it can be presented as a “pro-dye” for acidic structures such as lysosomes. As a result of an imine bond cleavage, a new fluorescent compound is released, whose substantially shifted excitation and emission wavelengths enable a more selective and effective imaging of lysosomes and endosomes. The presented report provides the chemical, physicochemical and optical profiles as well as biological assays and theoretical calculations.
Anthracene phytotoxicity in the freshwater flagellate alga Euglena agilis Carter
Authors: Kottuparambil Sreejith , Park Jihae
Published: October 2019

The freshwater flagellate alga Euglena agilis Carter was exposed to the polycyclic aromatic hydrocarbon (PAH) anthracene for 96 h under optimal photosynthetically active radiation (PAR), and responses of growth, photosynthetic pigment production, and photosynthetic efficiency were assessed. Anthracene reduced the growth rate (μ) and levels of chlorophyll a (Chl a), chlorophyll b (Chl b), and total carotenoids. The growth rate was more sensitive than photosynthetic parameters, with a median effective concentration (EC50) of 4.28 mg L−1. Between 5 and 15 mg L−1, anthracene inhibited the maximum quantum yield (Fv/Fm) of photosystem II (PSII) and the maximum photosynthetic electron transport rate through PSII (rETRmax) with EC50 values of 14.88 and 11.8 mg L−1, respectively. At all anthracene concentrations, intracellular reactive oxygen species (ROS) were elevated, indicating increased oxidative stress. Anthracene presumably reduced the PSII efficiency of photochemical energy regulation and altered the photochemistry through intracellular ROS formation. Acute exposure to PAHs may induce severe physiological changes in phytoplankton cells, which may influence vital ecological processes within the aquatic environments. Additionally, growth and Chl a content may serve as sensitive risk assessment parameters of anthracene toxicity in water management since EC50 values for both overlap with anthracene levels (8.3 mg L−1) permitted by the US Environmental Protection Agency (USEPA).
Bioprocessing of common pulses changed seed microstructures, and improved dipeptidyl peptidase-IV and α-glucosidase inhibitory activities
Authors: Di Stefano Elisa , Tsopmo Apollinaire , Oliviero Teresa , Fogliano Vincenzo , Udenigwe Chibuike C.
Published: October 2019

Type 2 diabetes mellitus (T2DM) is a leading cause of death globally. T2DM patients experience glucose intolerance, and inhibitors of dipeptidyl peptidase IV (DPP-IV) and α-glucosidase are used as drugs for T2DM management. DPP-IV and α-glucosidase inhibitors are also naturally contained in foods, but their potency can be affected by the food matrix and processing methods. In this study, germination and solid-state fermentation (SSF) were used to alter pulse seed microstructures, to convert compounds into more bioactive forms, and to improve their bioaccessibility. Germination substantially modified the seed microstructure, protein digestibility, contents and profiles of phenolic compounds in all the pulses. It also increased DPP-IV and α-glucosidase inhibitory activities in chickpeas, faba beans and yellow peas. Compared to germination, SSF withLactobacillus plantarumchanged the content and the profile of phenolic compounds mainly in yellow peas and green lentils because of greater disruption of the seed cell wall. In the same pulses, heat treatment and SSF of flour increased DPP-IV and α-glucosidase inhibitory activities. The results of this study suggest that germination and SSF withL. plantarumare effective and simple methods for modulating phenolic and protein profiles of common pulses and improve the action on DPP-IV and α-glucosidase.
Potential scrapie-associated polymorphisms of the prion protein gene (PRNP) in Korean native black goats
Authors: Kim Seon-Kwan , Kim Yong-Chan , Won Sae-Young , Jeong Byung-Hoon
Published: October 2019

Small ruminants, including sheep and goats are natural hosts of scrapie, and the progression of scrapie pathogenesis is strongly influenced by polymorphisms in the prion protein gene (PRNP). Although Korean native goats have been consumed as meat and health food, the evaluation of the susceptibility to scrapie in these goats has not been performed thus far. Therefore, we investigated the genotype and allele frequencies of PRNP polymorphisms in 211 Korean native goats and compared them with those in scrapie-affected animals from previous studies. We found a total of 12 single nucleotide polymorphisms (SNPs) including 10 nonsynonymous and 2 synonymous SNPs in Korean native goats. Significant differences in allele frequencies of PRNP codons 143 and 146 were found between scrapie-affected goats and Korean native goats (p < 0.01). By contrast, in PRNP codons 168, 211 and 222, there were no significant differences in the genotype and allele frequencies between scrapie-affected animals and Korean native goats. To evaluate structural changes caused by nonsynonymous SNPs, PolyPhen-2, PROVEAN and AMYCO analyses were performed. PolyPhen-2 predicted “possibly damaging” for W102G and R154H, “probably damaging” for G127S. AMYCO predicted relatively low for amyloid propensity of prion protein in Korean native black goats. This is the first study to evaluate the scrapie sensitivity and the first in silico evaluation of nonsynonymous SNPs in Korean native black goats.
IL-21 regulates SOCS1 expression in autoreactive CD8+ T cells but is not required for acquisition of CTL activity in the islets of non-obese diabetic mice
Authors: Sutherland Andrew P. R. , Graham Kate L. , Papadimitriou Michelle , Jhala Gaurang , Trivedi Prerak , Catterall Tara , Fynch Stacey , Kay Thomas W. H. , Thomas Helen E.
Published: October 2019

In type 1 diabetes, maturation of activated autoreactive CD8+ T cells to fully armed effector cytotoxic T lymphocytes (CTL) occurs within the islet. At present the signals required for the maturation process are poorly defined. Cytokines could potentially provide the necessary “third signal” required to generate fully mature CTL capable of killing insulin-producing β-cells. To determine whether autoreactive CTL within islets respond to cytokines we generated non-obese diabetic (NOD) mice with a reporter for cytokine signalling. These mice express a reporter gene, hCD4, under the control of the endogenous regulatory elements for suppressor of cytokine signalling (SOCS)1, which is itself regulated by pro-inflammatory cytokines. In NOD mice, the hCD4 reporter was expressed in infiltrated islets and the expression level was positively correlated with the frequency of infiltrating CD45+ cells. SOCS1 reporter expression was induced in transferred β-cell-specific CD8+ 8.3T cells upon migration from pancreatic draining lymph nodes into islets. To determine which cytokines induced SOCS1 promoter activity in islets, we examined hCD4 reporter expression and CTL maturation in the absence of the cytokine receptors IFNAR1 or IL-21R. We show that IFNAR1 deficiency does not confer protection from diabetes in 8.3 TCR transgenic mice, nor is IFNAR1 signalling required for SOCS1 reporter upregulation or CTL maturation in islets. In contrast, IL-21R-deficient 8.3 mice have reduced diabetes incidence and reduced SOCS1 reporter activity in islet CTLs. However IL-21R deficiency did not affect islet CD8+ T cell proliferation or expression of granzyme B or IFNγ. Together these data indicate that autoreactive CD8+ T cells respond to IL-21 and not type I IFNs in the islets of NOD mice, but neither IFNAR1 nor IL-21R are required for islet intrinsic CTL maturation.
Predicting low-concentration effects of pesticides
Authors: Liess Matthias , Henz Sebastian , Knillmann Saskia
Published: October 2019

We present a model to identify the effects of low toxicant concentrations. Due to inadequate models, such effects have so far often been misinterpreted as random variability. Instead, a tri-phasic relationship describes the effects of a toxicant when a broad range of concentrations is assessed: i) at high concentrations where substantial mortality occurs (LC50), we confirmed the traditional sigmoidal response curve (ii) at low concentrations about 10 times below the LC50, we identified higher survival than previously modelled, and (iii) at ultra-low concentrations starting at around 100 times below the LC50, higher mortality than previously modelled. This suggests that individuals benefit from low toxicant stress. Accordingly, we postulate that in the absence of external toxicant stress individuals are affected by an internal “System Stress” (SyS) and that SyS is reduced with increasing strength of toxicant stress. We show that the observed tri-phasic concentration-effect relationship can be modelled on the basis of this approach. Here we revealed that toxicant-related effects (LC5) occurred at remarkably low concentrations, 3 to 4 orders of magnitude below those concentrations inducing strong effects (LC50). Thus, the ECx-SyS model presented allows us to attribute ultra-low toxicant concentrations to their effects on individuals. This information will contribute to performing a more realistic environmental and human risk assessment.
Differential effects of synthetic media on long-term growth, starch accumulation and transcription of ADP-glucosepyrophosphorylase subunit genes in Landoltia punctata
Authors: Kittiwongwattana Chokchai
Published: October 2019

Murashige & Skoog (MS) and Hoagland’s media were previously used for in vitro culture of Landoltia punctata. During subsequent ex vitro culture, the use of MS medium resulted in a higher growth rate, compared to Hoagland’s medium. Thus, a higher starch content of L. punctata in MS medium was previously hypothesized. Here, L. punctata strain 5632 was isolated and characterized using morphological characteristics and the atpF-atpH intergenic region. During early cultivation stage, fresh weight and relative growth rate in MS medium were lower than Hoagland’s medium. Conversely, starch content in MS medium was considerably higher than in Hoagland’s medium. Medium effects on expression of genes coding for starch-biosynthesis ADP-glucosepyrophosphorylase (AGPase) were determined. Genomic fragments of small (LeAPS) and large (LeAPL1) AGPase subunits were characterized. Differential expression between each AGPase subunit genes was observed in both media. Additionally, in MS medium, the highest correlation coefficients between starch content and gene expression was found with LeAPS (0.81) and followed by LeAPL3 (0.67), LeAPL2 (0.65) and LeAPL1 (0.28). In Hoagland’s medium, the coefficients of LeAPL3 (0.83) and LeAPL2 (0.62) were higher than LeAPS (0.18) and LeAPL1 (−0.62). This suggested different levels of contributions of these genes in starch biosynthesis in both media.
Dependence of track etching kinetics on chemical reactivity around the ion path
Authors: Gorbunov S. A. , Rymzhanov R. A. , Volkov A. E.
Published: October 2019

Etching kinetics of swift heavy ions (SHI) tracks in olivine is investigated in frame of experimentally verified numerical approach. The model takes into account variation of induced chemical reactivity of the material around the whole ion trajectory with the nanometric accuracy. This enables a quantitative description of wet chemical etching of SHI tracks of different lengths and orientations towards to the sample surface. It is demonstrated that two different modes of etching, governed by diffusion of etchant molecules and by their reaction with the material must be observed in experiments using techniques with different resolution thresholds. Applicability limits of the optical microscopy for detection of heavy ion parameters by measuring of the lengthwise etching rates of the ion track are discussed.
Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transport
Authors: Oguro Ami , Imaoka Susumu
Published: October 2019

TMX2 is a thioredoxin family protein, but its functions have not been clarified. To elucidate the function of TMX2, we explored TMX2-interacting proteins by LC-MS. As a result, importin-β, Ran GTPase (Ran), RanGAP, and RanBP2 were identified. Importin-β is an adaptor protein which imports cargoes from cytosol to the nucleus, and is exported into the cytosol by interaction with RanGTP. At the cytoplasmic nuclear pore, RanGAP and RanBP2 facilitate hydrolysis of RanGTP to RanGDP and the disassembly of the Ran-importin-β complex, which allows the recycling of importin-β and reentry of Ran into the nucleus. Despite its interaction of TMX2 with importin-β, we showed that TMX2 is not a transport cargo. We found that TMX2 localizes in the outer nuclear membrane with its N-terminus and C-terminus facing the cytoplasm, where it co-localizes with importin-β and Ran. Ran is predominantly distributed in the nucleus, but TMX2 knockdown disrupted the nucleocytoplasmic Ran gradient, and the cysteine 112 residue of Ran was important in its regulation by TMX2. In addition, knockdown of TMX2 suppressed importin-β-mediated transport of protein. These results suggest that TMX2 works as a regulator of protein nuclear transport, and that TMX2 facilitates the nucleocytoplasmic Ran cycle by interaction with nuclear pore proteins.
Resolving the Architecture and Early Evolution of a Forearc Basin (Georgia Basin, Canada) Using Detrital Zircon
Authors: Huang Chuqiao , Dashtgard Shahin E. , Kent Bryan A. P. , Gibson H. Daniel , Matthews William A.
Published: October 2019

Convergent-margin basins (CMBs) are commonly associated with active arcs, and hence are rich in detrital zircon (DZ) whose ages closely reflect the timing of deposition. Consequently, maximum depositional ages (MDA) from DZ geochronology can be employed to resolve the stratigraphy and evolution of CMBs. Herein, we use DZ to revise the internal architecture of the lower Nanaimo Group, which partially comprises the fill of the (forearc) Georgia (or Nanaimo) Basin. Maximum depositional ages and multi-dimensional scaling of DZ age distributions are employed to determine chronologic equivalency of strata and assess sediment provenance variability within the pre-existing lithostratigraphic framework. The results are compared to a recently developed sequence stratigraphic framework for the lower Nanaimo Group. The basal lithostratigraphic unit of the Nanaimo Group, the Comox Formation (Fm), comprises strata that are neither time correlative nor genetically related. The three lithostratigraphic units directly overlying the Comox Fm (Haslam, Extension, and Protection formations) comprise strata with similar genetic affinities and MDAs that indicate deposition of these units was not always sequential and locally was contemporaneous. Through this work, we provide an example of how MDAs from DZ geochronology in CMBs can resolve basin-scale stratigraphic relations, and identify chronological changes in sediment provenance.
Crystal structure of the catalytic unit of GH 87-type α-1,3-glucanase Agl-KA from Bacillus circulans
Authors: Yano Shigekazu , Suyotha Wasana , Oguro Natsuki , Matsui Takashi , Shiga Shota , Itoh Takafumi , Hibi Takao , Tanaka Yoshikazu , Wakayama Mamoru , Makabe Koki
Published: October 2019

Glycoside hydrolase (GH) 87-type α-1,3-glucanase hydrolyses the α-1,3-glucoside linkages of α-1,3-glucan, which is found in fungal cell walls and extracellular polysaccharides produced by oral Streptococci. In this study, we report on the molecular structure of the catalytic unit of GH 87-type α-1,3-glucanase, Agl-KA, from Bacillus circulans, as determined by x-ray crystallography at a resolution of 1.82 Å. The catalytic unit constitutes a complex structure of two tandemly connected domains—the N-terminal galactose-binding-like domain and the C-terminal right-handed β-helix domain. While the β-helix domain is widely found among polysaccharide-processing enzymes, complex formation with the galactose-binding-like domain was observed for the first time. Biochemical assays showed that Asp1067, Asp1090 and Asp1091 are important for catalysis, and these residues are indeed located at the putative substrate-binding cleft, which forms a closed end and explains the product specificity.
A Curriculum Learning Strategy to Enhance the Accuracy of Classification of Various Lesions in Chest-PA X-ray Screening for Pulmonary Abnormalities
Authors: Park Beomhee , Cho Yongwon , Lee Gaeun , Lee Sang Min , Cho Young-Hoon , Lee Eun Sol , Lee Kyung Hee , Seo Joon Beom , Kim Namkug
Published: October 2019

We evaluated the efficacy of a curriculum learning strategy using two steps to detect pulmonary abnormalities including nodule[s], consolidation, interstitial opacity, pleural effusion, and pneumothorax with chest-PA X-ray (CXR) images from two centres. CXR images of 6069 healthy subjects and 3417 patients at AMC and 1035 healthy subjects and 4404 patients at SNUBH were obtained. Our approach involved two steps. First, the regional patterns of thoracic abnormalities were identified by initial learning of patch images around abnormal lesions. Second, Resnet-50 was fine-tuned using the entire images. The network was weakly trained and modified to detect various disease patterns. Finally, class activation maps (CAM) were extracted to localise and visualise the abnormal patterns. For average disease, the sensitivity, specificity, and area under the curve (AUC) were 85.4%, 99.8%, and 0.947, respectively, in the AMC dataset and 97.9%, 100.0%, and 0.983, respectively, in the SNUBH dataset. This curriculum learning and weak labelling with high-scale CXR images requires less preparation to train the system and could be easily extended to include various diseases in actual clinical environments. This algorithm performed well for the detection and classification of five disease patterns in CXR images and could be helpful in image interpretation.
Accelerating river blindness elimination by supplementing MDA with a vegetation “slash and clear” vector control strategy: a data-driven modeling analysis
Authors: Smith Morgan E. , Bilal Shakir , Lakwo Thomson L. , Habomugisha Peace , Tukahebwa Edridah , Byamukama Edson , Katabarwa Moses N. , Richards Frank O. , Cupp Eddie W. , Unnasch Thomas R. , Michael Edwin
Published: October 2019

Attention is increasingly focusing on how best to accelerate progress toward meeting the WHO’s 2030 goals for neglected tropical diseases (NTDs). For river blindness, a major NTD targeted for elimination, there is a long history of using vector control to suppress transmission, but traditional larvicide-based approaches are limited in their utility. One innovative and sustainable approach, “slash and clear”, involves clearing vegetation from breeding areas, and recent field trials indicate that this technique very effectively reduces the biting density of Simulium damnosum s.s. In this study, we use a Bayesian data-driven mathematical modeling approach to investigate the potential impact of this intervention on human onchocerciasis infection. We developed a novel “slash and clear” model describing the effect of the intervention on seasonal black fly biting rates and coupled this with our population dynamics model of Onchocerca volvulus transmission. Our results indicate that supplementing annual drug treatments with “slash and clear” can significantly accelerate the achievement of onchocerciasis elimination. The efficacy of the intervention is not very sensitive to the timing of implementation, and the impact is meaningful even if vegetation is cleared only once per year. As such, this community-driven technique will represent an important option for achieving and sustaining O. volvulus elimination.
Survey of bacteria associated with western corn rootworm life stages reveals no difference between insects reared in different soils
Authors: Ludwick Dalton C. , Ericsson Aaron C. , Meihls Lisa N. , Gregory Michelle L. J. , Finke Deborah L. , Coudron Thomas A. , Hibbard Bruce E. , Shelby Kent S.
Published: October 2019

Western corn rootworm (Diabrotica virgifera virgifera LeConte) is a serious pest of maize (Zea mays L.) in North America and parts of Europe. With most of its life cycle spent in the soil feeding on maize root tissues, this insect is likely to encounter and interact with a wide range of soil and rhizosphere microbes. Our knowledge of the role of microbes in pest management and plant health remains woefully incomplete, yet that knowledge could play an important role in effective pest management strategies. For this study, insects were reared on maize in soils from different locations. Insects from two different laboratory colonies (a diapausing and a non-diapausing colony) were sampled at each life stage to determine the possible core bacteriome. Additionally, soil was sampled at each life stage and resulting bacteria were identified to determine the possible contribution of soil to the rootworm bacteriome, if any. We analyzed the V4 hypervariable region of bacterial 16S rRNA genes with Illumina MiSeq to survey the different species of bacteria associated with the insects and the soils. The bacterial community associated with insects was significantly different from that in the soil. Some differences appear to exist between insects from non-diapausing and diapausing colonies while no significant differences in community composition existed between the insects reared on different soils. Despite differences in the bacteria present in immature stages and in male and female adults, there is a possible core bacteriome of approximately 16 operational taxonomic units (i.e., present across all life stages). This research may provide insights into Bt resistance development, improved nutrition in artificial rearing systems, and new management strategies.
Genome-wide differential expression profiling of lncRNAs and mRNAs associated with early diabetic cardiomyopathy
Authors: Pant Tarun , Dhanasekaran Anuradha , Bai Xiaowen , Zhao Ming , Thorp Edward B. , Forbess Joseph M. , Bosnjak Zeljko J. , Ge Zhi-Dong
Published: October 2019

Diabetic cardiomyopathy is one of the main causes of heart failure and death in patients with diabetes. There are no effective approaches to preventing its development in the clinic. Long noncoding RNAs (lncRNA) are increasingly recognized as important molecular players in cardiovascular disease. Herein we investigated the profiling of cardiac lncRNA and mRNA expression in type 2 diabetic db/db mice with and without early diabetic cardiomyopathy. We found that db/db mice developed cardiac hypertrophy with normal cardiac function at 6 weeks of age but with a decreased diastolic function at 20 weeks of age. LncRNA and mRNA transcripts were remarkably different in 20-week-old db/db mouse hearts compared with both nondiabetic and diabetic controls. Overall 1479 lncRNA transcripts and 1109 mRNA transcripts were aberrantly expressed in 6- and 20-week-old db/db hearts compared with nondiabetic controls. The lncRNA-mRNA co-expression network analysis revealed that 5 deregulated lncRNAs having maximum connections with differentially expressed mRNAs were BC038927, G730013B05Rik, 2700054A10Rik, AK089884, and Daw1. Bioinformatics analysis revealed that these 5 lncRNAs are closely associated with membrane depolarization, action potential conduction, contraction of cardiac myocytes, and actin filament-based movement of cardiac cells. This study profiles differently expressed lncRNAs in type 2 mice with and without early diabetic cardiomyopathy and identifies BC038927, G730013B05Rik, 2700054A10Rik, AK089884, and Daw1 as the core lncRNA with high significance in diabetic cardiomyopathy.
BCG instillation versus radical cystectomy for high-risk NMIBC with squamous/glandular histologic variants
Authors: Suh Jungyo , Moon Kyung Chul , Jung Jae Hyun , Lee Junghoon , Song Won Hoon , Kang Yu Jin , Jeong Chang Wook , Kwak Cheol , Kim Hyeon Hoe , Ku Ja Hyeon
Published: October 2019

This study aims to evaluate the effect of Bacillus Calmette-Guérin (BCG) instillation and radical cystectomy on high-risk NMIBC with squamous or glandular variants. We retrospectively reviewed the data of high-risk (T1 or CIS or HG or TaG1/G2 with multiple, recurrent, large tumor) NMIBC patients from January 2000 to December 2017. Comparative analysis of radical cystectomy, intravesical BCG, and observation groups was conducted in high-risk NMIBC with squamous or glandular histologic variants. Among the 1263 high-risk NMIBC patient, 62 (4.9%) were reported squamous or glandular histologic variants. Thirty patients underwent BCG instillation and 15 patients were subjected to radical cystectomy. Statistically significant differences were found between the three treatment groups in terms of underlying hypertension (p = 0.031), T stage (p = 0.022) and tumor multiplicity (p = 0.019). Similar 5-year OS (p = 0.893) and CSS (p = 0.811) were observed in each of BCG instillation and radical cystectomy group. BCG instillation showed survival benefit in both OS (p = 0.019) and CSS (p = 0.038) than in the observation group. In high-risk patients diagnosed with NMIBC bladder cancer with squamous or glandular histologic variants, both intravesical BCG and radical cystectomy showed survival gain. In conclusion, BCG instillation represents an appropriate treatment option in high-risk NMIBC with squamous or glandular histologic variant.
Molecular signatures associated with prostate cancer cell line (PC-3) exposure to inactivated Zika virus
Authors: Delafiori Jeany , Lima Estela de Oliveira , Dabaja Mohamed Ziad , Dias-Audibert Flávia Luísa , de Oliveira Diogo Noin , Melo Carlos Fernando Odir Rodrigues , Morishita Karen Noda , Sales Geovana Manzan , Ruiz Ana Lucia Tasca Gois , da Silva Gisele Goulart , Lancellotti Marcelo , Catharino Rodrigo Ramos
Published: October 2019

The recent outbreak of Zika virus (ZIKV) infection associated with microcephaly cases has elicited much research on the mechanisms involved in ZIKV-host cell interactions. It has been described that Zika virus impairs cell growth, raising a hypothesis about its oncolytic potential against cancer cells. ZIKV tumor cell growth inhibition was later confirmed for glioblastoma. It was also demonstrated that an inactivated ZIKV prototype (ZVp) based on bacterial outer membrane vesicles has antiproliferative activity upon other cancer cell lines, such as PC-3 prostate cancer cell. This study aims at understanding the pathways that might be involved with the antiproliferative effect of Zika virus against prostate cancer cells. A metabolomic approach based on high-resolution mass spectrometry analysis led to the identification of 21 statistically relevant markers of PC-3 cells treated with ZVp. The markers were associated with metabolic alterations that trigger lipid remodeling, endoplasmic reticulum stress, inflammatory mediators, as well as disrupted porphyrin and folate metabolism. These findings highlight molecular signatures of ZVp-induced response that may be involved on cellular pathways triggered by its antiproliferative effect. To our knowledge, this is the first reported metabolomic assessment of ZIKV effect on prostate cancer cells, a promising topic for further research.
Disparities in the Concentrations of Essential/Toxic Elements in the Blood and Scalp Hair of Lymphoma Patients and Healthy Subjects
Authors: Qayyum Muhammad Abdul , Shah Munir H.
Published: October 2019

Lymphoma is one of the fastest growing malignancies worldwide and imbalance in the concentrations of trace elements can play a significant role in the onset and progression of the disease. Selected essential and toxic elements (Fe, Zn, Cu, Mn, Ni, Cr, Cd and Pb) were analysed in the blood & scalp hair of lymphoma patients (n = 59 & 58, respectively) and controls (n = 61 & 60, respectively) by atomic absorption spectrometry. On the average, Ni, Cr, Cu and Cd revealed significantly higher contents in the blood and scalp hair of the patients than the controls (p < 0.05). The correlation study showed significantly diverse relationships among the elements in blood & scalp hair of the two donor groups. Variations in the elemental levels with different types of lymphoma (non-Hodgkin and Hodgkin) were also evaluated. Disparities in the elemental concentrations were also investigated for various types of non-Hodgkin (diffuse large B-cell lymphoma, follicular lymphoma and peripheral T-cell lymphoma) and Hodgkin lymphoma (mixed cellularity, nodular lymphocyte predominant and nodular sclerosing), as well as for different stages (I, II, III & IV) of the cancer. Multivariate statistical analysis showed considerably divergent associations of the elements in the patients and controls. The study indicated profound alteration of the elemental levels in the patients; it may be implicated in elemental-induced disorders including lymphoma.
Polyneuropathy in Gaucher disease type 1 and 3 – a descriptive case series
Authors: Andréasson Mattias , Solders Göran , Björkvall Cecilia K. , Machaczka Maciej , Svenningsson Per
Published: October 2019

Polyneuropathy (PNP) has been reported to be a possible phenotypic feature in Gaucher disease type 1 (GD1), while less is known about PNP in type 3 (GD3). We performed a cross-sectional study, exploring PNP in a Swedish GD cohort. Clinical assessment and blood biochemistry were carried out in 8 patients with GD1 and 11 patients with GD3. In patients with symptoms or clinical findings indicative of PNP, nerve conduction studies and quantitative sensory testing were performed. Assessments were compared to historic controls. A subclinical small fiber neuropathy (SFN) was demonstrated in 2 of 8 patients in the significantly (p = 0,021) older GD1 cohort. A large fiber PNP was evident in an additional 3 GD1 patients but could not be ascribed as disease manifestation. No GD3 patients exhibited neurophysiological evidence of small or large fiber PNP attributed to GD3. Compared to historic controls, no significant group differences were evident with regard to neuropathy rating scores. In summary, our study does not support large fiber PNP as a prevalent manifestation of GD. SFN is a possible feature in GD1, although small sample size limits definite conclusions. Our study provides novel data, arguing against clinically significant small or large fiber PNP in GD3.
Genomic characterization of intrinsic and acquired resistance to cetuximab in colorectal cancer patients
Authors: Bray Steven M. , Lee Jeeyun , Kim Seung Tae , Hur Joon Young , Ebert Philip J. , Calley John N. , Wulur Isabella H. , Gopalappa Thejaswini , Wong Swee Seong , Qian Hui-Rong , Ting Jason C. , Liu Jiangang , Willard Melinda D. , Novosiadly Ruslan D. , Park Young Suk , Park Joon Oh , Lim Ho Yeong , Kang Won Ki , Aggarwal Amit , Kim Hee Cheol , Reinhard Christoph
Published: October 2019

Anti-EGFR antibodies are effective in therapies for late-stage colorectal cancer (CRC); however, many tumours are unresponsive or develop resistance. We performed genomic analysis of intrinsic and acquired resistance to anti-EGFR therapy in prospectively collected tumour samples from 25 CRC patients receiving cetuximab (an EGFR inhibitor). Of 25 CRC patients, 13 displayed intrinsic resistance to cetuximab; 12 were intrinsically sensitive. We obtained six re-biopsy samples at acquired resistance from the intrinsically sensitive patients. NCOA4–RET and LMNA–NTRK1 fusions and NRG1 and GNAS amplifications were found in intrinsic-resistant patients. In cetuximab-sensitive patients, we found KRAS K117N and A146T mutations in addition to BRAF V600E, AKT1 E17K, PIK3CA E542K, and FGFR1 or ERBB2 amplifications. The comparison between baseline and acquired-resistant tumours revealed an extreme shift in variant allele frequency of somatic variants, suggesting that cetuximab exposure dramatically selected for rare resistant subclones that were initially undetectable. There was also an increase in epithelial-to-mesenchymal transition at acquired resistance, with a reduction in the immune infiltrate. Furthermore, characterization of an acquired-resistant, patient-derived cell line showed that PI3K/mTOR inhibition could rescue cetuximab resistance. Thus, we uncovered novel genomic alterations that elucidate the mechanisms of sensitivity and resistance to anti-EGFR therapy in metastatic CRC patients.
One-pot regioselective synthesis of substituted pyrazoles and isoxazoles in PEG-400/water medium by Cu-free nano-Pd catalyzed sequential acyl Sonogashira coupling–intramolecular cyclization
Authors: Thirukovela Narasimha Swamy , Balaboina Ramesh , Botla Vinayak , Vadde Ravinder , Jonnalagadda Sreekantha Babu , Vasam Chandra Sekhar
Published: October 2019

Catalyst efficacy of in situ generated Pd-nanoparticles in the regioselective one-pot synthesis of substituted pyrazoles and isoxazoles via sequential coupling-cyclization methodology in environmentally benign medium is described.
Effects of betalains on atherogenic risk factors in patients with atherosclerotic cardiovascular disease
Authors: Rahimi Parisa , Mesbah-Namin Seyed Alireza , Ostadrahimi Alireza , Abedimanesh Saeed , Separham Ahmad , Asghary Jafarabadi Mohammad
Published: October 2019

After consumption of betalain-rich supplements of red beetroot and betacyanins-rich supplements of Opuntia stricta, the betanin appears in urine and plasma to improve the lipid profile, blood pressure, homocysteine and glucose levels of the patients.
Controllable growth of Au nanostructures onto MoS2 nanosheets for dual-modal imaging and photothermal–radiation combined therapy
Authors: Liu Teng , Shen Sida , Huang Ying , Zhang Xiao , Lai Zhuangchai , Tran Thu Ha , Liu Zhuang , Cheng Liang
Published: October 2019

Multifunctional theranostic nanoagents are attractive to realize comprehensive imaging and effective treatment of tumours.
Correction: Perspectives for Ag2S NIR-II nanoparticles in biomedicine: from imaging to multifunctionality
Authors: Shen Yingli , Lifante José , Ximendes Erving , Santos Harrison D. A. , Ruiz Diego , Juárez Beatriz H. , Gutiérrez Irene Zabala , Vera Vivian Torres , Retama Jorge Rubio , Rodríguez Emma Martín , Ortgies Dirk H. , Jaque Daniel , Benayas Antonio , Rosal Blanca del
Published: October 2019

Correction for ‘Perspectives for Ag2S NIR-II nanoparticles in biomedicine: from imaging to multifunctionality’ by Yingli Shen, et al., Nanoscale, 2019, DOI: 10.1039/c9nr05733a.
Correction: Capacitive behaviour of nanocrystalline octacalcium phosphate (OCP) (Ca8H2(PO4)6·5H2O) as an electrode material for supercapacitors: biosupercaps
Authors: Tuncer Mustafa , Bakan Feray , Hamedani Ali Ansari , Hayat Soytas Serap , Gocmez Hasan , Erdem Emre
Published: October 2019

Correction for ‘Capacitive behaviour of nanocrystalline octacalcium phosphate (OCP) (Ca8H2(PO4)6·5H2O) as an electrode material for supercapacitors: biosupercaps’ by Mustafa Tuncer et al., Nanoscale, 2019, 11, 18375–18381.
Correction: A highly selective fluorescent probe for human NAD(P)H:quinone oxidoreductase 1 (hNQO1) detection and imaging in living tumor cells
Authors: Zhu Ya , Han Jialing , Zhang Qian , Zhao Zhou , Wang Jin , Xu Xiaowei , Hao Haiping , Zhang Jun
Published: October 2019

Correction for ‘A highly selective fluorescent probe for human NAD(P)H:quinone oxidoreductase 1 (hNQO1) detection and imaging in living tumor cells’ by Ya Zhuet al.,RSC Adv., 2019,9, 26729–26733.
Effectiveness of Rehabilitation Approaches Proposed to Children With Severe-to-Profound Prelinguistic Deafness on the Development of Auditory, Speech, and Language Skills: A Systematic Review
Authors: Demers Dominique , Bergeron François
Published: October 2019

Purpose

The purpose of this systematic review is to identify and evaluate the available scientific evidence on the effectiveness of rehabilitation approaches proposed to children with severe-to-profound prelinguistic deafness on the hearing, speech, and language skills development.

Method

Databases (PubMed, CINHAL, PsycInfo, Cochrane, ERIC, and EMBASE) were searched with relevant key words (children, deafness, rehabilitation approach, auditory, speech, and language). Studies published between 2000 and 2017 were included. The methodological quality of the studies was evaluated with the Quality Assessment Tool for Quantitative Studies, and the level of evidence was evaluated with the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Every step of the selection and analysis was made by 2 independent judges.

Results

Of 1,739 articles listed in different databases, 38 met the inclusion criteria and were selected for analysis. The majority of included articles present a relatively low level of evidence. Rehabilitation approaches that do not include signs appear more frequently associated with a better auditory, speech, and language development, except for receptive language, than approaches that included any form of signs.

Conclusion

More robust studies are needed to decide on the approach to prioritize with severe-to-profound deaf children.
Categorical and Dimensional Ratings of Emotional Speech: Behavioral Findings From the Morgan Emotional Speech Set
Authors: Morgan Shae D.
Published: October 2019

Purpose

Emotion classification for auditory stimuli typically employs 1 of 2 approaches (discrete categories or emotional dimensions). This work presents a new emotional speech set, compares these 2 classification methods for emotional speech stimuli, and emphasizes the need to consider the entire communication model (i.e., the talker, message, and listener) when studying auditory emotion portrayal and perception.

Method

Emotional speech from male and female talkers was evaluated using both categorical and dimensional rating methods. Ten young adult listeners (ages 19–28 years) evaluated stimuli recorded in 4 emotional speaking styles (Angry, Calm, Happy, and Sad). Talker and listener factors were examined for potential influences on emotional ratings using categorical and dimensional rating methods. Listeners rated stimuli by selecting an emotion category, rating the activation and pleasantness, and indicating goodness of category fit.

Results

Discrete ratings were generally consistent with dimensional ratings for speech, with accuracy for emotion recognition well above chance. As stimuli approached dimensional extremes of activation and pleasantness, listeners were more confident in their category selection, indicative of a hybrid approach to emotion classification. Female talkers were rated as more activated than male talkers, and female listeners gave higher ratings of activation compared to male listeners, confirming gender differences in emotion perception.

Conclusion

A hybrid model for auditory emotion classification is supported by the data. Talker and listener factors, such as gender, were found to impact the ratings of emotional speech and must be considered alongside stimulus factors in the design of future studies of emotion.
Identification of Hearing Loss in Individuals With Cognitive Impairment Using Portable Tablet Audiometer
Authors: Pletnikova Alexandra , Reed Nicholas S. , Amjad Halima , Yasar Sevil , Nowrangi Milap , Betz Joshua , Lin Frank R. , Oh Esther S.
Published: October 2019

Purpose

The purpose of this study was to determine the feasibility of using a tablet-based portable audiometer to identify hearing loss in a cognitively impaired population.

Method

In this study, we used a retrospective chart review of an outpatient memory clinic. During a quality initiative, older adult (
M
age
= 74.6) patients (
n
= 91) completed pure-tone hearing testing (0.5–4 kHz) via automated self-administration and technician-administered threshold testing (gold standard) on a tablet-based audiometer.

Results

Technician-administered auditory threshold testing was successfully conducted in all patients. A total of 54 of the 91 patients (59%) also had hearing thresholds reliably obtained with automated self-administration. In bivariate analyses, older age, lower Mini-Mental State Examination (MMSE) scores, lower education, male sex, and higher degree of hearing impairment were associated with higher odds of having an unreliable self-administered test defined as multiple recorded false positives at 2 or more test frequencies. In multivariable analysis, lower MMSE scores and poorer hearing were significantly associated with higher odds of having an unreliable self-administered test.

Conclusion

Technician-administered hearing threshold testing using a portable, tablet-based audiometer can be successfully administered to patients with cognitive impairment. Reliability of automated self-administration is limited in patients with lower MMSE scores.
Twisted quasar light curves: implications for continuum reverberation mapping of accretion disks
Authors: Chan J. H.-H. , Millon M. , Bonvin V. , Courbin F.
Published: October 2019

With the advent of high-cadence and multi-band photometric monitoring facilities, continuum reverberation mapping is becoming of increasing importance for the measurement of the physical size of quasar accretion disks. The method is based on measuring the time it takes for a signal to propagate from the center to the outer parts of the central engine, assuming the continuum light curve at a given wavelength has a time shift of the order of a few days with respect to light curves obtained at shorter wavelengths. We show that with high-quality light curves, this assumption is no longer valid and that light curves at different wavelengths are not only shifted in time, but also distorted: in the context of the lamp-post model and thin-disk geometry, the multi-band light curves are, in fact, convolved by a transfer function whose size increases with wavelength. We illustrate the effect with simulated light curves in the Large Synoptic Survey Telescope (LSST) ugrizy bands and examine the impact on the delay measurements when using three different methods, namely JAVELIN, CREAM, and PyCS. We find that current accretion disk sizes estimated from JAVELIN and PyCS are underestimated by ∼30% and that unbiased measurements are only obtained with methods that properly take the skewed transfer functions into account, as the CREAM code does. With the LSST-like light curves, we expect to achieve measurement errors below 5% with a typical two-day photometric cadence.