bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of microhematuria with mesangial hypercellularity, endocapillary hypercellularity, crescent score and renal outcomes in immunoglobulin A nephropathy
Authors: Bobart Shane A , Alexander Mariam P , Shawwa Khaled , Vaughan Lisa E , Ghamrawi Ranine , Sethi Sanjeev , Cornell Lynn , Glassock Richard J , Fervenza Fernando C , Zand Ladan 
Published: November 2019

Abstract

Background
Microhematuria is common in immunoglobulin A nephropathy (IgAN). However, current prognostication is based on proteinuria and mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, tubulointerstitial fibrosis and crescent (MEST-C) scores.

Methods
In this retrospective study, we evaluated whether MEST-C score components are associated with the presence of microhematuria at biopsy and whether the degree of microhematuria during follow-up is associated with change in estimated glomerular filtration rate (eGFR), after adjusting for clinical and histological parameters. We identified 125 patients with biopsy-proven IgAN and MEST-C scoring who were not on immunosuppressive therapy at biopsy. Microhematuria was defined as ≥3 red blood cells (RBCs)/high-power field (hpf).

Results
Of the 125 patients, 97 had microhematuria at baseline and were more likely to have M1, E1 and C ≥ 1 lesions (P &lt; 0.05 for all) compared with patients without microhematuria. Of the 125 patients, 72 had follow-up data available. An increase in the degree of microhematuria was significantly associated with an eGFR decline of −0.81 mL/min/1.73 m2 [95% confidence interval (CI) −1.44 to −0.19, P = 0.01], after adjusting for follow-up time, proteinuria and T score. Severe microhematuria (≥21 RBCs/hpf) was associated with an even larger decline in eGFR (−3.99 mL/min/1.73 m2; 95% CI −6.9411 to −1.0552, P = 0.008), after similar adjustments.

Conclusion
Degree of microhematuria during follow-up is an independent predictor of eGFR decline after adjusting for clinical and histological parameters. Therefore, monitoring the degree of microhematuria as well as proteinuria is important when evaluating patients with IgAN. Additional studies using improvement in microhematuria as a primary surrogate outcome are needed.
Nickel Toxicity Targets Cell Wall-Related Processes and PIN2-Mediated Auxin Transport to Inhibit Root Elongation and Gravitropic Responses in Arabidopsis
Authors: Leškov� Alexandra , Zvar�k Milan , Araya Takao , Giehl Ricardo F H 
Published: November 2019

Abstract
Contamination of soils with heavy metals, such as nickel (Ni), is a major environmental concern due to increasing pollution from industrial activities, burning of fossil fuels, incorrect disposal of sewage sludge, excessive manure application and the use of fertilizers and pesticides in agriculture. Excess Ni induces leaf chlorosis and inhibits plant growth, but the mechanisms underlying growth inhibition remain largely unknown. A detailed analysis of root development in Arabidopsis thaliana in the presence of Ni revealed that this heavy metal induces gravitropic defects and locally inhibits root growth by suppressing cell elongation without significantly disrupting the integrity of the stem cell niche. The analysis of auxin-responsive reporters revealed that excess Ni inhibits shootward auxin distribution. Furthermore, we found that PIN2 is very sensitive to Ni, as the presence of this heavy metal rapidly reduced PIN2 levels in roots. A transcriptome analysis also showed that Ni affects the expression of many genes associated with plant cell walls and that Ni-induced transcriptional changes are largely independent of iron (Fe). In addition, we raised evidence that excess Ni increases the accumulation of reactive oxygen species and disturbs the integrity and orientation of microtubules. Together, our results highlight which processes are primarily targeted by Ni to alter root growth and development.
Homogeneous Spinor Flow
Authors: Freibert Marco , Schiemanowski Lothar , Weiss Hartmut 
Published: November 2019

Abstract
We study the spinor flow on homogeneous spin manifolds. After providing the general setup we discuss the homogeneous spinor flow in dimension three and on almost abelian Lie groups in detail. As a further example, the flag manifold in dimension six is treated.
High-Content Image-Based Single-Cell Phenotypic Analysis for the Testicular Toxicity Prediction Induced by Bisphenol A and Its Analogs Bisphenol S, Bisphenol AF, and Tetrabromobisphenol A in a Three-Dimensional Testicular Cell Co-culture Model
Authors: Yin Lei , Siracusa Jacob Steven , Measel Emily , Guan Xueling , Edenfield Clayton , Liang Shenxuan , Yu Xiaozhong 
Published: November 2019

AbstractEmerging data indicate that structural analogs of bisphenol A (BPA) such as bisphenol S (BPS), tetrabromobisphenol A (TBBPA), and bisphenol AF (BPAF) have been introduced into the market as substitutes for BPA. Our previous study compared in vitro testicular toxicity using murine C18-4 spermatogonial cells and found that BPAF and TBBPA exhibited higher spermatogonial toxicities as compared with BPA and BPS. Recently, we developed a novel in vitro three-dimensional (3D) testicular cell co-culture model, enabling the classification of reproductive toxic substances. In this study, we applied the testicular cell co-culture model and employed a high-content image (HCA)-based single-cell analysis to further compare the testicular toxicities of BPA and its analogs. We also developed a machine learning (ML)-based HCA pipeline to examine the complex phenotypic changes associated with testicular toxicities. We found dose- and time-dependent changes in a wide spectrum of adverse endpoints, including nuclear morphology, DNA synthesis, DNA damage, and cytoskeletal structure in a single-cell-based analysis. The co-cultured testicular cells were more sensitive than the C18 spermatogonial cells in response to BPA and its analogs. Unlike conventional population-averaged assays, single-cell-based assays not only showed the levels of the averaged population, but also revealed changes in the sub-population. Machine learning-based phenotypic analysis revealed that treatment of BPA and its analogs resulted in the loss of spatial cytoskeletal structure, and an accumulation of M phase cells in a dose- and time-dependent manner. Furthermore, treatment of BPAF-induced multinucleated cells, which were associated with altered DNA damage response and impaired cellular F-actin filaments. Overall, we demonstrated a new and effective means to evaluate multiple toxic endpoints in the testicular co-culture model through the combination of ML and high-content image-based single-cell analysis. This approach provided an in-depth analysis of the multi-dimensional HCA data and provided an unbiased quantitative analysis of the phenotypes of interest.
Purchase Patterns, Socioeconomic Status, and Political Inclination
Authors: Dong Xiaowen , Jahani Eaman , Morales Alfredo J , Bozkaya Burçin , Lepri Bruno , Pentland Alex ´Sandy' 
Published: November 2019

Abstract
This paper analyzes millions of credit card transaction records during several months for tens of thousands of individuals from two different countries. The study shows that, purchase patterns are strongly correlated with important societal indices such as socioeconomic status and political inclination. The results suggest the possibility of understanding and predicting the evolution of such societal indices from purchase behavioral patterns, potentially at high temporal and spatial resolutions.
Activity‐dependent cleavage of dyskinesia‐related proline‐rich transmembrane protein 2 (PRRT2) by calpain in mouse primary cortical neurons
Authors: Hatta Daisuke , Shirotani Keiro , Hori Yuma , Kurotaki Naohiro , Iwata Nobuhisa 
Published: November 2019

AbstractMutations of PRRT2 (proline‐rich transmembrane protein 2) cause several neurological disorders, represented by paroxysmal kinesigenic dyskinesia (PKD), which is characterized by attacks of involuntary movements triggered by sudden voluntary movements. PRRT2 is reported to suppress neuronal excitation, but it is unclear how the function of PRRT2 is modulated during neuronal excitation. We found that PRRT2 is processed to a 12 kDa carboxy‐terminal fragment (12K‐CTF) by calpain, a calcium‐activated cysteine protease, in a neuronal activity‐dependent manner, predominantly via NMDA receptors or voltage‐gated calcium channels. Furthermore, we clarified that 12K‐CTF is generated by sequential cleavages at Q220 and S244. The amino‐terminal fragment (NTF) of PRRT2, which corresponds to PKD‐related truncated mutants, is not detected, probably due to rapid cleavage at multiple positions. Given that 12K‐CTF lacks most of the proline‐rich domain, this cleavage might be involved in the activity‐dependent enhancement of neuronal excitation perhaps through transient retraction of PRRT2's function. Therefore, PRRT2 might serve as a buffer for neuronal excitation, and lack of this function in PKD patients might cause neuronal hyperexcitability in their motor circuits.
Influence of electromagnetic radiation emitted by daily-use electronic devices on the Eyemate® system
Authors: Invernizzi Azzurra , Haykal Shereif , Lo Faro Valeria , Pennisi Vincenzo , Choritz Lars 
Published: November 2019

AbstractPurposeEyemate® is a system for the continual monitoring of intraocular pressure (IOP), comprised of an intraocular sensor, and a hand-held reader device. The eyemate®-IO sensor is surgically implanted in the eye during cataract surgery. Once implanted, the sensor communicates telemetrically with the hand-held device to activate and record IOP measurements. The aim of this study was to assess the possible influence of electromagnetic radiation emitted by daily-use electronic devices on the eyemate® IOP measurements.MethodsThe eyemate®-IO sensor was placed in a plastic bag, immersed in a sterile sodium chloride solution at 0.9% and placed in a water bath at 37°C. The antenna, connected to a laptop for recording the data, was positioned at a fixed distance of 1 cm from the sensor. Approximately two hours of “quasi-continuous” measurements was recorded for the baseline and for cordless phone, smart-phone and laptop. Repeated measures ANOVA was used to compare any possible differences between the baseline and the tested devices.ResultsFor baseline measurements, the sensor maintained a steady-state. The same behavior was observed with the devices measurements during active and inactive states.ConclusionWe found no evidence of signal drifts or fluctuations associated with the tested devices, thus showing a lack of electromagnetic interference with data transmission. Patients who already have the eyemate®-IO sensor implanted, or those considering it, can be informed that the electromagnetic radiation emitted by their daily-use electronic devices does not interfere with IOP measurements made by the eyemate®-IO sensor.
Within Visit Test-Retest Reliability of EEG Profiles in Children with Autism Spectrum Disorder and Typical Development
Authors: Levin April R. , Naples Adam J. , Scheffler Aaron Wolfe , Webb Sara J. , Shic Frederick , Sugar Catherine A. , Murias Michael , Bernier Raphael A. , Chawarska Katarzyna , Dawson Geraldine , Faja Susan , Jeste Shafali , Nelson Charles A. , McPartland James C. , Şentürk Damla ,   the Autism Biomarkers Consortium for Clinical Trials
Published: November 2019

AbstractBiomarker development is currently a high priority in neurodevelopmental disorder research. For many types of biomarkers (particularly biomarkers of diagnosis), reliability over short time periods is critically important. In the field of autism spectrum disorder (ASD), resting electroencephalography (EEG) power spectral densities (PSD) are well-studied for their potential as biomarkers. Classically, such data have been decomposed into pre-specified frequency bands (e.g., delta, theta, alpha, beta, and gamma). Recent technical advances, such as the Fitting Oscillations and One-Over-F (FOOOF) algorithm, allow for targeted characterization of the features that naturally emerge within an EEG PSD, permitting a more detailed characterization of the frequency band-agnostic shape of each individual’s EEG PSD. Here, using two resting EEGs collected a median of 6 days apart from 22 children with ASD and 25 typically developing (TD) controls during the Feasibility Visit of the Autism Biomarkers Consortium for Clinical Trials, we estimate within visit test-retest reliability based on characterization of the PSD shape in two ways: (1) Using the FOOOF algorithm we estimate six parameters (offset, slope, number of peaks, and amplitude, center frequency and bandwidth of the largest alpha peak) that characterize the shape of the EEG PSD; and (2) using nonparametric functional data analyses, we decompose the shape of the EEG PSD into a reduced set of basis functions that characterize individual power spectrum shapes. We show that individuals exhibit idiosyncratic PSD signatures that are stable over recording sessions using both characterizations. Our data show that EEG activity from a brief two-minute recording provides an efficient window into understanding brain activity at the single-subject level with desirable psychometric characteristics that persist across different analytical decomposition methods. This is a necessary step towards analytical validation of biomarkers based on the EEG PSD, and provides insights into parameters of the PSD that offer short-term reliability (and thus promise as potential biomarkers of trait or diagnosis) versus those that are more variable over the short term (and thus may index state or other rapidly dynamic measures of brain function). Future research should address longer-term stability of the PSD, for purposes such as monitoring development or response to treatment.
Non-affine displacements encode collective conformational fluctuations in proteins
Authors: Prakashchand Dube Dheeraj , Ahalawat Navjeet , Bandyopadhyay Satyabrata , Sengupta Surajit , Mondal Jagannath 
Published: November 2019

AbstractIdentifying subtle conformational fluctuations underlying the dynamics of bio macro-molecules is crucial for resolving their free energy landscape. We show that a collective variable, originally proposed for crystalline solids, is able to filter out essential macro-molecular motions more efficiently than other approaches. While homogenous or ‘affine’ deformations of the biopolymer are trivial, biopolymer conformations are complicated by the occurrence of in-homogenous or ‘non-affine’ displacements of atoms relative to their positions in the native structure. We show that these displacements encode functionally relevant conformations of macromolecule and, in combination with a formalism based upon time-structured independent component analysis, quantitatively resolve the free energy landscape of a number of macromolecules of hierarchical complexity. The kinetics of conformational transitions among the basins can now be mapped within the framework of a Markov state model. The non-affine modes, obtained by projecting out homogenous fluctuations from the local displacements, are found to be responsible for local structural changes required for transitioning between pairs of macro states.
Nα-terminal acetylation of proteins by NatA and NatB serves distinct physiological roles inSaccharomyces cerevisiae
Authors: Friedrich Ulrike A. , Zedan Mostafa , Hessling Bernd , Fenzl Kai , Gillet Ludovic , Barry Joseph , Knop Michael , Kramer Günter , Bukau Bernd 
Published: November 2019

SummaryN-terminal (Nt)-acetylation is a highly prevalent co-translational protein modification in eukaryotes, catalyzed by at least five Nt-acetyltransferases (Nat) with differing specificities. Nt-acetylation has been implicated in protein quality control but its broad biological significance remains elusive. We investigated the roles of the two major Nats ofS. cerevisiae, NatA and NatB, by performing transcriptome, translatome and proteome profiling ofnatAΔ andnatBΔ mutants. Our results do not support a general role of Nt-acetylation in protein degradation but reveal an unexpected range of Nat-specific phenotypes. NatA is implicated in systemic adaptation control, asnatAΔ mutants display altered expression of transposons, sub-telomeric genes, pheromone response genes and nuclear genes encoding mitochondrial ribosomal proteins. NatB predominantly affects protein folding, asnatBΔ mutants accumulate protein aggregates, induce stress responses and display reduced fitness in absence of the ribosome-associated chaperone Ssb. These phenotypic differences indicate that controlling Nat activities may serve to elicit distinct cellular responses.
Microtubules originate asymmetrically at the somatic Golgi and are guided via Kinesin2 to maintain polarity within neurons
Authors: Mukherjee Amrita , Brooks Paul , Bernard Fred , Guichet Antoine , Conduit Paul T. 
Published: November 2019

AbstractNeurons contain polarised microtubule arrays essential for neuronal function. How microtubule nucleation and polarity are regulated within neurons remains unclear. We show that γ-tubulin localises asymmetrically to the somatic Golgi withinDrosophilaneurons. Microtubules originate from the Golgi with an initial growth preference towards the axon. Their growing plus ends also turn towards and into the axon, adding to the plus-end-out microtubule pool. Any plus ends that reach a dendrite, however, do not readily enter, maintaining minus-end-out polarity. Both turning towards the axon and exclusion from dendrites depend on Kinesin-2, a plus-end-associated motor that guides growing plus ends along adjacent microtubules. We propose that Kinesin-2 engages with a polarised microtubule network within the soma to guide growing microtubules towards the axon; while at dendrite entry sites engagement with microtubules of opposite polarity generates a backward stalling force that prevents entry into dendrites and thus maintains minus-end-out polarity within proximal dendrites.
RH mapping by sequencing: chromosome-scale assembly of the duck genome
Authors: Rao Man , Vignal Alain , Morisson Mireille , Fillon Valérie , Leroux Sophie , Lhuillier Émeline , Esquerré Diane , Bouchez Olivier , Li Ning , Faraut Thomas 
Published: November 2019

AbstractLike many other species, the duck genome has been sequenced thanks to the technological breakthrough provided by the emergence of Next Generation Sequencing (NGS). The resulting de novo assemblies are however made of thousands of scattered scaffolds. To achieve chromosome-scale contiguity, long-range intermediate genome maps remain indispensable. Radiation Hybrid (RH) maps have been used to assist the generation of chromosome-scale genome assemblies by taking advantage of the high density SNP chips that provide a large number of markers that can be efficiently genotyped on the panel.In the absence of such a resource in duck, we sequenced 100 hybrid clones of a duck RH panel enabling direct genotyping of the assembly scaffolds on the panel. The rationale is to use scaffolds as markers and to genotype the scaffolds by sequencing the clones: the presence/absence of a scaffold in a particular sequenced hybrid is attested by the presence/absence of reads mapping specifically to this scaffold. The detection of scaffolds exhibiting a chromosomal breakage resulting from the irradiation process revealed itself to be a critical issue of this genotyping by sequencing process. This process resulted in the construction of RH vectors for 2,027 scaffolds, representing a total of about 1 Gb of sequences (95% of the current Duck genome assembly). The subsequent linkage analysis enabled the construction of RH maps and therefore to organize, i.e. order and orient, the scaffolds into pseudomolecules associated to the corresponding duck chromosomes. We describe here the whole mapping process, from sequence-based genotyping to the construction of comparative maps, as well as few examples of intra-chromosomal rearrangements that have been identified by the comparison with the chicken, turkey and zebra finch genomes and subsequently confirmed by FISH.We describe a method to order and orient sequence scaffolds into super-scaffolds spanning entire chromosomes. The method, which requires a pre-existing RH panel and sequence scaffolds from an NGS assembly, relies on a shallow sequencing of the RH clones. This approach was applied to the duck genome and produced chromosome-scale scaffolds for 29 out of the 41 duck chromosomes.
TUTase mediated site-directed access to clickable chromatin employing CRISPR-dCas9
Authors: George Jerrin Thomas , Azhar Mohd. , Aich Meghali , Sinha Dipanjali , Ambi Uddhav B. , Maiti Souvik , Chakraborty Debojyoti , Srivatsan Seergazhi G. 
Published: November 2019

AbstractLocus-specific interrogation of the genome using programmable CRISPR-based technologies is tremendously useful in dissecting the molecular basis of target gene function and modulating its downstream output. Although these tools are widely utilized in recruiting genetically encoded functional proteins, display of small molecules using this technique is not well developed due to inadequate labeling technologies. Here, we report the development of a modular technology, sgRNA-Click (sgR-CLK), which harnesses the power of bioorthogonal click chemistry for remodeling CRISPR to display synthetic molecules on target genes. A terminal uridylyl transferase (TUTase) was repurposed to construct an sgRNA containing multiple minimally invasive bioorthogonal clickable handles, which served as a Trojan horse on CRISPR-dCas9 system to guide synthetic tags site-specifically on chromatin employing copper-catalyzed or strain-promoted click reactions. Our results demonstrate that sgR-CLK could provide a simplified solution for site-directed display of small molecules to study as well as modulate the function of gene targets.
A principal component approach to improve association testing with polygenic risk scores
Authors: Coombes Brandon J. , Biernacka Joanna M. 
Published: November 2019

AbstractPolygenic risk scores (PRSs) have become an increasingly popular approach for demonstrating polygenic influences on complex traits and for establishing common polygenic signals between different traits. PRSs are typically constructed using pruning and thresholding (P+T), but the best choice of parameters is uncertain; thus multiple settings are used and the best is chosen. This optimization can lead to inflated type I error. To correct this, permutation procedures can be used but they can be computationally intensive. Alternatively, a single parameter setting can be chosen a priori for the PRS, but choosing suboptimal settings result in loss of power. We propose computing PRSs under a range of parameter settings, performing principal component analysis (PCA) on the resulting set of PRSs, and using the first PRS-PC in association tests. The first PC reweights the variants included in the PRS with new weights to achieve maximum variation over all PRS settings used. Using simulations, we compare the performance of the proposed PRS-PCA approach with a permutation test and a priori selection of p-value threshold. We then apply the approach to the Mayo Clinic Bipolar Disorder Biobank study to test for PRS association with psychosis using a variety of PRSs constructed from summary statistics from the largest studies of psychiatric disorders and related traits. The PRS-PCA approach is simple to implement, outperforms the other strategies in most scenarios, and provides an unbiased estimate of prediction performance. We therefore recommend it to be used PRS association studies where multiple phenotypes and/or PRSs are being investigated.