bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia
Authors: Gialluisi Alessandro , Andlauer Till F. M. , Mirza-Schreiber Nazanin , Moll Kristina , Becker Jessica , Hoffmann Per , Ludwig Kerstin U. , Czamara Darina , Pourcain Beate St , Honbolygó Ferenc , Tóth Dénes , Csépe Valéria , Huguet Guillaume , Chaix Yves , Iannuzzi Stephanie , Demonet Jean-Francois , Morris Andrew P. , Hulslander Jacqueline , Willcutt Erik G. , DeFries John C. , Olson Richard K. , Smith Shelley D. , Pennington Bruce F. , Vaessen Anniek , Maurer Urs , Lyytinen Heikki , Peyrard-Janvid Myriam , Leppänen Paavo H. T. , Brandeis Daniel , Bonte Milene , Stein John F. , Talcott Joel B. , Fauchereau Fabien , Wilcke Arndt , Kirsten Holger , Müller Bent , Francks Clyde , Bourgeron Thomas , Monaco Anthony P. , Ramus Franck , Landerl Karin , Kere Juha , Scerri Thomas S. , Paracchini Silvia , Fisher Simon E. , Schumacher Johannes , Nöthen Markus M. , Müller-Myhsok Bertram , Schulte-Körne Gerd
Published: October 2020

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p  < 2.8 × 10−6) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20–25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (atpT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase;p  = 8 × 10−13), bipolar disorder (1.53[1.44; 1.63];p = 1 × 10−43), schizophrenia (1.36[1.28; 1.45];p = 4 × 10−22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30];p = 3 × 10−12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96];p = 5 × 10−4), educational attainment (0.86[0.82; 0.91];p = 2 × 10−7), and intelligence (0.72[0.68; 0.76];p = 9 × 10−29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.
Genetic alterations of SUGP1 mimic mutant-SF3B1 splice pattern in lung adenocarcinoma and other cancers
Authors: Alsafadi Samar , Dayot Stephane , Tarin Malcy , Houy Alexandre , Bellanger Dorine , Cornella Michele , Wassef Michel , Waterfall Joshua J. , Lehnert Erik , Roman-Roman Sergio , Stern Marc-Henri , Popova Tatiana
Published: October 2020

Genes involved in 3′-splice site recognition during mRNA splicing constitute an emerging class of oncogenes. SF3B1 is the most frequently mutated splicing factor in cancer, and SF3B1 mutants corrupt branchpoint recognition leading to usage of cryptic 3′-splice sites and subsequent aberrant junctions. For a comprehensive determination of alterations leading to this splicing pattern, we performed a pan-TCGA screening for SF3B1-specific aberrant acceptor usage. While the most of aberrant 3′-splice patterns were explained by SF3B1 mutations, we also detected nine SF3B1 wild-type tumors (including five lung adenocarcinomas). Genomic profile analysis of these tumors identified somatic mutations combined with loss-of-heterozygosity in the splicing factor SUGP1 in five of these cases. Modeling of SUGP1 loss and mutations in cell lines showed that both alterations induced mutant-SF3B1-like aberrant splicing. Our study provides definitive evidence that genetic alterations of SUGP1 genocopy SF3B1 mutations in lung adenocarcinoma and other cancers.
An enhanced genetic model of relapsed IGH-translocated multiple myeloma evolutionary dynamics
Authors: Hoang Phuc H. , Cornish Alex J. , Sherborne Amy L. , Chubb Daniel , Kimber Scott , Jackson Graham , Morgan Gareth J. , Cook Gordon , Kinnersley Ben , Kaiser Martin , Houlston Richard S.
Published: October 2020

Most patients with multiple myeloma (MM) die from progressive disease after relapse. To advance our understanding of MM evolution mechanisms, we performed whole-genome sequencing of 80IGH-translocated tumour-normal newly diagnosed pairs and 24 matched relapsed tumours from the Myeloma XI trial. We identify multiple events as potentially important for survival and therapy-resistance at relapse including driver point mutations (e.g.,TET2), translocations (MAP3K14), lengthened telomeres, and increased genomic instability (e.g., 17p deletions). Despite heterogeneous mutational processes contributing to relapsed mutations across MM subtypes, increased AID/APOBEC activity is particularly associated with shorter progression time to relapse, and contributes to higher mutational burden at relapse. In addition, we identify three enhanced major clonal evolution patterns of MM relapse, independent of treatment strategies and molecular karyotypes, questioning the viability of “evolutionary herding” approach in treating drug-resistant MM. Our data show that MM relapse is associated with acquisition of new mutations and clonal selection, and suggest APOBEC enzymes among potential targets for therapy-resistant MM.
Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants
Authors: Zhao Xutong , Qiao Dandi , Yang Chaojie , Kasela Silva , Kim Wonji , Ma Yanlin , Shrine Nick , Batini Chiara , Sofer Tamar , Taliun Sarah A. Gagliano , Sakornsakolpat Phuwanat , Balte Pallavi P. , Prokopenko Dmitry , Yu Bing , Lange Leslie A. , Dupuis Josée , Cade Brian E. , Lee Jiwon , Gharib Sina A. , Daya Michelle , Laurie Cecelia A. , Ruczinski Ingo , Cupples L. Adrienne , Loehr Laura R. , Bartz Traci M. , Morrison Alanna C. , Psaty Bruce M. , Vasan Ramachandran S. , Wilson James G. , Taylor Kent D. , Durda Peter , Johnson W. Craig , Cornell Elaine , Guo Xiuqing , Liu Yongmei , Tracy Russell P. , Ardlie Kristin G. , Aguet François , VanDenBerg David J. , Papanicolaou George J. , Rotter Jerome I. , Barnes Kathleen C. , Jain Deepti , Nickerson Deborah A. , Muzny Donna M. , Metcalf Ginger A. , Doddapaneni Harshavardhan , Dugan-Perez Shannon , Gupta Namrata , Gabriel Stacey , Rich Stephen S. , O’Connor George T. , Redline Susan , Reed Robert M. , Laurie Cathy C. , Daviglus Martha L. , Preudhomme Liana K. , Burkart Kristin M. , Kaplan Robert C. , Wain Louise V. , Tobin Martin D. , London Stephanie J. , Lappalainen Tuuli , Oelsner Elizabeth C. , Abecasis Goncalo R. , Silverman Edwin K. , Barr R. Graham ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,   TOPMed Lung Working Group, Cho Michael H. , Manichaikul Ani
Published: October 2020

Chronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry.
Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae
Authors: Vizarraga David , Kawamoto Akihiro , Matsumoto U. , Illanes Ramiro , Pérez-Luque Rosa , Martín Jesús , Mazzolini Rocco , Bierge Paula , Pich Oscar Q. , Espasa Mateu , Sanfeliu Isabel , Esperalba Juliana , Fernández-Huerta Miguel , Scheffer Margot P. , Pinyol Jaume , Frangakis Achilleas S. , Lluch-Senar Maria , Mori Shigetarou , Shibayama Keigo , Kenri Tsuyoshi , Kato Takayuki , Namba Keiichi , Fita Ignacio , Miyata Makoto , Aparicio David
Published: October 2020

Mycoplasma pneumoniae is a bacterial human pathogen that causes primary atypical pneumonia. M. pneumoniae motility and infectivity are mediated by the immunodominant proteins P1 and P40/P90, which form a transmembrane adhesion complex. Here we report the structure of P1, determined by X-ray crystallography and cryo-electron microscopy, and the X-ray structure of P40/P90. Contrary to what had been suggested, the binding site for sialic acid was found in P40/P90 and not in P1. Genetic and clinical variability concentrates on the N-terminal domain surfaces of P1 and P40/P90. Polyclonal antibodies generated against the mostly conserved C-terminal domain of P1 inhibited adhesion of M. pneumoniae, and serology assays with sera from infected patients were positive when tested against this C-terminal domain. P40/P90 also showed strong reactivity against human infected sera. The architectural elements determined for P1 and P40/P90 open new possibilities in vaccine development against M. pneumoniae infections.
Analysis of translating mitoribosome reveals functional characteristics of translation in mitochondria of fungi
Authors: Itoh Yuzuru , Naschberger Andreas , Mortezaei Narges , Herrmann Johannes M. , Amunts Alexey
Published: October 2020

Mitoribosomes are specialized protein synthesis machineries in mitochondria. However, how mRNA binds to its dedicated channel, and tRNA moves as the mitoribosomal subunit rotate with respect to each other is not understood. We report models of the translating fungal mitoribosome with mRNA, tRNA and nascent polypeptide, as well as an assembly intermediate. Nicotinamide adenine dinucleotide (NAD) is found in the central protuberance of the large subunit, and the ATPase inhibitory factor 1 (IF1) in the small subunit. The models of the active mitoribosome explain how mRNA binds through a dedicated protein platform on the small subunit, tRNA is translocated with the help of the protein mL108, bridging it with L1 stalk on the large subunit, and nascent polypeptide paths through a newly shaped exit tunnel involving a series of structural rearrangements. An assembly intermediate is modeled with the maturation factor Atp25, providing insight into the biogenesis of the mitoribosomal large subunit and translation regulation.
Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer
Authors: Apóstolo Nuno , Smukowski Samuel N. , Vanderlinden Jeroen , Condomitti Giuseppe , Rybakin Vasily , ten Bos Jolijn , Trobiani Laura , Portegies Sybren , Vennekens Kristel M. , Gounko Natalia V. , Comoletti Davide , Wierda Keimpe D. , Savas Jeffrey N. , de Wit Joris
Published: October 2020

Excitatory and inhibitory neurons are connected into microcircuits that generate circuit output. Central in the hippocampal CA3 microcircuit is the mossy fiber (MF) synapse, which provides powerful direct excitatory input and indirect feedforward inhibition to CA3 pyramidal neurons. Here, we dissect its cell-surface protein (CSP) composition to discover novel regulators of MF synaptic connectivity. Proteomic profiling of isolated MF synaptosomes uncovers a rich CSP composition, including many CSPs without synaptic function and several that are uncharacterized. Cell-surface interactome screening identifies IgSF8 as a neuronal receptor enriched in the MF pathway. Presynaptic Igsf8 deletion impairs MF synaptic architecture and robustly decreases the density of bouton filopodia that provide feedforward inhibition. Consequently, IgSF8 loss impairs excitation/inhibition balance and increases excitability of CA3 pyramidal neurons. Our results provide insight into the CSP landscape and interactome of a specific excitatory synapse and reveal IgSF8 as a critical regulator of CA3 microcircuit connectivity and function.
Evolution of DNA replication origin specification and gene silencing mechanisms
Authors: Hu Y. , Tareen A. , Sheu Y-J. , Ireland W. T. , Speck C. , Li H. , Joshua-Tor L. , Kinney J. B. , Stillman B.
Published: October 2020

DNA replication in eukaryotic cells initiates from replication origins that bind the Origin Recognition Complex (ORC). Origin establishment requires well-defined DNA sequence motifs in Saccharomyces cerevisiae and some other budding yeasts, but most eukaryotes lack sequence-specific origins. A 3.9 Å structure of S. cerevisiae ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) bound to origin DNA revealed that a loop within Orc2 inserts into a DNA minor groove and an α-helix within Orc4 inserts into a DNA major groove. Using a massively parallel origin selection assay coupled with a custom mutual-information-based modeling approach, and a separate analysis of whole-genome replication profiling, here we show that the Orc4 α-helix contributes to the DNA sequence-specificity of origins in S. cerevisiae and Orc4 α-helix mutations change genome-wide origin firing patterns. The DNA sequence specificity of replication origins, mediated by the Orc4 α-helix, has co-evolved with the gain of ORC-Sir4-mediated gene silencing and the loss of RNA interference.
Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations
Authors: Brady Samuel W. , Liu Yanling , Ma Xiaotu , Gout Alexander M. , Hagiwara Kohei , Zhou Xin , Wang Jian , Macias Michael , Chen Xiaolong , Easton John , Mulder Heather L. , Rusch Michael , Wang Lu , Nakitandwe Joy , Lei Shaohua , Davis Eric M. , Naranjo Arlene , Cheng Cheng , Maris John M. , Downing James R. , Cheung Nai-Kong V. , Hogarty Michael D. , Dyer Michael A. , Zhang Jinghui
Published: October 2020

Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome data from 702 neuroblastoma samples. Forty percent of samples harbor at least one recurrent driver gene alteration and most aberrations, including MYCN, ATRX, and TERT alterations, differ in frequency by age. MYCN alterations occur at median 2.3 years of age, TERT at 3.8 years, and ATRX at 5.6 years. COSMIC mutational signature 18, previously associated with reactive oxygen species, is the most common cause of driver point mutations in neuroblastoma, including most ALK and Ras-activating variants. Signature 18 appears early and is continuous throughout disease evolution. Signature 18 is enriched in neuroblastomas with MYCN amplification, 17q gain, and increased expression of mitochondrial ribosome and electron transport-associated genes. Recurrent FGFR1 variants in six patients, and ALK N-terminal structural alterations in five samples, identify additional patients potentially amenable to precision therapy.
Exploring and applying the substrate promiscuity of a C-glycosyltransferase in the chemo-enzymatic synthesis of bioactive C-glycosides
Authors: Xie Kebo , Zhang Xiaolin , Sui Songyang , Ye Fei , Dai Jungui
Published: October 2020

Bioactive natural C-glycosides are rare and chemical C-glycosylation faces challenges while enzymatic C-glycosylation catalyzed by C-glycosyltransferases provides an alternative way. However, only a small number of C-glycosyltransferases have been found, and most of the discovered C-glycosyltransferases prefer to glycosylate phenols with an acyl side chain. Here, a promiscuous C-glycosyltransferase, AbCGT, which is capable of C-glycosylating scaffolds lacking acyl groups, is identified from Aloe barbadensis. Based on the substrate promiscuity of AbCGT, 16 C-glycosides with inhibitory activity against sodium-dependent glucose transporters 2 are chemo-enzymatically synthesized. The C-glycoside 46a shows hypoglycemic activity in diabetic mice and is biosynthesized with a cumulative yield on the 3.95 g L‒1 scale. In addition, the key residues involved in the catalytic selectivity of AbCGT are explored. These findings suggest that AbCGT is a powerful tool in the synthesis of lead compounds for drug discovery and an example for engineering the catalytic selectivity of C-glycosyltransferases.
Author Correction: Valorization of Colombian fique (Furcraea bedinghausii) for production of cellulose nanofibers and its application in hydrogels
Authors: Guancha-Chalapud Marcelo A. , Gálvez Jaime , Serna-Cock Liliana , Aguilar Cristobal N.
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
PN/PAs-WSe2 van der Waals heterostructures for solar cell and photodetector
Authors: Zheng Xinyi , Wei Yadong , Pang Kaijuan , Kaner Tolbert Ngeywo , Kong Dalin , Xu Xiaodong , Yang Jianqun , Li Xingji , Li Weiqi
Published: October 2020

By first-principles calculations, we investigate the geometric stability, electronic and optical properties of the type-II PN-WSe2 and type-I PAs-WSe2 van der Waals heterostructures(vdWH). They are p-type semiconductors with indirect band gaps of 1.09 eV and 1.08 eV based on PBE functional respectively. By applying the external gate field, the PAs-WSe2 heterostructure would transform to the type-II band alignment from the type-I. With the increasing of magnitude of the electric field, two heterostructures turn into the n-type semiconductors and eventually into metal. Especially, PN/PAs-WSe2 vdWH are both high refractive index materials at low frequencies and show negative refractive index at high frequencies. Because of the steady absorption in ultraviolet region, the PAs-WSe2 heterostructure is a highly sensitive UV detector material with wide spectrum. The type-II PN-WSe2 heterostructure possesses giant and broadband absorption in the near-infrared and visible regions, and its solar power conversion efficiency of 13.8% is higher than the reported GaTe–InSe (9.1%), MoS2/p-Si (5.23%) and organic solar cells (11.7%). It does project PN-WSe2 heterostructure a potential for application in excitons-based solar cells.
Urbanization and food consumption in India
Authors: Pandey Bhartendu , Reba Meredith , Joshi P. K. , Seto Karen C.
Published: October 2020

The shift towards urban living is changing food demand. Past studies on India show significant urban–rural differences in food consumption. However, a scientific understanding of the underlying relationships between urbanization and food consumption is limited. This study provides the first detailed analysis of how urbanization influences both quantity and diversity of food consumption in India by harnessing the strength of multiple datasets, including consumer expenditure surveys, satellite imagery, and census data. Our statistical analysis shows three main findings. First, in contrast to existing studies, we find that much of the variation in food consumption quantity is due to income and not urbanization. After controlling for income and state-level differences, our results show that average consumption is higher in urban than rural areas for fewer than 10% of all commodities. That is, there is nearly no difference in average consumption between urban and rural residents. Second, we find the influence of urbanization as a population share on food consumption diversity to be statistically insignificant (p-value > 0.1). Instead, the results show that infrastructure, market access, percentage working women in urban areas, and norms and institutions have a statistically significant influence. Third, all covariates of food consumption diversity we tested were found to be associated with urbanization. This suggests that urbanization influences on food consumption are both indirect and multidimensional. These results show that increases in the urban population size alone do not explain changes in food consumption in India. If we are to understand how food consumption may change in the future due to urbanization, the study points to the need for a more complex and multidimensional understanding of the urbanization process that goes beyond demographic shifts.
Coronavirus disease 2019 (COVID-19) in Italy: features on chest computed tomography using a structured report system
Authors: Grassi Roberto , Fusco Roberta , Belfiore Maria Paola , Montanelli Alessandro , Patelli Gianluigi , Urraro Fabrizio , Petrillo Antonella , Granata Vincenza , Sacco Palmino , Mazzei Maria Antonietta , Feragalli Beatrice , Reginelli Alfonso , Cappabianca Salvatore
Published: October 2020

To assess the use of a structured report in the Chest Computed Tomography (CT) reporting of patients with suspicious viral pneumonia by COVID-19 and the evaluation of the main CT patterns. This study included 134 patients (43 women and 91 men; 68.8 years of mean age, range 29–93 years) with suspicious COVID-19 viral infection evaluated by reverse transcription real-time fluorescence polymerase chain reaction (RT-PCR) test. All patients underwent CT examinations at the time of admission. CT images were reviewed by two radiologists who identified COVID-19 CT patterns using a structured reports. Temporal difference mean value between RT-PCRs and CT scan was 0.18 days ± 2.0 days. CT findings were positive for viral pneumonia in 94.0% patients while COVID-19 was diagnosed at RT-PCR in 77.6% patients. Time mean value to complete the structured report by radiologist was 8.5 min ± 2.4 min. The disease on chest CT predominantly affected multiple lobes and the main CT feature was ground glass opacity (GGO) with or without consolidation (96.8%). GGO was predominantly bilateral (89.3%), peripheral (80.3%), multifocal/patching (70.5%). Consolidation disease was predominantly bilateral (83.9%) with prevalent peripheral (87.1%) and segmental (47.3%) distribution. Additional CT signs were the crazy-paving pattern in 75.4% of patients, the septal thickening in 37.3% of patients, the air bronchogram sign in 39.7% and the “reversed halo” sign in 23.8%. Less frequent characteristics at CT regard discrete pulmonary nodules, increased trunk diameter of the pulmonary artery, pleural effusion and pericardium effusion (7.9%, 6.3%, 14.3% and 16.7%, respectively). Barotrauma sign was absent in all the patients. High percentage (54.8%) of the patients had mediastinal lymphadenopathy. Using a Chest CT structured report, with a standardized language, we identified that the cardinal hallmarks of COVID-19 infection were bilateral, peripheral and multifocal/patching GGO and bilateral consolidation with peripheral and segmental distribution.
The impact of dislocations on AlGaN/GaN Schottky diodes and on gate failure of high electron mobility transistors
Authors: Besendörfer Sven , Meissner Elke , Medjdoub Farid , Derluyn Joff , Friedrich Jochen , Erlbacher Tobias
Published: October 2020

GaN epitaxially grown on Si is a material for power electronics that intrinsically shows a high density of dislocations. We show by Conductive Atomic Force Microscopy (C-AFM) and Defect Selective Etching that even for materials with similar total dislocation densities substantially different subsets of dislocations with screw component act as current leakage paths within the AlGaN barrier under forward bias. Potential reasons are discussed and it will be directly shown by an innovative experiment that current voltage forward characteristics of AlGaN/GaN Schottky diodes shift to lower absolute voltages when such dislocations are present within the device. A local lowering of the Schottky barrier height around conductive dislocations is identified and impurity segregation is assumed as responsible root cause. While dislocation related leakage current under low reverse bias could not be resolved, breakdown of AlGaN/GaN Schottky diodes under high reverse bias correlates well with observed conductive dislocations as measured by C-AFM. If such dislocations are located near the drain side of the gate edge, failure of the gate in terms of breakdown or formation of percolation paths is observed for AlGaN/GaN high electron mobility transistors.
Significance of magnetic Reynolds number in a three-dimensional squeezing Darcy–Forchheimer hydromagnetic nanofluid thin-film flow between two rotating disks
Authors: Riasat Saima , Ramzan Muhammad , Kadry Seifedine , Chu Yu-Ming
Published: October 2020

The remarkable aspects of carbon nanotubes like featherweight, durability, exceptional electrical and thermal conduction capabilities, and physicochemical stability make them desirous materials for electrochemical devices. Having such astonishing characteristics of nanotubes in mind our aspiration is to examine the squeezing three dimensional Darcy–Forchheimer hydromagnetic nanofluid thin-film flow amid two rotating disks with suspended multiwalled carbon nanotubes (MWCNTs) submerged into the base fluid water. The analysis is done by invoking partial slip effect at the boundary in attendance of autocatalytic reactions. The mathematical model consists of axial and azimuthal momentum and magnetic fields respectively. The tangential and axial velocity profiles and components of the magnetic field are examined numerically by employing the bvp4c method for varying magnetic, rotational, and squeezing Reynolds number. The torque effect near the upper and lower disks are studied critically using their graphical depiction. The values of the torque at the upper and lower disks are obtained for rotational and squeezed Reynolds numbers and are found in an excellent concurrence when compared with the existing literature. Numerically it is computed that the torque at the lower disk is higher in comparison to the upper disk for mounting estimates of the squeezed Reynolds number and the dimensionless parameter for magnetic force in an axial direction. From the graphical illustrations, it is learned that thermal profile declines for increasing values of the squeezed Reynolds number.
In vivo magnetic particle imaging: angiography of inferior vena cava and aorta in rats using newly developed multicore particles
Authors: Mohtashamdolatshahi Azadeh , Kratz Harald , Kosch Olaf , Hauptmann Ralf , Stolzenburg Nicola , Wiekhorst Frank , Sack Ingolf , Hamm Bernd , Taupitz Matthias , Schnorr Jörg
Published: October 2020

Magnetic Particle Imaging (MPI) is a new imaging modality, which maps the distribution of magnetic nanoparticles (MNP) in 3D with high temporal resolution. It thus may be suited for cardiovascular imaging. Its sensitivity and spatial resolution critically depend on the magnetic properties of MNP. Therefore, we used novel multicore nanoparticles (MCP 3) for in-vivo MPI in rats and analyzed dose requirements, sensitivity and detail resolution. 8 rats were examined using a preclinical MPI scanner (Bruker Biospin GmbH, Germany) equipped with a separate receive coil. MCP 3 and Resovist were administered intravenously (i.v.) into the rats’ tail veins at doses of 0.1, 0.05 and 0.025 mmol Fe/kg followed by serial MPI acquisition with a temporal resolution of 46 volumes per second. Based on a qualitative visual scoring system MCP 3–MPI images showed a significantly (P ≤ 0.05) higher image quality than Resovist-MPI images. Morphological features such as vessel lumen diameters (DL) of the inferior vena cava (IVC) and abdominal aorta (AA) could be assessed along a 2-cm segment in mesenteric area only after administration of MCP 3 at dosages of 0.1, 0.05 mmol Fe/kg. The mean DL ± SD estimated was 2.7 ± 0.6 mm for IVC and 2.4 ± 0.7 mm for AA. Evaluation of DL of the IVC and AA was not possible in Resovist-MPI images. Our results show, that MCP 3 provide better image quality at a lower dosage than Resovist. MCP 3-MPI with a clinically acceptable dose of 0.05 mmol Fe/kg increased the visibility of vessel lumens compared to Resovist-based MPI towards possible detection of vascular abnormalities such as stenosis or aneurysms, in vivo.
Cholesterol derivatives make large part of the lipids from epidermal molts of the desert-adapted Gila monster lizard (Heloderma suspectum)
Authors: Torri Cristian , Falini Giuseppe , Montroni Devis , Fermani Simona , Teta Roberta , Mangoni Alfonso , Alibardi Lorenzo
Published: October 2020

In order to understand the cutaneous water loss in the desert-adapted and venomous lizard Heloderma suspectum, the microscopic structure and lipid composition of epidermal molts have been examined using microscopic, spectroscopic and chemical analysis techniques. The molt is formed by a variably thick, superficial beta-layer, an extensive mesos-region and few alpha-cells in its lowermost layers. The beta-layer contains most corneous beta proteins while the mesos-region is much richer in lipids. The proteins in the mesos-region are more unstructured than those located in the beta-layer. Most interestingly, among other lipids, high contents of cholesteryl-β-glucoside and cholesteryl sulfate were detected, molecules absent or present in traces in other species of squamates. These cholesterol derivatives may be involved in the stabilization and compaction of the mesos-region, but present a limited permeability to water movements. The modest resistance to cutaneous water-loss of this species is compensated by adopting other physiological strategies to limit thermal damage and water transpiration as previous eco-physiological studies have indicated. The increase of steroid derivatives may also be implicated in the heat shock response, influencing the relative behavior in this desert-adapted lizard.
Evaluation of the association between polymorphisms of PRM1 and PRM2 and the risk of male infertility: a systematic review, meta-analysis, and meta-regression
Authors: Nemati Houshang , Sadeghi Masoud , Nazeri Mehri , Mohammadi Mohana
Published: October 2020

Studies have reported the genetic gives rise to male infertility. The aim of the present meta-analysis was to evaluate the association between PRM1 (rs737008 and rs2301365) and PRM2 (rs1646022 and rs2070923) polymorphisms and susceptibility to male infertility. The association between PRM1 and PRM2 polymorphisms and the risk of male infertility was evaluated using specific search terms in the Web of Science, Cochrane Library, PubMed, and Scopus databases without language restriction until January 28, 2020. The association was determined by odds ratio (OR) and 95% confidence interval (CI) on five genetic models using Review Manager 5.3 software. The funnel plot analysis and sensitivity analysis were done by the Comprehensive Meta-analysis 2.0 software. Out of 261 records retrieved from the databases, 17 studies were analyzed in the meta-analysis, including the four PRM polymorphisms. The pooled results as OR (P-value) showed 0.96 (0.44), 1.04 (0.70), 0.94 (0.51), 0.94 (0.48), and 1.03 (0.72) for PRM1 rs737008 polymorphism and 1.67 (0.0007), 1.73 (0.06), 1.50 (0.007), 1.56 (0.004), and 1.62 (0.33) for PRM1 rs2301365 polymorphism in allele, homozygous, heterozygous, recessive, and dominant models, respectively. Moreover, the pooled results as OR (P-value) showed 1.19 (0.004), 1.15 (0.26), 1.08 (0.70), 1.05 (0.76), and 0.98 (0.82) for PRM2 rs1646022 and 0.88 (0.04), 0.84 (0.10), 1.05 (0.81), 0.90 (0.24), and 0.80 (0.02) for PRM2 rs2070923 in allele, homozygous, heterozygous, recessive, and dominant models, respectively. The results showed PRM1 rs2301365 and PRM2 rs1646022 polymorphisms were associated with an elevated risk of male infertility and PRM2 rs2070923 polymorphism had a protective role in infertile men.
Longitudinal changes in DTI parameters of specific spinal white matter tracts correlate with behavior following spinal cord injury in monkeys
Authors: Mishra Arabinda , Wang Feng , Chen Li Min , Gore John C.
Published: October 2020

This study aims to evaluate how parameters derived from diffusion tensor imaging reflect axonal disruption and demyelination in specific white matter tracts within the spinal cord of squirrel monkeys following traumatic injuries, and their relationships to function and behavior. After a unilateral section of the dorsal white matter tract of the cervical spinal cord, we found that both lesioned dorsal and intact lateral tracts on the lesion side exhibited prominent disruptions in fiber orientation, integrity and myelination. The degrees of pathological changes were significantly more severe in segments below the lesion than above. The lateral tract on the opposite (non-injured) side was minimally affected by the injury. Over time, RD, FA, and AD values of the dorsal and lateral tracts on the injured side closely tracked measurements of the behavioral recovery. This unilateral section of the dorsal spinal tract provides a realistic model in which axonal disruption and demyelination occur together in the cord. Our data show that specific tract and segmental FA and RD values are sensitive to the effects of injury and reflect specific behavioral changes, indicating their potential as relevant indicators of recovery or for assessing treatment outcomes. These observations have translational value for guiding future studies of human subjects with spinal cord injuries.
An integrated analysis of Maglemose bone points reframes the Early Mesolithic of Southern Scandinavia
Authors: Jensen Theis Zetner Trolle , Sjöström Arne , Fischer Anders , Rosengren Erika , Lanigan Liam Thomas , Bennike Ole , Richter Kristine Korzow , Gron Kurt Joseph , Mackie Meaghan , Mortensen Morten Fischer , Sørensen Lasse , Chivall David , Iversen Katrine Højholt , Taurozzi Alberto John , Olsen Jesper , Schroeder Hannes , Milner Nicky , Sørensen Mikkel , Collins Matthew James
Published: October 2020

The extensive peat bogs of Southern Scandinavia have yielded rich Mesolithic archaeological assemblages, with one of the most iconic artefacts being the bone point. Although great in number they remain understudied. Here we present a combined investigation of the typology, protein-based species composition, and absolute chronology of Maglemosian bone points. The majority of the bone points are made from cervids and bovines. However, changes both in species composition and barb morphology can be directly linked to a paucity of finds lasting nearly 600 years in Southern Scandinavia around 10,300 cal BP. We hypothesize that this hiatus was climate-driven and forced hunter-gatherers to abandon the lakes. Furthermore, the marked change in bone points coincides with a change in lithic technology. We, therefore, propose that the Maglemose culture in Southern Scandinavia is fundamentally divided into an Early Complex and a Late Complex.
The effects of cosolutes and crowding on the kinetics of protein condensate formation based on liquid–liquid phase separation: a pressure-jump relaxation study
Authors: Cinar Hasan , Winter Roland
Published: October 2020

Biomolecular assembly processes based on liquid–liquid phase separation (LLPS) are ubiquitous in the biological cell. To fully understand the role of LLPS in biological self-assembly, it is necessary to characterize also their kinetics of formation and dissolution. Here, we introduce the pressure-jump relaxation technique in concert with UV/Vis and FTIR spectroscopy as well as light microscopy to characterize the evolution of LLPS formation and dissolution in a time-dependent manner. As a model system undergoing LLPS we used the globular eye-lens protein γD-crystallin. As cosolutes and macromolecular crowding are known to affect the stability and dynamics of biomolecular condensates in cellulo, we extended our kinetic study by addressing also the impact of urea, the deep-sea osmolyte trimethylamine-N-oxide (TMAO) and a crowding agent on the transformation kinetics of the LLPS system. As a prerequisite for the kinetic studies, the phase diagram of γD-crystallin at the different solution conditions also had to be determined. The formation of the droplet phase was found to be a very rapid process and can be switched on and off on the 1–4 s timescale. Theoretical treatment using the Johnson–Mehl–Avrami–Kolmogorov model indicates that the LLPS proceeds via a diffusion-limited nucleation and growth mechanism at subcritical protein concentrations, a scenario which is also expected to prevail within biologically relevant crowded systems. Compared to the marked effect the cosolutes take on the stability of the LLPS region, their effect at biologically relevant concentrations on the phase transformation kinetics is very small, which might be a particular advantage in the cellular context, as a fast switching capability of the transition should not be compromised by the presence of cellular cosolutes.
Dsi-RNA knockdown of genes regulated by Foxo reduces glycogen and lipid accumulations in diapausing Culex pipiens
Authors: Olademehin Olatunde P. , Liu Chengyin , Rimal Binayak , Adegboyega Nathaniel F. , Chen Fu , Sim Cheolho , Kim Sung Joon
Published: October 2020

Culex pipiens is a major carrier of the West Nile Virus, the leading cause of mosquito-borne disease in the continental United States. Cx. pipiens survive overwinter through diapause which is an important survival strategy that is under the control of insulin signaling and Foxo by regulating energy metabolism. Three homologous candidate genes, glycogen synthase (glys), atp-binding cassette transporter (atp), and low-density lipoprotein receptor chaperone (ldlr), that are under the regulation of Foxo transcription factor were identified in Cx. pipiens. To validate the gene functions, each candidate gene was silenced by injecting the target dsi-RNA to female Cx. pipiens during the early phase of diapause. The dsi-RNA injected diapause-destined female post-adult eclosion were fed for 7 days with 10% glucose containing 1% d-[13C6]glucose. The effects of dsi-RNA knockdown on glucose metabolism in intact mosquitoes were monitored using 13C solid-state NMR and ATR-FTIR. Our finding shows that the dsi-RNA knockdown of all three candidate genes suppressed glycogen and lipid biosyntheses resulting in inhibition of long-term carbon energy storage in diapausing females.
Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23
Authors: Mulcrone Patrick L. , Edwards Shanique K. E. , Petrusca Daniela N. , Haneline Laura S. , Delgado-Calle Jesús , Roodman G. David
Published: October 2020

Multiple Myeloma (MM) induces bone destruction, decreases bone formation, and increases marrow angiogenesis in patients. We reported that osteocytes (Ocys) directly interact with MM cells to increase tumor growth and expression of Ocy-derived factors that promote bone resorption and suppress bone formation. However, the contribution of Ocys to enhanced marrow vascularization in MM is unclear. Since the MM microenvironment is hypoxic, we assessed if hypoxia and/or interactions with MM cells increases pro-angiogenic signaling in Ocys. Hypoxia and/or co-culture with MM cells significantly increased Vegf-a expression in MLOA5-Ocys, and conditioned media (CM) from MLOA5s or MM-MLOA5 co-cultured in hypoxia, significantly increased endothelial tube length compared to normoxic CM. Further, Vegf-a knockdown in MLOA5s or primary Ocys co-cultured with MM cells or neutralizing Vegf-a in MM-Ocy co-culture CM completely blocked the increased endothelial activity. Importantly, Vegf-a-expressing Ocy numbers were significantly increased in MM-injected mouse bones, positively correlating with tumor vessel area. Finally, we demonstrate that direct contact with MM cells increases Ocy Fgf23, which enhanced Vegf-a expression in Ocys. Fgf23 deletion in Ocys blocked these changes. These results suggest hypoxia and MM cells induce a pro-angiogenic phenotype in Ocys via Fgf23 and Vegf-a signaling, which can promote MM-induced marrow vascularization.
Range expansion of muskox lungworms track rapid arctic warming: implications for geographic colonization under climate forcing
Authors: Kafle Pratap , Peller Peter , Massolo Alessandro , Hoberg Eric , Leclerc Lisa-Marie , Tomaselli Matilde , Kutz Susan
Published: October 2020

Rapid climate warming in the Arctic results in multifaceted disruption of biodiversity, faunal structure, and ecosystem health. Hypotheses have linked range expansion and emergence of parasites and diseases to accelerating warming globally but empirical studies demonstrating causality are rare. Using historical data and recent surveys as baselines, we explored climatological drivers for Arctic warming as determinants of range expansion for two temperature-dependent lungworms,Umingmakstrongylus pallikuukensisandVarestrongylus eleguneniensis, of muskoxen (Ovibos moschatus) and caribou (Rangifer tarandus), in the Canadian Arctic Archipelago from 1980 through 2017. Our field data shows a substantial northward shift of the northern edge of the range for both parasites and increased abundance across the expanded ranges during the last decade. Mechanistic models parameterized with parasites’ thermal requirements demonstrated that geographical colonization tracked spatial expansion of permissive environments, with a temporal lag. Subtle differences in life histories, thermal requirements of closely related parasites, climate oscillations and shifting thermal balances across environments influence faunal assembly and biodiversity. Our findings support that persistence of host-parasite assemblages reflects capacities of parasites to utilize host and environmental resources in an ecological arena of fluctuating opportunity (alternating trends in exploration and exploitation) driving shifting boundaries for distribution across spatial and temporal scales.
Genome-wide identification, characterization, and expression patterns analysis of the SBP-box gene family in wheat (Triticum aestivum L.)
Authors: Li Ying , Song Qilu , Zhang Yamin , Li Zheng , Guo Jialin , Chen Xinhong , Zhang Gaisheng
Published: October 2020

SQUAMOSApromoter-binding protein (SBP)-box genes encode a family of plant-specific transcription factors that play roles in plant growth and development. The characteristics of SBP-box genes in rice (Oryza sativa) andArabidopsishave been reported, but their potential roles in wheat (Triticum aestivum) are not fully understood. In this study, 48SBP-box genes (TaSBPs) were identified; they were located in all wheat chromosomes except for 4B and 4D. SixTaSBPswere identified as tandem duplication genes that formed three tandem duplication pairs, while 22 were segmentally duplicated genes that formed 16 segmental duplication pairs. Subcellular localization prediction showed TaSBPs were located in nucleus. Among the 48TaSBPs, 24 were predicted to be putative targets ofTamiR156. Phylogenetic analysis showed that TaSBPs, AtSBPs, and OsSBPs that shared similar functions were clustered into the same subgroups. The phylogenetic relationships between the TaSBPs were supported by the identification of highly conserved motifs and gene structures. Four types ofcis-elements––transcription-related, development-related, hormone-related, and abiotic stress-related elements––were found in theTaSBPpromoters. Expression profiles indicated mostTaSBPsparticipate in flower development and abiotic stress responses. This study establishes a foundation for further investigation ofTaSBPgenes and provides novel insights into their biological functions.
A comparison of prognoses between surgical resection and radiofrequency ablation therapy for patients with hepatocellular carcinoma and esophagogastric varices
Authors: Wei Cheng-Yi , Chau Gar-Yang , Chen Ping-Hsien , Liu Chien-An , Huang Yi-Hsiang , Huo Teh-Ia , Hou Ming-Chih , Lin Han-Chieh , Su Yu-Hui , Wu Jaw-Ching , Su Chien-Wei
Published: October 2020

There has been insufficient investigation of the differences in long-term outcomes between surgical resection (SR) and radiofrequency ablation (RFA) among patients with hepatocellular carcinoma (HCC) and esophagogastric varices (EGV). We retrospectively enrolled 251 patients with treatment-naïve HCC and EGV who underwent SR or RFA as a first-line treatment. Prognostic factors were analyzed using a Cox proportional hazards model. A total of 68 patients underwent SR, and the remaining 183 patients received RFA. Patients who underwent SR were younger, had better liver functional reserves, and had larger tumors. After a median follow-up duration of 45.1 months, 151 patients died. The cumulative 5-year overall survival (OS) rate was significantly higher among patients who underwent SR than those treated with RFA (66.7% vs. 36.8%, p < 0.001). Multivariate analysis showed that age > 65 years, multiple tumors, RFA, albumin bilirubin grade > 1, and the occurrence of major peri-procedural morbidity were the independent risk factors that are predictive of poor OS. In conclusion, SR could be recommended as a first-line treatment modality for HCC patients with EGV if the patients are carefully selected and liver function is well preserved.
Large spin-Hall effect in non-equilibrium binary copper alloys beyond the solubility limit
Authors: Masuda Hiroto , Modak Rajkumar , Seki Takeshi , Uchida Ken-ichi , Lau Yong-Chang , Sakuraba Yuya , Iguchi Ryo , Takanashi Koki
Published: October 2020

Non-magnetic materials exhibiting large spin-Hall effect (SHE) are eagerly desired for high-performance spintronic devices. Here, we report that non-equilibrium Cu-Ir binary alloys with compositions beyond the solubility limit are candidates as spin-Hall materials, even though Cu and Ir do not exhibit remarkable SHE themselves. Thanks to non-equilibrium thin film fabrication, the Cu-Ir binary alloys are obtained over a wide composition range even though they are thermodynamically unstable in bulk form. We investigate the SHE of Cu-Ir by exploiting a combinatorial technique based on spin Peltier imaging, and find that the optimum Ir concentration for enhancing SHE is around 25 at.%. We achieve a large spin-Hall angle of 6.29 ± 0.19% for Cu76Ir24. In contrast to Cu-Ir, non-equilibrium Cu-Bi binary alloys do not show remarkable SHE. Our discovery opens a new direction for the exploration of spin-Hall materials.
Exploiting fourier transform infrared and Raman microspectroscopies on cancer stem cells from oral squamous cells carcinoma: new evidence of acquired cisplatin chemoresistance
Authors: Notarstefano Valentina , Sabbatini Simona , Pro Chiara , Belloni Alessia , Orilisi Giulia , Rubini Corrado , Byrne Hugh J. , Vaccari Lisa , Giorgini Elisabetta
Published: October 2020

Oral Squamous Cells Carcinoma (OSCC) is characterised by the risk of recurrence and the onset of a refractoriness response to chemotherapy drugs.
Simultaneous determination of Acetaminophen and dopamine based on a water-soluble pillar[6]arene and ultrafine Pd nanoparticle-modified covalent organic framework nanocomposite
Authors: Tan Xiaoping , Mu Tong , Wang Sheng , Li Jian , Huang Juan , Huang Huisheng , Pu Yan , Zhao Genfu
Published: October 2020

A novel electrochemical sensing platform for the simultaneous determination of AP and DA based on a water-soluble pillar[6]arene and ultrafine Pd nanoparticle-modified covalent organic framework nanocomposite.
Recent advances in non-fullerene organic solar cells: from lab to fab
Authors: Ma Lijiao , Zhang Shaoqing , Wang Jingwen , Xu Ye , Hou Jianhui
Published: October 2020

The key factors for OSC materials toward application mainly include high performance, thickness tolerance, low cost, simple fabrication processing, high stability, and an environmentally-friendly nature.
Selective photo-ablation of glioma cells using an enzyme activatable photosensitizer
Authors: Shen Zhenhua , Tung Ching-Hsuan
Published: October 2020

An activatable photosensitizer based on methylene blue was developed and validated for its efficacy in the selective killing of gamma-glutamyl transpeptidase expressing cells.
Template-assisted 2D self-assembled chiral Kagomé network for selective adsorption of coronene
Authors: Wang Yi , Tan Xiaoping , Pang Peng , Li Bang , Miao Xinrui , Cheng Xiaohong , Deng Wenli
Published: October 2020

Coadsorbed solvents can serve as a template to fabricate a Kagomé network, which could be used to select adsorption of coronene.