bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peak learning of mass spectrometry imaging data using artificial neural networks
Authors: Abdelmoula Walid M. , Lopez Begona Gimenez-Cassina , Randall Elizabeth C. , Kapur Tina , Sarkaria Jann N. , White Forest M. , Agar Jeffrey N. , Wells William M. , Agar Nathalie Y. R. 
Published: September 2021

AbstractMass spectrometry imaging (MSI) is an emerging technology that holds potential for improving, biomarker discovery, metabolomics research, pharmaceutical applications and clinical diagnosis. Despite many solutions being developed, the large data size and high dimensional nature of MSI, especially 3D datasets, still pose computational and memory complexities that hinder accurate identification of biologically relevant molecular patterns. Moreover, the subjectivity in the selection of parameters for conventional pre-processing approaches can lead to bias. Therefore, we assess if a probabilistic generative model based on a fully connected variational autoencoder can be used for unsupervised analysis and peak learning of MSI data to uncover hidden structures. The resulting msiPL method learns and visualizes the underlying non-linear spectral manifold, revealing biologically relevant clusters of tissue anatomy in a mouse kidney and tumor heterogeneity in human prostatectomy tissue, colorectal carcinoma, and glioblastoma mouse model, with identification of underlying m/z peaks. The method is applied for the analysis of MSI datasets ranging from 3.3 to 78.9 GB, without prior pre-processing and peak picking, and acquired using different mass spectrometers at different centers.
Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function
Authors: Špírek Mário , Taylor Martin R. G. , Belan Ondrej , Boulton Simon J. , Krejci Lumir 
Published: September 2021

AbstractThe RAD51 recombinase assembles as helical nucleoprotein filaments on single-stranded DNA (ssDNA) and mediates invasion and strand exchange with homologous duplex DNA (dsDNA) during homologous recombination (HR), as well as protection and restart of stalled replication forks. Strand invasion by RAD51-ssDNA complexes depends on ATP binding. However, RAD51 can bind ssDNA in non-productive ADP-bound or nucleotide-free states, and ATP-RAD51-ssDNA complexes hydrolyse ATP over time. Here, we define unappreciated mechanisms by which the RAD51 paralog complex RFS-1/RIP-1 limits the accumulation of RAD-51-ssDNA complexes with unfavorable nucleotide content. We find RAD51 paralogs promote the turnover of ADP-bound RAD-51 from ssDNA, in striking contrast to their ability to stabilize productive ATP-bound RAD-51 nucleoprotein filaments. In addition, RFS-1/RIP-1 inhibits binding of nucleotide-free RAD-51 to ssDNA. We propose that ‘nucleotide proofreading’ activities of RAD51 paralogs co-operate to ensure the enrichment of active, ATP-bound RAD-51 filaments on ssDNA to promote HR.
Identification of limb-specific Lmx1b auto-regulatory modules with Nail-patella syndrome pathogenicity
Authors: Haro Endika , Petit Florence , Pira Charmaine U. , Spady Conor D. , Lucas-Toca Sara , Yorozuya Lauren I. , Gray Austin L. , Escande Fabienne , Jourdain Anne-Sophie , Nguyen Andy , Fellmann Florence , Good Jean-Marc , Francannet Christine , Manouvrier-Hanu Sylvie , Ros Marian A. , Oberg Kerby C. 
Published: September 2021

AbstractLMX1B haploinsufficiency causes Nail-patella syndrome (NPS; MIM 161200), characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma. Accordingly in mice, Lmx1b has been shown to play crucial roles in the development of the limb, kidney and eye. Although one functional allele of Lmx1b appears adequate for development, Lmx1b null mice display ventral-ventral distal limbs with abnormal kidney, eye and cerebellar development, more disruptive, but fully concordant with NPS. In Lmx1b functional knockouts (KOs), Lmx1b transcription in the limb is decreased nearly 6-fold, indicating autoregulation. Herein, we report on two conserved Lmx1b-associated cis-regulatory modules (LARM1 and LARM2) that are bound by Lmx1b, amplify Lmx1b expression with unique spatial modularity in the limb, and are necessary for Lmx1b-mediated limb dorsalization. These enhancers, being conserved across vertebrates (including coelacanth, but not other fish species), and required for normal locomotion, provide a unique opportunity to study the role of dorsalization in the fin to limb transition. We also report on two NPS patient families with normal LMX1B coding sequence, but with loss-of-function variations in the LARM1/2 region, stressing the role of regulatory modules in disease pathogenesis.
Intranasal vaccination with a recombinant protein CTA1-DD-RBF protects mice against hRSV infection
Authors: Li Hai , Ren Hu , Zhang Yan , Cao Lei , Xu Wenbo 
Published: September 2021

AbstractHuman respiratory syncytial virus (hRSV) infection is a major pediatric health concern worldwide. Despite more than half a century of efforts, there is still no commercially available vaccine. In this study, we constructed and purified the recombinant protein CTA1-DD-RBF composed of a CTA1-DD mucosal adjuvant and prefusion F protein (RBF) usingEscherichia coliBL21 cells. We studied the immunogenicity of CTA1-DD-RBF in mice. Intranasal immunization with CTA1-DD-RBF stimulated hRSV F-specific IgG1, IgG2a, sIgA, and neutralizing antibodies as well as T cell immunity without inducing lung immunopathology upon hRSV challenge. Moreover, the protective immunity of CTA1-DD-RBF was superior to that of the RBF protein, as confirmed by the assessment of serum-neutralizing activity and viral clearance after challenge. Compared to formalin-inactivated hRSV (FI-RSV), intranasal immunization with CTA1-DD-RBF induced a Th1 immune response. In summary, intranasal immunization with CTA1-DD-RBF is safe and effective in mice. Therefore, CTA1-DD-RBF represents a potential mucosal vaccine candidate for the prevention of human infection with hRSV.
Insights into the origin of the invasive populations of Trioza erytreae in Europe using microsatellite markers and mtDNA barcoding approaches
Authors: Ruíz-Rivero Omar , Garcia-Lor Andrés , Rojas-Panadero Borja , Franco José Carlos , Khamis Fathiya M. , Kruger Kerstin , Cifuentes Dina , Bielza Pablo , Tena Alejandro , Urbaneja Alberto , Pérez-Hedo Meritxell 
Published: September 2021

AbstractThe African citrus psyllid Trioza erytreae is one of the major threats to citrus industry as the vector of the incurable disease known as huanglongbing (HLB) or citrus greening. The psyllid invaded the northwest of the Iberian Peninsula 6 years ago. The invasion alarmed citrus growers in the Mediterranean basin, the largest citrus producing area in Europe, which is still free of HLB. Before our study, no research had been carried out on the genetic diversity of T. erytreae populations that have invaded the Iberian Peninsula and the archipelagos of the Macaronesia (Madeira and the Canary Islands). In this study, combining microsatellites markers and mtDNA barcoding analysis, we characterize the genetic diversity, structure and maternal relationship of these new invasive populations of T. erytreae and those from Africa. Our results suggest that the outbreaks of T. erytreae in the Iberian Peninsula may have derived from the Canary Islands. The populations of T. erytreae that invaded Macaronesia and the Iberian Peninsula are likely to have originated from southern Africa. We anticipate our results to be a starting point for tracking the spread of this invasive pest outside of Africa and to be important for optimizing contingency and eradication plans in newly invaded and free areas.
Body and wing size, but not wing shape, vary along a large-scale latitudinal gradient in a damselfly
Authors: Outomuro David , Golab Maria J. , Johansson Frank , Sniegula Szymon 
Published: September 2021

AbstractLarge-scale latitudinal studies that include both north and south edge populations and address sex differences are needed to understand how selection has shaped trait variation. We quantified the variation of flight-related morphological traits (body size, wing size, ratio between wing size and body size, and wing shape) along the whole latitudinal distribution of the damselflyLestes sponsa, spanning over 2700 km. We tested predictions of geographic variation in the flight-related traits as a signature of: (1) stronger natural selection to improve dispersal in males and females at edge populations; (2) stronger sexual selection to improve reproduction (fecundity in females and sexual behaviors in males) at edge populations. We found that body size and wing size showed a U-shaped latitudinal pattern, while wing ratio showed the inverse shape. However, wing shape varied very little along the latitudinal gradient. We also detected sex-differences in the latitudinal patterns of variation. We discuss how latitudinal differences in natural and sexual selection regimes can lead to the observed quadratic patterns of variation in body and wing morphology via direct or indirect selection. We also discuss the lack of latitudinal variation in wing shape, possibly due to aerodynamic constraints.
Heart failure clinical care analysis uncovers risk reduction opportunities for preserved ejection fraction subtype
Authors: Levinson Rebecca T. , Vaitinidin Nataraja Sarma , Farber-Eger Eric , Roden Dan M. , Lasko Thomas A. , Wells Quinn S. , Mosley Jonathan D. 
Published: September 2021

AbstractHeart failure (HF) has no cure and, for HF with preserved ejection fraction (HFpEF), no life-extending treatments. Defining the clinical epidemiology of HF could facilitate earlier identification of high-risk individuals. We define the clinical epidemiology of HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]), identified among 2.7 million individuals receiving routine clinical care. Differences in patterns and rates of accumulation of comorbidities, frequency of hospitalization, use of specialty care, were defined for each HF subtype. Among 28,156 HF cases, 8322 (30%) were HFpEF and 11,677 (42%) were HFrEF. HFpEF was the more prevalent subtype among older women. 177 Phenotypes differentially associated with HFpEF versus HFrEF. HFrEF was more frequently associated with diagnoses related to ischemic cardiac injury while HFpEF was associated more with non-cardiac comorbidities and HF symptoms. These comorbidity patterns were frequently present 3 years prior to a HFpEF diagnosis. HF subtypes demonstrated distinct patterns of clinical co-morbidities and disease progression. For HFpEF, these comorbidities were often non-cardiac and manifested prior to the onset of a HF diagnosis. Recognizing these comorbidity patterns, along the care continuum, may present a window of opportunity to identify individuals at risk for developing incident HFpEF.
Reproducibility in the UK biobank of genome-wide significant signals discovered in earlier genome-wide association studies
Authors: O’Sullivan Jack W. , Ioannidis John P. A. 
Published: September 2021

AbstractWith the establishment of large biobanks, discovery of single nucleotide variants (SNVs, also known as single nucleotide polymorphisms (SNVs)) associated with various phenotypes has accelerated. An open question is whether genome-wide significant SNVs identified in earlier genome-wide association studies (GWAS) are replicated in later GWAS conducted in biobanks. To address this, we examined a publicly available GWAS database and identified two, independent GWAS on the same phenotype (an earlier, “discovery” GWAS and a later, “replication” GWAS done in the UK biobank). The analysis evaluated 136,318,924 SNVs (of which 6289 reached P < 5e−8 in the discovery GWAS) from 4,397,962 participants across nine phenotypes. The overall replication rate was 85.0%; although lower for binary than quantitative phenotypes (58.1% versus 94.8% respectively). There was a 18.0% decrease in SNV effect size for binary phenotypes, but a 12.0% increase for quantitative phenotypes. Using the discovery SNV effect size, phenotype trait (binary or quantitative), and discovery P value, we built and validated a model that predicted SNV replication with area under the Receiver Operator Curve = 0.90. While non-replication may reflect lack of power rather than genuine false-positives, these results provide insights about which discovered associations are likely to be replicated across subsequent GWAS.
Linear unmixing protocol for hyperspectral image fusion analysis applied to a case study of vegetal tissues
Authors: Gómez-Sánchez Adrián , Marro Mónica , Marsal Maria , Zacchetti Sara , Rocha de Oliveira Rodrigo , Loza-Alvarez Pablo , de Juan Anna 
Published: September 2021

AbstractHyperspectral imaging (HSI) is a useful non-invasive technique that offers spatial and chemical information of samples. Often, different HSI techniques are used to obtain complementary information from the sample by combining different image modalities (Image Fusion). However, issues related to the different spatial resolution, sample orientation or area scanned among platforms need to be properly addressed. Unmixing methods are helpful to analyze and interpret the information of HSI related to each of the components contributing to the signal. Among those, Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) offers very suitable features for image fusion, since it can easily cope with multiset structures formed by blocks of images coming from different samples and platforms and allows the use of optional and diverse constraints to adapt to the specific features of each HSI employed. In this work, a case study based on the investigation of cross-sections from rice leaves by Raman, synchrotron infrared and fluorescence imaging techniques is presented. HSI of these three different techniques are fused for the first time in a single data structure and analyzed by MCR-ALS. This example is challenging in nature and is particularly suitable to describe clearly the necessary steps required to perform unmixing in an image fusion context. Although this protocol is presented and applied to a study of vegetal tissues, it can be generally used in many other samples and combinations of imaging platforms.
The relationship of polluted air and drinking water sources with the prevalence of systemic lupus erythematosus: a provincial population-based study
Authors: Chen Jiaqi , Qu Wenqiang , Sun Li , Chen Jiansheng , Kong Wei , Wang Fan , Pan Wenyou , Liu Lin , Wu Min , Ding Fuwan , Hu Huaixia , Ding Xiang , Wei Hua , Zou Yaohong , Qian Xian , Wang Meimei , Wu Jian , Tao Juan , Tan Jun , Da Zhanyun , Zhang Miaojia , Li Jing , Liang Jun , Feng Xuebing , Geng Linyu , Sun Lingyun 
Published: September 2021

AbstractEnvironmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.
Evaluation of antigenicity and nutritional properties of enzymatically hydrolyzed cow milk
Authors: Liang Xiaona , Qian Guanlin , Sun Jing , Yang Mei , Shi Xinyang , Yang Hui , Wu Junrui , Wang Zongzhou , Zheng Yan , Yue Xiqing 
Published: September 2021

AbstractWhile enzymatic hydrolysis is an effective method for lowering the antigenicity of cow milk (CM), research regarding the antigenicity and nutritional traits of CM hydrolysate is limited. Here, we evaluated the protein content, amino acid composition, sensory traits, color, flow behavior, and antigenicity of CM following enzymatic hydrolysis. The results showed that enzymatic hydrolysis increased the degree of hydrolysis, destroyed allergenic proteins, including casein, β-lactoglobulin, and ɑ-lactalbumin, and significantly increased the content of free amino acids and nutritional quality. In particular, the antigenicity of CM was significantly reduced from 44.05 to 86.55% (P < 0.5). Simultaneously, the taste, color, and flow behavior of CM were altered, the sweetness and richness intensity decreased significantly (P < 0.5), and astringency and bitterness were produced. A slightly darker and more yellow color was observed in CM hydrolysate. In addition, apparent viscosity decreased and shear stress significantly increased with increasing shear rate intensity. The results will provide a solid theoretical foundation for the development of high-quality hypoallergenic dairy products.
Low dose inocula of SARS-CoV-2 Alpha variant transmits more efficiently than earlier variants in hamsters
Authors: Mok Bobo Wing-Yee , Liu Honglian , Deng Shaofeng , Liu Jiayan , Zhang Anna Jinxia , Lau Siu-Ying , Liu Siwen , Tam Rachel Chun-Yee , Cremin Conor J. , Ng Timothy Ting-Leung , Leung Jake Siu-Lun , Lee Lam-Kwong , Wang Pui , To Kelvin Kai-Wang , Chan Jasper Fuk-Woo , Chan Kwok-Hung , Yuen Kwok-Yung , Siu Gilman Kit-Hang , Chen Honglin 
Published: September 2021

AbstractEmerging variants of SARS-CoV-2 have been shown to rapidly replace original circulating strains in humans soon after they emerged. There is a lack of experimental evidence to explain how these natural occurring variants spread more efficiently than existing strains of SARS-CoV-2 in transmission. We found that the Alpha variant (B.1.1.7) increased competitive fitness over earlier parental D614G lineages in in-vitro and in-vivo systems. Using hamster transmission model, we further demonstrated that the Alpha variant is able to replicate and shed more efficiently in the nasal cavity of hamsters than other variants with low dose and short duration of exposure. The capability to initiate effective infection with low inocula may be one of the key factors leading to the rapid transmission of emerging variants of SARS-CoV-2.
Ab initio thermodynamics reveals the nanocomposite structure of ferrihydrite
Authors: Sassi Michel , Chaka Anne M. , Rosso Kevin M. 
Published: September 2021

AbstractFerrihydrite is a poorly crystalline iron oxyhydroxide nanomineral that serves a critical role as the most bioavailable form of ferric iron for living systems. However, its atomic structure and composition remain unclear due in part to ambiguities in interpretation of X-ray scattering results. Prevailing models so far have not considered the prospect that at the level of individual nanoparticles multiple X-ray indistinguishable phases could coexist. Using ab initio thermodynamics we show that ferrihydrite is likely a nanocomposite of distinct structure types whose distribution depends on particle size, temperature, and hydration. Nanoparticles of two contrasting single-phase ferrihydrite models of Michel and Manceau are here shown to be thermodynamically equivalent across a wide range of temperature and pressure conditions despite differences in their structural water content. Higher temperature and water pressure favor the formation of the former, while lower temperature and water pressure favor the latter. For aqueous suspensions at ambient conditions, their coexistence is maximal for particle sizes up to 12 nm. The predictions inform and help resolve different observations in various experiments.
Enhanced coherence of all-nitride superconducting qubits epitaxially grown on silicon substrate
Authors: Kim Sunmi , Terai Hirotaka , Yamashita Taro , Qiu Wei , Fuse Tomoko , Yoshihara Fumiki , Ashhab Sahel , Inomata Kunihiro , Semba Kouichi 
Published: September 2021

AbstractImproving the coherence of superconducting qubits is a fundamental step towards the realization of fault-tolerant quantum computation. However, coherence times of quantum circuits made from conventional aluminum-based Josephson junctions are limited by the presence of microscopic two-level systems in the amorphous aluminum oxide tunnel barriers. Here, we have developed superconducting qubits based on NbN/AlN/NbN epitaxial Josephson junctions on silicon substrates which promise to overcome the drawbacks of qubits based on Al/AlOx/Al junctions. The all-nitride qubits have great advantages such as chemical stability against oxidation, resulting in fewer two-level fluctuators, feasibility for epitaxial tunnel barriers that reduce energy relaxation and dephasing, and a larger superconducting gap of ~5.2 meV for NbN, compared to ~0.3 meV for aluminum, which suppresses the excitation of quasiparticles. By replacing conventional MgO by a silicon substrate with a TiN buffer layer for epitaxial growth of nitride junctions, we demonstrate a qubit energy relaxation time $${T}_{1}=16.3\;{{\upmu }}{{{{{\rm{s}}}}}}$$

T

1

=
16.3

μ
s
and a spin-echo dephasing time $${T}_{2}=21.5\;{{\upmu }}{{{{{\rm{s}}}}}}$$

T

2

=
21.5

μ
s
. These significant improvements in quantum coherence are explained by the reduced dielectric loss compared to the previously reported $${T}_{1}\approx {T}_{2}\approx 0.5\;{{\upmu }}{{{{{\rm{s}}}}}}$$

T

1

≈

T

2

≈
0.5

μ
s
of NbN-based qubits on MgO substrates. These results are an important step towards constructing a new platform for superconducting quantum hardware.
Conventional protein kinase C in the brain: repurposing cancer drugs for neurodegenerative treatment?
Authors: Lordén Gema , Newton Alexandra C. 
Published: September 2021

Abstract
Protein Kinase C (PKC) isozymes are tightly regulated kinases that transduce a myriad of signals from receptor-mediated hydrolysis of membrane phospholipids. They play an important role in brain physiology, and dysregulation of PKC activity is associated with neurodegeneration. Gain-of-function mutations in PKCα are associated with Alzheimer’s disease (AD) and mutations in PKCγ cause spinocerebellar ataxia (SCA) type 14 (SCA14). This article presents an overview of the role of the conventional PKCα and PKCγ in neurodegeneration and proposes repurposing PKC inhibitors, which failed in clinical trials for cancer, for the treatment of neurodegenerative diseases.