bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the Stability of Yeast rad52 Mutant Proteins Uncovers Post-translational and Transcriptional Regulation of Rad52p
Authors: Asleson Erin N , Livingston Dennis M 
Published: April 2021

Abstract
We investigated the stability of the Saccharomyces cerevisiae Rad52 protein to learn how a cell controls its quantity and longevity. We measured the cellular levels of wild-type and mutant forms of Rad52p when expressed from the RAD52 promoter and the half-lives of the various forms of Rad52p when expressed from the GAL1 promoter. The wild-type protein has a half-life of 15 min. rad52 mutations variably affect the cellular levels of the protein products, and these levels correlate with the measured half-lives. While missense mutations in the N terminus of the protein drastically reduce the cellular levels of the mutant proteins, two mutations—one a deletion of amino acids 210-327 and the other a missense mutation of residue 235—increase the cellular level and half-life more than twofold. These results suggest that Rad52p is subject to post-translational regulation. Proteasomal mutations have no effect on Rad52p half-life but increase the amount of RAD52 message. In contrast to Rad52p, the half-life of Rad51p is &gt;2 hr, and RAD51 expression is unaffected by proteasomal mutations. These differences between Rad52p and Rad51p suggest differential regulation of two proteins that interact in recombinational repair.
Genetic Selection for Modulators of a Retinoic-Acid-Responsive Reporter in Human Cells
Authors: Richards Burt , Karpilow Jon , Dunn Christine , Peterson Isaac , Maxfield Andrew , Zharkikh Ludmilla , Abedi Majid , Hurlburt Anthony , Hardman Joshua , Hsu Forrest , Li Wenhua , Rebentisch Matthew , Sandrock Robert , Sandrock Tanya , Kamb Alexander , Teng David H-F 
Published: April 2021

Abstract
We used a genetic screening methodology, a human cell line bearing a retinoic-acid-responsive enhanced GFP reporter, and a flow sorter to recover dominant modulators of reporter expression. Four inducers and three suppressors that were fused to the C terminus of a protein scaffold for stability were isolated and their mechanisms of action studied. Mutagenesis experiments indicated that six of these dominant agents exerted their effects at the protein level. The single cDNA coding fragment that was isolated comprised the central 64-amino-acid section of human cyclophilin B, which contained its peptidyl-prolyl isomerase domain; this cyclophilin fragment repressed expression of the retinoic-acid-responsive reporter. The remaining clones encoded peptides shorter than 30 amino acids unrelated to known gene open reading frames. Genetic epistasis studies between the strongest inducer, R3, and a dominant-negative mutant of RARα suggest that the two factors function in the same pathway. Transcript microarray analyses suggest that R3 induced a subset of the retinoid-responsive genes in melanoma cells. Finally, yeast two-hybrid assays and co-immunoprecipitation studies of human cell extracts identified PAT1 as a protein that interacts with R3.
Mitochondria Are Inherited From theMATa Parent in Crosses of the Basidiomycete FungusCryptococcus neoformans
Authors: Yan Zhun , Xu Jianping 
Published: April 2021

AbstractPrevious studies demonstrated that mitochondrial DNA (mtDNA) was uniparentally transmitted in laboratory crosses of the pathogenic yeast Cryptococcus neoformans. To begin understanding the mechanisms, this study examined the potential role of the mating-type locus on mtDNA inheritance in C. neoformans. Using existing isogenic strains (JEC20 and JEC21) that differed only at the mating-type locus and a clinical strain (CDC46) that possessed a mitochondrial genotype different from JEC20 and JEC21, we constructed strains that differed only in mating type and mitochondrial genotype. These strains were then crossed to produce hyphae and sexual spores. Among the 206 single spores analyzed from six crosses, all but one inherited mtDNA from the MATa parents. Analyses of mating-type alleles and mtDNA genotypes of natural hybrids from clinical and natural samples were consistent with the hypothesis that mtDNA is inherited from the MATa parent in C. neoformans. To distinguish two potential mechanisms, we obtained a pair of isogenic strains with different mating-type alleles, mtDNA types, and auxotrophic markers. Diploid cells from mating between these two strains were selected and 29 independent colonies were genotyped. These cells did not go through the hyphal stage or the meiotic process. All 29 colonies contained mtDNA from the MATa parent. Because no filamentation, meiosis, or spore formation was involved in generating these diploid cells, our results suggest a selective elimination of mtDNA from the MATα parent soon after mating. To our knowledge, this is the first demonstration that mating type controls mtDNA inheritance in fungi.
Evidence for Diversifying Selection on Erythrocyte-Binding Antigens of Plasmodium falciparum and P. vivax
Authors: Baum Jake , Thomas Alan W , Conway David J 
Published: April 2021

Abstract
Malaria parasite antigens involved in erythrocyte invasion are primary vaccine candidates. The erythrocyte-binding antigen 175K (EBA-175) of Plasmodium falciparum binds to glycophorin A on the human erythrocyte surface via an N-terminal cysteine-rich region (termed region II) and is a target of antibody responses. A survey of polymorphism in a malaria-endemic population shows that nucleotide alleles in eba-175 region II occur at more intermediate frequencies than expected under neutrality, but polymorphisms in the homologous domains of two closely related genes, eba-140 (encoding a second erythrocyte-binding protein) and Ψeba-165 (a putative pseudogene), show an opposite trend. McDonald-Kreitman tests employing interspecific comparison with the orthologous genes in P. reichenowi (a closely related parasite of chimpanzees) reveal a significant excess of nonsynonymous polymorphism in P. falciparum eba-175 but not in eba-140. An analysis of the Duffy-binding protein gene, encoding a major erythrocyte-binding antigen in the other common human malaria parasite P. vivax, also reveals a significant excess of nonsynonymous polymorphisms when compared with divergence from its ortholog in P. knowlesi (a closely related parasite of macaques). The results suggest that EBA-175 in P. falciparum and DBP in P. vivax are both under diversifying selection from acquired human immune responses.
Selection in a Subdivided Population With Dominance or Local Frequency Dependence
Authors: Cherry Joshua L 
Published: April 2021

Abstract
The interplay between population structure and natural selection is an area of great interest. It is known that certain types of population subdivision do not alter fixation probabilities of selected alleles under genic, frequency-independent selection. In the presence of dominance for fitness or frequency-dependent selection these same types of subdivision can have large effects on fixation probabilities. For example, the barrier to fixation of a fitter allele due to underdominance is reduced by subdivision. Analytic results presented here relate a subdivided population that conforms to a finite island model to an approximately equivalent panmictic population. The size of this equivalent population is different from (larger than) the actual size of the subdivided population. Selection parameters are also different in the hypothetical equivalent population. As expected, the degree of dominance is lower in the equivalent population. The results are not limited to dominance but cover any form of polynomial frequency dependence.
Adaptive sequential Monte Carlo for posterior inference and model selection among complex geological priors
Authors: Amaya M , Linde N , Laloy E 
Published: April 2021

SUMMARY
Bayesian model selection enables comparison and ranking of conceptual subsurface models described by spatial prior models, according to the support provided by available geophysical data. Deep generative neural networks can efficiently encode such complex spatial priors, thereby, allowing for a strong model dimensionality reduction that comes at the price of enhanced non-linearity. In this setting, we explore a recent adaptive sequential Monte Carlo (ASMC) approach that builds on annealed importance sampling (AIS); a method that provides both the posterior probability density function (PDF) and the evidence (a central quantity for Bayesian model selection) through a particle approximation. Both techniques are well suited to parallel computation and rely on importance sampling over a sequence of intermediate distributions, linking the prior and the posterior PDF. Each subsequent distribution is approximated by updating the particle weights and states, compared with the previous approximation, using a small pre-defined number of Markov chain Monte Carlo (MCMC) proposal steps. Compared with AIS, the ASMC method adaptively tunes the tempering between neighboring distributions and performs resampling of particles when the variance of the particle weights becomes too large. We evaluate ASMC using two different conceptual models and associated synthetic cross-hole ground penetrating radar tomography data. For the most challenging test case, we find that the ASMC method is faster and more reliable in locating the posterior PDF than state-of-the-art adaptive MCMC. The evidence estimates are found to be robust with respect to the choice of ASMC algorithmic variables and much less sensitive to the model proposal type than MCMC. The variance of the evidence estimates are best estimated by replication of ASMC runs, while approximations based on single runs provide comparable estimates when using a sufficient number of proposal steps in approximating each intermediate distribution.
Association of Antiribosomal P Antibody with Neurological and Systemic Manifestations in Patients with Systemic Lupus Erythematosus in Southwestern Colombia
Authors: Marín Juan-David , Vargas Sthephany , Ruiz-Ordoñez Ingrid , Posso-Osorio Iván , Nieto-Aristizábal Ivana , Barrera María Claudia , Ríos-Serna Lady J , Tobón Gabriel J 
Published: April 2021

Abstract

Background
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous pathogenesis, various clinical manifestations, and a broad spectrum of autoantibodies which recognize different cellular components. This study examines the clinical significance and serological associations of serum antiribosomal P antibodies (anti-P) derived from SLE patients in a population from southwestern Colombia.

Methods
We performed a cross-sectional study of 66 SLE patients. Serum antiribosomal P0 autoantibodies were detected by line immunoassay using the ANA-LIA MAXX kit and processed on the automated HumaBlot 44FA system (Human Diagnostics, Germany).

Results
Of the 66 SLE patients included in the study, 17 patients (25.76%) showed anti-P positivity by line immunoassay (IA), 47 (71.21%) were negative, and results from 2 patients were indeterminate. We did not find an association with neuropsychiatric SLE (NPSLE), renal, or hepatic disorders (P &gt; 0.05). Laboratory findings indicated that anti-P positivity was significantly associated to anti-Smith (P = 0.001), anti-Ro60/SSA (P = 0.046), and anti-dsDNA antibodies (P = 0.034), the latter being true only when performed using indirect immunofluorescence (IIF).

Conclusion
The anti-P antibodies are not associated with clinical manifestations such as NPSLE, lupus nephritis, or hepatic involvement in the southwest Colombian SLE population. Moreover, we confirmed previously reported association between anti-P antibody, serum anti-dsDNA, and anti-Smith.
Establishment and Development of a Quality Evaluation Method for Sangbaipi Decoction
Authors: Bao Huiwei , Yang Huailei , Li Jize , Xu Yang , Huang Xiaowei 
Published: April 2021

Abstract

Background
Sangbaipi decoction (SD), a traditional Chinese “Ancient Classical Prescription” consisting of eight medicinal materials, is usually used to treat asthma due to excess lung Qi and phlegm fire.

Objective
To establish a comprehensive quality evaluation method for SD.

Methods
HPLC fingerprint analysis, hierarchical cluster analysis (HCA), and principal component analysis (PCA) were applied for the quality control of SD prepared from different batches of medicinal materials. A total of 10 batches of SD samples were prepared and analyzed.

Results
A total of 24 common peaks and six active components (gardenoside, rutin, berberine, palmatine, baicalein, and wogonin) were identified in the HPLC fingerprint of SD. The ten batches of SD samples were divided into four groups via HCA and PCA. The HPLC fingerprint similarities of the 10 batch samples were 0.934 or higher. The precision, stability, repeatability, and other methodological indexes suggested that the developed method met the requirements for qualitative fingerprint research.

Conclusion
The results indicated that HPLC fingerprints combined with PCA and multicomponent determination can be successfully applied to SD quality control. This study also provides a basis for a more comprehensive quality evaluation method for SD.

Highlights
The fingerprint of SD, a TCM famous classical formula, was established by HPLC in this paper. Moreover, contents of six pharmacodynamic related components in SD were determined simultaneously in order to establish a comprehensive quality evaluation method of SD. This study can also provide a basis for raw material selection, quality evaluation, extraction process, preparation development and pharmacodynamic material basis research of SD.
Impact of Original and Artificially Improved Artificial Intelligence–based Computer-aided Diagnosis on Breast US Interpretation
Authors: Berg Wendie A , Gur David , Bandos Andriy I , Nair Bronwyn , Gizienski Terri-Ann , Tyma Cathy S , Abrams Gordon , Davis Katie M , Mehta Amar S , Rathfon Grace , Waheed Uzma X , Hakim Christiane M 
Published: April 2021

Abstract

Objective
For breast US interpretation, to assess impact of computer-aided diagnosis (CADx) in original mode or with improved sensitivity or specificity.

Methods
In this IRB approved protocol, orthogonal-paired US images of 319 lesions identified on screening, including 88 (27.6%) cancers (median 7 mm, range 1–34 mm), were reviewed by 9 breast imaging radiologists. Each observer provided BI-RADS assessments (2, 3, 4A, 4B, 4C, 5) before and after CADx in a mode-balanced design: mode 1, original CADx (outputs benign, probably benign, suspicious, or malignant); mode 2, artificially-high-sensitivity CADx (benign or malignant); and mode 3, artificially-high-specificity CADx (benign or malignant). Area under the receiver operating characteristic curve (AUC) was estimated under each modality and for standalone CADx outputs. Multi-reader analysis accounted for inter-reader variability and correlation between same-lesion assessments.

Results
AUC of standalone CADx was 0.77 (95% CI: 0.72–0.83). For mode 1, average reader AUC was 0.82 (range 0.76–0.84) without CADx and not significantly changed with CADx. In high-sensitivity mode, all observers’ AUCs increased: average AUC 0.83 (range 0.78–0.86) before CADx increased to 0.88 (range 0.84–0.90), P &lt; 0.001. In high-specificity mode, all observers’ AUCs increased: average AUC 0.82 (range 0.76–0.84) before CADx increased to 0.89 (range 0.87–0.92), P &lt; 0.0001. Radiologists responded more frequently to malignant CADx cues in high-specificity mode (42.7% vs 23.2% mode 1, and 27.0% mode 2, P = 0.008).

Conclusion
Original CADx did not substantially impact radiologists’ interpretations. Radiologists showed improved performance and were more responsive when CADx produced fewer false-positive malignant cues.
SPRINT, system parameters recurrent invasive tracking: a fast and least-cost online calibration strategy for adaptive optics
Authors: Heritier C T , Fusco T , Oberti S , Neichel B , Esposito S , Madec P-Y 
Published: April 2021

ABSTRACT
Future large adaptive telescopes will trigger new constraints for the calibration of adaptive optics (AO) systems equipped with pre-focal deformable mirrors (DMs). The image of the DM actuator grid, as seen by the wavefront sensor (WFS), may evolve during the operations because of the flexures of the opto-mechanical components present in the optical path. This will result in a degraded AO performance that will affect the scientific operation. To overcome this challenge, it will be necessary to regularly monitor and compensate for these DM/WFS mis-registrations, either by physically realigning some optical components or by updating the control matrix of the system. In this paper, we present a new strategy to track mis-registrations using a pseudo-synthetic model of the AO system. The method is based on an invasive approach where signals are acquired on-sky, before or during the scientific operations, and fed to the model to extract the mis-registration parameters. We introduce a method to compute the most sensitive modes to these mis-registrations that allows us to reduce the number of degrees of freedom required by the algorithm and to minimize the effect on the scientific performance. We demonstrate that, by using only a few of these well-selected signals, the method provides very good accuracy for parameter estimation, well under the targeted accuracy, and has a negligible effect on the scientific path. In addition, the method appears to be very robust to varying operating conditions of noise and atmospheric turbulence and it performs equally for both pyramid and Shack–Hartmann WFSs.
Transgene codon usage drives viral fitness and therapeutic efficacy in oncolytic adenoviruses
Authors: Núñez-Manchón Estela , Farrera-Sal Martí , Otero-Mateo Marc , Castellano Giancarlo , Moreno Rafael , Medel David , Alemany Ramon , Villanueva Eneko , Fillat Cristina 
Published: April 2021

Abstract
Arming oncolytic adenoviruses with therapeutic transgenes is a well-established strategy for multimodal tumour attack. However, this strategy sometimes leads to unexpected attenuated viral replication and a loss of oncolytic effects, preventing these viruses from reaching the clinic. Previous work has shown that altering codon usage in viral genes can hamper viral fitness. Here, we have analysed how transgene codon usage impacts viral replication and oncolytic activity. We observe that, although transgenes with optimized codons show high expression levels at the first round of infection, they impair viral fitness and are therefore not expressed in a sustained manner. Conversely, transgenes encoded by suboptimal codons do not compromise viral replication and are thus stably expressed over time, allowing a greater oncolytic activity both in vitro and in vivo. Altogether, our work shows that fine-tuning codon usage leads to a concerted optimization of transgene expression and viral replication paving the way for the rational design of more efficacious oncolytic therapies.
The Modulatory Effect of Quantitative Sensory Testing in Shoulder Pain: A Systematic Review and Meta-Analysis
Authors: Lyng Kristian Damgaard , Thorsen Jens Bredbjerg Brock , Larsen Dennis Boye , Petersen Kristian Kjær 
Published: April 2021

Abstract

Background
The underlying mechanisms for shoulder pain (SP) are still widely unknown. Previous reviews have reported signs of altered pain processing in SP measured with quantitative sensory testing (QST). Evidence suggests that QST might hold predictive value for SP after an intervention, yet it is not known whether QST profiles can be modulated in response to different treatments. Therefore, this systematic review and meta-analysis aimed to assess whether QST parameters can be modified by interventions for patients with SP.

Methods
Three databases were searched to identify eligible studies. Eligible studies had a prospective design, with at least one QST variable as an outcome in conjunction with an intervention measured before and after the intervention. Studies that involved SP caused by spinal or brain injury and studies looking at combined chronic neck pain and SP were excluded.

Results
Nineteen studies investigating SP were eligible for inclusion in this review. Pressure pain threshold (PPT) was the most frequently used QST parameter to investigate local and widespread hyperalgesia. A meta-analysis was performed on data from 10 studies with a total of 16 interventions. Results demonstrated an overall acute effect (&lt;24 hours after intervention) of interventions in favor of local decreased pain sensitivity and remote decreased pain sensitivity when PPTs before and after interventions were compared.

Conclusions
This study demonstrates that interventions such as exercise and manual therapy can modulate PPTs acutely, both locally and remotely, in patients with SP. Further research investigating the acute and long-term modulatory ability of these interventions on other QST parameters is needed in patients with SP.
O02 Low birthweight is associated with decreased grip strength and reduced leg muscle mass in middle age: findings from the UK Biobank imaging enhancement
Authors: Curtis Elizabeth M , D'Angelo Stefania , Ashai Shanze , Ward Kate , Raisi-Estbragh Zahra , Petersen Steffen , Cooper Cyrus , Harvey Nicholas C 
Published: April 2021

Abstract
Background/Aims
Low birthweight has been shown to be associated with poorer musculoskeletal health in later life in a variety of epidemiological studies. We investigated relationships between birthweight and magnetic resonance imaging (MRI) measures of muscle volume, and between birthweight and measures of grip strength in UK Biobank.
Methods
UK Biobank is a large prospective cohort of men and women aged 40-69 years, including a detailed baseline assessment in which birthweight was collected by self-report. A subset of participants underwent MRI examination with the dual-echo Dixon Vibe protocol, from neck to knees. Automated body composition analysis was performed using the AMRA ProfilerTM system, to segment and quantify total thigh muscle volume. Grip strength was assessed using a Jamar hydraulic hand dynamometer. Associations between birthweight, and thigh muscle volume or grip strength (expressed as Fisher-Yates z-scores) were investigated using multivariate linear regression analysis. This study was conducted under generic ethics approval (NRES:11/NW/0382).
Results
13,048 participants [5,508 men, mean (SD) age 61.9 (7.6) years and 7,540 women, age 60.9 (7.2) years] were able to recall their birthweight and underwent MRI body composition analysis or had a measurement of grip strength. In both men and women, higher birthweight was associated with greater thigh muscle volume (adjusted for age and body mass index (BMI)): men, β (95% CI): 0.23 (0.16,0.30) SD/kg, p &lt; 0.001; women, β (95% CI): 0.28 (0.22,0.35) SD/kg, p &lt; 0.001. Higher birthweight was also associated with higher grip strength (adjusted for age and height); men, β (95% CI): 0.09 (0.06,0.13) SD/kg, p &lt; 0.001; women, β (95% CI): 0.06 (0.02,0.09) SD/kg, p = 0.001. All associations were robust to additional adjustment for current smoking and physical activity.
Conclusion
Birthweight was positively associated with MRI measures of thigh muscle volume and grip strength in a population of middle-aged UK adults. These findings provide novel evidence in support of the developmental programming hypothesis and suggest that interventions to optimise birthweight may help to prevent sarcopenia and reduce the risk of falls in future generations. (Project 3593)
Disclosure
E.M. Curtis: None. S. D'Angelo: None. S. Ashai: None. K. Ward: None. Z. Raisi-Estbragh: None. S. Petersen: None. C. Cooper: None. N.C. Harvey: None.