bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tubulin acetylation enhances lung cancer resistance to paclitaxel-induced cell death through Mcl-1 stabilization
Authors: Wattanathamsan Onsurang , Thararattanobon Rawikorn , Rodsiri Ratchanee , Chanvorachote Pithi , Vinayanuwattikun Chanida , Pongrakhananon Varisa 
Published: April 2021

AbstractThe posttranslational modifications (PTMs) of microtubules have been reported to play an important role in cancer aggressiveness, including apoptosis resistance. In this study, we aimed to investigate the biological role of microtubule PTMs in the regulation of paclitaxel responsiveness. The acetylated tubulin (Ace-tub) level was strongly associated with paclitaxel sensitivity, as observed in patient-derived primary lung cancer cells and xenografted immunodeficient mice. We showed that paclitaxel-resistant H460 lung cancer cells, generated by a stepwise increase in paclitaxel, exhibited markedly increased tubulin acetylation and consequently acquired paclitaxel resistance. Upregulation of tubulin acetylation by overexpression of α-tubulin acetyltransferase 1 wild-type (αTAT1wt), an enzyme required for acetylation, or by treatment with trichostatin A (TSA), a histone deacetylase 6 (HDAC6) inhibitor, significantly attenuated paclitaxel-induced apoptosis. Investigation of the underlying mechanism revealed that the levels of antiapoptotic Mcl-1 appeared to increase in αTAT1wt-overexpressing and TSA-treated cells compared to control cells, whereas the levels of other antiapoptotic regulatory proteins were unchanged. On the other hand, decreased tubulin acetylation by αTAT1 RNA interference downregulated Mcl-1 expression in patient-derived primary lung cancer and paclitaxel-resistant lung cancer cells. A microtubule sedimentation assay demonstrated that Mcl-1 binds to microtubules preferentially at Ace-type, which prolongs the Mcl-1 half-life (T1/2). Furthermore, immunoprecipitation analysis revealed that polyubiquitination of Mcl-1 was extensively decreased in response to TSA treatment. These data indicate that tubulin acetylation enhances the resistance to paclitaxel-induced cell death by stabilizing Mcl-1 and protecting it from ubiquitin–proteasome-mediated degradation.
The Pah-R261Q mouse reveals oxidative stress associated with amyloid-like hepatic aggregation of mutant phenylalanine hydroxylase
Authors: Aubi Oscar , Prestegård Karina S. , Jung-KC Kunwar , Shi Tie-Jun Sten , Ying Ming , Grindheim Ann Kari , Scherer Tanja , Ulvik Arve , McCann Adrian , Spriet Endy , Thöny Beat , Martinez Aurora 
Published: April 2021

AbstractPhenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH), leading to systemic accumulation of L-phenylalanine (L-Phe) that may reach neurotoxic levels. A homozygous Pah-R261Q mouse, with a highly prevalent misfolding variant in humans, reveals the expected hepatic PAH activity decrease, systemic L-Phe increase, L-tyrosine and L-tryptophan decrease, and tetrahydrobiopterin-responsive hyperphenylalaninemia. Pah-R261Q mice also present unexpected traits, including altered lipid metabolism, reduction of liver tetrahydrobiopterin content, and a metabolic profile indicative of oxidative stress. Pah-R261Q hepatic tissue exhibits large ubiquitin-positive, amyloid-like oligomeric aggregates of mutant PAH that colocalize with selective autophagy markers. Together, these findings reveal that PKU, customarily considered a loss-of-function disorder, can also have toxic gain-of-function contribution from protein misfolding and aggregation. The proteostasis defect and concomitant oxidative stress may explain the prevalence of comorbid conditions in adult PKU patients, placing this mouse model in an advantageous position for the discovery of mutation-specific biomarkers and therapies.
Limits to visual representational correspondence between convolutional neural networks and the human brain
Authors: Xu Yaoda , Vaziri-Pashkam Maryam 
Published: April 2021

AbstractConvolutional neural networks (CNNs) are increasingly used to model human vision due to their high object categorization capabilities and general correspondence with human brain responses. Here we evaluate the performance of 14 different CNNs compared with human fMRI responses to natural and artificial images using representational similarity analysis. Despite the presence of some CNN-brain correspondence and CNNs’ impressive ability to fully capture lower level visual representation of real-world objects, we show that CNNs do not fully capture higher level visual representations of real-world objects, nor those of artificial objects, either at lower or higher levels of visual representations. The latter is particularly critical, as the processing of both real-world and artificial visual stimuli engages the same neural circuits. We report similar results regardless of differences in CNN architecture, training, or the presence of recurrent processing. This indicates some fundamental differences exist in how the brain and CNNs represent visual information.
Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase
Authors: Azadmanesh Jahaun , Lutz William E. , Coates Leighton , Weiss Kevin L. , Borgstahl Gloria E. O. 
Published: April 2021

AbstractHuman manganese superoxide dismutase is a critical oxidoreductase found in the mitochondrial matrix. Concerted proton and electron transfers are used by the enzyme to rid the mitochondria of O2•−. The mechanisms of concerted transfer enzymes are typically unknown due to the difficulties in detecting the protonation states of specific residues and solvent molecules at particular redox states. Here, neutron diffraction of two redox-controlled manganese superoxide dismutase crystals reveal the all-atom structures of Mn3+ and Mn2+ enzyme forms. The structures deliver direct data on protonation changes between oxidation states of the metal. Observations include glutamine deprotonation, the involvement of tyrosine and histidine with altered pKas, and four unusual strong-short hydrogen bonds, including a low barrier hydrogen bond. We report a concerted proton and electron transfer mechanism for human manganese superoxide dismutase from the direct visualization of active site protons in Mn3+ and Mn2+ redox states.
Benzylic C−H acylation by cooperative NHC and photoredox catalysis
Authors: Meng Qing-Yuan , Lezius Lena , Studer Armido 
Published: April 2021

AbstractMethods that enable site selective acylation of sp3 C-H bonds in complex organic molecules are not well explored, particularly if compared with analogous transformations of aromatic and vinylic sp2 C-H bonds. We report herein a direct acylation of benzylic C-H bonds by merging N-heterocyclic carbene (NHC) and photoredox catalysis. The method allows the preparation of a diverse range of benzylic ketones with good functional group tolerance under mild conditions. The reaction can be used to install acyl groups on highly functionalized natural product derived compounds and the C-H functionalization works with excellent site selectivity. The combination of NHC and photoredox catalysis offers options in preparing benzyl aryl ketones.
Robustness and plasticity in Drosophila heat avoidance
Authors: Simões José Miguel , Levy Joshua I. , Zaharieva Emanuela E. , Vinson Leah T. , Zhao Peixiong , Alpert Michael H. , Kath William L. , Para Alessia , Gallio Marco 
Published: April 2021

AbstractSimple innate behavior is often described as hard-wired and largely inflexible. Here, we show that the avoidance of hot temperature, a simple innate behavior, contains unexpected plasticity in Drosophila. First, we demonstrate that hot receptor neurons of the antenna and their molecular heat sensor, Gr28B.d, are essential for flies to produce escape turns away from heat. High-resolution fly tracking combined with a 3D simulation of the thermal environment shows that, in steep thermal gradients, the direction of escape turns is determined by minute temperature differences between the antennae (0.1°–1 °C). In parallel, live calcium imaging confirms that such small stimuli reliably activate both peripheral thermosensory neurons and central circuits. Next, based on our measurements, we evolve a fly/vehicle model with two symmetrical sensors and motors (a “Braitenberg vehicle”) which closely approximates basic fly thermotaxis. Critical differences between real flies and the hard-wired vehicle reveal that fly heat avoidance involves decision-making, relies on rapid learning, and is robust to new conditions, features generally associated with more complex behavior.
Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling
Authors: Brunt Lucy , Greicius Gediminas , Rogers Sally , Evans Benjamin D. , Virshup David M. , Wedgwood Kyle C. A. , Scholpp Steffen 
Published: April 2021

AbstractWnt signaling regulates cell proliferation and cell differentiation as well as migration and polarity during development. However, it is still unclear how the Wnt ligand distribution is precisely controlled to fulfil these functions. Here, we show that the planar cell polarity protein Vangl2 regulates the distribution of Wnt by cytonemes. In zebrafish epiblast cells, mouse intestinal telocytes and human gastric cancer cells, Vangl2 activation generates extremely long cytonemes, which branch and deliver Wnt protein to multiple cells. The Vangl2-activated cytonemes increase Wnt/β-catenin signaling in the surrounding cells. Concordantly, Vangl2 inhibition causes fewer and shorter cytonemes to be formed and reduces paracrine Wnt/β-catenin signaling. A mathematical model simulating these Vangl2 functions on cytonemes in zebrafish gastrulation predicts a shift of the signaling gradient, altered tissue patterning, and a loss of tissue domain sharpness. We confirmed these predictions during anteroposterior patterning in the zebrafish neural plate. In summary, we demonstrate that Vangl2 is fundamental to paracrine Wnt/β-catenin signaling by controlling cytoneme behaviour.
Electronic structure of aqueous two-dimensional photocatalyst
Authors: Kang Dawei , Kong Xianghua , Michaud-Rioux Vincent , Chen Ying-Chih , Mi Zetian , Guo Hong 
Published: April 2021

AbstractThe electronic structure, in particular the band edge position, of photocatalyst in presence of water is critical for photocatalytic water splitting. We propose a direct and systematic density functional theory (DFT) scheme to quantitatively predict band edge shifts and their microscopic origins for aqueous 2D photocatalyst, where thousands of atoms or more are able to be involved. This scheme is indispensable to correctly calculate the electronic structure of 2D photocatalyst in the presence of water, which is demonstrated in aqueous MoS2, GaS, InSe, GaSe and InS. It is found that the band edge of 2D photocatalysts are not rigidly shifted due to water as reported in previous studies of aqueous systems. Specifically, the CBM shift is quantitatively explained by geometric deformation, water dipole and charge redistribution effect while the fourth effect, i.e., interfacial chemical contact, is revealed in the VBM shift. Moreover, the revealed upshift of CBM in aqueous MoS2should thermodynamically help carriers to participate in hydrogen evolution reaction (HER), which underpin the reported experimental findings that MoS2is an efficient HER photocatalyst. Our work paves the way to design 2D materials in general as low-cost and high-efficiency photocatalysts.
Assortative social mixing and sex disparities in tuberculosis burden
Authors: Shaweno Debebe , Horton Katherine C. , Hayes Richard J. , Dodd Peter J. 
Published: April 2021

AbstractGlobally, men have higher tuberculosis (TB) burden but the mechanisms underlying this sex disparity are not fully understood. Recent surveys of social mixing patterns have established moderate preferential within-sex mixing in many settings. This assortative mixing could amplify differences from other causes. We explored the impact of assortative mixing and factors differentially affecting disease progression and detection using a sex-stratified deterministic TB transmission model. We explored the influence of assortativity at disease-free and endemic equilibria, finding stronger effects during invasion and on increasing male:female prevalence (M:F) ratios than overall prevalence. Variance-based sensitivity analysis of endemic equilibria identified differential progression as the most important driver of M:F ratio uncertainty. We fitted our model to prevalence and notification data in exemplar settings within a fully Bayesian framework. For our high M:F setting, random mixing reduced equilibrium M:F ratios by 12% (95% CrI 0–30%). Equalizing male case detection there led to a 20% (95% CrI 11–31%) reduction in M:F ratio over 10 years—insufficient to eliminate sex disparities. However, this potentially achievable improvement was associated with a meaningful 8% (95% CrI 4–14%) reduction in total TB prevalence over this time frame.
Sequence-based GWAS and post-GWAS analyses reveal a key role of SLC37A1, ANKH, and regulatory regions on bovine milk mineral content
Authors: Sanchez Marie-Pierre , Rocha Dominique , Charles Mathieu , Boussaha Mekki , Hozé Chris , Brochard Mickaël , Delacroix-Buchet Agnès , Grosperrin Philippe , Boichard Didier 
Published: April 2021

AbstractThe mineral composition of bovine milk plays an important role in determining its nutritional and cheese-making value. Concentrations of the main minerals predicted from mid-infrared spectra produced during milk recording, combined with cow genotypes, provide a unique opportunity to decipher the genetic determinism of these traits. The present study included 1 million test-day predictions of Ca, Mg, P, K, Na, and citrate content from 126,876 Montbéliarde cows, of which 19,586 had genotype data available. All investigated traits were highly heritable (0.50–0.58), with the exception of Na (0.32). A sequence-based genome-wide association study (GWAS) detected 50 QTL (18 affecting two to five traits) and positional candidate genes and variants, mostly located in non-coding sequences. In silico post-GWAS analyses highlighted 877 variants that could be regulatory SNPs altering transcription factor (TF) binding sites or located in non-coding RNA (mainly lncRNA). Furthermore, we found 47 positional candidate genes and 45 TFs highly expressed in mammary gland compared to 90 other bovine tissues. Among the mammary-specific genes, SLC37A1 and ANKH, encoding proteins involved in ion transport were located in the most significant QTL. This study therefore highlights a comprehensive set of functional candidate genes and variants that affect milk mineral content.
Solubility of Ketoconazole (antifungal drug) in SC-CO2 for binary and ternary systems: measurements and empirical correlations
Authors: Sodeifian Gholamhossein , Sajadian Seyed Ali , Razmimanesh Fariba , Hazaveie Seyed Mojtaba 
Published: April 2021

AbstractOne of the main steps in choosing the drug nanoparticle production processes by supercritical carbon dioxide (SC-CO2) is determining the solubility of the solid solute. For this purpose, the solubility of Ketoconazole (KTZ) in the SC-CO2, binary system, as well as in the SC-CO2-menthol (cosolvent), ternary system, was measured at 308–338 K and 12–30 MPa using the static analysis method. The KTZ solubility in the SC-CO2 ranged between 0.20 × 10–6 and 8.02 × 10–5, while drug solubility in the SC-CO2 with cosolvent varied from 1.2 × 10–5 to 1.96 × 10–4. This difference indicated the significant effect of menthol cosolvent on KTZ solubility in the SC-CO2. Moreover, KTZ solubilities in the two systems were correlated by several empirical and semiempirical models. Among them, Sodeifian et al., Bian et al., MST, and Bartle et al. models can more accurately correlate experimental data for the binary system than other used models. Also, the Sodeifian and Sajadian model well fitted the solubility data of the ternary system with AARD% = 6.45, Radj = 0.995.
A Nationwide Study Examining Deafness Among Hospitalized Adults
Authors: Harris Ché Matthew , Kotwal Susrutha , Wright Scott Mitchell 
Published: April 2021

Background
It is unknown whether hospital outcomes differ among nonspeaking deaf patients compared to those without this disability.

Objective
This article aims to compare clinical outcomes and utilization data among patients with and without deafness.

Design
This study used a retrospective cohort study.

Setting and Participants
The participants included Nationwide Inpatient Sample, year 2017, hospitalized adults with and without diagnostic codes related to deafness and inability to speak.

Method
Multiple logistic and linear regression were used to compare in-hospital outcomes.

Results

Thirty million four hundred one thousand one hundred seventeen adults were hospitalized, and 7,180 had deafness and inability to speak related coding. Patients with deafness were older (mean age ±
SEM
: 59.2 ± 0.51 vs. 57.9 ± 0.09 years,
p
= .01), and less likely female (47.0% vs. 57.7%,
p
< .01) compared to controls. Those with deafness had more comorbidities compared to the controls (Charlson comorbidity score ≥ 3: 31.2% vs. 27.8%,
p
< .01). Mortality was higher among deaf versus controls (3.6% vs. 2.2%;
p
< .01); this translated into higher adjusted odds of mortality (adjusted odds ratio = 1.7. [confidence interval (CI) 1.3–2.4];
p
= .01). Deaf patients had lower odds of being discharged home compared to controls {aOR} = 0.6, (CI) 0.55–0.73];
p
< .01. Length of stay was longer (adjusted mean difference = 1.5 days CI [0.7–2.3];
p
< .01) and hospital charges were higher, but not significantly so (adjusted mean difference = $4,193 CI [−$1,935–$10,322];
p
= .18) in patients with deafness.

Conclusions
Hospitalized nonspeaking deaf patients had higher mortality and longer hospital stays compared to those without this condition. These results suggest that specialized attention may be warranted when deaf patients are admitted to our hospitals in hopes of reducing disparities in outcomes.

Supplemental Material

https://doi.org/10.23641/asha.14336663
Dysphagia Phenotypes in Spinal Muscular Atrophy: The Past, Present, and Promise for the Future
Authors: McGrattan Katlyn Elizabeth , Graham Robert J. , DiDonato Christine J. , Darras Basil T. 
Published: April 2021

PurposeThe aim of this study was to provide clinicians with an overview of literature relating to dysphagia in spinal muscular atrophy (SMA) to guide assessment and treatment.MethodIn this clinical focus article, we review literature published in Scopus and PubMed between 1990 and 2020 pertaining to dysphagia in SMA across the life span. Original research articles that were published in English were included. Searches were conducted within four themes of inquiry: (a) etiology and phenotypes, (b) respiratory systemic deficits and management, (c) characteristics of natural history dysphagia and its treatment, and (d) dysphagia outcomes with disease-modifying therapies. Articles for the first two themes were selected by content experts who identified the most salient articles that would provide clinicians foundational background knowledge about SMA. Articles for the third theme were identified using search terms, includingspinal muscular atrophy,swallow,dysphagia,bulbar, nutrition,g-tube,alternative nutrition,jaw,mouth,palate,ORmandible. Search terms for the fourth theme includedspinal muscular atrophyANDnusinersenORAVXS-101/onasemnogene abeparvovec-xioi.Review of Pertinent LiteratureTwenty-nine articles were identified. Findings across identified articles support the fact that patients with SMA who do not receive disease-modifying therapy exhibit clinically significant deficits in oropharyngeal swallow function. Few investigations provided systematic information regarding the underlying physiological deficits responsible for this loss in function, the timing of the degradation, or how disease-modifying therapies change these outcomes.ConclusionFuture research outlining the physiological and functional oropharyngeal swallowing deficits among patients with SMA who receive disease-modifying therapy is critical in developing standards of dysphagia care to guide clinicians.
Changes in Heart Rate Variability Following Acoustic Therapy in Individuals With Tinnitus
Authors: Reinhart Paul , Griffin Kendra , Micheyl Christophe 
Published: April 2021

Purpose
The aim of the study was to investigate changes in autonomic function, as measured by heart rate variability, in individuals with tinnitus following acoustic therapy implemented using tinnitus maskers presented via hearing aids.

Method
Twenty-six individuals with tinnitus and hearing impairment completed an 8-week field trial wearing hearing aids providing acoustic therapy via three tinnitus masker options set just below minimum masking level. Tinnitus handicap was measured using the Tinnitus Handicap Inventory at baseline (before starting acoustic therapy) and posttreatment (at end of 8-week trial). Resting heart rate and heart rate variability were measured using electrocardiography at baseline and posttreatment.

Results
There was a significant decrease in tinnitus handicap posttreatment compared to baseline. There was no change in heart rate, but there was a significant increase in heart rate variability posttreatment compared to baseline.

Conclusions
Acoustic therapy using tinnitus maskers delivered via hearing aids provided tinnitus relief and produced a concurrent increase in heart rate variability, suggesting a decrease in stress. Heart rate variability is a potential biomarker for tracking efficacy of acoustic therapy; however, further research is required.
A novel face recognition method based on fusion of LBP and HOG
Authors: Chen Ting , Gao Tao , Li Shuying , Zhang Xi , Cao Jinpei , Yao Dachun , Li Yh 
Published: April 2021

AbstractAs one of the hot topics in the field of computer vision research, face recognition technology has received significant attention due to its potentiality for a wide range of applications in government as well as commercial purposes. In practical applications, although several existing face recognition methods have achieved good performances in specific scenes, they easily suffer from a sharp decline in recognition rate if affected by different conditions of light, expression, posture and occlusion. Among many factors, influences of complex illuminations on face recognition are particularly significant. To further improve the performance of the existing local binary pattern (LBP) operator, neighbourhood weighted average LBP (NWALBP) is first proposed for fully considering the strong correlations between pixel pairs in the neighbourhood, which extends the traditional LBP uni‐layer neighbourhood template window to the bi‐layer neighbourhood template window and calculates the weighted average of bi‐layer neighbourhood pixels in each direction. Then, inspired by center symmetric LBP (CS‐LBP), centre symmetric NWALBP (CS‐NWALBP) is further proposed, which can effectively reduce computation complexity by only comparing the weighted average values of the neighbourhood pixels that are symmetric about the centre pixel. Finally, by combining the merit of histogram of oriented gradient (HOG), a feature fusion algorithm named CS‐NWALBP+HOG is suggested. Several experiments have eventually demonstrated that our proposed algorithms have more robust performance under complex illumination conditions if compared with many other latest algorithms.