bluuebunny/crossref_metadata_2025_split huggingface dataset:
Copper dependent ERK1/2 phosphorylation is essential for the viability of neurons and not glia
Authors: Chakraborty Kaustav , Kar Sumanta , Rai Bhawana , Bhagat Reshma , Naskar Nabanita , Seth Pankaj , Gupta Arnab , Bhattacharjee Ashima 
Published: February 2022

AbstractIntracellular copper [Cu(I)] has been hypothesized to play role in the differentiation of the neurons. This necessitates understanding the role of Cu(I) not only in the neurons but also in the glia considering their anatomical proximity, contribution towards ion homeostasis, and neurodegeneration. In this study, we did a systematic investigation of the changes in the cellular copper homeostasis during neuronal and glial differentiation and the pathways triggered by them. Our study demonstrates increased mRNA for the plasma membrane copper transporter CTR1 leading to increased Cu(I) during the neuronal (PC-12) differentiation. ATP7A is retained in the trans-Golgi network (TGN) despite high Cu(I) demonstrating its utilization towards the neuronal differentiation. Intracellular copper triggers pathways essential for neurite generation and ERK1/2 activation during the neuronal differentiation. ERK1/2 activation also accompanies the differentiation of the foetal brain derived neuronal progenitor cells. The study demonstrates that ERK1/2 phosphorylation is essential for the viability of the neurons. In contrast, differentiated C-6 (glia) cells contain low intracellular copper and significant downregulation of the ERK1/2 phosphorylation demonstrating that ERK1/2 activation does not regulate the viability of the glia. But ATP7A shows vesicular localization despite low copper in the glia. In addition to the TGN, ATP7A localizes into RAB11 positive recycling endosomes in the glial neurites. Our study demonstrates the role of copper dependent ERK1/2 phosphorylation in the neuronal viability. Whereas glial differentiation largely involves sequestration of Cu(I) into the endosomes potentially (i) for ready release and (ii) rendering cytosolic copper unavailable for pathways like the ERK1/2 activation.
Physiologically relevant hCys concentrations mobilize MeHg from rabbit serum albumin to form MeHg–hCys complexes
Authors: Bridle Tristen G , Doroudian Maryam , White Wade , Gailer Jürgen 
Published: February 2022

Abstract
Methylmercury (MeHg) is one of the most potent neurotoxins to which humans are exposed via the consumption of fish, from which it is effectively absorbed via the gastrointestinal tract into the bloodstream. Its interactions with plasma proteins, small-molecular-weight (SMW) molecules, and red blood cells, however, are incompletely understood, but critical as they determine whether and how much MeHg reaches target organs. To better define the role that SMW thiols play in the delivery of MeHg to known transporters located at the placental and blood–brain barrier, we have employed size exclusion chromatography–inductively coupled plasma-atomic emission spectroscopy to analyze MeHg-spiked rabbit plasma in the absence and presence of SMW thiols dissolved in the phosphate-buffered saline buffer mobile phase. While 300 μM methionine did not affect the binding of MeHg to rabbit serum albumin (RSA), cysteine (Cys), homocysteine (hCys), and glutathione resulted in the elution of the main Hg peak in the SMW elution range. In addition, 50 μM of hCys or Cys in the mobile phase resulted in the mobilization of MeHg from RSA in rabbit plasma and from pure RSA in solution. The Hg peak that eluted in the SMW elution range (50 μM of hCys) was identified by electrospray ionization–mass spectrometry as an MeHg–hCys complex. Since l-type amino acid transporters are present at the blood–brain barrier (BBB), which facilitate the uptake of MeHg–Cys species into the brain, our results contribute to establish the bioinorganic mechanisms that deliver MeHg to the BBB, which is critical to predict organ-based adverse health effects.
A real world comparison of HepB (Engerix-B®) and HepB-CpG (Heplisav-B®) vaccine seroprotection in patients receiving maintenance dialysis
Authors: Manley Harold J , Aweh Gideon , Frament Jill , Ladik Vladimir , Lacson Eduardo K 
Published: February 2022

Abstract

Background
Vaccination against hepatitis B virus (HBV) is recommended for dialysis patients. Two reports comparing seroprotection (SP) rates following HepB and HepB-CpG in vaccine-naïve patients with chronic kidney disease enrolled few dialysis patients (n = 122 combined). SP rates in a subset of dialysis patients were not reported or not powered to detect statistically significant differences. SP rates in those requiring additional vaccine series or booster doses are not known.

Methods
A retrospective cohort analysis including dialysis patients completing HepB or HepB-CpG vaccination between January 2019 and December 2020. Vaccine-naïve patients received a series of HepB or HepB-CpG (Series 1). A repeat series was given to nonresponders (Series 2). A booster regimen consists of one dose of either vaccine. Primary outcome was achieving SP (anti-HBs &gt;10 mIU/mL) at least 60 days after the last HBV vaccine dose for Series 1 and Series 2, and achieving SP at least 3 weeks post-booster.

Results
For Series 1 (n = 3509), SP after HepB vaccination was significantly higher (62.9% versus 50.1% for HepB-CpG; P &lt; 0.0001). Series 2 (n = 1040) and booster (n = 2028) SP rates were similar between vaccines. Patients that received up to four HepB-CpG doses had higher SP rates compared with four doses of HepB (82.0% versus 62.9%, respectively; P &lt; 0.0001).

Conclusions
SP rates in hepatitis B vaccine-naïve dialysis patients administered a recommended four doses of HepB were higher than those recommended two doses of HepB-CpG. SP rates were higher and achieved sooner if HepB-CpG was utilized initially and, if needed, for Series 2. Optimal HepB-CpG dosing deserves further study.
The origin and evolution of a plant resistosome
Authors: Gong Zhen , Qi Jinfeng , Hu Meijuan , Bi Guozhi , Zhou Jian-Min , Han Guan-Zhu 
Published: February 2022

AbstractThe nucleotide-binding, leucine-rich receptor (NLR) protein HOPZ-ACTIVATED RESISTANCE 1 (ZAR1), an immune receptor, interacts with HOPZ-ETI-DEFICIENT 1 (ZED1)-related kinases (ZRKs) and AVRPPHB SUSCEPTIBLE 1-like proteins to form a pentameric resistosome, triggering immune responses. Here, we show that ZAR1 emerged through gene duplication and that ZRKs were derived from the cell surface immune receptors wall-associated protein kinases (WAKs) through the loss of the extracellular domain before the split of eudicots and monocots during the Jurassic period. Many angiosperm ZAR1 orthologs, but not ZAR1 paralogs, are capable of oligomerization in the presence of AtZRKs and triggering cell death, suggesting that the functional ZAR1 resistosome might have originated during the early evolution of angiosperms. Surprisingly, inter-specific pairing of ZAR1 and AtZRKs sometimes results in the formation of a resistosome in the absence of pathogen stimulation, suggesting within-species compatibility between ZAR1 and ZRKs as a result of co-evolution. Numerous concerted losses of ZAR1 and ZRKs occurred in angiosperms, further supporting the ancient co-evolution between ZAR1 and ZRKs. Our findings provide insights into the origin of new plant immune surveillance networks.
Hexose translocation mediated by SlSWEET5b is required for pollen maturation in Solanum lycopersicum
Authors: Ko Han-Yu , Tseng Hsuan-Wei , Ho Li-Hsuan , Wang Lu , Chang Tzu-Fang , Lin Annie , Ruan Yong-Ling , Neuhaus H Ekkehard , Guo Woei-Jiun 
Published: February 2022

Abstract
Pollen fertility is critical for successful fertilization and, accordingly, for crop yield. While sugar unloading affects the growth and development of all types of sink organs, the molecular nature of sugar import to tomato (Solanum lycopersicum) pollen is poorly understood. However, sugar will eventually be exported transporters (SWEETs) have been proposed to be involved in pollen development. Here, reverse transcription-quantitative polymerase chain reaction (PCR) revealed that SlSWEET5b was markedly expressed in flowers when compared to the remaining tomato SlSWEETs, particularly in the stamens of maturing flower buds undergoing mitosis. Distinct accumulation of SlSWEET5b-β-glucuronidase activities was present in mature flower buds, especially in anther vascular and inner cells, symplasmic isolated microspores (pollen grains), and styles. The demonstration that SlSWEET5b-GFP fusion proteins are located in the plasma membrane supports the idea that the SlSWEET5b carrier functions in apoplasmic sugar translocation during pollen maturation. This is consistent with data from yeast complementation experiments and radiotracer uptake, showing that SlSWEET5b operates as a low-affinity hexose-specific passive facilitator, with a Km of ∼36 mM. Most importantly, RNAi-mediated suppression of SlSWEET5b expression resulted in shrunken nucleus-less pollen cells, impaired germination, and low seed yield. Moreover, stamens from SlSWEET5b-silenced tomato mutants showed significantly lower amounts of sucrose (Suc) and increased invertase activity, indicating reduced carbon supply and perturbed Suc homeostasis in these tissues. Taken together, our findings reveal the essential role of SlSWEET5b in mediating apoplasmic hexose import into phloem unloading cells and into developing pollen cells to support pollen mitosis and maturation in tomato flowers.
The role of contractors in the uptake of precision farming—A spatial economic analysis
Authors: Wang Yanbing , Huber Robert , Finger Robert 
Published: February 2022

Abstract
Contractors will play a vital role in providing farms with access to new precision farming technologies, especially in small-scale farming systems. We investigate the impact of spatial competition among contractors on the uptake of precision farming and the effectiveness of policy interventions, considering alternative spatial price schedules. Conceptual analyses show that a lack of spatial competition among contractors hinders uptake of precision farming technology. The effectiveness of policy interventions to support precision farming also depends on the market structure and contractors’ price schedules. In addition, we illustrate the results in a Swiss case study based on a specific contractors’ service market of plant protection technologies.
Hidden Performance: Salary History Bans and the Gender Pay Gap
Authors: Davis Jesse , Ouimet Paige , Wang Xinxin 
Published: February 2022

Abstract
As of 2019, salary history bans were enacted by 17 states and Puerto Rico with the stated purpose of reducing the gender pay gap. We argue that salary history bans may negatively affect wages as employers lose an informative signal of worker productivity. We empirically evaluate these laws using a large panel dataset of disaggregated wages covering all public-sector employees in 36 states and find, on average, that salary history bans lead to a 3% decrease in new-hire wages. We find no decrease in the gender pay gap in the full sample and a modest 1.5% increase in the relative wages of women, as compared to men, among new hires most likely to have experienced gender discrimination historically.
Mortgage Debt, Hand-to-Mouth Households, and Monetary Policy Transmission
Authors: Agarwal Sumit , Deng Yongheng , Gu Quanlin , He Jia , Qian Wenlan , Ren Yuan 
Published: February 2022

Abstract
Using a representative sample of credit card holders from a leading Chinese commercial bank, we investigate how consumers respond to an unexpected interest rate decrease that automatically reduces interest expenses for all mortgage borrowers in the country and thereby generates significant positive disposable-income shocks. Our difference-in-differences analysis shows that compared with homeowners without mortgage obligations, mortgage borrowers increased their monthly credit card spending by 8.7% after the 230-bps mortgage rate reduction announced in September 2008. We find a significant spending response both immediately after the announcement and during the post-reset period. The credit card delinquency rate also decreased after the mortgage rate reset. Subsequent to an interest-rate increase episode, mortgage borrowers symmetrically reduced their credit card spending. Hand-to-mouth mortgage borrowers experienced a more pronounced spending increase. The debt-service channel plays an important role in transmitting monetary policy—our estimate implies a marginal propensity to consume 0.40–0.54 through credit card spending.
Full-Likelihood Genomic Analysis Clarifies a Complex History of Species Divergence and Introgression: The Example of theerato-saraGroup ofHeliconiusButterflies
Authors: Thawornwattana Yuttapong , Seixas Fernando A , Yang Ziheng , Mallet James 
Published: February 2022

AbstractIntrogressive hybridization plays a key role in adaptive evolution and species diversification in many groups of species. However, frequent hybridization and gene flow between species make estimation of the species phylogeny and key population parameters challenging. Here, we show that by accounting for phasing and using full-likelihood methods, introgression histories and population parameters can be estimated reliably from whole-genome sequence data. We employ the multispecies coalescent (MSC) model with and without gene flow to infer the species phylogeny and cross-species introgression events using genomic data from six members of the erato-sara clade of Heliconius butterflies. The methods naturally accommodate random fluctuations in genealogical history across the genome due to deep coalescence. To avoid heterozygote phasing errors in haploid sequences commonly produced by genome assembly methods, we process and compile unphased diploid sequence alignments and use analytical methods to average over uncertainties in heterozygote phase resolution. There is robust evidence for introgression across the genome, both among distantly related species deep in the phylogeny and between sister species in shallow parts of the tree. We obtain chromosome-specific estimates of key population parameters such as introgression directions, times and probabilities, as well as species divergence times and population sizes for modern and ancestral species. We confirm ancestral gene flow between the sara clade and an ancestral population of Heliconius telesiphe, a likely hybrid speciation origin for Heliconius hecalesia, and gene flow between the sister species Heliconius erato and Heliconius himera. Inferred introgression among ancestral species also explains the history of two chromosomal inversions deep in the phylogeny of the group. This study illustrates how a full-likelihood approach based on the MSC makes it possible to extract rich historical information of species divergence and gene flow from genomic data. [3s; bpp; gene flow; Heliconius; hybrid speciation; introgression; inversion; multispecies coalescent]
The Implications of Incongruence between Gene Tree and Species Tree Topologies for Divergence Time Estimation
Authors: Carruthers Tom , Sun Miao , Baker William J , Smith Stephen A , de Vos Jurriaan M , Eiserhardt Wolf L 
Published: February 2022

Abstract
Phylogenetic analyses are increasingly being performed with data sets that incorporate hundreds of loci. Due to incomplete lineage sorting, hybridization, and horizontal gene transfer, the gene trees for these loci may often have topologies that differ from each other and from the species tree. The effect of these topological incongruences on divergence time estimation has not been fully investigated. Using a series of simulation experiments and empirical analyses, we demonstrate that when topological incongruence between gene trees and the species tree is not accounted for, the temporal duration of branches in regions of the species tree that are affected by incongruence is underestimated, whilst the duration of other branches is considerably overestimated. This effect becomes more pronounced with higher levels of topological incongruence. We show that this pattern results from the erroneous estimation of the number of substitutions along branches in the species tree, although the effect is modulated by the assumptions inherent to divergence time estimation, such as those relating to the fossil record or among-branch-substitution-rate variation. By only analyzing loci with gene trees that are topologically congruent with the species tree, or only taking into account the branches from each gene tree that are topologically congruent with the species tree, we demonstrate that the effects of topological incongruence can be ameliorated. Nonetheless, even when topologically congruent gene trees or topologically congruent branches are selected, error in divergence time estimates remains. This stems from temporal incongruences between divergence times in species trees and divergence times in gene trees, and more importantly, the difficulty of incorporating necessary assumptions for divergence time estimation. [Divergence time estimation; gene trees; species tree; topological incongruence.]
The Effect of Cancer Rehabilitation on Functional Outcomes in a Patient With Stage IV Melanoma With Subsequent Brain Metastases: A Case Report
Authors: Bucio Daniela , Bertram Jessica 
Published: February 2022

Background and Purpose:
Malignant melanoma has a high propensity to metastasize, specifically to the brain. Research has shown that incorporating oncology rehabilitation as part of the interdisciplinary care team promotes independence in functional mobility that leads to an improvement in a patient's quality of life.

Case Description:
A 70-year-old man presented with recurrent melanoma to the brain 10 years after initial diagnosis. Multiple brain metastases led to left hemiparesis of the arm and leg. Left-sided weakness affected his ability to perform activities of daily living and exercise regularly. The confounding impairments in balance resulted in multiple falls at home.

Interventions:
Interventions included balance training on various surfaces, core and proximal lower extremity strengthening, aerobic conditioning, and implementation of a home exercise program.

Outcomes:
The patient attended outpatient cancer rehabilitation for 19 weeks and discharged from physical therapy with a reported 47.7% improvement in global physical health and 26.7% improvement in global mental health on the PROMIS tool. At discharge, performance on the Five Times Sit to Stand Test, Timed Up and Go Test, and Dynamic Gait Index was below cutoff scores, indicating the patient was no longer a high risk for falls at home.

Discussion:
Physical therapy specifically tailored for the oncology patient allows for a customized rehabilitation approach that incorporates oncologic medical history and treatment into the episode of care, with the ultimate goal of improving quality of life and function throughout the patient's cancer journey.
Access to Physical Rehabilitation for a Range of Adverse Physical Effects Following Different Types of Breast Cancer Surgery
Authors: McGhee Deirdre E. , Steele Julie R. 
Published: February 2022

Purpose:
To investigate the access to physical rehabilitation for a range of adverse physical effects following different types of breast cancer surgery.

Methods:
Online survey of 632 Australian women (mean age = 59.8 years, SD = 9.6) grouped according to their breast cancer surgery, (i) breast-conserving surgery (BCS; n = 228), (ii) mastectomy (MAST; n = 208), (iii) breast reconstruction (BRS; n = 196), who retrospectively reported whether they received any physical rehabilitation for 6 adverse physical effects. Fisher's exact tests were used to compare the frequency of respondents who received physical rehabilitation for each adverse physical effect among the 3 groups. The percentage of the entire cohort of respondents (n = 632) who had lymph nodes removed, postoperative complications, or preexisting musculoskeletal issues who received physical rehabilitation was also tabulated.

Results:
No significant difference was found among the 3 groups in the percentage of respondents who received physical rehabilitation for most adverse physical effects (scar: P = .27; shoulder: P = .11; torso: P = .76; physical discomfort disturbing sleep: P = .74), except lymphedema (P = .001) and breast support issues (P = .01), which were significantly less for the BRS and BCS groups. Less than 50% of respondents following all types of breast cancer surgery received physical rehabilitation for issues associated with scars, the torso, and physical discomfort disturbing sleep, whereas more than 70% received physical rehabilitation for shoulder issues and lymphedema.

Conclusion:
Access to physical rehabilitation was similar following the different types of breast cancer surgery; however, gaps were identified for adverse physical effects associated with scars, torso, and physical discomfort disturbing sleep, where access was less than that for shoulder issues and lymphedema.
Additional risk factors associated with thrombosis and pregnancy morbidity in a unique cohort of antiphospholipid antibody-positive patients
Authors: Li Chun , Zuo Yu , Zhang Song , Makris Una E. , Karp David R. , Li Zhanguo 
Published: February 2022

Abstract

Background:
Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition with significant morbidity. The objective of this study was to identify additional clinical and epidemiological risks of arterial thrombosis, venous thrombosis, and pregnancy morbidities in a large cohort of persistent antiphospholipid antibodies (aPLs)-positive carriers.

Methods:
This was a cross-sectional cohort study of 453 consecutive patients with a documented positive aPL who attended Peking University People's Hospital. Among 453 patients screened, 297 patients had persistent positive aPL. We compared asymptomatic aPL carriers with thrombotic and obstetric APS patients. And the univariate analysis and multivariable logistic regression were used to evaluate the association between different risk factors and APS clinical manifestations. The levels of circulating markers of neutrophil extracellular traps (NETs) (cell-free DNA and citrullinated histone H3 [Cit-H3]) were assessed and compared among aPL-positive carriers with or without autoimmune disease and APS patients.

Results:
Additional risk factors associated with arterial thrombosis among aPL-positive carriers included: smoking (odds ratio [OR] = 6.137, 95% confidence interval [CI] = 2.408–15.637, P
= 0.0001), hypertension (OR = 2.368, 95% CI = 1.249–4.491, P
= 0.008), and the presence of underlying autoimmune disease (OR = 4.401, 95% CI = 2.387–8.113, P < 0.001). Additional risks associated with venous thrombosis among aPL carriers included: smoking (OR = 4.594, 95% CI = 1.681–12.553, P
= 0.029) and the presence of underlying autoimmune disease (OR = 6.330, 95% CI = 3.355–11.940, P < 0.001). The presence of underlying autoimmune disease (OR = 3.301, 95% CI = 1.407–7.744, P
= 0.006) is the additional risk, which demonstrated a significant association with APS pregnancy morbidity. Higher circulating levels of cell-free DNA and Cit-H3 were observed among APS patients and aPL patients with autoimmune diseases compared with those aPL carriers without underlying autoimmune diseases. Furthermore, control neutrophils that are conditioned with APS patients’ sera have more pronounced NET release compared with those treated with aPL carriers’ sera without underlying autoimmune diseases.

Conclusion:
We identified several potential additional risk factors for APS clinical manifestations among a large cohort of Chinese aPL carriers. Our data may help physicians to risk stratify aPL-positive Asian patients.