bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between APOE genotype and microglial cell morphology
Authors: Kloske Courtney M , Gearon Mary D , Weekman Erica M , Rogers Colin , Patel Ela , Bachstetter Adam , Nelson Peter T , Wilcock Donna M 
Published: April 2023

Abstract
APOE is the largest genetic risk factor for late-onset Alzheimer disease (AD) with E4 conferring an increased risk for AD compared to E3. The ApoE protein can impact diverse pathways in the brain including neuroinflammation but the precise impact of ApoE isoforms on inflammation remains unknown. As microglia are a primary source of neuroinflammation, this study determined whether ApoE isoforms have an impact on microglial morphology and activation using immunohistochemistry and digital analyses. Analysis of ionized calcium-binding adaptor molecule 1 (Iba1) immunoreactivity indicated greater microglial activation in both the hippocampus and superior and middle temporal gyrus (SMTG) in dementia participants versus non-demented controls. Further, only an increase in activation was seen in E3-Dementia participants in the entire SMTG, whereas in the grey matter of the SMTG, only a diagnosis of dementia impacted activation. Specific microglial morphologies showed a reduction in ramified microglia in the dementia group. For rod microglia, a reduction was seen in E4-Control patients in the hippocampus whereas in the SMTG an increase was seen in E4-Dementia patients. These findings suggest an association between ApoE isoforms and microglial morphologies and highlight the importance of considering ApoE isoforms in studies of AD pathology.
Insights into the role of PHLPP2/Akt/GSK3β/Fyn kinase/Nrf2 trajectory in the reno-protective effect of rosuvastatin against colistin-induced acute kidney injury in rats
Authors: Shafik Marihan S , El-Tanbouly Dalia M , Bishr Abeer , Attia Amina S 
Published: April 2023

Abstract

Objectives
Oxidative stress-mediated colistin’s nephrotoxicity is associated with the diminished activity of nuclear factor erythroid 2-related factor 2 (Nrf2) that is primarily correlated with cellular PH domain and leucine-rich repeat protein phosphatase (PHLPP2) levels. This study investigated the possible modulation of PHLPP2/protein kinase B (Akt) trajectory as a critical regulator of Nrf2 stability by rosuvastatin (RST) to guard against colistin-induced oxidative renal damage in rats.

Methods
Colistin (300,000 IU/kg/day; i.p.) was injected for 6 consecutive days, and rats were treated simultaneously with RST orally at 10 or 20 mg/kg.

Key findings
RST enhanced renal nuclear Nrf2 translocation as revealed by immunohistochemical staining to boost the renal antioxidants, superoxide dismutase (SOD) and reduced glutathione (GSH) along with a marked reduction in caspase-3. Accordingly, rats treated with RST showed significant restoration of normal renal function and histological features. On the molecular level, RST effectively decreased the mRNA expression of PHLPP2 to promote Akt phosphorylation. Consequently, it deactivated GSK-3β and reduced the gene expression of Fyn kinase in renal tissues.

Conclusions
RST could attenuate colistin-induced oxidative acute kidney injury via its suppressive effect on PHLPP2 to endorse Nrf2 activity through modulating Akt/GSK3 β/Fyn kinase trajectory.
A Bayesian feature allocation model for identifying cell subpopulations using CyTOF data
Authors: Lui Arthur , Lee Juhee , Thall Peter F , Daher May , Rezvani Katy , Basar Rafet 
Published: April 2023

Abstract
A Bayesian feature allocation model (FAM) is presented for identifying cell subpopulations based on multiple samples of cell surface or intracellular marker expression level data obtained by cytometry by time of flight (CyTOF). Cell subpopulations are characterized by differences in marker expression patterns, and cells are clustered into subpopulations based on their observed expression levels. A model-based method is used to construct cell clusters within each sample by modeling subpopulations as latent features, using a finite Indian buffet process. Non-ignorable missing data due to technical artifacts in mass cytometry instruments are accounted for by defining a static missingship mechanism. In contrast with conventional cell clustering methods, which cluster observed marker expression levels separately for each sample, the FAM-based method can be applied simultaneously to multiple samples, and also identify important cell subpopulations likely to be otherwise missed. The proposed FAM-based method is applied to jointly analyse three CyTOF datasets to study natural killer (NK) cells. Because the subpopulations identified by the FAM may define novel NK cell subsets, this statistical analysis may provide useful information about the biology of NK cells and their potential role in cancer immunotherapy which may lead, in turn, to development of improved NK cell therapies.
Social considerations in surgical management of Flood syndrome: a case report
Authors: Ekhteraei Setareh , Alsafar Ahmed 
Published: April 2023

Abstract
Flood syndrome, first described by Dr. Frank Flood in 1961, is a rare condition involving the leakage of ascitic fluid through a ruptured ventral hernia. Most commonly, it occurs in patients with advanced, decompensated liver cirrhosis leading to significant amounts of ascites. Currently, there is no standard of care for Flood syndrome due to its very rare nature. Our case report details the medical, surgical and social aspects of a 45-year-old unhoused male with Flood syndrome with post-surgical complications and subsequent infection. This paper aims to add to the sparse literature on Flood syndrome and to discuss some of the complications and treatment approaches for this condition.
First light and reionization epoch simulations (FLARES) XI: [O iii] emitting galaxies at 5 &lt; z &lt; 10
Authors: Wilkins Stephen M , Lovell Christopher C , Vijayan Aswin P , Irodotou Dimitrios , Adams Nathan J , Roper William J , Caruana Joseph , Matthee Jorryt , Seeyave Louise T C , Conselice Christopher J , Pérez-González Pablo G , Turner Jack C , Donnellan James M S , Verma Aprajita , Trussler J A A 
Published: April 2023

ABSTRACT
JWST has now made it possible to probe the rest-frame optical line emission of high-redshift galaxies extending to z ≈ 9, and potentially beyond. To aid in the interpretation of these emerging constraints, in this work we explore predictions for [O iii]λλ4960, 5008 Å emission in high-redshift galaxies using the First Light and Reionization Epoch Simulations (Flares). We produce predictions for the [O iii] luminosity function, its correlation with the UV luminosity, and the distribution of equivalent widths (EWs). We also explore how the [O iii] EW correlates with physical properties including specific star formation rate, metallicity, and dust attenuation. Our predictions are largely consistent with recent observational constraints on the luminosity function, average EWs, and line ratios. However, they fail to reproduce the observed tail of high-EW sources and the number density of extreme line emitters. Possibilities to explain these discrepancies include an additional source of ionizing photons and/or greater stochasticity in star formation in the model or photometric scatter and/or bias in the observations. With JWST now rapidly building larger samples and a wider range of emission lines the answer to this remaining discrepancy should be available imminently.
Nustar observation of the binary system 4U 0114 + 65
Authors: Abdallah Mohammed H , Samir Rasha M , Leahy Denis A , Shaker Ashraf A 
Published: April 2023

ABSTRACT
The high-mass X-ray binary system 4U 0114 + 65 was observed by Nustar in October 2019 and by XMM-Newton in August 2015. Here we performed spectral and timing analysis of the Nustar observation and carry out timing analysis on the XMM-Newton data. We measured the spin period of the neutron star from both observations and found a spin-up rate $\dot{p}$ = 1.54 ± 0.38 × 10−6$\mathrm{s\, s}^{-1}$ . During the Nustar observation, two flares occurred, one shortly after the start of the observation and the other near the end separated by a long period of low/quiescent state. The large and sudden flares mostly resulted from accretion of corotating interaction region (CIR) material. A common spectral model to high mass X-ray binaries (HMXBs), powerlaw with high energy cutoff and absorption at low energy, gave a good fit to both flaring and quiescent states. A fluorescent iron line was not required in fitting any of the states. On the other hand, very tentative evidence of Cyclotron Resonant Scattering Feature (CRSF) at ∼17 keV was found during fitting using cyclabs model; however, fitting improvement was not significant enough to confirm its detection, plus a very narrow width (&lt;1 keV) was obtained for the line and its first harmonic. Visual inspection of the spectra showed a deficiency of emission near the expected first and second harmonic. Another important feature visually noticed in the spectra is the presence of hard tail above 50 keV. This could be explained by the shocked material bounding the CIR.
An ultrafast outflow in the black hole candidate MAXI J1810−222?
Authors: Del Santo M , Pinto C , Marino A , D’Aì A , Petrucci P-O , Malzac J , Ferreira J , Pintore F , Motta S E , Russell T D , Segreto A , Sanna A 
Published: April 2023

ABSTRACT
The transient X-ray source MAXI J1810−222 was discovered in 2018 and has been active ever since. A long combined radio and X-ray monitoring campaign was performed with Australia Telescope Compact Array and Swift, respectively. It has been proposed that MAXI J1810−222 is a relatively distant black hole X-ray binary, albeit showing a very peculiar outburst behaviour. Here, we report on the spectral study of this source making use of a large sample of NICER observations performed between 2019 February and 2020 September. We detected a strong spectral absorption feature at ∼1 keV, which we have characterized with a physical photoionization model. Via a deep scan of the parameters space, we obtained evidence for a spectral-state dependent outflow, with mildly relativistic speeds. In particular, the soft and intermediate states point to a hot plasma outflowing at 0.05–0.15c. This speeds rule-out thermal winds and hence, they suggest that such outflows could be radiation pressure or (most likely) magnetically driven winds. Our results are crucial to test current theoretical models of wind formation in X-ray binaries.
Beginner's Guide on the Use of PAML to Detect Positive Selection
Authors: Álvarez-Carretero Sandra , Kapli Paschalia , Yang Ziheng 
Published: April 2023

AbstractThe CODEML program in the PAML package has been widely used to analyze protein-coding gene sequences to estimate the synonymous and nonsynonymous rates (dS and dN) and to detect positive Darwinian selection driving protein evolution. For users not familiar with molecular evolutionary analysis, the program is known to have a steep learning curve. Here, we provide a step-by-step protocol to illustrate the commonly used tests available in the program, including the branch models, the site models, and the branch-site models, which can be used to detect positive selection driving adaptive protein evolution affecting particular lineages of the species phylogeny, affecting a subset of amino acid residues in the protein, and affecting a subset of sites along prespecified lineages, respectively. A data set of the myxovirus (Mx) genes from ten mammal and two bird species is used as an example. We discuss a new feature in CODEML that allows users to perform positive selection tests for multiple genes for the same set of taxa, as is common in modern genome-sequencing projects. The PAML package is distributed at https://github.com/abacus-gene/paml under the GNU license, with support provided at its discussion site (https://groups.google.com/g/pamlsoftware). Data files used in this protocol are available at https://github.com/abacus-gene/paml-tutorial.
Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis
Authors: Sarnak Mark J , Agarwal Rajiv , Boudville Neil , Chowdhury Pradip C P , Eckardt Kai-Uwe , Gonzalez Carlos R , Kooienga Laura A , Koury Mark J , Ntoso Kwabena A , Luo Wenli , Parfrey Patrick S , Vargo Dennis L , Winkelmayer Wolfgang C , Zhang Zhiqun , Chertow Glenn M 
Published: April 2023

ABSTRACT

Background
Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear.

Methods
We conducted a post hoc analysis of patients in the INNO2VATE trials receiving peritoneal dialysis at baseline. The prespecified primary safety endpoint was time to first major cardiovascular event (MACE; defined as all-cause mortality or nonfatal myocardial infarction or stroke). The primary efficacy endpoint was mean change in hemoglobin from baseline to the primary evaluation period (Weeks 24–36).

Results
Of the 3923 patients randomized in the two INNO2VATE trials, 309 were receiving peritoneal dialysis (vadadustat, n = 152; darbepoetin alfa, n = 157) at baseline. Time to first MACE was similar in the vadadustat and darbepoetin alfa groups [hazard ratio 1.10; 95% confidence interval (CI) 0.62, 1.93]. In patients receiving peritoneal dialysis, the difference in mean change in hemoglobin concentrations was −0.10 g/dL (95% CI −0.33, 0.12) in the primary evaluation period. The incidence of treatment-emergent adverse events (TEAEs) was 88.2% versus 95.5%, and serious TEAEs was 52.6% versus 73.2% in the vadadustat and darbepoetin alfa groups, respectively.

Conclusions
In the subgroup of patients receiving peritoneal dialysis in the phase 3 INNO2VATE trials, safety and efficacy of vadadustat were similar to darbepoetin alfa.
Shuangqing Forum on carbon neutrality in construction and architecture
Authors: Zhu He 
Published: April 2023

ABSTRACT
The Natural Science Foundation of China (NSFC) held the 326th Shuangqing Forum on 22 February 2023. As the first forum of 2023 and one of the first in-person activities post-COVID, a topic of national and global significance was chosen: the challenges, for basic sciences, of reaching carbon neutrality in construction and architecture. National Science Review (NSR) attended this forum, as several presentations related to materials science and information science would appeal to the broad audience of NSR. In the plenary session, four members of the Chinese Academy of Engineering (CAE), Profs. Jiaping Liu, Jianguo Wang, Weimin Zhuang and Hongyuan Mei, provided an overview of the challenges facing construction and architecture industries in the run-up to carbon neutrality.
Theorising Evidence Law
Authors: Roberts Paul 
Published: April 2023

Abstract—
What does it mean for a specialist department of legal studies, such as the Law of Evidence, to have, or to acquire, ‘philosophical foundations’? In what sense are the theoretical foundations of procedural scholarship and teaching distinctively or uniquely philosophical? The publication of Philosophical Foundations of Evidence Law (OUP, 2021), edited by Christian Dahlman, Alex Stein and Giovanni Tuzet, presents a valuable opportunity to reflect on these existential questions of disciplinary constitution, methodology and design. This review article critically examines the volume’s idiosyncratic selection of topics, structural taxonomy, epistemological priorities, and enigmatic thesis that modern evidence law is turning from rules to reasons as its organising intellectual framework. Whilst the volume is impressively interdisciplinary and cosmopolitan in authorship and outlook, some doubts are expressed about its implicit US orientation, limited engagement with institutional or doctrinal details, and marginalisation of normative criminal jurisprudence.
Evolution of Lipochitooligosaccharide Binding to a LysM-RLK for Nodulation in Medicago truncatula
Authors: Cullimore Julie , Fliegmann Judith , Gasciolli Virginie , Gibelin-Viala Chrystel , Carles Noémie , Luu Thi-Bich , Girardin Ariane , Cumener Marie , Maillet Fabienne , Pradeau Stéphanie , Fort Sébastien , Bono Jean-Jacques , Gough Clare , Lefebvre Benoit 
Published: April 2023

Abstract
Lysin motif receptor–like kinases (LysM-RLKs) are involved in the perception of chitooligosaccharides (COs) and related lipochitooligosaccharides (LCOs) in plants. Expansion and divergence of the gene family during evolution have led to various roles in symbiosis and defense. By studying proteins of the LYR-IA subclass of LysM-RLKs of the Poaceae, we show here that they are high-affinity LCO-binding proteins with a lower affinity for COs, consistent with a role in LCO perception to establish arbuscular mycorrhiza (AM). In Papilionoid legumes, whole-genome duplication has resulted in two LYR-IA paralogs, MtLYR1 and MtNFP in Medicago truncatula, with MtNFP playing an essential role in root nodule symbiosis with nitrogen-fixing rhizobia. We show that MtLYR1 has retained the ancestral LCO-binding characteristic and is dispensable for AM. Domain swapping between the three LysMs of MtNFP and MtLYR1 and mutagenesis in MtLYR1 suggest that the MtLYR1 LCO-binding site is on the second LysM and that divergence in MtNFP led to better nodulation, but surprisingly with decreased LCO binding. These results suggest that divergence of the LCO-binding site has been important for the evolution of a role of MtNFP in nodulation with rhizobia.
The Peroxisomal β-Oxidative Pathway and Benzyl Alcohol O-Benzoyltransferase HSR201 Cooperatively Contribute to the Biosynthesis of Salicylic Acid
Authors: Kotera Yu , Komori Hirotomo , Tasaki Kosuke , Takagi Kumiko , Imano Sayaka , Katou Shinpei 
Published: April 2023

Abstract
The phytohormone salicylic acid (SA) regulates plant defense responses against pathogens. Previous studies have suggested that SA is mainly produced from trans-cinnamic acid (CA) in tobacco, but the underlying mechanisms remain largely unknown. SA synthesis is activated by wounding in tobacco plants in which the expression of WIPK and SIPK, two stress-related mitogen-activated protein kinases, is suppressed. Using this phenomenon, we previously revealed that HSR201 encoding benzyl alcohol O-benzoyltransferase is required for pathogen signal–induced SA synthesis. In this study, we further analyzed the transcriptomes of wounded WIPK-/SIPK-suppressed plants and found that the expression of NtCNL, NtCHD and NtKAT1, homologous to cinnamate-coenzyme A (CoA) ligase (CNL), cinnamoyl-CoA hydratase/dehydrogenase (CHD) and 3-ketoacyl-CoA thiolase (KAT), respectively, is associated with SA biosynthesis. CNL, CHD and KAT constitute a β-oxidative pathway in the peroxisomes and produce benzoyl-CoA, a precursor of benzenoid compounds in petunia flowers. Subcellular localization analysis showed that NtCNL, NtCHD and NtKAT1 localize in the peroxisomes. Recombinant NtCNL catalyzed the formation of CoA esters of CA, whereas recombinant NtCHD and NtKAT1 proteins converted cinnamoyl-CoA to benzoyl-CoA, a substrate of HSR201. Virus-induced gene silencing of any one of NtCNL, NtCHD and NtKAT1 homologs compromised SA accumulation induced by a pathogen-derived elicitor in Nicotiana benthamiana leaves. Transient overexpression of NtCNL in N. benthamiana leaves resulted in SA accumulation, which was enhanced by co-expression of HSR201, although overexpression of HSR201 alone did not cause SA accumulation. These results suggested that the peroxisomal β-oxidative pathway and HSR201 cooperatively contribute to SA biosynthesis in tobacco and N. benthamiana.
JA-Regulated AaGSW1–AaYABBY5/AaWRKY9 Complex Regulates Artemisinin Biosynthesis in Artemisia annua
Authors: Kayani Sadaf-Ilyas , Yanan Ma , Fu Xueqing , Shen Qian , Li Yongpeng , Rahman Saeed-ur , Peng Bowen , Huang Liu , Tang Kexuan 
Published: April 2023

Abstract
Artemisinin, a sesquiterpene lactone obtained from Artemisia annua, is an essential therapeutic against malaria. YABBY family transcription factor AaYABBY5 is an activator of AaCYP71AV1 (cytochrome P450–dependent hydroxylase) and AaDBR2 (double-bond reductase 2); however, the protein–protein interactions of AaYABBY5, as well as the mechanism of its regulation, have not yet been elucidated. AaWRKY9 protein is a positive regulator of artemisinin biosynthesis that activates AaGSW1 (glandular trichome–specific WRKY1) and AaDBR2 (double-bond reductase 2). In this study, YABBY–WRKY interactions are revealed to indirectly regulate artemisinin production. AaYABBY5 significantly increased the activity of the luciferase (LUC) gene fused to the promoter of AaGSW1. Toward the molecular basis of this regulation, AaYABBY5 interaction with AaWRKY9 protein was found. The combined effectors AaYABBY5 + AaWRKY9 showed synergistic effects toward the activities of AaGSW1 and AaDBR2 promoters, respectively. In AaYABBY5 overexpression plants, the expression of GSW1 was found to be significantly increased when compared to that of AaYABBY5 antisense or control plants. In addition, AaGSW1 was identified as an upstream activator of AaYABBY5. Further, it was found that AaJAZ8, a transcriptional repressor of jasmonate signaling, interacted with AaYABBY5 and attenuated its activity. Co-expression of AaYABBY5 and anti-AaJAZ8 in A. annua increased the activity of AaYABBY5 toward artemisinin biosynthesis. This current study provides the first indication of the molecular basis of regulation of artemisinin biosynthesis through YABBY–WRKY interactions, which are regulated through AaJAZ8. This knowledge presents AaYABBY5 overexpression plants as a powerful genetic resource for artemisinin biosynthesis.
Impact of the microbiome on mosquito-borne diseases
Authors: Shi Huicheng , Yu Xi , Cheng Gong 
Published: April 2023

Abstract
Mosquito-borne diseases present a significant threat to human health, with the possibility of outbreaks of new mosquito-borne diseases always looming. Unfortunately, current measures to combat these diseases such as vaccines and drugs are often either unavailable or ineffective. However, recent studies on microbiomes may reveal promising strategies to fight these diseases. In this review, we examine recent advances in our understanding of the effects of both the mosquito and vertebrate microbiomes on mosquito-borne diseases. We argue that the mosquito microbiome can have direct and indirect impacts on the transmission of these diseases, with mosquito symbiotic microorganisms, particularly Wolbachia bacteria, showing potential for controlling mosquito-borne diseases. Moreover, the skin microbiome of vertebrates plays a significant role in mosquito preferences, while the gut microbiome has an impact on the progression of mosquito-borne diseases in humans. As researchers continue to explore the role of microbiomes in mosquito-borne diseases, we highlight some promising future directions for this field. Ultimately, a better understanding of the interplay between mosquitoes, their hosts, pathogens, and the microbiomes of mosquitoes and hosts may hold the key to preventing and controlling mosquito-borne diseases.