bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis of lysophosphatidylserine receptor GPR174 ligand recognition and activation
Authors: Liang Jiale , Inoue Asuka , Ikuta Tatsuya , Xia Ruixue , Wang Na , Kawakami Kouki , Xu Zhenmei , Qian Yu , Zhu Xinyan , Zhang Anqi , Guo Changyou , Huang Zhiwei , He Yuanzheng 
Published: February 2023

AbstractLysophosphatidylserine (LysoPS) is a lipid mediator that induces multiple cellular responses through binding to GPR174. Here, we present the cryo-electron microscopy (cryo-EM) structure of LysoPS-bound human GPR174 in complex with Gsprotein. The structure reveals a ligand recognition mode, including the negatively charged head group of LysoPS forms extensive polar interactions with surrounding key residues of the ligand binding pocket, and the L-serine moiety buries deeply into a positive charged cavity in the pocket. In addition, the structure unveils a partially open pocket on transmembrane domain helix (TM) 4 and 5 for a lateral entry of ligand. Finally, the structure reveals a Gsengaging mode featured by a deep insertion of a helix 5 (αH5) and extensive polar interactions between receptor and αH5. Taken together, the information revealed by our structural study provides a framework for understanding LysoPS signaling and a rational basis for designing LysoPS receptor-targeting drugs.
Novel plant–frugivore network on Mauritius is unlikely to compensate for the extinction of seed dispersers
Authors: Heinen Julia H. , Florens F. B. Vincent , Baider Cláudia , Hume Julian P. , Kissling W. Daniel , Whittaker Robert J. , Rahbek Carsten , Borregaard Michael K. 
Published: February 2023

AbstractInsular communities are particularly vulnerable to anthropogenic extinctions and introductions. Changes in composition of island frugivore communities may affect seed dispersal within the native plant community, risking ecological shifts and ultimately co-extinction cascades. Introduced species could potentially mitigate these risks by replacing ecological functions of extinct species, but conclusive evidence is lacking. Here, we investigate changes in plant–frugivore interactions involving frugivorous birds, mammals and reptiles in Mauritius, an oceanic island with an exceptionally well-specified frugivore community and well-described species introduction history. We demonstrate substantial losses of binary interaction partnerships (at the species level) resulting from native species extinctions, but also gains of equal numbers of novel interactions with introduced species, potentially supporting the idea that non-native species might compensate for lost seed dispersal. However, closer investigation of animal seed handling behaviour reveals that most interactions with seed dispersers are replaced by ecologically different interactions with seed predators. Therefore, restoration of seed dispersal functionality in this novel plant–frugivore community is unlikely.
Brain expression quantitative trait locus and network analyses reveal downstream effects and putative drivers for brain-related diseases
Authors: de Klein Niek , Tsai Ellen A. , Vochteloo Martijn , Baird Denis , Huang Yunfeng , Chen Chia-Yen , van Dam Sipko , Oelen Roy , Deelen Patrick , Bakker Olivier B. , El Garwany Omar , Ouyang Zhengyu , Marshall Eric E. , Zavodszky Maria I. , van Rheenen Wouter , Bakker Mark K. , Veldink Jan , Gaunt Tom R. , Runz Heiko , Franke Lude , Westra Harm-Jan 
Published: February 2023

AbstractIdentification of therapeutic targets from genome-wide association studies (GWAS) requires insights into downstream functional consequences. We harmonized 8,613 RNA-sequencing samples from 14 brain datasets to create the MetaBrain resource and performed cis- and trans-expression quantitative trait locus (eQTL) meta-analyses in multiple brain region- and ancestry-specific datasets (n ≤ 2,759). Many of the 16,169 cortex cis-eQTLs were tissue-dependent when compared with blood cis-eQTLs. We inferred brain cell types for 3,549 cis-eQTLs by interaction analysis. We prioritized 186 cis-eQTLs for 31 brain-related traits using Mendelian randomization and co-localization including 40 cis-eQTLs with an inferred cell type, such as a neuron-specific cis-eQTL (CYP24A1) for multiple sclerosis. We further describe 737 trans-eQTLs for 526 unique variants and 108 unique genes. We used brain-specific gene-co-regulation networks to link GWAS loci and prioritize additional genes for five central nervous system diseases. This study represents a valuable resource for post-GWAS research on central nervous system diseases.
The diachronic trend of female and male stature in Milan over 2000 years
Authors: Biehler-Gomez Lucie , del Bo Beatrice , Petrosino Daniele , Morandini Paolo , Mattia Mirko , Palazzolo Luca , Guerrini Uliano , Cattaneo Cristina 
Published: February 2023

AbstractStature is a biological trait directly determined by the interaction of genetic and environmental components. As such, it is often evaluated as an indicator for the reconstruction of skeletal biological profiles, past health, and social dynamics of human populations. Based on the analysis of 549 skeletons from the CAL (Collezione Antropologica LABANOF), a study of the diachronic trend of male and female adult stature in Milan (Italy) is being proposed here, covering a time span of about 2000 years, ranging from the Roman era to present-days. The skeletons, from necropolises dedicated to the less wealthy classes of Milanese society, were assigned to one of following five historical periods: Roman Era (first–fifth centuries AD), Early Middle Ages (sixth–tenth centuries AD), Late Middle Ages (eleventh–fifteenth centuries AD), Modern Era (sixteenth–eighteenth centuries AD) and Contemporary Era (nineteenth–twentieth centuries AD), and their stature was estimated according to the regression formulae of Trotter (1970). The collected data were then subjected to statistical analyses with ANOVA using R software. Although stature values showed an ample standard deviation in all periods, statistical analyses showed that stature did not significantly vary across historical periods in Milan for both sexes. This is one of the rare studies showing no diachronic changes in the trend of stature in Europe.
A multidimensional ODE-based model of Alzheimer’s disease progression
Authors: Bossa Matías Nicolás , Sahli Hichem 
Published: February 2023

AbstractData-driven Alzheimer’s disease (AD) progression models are useful for clinical prediction, disease mechanism understanding, and clinical trial design. Most dynamic models were inspired by the amyloid cascade hypothesis and described AD progression as a linear chain of pathological events. However, the heterogeneity observed in healthy and sporadic AD populations challenged the amyloid hypothesis, and there is a need for more flexible dynamical models that accompany this conceptual shift. We present a statistical model of the temporal evolution of biomarkers and cognitive tests that allows diverse biomarker paths throughout the disease. The model consists of two elements: a multivariate dynamic model of the joint evolution of biomarkers and cognitive tests; and a clinical prediction model. The dynamic model uses a system of ordinary differential equations to jointly model the rate of change of an individual’s biomarkers and cognitive tests. The clinical prediction model is an ordinal logistic model of the diagnostic label. Prognosis and time-to-onset predictions are obtained by computing the clinical label probabilities throughout the forecasted biomarker trajectories. The proposed dynamical model is interpretable, free of one-dimensional progression hypotheses or disease staging paradigms, and can account for the heterogeneous dynamics observed in sporadic AD. We developed the model using longitudinal data from the Alzheimer’s Disease Neuroimaging Initiative. We illustrate the patterns of biomarker rates of change and the model performance to predict the time to conversion from MCI to dementia.
Novel Bromo and methoxy substituted Schiff base complexes of Mn(II), Fe(III), and Cr(III) for anticancer, antimicrobial, docking, and ADMET studies
Authors: Abdel-Rahman Laila H. , Abdelghani Amani A. , AlObaid Abeer A. , El-ezz Doaa Abou , Warad Ismail , Shehata Mohamed R. , Abdalla Ehab M. 
Published: February 2023

AbstractIn this study, four new Mn(II), Fe(III), and Cr(III) complexes with two Schiff base ligands namely, 4-bromo-2-[(E)-{[4-(2-hydroxyethyl)phenyl]imino}methyl]phenol (HL1) and 2-[(E)-{[4-(2-hydroxyethyl)phenyl]imino}methyl]-4-methoxy phenol (HL2) have been synthesized and characterized. Different analytical and spectral methods have been used to characterize the ligands and their complexes. General formulas of [M(L)Cl2(H2O)2] for FeL1, CrL1 and CrL2, and [M(L)Cl(H2O)3] for MnL2 were proposed. HOMO and LUMO energies, as well as the electrical characteristics, have been calculated using DFT/B3LYP calculations with Gaussian 09 program. The optimized lowest energy configurations of the complexes are proven. The disc diffusion technique was used to test the pharmacological activities' antibacterial efficacy against diverse bacterial and fungus species. The MTT technique was used to assess the in vitro cytotoxicity of the ligands and their metal complexes on the Hep-G2 human liver carcinoma cell line and the MCF-7 human breast cancer cell line. All compounds displayed better activity compared to the free ligands. MnL2 complex showed predominant activity when compared to the other complexes with an IC50 value of 2.6 ± 0.11 μg/ml against Hep-G2, and against MCF-7 the IC50 value was 3.0 ± 0.2 μg/ml which is less than the standard drug cisplatin (4.0 μg/ml). UV–vis electronic spectrum and gel electrophoresis techniques have been used to investigate the compounds’ affinity to bind and cleavage CT-DNA. The interaction’s binding constants, or Kb, have been identified, and it was discovered that the new complexes' binding affinities are in the order of FeL1 > MnL2 > CrL2 > CrL1, and the binding mechanism has been suggested. To assess the kind of binding and binding affinity of the investigated drugs with human DNA, a molecular docking study was carried out (PDB:1bna). The acquired results supported the intercalation binding mechanism proposed in the experimental part and revealed that complexes may be inserted into the DNA molecule to stop DNA replication. According to ADMET data, the synthesized compounds have a high bioavailability profile and their physicochemical and pharmacological features remained within Lipinski's RO5 predicted limitations.
Quantification of the methodological error in kinematic evaluation of the DRUJ using dynamic CT
Authors: Oonk J. G. M. , Dobbe J. G. G. , Strackee S. D. , Strijkers G. J. , Streekstra G. J. 
Published: February 2023

AbstractDistal radio-ulnar joint (DRUJ) motion analysis using dynamic CT is gaining popularity. Following scanning and segmentation, 3D bone models are registered to (4D-)CT target frames. Imaging errors like low signal-to-noise ratio (SNR), limited Z-coverage and motion artefacts influence registration, causing misinterpretation of joint motion. This necessitates quantification of the methodological error. A cadaver arm and dynamic phantom were subjected to multiple 4D-CT scans, while varying tube charge-time product and phantom angular velocity, to evaluate the effects of SNR and motion artefacts on registration accuracy and precision. 4D-CT Z-coverage is limited by the scanner. To quantify the effects of different Z-coverages on registration accuracy and precision, 4D-CT was simulated by acquiring multiple spiral 3D-CT scans of the cadaver arm. Z-coverage was varied by clipping the 3D bone models prior to registration. The radius position relative to the ulna was obtained from the segmentation image. Apparent relative displacement seen in the target images is caused by registration errors. Worst-case translations were 0.45, 0.08 and 1.1 mm for SNR-, Z-coverage- and motion-related errors respectively. Worst-case rotations were 0.41, 0.13 and 6.0 degrees. This study showed that quantification of the methodological error enables composition of accurate and precise DRUJ motion scanning protocols.
The effect of a brief, unplanned treatment delay on neovascular age-related macular degeneration patients: a retrospective cohort study
Authors: Zehden Jason Adam , Ghosh Arko , Soundararajan Srinath , Tsujimoto Tamy Harumy Moraes , Jiang Huijun , Lin Feng-Chang , Blahnik Tyler , Fleischman David , Zhang Alice Yang 
Published: February 2023

AbstractNon-compliance to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy can result in increased disease activity in neovascular age-related macular degeneration (nAMD). Our study aims to determine effects of unplanned delay in anti-VEGF injection treatment for nAMD. This retrospective observational study included patients with delays in receiving intravitreal injections for nAMD treatment from March to May 2020 by at least 21 days. Baseline demographic and clinical characteristics, visual acuity (VA), central macular thickness (CMT) measured on optical coherence tomography (OCT), and duration of delayed treatment were analyzed for 3 time points, the pre-delay visit (v1) and post-delay visits (v2 and v3). Data were compared to age-matched controls treated for nAMD in 2019 without delay. Demographic characteristics were compared using two-sample t-tests for continuous variables and Pearson’s chi-square tests for categorical variables. For the two primary outcomes of interest, VA and CMT, means and standard deviations were reported for each combination of group and time. Each outcome was modeled using a linear mixed model with the group, time and group-time interaction as fixed effects. A total of 69 patients (99 eyes) in the treatment delay group and 44 patients (69 eyes) in the control group were identified. Statistically significant differences between control and delayed groups were detected for VA (difference in mean logMAR = 0.16; 95% CI 0.06, 0.27; p = 0.002) and CMT (difference in mean CMT = 29; 95% CI 12, 47; p = 0.001) at v2. No differences were detected for v1 and v3 time points for both outcomes. An unplanned delay in intravitreal injection treatment for nAMD resulted in an increase in CMT and worsening of VA compared to controls observed at v2. At v3, CMT and VA recovered to near v1 levels. This study demonstrates that a one-time, brief interruption in treatment for nAMD results in reversible, temporary worsening.
Design and fabrication of superhydrophobic cellulose nanocrystal films by combination of self-assembly and organocatalysis
Authors: Alimohammadzadeh Rana , Sanhueza Italo , Córdova Armando 
Published: February 2023

AbstractCellulose nanocrystals, which have unique properties of high aspect ratio, high surface area, high mechanical strength, and a liquid crystalline nature, constitute a renewable nanomaterial with great potential for several uses (e.g., composites, films and barriers). However, their intrinsic hydrophilicity results in materials that are moisture sensitive and exhibit poor water stability. This limits their use and competitiveness as a sustainable alternative against fossil-based materials/plastics in packaging, food storage, construction and materials application, which cause contamination in our oceans and environment. To make cellulose nanocrystal films superhydrophobic, toxic chemicals such as fluorocarbons are typically attached to their surfaces. Hence, there is a pressing need for environmentally friendly alternatives for their modification and acquiring this important surface property. Herein, we describe the novel creation of superhydrophobic, fluorocarbon-free and transparent cellulose nanocrystal films with functional groups by a bioinspired combination of self-assembly and organocatalytic surface modification at the nanoscale using food approved organic acid catalysts. The resulting film-surface is superhydrophobic (water contact angle > 150°) and has self-cleaning properties (the lotus effect). In addition, the superhydrophobic cellulose nanocrystal films have excellent water stability and significantly decreased oxygen permeability at high relative humidity with oxygen transmission rates better than those of commonly used plastics.
[18F]Tosyl fluoride as a versatile [18F]fluoride source for the preparation of 18F-labeled radiopharmaceuticals
Authors: Zhou Dong , Chu Wenhua , Xu Jinbin , Schwarz Sally , Katzenellenbogen John A. 
Published: February 2023

AbstractPositron emission tomography (PET) is an in vivo imaging technology that utilizes positron-emitting radioisotope-labeled compounds as PET radiotracers that are commonly used in clinic and in various research areas, including oncology, cardiology, and neurology. Fluorine-18 is the most widely used PET-radionuclide and commonly produced by proton bombardment of 18O-enriched water in a cyclotron. The [18F]fluoride thus obtained generally requires processing by azeotropic drying in order to completely remove H2O before it can be used for nucleophilic radiofluorination. In general, the drying step is important in facilitating the radiofluorination reactions and the preparation of 18F-labeled PET radiotracers. In this communication, we have demonstrated the feasibility of using [18F]tosyl fluoride ([18F]TsF) as a versatile [18F]fluoride source for radiofluorination to bypass the azeotropic drying step, and we have developed a continuous flow solid-phase radiosynthesis strategy to generate [18F]TsF in a form that is excellent for radiofluorination. [18F]TsF shows high reactivity in radiofluorination and provides the features suitable for preparing PET radiotracers on a small scale and exploring novel radiolabeling technologies. Thus, using [18F]TsF as a [18F]fluoride source is a promising strategy that facilitates radiofluorination and provides a convenient and efficient solution for the preparation of 18F-labeled radiopharmaceuticals that is well matched to the emerging trends in PET imaging technologies.
Targeted delivery of paclitaxel drug using polymer-coated magnetic nanoparticles for fibrosarcoma therapy: in vitro and in vivo studies
Authors: Al-Obaidy Rusul , Haider Adawiya J. , Al-Musawi Sharafaldin , Arsad Norhana 
Published: February 2023

AbstractFibrosarcoma is a rare type of cancer that affects cells known as fibroblasts that are malignant, locally recurring, and spreading tumor in fibrous tissue. In this work, an iron plate immersed in an aqueous solution of double added deionized water, supplemented with potassium permanganate solution (KMnO4) was carried out by the pulsed laser ablation in liquid method (PLAIL). Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized using different laser wavelengths (1064, 532, and 266 nm) at a fluence of 28 J/cm2with 100 shots of the iron plate to control the concentration, shape and size of the prepared high-stability SPIONs. The drug nanocarrier was synthesized by coating SPION with paclitaxel (PTX)-loaded chitosan (Cs) and polyethylene glycol (PEG). This nanosystem was functionalized by receptors that target folate (FA). The physiochemical characteristics of SPION@Cs-PTX-PEG-FA nanoparticles were evaluated and confirmed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-Ray diffraction (XRD), atomic force microscopy (AFM), and dynamic light scattering (DLS) methods. Cell internalization, cytotoxicity assay (MTT), apoptosis induction, and gene expression of SPION@Cs-PTX-PEG-FA were estimated in fibrosarcoma cell lines, respectively. In vivo studies used BALB/c tumor-bearing mice. The results showed that SPION@Cs-PTX-PEG-FA exhibited suitable physical stability, spherical shape, desirable size, and charge. SPION@Cs-PTX-PEG-FA inhibited proliferation and induced apoptosis of cancer cells (P < 0.01). The results of the in vivo study showed that SPION@Cs-PTX-PEG-FA significantly decreased tumor size compared to free PTX and control samples (P < 0.05), leading to longer survival, significantly increased splenocyte proliferation and IFN-γ level, and significantly decreased the level of IL-4. All of these findings indicated the potential of SPION@Cs-PTX-PEG-FA as an antitumor therapeutic agent.
Measuring visual information gathering in individuals with ultra low vision using virtual reality
Authors: Kartha Arathy , Sadeghi Roksana , Bradley Chris , Tran Chau , Gee Will , Dagnelie Gislin 
Published: February 2023

AbstractPeople with ULV (visual acuity ≤ 20/1600 or 1.9 logMAR) lack form vision but have rudimentary levels of vision that can be used for a range of activities in daily life. However, current clinical tests are designed to assess form vision and do not provide information about the range of visually guided activities that can be performed in daily life using ULV. This is important to know given the growing number of clinical trials that recruit individuals with ULV (e.g., gene therapy, stem cell therapy) or restore vision to the ULV range in the blind (visual prosthesis). In this study, we develop a set of 19 activities (items) in virtual reality involving spatial localization/detection, motion detection, and direction of motion that can be used to assess visual performance in people with ULV. We estimated measures of item difficulty and person ability on a relative d prime (d′) axis using a signal detection theory based analysis for latent variables. The items represented a range of difficulty levels (− 1.09 to 0.39 in relative d′) in a heterogeneous group of individuals with ULV (− 0.74 to 2.2 in relative d′) showing the instrument’s utility as an outcome measure in clinical trials.
Lysosomal phospholipase A2 contributes to the biosynthesis of the atypical late endosome lipid bis(monoacylglycero)phosphate
Authors: Chen Jacinda , Cazenave-Gassiot Amaury , Xu Yimeng , Piroli Paola , Hwang Robert , DeFreitas Laura , Chan Robin Barry , Di Paolo Gilbert , Nandakumar Renu , Wenk Markus R. , Marquer Catherine 
Published: February 2023

AbstractThe late endosome/lysosome (LE/Lys) lipid bis(monoacylglycero)phosphate (BMP) plays major roles in cargo sorting and degradation, regulation of cholesterol and intercellular communication and has been linked to viral infection and neurodegeneration. Although BMP was initially described over fifty years ago, the enzymes regulating its synthesis remain unknown. The first step in the BMP biosynthetic pathway is the conversion of phosphatidylglycerol (PG) into lysophosphatidylglycerol (LPG) by a phospholipase A2 (PLA2) enzyme. Here we report that this enzyme is lysosomal PLA2 (LPLA2). We show that LPLA2 is sufficient to convert PG into LPG in vitro. We show that modulating LPLA2 levels regulates BMP levels in HeLa cells, and affects downstream pathways such as LE/Lys morphology and cholesterol levels. Finally, we show that in a model of Niemann-Pick disease type C, overexpressing LPLA2 alleviates the LE/Lys cholesterol accumulation phenotype. Altogether, we shed new light on BMP biosynthesis and contribute tools to regulate BMP-dependent pathways.