bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Lack of a QBO‐MJO Connection in Climate Models With a Nudged Stratosphere
Authors: Martin Zane K. , Simpson Isla R. , Lin Pu , Orbe Clara , Tang Qi , Caron Julie M. , Chen Chih‐Chieh , Kim Hyemi , Leung L. Ruby , Richter Jadwiga H. , Xie Shaocheng 
Published: August 2023

AbstractThe observed stratospheric quasi‐biennial oscillation (QBO) and the tropospheric Madden‐Julian oscillation (MJO) are strongly connected in boreal winter, with stronger MJO activity when lower‐stratospheric winds are easterly. However, the current generation of climate models with internally generated representations of the QBO and MJO do not simulate the observed QBO‐MJO connection, for reasons that remain unclear. This study builds on prior work exploring the QBO‐MJO link in climate models whose stratospheric winds are relaxed toward reanalysis, reducing stratospheric biases in the model and imposing a realistic QBO. A series of ensemble experiments are performed using four state‐of‐the‐art climate models capable of representing the MJO over the period 1980–2015, each with similar nudging in the stratosphere. In these four models, nudging leads to a good representation of QBO wind and temperature signals, however no model simulates the observed QBO‐MJO relationship. Biases in MJO vertical structure and cloud‐radiative feedbacks are investigated, but no conclusive model bias or mechanism is identified that explains the lack of a QBO‐MJO connection.
Early ascending growth is associated with maternal lipoprotein profile during mid and late pregnancy and in cord blood
Authors: Blanco Sequeiros Elina , Tuomaala Anna-Kaisa , Tabassum Rubina , Bergman Paula H. , Koivusalo Saila B. , Huvinen Emilia 
Published: August 2023

Abstract
Introduction
Intrauterine conditions and accelerating early growth are associated with childhood obesity. It is unknown, whether fetal programming affects the early growth and could alterations in the maternal-fetal metabolome be the mediating mechanism. Therefore, we aimed to assess the associations between maternal and cord blood metabolite profile and offspring early growth.

Methods
The RADIEL study recruited 724 women at high risk for gestational diabetes mellitus (GDM) BMI ≥ 30 kg/m2 and/or prior GDM) before or in early pregnancy. Blood samples were collected once in each trimester, and from cord. Metabolomics were analyzed by targeted nuclear magnetic resonance (NMR) technique. Following up on offsprings’ first 2 years growth, we discovered 3 distinct growth profiles (ascending n = 80, intermediate n = 346, and descending n = 146) by using latent class mixed models (lcmm).

Results
From the cohort of mother-child dyads with available growth profile data (n = 572), we have metabolomic data from 232 mothers from 1st trimester, 271 from 2nd trimester, 277 from 3rd trimester and 345 from cord blood. We have data on 220 metabolites in each trimester and 70 from cord blood. In each trimester of pregnancy, the mothers of the ascending group showed higher levels of VLDL and LDL particles, and lower levels of HDL particles (p < 0.05). When adjusted for gestational age, birth weight, sex, delivery mode, and maternal smoking, there was an association with ascending profile and 2nd trimester total cholesterol in HDL2, 3rd trimester total cholesterol in HDL2 and in HDL, VLDL size and ratio of triglycerides to phosphoglycerides (TG/PG ratio) in cord blood (p ≤ 0.002).

Conclusion
Ascending early growth was associated with lower maternal total cholesterol in HDL in 2nd and 3rd trimester, and higher VLDL size and more adverse TG/PG ratio in cord blood.

Clinical trial registration
ClinicalTrials.gov, http://www.clinicaltrials.com, NCT01698385.
Lipid saturation controls nuclear envelope function
Authors: Romanauska Anete , Köhler Alwin 
Published: August 2023

AbstractThe nuclear envelope (NE) is a spherical double membrane with elastic properties. How NE shape and elasticity are regulated by lipid chemistry is unknown. Here we discover lipid acyl chain unsaturation as essential for NE and nuclear pore complex (NPC) architecture and function. Increased lipid saturation rigidifies the NE and the endoplasmic reticulum into planar, polygonal membranes, which are fracture prone. These membranes exhibit a micron-scale segregation of lipids into ordered and disordered phases, excluding NPCs from the ordered phase. Balanced lipid saturation is required for NPC integrity, pore membrane curvature and nucleocytoplasmic transport. Oxygen deprivation amplifies the impact of saturated lipids, causing NE rigidification and rupture. Conversely, lipid droplets buffer saturated lipids to preserve NE architecture. Our study uncovers a fundamental link between lipid acyl chain structure and the integrity of the cell nucleus with implications for nuclear membrane malfunction in ischaemic tissues.
Programmable multispecific DNA-origami-based T-cell engagers
Authors: Wagenbauer Klaus F. , Pham Nhi , Gottschlich Adrian , Kick Benjamin , Kozina Viktorija , Frank Christopher , Trninic Daniela , Stömmer Pierre , Grünmeier Ruth , Carlini Emanuele , Tsiverioti Christina Angeliki , Kobold Sebastian , Funke Jonas J. , Dietz Hendrik 
Published: August 2023

AbstractMultispecific antibodies have emerged as versatile therapeutic agents, and therefore, approaches to optimize and streamline their design and assembly are needed. Here we report on the modular and programmable assembly of IgG antibodies, F(ab) and scFv fragments on DNA origami nanocarriers. We screened 105 distinct quadruplet antibody variants in vitro for the ability to activate T cells in the presence of target cells. T-cell engagers were identified, which in vitro showed the specific and efficient T-cell-mediated lysis of five distinct target cell lines. We used these T-cell engagers to target and lyse tumour cells in vivo in a xenograft mouse tumour model. Our approach enables the rapid generation, screening and testing of bi- and multispecific antibodies to facilitate preclinical pharmaceutical development from in vitro discovery to in vivo proof of concept.
Single-molecule analysis of DNA base-stacking energetics using patterned DNA nanostructures
Authors: Banerjee Abhinav , Anand Micky , Kalita Simanta , Ganji Mahipal 
Published: August 2023

AbstractThe DNA double helix structure is stabilized by base-pairing and base-stacking interactions. However, a comprehensive understanding of dinucleotide base-stacking energetics is lacking. Here we combined multiplexed DNA-based point accumulation in nanoscale topography (DNA-PAINT) imaging with designer DNA nanostructures and measured the free energy of dinucleotide base stacking at the single-molecule level. Multiplexed imaging enabled us to extract the binding kinetics of an imager strand with and without additional dinucleotide stacking interactions. The DNA-PAINT data showed that a single additional dinucleotide base stacking results in up to 250-fold stabilization for the DNA duplex nanostructure. We found that the dinucleotide base-stacking energies vary from −0.95 ± 0.12 kcal mol−1 to −3.22 ± 0.04 kcal mol−1 for C|T and A|C base-stackings, respectively. We demonstrate the application of base-stacking energetics in designing DNA-PAINT probes for multiplexed super-resolution imaging, and efficient assembly of higher-order DNA nanostructures. Our results will aid in designing functional DNA nanostructures, and DNA and RNA aptamers, and facilitate better predictions of the local DNA structure.
Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial
Authors: Lin Yi , Raje Noopur S. , Berdeja Jesús G. , Siegel David S. , Jagannath Sundar , Madduri Deepu , Liedtke Michaela , Rosenblatt Jacalyn , Maus Marcela V. , Massaro Monica , Petrocca Fabio , Yeri Ashish , Finney Olivia , Caia Andrea , Yang Zhihong , Martin Nathan , Campbell Timothy B. , Rytlewski Julie , Fuller Jaymes , Hege Kristen , Munshi Nikhil C. , Kochenderfer James N. 
Published: August 2023

AbstractIdecabtagene vicleucel (ide-cel) is a B-cell-maturation antigen (BCMA)-directed chimeric antigen receptor T cell therapy. We performed a post hoc analysis of a single-arm phase 1 multicenter study in relapsed/refractory multiple myeloma (CRB-401) (n = 62; median follow-up, 18.1 months). The primary endpoint was safety outcomes, and secondary endpoints included overall response rate (ORR), complete response (CR) and very good partial response (VGPR). The study met its primary endpoint with low rates of grade 3/grade 4 cytokine release syndrome (6.5%) and neurotoxicity (1.6%). ORR was 75.8%; 64.5% achieved VGPR or better and 38.7% achieved CR or stringent CR. Among exploratory endpoints, median duration of response, progression-free survival (PFS) and overall survival were 10.3, 8.8 and 34.2 months, respectively, and ide-cel expansion in blood and bone marrow correlated with clinical efficacy and postinfusion reduction of soluble BCMA. Patients with PFS ≥ 18 months had more naive and less exhausted T cells in apheresis material and improved functional T cell phenotype in the drug product compared with those with less durable responses. These results confirm ide-cel safety, tolerability and efficacy and describe T cell qualities that correlate with durable response. Clinicaltrials.gov identifier : NCT02658929.
Orbitofrontal cortex control of striatum leads economic decision-making
Authors: Gore Felicity , Hernandez Melissa , Ramakrishnan Charu , Crow Ailey K. , Malenka Robert C. , Deisseroth Karl 
Published: August 2023

AbstractAnimals must continually evaluate stimuli in their environment to decide which opportunities to pursue, and in many cases these decisions can be understood in fundamentally economic terms. Although several brain regions have been individually implicated in these processes, the brain-wide mechanisms relating these regions in decision-making are unclear. Using an economic decision-making task adapted for rats, we find that neural activity in both of two connected brain regions, the ventrolateral orbitofrontal cortex (OFC) and the dorsomedial striatum (DMS), was required for economic decision-making. Relevant neural activity in both brain regions was strikingly similar, dominated by the spatial features of the decision-making process. However, the neural encoding of choice direction in OFC preceded that of DMS, and this temporal relationship was strongly correlated with choice accuracy. Furthermore, activity specifically in the OFC projection to the DMS was required for appropriate economic decision-making. These results demonstrate that choice information in the OFC is relayed to the DMS to lead accurate economic decision-making.
Molecular modelling and site-directed mutagenesis provide insight into saccharide pyruvylation by the Paenibacillus alvei CsaB enzyme
Authors: Stefanović Cordula , Hager-Mair Fiona F. , Breslmayr Erik , López-Guzmán Arturo , Lim Charlie , Blaukopf Markus , Kosma Paul , Oostenbrink Chris , Ludwig Roland , Schäffer Christina 
Published: August 2023

AbstractPyruvylation is a biologically versatile but mechanistically unexplored saccharide modification. 4,6-Ketal pyruvylated N-acetylmannosamine within bacterial secondary cell wall polymers serves as a cell wall anchoring epitope for proteins possessing a terminal S-layer homology domain trimer. The pyruvyltransferase CsaB from Paenibacillus alvei served as a model to investigate the structural basis of the pyruvyltransfer reaction by a combination of molecular modelling and site-directed mutagenesis together with an enzyme assay using phosphoenolpyruvate (PEP; donor) and synthetic β-D-ManNAc-(1 → 4)-α-D-GlcNAc-diphosphoryl-11-phenoxyundecyl (acceptor). CsaB protein structure modelling was done using Phyre2 and I-Tasser based on the partial crystal structure of the Schizosaccharomyces pombe pyruvyltransferase Pvg1p and by AlphaFold. The models informed the construction of twelve CsaB mutants targeted at plausible PEP and acceptor binding sites and KM and kcat values were determined to evaluate the mutants, indicating the importance of a loop region for catalysis. R148, H308 and K328 were found to be critical to PEP binding and insight into acceptor binding was obtained from an analysis of Y14 and F16 mutants, confirming the modelled binding sites and interactions predicted using Molecular Operating Environment. These data lay the basis for future mechanistic studies of saccharide pyruvylation as a novel target for interference with bacterial cell wall assembly.
Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management
Authors: Agu P. C. , Afiukwa C. A. , Orji O. U. , Ezeh E. M. , Ofoke I. H. , Ogbu C. O. , Ugwuja E. I. , Aja P. M. 
Published: August 2023

AbstractMolecular docking is a computational technique that predicts the binding affinity of ligands to receptor proteins. Although it has potential uses in nutraceutical research, it has developed into a formidable tool for drug development. Bioactive substances called nutraceuticals are present in food sources and can be used in the management of diseases. Finding their molecular targets can help in the creation of disease-specific new therapies. The purpose of this review was to explore molecular docking's application to the study of dietary supplements and disease management. First, an overview of the fundamentals of molecular docking and the various software tools available for docking was presented. The limitations and difficulties of using molecular docking in nutraceutical research are also covered, including the reliability of scoring functions and the requirement for experimental validation. Additionally, there was a focus on the identification of molecular targets for nutraceuticals in numerous disease models, including those for sickle cell disease, cancer, cardiovascular, gut, reproductive, and neurodegenerative disorders. We further highlighted biochemistry pathways and models from recent studies that have revealed molecular mechanisms to pinpoint new nutraceuticals' effects on disease pathogenesis. It is convincingly true that molecular docking is a useful tool for identifying the molecular targets of nutraceuticals in the management of diseases. It may offer information about how nutraceuticals work and support the creation of new therapeutics. Therefore, molecular docking has a bright future in nutraceutical research and has a lot of potentials to lead to the creation of brand-new medicines for the treatment of disease.
Effect of caffeine and other xanthines on liver sinusoidal endothelial cell ultrastructure
Authors: Mao Hong , Szafranska Karolina , Kruse Larissa , Holte Christopher , Wolfson Deanna L. , Ahluwalia Balpreet Singh , Whitchurch Cynthia B. , Cole Louise , Lockwood Glen P. , Diekmann Robin , Le Couteur David , Cogger Victoria C. , McCourt Peter A. G. 
Published: August 2023

AbstractXanthines such as caffeine and theobromine are among the most consumed psychoactive stimulants in the world, either as natural components of coffee, tea and chocolate, or as added ingredients. The present study assessed if xanthines affect liver sinusoidal endothelial cells (LSEC). Cultured primary rat LSEC were challenged with xanthines at concentrations typically obtained from normal consumption of xanthine-containing beverages, food or medicines; and at higher concentrations below the in vitro toxic limit. The fenestrated morphology of LSEC were examined with scanning electron and structured illumination microscopy. All xanthine challenges had no toxic effects on LSEC ultrastructure as judged by LSEC fenestration morphology, or function as determined by endocytosis studies. All xanthines in high concentrations (150 μg/mL) increased fenestration frequency but at physiologically relevant concentrations, only theobromine (8 μg/mL) showed an effect. LSEC porosity was influenced only by high caffeine doses which also shifted the fenestration distribution towards smaller pores. Moreover, a dose-dependent increase in fenestration number was observed after caffeine treatment. If these compounds induce similar changes in vivo, age-related reduction of LSEC porosity can be reversed by oral treatment with theobromine or with other xanthines using targeted delivery.
Intelligent diagnostic model for malaria parasite detection and classification using imperative inception-based capsule neural networks
Authors: Madhu Golla , Mohamed Ali Wagdy , Kautish Sandeep , Shah Mohd Asif , Ali Irfan 
Published: August 2023

AbstractMalaria is an acute fever sickness caused by the Plasmodium parasite and spread by infected Anopheles female mosquitoes. It causes catastrophic illness if left untreated for an extended period, and delaying exact treatment might result in the development of further complications. The most prevalent method now available for detecting malaria is the microscope. Under a microscope, blood smears are typically examined for malaria diagnosis. Despite its advantages, this method is time-consuming, subjective, and requires highly skilled personnel. Therefore, an automated malaria diagnosis system is imperative for ensuring accurate and efficient treatment. This research develops an innovative approach utilizing an urgent, inception-based capsule network to distinguish parasitized and uninfected cells from microscopic images. This diagnostic model incorporates neural networks based on Inception and Imperative Capsule networks. The inception block extracts rich characteristics from images of malaria cells using a pre-trained model, such as Inception V3, which facilitates efficient representation learning. Subsequently, the dynamic imperative capsule neural network detects malaria parasites in microscopic images by classifying them into parasitized and healthy cells, enabling the detection of malaria parasites. The experiment results demonstrate a significant improvement in malaria parasite recognition. Compared to traditional manual microscopy, the proposed system is more accurate and faster. Finally, this study demonstrates the need to provide robust and efficient diagnostic solutions by leveraging state-of-the-art technologies to combat malaria.
Molecular insights into recognition of GUCY2C by T-cell engaging bispecific antibody anti-GUCY2CxCD3
Authors: Rampuria Pragya , Mosyak Lidia , Root Adam R. , Svenson Kristine , Agostino Michael J. , LaVallie Edward R. 
Published: August 2023

AbstractThe intestinal epithelial receptor Guanylyl Cyclase C (GUCY2C) is a tumor-associated cell surface antigen expressed across gastrointestinal malignancies that can serve as an efficacious target for colorectal cancer immunotherapy. Here, we describe a yeast surface-display approach combined with an orthogonal peptide-based mapping strategy to identify the GUCY2C binding epitope of a novel anti-GUCY2CxCD3 bispecific antibody (BsAb) that recently advanced into the clinic for the treatment of cancer. The target epitope was localized to the N-terminal helix H2 of human GUCY2C, which enabled the determination of the crystal structure of the minimal GUCY2C epitope in complex with the anti-GUCY2C antibody domain. To understand if this minimal epitope covers the entire antibody binding region and to investigate the impact of epitope position on the antibody’s activity, we further determined the structure of this interaction in the context of the full-length extracellular domain (ECD) of GUCY2C. We found that this epitope is positioned on the protruding membrane-distal helical region of GUCY2C and that its specific location on the surface of GUCY2C dictates the close spatial proximity of the two antigen arms in a diabody arrangement essential to the tumor killing activity of GUCY2CxCD3 BsAb.
Development and analysis of a nano-triangular wave-shaped polarizer
Authors: Hokari Ryohei , Takakuwa Kyohei , Shiomoto Kengo , Kuwano Genki , Kurihara Kazuma 
Published: August 2023

AbstractAs society becomes smarter, advanced optical sensing and imaging technologies utilizing visible and near-infrared regions have become increasingly prevalent. Wire-grid polarizers, which are available for broadband electromagnetic waves, are effective in improving the signal-to-noise ratio of such optical systems and enabling more advanced object detection and analysis. However, to be implemented in everyday products, low-cost manufacturing methods must be developed while maintaining high-performance optical functions. To meet these requirements, we conducted an analysis of the geometry of wire-grid polarizers, and designed and developed a wire-grid polarizer with a nano-triangular wave-shaped structure that can be fabricated using general-purpose manufacturing equipment. Once the mould is prepared, this polarizer can be fabricated via nanoimprinting and metal deposition with a normal angle or electroless plating processes. The polarizer fabricated through electroless Ni plating achieves a transmittance of 40%, which is approximately 1.4 times higher than that achieved in a previous study using electroless Ni plating on a rectangular structure with the same period. In addition, the polarizer fabricated through normal angle Al deposition operates over a wide range of wavelengths from visible light to near-infrared, and achieves a polarization extinction ratio of 24 dB at a wavelength of 550 nm and a high transmittance of 81%. High-performance polarizers can be obtained through normal-angle deposition using general-purpose equipment in contrast to the oblique-angle deposition method employed in the manufacture of conventional rectangular structure-based wire-grid polarizers, thereby contributing to cost reduction and improved manufacturability.
Hybrid collagen–cellulose–Fe3O4@TiO2 magnetic bio-sponges derived from animal skin waste and Kenaf fibers for wastewater remediation
Authors: Assanvo E. F. , Nagaraj S. , Boa D. , Thanikaivelan P. 
Published: August 2023

AbstractWater pollution from synthetic dyes and oil spills has a significant impact on the environment and living species. Here, we developed a low-cost, environmentally friendly and easily biodegradable magnetic hybrid bio-sponge nanocomposite from renewable resources such as collagen and cellulose (Kenaf fibre cellulose–collagen, KFCC). We loaded it with magnetic bimetallic Fe3O4@TiO2 (BFT) NPs to produce a photocatalyst material (KFCC-BFT) for the treatment of colored wastewater as well as a sorbent for oil–water separation. The characterization of the bimetallic BFT NPs by XRD, HRTEM and VSM showed the deposition of TiO2 particles onto the surface of Fe3O4 with lattice interlayers spacing of 0.24 and 0.33 nm for Fe3O4 and TiO2, respectively with ferromagnetic property. The UV–vis diffuse reflectance spectra result indicated that the band gap energy of bio-sponges decreases with the increase of the bimetallic moiety. The photocatalytic efficiency of the as-prepared magnetic hybrid bio-sponge in the degradation of crystal violet dye was up to 91.2% under visible light conditions and 86.6% under direct sunlight exposure. Furthermore, the magnetic hybrid bio-sponge was used to separate motor oil from water (> 99%) and had a high oil sorption capacity of 46.1 g/g. Investigation of the recyclability and reusability performance for 9 cycles revealed that the bio-sponge had a high sorption capacity for up to 5 cycles. Our results suggest that the bio-polymer-supported BFT hybrid nanocomposite is a cost-effective and easily biodegradable photocatalyst and has great potential for real-field environmental remediation applications.