bluuebunny/crossref_metadata_2025_split huggingface dataset:
WWC1/2 regulate spinogenesis and cognition in mice by stabilizing AMOT
Authors: Cao Runyi , Zhu Rui , Sha Zhao , Qi Sixian , Zhong Zhenxing , Zheng Fengyun , Lei Yubin , Tan Yanfeng , Zhu Yuwen , Wang Yu , Wang Yi , Yu Fa-Xing 
Published: August 2023

AbstractWWC1 regulates episodic learning and memory, and genetic nucleotide polymorphism ofWWC1is associated with neurodegenerative diseases such as Alzheimer’s disease. However, the molecular mechanism through which WWC1 regulates neuronal function has not been fully elucidated. Here, we show that WWC1 and its paralogs (WWC2/3) bind directly to angiomotin (AMOT) family proteins (Motins), and recruit USP9X to deubiquitinate and stabilize Motins. Deletion ofWWCgenes in different cell types leads to reduced protein levels of Motins. In mice, neuron-specific deletion ofWwc1andWwc2results in reduced expression of Motins and lower density of dendritic spines in the cortex and hippocampus, in association with impaired cognitive functions such as memory and learning. Interestingly, ectopic expression of AMOT partially rescues the neuronal phenotypes associated withWwc1/2deletion. Thus, WWC proteins modulate spinogenesis and cognition, at least in part, by regulating the protein stability of Motins.
Inhibition of autotaxin alleviates pathological features of hepatic encephalopathy at the level of gut–liver–brain axis: an experimental and bioinformatic study
Authors: Sepehrinezhad Ali , Shahbazi Ali , Joghataei Mohammad Taghi , Larsen Fin Stolze , Sahab Negah Sajad 
Published: August 2023

AbstractThere is accumulating evidence that the circulatory levels of autotaxin (ATX) and lysophosphatidic acid (LPA) are increased in patients with severe liver disease. However, the potential role of the ATX-LPA axis in hepatic encephalopathy (HE) remains unclear. Our study aimed to investigate the role of the ATX-LPA signaling pathway in mice with thioacetamide (TAA) induced acute HE. To show the role of the ATX-LPA axis in the context of HE, we first measured the involvement of ATX-LPA in the pathogenesis of TAA-induced acute HE. Then, we compared the potential effects of ATX inhibitor (HA130) on astrocyte responses at in vitro and gut–liver–brain axis at in vivo levels. The inflammatory chemokine (C–C motif) ligand 3 was significantly increased in the hyperammonemic condition and could be prevented by ATX inhibition in astrocytes at in vitro level. Further statistical tests revealed that plasma and tissue pro-inflammatory cytokines were inhibited by HA130 in mice. Furthermore, the stage of HE was significantly improved by HA130. The most surprising result was that HA130 alleviated immune infiltrating cells in the liver and intestine and decreased mucus-secreting cells in the intestine. Further analysis showed that the levels of liver enzymes in serum were significantly decreased in response to ATX inhibition. Surprisingly, our data indicated that HA130 could recover permeabilization of the blood-brain barrier, neuroinflammation, and recognition memory. Besides that, we found that the changes of Interleukin-1 (IL-1) and aquaporin-4 (AQP4) in HE might have a connection with the glymphatic system based on bioinformatics analyses. Taken together, our data showed that the ATX-LPA axis contributes to the pathogenesis of HE and that inhibition of ATX improves HE.
Polymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation
Authors: Horváth Dániel , Dürvanger Zsolt , K. Menyhárd Dóra , Sulyok-Eiler Máté , Bencs Fruzsina , Gyulai Gergő , Horváth Péter , Taricska Nóra , Perczel András 
Published: August 2023

AbstractA large group of hormones are stored as amyloid fibrils in acidic secretion vesicles before they are released into the bloodstream and readopt their functional state. Here, we identify an evolutionarily conserved hexapeptide sequence as the major aggregation-prone region (APR) of gastrointestinal peptides of the glucagon family: xFxxWL. We determine nine polymorphic crystal structures of the APR segments of glucagon-like peptides 1 and 2, and exendin and its derivatives. We follow amyloid formation by CD, FTIR, ThT assays, and AFM. We propose that the pH-dependent changes of the protonation states of glutamate/aspartate residues of APRs initiate switching between the amyloid and the folded, monomeric forms of the hormones. We find that pH sensitivity diminishes in the absence of acidic gatekeepers and amyloid formation progresses over a broad pH range. Our results highlight the dual role of short aggregation core motifs in reversible amyloid formation and receptor binding.
A genetically encoded sensor for visualizing leukotriene B4 gradients in vivo
Authors: Tamás Szimonetta Xénia , Roux Benoit Thomas , Vámosi Boldizsár , Dehne Fabian Gregor , Török Anna , Fazekas László , Enyedi Balázs 
Published: August 2023

AbstractLeukotriene B4 (LTB4) is a potent lipid chemoattractant driving inflammatory responses during host defense, allergy, autoimmune and metabolic diseases. Gradients of LTB4 orchestrate leukocyte recruitment and swarming to sites of tissue damage and infection. How LTB4 gradients form and spread in live tissues to regulate these processes remains largely elusive due to the lack of suitable tools for monitoring LTB4 levels in vivo. Here, we develop GEM-LTB4, a genetically encoded green fluorescent LTB4 biosensor based on the human G-protein-coupled receptor BLT1. GEM-LTB4 shows high sensitivity, specificity and a robust fluorescence increase in response to LTB4 without affecting downstream signaling pathways. We use GEM-LTB4 to measure ex vivo LTB4 production of murine neutrophils. Transgenic expression of GEM-LTB4 in zebrafish allows the real-time visualization of both exogenously applied and endogenously produced LTB4 gradients. GEM-LTB4 thus serves as a broadly applicable tool for analyzing LTB4 dynamics in various experimental systems and model organisms.
Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis
Authors: Sinner Pia , Peckert-Maier Katrin , Mohammadian Hashem , Kuhnt Christine , Draßner Christina , Panagiotakopoulou Vasiliki , Rauber Simon , Linnerbauer Mathias , Haimon Zhana , Royzman Dmytro , Kronenberg-Versteeg Deborah , Ramming Andreas , Steinkasserer Alexander , Wild Andreas B. 
Published: August 2023

AbstractMicroglial activation during neuroinflammation is crucial for coordinating the immune response against neuronal tissue, and the initial response of microglia determines the severity of neuro-inflammatory diseases. The CD83 molecule has been recently shown to modulate the activation status of dendritic cells and macrophages. Although the expression of CD83 is associated with early microglia activation in various disease settings, its functional relevance for microglial biology has been elusive. Here, we describe a thorough assessment of CD83 regulation in microglia and show that CD83 expression in murine microglia is not only associated with cellular activation but also with pro-resolving functions. Using single-cell RNA-sequencing, we reveal that conditional deletion of CD83 results in an over-activated state during neuroinflammation in the experimental autoimmune encephalomyelitis model. Subsequently, CD83-deficient microglia recruit more pathogenic immune cells to the central nervous system, deteriorating resolving mechanisms and exacerbating the disease. Thus, CD83 in murine microglia orchestrates cellular activation and, consequently, also the resolution of neuroinflammation.
Self-assembly of CIP4 drives actin-mediated asymmetric pit-closing in clathrin-mediated endocytosis
Authors: Yu Yiming , Yoshimura Shige H. 
Published: August 2023

AbstractClathrin-mediated endocytosis is pivotal to signal transduction pathways between the extracellular environment and the intracellular space. Evidence from live-cell imaging and super-resolution microscopy of mammalian cells suggests an asymmetric distribution of actin fibres near the clathrin-coated pit, which induces asymmetric pit-closing rather than radial constriction. However, detailed molecular mechanisms of this ‘asymmetricity’ remain elusive. Herein, we used high-speed atomic force microscopy to demonstrate that CIP4, a multi-domain protein with a classic F-BAR domain and intrinsically disordered regions, is necessary for asymmetric pit-closing. Strong self-assembly of CIP4 via intrinsically disordered regions, together with stereospecific interactions with the curved membrane and actin-regulating proteins, generates a small actin-rich environment near the pit, which deforms the membrane and closes the pit. Our results provide mechanistic insights into how disordered and structured domain collaboration promotes spatio-temporal actin polymerisation near the plasma membrane.
Modulating adsorbed hydrogen drives electrochemical CO2-to-C2 products
Authors: Feng Jiaqi , Zhang Libing , Liu Shoujie , Xu Liang , Ma Xiaodong , Tan Xingxing , Wu Limin , Qian Qingli , Wu Tianbin , Zhang Jianling , Sun Xiaofu , Han Buxing 
Published: August 2023

AbstractElectrocatalytic CO2reduction is a typical reaction involving two reactants (CO2and H2O). However, the role of H2O dissociation, which provides active *H species to multiple protonation steps, is usually overlooked. Herein, we construct a dual-active sites catalyst comprising atomic Cu sites and Cu nanoparticles supported on N-doped carbon matrix. Efficient electrosynthesis of multi-carbon products is achieved with Faradaic efficiency approaching 75.4% with a partial current density of 289.2 mA cm−2at −0.6 V. Experimental and theoretical studies reveal that Cu nanoparticles facilitate the C-C coupling step through *CHO dimerization, while the atomic Cu sites boost H2O dissociation to form *H. The generated *H migrate to Cu nanoparticles and modulate the *H coverage on Cu NPs, and thus promote *CO-to-*CHO. The dual-active sites effect of Cu single-sites and Cu nanoparticles gives rise to the catalytic performance.
Facilitators and barriers to detection and treatment of depression, anxiety and experiences of domestic violence in pregnant women
Authors: Abrahams Zulfa , Boisits Sonet , Schneider Marguerite , Honikman Simone , Lund Crick 
Published: August 2023

AbstractIn South Africa, symptoms of common mental disorders (CMDs) such as depression and anxiety are highly prevalent during the perinatal period and linked to experiences of domestic violence. However, limited routine detection and treatment is available to pregnant women with these problems, even though evidence suggests that screening and treating CMDs during pregnancy improves the health and economic outcomes of mothers and their children, and has been suggested as a key approach to improving the health of perinatal women and children. We investigated facilitators and barriers of service-providers and service-users in detecting and treating pregnant women with symptoms of CMDs and experiences of domestic violence. This study was conducted in four midwife obstetric units (MOUs) in Cape Town, South Africa, and in the non-profit organisations providing community-based support in the communities surrounding the MOUs. Service-provider perspectives were informed by qualitative interviews with 37 healthcare workers providing care to pregnant women. Qualitative interviews with 38 pregnant women attending the same MOUs for their first antenatal care visit provided service-user perspectives. Facilitators identified included the availability of a mental health screening questionnaire and the perceived importance of detection and treatment by both service-providers and -users. Barriers contributing to the low detection rates included service-users concerns about the lack of confidentiality and feelings of shame related to experiences of domestic violence as well as service providers discomfort in dealing with mental health issues, their limited time available and heavy patient load. In addition, service-providers highlighted the lack of standardised referral pathways and the poor uptake of referrals by women with symptoms of depression and anxiety, or experiences of domestic violence. While the system-level barriers need to be addressed at a policy level, the patient- and provider-level barriers identified indicate the need to strengthen health systems by training antenatal care nurses to detect symptoms of CMDs and experiences of domestic violence in pregnant women, developing standardised referral pathways and training lay healthcare workers to provide treatment for mild symptoms of depression and anxiety.
Drosophila innate immunity suppresses the survival of xenografted mammalian tumor cells
Authors: Aida Ayaka , Yuswan Kevin , Kawai Yoichi , Hasegawa Keita , Nakajima Yu-ichiro , Kuranaga Erina 
Published: July 2023

AbstractPatient-derived xenograft (PDX) is an emerging tool established in immunodeficient vertebrate models to assess individualized treatments for cancer patients. Current xenograft models are deficient in adaptive immune systems. However, the precise role of the innate immunity in the xenograft models is unknown. With conserved signaling pathways and established genetic tools, Drosophila has contributed to the understanding of the mechanism of tumor growth as well as tumor–host interactions for decades, making it a promising candidate model for studying whether or not the hosts’ innate immunity can accommodate transplanted human tumor cells. Here we show initial observations that assess the behavior and impact of several human tumor cell lines when transplanted into Drosophila. We found that some injected cell lines persisted for a longer duration and reduced hosts’ lifespan. In particular, the human lung cancer cell line A549 were observed adjacent to the fly host tissues. We examined two factors that affect the survivability of cancer cells: (1) the optimal temperature of each cell line and (2) the innate immunity of Drosophila hosts. Especially, transplanted human tumor cells survived longer in immunodeficient flies, suggesting that the host innate immune system impedes the growth of xenografted cells. Our attempts for xenografting fly models thus provide necessary steps to overcome for establishing PDX cancer models using invertebrates.
Altered functional connectivity and network excitability in a model of cortical dysplasia
Authors: Aquiles A. , Fiordelisio T. , Luna-Munguia H. , Concha L. 
Published: July 2023

AbstractFocal cortical dysplasias (FCDs) are malformations of cortical development that often result in medically refractory epilepsy, with a greater incidence in the pediatric population. The relationship between the disturbed cortical morphology and epileptogenic activity of FCDs remains unclear. We used the BCNU (carmustine 1-3-bis-chloroethyl-nitrosourea) animal model of cortical dysplasia to evaluate neuronal and laminar alterations and how these result in altered activity of intracortical networks in early life. We corroborated the previously reported morphological anomalies characteristic of the BCNU model, comprising slightly larger and rounder neurons and abnormal cortical lamination. Next, the neuronal activity of live cortical slices was evaluated through large field-of-view calcium imaging as well as the neuronal response to a stimulus that leads to cortical hyperexcitability (pilocarpine). Examination of the joint activity of neuronal calcium time series allowed us to identify intracortical communication patterns and their response to pilocarpine. The baseline power density distribution of neurons in the cortex of BCNU-treated animals was different from that of control animals, with the former showing no modulation after stimulus. Moreover, the intracortical communication pattern differed between the two groups, with cortexes from BCNU-treated animals displaying decreased inter-layer connectivity as compared to control animals. Our results indicate that the altered anatomical organization of the cortex of BCNU-treated rats translates into altered functional networks that respond abnormally to a hyperexcitable stimulus and highlight the role of network dysfunction in the pathophysiology of cortical dysplasia.
Improved reverse Monte Carlo analysis of optical property of Fe and Ni from reflection electron energy loss spectroscopy spectra
Authors: Li Z. , Gong J. M. , Da B. , Tóth J. , Tőkési K. , Zeng R. G. , Ding Z. J. 
Published: August 2023

AbstractThe energy loss functions (ELFs) of Fe and Ni have been derived from measured reflection electron energy loss spectroscopy (REELS) spectra by a reverse Monte Carlo analysis in our previous work. In this work, we present further improvements of ELFs for these metals. For Fe, we have updated ELFs at primary electron energies of 2 keV and 3 keV in a wider photon energy region (0–180 eV) with a better accuracy, which is verified by sum rules. Regarding to Ni, we supplement the ELF at primary energy of 5 keV and we also improve the data accuracy at 3 keV. Applying these new and more accurate ELFs we present the optical constants and dielectric functions for the two metals. The improvements were highlighted by comparing our present results with the previous data.
The plasma metabolome of long COVID patients two years after infection
Authors: López-Hernández Yamilé , Monárrez-Espino Joel , López David Alejandro García , Zheng Jiamin , Borrego Juan Carlos , Torres-Calzada Claudia , Elizalde-Díaz José Pedro , Mandal Rupasri , Berjanskii Mark , Martínez-Martínez Eduardo , López Jesús Adrián , Wishart David S. 
Published: August 2023

AbstractOne of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as “long COVID”) which has emerged as a consequence of the SARS-CoV-2 epidemic. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. In this study, our goal was to assess the plasma metabolome in a total of 100 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC–MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin were measured in long COVID patients by immunoenzymatic assay. The comparison of paired COVID-19/long COVID-19 samples revealed 53 metabolites that were statistically different. Compared to controls, 27 metabolites remained dysregulated even after two years. Post-COVID-19 patients displayed a heterogeneous metabolic profile. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients. Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection.
Spatial and spectral characteristics in realizations of broadband terahertz spectroscopy on a subwavelength scale
Authors: Guidi Alexis N. , Mitchell Michael E. , Holzman Jonathan F. 
Published: July 2023

AbstractIn this work, we take aim at the fundamental challenge for realizations of broadband terahertz (THz) spectroscopy on a subwavelength scale. We introduce apertured THz microjets in this effort to resolve the fundamental limits of spatial resolution and spectral bandwidth. The THz microjets are formed as intense foci at the rear of engineered (microcomposite) spheres and are coupled through subwavelength (circular) apertures. Such coupling enables effective transmission of THz power through samples with broad spectral bandwidths and fine spatial resolutions. We show that the apertures function as high-pass filters, with their diameter d enabling strong transmission above a cutoff frequency fc. Our theoretical and experimental results reveal that the values for d and fc are prescribed by a fixed spatial-spectral product dfc, whereby reductions in d (to improve the spatial resolution) can raise fc into the targeted spectrum (at the expense of spectral bandwidth). We use this understanding to demonstrate broadband (0.3–0.7 THz) THz spectroscopy of lactose at the subwavelength (365 µm) scale. These results for apertured THz microjets represent a 20-fold improvement in spatial resolution over analogous apertured THz plane waves. Overall, our findings show promise for studies of carcinogenesis, pathogenesis, and the like.
Comparative chloroplast genomics and insights into the molecular evolution of Tanaecium (Bignonieae, Bignoniaceae)
Authors: Frazão Annelise , Thode Verônica A. , Lohmann Lúcia G. 
Published: August 2023

AbstractSpecies of Tanaecium (Bignonieae, Bignoniaceae) are lianas distributed in the Neotropics and centered in the Amazon. Members of the genus exhibit exceptionally diverse flower morphology and pollination systems. Here, we sequenced, assembled, and annotated 12 complete and four partial chloroplast genomes representing 15 Tanaecium species and more than 70% of the known diversity in the genus. Gene content and order were similar in all species of Tanaecium studied, with genome sizes ranging between 158,470 and 160,935 bp. Tanaecium chloroplast genomes have 137 genes, including 80–81 protein-coding genes, 37 tRNA genes, and four rRNA genes. No rearrangements were found in Tanaecium plastomes, but two different patterns of boundaries between regions were recovered. Tanaecium plastomes show nucleotide variability, although only rpoA was hypervariable. Multiple SSRs and repeat regions were detected, and eight genes were found to have signatures of positive selection. Phylogeny reconstruction using 15 Tanaecium plastomes resulted in a strongly supported topology, elucidating several relationships not recovered previously and bringing new insights into the evolution of the genus.
Influence of rutin and its combination with metformin on vascular functions in type 1 diabetes
Authors: David Sheba R. , Lai Penny Pei Ni , Chellian Jestin , Chakravarthi Srikumar , Rajabalaya Rajan 
Published: August 2023

AbstractThe present work examined the effect of oral administration of rutin and its combination with metformin, an antidiabetic drug on blood glucose, total cholesterol and triglycerides level and vascular function in streptozotocin (STZ) -induced diabetic rats. Male Sprague Dawley rats were rendered diabetic by a single intraperitoneal injection of STZ (50 mg/kg). Rutin and metformin were orally administered to diabetic rats at a dose of 100 mg/kg and 300 mg/kg body weight/day, respectively, for 4 weeks. Plasma analysis was conducted to determine changes in the plasma glucose and lipid levels. Rat aortic ring reactivity in response to endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) relaxants, and to the α1-adrenergic agonist phenylephrine (PE) were recorded. Histology of pancreas, liver and kidney were evaluated. In results, rutin and metformin alone and in combination has led to significant improvements in blood glucose, cholesterol and triglyceride levels compared to diabetic group. Diabetic aortic rings showed significantly greater contraction in response to PE, and less relaxation in response to ACh and SNP. Treatment with rutin and metformin in combination significantly reduced PE-induced contraction and increased ACh-induced and SNP-induced relaxation in diabetes when compared to rutin or metformin alone. Significant histological improvements were seen with combination therapy. In conclusion, rutin and metformin combination therapy has the most potentiality for restoring blood glucose and lipid level as well as vascular function.