bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site effects depth denoising and signal enhancement using dual-projection based ICA model
Authors: Hao Yuxing , Xu Huashuai , Xia Mingrui , Yan Chenwei , Zhang Yunge , Zhou Dongyue , Kärkkäinen Tommi , Nickerson Lisa D. , Li Huanjie , Cong Fengyu 
Published: April 2023

AbstractCombining magnetic resonance imaging (MRI) data from multi-site studies is a popular approach for constructing larger datasets to greatly enhance the reliability and reproducibility of neuroscience research. However, the scanner/site variability is a significant confound that complicates the interpretation of the results, so effective and complete removal of the scanner/site variability is necessary to realize the full advantages of pooling multi-site datasets. Independent component analysis (ICA) and general linear model (GLM) based denoising methods are the two primary methods used to denoise scanner/site-related effects. Unfortunately, there are challenges with both ICA-based and GLM-based denoising methods to remove site effects completely when the signals of interest and scanner/site-related noises are correlated, which may occur in neuroscience studies. In this study, we propose an effective and powerful denoising strategy that implements dual-projection (DP) theory based on ICA to remove the scanner/site-related effects more completely. This method can separate the signal effects correlated with noise variables from the identified noise effects for removal without losing signals of interest. Both simulations and vivo structural MRI datasets, including a dataset from Autism Brain Imaging Data Exchange II and a traveling subject dataset from the Strategic Research Program for Brain Sciences, were used to test the proposed GLM- and ICA-based denoising methods and our DP-based ICA denoising method. Results show that DP-based ICA
Hyper-Cryptic Radiation of a Tropical Montane Plant Lineage
Authors: Olivares Ingrid , Tusso Sergio , SanÍn MarÍa JosÉ , Kessler Michael , Shimizu Kentaro K. 
Published: April 2023

ABSTRACTSpecies are seen as the fundamental unit of biotic diversity, and thus their delimitation is crucial for defining measures for diversity assessments and studying evolution. Differences between species have traditionally been associated with variation in morphology. And yet, the discovery of cryptic diversity suggests that the evolution of distinct lineages does not necessarily involve trait differences. Here, we analyze 1,684,987 variant sites and over 4000 genes for more than 400 samples to show how a tropical montane plant lineage (Geonoma undataspecies complex) is composed of numerous unrecognized genetic groups that are not morphologically distinct. We find that 11 to 14 clades do not correspond to the three currently recognized species. Most clades are genetically independent and geographic distance and topography are the most important factors determining this genetic divergence. This lineage does not match the model of an adaptive radiation, but instead, constitutes the first example of a hyper-cryptic plant radiation in tropical mountains.
Mtfp1ablation enhances mitochondrial respiration and protects against hepatic steatosis
Authors: Patitucci Cecilia , Hernández-Camacho Juan Diego , Vimont Elodie , Cokelaer Thomas , Chaze Thibault , Giai Gianetto Quentin , Matondo Mariette , Gazi Anastasia , Nemazanyy Ivan , Stroud David A. , Hock Daniella H. , Donnarumma Erminia , Wai Timothy 
Published: April 2023

AbstractHepatic steatosis is the result of an imbalance between nutrient delivery and metabolism in the liver. It is the first hallmark of Non-alcoholic fatty liver disease (NAFLD) and is characterized by the accumulation of excess lipids in the liver that can drive liver failure, inflammation, and cancer. Mitochondria control the fate and function of cells and compelling evidence implicates these multifunctional organelles in the appearance and progression of liver dysfunction, although it remains to be elucidated which specific mitochondrial functions are actually causally linked to NAFLD. Here, we identified Mitochondrial Fission Process 1 protein (MTFP1) as a key regulator of mitochondrial and metabolic activity in the liver. Deletion ofMtfp1in hepatocytes is physiologically benign in mice yet leads to the upregulation of oxidative phosphorylation (OXPHOS) activity and mitochondrial respiration, independently of mitochondrial biogenesis. Consequently, hepatocyte-specific knockout mice are protected against high fat diet-induced hepatic steatosis and metabolic dysregulation. Additionally, we find that deletion ofMtfp1in liver mitochondria inhibits mitochondrial permeability transition pore opening in hepatocytes, conferring protection against apoptotic liver damage in vivo and ex vivo. Our work uncovers novel functions of MTFP1 in the liver, positioning this gene as an unexpected regulator of OXPHOS and a therapeutic candidate for NAFLD.
Mechanism of ozone alleviation of malignant ascites in hepatocellular carcinoma through inhibition of NETs
Authors: Han Feng , Guo Jiayou , Mu Mingchen , Bian Ka , Cui Zhenting , Duan Qiong , Ma Jianxin , Jin Lai , Liu Wentao , Chen Fanghong 
Published: April 2023

AbstractMalignant ascites in hepatocellular carcinoma is usually a sign of advanced disease and poor prognosis and is also thought to be associated with chronic inflammation mediated by neutrophil extracellular trap networks (NETs). Whereas ozone, a strong oxidant, has significant antibacterial and anti-inflammatory effects, its effectiveness in treating malignant liver ascites is unclear.cOzone showed significant anti-peritoneal fluid production properties in H22 tumor-bearing mice, and ozone reduced peritoneal fluid production by activating AMPK and up-regulating SR-A phagocytosis damage-associated molecular patterns (DAMPs) to reduce the production of NETs. This suggests that ozone could be used as a new drug for the treatment of malignant ascites in hepatocellular carcinoma.
Network inference from temporal phosphoproteomics informed by protein-protein interactions
Authors: Plank Michael 
Published: April 2023

AbstractNetwork inference from time-course data holds the promise to overcome challenges associated with other methods for deciphering cell signaling networks. Integration of protein-protein interactions in this process is frequently employed to limit wiring options.In this study, a graph approach for the analysis of data of high temporal resolution is introduced and applied to a 5 s resolution phosphoproteomics dataset. Steiner trees informed by protein-protein interactions are constructed on individual time slices, which are then stitched together into a temporal signaling network.Systematic benchmarking against existing knowledge indicates that the approach enriches signaling-relevant edges. The workflow is compatible with future extensions for reliably extracting extended signaling paths.
Computational Insight into Anti-Obesity Effects of Combined Some Phytobiotics to GLP1R (Glucagon-Like Peptide 1 Receptor) Protein inAnas javanica
Authors: Damayanti CA , Harahap MAY , Wibowo S , Sjofjan O , Djunaidi IH 
Published: April 2023

ABSTRACTDamayanti CA, Harahap MAY, Wibowo S, Sjofjan O, Djunaidi IH. 2023. Computational Insight into Anti-Obesity Effects of Indonesian Phytobiotics to GLP1R (Glucagon-Like Peptide 1 Receptor) Protein inAnas javanica.Mojosari ducks (Anas javanica) is native Indonesia laying ducks was a egg producing type with quite high egg production, must be maintain body weight to propotional condition as laying duck. If the body weight surpasses normal, it can lead to obesity and reduce the eggs quality. One of the proteins closely related to obesity and hyperglycemia is GLP1R (Glucagon-Like Peptide 1 Receptor). The increase in GLP1R activity by one of the compounds that have been widely researched is loureirin B. Interaction between loureirin B and GLP1R increases insulin production in the body so that hyperglycemia and body weight can be controlled properly. Exploration of phytobiotic compounds from Indonesia is needed to find the substitution of loureirin B as an anti-obesity agent. According to the findings of in silico study (protein modeling and molecular docking), cynaroside (−9.2 kcal/mol), 14-Deoxy-11,12-didehydroandrographolide (−9.1 kcal/mol), rutin (−8.8 kcal/mol), andrographidine E (−8.6 kcal/mol), and cianidanol (−7.8 kcal/mol) had stronger binding affinity than loureirin B (−7.4 kcal/mol). Andrographidine E, derived from the plantAndrographis paniculata, is the best candidate for GLP1R agonist. The binding affinity that Andrographidine E has is lower than control compounds, so it is easier for bonds to occur between proteins and such compounds. In addition, the interacting amino acids do not have unfavourable bonds that make it more stable than other candidates. Results from clinical studies show that the use ofA. paniculatacan reduce glucose levels.
Voluntary muscle activation in people with Multiple Sclerosis is reduced across a wide range of forces following maximal effort fatiguing contractions
Authors: Brotherton Emily J. , Sabapathy Surendran , Heshmat Saman , Kavanagh Justin J. 
Published: April 2023

ABSTRACTPeople with Multiple Sclerosis typically exhibit greater levels of exercise-induced fatigue compared to healthy individuals. However, it is unknown if voluntary muscle activation is affected over a range of contraction forces in people with MS who have exercise-induced fatigue. The purpose of this study was to use transcranial magnetic stimulation (TMS) and electrical muscle stimulation to examine muscle activation during exercise-induced fatigue. Ten people with relapsing-remitting MS (39 ± 7 years) and 10 healthy controls (40 ± 5 years) performed elbow flexions at 25%, 50%, 75%, 90%, and 100% MVC while electromyography (EMG) of the biceps brachii was recorded. Sustained elbow flexion MVCs were then performed until force declined to 60% of baseline MVC, and the target contraction intensities of 25%, 50%, 75%, 90%, and 100% MVC were examined again. The Fatigue Severity Scale was higher for the MS group (P< 0.01). Exercise-induced fatigue caused a reduction in biceps EMG amplitude for the MS group across all contraction intensities (P< 0.01), which was not aligned with changes in MEP amplitude (P= 0.25). Exercise-induced fatigue reduced motor cortical voluntary activation in the MS group across all contraction intensities (P< 0.01), as well as increased MS time-to-peak force (P <0.01) and half relaxation time for TMS evoked twitches (P= 0.03). These findings provide evidence that MS-related fatigability during maximal contractions is due to the inability for the motor cortex to drive the muscle, with possible contributions from altered contractile properties in the MS muscle.NEW & NOTEWORTHYWe use transcranial magnetic stimulation to demonstrate that people with relapsing-remitting Multiple Sclerosis (MS) have a reduced ability to activate muscle following maximal effort fatiguing contractions. Although our MS participants reported greater symptoms of fatigue via the Fatigue Severity Scale, their reduced ability to activate muscle was more associated with the duration of disease.
Similar but distinct: the impact of biomechanical forces and culture age on the production, cargo loading, and biological efficacy of human megakaryocytic extracellular vesicles for applications in cell and gene therapies
Authors: Thompson Will , Papoutsakis Eleftherios Terry 
Published: April 2023

AbstractMegakaryocytic extracellular vesicles (MkEVs) promote the growth and megakaryopoiesis of hematopoietic stem and progenitor cells (HSPCs) largely through endogenous miR-486-5p and miR-22-3p cargo. Here, we examine the impact of biomechanical force and culture age/differentiation on the formation, properties, and biological efficacy of MkEVs. We applied biomechanical force to Mks using two methods: shake flask cultures and a syringe pump system. Force increased MkEV production in a magnitude-dependent manner, with similar trends emerging regardless of whether flow cytometry or nanoparticle tracking analysis (NTA) was used for MkEV counting. Both methods produced MkEVs that were relatively depleted of miR-486-5p and miR-22-3p cargo. However, while the shake flask-derived MkEVs were correspondingly less effective in promoting megakaryocytic differentiation of HSPCs, the syringe pump-derived MkEVs were more effective in doing so, suggesting the presence of unique, unidentified miRNA cargo components. Higher numbers of MkEVs were also produced by “older” Mk cultures, though miRNA cargo levels and MkEV bioactivity were unaffected by culture age. A reduction in MkEV production by Mks derived from late-differentiating HSPCs was also noted. Taken together, our results demonstrate that biomechanical force has an underappreciated and deeply influential role in MkEV biology, though that role may vary significantly depending on the nature of the force. Given the ubiquity of biomechanical force in vivo and in biomanufacturing, this phenomenon must be grappled with before MkEVs can attain clinical relevance.Abstract Figure
Exploration of T-cell immune responses by expression of a dominant-negative SHP1 and SHP2
Authors: Taylor Julia , Bulek Anna , Gannon Isaac , Robson Mathew , Kokalaki Evangelia , Grothier Thomas , McKenzie Callum , El-Kholy Mohamed , Stavrou Maria , Traynor-White Charlotte , Lim Wen-Chean , Panagiotou Panagiota , Srivastava Saket , Baldan Vania , Silibourne James , Ferrari Mathieu , Pule Martin , Thomas Simon 
Published: April 2023

AbstractSHP1 and SHP2 are SH2 domain-containing proteins which have inhibitory phosphatase activity when recruited to phosphorylated ITIMs and ITSMs on inhibitory immune receptors. Consequently, SHP1 and SHP2 are key proteins in the transmission of inhibitory signals within T cells, constituting an important point of convergence for diverse inhibitory receptors. Therefore, SHP1 and SHP2 inhibition may represent a strategy for preventing immunosuppression of T cells mediated by cancers hence improving immunotherapies directed against these malignancies. Both SHP1 and SHP2 contain dual SH2 domains responsible for localization to the endodomain of inhibitory receptors and a protein tyrosine phosphatase domain which dephosphorylates and thus inhibits key mediators of T cell activation. We explored the interaction of the isolated SH2 domains of SHP1 and SHP2 to inhibitory motifs from PD1 and identified strong binding of both SH2 domains from SHP2 and more moderate binding in the case of SHP1. We next explored whether these a truncated form of SHP1/2 comprising only of SH2 domains (dSHP1/2) could act in a dominant negative fashion by preventing docking of the wild type proteins. When co-expressed with CARs we found that dSHP2 but not dSHP1 could alleviate immunosuppression mediated by PD1. We next explored the capacity of dSHP2 to bind with other inhibitory receptors and observed several potential interactions. In vivo we observed that the expression of PDL1 on tumor cells impaired the ability of CAR T cells to mediate tumor rejection and this effect was partially reversed by the co-expression of dSHP2 albeit at the cost of reduced CAR T cell proliferation. Modulation of SHP1 and SHP2 activity in engineered T cells through the expression of these truncated variants may enhance T cell activity and hence efficacy in the context of cancer immunotherapy.
The neurovascular unit of capillary blood vessels in the rat nervous system. A rapid-Golgi electron microscopic study
Authors: Larriva-Sahd Jorge , Martínez-Cabrera Gema , Lozano-Flores Carlos , Concha Luis , Varela-Echavarría Alfredo 
Published: April 2023

AbstractWe describe a pericapillary organ in the rat forebrain and cerebellar cortex. It consists of series of tripartite synapses enveloped by astrocytic endfeet linked to the capillary wall by synaptic extensions. Reciprocal specializations of the pericyte-capillary blood vessel with such specialized synapses suggests a mechanoreceptor role. In Golgi impregnated and 3D reconstructions of cerebral cortex and thalamus, series of tripartite synapses appear sequentially ordered in a tributary dendrite paralleled by synaptic outgrowths termed here golf club-like extensions apposed to a longitudinal crest from the capillary basal lamina. To facilitate identification of principal cell dendrites and arriving axons to these putative mechanosensory structures, we utilized the cerebellar cortex since it has a well known organization and observed that afferent fibers and interneurons display interactions with the capillary wall. Afferent mossy fiber rosettes and ascending granule cell axons and dendrites define pericapillary on passage interactions surrounded by endfeet. The ability of such structures to modulate synaptic transmission is supported by the presence of mRNA of the mechanosensitive channel Piezo 1 in the mossy fiber rosettes, pyramidal isocortical and thalamic neurons. This suggests that ascending impulses to the cerebellar and cortical targets are presynaptically modulated by the reciprocal interaction with the mechanosensory pericapillary organ.
Honey bees (Apis mellifera) decrease the fitness of plants they pollinate
Authors: Travis Dillon J. , Kohn Joshua R. 
Published: April 2023

AbstractMost flowering plants require animal pollination and are visited by multiple pollinator species. Historically, the effects of pollinators on plant fitness have been compared using the number of pollen grains they deposit, and the number of seeds or fruits produced following a visit to a virgin flower. While useful, these methods fail to consider differences in pollen quality and the fitness of zygotes resulting from pollination by different floral visitors. Here we show that, for three common native self-compatible plants in Southern California, super-abundant, non-native honey bees (Apis melliferaL.) visit more flowers on an individual before moving to the next plant compared to the suite of native insect visitors. This likely increases the transfer of self-pollen. Offspring produced after honey bee pollination have similar fitness to those resulting from hand self-pollination and both are far less fit than those produced after pollination by native insects or by cross-pollination. Because honey bees often forage methodically, visiting many flowers on each plant, low offspring fitness may commonly result from honey bee pollination of self-compatible plants. To our knowledge, this is the first study to directly compare the fitness of offspring resulting from honey bee pollination to that of other floral visitors.
A mannitol-based buffer improves single-cell RNA sequencing of high-salt marine cells
Authors: Scully Tal , Klein Allon 
Published: April 2023

AbstractSingle-cell RNA sequencing (scRNA-seq) enables discovery of novel cell states by transcriptomic profiling with minimal prior knowledge, making it useful for studying non-model organisms. For most marine organisms, however, cells are viable at a higher salinity than is compatible with scRNA-seq, impacting data quality and cell representation. We show that a low-salinity phosphate buffer supplemented with D-mannitol (PBS-M) enables higher-quality scRNA-seq of blood cells from the tunicateCiona robusta. Using PBS-M reduces cell death and ambient mRNA, revealing cell states not otherwise detected. This simple protocol modification could enable or improve scRNA-seq for the majority of marine organisms.
Differentiation between Descending Thoracic Aortic Diseases using Machine Learning and Plasma Proteomic Signatures
Authors: Momenzadeh Amanda , Kreimer Simion , Guo Dongchuan , Ayres Matthew , Berman Daniel , Chyu Kuang-Yuh , Shah Prediman K , Milewicz Dianna , Azizzadeh Ali , Meyer Jesse G. , Parker Sarah 
Published: April 2023

AbstractBackgroundDescending thoracic aortic aneurysms and dissections can go undetected until severe and catastrophic, and few clinical indices exist to screen for aneurysms or predict risk of dissection.MethodsThis study generated a plasma proteomic dataset from 75 patients with descending type B dissection (Type B) and 62 patients with descending thoracic aortic aneurysm (DTAA). Standard statistical approaches were compared to supervised machine learning (ML) algorithms to distinguish Type B from DTAA cases. Quantitatively similar proteins were clustered based on linkage distance from hierarchical clustering and ML models were trained with uncorrelated protein lists across various linkage distances with hyperparameter optimization using 5-fold cross validation. Permutation importance (PI) was used for ranking the most important predictor proteins of ML classification between disease states and the proteins among the top 10 PI protein groups were submitted for pathway analysis.ResultsOf the 1,549 peptides and 198 proteins used in this study, no peptides and only one protein, hemopexin (HPX), were significantly different at an adjusted p-value <0.01 between Type B and DTAA cases. The highest performing model on the training set (Support Vector Classifier) and its corresponding linkage distance (0.5) were used for evaluation of the test set, yielding a precision-recall area under the curve of 0.7 to classify between Type B from DTAA cases. The five proteins with the highest PI scores were immunoglobulin heavy variable 6-1 (IGHV6-1), lecithin-cholesterol acyltransferase (LCAT), coagulation factor 12 (F12), HPX, and immunoglobulin heavy variable 4-4 (IGHV4-4). All proteins from the top 10 most important correlated groups generated the following significantly enriched pathways in the plasma of Type B versus DTAA patients: complement activation, humoral immune response, and blood coagulation.ConclusionsWe conclude that ML may be useful in differentiating the plasma proteome of highly similar disease states that would otherwise not be distinguishable using statistics, and, in such cases, ML may enable prioritizing important proteins for model prediction.
Novel discovery of a lymphatic bridge connecting Schlemm’s canal to limbal and conjunctival lymphatic pathway
Authors: Yang Yujia , Shi Meng , Li Guangyu , Shen Lejun , Chen Lu 
Published: April 2023

AbstractPurposeSchlemm’s canal (SC) is a critical structure regulating aqueous humor (AH) drainage and intraocular pressure (IOP). It is known that in the conventional outflow pathway, AH flows from SC to episcleral veins. We recently reported a high-resolution three-dimensional (3D) imaging technology for intact eyeballs, SC and ocular surface. Using this advanced technology, we herein report the discovery of a new structure, termed lymphatic bridge, that directly connects SC to the limbal and conjunctival lymphatic pathway. Further investigation on this novel outflow pathway may provide new mechanisms and therapeutic approaches for glaucoma.MethodsAs reported previously, intact eyeballs were harvested from Prox-1-GFP (green fluorescent protein) mice and processed by a tissue clearing technique with CLARITY. Samples were immunolabeled with specific antibodies for CD31 (pan-endothelial marker) and LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1) and imaged by light-sheet fluorescent microscopy. The limbal areas were examined to locate connecting channels between SC and limbal and conjunctival lymphatic vessels. Moreover, in vivo anterior chamber dye injection was performed with Texas Red dextran for functional analysis on AH outflow.ResultsA novel lymphatic bridge structure that expressed both Prox-1 and LYVE-1 was discovered between the SC and limbal lymphatic vessels connected with conjunctival lymphatic pathway. Results from the anterior chamber dye injection showed AH drainage into the conjunctival lymphatic outflow pathway.ConclusionsThis study provides the first evidence on the direct connection between SC and limbal and conjunctival lymphatic pathway. This new pathway is distinctive from the conventional episcleral vein pathway and merits further investigation.