bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinopyroxenite Xenoliths Record Magma Transport and Crystallization in the Middle and Upper Crust: A Case Study from the Rockeskyllerkopf Volcanic Complex, West Eifel, Germany
Authors: Shaw Cliff S J 
Published: March 2024

Abstract
Clinopyroxenite xenoliths comprising cumulus clinopyroxene ± amphibole together with intercumulus phlogopite ± olivine ± apatite ± titanite form a large part of the xenolith load in the oldest deposits of the Rockeskyllerkopf Volcanic Complex (RVC) in the West Eifel volcanic field. The xenoliths also contain xenocrysts of olivine and clinopyroxene derived from mantle peridotite and clinopyroxene from lower crustal granulite. The clinopyroxenite xenoliths are divided into five groups on the basis of their modal mineralogy and mineral compositions. Groups 1 to 4 define a continuous compositional trend indicative of fractionation of a mafic alkaline magma. Group 5 xenoliths are compositionally distinct and have been tentatively linked to high pressure crystallization of phonolitic magma within the RVC system. Thermobarometry of the group 1 to 4 xenoliths indicates that they crystallized between 1 and 4 kilobars, equivalent to a depth of 4 to 14 km. Group 1 to 3 xenoliths all crystallized at between 1050°C and 1150°C, whereas the amphibole-rich group 4 xenoliths give temperature estimates of ~900°C. The clinopyroxenites share a common parent magma with clinopyroxene–phlogopite veins found in subcontinental lithospheric mantle xenoliths. However, the vein forming mama was richer in incompatible elements, in particular Zr and Hf and is interpreted to be an early formed batch of magma with the clinopyroxenites crystallizing from magma derived from the same mantle, which had been depleted by the earlier phase of melting. Intrusion of magma began around 155 ky prior to the eruption of the RVC. Fe–Mg interdiffusion profiles in zoned clinopyroxene show that the magma that formed the xenoliths was present in the crust for up to 28 ky prior to the eruption. However, most samples give interdiffusion times between 1.5 and 9.9 ky. Based on xenocryst residence times and the calculated P–T conditions for clinopyroxene, there were at least seven separate batches of magma emplaced below Rockeskyllerkopf, probably as sills.
Machine Learning in Petrology: State-of-the-Art and Future Perspectives
Authors: Petrelli Maurizio 
Published: March 2024

Abstract
This article reports on the state-of-the-art and future perspectives of machine learning (ML) in petrology. To achieve this goal, it first introduces the basics of ML, including definitions, core concepts, and applications. Then, it starts reviewing the state-of-the-art of ML in petrology. Established applications mainly concern the so-called data-driven discovery and involve specific tasks like clustering, dimensionality reduction, classification, and regression. Among them, clustering and dimensionality reduction have been demonstrated to be valuable for decoding the chemical record stored in igneous and metamorphic phases and to enhance data visualization, respectively. Classification and regression tasks find applications, for example, in petrotectonic discrimination and geo-thermobarometry, respectively. The main core of the manuscript consists of depicting emerging trends and the future directions of ML in petrological investigations. I propose a future scenario where ML methods will progressively integrate and support established petrological methods in automating time-consuming and repetitive tasks, improving current models, and boosting discovery. In this framework, promising applications include (1) the acquisition of new multimodal petrologic data; (2) the development of data fusion techniques, physics-informed ML models, and ML-supported numerical simulations; and (3) the continuous exploration of the ML potential in petrology. To boost the contribution of ML in petrology, our main challenges are: (1) to improve the ability of ML models to capture the complexity of petrologic processes, (2) progressively link ML algorithms with the physical and thermodynamic nature of the investigated problems, and (3) to start a collaborative effort among researchers coming from different disciplines, both in research and teaching.
Histopathological comparison of Sjögren-related features between paired labial and parotid salivary gland biopsies of sicca patients
Authors: Nakshbandi Uzma , van Ginkel Martha S , Verstappen Gwenny M P J , Spijkervet Fred K L , Arends Suzanne , Haacke Erlin A , Liefers Silvia C , Vissink Arjan , Bootsma Hendrika , Kroese Frans G M , van der Vegt Bert 
Published: March 2024

Abstract

Objectives
To compare focus score and other histopathological features between paired labial and parotid salivary gland biopsies in a diagnostic cohort of suspected Sjögren’s disease (SjD) patients.

Methods
Labial and parotid salivary gland biopsies were simultaneously obtained from patients with sicca complaints, suspected of having SjD. Biopsies were formalin fixed and paraffin embedded. Sections were stained with haematoxylin & eosin, and for CD3, CD20, CD45, cytokeratin, CD21, Bcl6, activation-induced deaminase (AID) and IgA/IgG. Focus score and other histopathological features characteristic for SjD were analysed.

Results
Based on the expert opinion of three experienced rheumatologists, 36 patients were diagnosed as SjD and 63 as non-SjD sicca patients. When taking all patients together, absolute agreement of various histopathological features between labial and parotid biopsies was high and varied between 80% (focus score) and 93% [(pre-)lymphoepithelial lesions (LELs)]. More labial gland biopsies had a focus score ≥1 compared with their parotid counterpart. Accordingly, the area of infiltrate was larger in labial gland biopsies. When considering only SjD patients, labial glands contained significantly fewer B-lymphocytes and germinal centres/mm2, and less severe LELs compared with parotid glands.

Conclusion
Labial and parotid glands from SjD patients contain similar histopathological key features, and thus both glands can be used for diagnosis and classification of SjD. However, parotid salivary glands reveal more evident B-lymphocyte-related features, while labial glands exhibit more inflammation, which may be partially unrelated to SjD.
Sulforaphane Improves Redox Homeostasis and Right Ventricular Contractility in a Model of Pulmonary Hypertension
Authors: Conzatti Adriana , Colombo Rafael , Siqueira Rafaela , Campos-Carraro Cristina , Turck Patrick , Luz de Castro Alexandre , Belló-Klein Adriane , Sander da Rosa Araujo Alex 
Published: March 2024

Abstract:
Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance (PVR), imposing overload on the right ventricle (RV) and imbalance of the redox state. Our study investigated the influence of treatment with sulforaphane (SFN), found in cruciferous vegetables, on RV remodeling and redox homeostasis in monocrotaline (MCT)-induced PAH. Male Wistar rats were separated into 4 groups: control (CTR); CTR + SFN; MCT; and MCT + SFN. PAH induction was implemented by a single dose of MCT (60 mg/kg intraperitoneally). Treatment with SFN (2.5 mg/kg/day intraperitoneally) started on the seventh day after the MCT injection and persisted for 2 weeks. After 21 days of PAH induction, echocardiographic, hemodynamic, and oxidative stress evaluation was performed. The MCT group showed an increase in RV hypertrophy, RV systolic area, RV systolic, mean pulmonary artery pressure, and PVR and exhibited a decrease in the RV outflow tract acceleration time/ejection time ratio, RV fractional shortening, and tricuspid annular plane systolic excursion compared to CTR (P < 0.05). SFN-treated PAH attenuated detrimental changes in tricuspid annular plane systolic excursion, mean pulmonary artery pressure, and PVR parameters. Catalase levels and the glutathione/Glutathione disulfide (GSSG) ratio were diminished in the MCT group compared to CTR (P < 0.05). SFN increased catalase levels and normalized the glutathione/GSSG ratio to control levels (P < 0.05). Data express the benefit of SFN treatment on the cardiac function of rats with PAH associated with the cellular redox state.
MURAMYL DIPEPTIDE CAUSES MITOCHONDRIAL DYSFUNCTION AND INTESTINAL INFLAMMATORY CYTOKINE RESPONSES IN RATS
Authors: Zhao Lu-Jia , Dai Xiao-Yong , Ye You-Wen , Pang Xiu-Feng , Jiang Meng , Tan Wan-Yi , Xu Ying-Hui , Su Ji-Feng , Shi Bin 
Published: March 2024

ABSTRACT

Introduction: Intestinal flora and the translocation of its products, such as muramyl dipeptide (MDP), are common causes of sepsis. MDP is a common activator of the intracellular pattern recognition receptor NOD2, and MDP translocation can cause inflammatory damage to the small intestine and systemic inflammatory responses in rats. Therefore, this study investigated the effects of MDP on the intestinal mucosa and distant organs during sepsis and the role of the NOD2/AMPK/LC3 pathway in MDP-induced mitochondrial dysfunction in the intestinal epithelium. Methods: Fifty male Sprague Dawley rats were randomly divided into five treatment groups: lipopolysaccharide (LPS) only, 1.5 and 15 mg/kg MDP+LPS, and 1.5 and 15 mg/kg MDP+short-peptide enteral nutrition (SPEN)+LPS. The total caloric intake was the same per group. The rats were euthanized 24 h after establishing the model, and peripheral blood and small intestinal mucosal and lung tissues were collected. Results: Compared to the LPS group, both MDP+LPS groups had aggravated inflammatory damage to the intestinal mucosal and lung tissues, increased IL-6 and MDP production, increased NOD2 expression, decreased AMPK and LC3 expression, increased mitochondrial reactive oxygen species production, and decreased mitochondrial membrane potential. Compared to the MDP+LPS groups, the MDP+SPEN+LPS groups had decreased IL-6 and MDP production, increased AMPK and LC3 protein expression, and protected mitochondrial and organ functions. Conclusions: MDP translocation reduced mitochondrial autophagy by regulating the NOD2/AMPK/LC3 pathway, causing mitochondrial dysfunction. SPEN protected against MDP-induced impairment of intestinal epithelial mitochondrial function during sepsis.
Qipengyuania benthica sp. nov. and Qipengyuania profundimaris sp. nov., two novel Erythrobacteraceae members isolated from deep-sea environments
Authors: Wang Yuan , You Hao , Bu Yu-Xin , Zhou Peng , Xu Lin , Fu Ge-Yi , Xu Xue-Wei 
Published: March 2024

Two Gram-stain-negative, rod-shaped and non-motile strains, designated as DY56-A-20T and G39T, were isolated from deep-sea sediment of the Pacific Ocean and deep-sea seawater of the Indian Ocean, respectively. Strain DY56-A-20T was found to grow at 15–37 °C (optimum, 28 °C), at pH 6.0–10.0 (optimum, pH 6.5–7.0) and in 0.5–6.0 % (w/v) NaCl (optimum, 1.0–2.0 %), while strain G39T was found to grow at 10–42 °C (optimum, 35–40 °C), at pH 5.5–10.0 (optimum, pH 6.5–7.0) and in 0–12.0 % (w/v) NaCl (optimum, 1.0–2.0 %). The 16S rRNA gene sequence identity analysis indicated that strain DY56-A-20T had the highest sequence identity with Qipengyuania marisflavi KEM-5T (97.6 %), while strain G39T displayed the highest sequence identity with Qipengyuania citrea H150T (98.8 %). The phylogenomic reconstruction indicated that both strains formed independent clades within the genus Qipengyuania. The digital DNA–DNA hybridization and average nucleotide identity values between strains DY56-A-20T/G39T and Qipengyuania/Erythrobacter type strains were 17.8–23.8 % and 70.7–81.1 %, respectively, which are below species delineation thresholds. The genome DNA G+C contents were 65.0 and 63.5 mol% for strains DY56-A-20T and G39T, respectively. The predominant cellular fatty acids (>10 %) of strain DY56-A-20T were C17 : 1
ω6c, summed feature 8 and summed feature 3, and the major cellular fatty acids of strain G39T were C17 : 1
ω6c and summed feature 8. The major polar lipids in both strains were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, sphingoglycolipid and an unidentified polar lipid. The only respiratory quinone present in both strains was ubiquinone-10. Based on those genotypic and phenotypic results, the two strains represent two novel species belonging to the genus Qipengyuania, for which the names Qipengyuania benthica sp. nov. and Qipengyuania profundimaris sp. nov. are proposed. The type strain of Q. benthica is DY56-A-20T (=MCCC M27941T=KCTC 92309T), and the type strain of Q. profundimaris is G39T (=MCCC M30353T=KCTC 8208T).
Spatially resolved niche and tumor microenvironmental alterations in gastric cancer peritoneal metastases
Authors: Zhao Joseph J. , Ong Johnny Chin-Ann , Srivatsava Supriya , Ann Chia Daryl Kai , Ma Haoran , Huang Kiekyon , Sheng Taotao , Ramnarayanan Kalpana , Ong Xuewen , Tay Su Ting , Hagihara Takeshi , Keng Tan Angie Lay , Ching Teo Melissa Ching , Tan Qiu Xuan , Ng Gillian , Tan Joey Wee-Shan , Hsien Ng Matthew Chau , Gwee Yong Xiang , Walsh Robert , Shabbir Asim , Kim Guowei , Tay Yvonne , Her Zhisheng , Leoncini Giuseppe , Teh Bin Tean , Hong Jing Han , Kiat Tay Ryan Yong , Teo Chong Boon , Dings Mark P. G. , Bijlsma Maarten , Yew Lum Jeffrey Huey , Law Jia Hao , Pietrantonio Filippo , Blum Steven M. , van Laarhoven Hanneke , Klempner Samuel J. , Yong Wei Peng , Yan So Jimmy Bok , Chen Qingfeng , Tan Patrick , Sundar Raghav 
Published: March 2024

AbstractPeritoneal metastases (PM) in gastric cancer (GC) portend a poor prognosis, yet our understanding of tumor microenvironmental (TME) characteristics associated with GCPM remain limited. Here, we analyzed intrinsic genomic alterations and transcriptomic programs predictive of GCPM in a prospective cohort of 248 patients, identifyingCDH1,PIGR, andELF3mutations as predictors. By inspecting the spatial dynamics of the TME, we find that tumor compartment infiltration of pro-tumorigenic cell types such as inflammatory cancer-associated fibroblasts (CAFs) predict peritoneal recurrence. Next, in a cross-sectional study of 205 samples from 55 patients, distinct pathways and immune compositions in GCPM relative to liver metastases highlight the TME’s significance in transcoelomic metastases. Notably, several putative therapeutic targets exhibited distinct expression patterns between PTs and PMs. We also observed increased immune infiltration in GCPMs treated with systemic immunotherapy and intraperitoneal chemotherapy. Our findings highlight transcriptomic variations and niche reprogramming in the GCPM peritoneal environment, revealing roles of myeloid dendritic cells, effector memory CD8+ T cells, and CAFs in metastatic progression.Statement of significanceComprehensive molecular profiling of gastric cancer primary and peritoneal tumors unveils crucial insights into the distinct molecular and immune landscape of peritoneal metastases. Identifying predictive markers and therapeutic targets emphasizes the significance of tumor microenvironment alterations in guiding future therapies for gastric cancer peritoneal metastasis.
SPACe (Swift Phenotypic Analysis of Cells): an open-source, single cell analysis of Cell Painting data
Authors: Stossi Fabio , Singh Pankaj K. , Marini Michela , Safari Kazem , Szafran Adam T. , Tostado Alejandra Rivera , Candler Christopher D. , Mancini Maureen G. , Mosa Elina A. , Bolt Michael J. , Labate Demetrio , Mancini Michael A. 
Published: March 2024

ABSTRACTPhenotypic profiling by high throughput microscopy has become one of the leading tools for screening large sets of perturbations in cellular models. Of the numerous methods used over the years, the flexible and economical Cell Painting (CP) assay has been central in the field, allowing for large screening campaigns leading to a vast number of data-rich images. Currently, to analyze data of this scale, available open-source software (i.e., CellProfiler) requires computational resources that are not available to most laboratories worldwide. In addition, the image-embedded cell-to-cell variation of responses within a population, while collected and analyzed, is usually averaged and unused. Here we introduce SPACe (SwiftPhenotypicAnalysis ofCells), an open source, Python-based platform for the analysis of single cell image-based morphological profiles produced by CP experiments. SPACe can process a typical dataset approximately ten times faster than CellProfiler on common desktop computers without loss in mechanism of action (MOA) recognition accuracy. It also computes directional distribution-based distances (Earth Mover’s Distance – EMD) of morphological features for quality control and hit calling. We highlight several advantages of SPACe analysis on CP assays, including reproducibility across multiple biological replicates, easy applicability to multiple (∼20) cell lines, sensitivity to variable cell-to-cell responses, and biological interpretability to explain image-based features. We ultimately illustrate the advantages of SPACe in a screening campaign of cell metabolism small molecule inhibitors which we performed in seven cell lines to highlight the importance of testing perturbations across models.
Optical Control of Cardiac Electrophysiology by the Photochromic Ligand AB2
Authors: Fehrentz Timm , Amin Ehsan , Görldt Nicole , Strasdeit Tobias , Moussavi-Torshizi S. Erfan , Leippe Philipp , Trauner Dirk , Meyer Christian , Frey Norbert , Sasse Philipp , Klöcker Nikolaj 
Published: March 2024

AbstractVentricular arrhythmias (VAs) may occur in both the structurally normal and diseased heart. Particularly, patients suffering from ischemic heart disease and heart failure are at high risk of recurrent VA eventually leading to sudden cardiac death (SCD). While high-voltage shocks delivered by an implantable defibrillator may prevent SCD, these interventions themselves impair quality of life and raise both morbidity and mortality, which accentuates the need for developing novel defibrillation techniques. Here, we report the photochromic ligand azobupivacaine 2 (AB2) to enable gradual control of cardiac electrophysiology by light. By reversibly blocking voltage-gated both Na+and K+channels, photoswitching of AB2 modulates both the ventricular effective refractory period and conduction velocity thereby converting VA into sinus rhythm in an ex-vivo intact heart model. Thus, AB2 opens the door to the development of an optical defibrillator based on photopharmacology.
A dynamin-like protein in the human malaria parasite plays an essential role in mitochondrial homeostasis and fission during asexual blood stages
Authors: Thakur Vandana , Singh Shweta , Rathore Sumit , Muneer Azhar , Islam Md. Muzahidul , Dutta Gaurav , Banday Mudassir M. , Arora Priya , Hossain Mohammad E. , Jain Shaifali , Ali Shakir , Mohmmed Asif 
Published: March 2024

ABSTRACTMalaria parasite harbors a single mitochondrion and its proper segregation during the parasite multiplication is crucial for propagation of the parasite within the host. Mitochondrial fission machinery consists of a number of proteins that associate with mitochondrial membrane during segregation. Here, we have identified a dynamin-like protein inP. falciparum,PfDyn2, and deciphered its role in mitochondrial division, segregation and homeostasis. GFP targeting approach combined with high resolution microscopy studies showed that thePfDyn2 associates with mitochondrial membrane to form a clip/hairpin loop like structure around it at specific sites during mitochondrial division. The C-terminal degradation tag mediated inducible knock-down (iKD) ofPfDyn2 resulted in significant inhibition of parasite growth.PfDyn2-iKD hindered mitochondrial development and functioning, decreased mtDNA replication, and induced mitochondrial oxidative-stress, ultimately causing parasite death. Further, treatment of parasites with dynamin specific inhibitors disrupted the recruitment ofPfDyn2 on the mitochondria, blocked mitochondrial development, and induced oxidative stress. Regulated overexpression of a phosphorylation mutant ofPfDyn2 (Ser-612-Ala) had no effect on the recruitment ofPfDyn2 on the mitochondria; normal mitochondrial division and parasite growth showed that phosphorylation/dephosphorylation of this conserved serine residue (Ser612) may not be responsible for regulating recruitment ofPfDyn2 to the mitochondrion. Overall, we show essential role ofPfDyn2 in mitochondrial dynamics and fission as well as in maintaining its homeostasis during asexual cycle of the parasite.
Analytical Methods and Platforms for circRNA Vector Engineering to Improve Circularization Efficiency
Authors: Sun Yali , Khimani Anis H. , Tong Yanhong , Lu Zhi-xiang 
Published: March 2024

AbstractCircular RNAs (circRNAs) have emerged as pivotal players in RNA therapeutics. Unlike linear counterparts, circRNAs possess a closed-loop structure, conferring them with enhanced stability and resistance to degradation. This resilience makes them promising candidates for diagnostic and therapeutic applications. The ribozyme-based strategy stands out as the predominant method for synthetic circRNA production. In this strategy, ribozymes (catalytic RNA molecules) facilitate the circularization process by precisely cleaving and promoting the formation of a covalent circular structure. In the report, we detail analytical methods for circRNA vector engineering to enhance circularization efficiency. This approach will capture the attention of researchers interested in optimizing RNA circularization efficiency, as well as those focused on exploring key elements for ribozyme catalytic activity.
Engineering Substrate Channeling in Assembly-Line Terpene Biosynthesis
Authors: Wenger Eliott S. , Schultz Kollin , Marmorstein Ronen , Christianson David W. 
Published: March 2024

AbstractFusicoccadiene synthase fromP. amygdala(PaFS) is a bifunctional assembly-line terpene synthase containing a prenyltransferase domain that generates geranylgeranyl diphosphate (GGPP) from dimethylallyl diphosphate (DMAPP) and three equivalents of isopentenyl diphosphate (IPP), and a cyclase domain that converts GGPP into fusicoccadiene, a precursor of the diterpene glycoside Fusicoccin A. The two catalytic domains are linked by a flexible 69-residue polypeptide segment. The prenyltransferase domain mediates oligomerization to form predominantly octamers, and cyclase domains are randomly splayed out around the prenyltransferase core. Previous studies suggest that substrate channeling is operative in catalysis, since most of the GGPP formed by the prenyltransferase remains on the protein for the cyclization reaction. Here, we demonstrate that the flexible linker is not required for substrate channeling, nor must the prenyltransferase and cyclase domains be covalently linked to sustain substrate channeling. Moreover, substrate competition experiments with other diterpene cyclases indicate that the PaFS prenyltransferase and cyclase domains are preferential partners regardless of whether they are covalently linked or not. The cryo-EM structure of engineered “linkerless” construct PaFSLL, in which the 69-residue linker is spliced out and replaced with the tripeptide PTQ, reveals that cyclase pairs associate with all four sides of the prenyltransferase octamer. Taken together, these results suggest that optimal substrate channeling is achieved when a cyclase domain associates with the side of the prenyltransferase octamer, regardless of whether the two domains are covalently linked and regardless of whether this interaction is transient or locked in place.