bluuebunny/crossref_metadata_2025_split huggingface dataset:
γ-Secretase in Alzheimer’s disease
Authors: Hur Ji-Yeun 
Published: April 2022

AbstractAlzheimer’s disease (AD) is caused by synaptic and neuronal loss in the brain. One of the characteristic hallmarks of AD is senile plaques containing amyloid β-peptide (Aβ). Aβ is produced from amyloid precursor protein (APP) by sequential proteolytic cleavages by β-secretase and γ-secretase, and the polymerization of Aβ into amyloid plaques is thought to be a key pathogenic event in AD. Since γ-secretase mediates the final cleavage that liberates Aβ, γ-secretase has been widely studied as a potential drug target for the treatment of AD. γ-Secretase is a transmembrane protein complex containing presenilin, nicastrin, Aph-1, and Pen-2, which are sufficient for γ-secretase activity. γ-Secretase cleaves >140 substrates, including APP and Notch. Previously, γ-secretase inhibitors (GSIs) were shown to cause side effects in clinical trials due to the inhibition of Notch signaling. Therefore, more specific regulation or modulation of γ-secretase is needed. In recent years, γ-secretase modulators (GSMs) have been developed. To modulate γ-secretase and to understand its complex biology, finding the binding sites of GSIs and GSMs on γ-secretase as well as identifying transiently binding γ-secretase modulatory proteins have been of great interest. In this review, decades of findings on γ-secretase in AD are discussed.
Active lithoautotrophic and methane-oxidizing microbial community in an anoxic, sub-zero, and hypersaline High Arctic spring
Authors: Magnuson Elisse , Altshuler Ianina , Fernández-Martínez Miguel Á , Chen Ya-Jou , Maggiori Catherine , Goordial Jacqueline , Whyte Lyle G 
Published: April 2022

Abstract
Lost Hammer Spring, located in the High Arctic of Nunavut, Canada, is one of the coldest and saltiest terrestrial springs discovered to date. It perennially discharges anoxic (&lt;1 ppm dissolved oxygen), sub-zero (~−5 °C), and hypersaline (~24% salinity) brines from the subsurface through up to 600 m of permafrost. The sediment is sulfate-rich (1 M) and continually emits gases composed primarily of methane (~50%), making Lost Hammer the coldest known terrestrial methane seep and an analog to extraterrestrial habits on Mars, Europa, and Enceladus. A multi-omics approach utilizing metagenome, metatranscriptome, and single-amplified genome sequencing revealed a rare surface terrestrial habitat supporting a predominantly lithoautotrophic active microbial community driven in part by sulfide-oxidizing Gammaproteobacteria scavenging trace oxygen. Genomes from active anaerobic methane-oxidizing archaea (ANME-1) showed evidence of putative metabolic flexibility and hypersaline and cold adaptations. Evidence of anaerobic heterotrophic and fermentative lifestyles were found in candidate phyla DPANN archaea and CG03 bacteria genomes. Our results demonstrate Mars-relevant metabolisms including sulfide oxidation, sulfate reduction, anaerobic oxidation of methane, and oxidation of trace gases (H2, CO2) detected under anoxic, hypersaline, and sub-zero ambient conditions, providing evidence that similar extant microbial life could potentially survive in similar habitats on Mars.
Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph)
Authors: Walther Andreas , Mackens-Kiani Anne , Eder Julian , Herbig Maik , Herold Christoph , Kirschbaum Clemens , Guck Jochen , Wittwer Lucas Daniel , Beesdo-Baum Katja , Kräter Martin 
Published: April 2022

AbstractPathophysiological landmarks of depressive disorders are chronic low-grade inflammation and elevated glucocorticoid output. Both can potentially interfere with cytoskeleton organization, cell membrane bending and cell function, suggesting altered cell morpho-rheological properties like cell deformability and other cell mechanical features in depressive disorders. We performed a cross-sectional case-control study using the image-based morpho-rheological characterization of unmanipulated blood samples facilitating real-time deformability cytometry (RT-DC). Sixty-nine pre-screened individuals at high risk for depressive disorders and 70 matched healthy controls were included and clinically evaluated by Composite International Diagnostic Interview leading to lifetime and 12-month diagnoses. Facilitating deep learning on blood cell images, major blood cell types were classified and morpho-rheological parameters such as cell size and cell deformability of every individual cell was quantified. We found peripheral blood cells to be more deformable in patients with depressive disorders compared to controls, while cell size was not affected. Lifetime persistent depressive disorder was associated with increased cell deformability in monocytes and neutrophils, while in 12-month persistent depressive disorder erythrocytes deformed more. Lymphocytes were more deformable in 12-month major depressive disorder, while for lifetime major depressive disorder no differences could be identified. After correction for multiple testing, only associations for lifetime persistent depressive disorder remained significant. This is the first study analyzing morpho-rheological properties of entire blood cells and highlighting depressive disorders and in particular persistent depressive disorders to be associated with increased blood cell deformability. While all major blood cells tend to be more deformable, lymphocytes, monocytes, and neutrophils are mostly affected. This indicates that immune cell mechanical changes occur in depressive disorders, which might be predictive of persistent immune response.
The role of sphingosine-1-phosphate in bone remodeling and osteoporosis
Authors: Grewe Justus M. , Knapstein Paul-Richard , Donat Antonia , Jiang Shan , Smit Daniel J. , Xie Weixin , Keller Johannes 
Published: April 2022

AbstractOsteoporosis is a systemic bone disease that affects more than 200 million people worldwide and is caused by the disruption of the equilibrium between osteoclastic bone resorption and osteoblastic bone formation. Sphingosine-1-phosphate (S1P) is a natural, bioactive sphingolipid that has been shown to play a major role in cardiovascular and immunological pathologies by regulating biological and cellular processes, including migration, differentiation, proliferation and survival. Recent studies also suggest a central role for S1P in bone diseases, including osteoporosis; however, the effects of S1P, particularly in bone metabolism, remain to be further elucidated. In this review, we summarize the available literature on the role of S1P in bone metabolism with a focus on osteoporosis. On the cellular level, S1P acts as an osteoclast-osteoblast coupling factor to promote osteoblast proliferation and bone formation. Moreover, the recruitment of osteoclast precursors to resorption sites is regulated by the interplay of S1P gradients and S1P receptor expression. From a clinical perspective, increasing evidence suggests that systemically elevated S1P blood levels may serve as an independent risk factor for osteoporosis-related fractures. Taken together, S1P signaling is a potential therapeutic target and may serve as a novel biomarker in patients with systemic bone disease.
HucMSC-derived exosomes delivered BECN1 induces ferroptosis of hepatic stellate cells via regulating the xCT/GPX4 axis
Authors: Tan Youwen , Huang Yan , Mei Rong , Mao Fei , Yang Dakai , Liu Jinwen , Xu Wenrong , Qian Hui , Yan Yongmin 
Published: April 2022

AbstractActivated hepatic stellate cells (HSCs) are significant in liver fibrosis. Our past investigations have shown that human umbilical cord mesenchymal stem cells (hucMSCs) and their secreted exosomes (MSC-ex) could alleviate liver fibrosis via restraining HSCs activation. However, the mechanisms underlying the efficacy were not clear. Ferroptosis is a regulatory cell death caused by excessive lipid peroxidation, and it plays a vital role in the occurrence and development of liver fibrosis. In the present study, we aimed to study the proferroptosis effect and mechanism of MSC-ex in HSCs. MSC-ex were collected and purified from human umbilical cord MSCs. Proferroptosis effect of MSC-ex was examined in HSCs line LX-2 and CCl4 induced liver fibrosis in mice. Gene knockdown or overexpression approaches were used to investigate the biofactors in MSC-ex-mediated ferroptosis regulation. Results: MSC-ex could trigger HSCs ferroptosis by promoting ferroptosis-like cell death, ROS formation, mitochondrial dysfunction, Fe2+ release, and lipid peroxidation in human HSCs line LX-2. Glutathione peroxidase 4 (GPX4) is a crucial regulator of ferroptosis. We found that intravenous injection of MSC-ex significantly decreased glutathione peroxidase 4 (GPX4) expression in activated HSCs and collagen deposition in experimental mouse fibrotic livers. Mechanistically, MSC-ex derived BECN1 promoted HSCs ferroptosis by suppressing xCT-driven GPX4 expression. In addition, ferritinophagy and necroptosis might also play a role in MSC-ex-promoted LX-2 cell death. Knockdown of BECN1 in MSC diminished proferroptosis and anti-fibrosis effects of MSC-ex in LX-2 and fibrotic livers. MSC-ex may promote xCT/GPX4 mediated HSCs ferroptosis through the delivery of BECN1 and highlights BECN1 as a potential biofactor for alleviating liver fibrosis.
Large barocaloric effect in intermetallic La1.2Ce0.8Fe11Si2H1.86 materials driven by low pressure
Authors: Liu Yanfeng , Zheng Xinqi , Liang Feixiang , Hu Fengxia , Huang Qingzhen , Li Zhe , Liu Jian 
Published: April 2022

AbstractBarocaloric materials are particularly promising for green and efficient solid-state cooling technology because of their great potential in terms of cooling performance. However, intermetallic materials with outstanding barocaloric effects under low hydrostatic pressure are especially lacking, which has severely delayed the development of barocaloric refrigeration. Here, in a rare-earth intermetallic La-Ce-Fe-Si-H, we achieve a giant specific barocaloric temperature change of 8 K per kbar according to direct measurements of the adiabatic temperature change ΔTBCE under hydrostatic pressure, which is confirmed by a phenomenological transition simulation. This barocaloric strength is significantly better than those in previously reported phase-transitioned alloys. By using a cutting-edge in situ neutron diffraction technique operating under simultaneously varying temperature, magnetic field, and hydrostatic pressure, we reveal that the large isotropic transition volume change in La-Ce-Fe-Si-H plays a crucial role in the giant barocaloric effect. Additionally, we employ Landau expansion theory to demonstrate that the high sensitivity of the transition temperature to the applied pressure produces the sizable ΔTBCE in the itinerant electron metamagnetic transition alloys. Our results provide insight into the development of high-performance barocaloric materials and related cooling systems.
Freestanding non-covalent thin films of the propeller-shaped polycyclic aromatic hydrocarbon decacyclene
Authors: van der Ham Alex , Liu Xue , Calvani Dario , Melcrová Adéla , Kozdra Melania , Buda Francesco , Overkleeft Herman S. , Roos Wouter H. , Filippov Dmitri V. , Schneider Grégory F. 
Published: April 2022

AbstractMolecularly thin, nanoporous thin films are of paramount importance in material sciences. Their use in a wide range of applications requires control over their chemical functionalities, which is difficult to achieve using current production methods. Here, the small polycyclic aromatic hydrocarbon decacyclene is used to form molecular thin films, without requiring covalent crosslinking of any kind. The 2.5 nm thin films are mechanically stable, able to be free-standing over micrometer distances, held together solely by supramolecular interactions. Using a combination of computational chemistry and microscopic imaging techniques, thin films are studied on both a molecular and microscopic scale. Their mechanical strength is quantified using AFM nanoindentation, showing their capability of withstanding a point load of 26 ± 9 nN, when freely spanning over a 1 μm aperture, with a corresponding Young’s modulus of 6 ± 4 GPa. Our thin films constitute free-standing, non-covalent thin films based on a small PAH.
Creep-dilatancy development at a transform plate boundary
Authors: Sultan Nabil , Murphy Shane , Riboulot Vincent , Géli Louis 
Published: April 2022

AbstractHow tectonic plates slip slowly and episodically along their boundaries, is a major, open question in earthquake science. Here, we use offshore in-situ sediment pore-pressure acquired in the proximity of the active offshore Main Marmara Fault and onshore geodetic time-series data set from a single GPS station to demonstrate the pore-pressure/deformation coupling during a 10-month slow-slip event. We show that pore pressure fluctuations are the expression of hydro-mechanical process affecting the deep seismogenic zone and indicate that small disturbances in geodetic data may have important meaning in terms of transient deformations. These results have major implications in understanding the spatial impact of slow-slip processes and their role in earthquake cycles. We demonstrate that piezometers measuring along a transform fault can help define the time scale regulating the coupling between slow-slip events and earthquake nucleation process.
Microscopic theory of light-induced ultrafast skyrmion excitation in transition metal films
Authors: Viñas Boström Emil , Rubio Angel , Verdozzi Claudio 
Published: April 2022

AbstractMagnetic skyrmions are topological excitations of great promise for compact and efficient memory storage. However, to interface skyrmionics with electronic devices requires efficient and reliable ways of creating and destroying such excitations. In this work, we unravel the microscopic mechanism behind ultrafast skyrmion generation by femtosecond laser pulses in transition metal thin films. We employ a theoretical approach based on a two-band electronic model, and show that by exciting the itinerant electronic subsystem with a femtosecond laser ultrafast skyrmion nucleation can occur on a 100 fs timescale. By combining numerical simulations with an analytical treatment of the strong s–d exchange limit, we identify the coupling between electronic currents and the localized d-orbital spins, mediated via Rashba spin–orbit interactions among the itinerant electrons, as the microscopic and central mechanism leading to ultrafast skyrmion generation. Our results show that an explicit treatment of itinerant electron dynamics is crucial to understand optical skyrmion generation.
Processing of high temperature alumina/aluminum titanate ceramic composites from clean sources
Authors: Besisa Nada H. A. , Besisa Dina H. A. , Ewais Emad M. M. 
Published: April 2022

AbstractProducing new technological materials with high performance from clean sources has become a global requirement. Alumina/aluminum titanate (Al2O3/Al2TiO5) composites are high-temperature portentous materials used in various advanced applications. In this work, different Al2O3/Al2TiO5 composites were obtained with high thermal and mechanical properties for high-temperature applications by a low-cost process. The targeted composites were produced from calcined alumina and, rutile ore extracted from the Egyptian black sands by pressureless sintering at a temperature of 1650 °C/2 h. Rutile was added to alumina with a different content (0–40 wt%) to promote its sinterability and thermo-mechanical response. Evaluation of the produced composites in terms of phase composition, densification, microstructural features, mechanical and thermal properties was investigated. The results indicated that the addition of small amounts of rutile (10 and 20 wt%) succeeded in forming a stable Al2O3/Al2TiO5 composite structure. However, higher content of rutile led to the formation of Al2TiO5 rich matrix composites. Moreover, highly dense composites with harmonic microstructure and enhanced mechanical strength were attained by increasing the rutile content. The composite with only 10 wt% rutile addition gave the highest density of 3.6 g/cm3 and the highest cold crushing strength and modulus of rupture values of 488.73 MPa and 106.19 MPa, respectively. Notably, the addition of rutile has a substantial effect on promoting the thermal properties and thermal stability of the obtained composites up to a high temperature of 1400 °C. The present study shows that addition of rutile ore to alumina is one economical way of improving the densification and thermal expansion of Al2O3 for high temperature applications. Using a clean source such as rutile ore that contains some thermal stabilizers as Fe2O3, Al2O3, SiO2, ZrO2, and MgO instead of pure TiO2 has played a noticeable role in improving the reaction sintering and resulting in a highly qualified material. Thus, sintered Al2O3/Al2TiO5 composites can be considered as a promising high-temperature material for advanced applications.
Effects of intramuscularly injected plant-derived antimicrobials in the mouse model
Authors: Johnson Elizabeth J. , Duan Jingyue Ellie , Srirattana Kanokwan , Venkitanarayanan Kumar , Tulman Edan R. , Tian Xiuchun Cindy 
Published: April 2022

AbstractWith increasing antibiotic resistance, the use of plant derived antimicrobials (PDAs) has gained momentum. Here, we investigated the toxicity of trans-cinnamaldehyde, eugenol, and carvacrol after intramuscular injection in mice. Two doses of each PDA—300 and 500 mg/kg body weight—and vehicle controls were injected into the muscle of the right hind limb of CD-1 adult mice (n = 8/treatment). Ten physical/behavioral parameters were monitored hourly for 2 h and twice daily for 4 days post-injection together with postmortem examination of leg muscles and organs. Within the first 2 days of carvacrol treatment, one male died in each dose level and a third male receiving 500 mg/kg was removed from the study. No mortality was seen with any other treatment. Among all 81 parameters examined, significant higher relative liver weights (300 and 500 mg/kg eugenol groups; P < 0.05) and relative kidney weights (300 mg/kg carvacrol group; P < 0.001) were observed. Taken together, little to mild toxicity was seen for trans-cinnamaldehyde and eugenol, respectively, while carvacrol exerted more toxicity in males. This study lays the foundation for future extensive work with large sample size, varied treatment durations, and additional treatment levels.
Challenging monogamy in a spider with nontraditional sexual behavior
Authors: Bollatti Fedra , Simian Catalina , Peretti Alfredo V. , Aisenberg Anita 
Published: April 2022

AbstractEach species and sex can develop different reproductive strategies to optimize their fitness while assigning reproductive effort. Allocosasenex is a sex-role reversed spider whose males construct long burrows in the sand. They wait for wandering females to approach, assess their sexual partners and donate their constructions to females after copulation. Females stay in the burrow and lay their egg-sac. When offspring are ready for dispersion, females leave the burrow and gain access to new mating opportunities. Males are choosy during mate courtship, preferring to mate with virgin females over copulated ones, which can even be cannibalized if males reject them. This situation turns new mating opportunities dangerous for copulated females. We wondered whether a copulated female inside the previous mate's burrow responds to courtship from a new male and if this new male can copulate, avoiding burrow construction costs. We also explored whether courtship and copulation behaviors during the first sexual encounter affected the probability of occurrence of a second copulation. For that purposes we exposed copulated females inside male burrows to new males (non-donor males). Males could locate and court females inside the previous male's burrow, and females accepted a second copulation. Hence, A.senex females are not monogamous as was expected but increase their reproductive success by copulating with non-donor males. Also, males can develop opportunistic tactics, suggesting a more dynamic mating system for this sex-role reversed spider than assumed.
Relationships between species richness and ecosystem services in Amazonian forests strongly influenced by biogeographical strata and forest types
Authors: Steur Gijs , ter Steege Hans , Verburg René W. , Sabatier Daniel , Molino Jean-François , Bánki Olaf S. , Castellanos Hernan , Stropp Juliana , Fonty Émile , Ruysschaert Sofie , Galbraith David , Kalamandeen Michelle , van Andel Tinde R. , Brienen Roel , Phillips Oliver L. , Feeley Kenneth J. , Terborgh John , Verweij Pita A. 
Published: April 2022

AbstractDespite increasing attention for relationships between species richness and ecosystem services, for tropical forests such relationships are still under discussion. Contradicting relationships have been reported concerning carbon stock, while little is known about relationships concerning timber stock and the abundance of non-timber forest product producing plant species (NTFP abundance). Using 151 1-ha plots, we related tree and arborescent palm species richness to carbon stock, timber stock and NTFP abundance across the Guiana Shield, and using 283 1-ha plots, to carbon stock across all of Amazonia. We analysed how environmental heterogeneity influenced these relationships, assessing differences across and within multiple forest types, biogeographic regions and subregions. Species richness showed significant relationships with all three ecosystem services, but relationships differed between forest types and among biogeographical strata. We found that species richness was positively associated to carbon stock in all biogeographical strata. This association became obscured by variation across biogeographical regions at the scale of Amazonia, resembling a Simpson’s paradox. By contrast, species richness was weakly or not significantly related to timber stock and NTFP abundance, suggesting that species richness is not a good predictor for these ecosystem services. Our findings illustrate the importance of environmental stratification in analysing biodiversity-ecosystem services relationships.
Fast fluoride ion conduction of NH4(Mg1-xLix)F3-x and (NH4)2(Mg1-xLix)F4-x assisted by molecular cations
Authors: Motohashi Kota , Matsukawa Yosuke , Nakamura Takashi , Kimura Yuta , Kuwata Naoaki , Uchimoto Yoshiharu , Amezawa Koji 
Published: April 2022

AbstractAiming development of the fast anion conductors, we proposed a new material design using flexible molecular cation as a host cation, and demonstrated it with fluoride ion conduction in NH4MgF3 and (NH4)2MgF4 based materials. Dominant fluoride ion conduction with relatively high conductivities of 4.8 × 10–5 S cm−1 and 8.4 × 10–6 S cm−1 were achieved at 323 K in (NH4)2(Mg0.85Li0.15)F3.85 and NH4(Mg0.9Li0.1)F2.9, respectively. It is implied that the molecular cation in the host lattice can assist the anion conduction. Our findings suggest molecular cation-containing compounds can be attractive material groups for fast anion conductors.