bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transferrin plays a central role in coagulation balance by interacting with clotting factors
Authors: Tang Xiaopeng , Zhang Zhiye , Fang Mingqian , Han Yajun , Wang Gan , Wang Sheng , Xue Min , Li Yaxiong , Zhang Li , Wu Jian , Yang Biqing , Mwangi James , Lu Qiumin , Du Xiaoping , Lai Ren 
Published: December 2019

AbstractCoagulation balance is maintained through fine-tuned interactions among clotting factors, whose physiological concentrations vary substantially. In particular, the concentrations of coagulation proteases (pM to nM) are much lower than their natural inactivator antithrombin (AT, ~ 3 μM), suggesting the existence of other coordinators. In the current study, we found that transferrin (normal plasma concentration ~40 μM) interacts with fibrinogen, thrombin, factor XIIa (FXIIa), and AT with different affinity to maintain coagulation balance. Normally, transferrin is sequestered by binding with fibrinogen (normal plasma concentration ~10 μM) at a molar ratio of 4:1. In atherosclerosis, abnormally up-regulated transferrin interacts with and potentiates thrombin/FXIIa and blocks AT’s inactivation effect on coagulation proteases by binding to AT, thus inducing hypercoagulability. In the mouse model, transferrin overexpression aggravated atherosclerosis, whereas transferrin inhibition via shRNA knockdown or treatment with anti-transferrin antibody or designed peptides interfering with transferrin-thrombin/FXIIa interactions alleviated atherosclerosis. Collectively, these findings identify that transferrin is an important clotting regulator and an adjuster in the maintenance of coagulation balance and modifies the coagulation cascade.
The calcium channel subunit α2δ-3 organizes synapses via an activity-dependent and autocrine BMP signaling pathway
Authors: Hoover Kendall M. , Gratz Scott J. , Qi Nova , Herrmann Kelsey A. , Liu Yizhou , Perry-Richardson Jahci J. , Vanderzalm Pamela J. , O’Connor-Giles Kate M. , Broihier Heather T. 
Published: December 2019

AbstractSynapses are highly specialized for neurotransmitter signaling, yet activity-dependent growth factor release also plays critical roles at synapses. While efficient neurotransmitter signaling relies on precise apposition of release sites and neurotransmitter receptors, molecular mechanisms enabling high-fidelity growth factor signaling within the synaptic microenvironment remain obscure. Here we show that the auxiliary calcium channel subunit α2δ-3 promotes the function of an activity-dependent autocrine Bone Morphogenetic Protein (BMP) signaling pathway at the Drosophila neuromuscular junction (NMJ). α2δ proteins have conserved synaptogenic activity, although how they execute this function has remained elusive. We find that α2δ-3 provides an extracellular scaffold for an autocrine BMP signal, suggesting a mechanistic framework for understanding α2δ’s conserved role in synapse organization. We further establish a transcriptional requirement for activity-dependent, autocrine BMP signaling in determining synapse density, structure, and function. We propose that activity-dependent, autocrine signals provide neurons with continuous feedback on their activity state for modulating both synapse structure and function.
Engineered E. coli Nissle 1917 for the delivery of matrix-tethered therapeutic domains to the gut
Authors: Praveschotinunt Pichet , Duraj-Thatte Anna M. , Gelfat Ilia , Bahl Franziska , Chou David B. , Joshi Neel S. 
Published: December 2019

AbstractMucosal healing plays a critical role in combatting the effects of inflammatory bowel disease, fistulae and ulcers. While most treatments for such diseases focus on systemically delivered anti-inflammatory drugs, often leading to detrimental side effects, mucosal healing agents that target the gut epithelium are underexplored. We genetically engineer Escherichia coli Nissle 1917 (EcN) to create fibrous matrices that promote gut epithelial integrity in situ. These matrices consist of curli nanofibers displaying trefoil factors (TFFs), known to promote intestinal barrier function and epithelial restitution. We confirm that engineered EcN can secrete the curli-fused TFFs in vitro and in vivo, and is non-pathogenic. We observe enhanced protective effects of engineered EcN against dextran sodium sulfate-induced colitis in mice, associated with mucosal healing and immunomodulation. This work lays a foundation for the development of a platform in which the in situ production of therapeutic protein matrices from beneficial bacteria can be exploited.
Reactive metabolite production is a targetable liability of glycolytic metabolism in lung cancer
Authors: Luengo Alba , Abbott Keene L. , Davidson Shawn M. , Hosios Aaron M. , Faubert Brandon , Chan Sze Ham , Freinkman Elizaveta , Zacharias Lauren G. , Mathews Thomas P. , Clish Clary B. , DeBerardinis Ralph J. , Lewis Caroline A. , Vander Heiden Matthew G. 
Published: December 2019

AbstractIncreased glucose uptake and metabolism is a prominent phenotype of most cancers, but efforts to clinically target this metabolic alteration have been challenging. Here, we present evidence that lactoylglutathione (LGSH), a byproduct of methylglyoxal detoxification, is elevated in both human and murine non-small cell lung cancers (NSCLC). Methylglyoxal is a reactive metabolite byproduct of glycolysis that reacts non-enzymatically with nucleophiles in cells, including basic amino acids, and reduces cellular fitness. Detoxification of methylglyoxal requires reduced glutathione (GSH), which accumulates to high levels in NSCLC relative to normal lung. Ablation of the methylglyoxal detoxification enzyme glyoxalase I (Glo1) potentiates methylglyoxal sensitivity and reduces tumor growth in mice, arguing that targeting pathways involved in detoxification of reactive metabolites is an approach to exploit the consequences of increased glucose metabolism in cancer.
The tin1 gene retains the function of promoting tillering in maize
Authors: Zhang Xuan , Lin Zhelong , Wang Jian , Liu Hangqin , Zhou Leina , Zhong Shuyang , Li Yan , Zhu Can , Liu Jiacheng , Lin Zhongwei 
Published: December 2019

AbstractSweet maize and popcorn retain tillering growth habit during maize diversification. However, the underlying molecular genetic mechanism remains unknown. Here, we show that the retention of maize tillering is controlled by a major quantitative trait locus (QTL), tin1, which encodes a C2H2-zinc-finger transcription factor that acts independently of tb1. In sweet maize, a splice-site variant from G/GT to C/GT leads to intron retention, which enhances tin1 transcript levels and consequently increases tiller number. Comparative genomics analysis and DNA diversity analysis reveal that tin1 is under parallel selection across different cereal species. tin1 is involved in multiple pathways, directly represses two tiller-related genes, gt1 and Laba1/An-2, and interacts with three TOPLESS proteins to regulate the outgrowth of tiller buds. Our results support that maize tin1, derived from a standing variation in wild progenitor teosinte population, determines tillering retention during maize diversification.
Stabilization of point-defect spin qubits by quantum wells
Authors: Ivády Viktor , Davidsson Joel , Delegan Nazar , Falk Abram L. , Klimov Paul V. , Whiteley Samuel J. , Hruszkewycz Stephan O. , Holt Martin V. , Heremans F. Joseph , Son Nguyen Tien , Awschalom David D. , Abrikosov Igor A. , Gali Adam 
Published: December 2019

AbstractDefect-based quantum systems in wide bandgap semiconductors are strong candidates for scalable quantum-information technologies. However, these systems are often complicated by charge-state instabilities and interference by phonons, which can diminish spin-initialization fidelities and limit room-temperature operation. Here, we identify a pathway around these drawbacks by showing that an engineered quantum well can stabilize the charge state of a qubit. Using density-functional theory and experimental synchrotron X-ray diffraction studies, we construct a model for previously unattributed point defect centers in silicon carbide as a near-stacking fault axial divacancy and show how this model explains these defects’ robustness against photoionization and room temperature stability. These results provide a materials-based solution to the optical instability of color centers in semiconductors, paving the way for the development of robust single-photon sources and spin qubits.
Strong optical response and light emission from a monolayer molecular crystal
Authors: Zhao Huijuan , Zhao Yingbo , Song Yinxuan , Zhou Ming , Lv Wei , Tao Liu , Feng Yuzhang , Song Biying , Ma Yue , Zhang Junqing , Xiao Jun , Wang Ying , Lien Der-Hsien , Amani Matin , Kim Hyungjin , Chen Xiaoqing , Wu Zhangting , Ni Zhenhua , Wang Peng , Shi Yi , Ma Haibo , Zhang Xiang , Xu Jian-Bin , Troisi Alessandro , Javey Ali , Wang Xinran 
Published: December 2019

AbstractExcitons in two-dimensional (2D) materials are tightly bound and exhibit rich physics. So far, the optical excitations in 2D semiconductors are dominated by Wannier-Mott excitons, but molecular systems can host Frenkel excitons (FE) with unique properties. Here, we report a strong optical response in a class of monolayer molecular J-aggregates. The exciton exhibits giant oscillator strength and absorption (over 30% for monolayer) at resonance, as well as photoluminescence quantum yield in the range of 60–100%. We observe evidence of superradiance (including increased oscillator strength, bathochromic shift, reduced linewidth and lifetime) at room-temperature and more progressively towards low temperature. These unique properties only exist in monolayer owing to the large unscreened dipole interactions and suppression of charge-transfer processes. Finally, we demonstrate light-emitting devices with the monolayer J-aggregate. The intrinsic device speed could be beyond 30 GHz, which is promising for next-generation ultrafast on-chip optical communications.
Strong time dependence of ocean acidification mitigation by atmospheric carbon dioxide removal
Authors: Hofmann M. , Mathesius S. , Kriegler E. , Vuuren D. P. van , Schellnhuber H. J. 
Published: December 2019

AbstractIn Paris in 2015, the global community agreed to limit global warming to well below 2 $${}^{\circ }$$

∘

C, aiming at even 1.5 $${}^{\circ }$$

∘

C. It is still uncertain whether these targets are sufficient to preserve marine ecosystems and prevent a severe alteration of marine biogeochemical cycles. Here, we show that stringent mitigation strategies consistent with the 1.5 $${}^{\circ }$$

∘

C scenario could, indeed, provoke a critical difference for the ocean’s carbon cycle and calcium carbonate saturation states. Favorable conditions for calcifying organisms like tropical corals and polar pteropods, both of major importance for large ecosystems, can only be maintained if CO$${}_{2}$$

2

emissions fall rapidly between 2025 and 2050, potentially requiring an early deployment of CO$${}_{2}$$

2

removal techniques in addition to drastic emissions reduction. Furthermore, this outcome can only be achieved if the terrestrial biosphere remains a carbon sink during the entire 21st century.
Creation and annihilation of topological meron pairs in in-plane magnetized films
Authors: Gao N. , Je S. -G. , Im M. -Y. , Choi J. W. , Yang M. , Li Q. , Wang T. Y. , Lee S. , Han H. -S. , Lee K. -S. , Chao W. , Hwang C. , Li J. , Qiu Z. Q. 
Published: December 2019

AbstractMerons which are topologically equivalent to one-half of skyrmions can exist only in pairs or groups in two-dimensional (2D) ferromagnetic (FM) systems. The recent discovery of meron lattice in chiral magnet Co8Zn9Mn3 raises the immediate challenging question that whether a single meron pair, which is the most fundamental topological structure in any 2D meron systems, can be created and stabilized in a continuous FM film? Utilizing winding number conservation, we develop a new method to create and stabilize a single pair of merons in a continuous Py film by local vortex imprinting from a Co disk. By observing the created meron pair directly within a magnetic field, we determine its topological structure unambiguously and explore the topological effect in its creation and annihilation processes. Our work opens a pathway towards developing and controlling topological structures in general magnetic systems without the restriction of perpendicular anisotropy and Dzyaloshinskii–Moriya interaction.
The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia
Authors: Metzner Christoph , Zurowski Bartosz , Steuber Volker 
Published: December 2019

AbstractDespite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits. Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.
Relaxin reverses maladaptive remodeling of the aged heart through Wnt-signaling
Authors: Martin Brian , Gabris Beth , Barakat Amr F. , Henry Brian L. , Giannini Marianna , Reddy Rajiv P. , Wang Xuewen , Romero Guillermo , Salama Guy 
Published: December 2019

AbstractHealthy aging results in cardiac structural and electrical remodeling that increases susceptibility to cardiovascular diseases. Relaxin, an insulin-like hormone, suppresses atrial fibrillation, inflammation and fibrosis in aged rats but the mechanisms-of-action are unknown. Here we show that relaxin treatment of aged rats reverses pathological electrical remodeling (increasing Nav1.5 expression and localization of Connexin43 to intercalated disks) by activating canonical Wnt signaling. In isolated adult ventricular myocytes, relaxin upregulated Nav1.5 (EC50 = 1.3 nM) by a mechanism inhibited by the addition of Dickkopf-1. Furthermore, relaxin increased the levels of connexin43, Wnt1, and cytosolic and nuclear β-catenin. Treatment with Wnt1 or CHIR-99021 (a GSK3β inhibitor) mimicked the relaxin effects. In isolated fibroblasts, relaxin blocked TGFβ-induced collagen elevation in a Wnt dependent manner. These findings demonstrate a close interplay between relaxin and Wnt-signaling resulting in myocardial remodeling and reveals a fundamental mechanism of great therapeutic potential.
A multistage elastocaloric refrigerator and heat pump with 28 K temperature span
Authors: Snodgrass Ryan , Erickson David 
Published: December 2019

AbstractElastocaloric refrigerators are a promising alternative to the vapor compression cycle because they do not require refrigerants with high global warming potential. However, these coolers have yet to achieve temperatures low enough to — for example — be used as standard household refrigerators. We built one-stage, two-stage, and three-stage elastocaloric cooling systems to determine if staging of the elastocaloric effect could significantly expand temperature span. Our three-stage system achieved 1.5 times the maximum temperature span of our single-stage system, and produced the highest temperature span of any elastocaloric device to-date at 28.3 °C, where previously the record was 19.9 °C. Interestingly, we found that multistage systems can achieve equivalent temperature spans but at higher coefficients of performance compared to similarly-constructed single-stage systems.
ThSSim: A novel tool for simulation of reservoir thermal stratification
Authors: Noori Roohollah , Tian Fuqiang , Ni Guangheng , Bhattarai Rabin , Hooshyaripor Farhad , Klöve Bjön 
Published: December 2019

AbstractThis study presents a novel tool, ThSSim, for simulation of thermal stratification (ThS) in reservoirs. ThSSim is a simple and flexible reduced-order model-based the basis function (RMBF) that combines CE-QUAL-W2 (W2) and proper orthogonal decomposition (POD). In a case study, it was used to simulate water temperature in the Karkheh Reservoir (KR), Iran, for the period 2019–2035. ThSSim consists of two space- and time-dependent components that add predictive ability to the RMBF, a major refinement that extends its practical applications. Water temperature simulations by the W2 model at three-hour time intervals for the KR were used as input data to the POD model to develop ThSSim. To add predictive ability to ThSSim and considering that space-dependent components are not a function of time, we extrapolated the first three time-dependent components by September 30, 2035. We checked the predictive ability of ThSSim against water temperature profiles measured during eight sampling campaigns. We then applied ThSSim to simulate water temperature in the KR for 2019–2035. Simulated water temperature values matched well those measured and obtained by W2. ThSSim results showed an increasing trend for surface water temperature during the simulation period, with a reverse trend observed for water temperature in the bottom layers for three seasons (spring, summer and autumn). The results also indicated decreasing and increasing trends in onset and breakdown of thermal stability, respectively, so that the duration of ThS increased from 278 days in 2019 to 293 days in 2035. ThSSim is thus useful for reservoir temperature simulations. Moreover, the approach used to develop ThSSim is widely applicable to other fields of science and engineering.
Patient-specific Hemodynamics of Severe Carotid Artery Stenosis Before and After Endarterectomy Examined by 4D Flow MRI
Authors: Ko Seungbin , Lee Jeesoo , Song Simon , Kim Doosang , Lee Sang Hyung , Cho Jee-Hyun 
Published: December 2019

AbstractCarotid endarterectomy (CEA) influences the carotid endoluminal anatomy, which results in hemodynamic changes before and after surgery. We investigated the hemodynamics of severe carotid artery stenosis before and after conventional endarterectomy with/without patch repair. An in vitro experiment utilizing carotid phantoms, which underwent a procedure that emulated CEA with/without the patch repair, was performed with a high-spatiotemporal resolution using 4D flow MRI. We evaluated an abnormal region of carotids, which consists of the normalized time-averaged wall shear stress (NTA|WSS|) and the oscillatory shear index (OSI), to account for continuous high-shear regions (high NTA|WSS| and low OSI) and chaotic low-shear regions, i.e., stenosis-prone regions (low NTA|WSS| and high OSI). The use of normalized hemodynamic parameters (e.g., NTA|WSS|) allowed comparison of diverse cases with different conditions of hemodynamics and vessel geometry. We observed that the stenosis-prone regions of the carotids with patches were noticeably larger than the corresponding regions in no-patch carotids. A large recirculating flow zone found in the stenosis-prone region of the internal carotid artery (ICA) of the postoperative carotids with patches partially blocks the flow path into ICA, and consequently the flow rate was not recovered after surgery unlike an expectation.
Reference gene screening of Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans for quantitative real-time PCR studies
Authors: Verbrugghe Elin , Pasmans Frank , Martel An 
Published: December 2019

AbstractReal-time quantitative PCR studies largely depend on reference genes for the normalization of gene expression. Stable reference genes should be accurately selected in order to obtain reliable results. We here present a study screening commonly used reference genes (TEF1F,α-centractin,Ctsyn1,GAPDH,R6046,APRTandTUB) in the chytrid fungiBatrachochytrium dendrobatidis(Bd) andBatrachochytrium salamandrivorans(Bsal), which cause the lethal amphibian skin disease chytridiomycosis. We evaluated the stability of the reference gene candidates during different growth stages of the fungi, using different statistical software packages: ΔCT, BestKeeper, GeNorm, NormFinder and RefFinder. In order to reflect thein vivosituation, the stability of the candidates was assessed when taking all growth stages into account. Using anex-vivoapproach, we tested whether the expression ofGAPDH,TUB,R6046andAPRT(Bd) andGAPDH,TUB,R6046andα-centractin(Bsal) remained stable when these fungi came in contact with host tissue. Finally, their role asin vivoreference genes was examined in skin tissue of experimentally infected midwife toads (Alytes obstetricans) (Bd) and fire salamanders (Salamandra salamandra) (Bsal). Summarized, the present study provides guidance for selecting appropriate reference genes when analyzing expression patterns of these fungal organisms during different growth stages and inBd- orBsal-infected tissues.
Trim33 (Tif1γ) is not required for skeletal muscle development or regeneration but suppresses cholecystokinin expression
Authors: Parks Cassie A. , Pak Katherine , Pinal-Fernandez Iago , Huang Wilson , Derfoul Assia , Mammen Andrew L. 
Published: December 2019

AbstractThe expression of Trim33 (Tif1γ) increases in skeletal muscles during regeneration and decreases upon maturation. Although Trim33 is required for the normal development of other tissues, its role in skeletal muscle is unknown. The current study aimed to define the role of Trim33 in muscle development and regeneration. We generated mice with muscle-specific conditional knockout of Trim33 by combining floxed Trim33 and Cre recombinase under the Pax7 promoter. Muscle regeneration was induced by injuring mouse muscles with cardiotoxin. We studied the consequences of Trim33 knockdown on viability, body weight, skeletal muscle histology, muscle regeneration, and gene expression. We also studied the effect of Trim33 silencing in satellite cells and the C2C12 mouse muscle cell line. Although Trim33 knockdown mice weighed less than control mice, their skeletal muscles were histologically unremarkable and regenerated normally following injury. Unexpectedly, RNAseq analysis revealed dramatically increased expression of cholecystokinin (CCK) in regenerating muscle from Trim33 knockout mice, satellite cells from Trim33 knockout mice, and C2C12 cells treated with Trim33 siRNA. Trim33 knockdown had no demonstrable effect on muscle differentiation or regeneration. However, Trim33 knockdown induced CCK expression in muscle, suggesting that suppression of CCK expression requires Trim33.