Miracle-dz/UniFAR-FTUs huggingface dataset:
EFHD2 cooperates with E3 ubiquitin ligase Smurf1 to facilitate virus infection by promoting the degradation of TRAF6 in teleost fish

ABSTRACT The ubiquitin-proteasome system is one of the most important protein stability regulation systems. It can precisely regulate host immune responses by targeting signaling proteins. TRAF6 is a crucial E3 ubiquitin ligase in host antiviral signaling pathway. Here, we discovered that EF-hand domain-containing protein D2 (EFHD2) collaborated with the E3 ubiquitin ligase Smurf1 to potentiate the degradation of TRAF6, hence facilitating RNA virus Siniperca chuatsi rhabdovirus infection. The mechanism analysis revealed that EFHD2 interacted with Smurf1 and enhanced its protein stability by impairing K48-linked polyubiquitination of Smurf1, thereby promoting Smurf1-catalyzed degradation of TRAF6. This study initially demonstrated a novel mechanism by which viruses utilize host EFHD2 to achieve immune escape and provided a new perspective on the exploration of mammalian innate immunity. IMPORTANCE Viruses induce host cells to activate several antiviral signaling pathways. TNF receptor-associated factor 6 (TRAF6) plays an essential role in these pathways. Numerous studies have been done on the mechanisms of TRAF6-mediated resistance to viral invasion. However, little is known about the strategies that viruses employ to antagonize TRAF6-mediated antiviral signaling pathway. Here, we discovered that EFHD2 functions as a host factor to promote viral replication. Mechanistically, EFHD2 potentiates Smurf1 to catalyze the ubiquitin-proteasomal degradation of TRAF6 by promoting the deubiquitination and stability of Smurf1, which in turn inhibits the production of proinflammatory cytokines and interferons. Our study also provides a new perspective on mammalian resistance to viral invasion. Viruses induce host cells to activate several antiviral signaling pathways. TNF receptor-associated factor 6 (TRAF6) plays an essential role in these pathways. Numerous studies have been done on the mechanisms of TRAF6-mediated resistance to viral invasion. However, little is known about the strategies that viruses employ to antagonize TRAF6-mediated antiviral signaling pathway. Here, we discovered that EFHD2 functions as a host factor to promote viral replication. Mechanistically, EFHD2 potentiates Smurf1 to catalyze the ubiquitin-proteasomal degradation of TRAF6 by promoting the deubiquitination and stability of Smurf1, which in turn inhibits the production of proinflammatory cytokines and interferons. Our study also provides a new perspective on mammalian resistance to viral invasion.
Multicenter evaluation of the Selux Next-Generation Phenotyping antimicrobial susceptibility testing system

ABSTRACT The Selux Next-Generation Phenotyping (NGP) system (Charlestown, MA) is a new antimicrobial susceptibility testing system that utilizes two sequential assays performed on all wells of doubling dilution series to determine MICs. A multicenter evaluation of the performance of the Selux NGP system compared with reference broth microdilution was conducted following FDA recommendations and using FDA-defined breakpoints. A total of 2,488 clinical and challenge isolates were included; gram-negative isolates were tested against 24 antimicrobials, and gram-positive isolates were tested against 15 antimicrobials. Data is provided for all organism-antimicrobial combinations evaluated, including those that did and did not meet FDA performance requirements. Overall very major error and major error rates were less than 1% (31/3,805 and 107/15,606, respectively), essential agreement and categorical agreement were >95%, reproducibility was ≥95%, and the average time-to-result (from time of assay start to time of MIC result) was 5.65 hours.
The Natural History and Treatment of Meningiomas: An Update

Abstract Meningiomas are the most frequent nonmalignant tumors of the central nervous system (CNS). Despite their benign nature and slow-growing pattern, if not diagnosed early, these tumors may reach relatively large sizes causing significant morbidity and mortality. Some variants are located in hard-to-access locations, compressing critical neurovascular structures, and making the surgical management even more challenging. Although most meningiomas have a good long-term prognosis after treatment, there are still controversies over their management in a subset of cases. While surgery is the first-line treatment, the use of fractionated radiotherapy or stereotactic radiosurgery is indicated for residual or recurrent tumors, small lesions, and tumors in challenging locations. Advances in molecular genetics and ongoing clinical trial results have recently helped both to refine the diagnosis and provide hope for effective biomolecular target-based medications for treatment. This article reviews the natural history and current therapeutic options for CNS meningiomas.
La fractura del escafoides carpiano en edad avanzada: Análisis en un área de alta incidencia

Resumen Introducción y objetivos La fractura de escafoides es la más común dentro de las fracturas del carpo. El objetivo de nuestro trabajo es realizar un estudio analizando los resultados de las fracturas de escafoides en gente de edad avanzada. Material y método Se realizó un estudio observacional retrospectivo recogiendo todas las fracturas de escafoides en pacientes de más de 65 años diagnosticadas del 2016 al 2020. Se recogieron las variables de edad, género, lateralidad, tipo de traumatismo, lugar del traumatismo, estabilidad de la fractura, clasificación según Herbert, trazo de fractura, presencia de lesiones asociadas, afectación de la mano dominante, tipo de tratamiento realizado y ausencia o no de consolidación. Resultados Se registraron 24 pacientes con fractura de escafoides de más de 65 años. El 75% eran mujeres. La tasa de incidencia fue de 5,49 fracturas por cada 100.000 habitantes. Se halló una incidencia de pseudoartrosis del 8,3%. Se manejaron quirúrgicamente el 8,3% y fueron clasificadas como A2 el 37,5% de las fracturas. Conclusión La tasa de incidencia de la fractura de escafoides en pacientes de más de 65 años hallada en nuestra área sanitaria es superior a la referida en los escasos estudios previos. Se observó prevalencia del género femenino y no se hallaron diferencias significativas para la consolidación de la fractura al comparar manejo conservador y quirúrgico. Abstract Introduction The scaphoid fracture is the most common carpal fracture. This study aimed to analyze scaphoid fracture outcomes in elderly subjects. Method This study is retrospective and observational based on all scaphoid fractures in patients over 65 years old diagnosed from 2016 to 2020. The analyzed variables included age, gender, laterality, trauma type, trauma location, fracture stability, Herbert classification, fracture line, associated injuries, dominant hand involvement, treatment type, and consolidation presence or absence. Results The study included 24 patients over 65 years old with scaphoid fractures. Seventy-five percent of the subjects were women. The incidence rate was 5.49 fractures per 100,000 inhabitants. The nonunion incidence was 8.3%. Treatment was surgical for 8.3% of patients, and 37.5% of the fractures were classified as A2. Conclusion The incidence rate of scaphoid fracture in patients over 65 years in our healthcare area is higher than the few previous reports. The female gender was more affected, and there were no significant differences in fracture consolidation when comparing conservative and surgical management.
Comparing the Origin-Destination Matrices from Travel Demand Model and Social Media Data

In this paper the authors use Twitter data and a recently developed algorithm at the University of California Santa Barbara to extract Origin-Destination pairs in the Greater Los Angeles metropolitan area known as the Southern California Association of Governments (SCAG) region. This algorithm contains two steps: individual-based trajectory detection and place-based trip aggregation. In essence, if a person tweeted in different TAZs within 4 hours, it is considered to be one OD-trip. The extracted OD-trips were aggregated into 30 minute intervals. Then, the authors compare these trips with a traditional travel demand model (SCAG, 2012, 4-step model). Substantial spatial heterogeneity is found and a variety of social factors including the tweeting demographics. In this paper the authors illustrate the results from a spatially autoregressive regression model and a three-class latent class regression model that convert tweet derived trips to four-step trips accounting for zonal and trip-maker heterogeneity. In these regression models the authors use measures of business density and diversity, and population density as added explanatory/control variables, so that a unit contribution of a tweet trip can be adjusted by land-use effects and the trip producing zones in the twitter data can be explained in a more complete way. Preliminary results are encouraging and show the usefulness of harvested large-scale mobility data from location-based social media. The results also show the added value of latent class regression models in this experiment. The paper concludes with a review of next steps.
Yükseköğretim kurumlarinda yaban hayati eğitimi, önemi ve karşilaşilan sorunlar

As an historical process, wildlife educations in higher learning institutions have some differences in Turkey compared to those of the developed western countries. Especially, opening of the wildlife programs and departments has not received the necessary attention until recent years in Turkey. Wildlife education is given as associate degree, undergraduate and postgraduate levels in the Universities of Turkey. The number of associate degree programmes, named as “Hunting and Wildlife”, is increasing day by day within various universities. Departments of Wildlife Ecology and Management are mostly located within the forestry faculties. Only in Usak University, "Department of Wildlife Ecology and Management" is placed in the Faculty of Agriculture and Natural Sciences. In this review, the importance of wildlife education, its historical process in both Turkey and especially in developed western countries, its contribution to the economy, job opportunities, encountered problems and solutions were discussed. Keywords: Wildlife, Universities, Education, Economy
Power Plastics: A Hybrid Lagrangian/Eulerian Solver for Mesoscale Inelastic Flows

We present a novel hybrid Lagrangian/Eulerian method for simulating inelastic flows that generates high-quality particle distributions with adaptive volumes. At its core, our approach integrates an updated Lagrangian time discretization of continuum mechanics with the Power Particle-In-Cell geometric representation of deformable materials. As a result, we obtain material points described by optimized density kernels that precisely track the varying particle volumes both spatially and temporally. For efficient CFL-rate simulations, we also propose an implicit time integration for our system using a non-linear Gauss-Seidel solver inspired by X-PBD, viewing Eulerian nodal velocities as primal variables. We demonstrate the versatility of our method with simulations of mesoscale bubbles, sands, liquid, and foams.
Online Scene CAD Recomposition via Autonomous Scanning

Autonomous surface reconstruction of 3D scenes has been intensely studied in recent years, however, it is still difficult to accurately reconstruct all the surface details of complex scenes with complicated object relations and severe occlusions, which makes the reconstruction results not suitable for direct use in applications such as gaming and virtual reality. Therefore, instead of reconstructing the detailed surfaces, we aim to recompose the scene with CAD models retrieved from a given dataset to faithfully reflect the object geometry and arrangement in the given scene. Moreover, unlike most of the previous works on scene CAD recomposition requiring an offline reconstructed scene or captured video as input, which leads to significant data redundancy, we propose a novel online scene CAD recomposition method with autonomous scanning, which efficiently recomposes the scene with the guidance of automatically optimized Next-Best-View (NBV) in a single online scanning pass. Based on the key observation that spatial relation in the scene can not only constrain the object pose and layout optimization but also guide the NBV generation, our system consists of two key modules: relation-guided CAD recomposition module that uses relation-constrained global optimization to get accurate object pose and layout estimation, and relation-aware NBV generation module that makes the exploration during the autonomous scanning tailored for our composition task. Extensive experiments have been conducted to show the superiority of our method over previous methods in scanning efficiency and retrieval accuracy as well as the importance of each key component of our method.
Optimal Design of Robotic Character Kinematics

The kinematic motion of a robotic character is defined by its mechanical joints and actuators that restrict the relative motion of its rigid components. Designing robots that perform a given target motion as closely as possible with a fixed number of actuated degrees of freedom is challenging, especially for robots that form kinematic loops. In this paper, we propose a technique that simultaneously solves for optimal design and control parameters for a robotic character whose design is parameterized with configurable joints. At the technical core of our technique is an efficient solution strategy that uses dynamic programming to solve for optimal state, control, and design parameters, together with a strategy to remove redundant constraints that commonly exist in general robot assemblies with kinematic loops. We demonstrate the efficacy of our approach by either editing the design of an existing robotic character, or by optimizing the design of a new character to perform a desired motion.
Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases

Proteolytic cell surface release (‘shedding’) of the prion protein (PrP), a broadly expressed GPI-anchored glycoprotein, by the metalloprotease ADAM10 impacts on neurodegenerative and other diseases in animal and in vitro models. Recent studies employing the latter also suggest shed PrP (sPrP) to be a ligand in intercellular communication and critically involved in PrP-associated physiological tasks. Although expectedly an evolutionary conserved event, and while soluble forms of PrP are present in human tissues and body fluids, neither proteolytic PrP shedding and its cleavage site nor involvement of ADAM10 or the biological relevance of this process have been demonstrated for the human body thus far. In this study, cleavage site prediction and generation (plus detailed characterization) of sPrP-specific antibodies enabled us to identify PrP cleaved at tyrosin 226 as the physiological and strictly ADAM10-dependent shed form in humans. Using cell lines, neural stem cells and brain organoids, we show that shedding of human PrP can be stimulated by PrP-binding ligands without targeting the protease, which may open novel therapeutic perspectives. Site-specific antibodies directed against human sPrP also detect the shed form in brains of cattle, sheep and deer, hence in all most relevant species naturally affected by fatal and transmissible prion diseases. In human and animal prion diseases, but also in patients with Alzheimer’s disease, sPrP relocalizes from a physiological diffuse tissue pattern to intimately associate with extracellular aggregates of misfolded proteins characteristic for the respective pathological condition. Findings and research tools presented here will accelerate novel insight into the roles of PrP shedding (as a process) and sPrP (as a released factor) in neurodegeneration and beyond.
Fetal lung vascular development is disrupted by mechanical compression and rescued by administration of amniotic fluid stem cell extracellular vesicles via regulation of the Hippo signaling pathway

Postnatal pulmonary hypertension is the biggest treatment challenge and major determinant for poor outcome in infants with congenital diaphragmatic hernia (CDH). CDH lungs are hypoplastic and exhibit vascular remodeling, whose pathogenesis remains poorly understood. Using a novel micro-static compression system, herein we found that mechanical compression induces vascular remodeling and downregulation of key angiogenic markers in rat and human fetal lung models, with similar features observed in CDH fetal lung autopsy samples. These fetal lung vascular changes are reversed back to normal upon administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC-EVs), a regenerative approach previously shown to restore lung branching morphogenesis and epithelial differentiation in CDH models. Exploring pathways that are dysregulated in CDH lungs and involved in mechanotransduction, we found that compressed fetal lungs had altered expression of Hippo signaling factors that was restored upon AFSC-EV administration. We found that AFSC-EV cargo contains some miRNAs involved in lung vascular development and Hippo pathway, indicating that AFSC-EV regenerative effects is associated with the delivery of specific miRNAs. This study uncovers the role of mechanical compression that herniated organs exert on CDH fetal lungs and proposes a new cell-free strategy to restore normal fetal lung vascular development.
A brief review of isotopically light Li – a feature of the enriched mantle?

Lithium isotope geochemistry is increasingly being used to trace deep-earth processes, reflecting the observed large variation of Li isotope ratios in mantle-derived rocks, including peridotite xenoliths associated with ancient continents. We briefly review the Li isotopic compositions of major geochemical reservoirs, the assumed mechanisms of Li isotopic fractionation, and, in particular, the origins of isotopically light Li in mantle-derived rocks based on the latest developments in Li isotope geochemistry. Comparison of Li isotope data with existing Sr-Nd isotope ratios reflects the subduction-recycling of ancient oceanic crust and the reappearance of Li in volcanic rocks. This circulation may play an important role in generating the isotopically light-Li component in the mantle – perhaps the enriched mantle end member defined by the Sr-Nd isotopic compositions of oceanic basalts.
Caveolin scaffolding domain (CSD) peptide LTI-2355 modulates the phagocytic and synthetic activity of lung derived myeloid cells in Idiopathic Pulmonary Fibrosis (IPF) and Post-acute sequelae of COVID-fibrosis (PASC-F)

Rationale The role of the innate immune system in Idiopathic Pulmonary Fibrosis (IPF) remains poorly understood. However, a functional myeloid compartment is required to remove dying cells and cellular debris, and to mediate innate immune responses against pathogens. Aberrant macrophage activity has been described in patients with Post-acute sequelae of COVID fibrosis (PASC-F). Therefore, we examined the functional and synthetic properties of myeloid cells isolated from normal donor lung and lung explant tissue from both IPF and PASC-F patients and explored the effect of LTI-2355, a Caveolin Scaffolding Domain (CSD) peptide, on these cells. Methods & Results CD45+ myeloid cells isolated from lung explant tissue from IPF and PASC-F patients exhibited an impaired capacity to clear autologous dead cells and cellular debris. Uptake of pathogen-coated bioparticles was impaired in myeloid cells from both fibrotic patient groups independent of type of pathogen highlighting a cell intrinsic functional impairment. LTI-2355 improved the phagocytic activity of both IPF and PASC-F myeloid cells, and this improvement was paired with decreased pro-inflammatory and pro-fibrotic synthetic activity. LTI-2355 was also shown to primarily target CD206-expressing IPF and PASC-F myeloid cells. Conclusions Primary myeloid cells from IPF and PASC-F patients exhibit dysfunctional phagocytic and synthetic properties that are reversed by LTI-2355. Thus, these studies highlight an additional mechanism of action of a CSD peptide in the treatment of IPF and progressive fibrotic lung disease.
ThermoLink: Bridging Disulfide Bond and Enzyme Thermostability through Database Construction and Machine Learning Prediction

Disulfide bonds (SS bonds), covalently formed by sulfur atoms in cysteine residues, play a crucial role in protein folding and structure stability. Due to their significance, artificial disulfide bonds are often introduced to enhance the thermostability of proteins. Although an increasing number of tools can assist with this task, significant amounts of time and resources were often wasted due to inadequate consideration. To enhance the accuracy and efficiency of designing disulfide bonds for protein thermostability improvement, we first collected disulfide-bond data with protein thermostability data from extensive literature sources. Then, various sequence- and structure-based features were extracted, and machine learning models were constructed to predict whether a disulfide bond could improve protein thermostability. Among all models, the neighborhood context model using the Adaboost-DT algorithm performs the best, and the AUC-ROC score and accuracy are 0.773 and 0.714, respectively. Alongside this, we also found that AlphaFold2 exhibits a high superiority in predicting disulfide bonds, and the coevolutionary relationship between residue pairs, to some extent, could also guide artificial disulfide-bond design. The SS-bond data has been integrated into an online server, named ThermoLink, available at guolab.mpu. edu.mo/thermoLink. Key Messages We manually curated a database of disulfide bonds and their impacts on protein thermostability from the literature. AlphaFold2 exhibits a high superiority in predicting disulfide bonds, and to some extent, the conservation and co-evolutionary information of the residue pairs involved in disulfide bonds could also guide artificial disulfide-bond design. Machine learning models were developed to predict potential disulfide bonds with the aim of improving protein thermostability, offering an extended design strategy beginning with existing SS-bond prediction tools to optimize variant selection. This work provides valuable data and theoretical support for a more precise design of disulfide bonds for improving protein thermostability.
Federal Reserve Bank of Minneapolis Research Department Staff Report 309 Usc Fbe Macroeconomics and International Finance Workshop Presented

We derive the quantitative implications of growth theory for U.S. corporate equity plus net debt over the period 1960–2001. There were large secular movements in corporate equity values relative to GDP, with dramatic declines in the 1970s and dramatic increases starting in the 1980s and continuing throughout the 1990s. During the same period, there was little change in the capital-output ratio or earnings share of output. We ask specifically whether the theory accounts for these observations. We find that it does, with the critical factor being changes in the U.S. tax and regulatory system. We find that the theory also accounts for the even larger movements in U.K. equity values relative to GDP in this period. and three anonymous referees for their comments. We thank Martin Weale and Shane Duffield for their help with U.K. data. We also thank the National Science Foundation for financial support. The views expressed herein are those of the authors and not necessarily those of the Federal Reserve Bank of Minneapolis or the Federal Reserve System.