Miracle-dz/UniFAR-FTUs huggingface dataset:
Cannabinoid Receptor 2 (CB2) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes

Cannabinoid receptor 2 (CB2) is a promising therapeutic target for immunological modulation. There is, however, a deficit of knowledge regarding CB2 signaling and function in human primary immunocompetent cells. We applied an experimental paradigm which closely models the in situ state of human primary leukocytes (PBMC; peripheral blood mononuclear cells) to characterize activation of a number of signaling pathways in response to a CB2-selective ligand (HU308). We observed a “lag” phase of unchanged cAMP concentration prior to development of classically-expected Gαi-mediated inhibition of cAMP synthesis. Application of G protein inhibitors revealed that this apparent lag was a result of counteraction of Gαi effects by concurrent Gαs activation. Monitoring downstream signaling events, activation of p38 was mediated by Gαi whereas ERK1/2 and Akt phosphorylation were mediated by Gαi-coupled βγ. Activation of CREB integrated multiple components; Gαs and βγ mediated ∼85% of the response, while ∼15% was attributed to Gαi. Responses to HU308 had an important functional outcome – secretion of interleukins 6 (IL-6) and 10 (IL-10). IL-2, IL-4, IL-12, IL-13, IL-17A, MIP-1α, and TNF-α were unaffected. IL-6/IL-10 induction had a similar G protein coupling profile to CREB activation. All response potencies were consistent with that expected for HU308 acting via CB2. Additionally, signaling and functional effects were completely blocked by a CB2-selective inverse agonist, giving additional evidence for CB2 involvement. This work expands the current paradigm regarding cannabinoid immunomodulation and reinforces the potential utility of CB2 ligands as immunomodulatory therapeutics. Significance statement Cannabinoid receptor 2 (CB2) is a G protein-coupled receptor which plays a complex role in immunomodulation and is a promising target in a range of disorders with immune system involvement. However, to date the majority of the studies in this field have been performed on cell lines, rodent models, or stimulated primary cells. Here we provide a detailed account of CB2-mediated signaling in primary human immune cells under conditions which closely mimic their in vivo state. We reveal a complex signaling system involving an unprecedented CB2 signaling pathway and leading to immunomodulatory functional outcomes. This work provides not only a critical foundation impacting CB2-targeted drug discovery, but reveals important wider considerations for GPCR signaling studies and model validity. Table of Contents Summary Figure
Cellular immune response in infected mice to NSP protein encoded by the negative strand NS RNA of influenza A virus

Influenza A virus belongs to a family of enveloped viruses with an RNA genome of negative polarity consisting of 8 RNA segments. The transcription of this RNA genome results in the synthesis of positive-sense mRNAs that translate up to 16 unique viral proteins with the help of splicing and translational shift mechanisms. The 8th NS segment encodes the NS1 protein (27 kDa), which is an active interferon antagonist, and the nuclear export protein NEP (14 organism post viral infection, the generation of spleen leucocytes specific to this protein was studied in mice after two sequential infections with influenza A viruses of H1N1 and H3N2 subtypes. It was found that leucocyte clones specifically recognizing a peptide domain in the central region of the NSP protein (amino acid positions 82-119) were generated in mice infected with influenza A viruses. In silico prediction has shown strong major histocompatibility complex-1 (MHC-I) and MHC-II specific epitopes in this central domain of the NSP. Comparative analysis of the influenza H3N2 viruses circulating in humans during 1968-2018 has shown high NSP variability, which was similar to that shown for the hemagglutinin (HA) and neuraminidase (NA) proteins. The highest variability was found to be in the N- and C-terminal parts of the NSP. These observations suggest that synthesis of the NSP protein occurs in infected animals and further support a bipolar (ambisense) strategy of the RNA genome of human influenza A virus.
Control of a large flexible space structure with moving-bank multiple model adaptive algorithms

The development and performance of moving-bank multiple model adaptive control (MMAC) algorithms for quelling vibrations induced in the SPICE 2 space structure are presented. The structure consists of a large platform and a smaller platform connected by three legs in a tripod fashion. Deviations of the line-of-sight vector from the center of the large platform to the center of the smaller platform are used for linear quadratic Gaussian (LQG) controller performance evaluation. The parameter estimator implements the maximum entropy with an identity covariance (ME/I) algorithm, the moving-bank logic employs parameter position monitoring, and the controller uses the modified MMAC method. Whereas parameter variations of two percent caused instabilities in the single filter/controller design, the MMAC algorithm provides an excellent method to estimate a wide range of parameter variations and to quell oscillations in the structure. <<ETX>>
Walker-256 Tumor: Experimental Model, Implantation Sites and Number of Cells for Ascitic and Solid Tumor Development

1 Federal University of Mato Grosso do Sul, Faculty of Medicine, Graduate Program in Health and Development in the Midwestern Region, Campo Grande, Mato Grosso do Sul, Brazil. 2 Federal University of Mato Grosso do Sul, Graduating in Food Technology at the Faculty of Pharmaceutical Sciences, Food and Nutrition, Campo Grande, Mato Grosso do Sul, Brazil. 3 Federal University of Mato Grosso do Sul, Faculty of Medicine, Program in Health and Development in the Midwestern Region, Stem Cell, Cell Therapy and Toxicological Genetics Research Centre, Maria Aparecida Pedrossian, University Hospital, Brazilian Hospital Services Company, Campo Grande, Mato Grosso do Sul, Brazil. 4 Federal University of Mato Grosso do Sul, Associate Professor at the Faculty of Pharmaceutical Sciences, Food and Nutrition, Postgraduate Program in Health and Development in the Midwestern Region, Campo Grande, Mato Grosso do Sul, Brazil.
An integrative Chinese lexical analyzer based on maximum matching and second-maximum matching segmentation

This paper demonstrates an integrative lexical analysis mechanism to solve the limitation of the existing lexical analysis systems with "pipelining". The integrative lexical analysis mechanism extends the Maximum Matching and Second-Maximum Matching model, POS (part of speech) and all the candidate words is included in the directed graph. The Dijkstra algorithm is applied to find the minimum cost path in the directed graph. With the integrative model, word segmentation, POS tagging and unknown words recognition are accomplished synchronously, the conflicts of all tasks of lexical analysis are avoided, high precision can be gained. The open test indicates the precision of the system is 98.65% and recall is 98.96%.
The human Ska complex and Ndc80 complex interact to form a load-bearing assembly that strengthens kinetochore-microtubule attachments

Accurate segregation of chromosomes relies on the force-bearing capabilities of the kinetochore to robustly attach chromosomes to dynamic microtubule tips. The human Ska complex and Ndc80 complex are outer-kinetochore components that bind microtubules and are required to fully stabilize kinetochore-microtubule attachments in vivo. While purified Ska complex tracks with disassembling microtubule tips, it remains unclear whether the Ska complex-microtubule interaction is sufficiently strong to make a significant contribution to kinetochore-microtubule coupling. Alternatively, Ska complex might affect kinetochore coupling indirectly, through recruitment of phospho-regulatory factors. Using optical tweezers, we show that the Ska complex itself bears load on microtubule tips, strengthens Ndc80 complex-based tip attachments, and increases the switching dynamics of the attached microtubule tips. Crosslinking mass spectrometry suggests the Ska complex directly binds Ndc80 complex through interactions between the Ska3 unstructured C-terminal region and the coiled-coil regions of each Ndc80 complex subunit. Deletion of the Ska complex microtubule-binding domain or the Ska3 C-terminus prevents Ska complex from strengthening Ndc80 complex-based attachments. Together our results indicate that the Ska complex can directly strengthen the kinetochore microtubule interface and regulate microtubule tip dynamics by forming an additional connection between the Ndc80 complex and the microtubule. SIGNIFICANCE STATEMENT Microtubules are dynamic, tube-like structures that drive the segregation of duplicated chromosomes during cell division. The Ska complex is part of a molecular machine that forms force-bearing connections between chromosomes and microtubule ends. Depletion of the Ska complex destabilizes these connections and disrupts cell division. The Ska complex binds microtubules but it is unknown if it directly holds force at microtubules or indirectly stabilizes the connections. Here, we show that the Ska complex makes a direct force-bearing linkage with microtubule ends and assembles with another microtubule binding component, the Ndc80 complex, to strengthen its ability to withstand force. Our results suggest that the Ska and Ndc80 complexes work together to maintain the connections between chromosomes and microtubule ends.
Apolipoprotein L9 interacts with LC3/GABARAP and is a microtubule-associated protein with a widespread subcellular distribution

ABSTRACT Mouse Apolipoprotein L9 is a 34-kDa phosphatidylethanolamine (PE)-binding protein. The gene is present only in mouse and rat genomes; hence it is restricted to two species. To understand why, it is essential to uncover details about its functions in cellular processes. Here we show that ApoL9 interacts with the proteins of the LC3 and GABARAP subfamilies, which are key players in macroautophagy. In vitro binding studies show a strong association with GABARAP, and in amino acid-starved cells it preferentially interacts with lipidated LC3B, likely by binding to its PE moiety through its lipid-binding domain. On treatment with autophagy inhibitors bafilomycin A1 and chloroquine, ApoL9 is found near swollen mitochondria and on lysosomes/LAMP1-positive compartments. However, ApoL9 itself does not seem to be degraded as a result of autophagy, suggesting that it is not an autophagy cargo receptor. Deletions in a putative transmembrane region between amino acids 110 and 145 abolish binding to PE. In addition, ApoL9 can redistribute to stress granules, can homo-oligomerize, and is a microtubule-associated protein. In short, its distribution in the cell is quite widespread, suggesting that it could have functions at the intersection of membrane binding and reorganization, autophagy, cellular stress and intracellular lipid transport. This article has an associated First Person interview with the first author of the paper. Summary: This article is about how Apolipoprotein L9, a lipid-binding protein, has versatile properties and influences a variety of processes taking place inside an animal cell.
Improving the quality of tracheostomy care

Educational aims To understand the current challenges in the care of tracheostomy patients To understand principles of quality improvement collaboration and how this can improve the quality of care for tracheostomy patients Summary The UK National Confidential Enquiry into Patient Outcomes and Death illustrates that there remains significant morbidity and mortality relating to patients with a tracheostomy, with much preventable harm. Challenges include the inherent complexity of the patient's underlying condition, wide variations in tracheostomy management, variable delivery of education for staff, patients and families, and difficult coordination of care between such a variety of individuals involved in performing, managing and ultimately removing tracheostomies. Quality-improvement collaboratives are groups of institutions with a common purpose who work together to drive positive change. They help support clinicians in developing skills and teams necessary to design and sustain quality-improvement cycles. They are a cost-effective way of rapidly disseminating improvement strategies and engaging in shared learning across institutions around the world. The Global Tracheostomy Collaborative aims to improve quality of care and outcomes through five interdependent key drivers: coordinated multidisciplinary team care, education, institution-wide protocols, family and patient-centred care, and metrics and outcomes using a specifically designed database.
High-grade serous ovarian cancer subtypes are similar across populations

Background Three to four gene expression-based subtypes of high-grade serous ovarian cancer (HGSC) have been previously reported. We sought to systematically determine the similarity of HGSC subtypes between populations. Methods We performed k-means clustering (k = 3 and k = 4) in five publicly-available HGSC mRNA expression datasets with >130 tumors. Within each population, we summarized differential expression patterns for each cluster as moderated t statistic vectors using Significance Analysis of Microarrays. We calculated Pearsons correlations of these vectors to determine similarities and differences in expression patterns between clusters. We defined syn-clusters (SC) as sets of clusters that were strongly correlated across populations, and associated their expression patterns with biological pathways using geneset overrepresentation analyses. Results Across populations, for k = 3, moderated t score correlations for clusters 1, 2 and 3, respectively, ranged between 0.77-0.85, 0.80-0.90, and 0.65-0.77. For k = 4, correlations for clusters 1-4, respectively, ranged between 0.77-0.85, 0.83-0.89, 0.51-0.76, and 0.61-0.75. Within populations, comparing analogous clusters (k = 3 versus k = 4), correlations were high for clusters 1 and 2 (0.91-1.00), but were lower for cluster 3 (0.22-0.80). The results are similar using non-negative matrix factorization. SC1 corresponds to previously-reported mesenchymal-like, SC2 to proliferative-like, SC3 to immunoreactive-like, and SC4 to differentiated-like subtypes. Conclusions The ability to robustly identify correlated clusters across number of centroids, populations, and clustering methods provides strong evidence that at least three different HGSC subtypes exist. The mesenchymal-like and proliferative-like subtypes are remarkably consistent and could be uniquely targeted for treatment.
Performance of Chia on Different Sowing Dates: Characteristics of Growth Rate, Leaf Area Index, Shoot Dry Matter Partitioning and Grain Yield

The objective of this study was to comparatively determine the characteristics of growth rate, leaf area index, shoot dry mass partitioning and grain yield of chia plants (Salvia hispanica L.) on different sowing dates. A field experiment was conducted in the crop year of 2016/2017 in five sowing dates (09/22/16, 10/28/16, 01/03/17, 02/08/17 and 03/24/17) with a randomized complete block design and four replicates. Plant growth was determined through field samplings to determine the dry matter mass and leaf area performed every 15 days. The following physiological indexes were calculated: relative growth rate, absolute growth rate, net assimilation rate, leaf area ratio, specific leaf area and leaf mass ratio. To weekly evaluate plant height, ten plants per plot were marked after emergence, and the final height was considered when plants reached physiological maturity. A useful area of 2.10 m² per plot was collected for evaluating grain yield. The physiological indexes indicated that at earlier sowing dates there is a greater plant growth, either in shoot dry matter mass, height and leaf area index. The leaf area index of branches is progressively increased with plant development and contributes significantly to total leaf area index of chia plants in all studied sowing dates. The main stem represents between 60 and 70% of the shoot dry matter accumulated in the early sowing dates, and between 40 and 50% in late sowing. The best sowing date in terms of grain yield is 01/03/17.
Gene Expression and Molecular Differences in Two Wheat Genotypes under Salt and Drought Stresses

T HIS STUDY was conducted to point out some highlights on the difference between two contrasting tolerant wheat varieties regarding to genetic expression and molecular characterization under salt and drought stress. Two different tolerant wheat genotypes namely, Gemmiza9 (sensitive) and Sakha93 (tolerant) were used to investigate the molecular and genetic differences under salt and drought stress. Stress treatments were used NaCl and poly ethylene glycol (PEG) of different levels. Sodium dodecyl sulphate polyacrylamide gel electrophoresis(SDS PAGE) analysis was revealed three disappeared bands with 15, 25, 90 kilodalton (KD) in salt treated plants of Gemmiza9 and appeared these bands as constant in controlled and salt treated plants of Sakha93. Contradict vision for protein profile was under drought stress that constant bands were disappeared and new synthetic bands were exhibited in both Gemmiza9 and Sakha93. Moreover, Random amplification of polymorphic DNA (RAPD) markers were produced several number of unique bands in Sakha93. Primer 2 generated unique bands in Gemmiza9. Simple sequence repeats (SSR) markers were 100% polymorphism. WMC_179 marker out of six markers was present unique alleles only in Sakha93. This marker might be practical and advantageous to the genotype that recognized to tolerance QTL markers alleles to utilize in marker assisted selection in further study. Comparison between RAPD and SSR markers was revealed that QND was less (0.06) in RAPD than in SSR (0.56). EMI was higher (0.31) in RAPD than in SSR (0.23). Nonetheless, the findings might be valuable and helpful to identify the genetic and molecular characterizations of different tolerant genotypes.
Picturephone: A Game for Sketch Data Capture

This article introduces Picturephone, a sketch-based game forcollectingdataonhowpeoplemakeanddescribesketches. The approach is based on the technique of human computation, where players provide information about drawings in exchange for entertainment. The system collects raw sketch input and associates it with human-provided text descriptions. Researchers may browse and download this data for their own purposes. The proposed sketching game has users describe drawings textually in one phase followed by another phase of drawing based on a text description. To score points, users must reconstruct a drawing based on a text description or vice-versa. A third phase asks users to judge the work of other players, which awards points appropriately. The Picturephone game system architecture is briefly described, followed by a discussion of future work on sketching games as a platform for researching sketch recognition and interaction. Author Keywords Sketch recognition, human computation, games, calligraphic interfaces
Distribusi Spasial Kerapatan Mangrove Menggunakan Citra Sentinel-2A Di TAHURA Ngurah Rai Bali

The mangrove forest of TAHURA Ngurah Rai is one of the mangrove ecosystems in Bali that suffered damages and density changes due to natural factors and human activities. Remote sensing is one of the technology that can be used to estimate the density of mangrove canopy in TAHURA Ngurah Rai. The purpose of this study was to find the best vegetation index for estimating mangrove canopy density out and map it spatially using Sentinel-2A image. The method of this research is using vegetation index NDVI, EVI and mRE-SR to estimate mangrove canopy density. Field data was collected using Stratified Random and Proportional Sampling method by taking photo of the density of canopy using camera with Fish Eye lens on 34 plot. The results of this study show the satistic test of the linear model of the vegetation index with the mangrove canopy density value on the NDVI index (r = 0.8165, R2 = 0.6667, RMSE = ± 8.1508), EVI (r = 0.8597, R2 = 0.7390, RMSE = ± 7.8117), and mRE-SR (r = 0.9277, R2 = 0.8607, RMSE = ± 4.9571). The conclusion of this research is mRE-SR vegetation index able to map mangrove canopy density better than NDVI and EVI vegetation index with 86.07% accuracy. The mangrove spatial distribution generated from the mRE-SR model is 1002.22 Ha with 3.24 Ha categorized as very high density, 94.82 Ha categorized as high density, 333 Ha categorized as medium density, 402.38 Ha categorized as low density, and categorized as very low density is up to 168.76 Ha.
The Static Semantics of the Green-Marl Graph Analysis Language: Formal Specification, Declarative Implementation and Integration with a Compiler Back-end

Green-Marl is a domain specific language for efficient graph analysis. In this thesis, we define the formal static semantics of the language and provide an implementation in the Spoofax language workbench. The type system of Green-Marl includes limited forms of name-dependent types, overloading, parametric polymorphism, and inference. We give a formal specification that covers all aspects of this type system. We also describe our implementation of the type system in the Spoofax language workbench, where we focus on the capabilities of Spoofax's meta-languages to describe the type system. Green-Marl provides several parallel language constructs, as well as constructs to mitigate data races that can occur in parallel regions. We give a formal description of a symbolic, tree-based dependence analysis that can check the invariants of the mitigation strategies and find potential data races. We employ a rewrite system for the implementation of this analysis in the Spoofax language workbench. Finally, we discuss the integration of these analyses with successive program transformation steps. Each transformation step is informed by the static analysis. However, transformation steps invalidate parts of the analysis results, which inhibits the successive steps. A naive approach to re-analyse the program after every transformation step does not scale. Therefore, we incrementally update analysis results after each transformation step.
Isoleucine Regulates the Synthesis of Pancreatic Enzymes via the Activation of mRNA Expression and Phosphorylation in the Mammalian Target of Rapamycin Signalling Pathways in Pancreatic Tissues

This study aimed to investigate the effects of isoleucine (Ile) on the synthesis and secretion of digestive enzymes and cellular signalling in the pancreatic tissue of dairy goats. The pancreatic tissues were incubated in buffer containing 0, 0.40, 0.80, and 1.60 mM Ile. High levels of Ile significantly increased the buffer release and total concentration of ɑ-amylase in the tissues (P < 0.001). The total trypsin and chymotrypsin concentrations in each of the Ile groups were significantly higher than those in the control group (P < 0.05); however, lipase was not affected. High levels of Ile significantly increased ɑ-amylase mRNA expression (P < 0.001) but had no effect on the mRNA expression of trypsin, chymotrypsin, or lipase. Ile did not affect S6K1 phosphorylation levels. High levels of Ile significantly increased the expression of the γ isoform of 4EBP1 (P < 0.001), which indicated that the phosphorylation of 4EBP1 was significantly increased. The phosphorylation level of eEF2 gradually decreased with the addition of Ile (P < 0.001). These results suggested that high doses of Ile can regulate the excretion of enzymes, especially ɑ-amylase, in the pancreatic tissues of dairy goats by modulating mTOR signalling, and this regulation is independent of the mTOR-S6K1 pathway.