Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycyrrhetinic acid induces cytoprotective autophagy via the inositol-requiring enzyme 1α-c-Jun N-terminal kinase cascade in non-small cell lung cancer cells

Glycerrhetinic acid (GA), one of the main bioactive constituents of Glycyrrhiza uralensis Fisch, exerts anti-cancer effects on various cancer cells. We confirmed that GA inhibited cell proliferation and induced apoptosis in non-small cell lung cancer A549 and NCI-H1299 cells. GA also induced expression of autophagy marker phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and punta formation of green fluorescent protein microtubule-associated protein light-chain 3. We further proved that expression of GA-increased autophagy marker was attributed to activation instead of suppression of autophagic flux. The c-jun N-terminal kinase (JNK) pathway was activated after incubation with GA. Pretreatment with the JNK inhibitor SP600125 or silencing of the JNK pathway by siRNA of JNK or c-jun decreased GA-induced autophagy. The endoplasmic reticulum (ER) stress responses were also apparently stimulated by GA by triggering the inositol-requiring enzyme 1α (IRE1α) pathway. The GA-induced JNK pathway activation and autophagy were decreased by IRE1α knockdown, and inhibition of autophagy or the JNK cascade increased GA-stimulated IRE1α expression. In addition, GA-induced cell proliferative inhibition and apoptosis were increased by inhibition of autophagy or the JNK pathway. Our study was the first to demonstrate that GA induces cytoprotective autophagy in non-small cell lung cancer cells by activating the IRE1α-JNK/c-jun pathway. The combined treatment of autophagy inhibitors markedly enhances the anti-neoplasmic activity of GA. Such combination shows potential as a strategy for GA or GA-contained prescriptions in cancer therapy.
Model building in IIA : Intersecting brane worlds

Angel M. Uranga IFT, Madrid, and CERN, Geneva Lecture 1. Model building in IIA: Intersecting brane worlds We review the construction of chiral four-dimensional compactifications of type IIA string theory with intersecting D6-branes. Such models lead to four-dimensional theories with non-abelian gauge interactions and charged chiral fermions. We discuss the application of these techniques to building of models with spectrum as close as possible to the Standard Model, and review their main phenomenological properties.
Salient object detection in video streams

In this paper we propose a complete framework for automatic detection and tracking of salient objects in video streams. The video flow is firstly segmented into shots based on scale space filtering graph partition method. For each detected shot the associated static summary is developed using a leap keyframe extraction method. Based on the representative images we introduce next a combined spatial and temporal video attention model that is able to recognize both interesting objects and actions in image sequences. The approach extends the state-of-the-art image region based contrast saliency with a temporal attention model. Different types of motion presented in the current shot are determined using a set of homographic transforms, estimated by recursively applying the RANSAC algorithm on the interest point correspondence. Finally, a decision is taken based on the combined information from both saliency maps. The experimental results validate the proposed framework and demonstrate that our approach is suitable for various types of videos and is robust to noise and low resolution.
Characterization of the Genes Encoding the Cytosolic and Plastidial Forms of ADP-Glucose Pyrophosphorylase in Wheat Endosperm1

In most species, the synthesis of ADP-glucose (Glc) by the enzyme ADP-Glc pyrophosphorylase (AGPase) occurs entirely within the plastids in all tissues so far examined. However, in the endosperm of many, if not all grasses, a second form of AGPase synthesizes ADP-Glc outside the plastid, presumably in the cytosol. In this paper, we show that in the endosperm of wheat (Triticum aestivum), the cytosolic form accounts for most of the AGPase activity. Using a combination of molecular and biochemical approaches to identify the cytosolic and plastidial protein components of wheat endosperm AGPase we show that the large and small subunits of the cytosolic enzyme are encoded by genes previously thought to encode plastidial subunits, and that a gene, Ta.AGP. S.1, which encodes the small subunit of the cytosolic form of AGPase, also gives rise to a second transcript by the use of an alternate first exon. This second transcript encodes an AGPase small subunit with a transit peptide. However, we could not find a plastidial small subunit protein corresponding to this transcript. The protein sequence of the purified plastidial small subunit does not match precisely to that encoded by Ta.AGP. S.1 or to the predicted sequences of any other known gene from wheat or barley (Hordeum vulgare). Instead, the protein sequence is most similar to those of the plastidial small subunits from chickpea (Cicer arietinum) and maize (Zea mays) and rice (Oryza sativa) seeds. These data suggest that the gene encoding the major plastidial small subunit of AGPase in wheat endosperm has yet to be identified.
epicardin: A novel basic helix‐loop‐helix transcription factor gene expressed in epicardium, branchial arch myoblasts, and mesenchyme of developing lung, gut, kidney, and gonads

We report the cloning, chromosomal localization, and analysis of the expression pattern of epicardin, a member of the basic helix‐loop‐helix (bHLH) family of transcription factors. Within its bHLH domain, the human and murine epicardin genes were most similar to paraxis, a bHLH gene important for segmentation of embryonic paraxial mesoderm. In situ hybridization studies revealed strong epicardin expression in murine embryos at 9.5 days postcoitum (dpc) in a region of the septum transversum at the base of the heart known as the proepicardial organ. This mesenchymal structure extends villous projections from which epicardial precursor cells emerge and migrate out over the surface of the myocardium. Strong expression was seen in individual migratory cells and clusters at 9.5 dpc and in a continuous epicardial cell layer in more mature hearts. Also from 9.5 dpc, epicardin transcripts were seen in endocardial cushions of the atrioventricular canal and outflow tract, in skeletal myoblasts within branchial arches and in condensing mesenchyme of gut, kidney, urinary tract, gonads, spleen, and lung. Northern analysis showed that expression persisted in mature visceral organs and heart, but was transient in skeletal muscle. The central role played by bHLH factors in pathways for tissue determination in the embryo suggests a function for epicardin in specification of select mesodermal cell populations associated with heart, cranial skeletal muscle, gut, and urogenital system. Dev. Dyn. 1998;213:105–113. © 1998 Wiley‐Liss, Inc.
Insulin-like growth factor 1 induction of differentiation of porcine preadipocytes.

The role of insulin-like growth factor I (IGF-1) in the development of the porcine preadipocyte was studied. Primary cultures of stromal-vascular cells (containing preadipocytes) were derived from s.c. adipose tissue of pigs at 1 d of age by enzyme digestion and centrifugation. Cells were cultured for a total of 15 d. Cells were exposed to IGF-1 at concentrations of 0, 5, 25 or 50 ng/ml medium during one of four time periods: d 1-15, d 1-5, d 13-15, or 4 h on d 15 of culture. IGF-1 had a mitogenic effect on cells during the first three time periods as determined by coulter counting. IGF-1 induced the enzymatic differentiation of porcine preadipocytes following exposure for either the entire 15 d of culture or for only 48 h (d 13-15) after confluency had been attained (d 5). Histochemically, lipid accumulation over time paralleled changes in enzyme activity. Incubation of IGF-1 with the cell cultures during the logarithmic phase of growth (d 1-5) or for 4 h on d 15 did not affect enzyme activity. These data indicate that IGF-1 can induce the differentiation of porcine preadipocytes after the cells leave the logarithmic phase of growth through action on post-confluent events.
Cystathionine γ-Lyase-deficient Mice Require Dietary Cysteine to Protect against Acute Lethal Myopathy and Oxidative Injury*

Cysteine is considered a nonessential amino acid in mammals as it is synthesized from methionine via trans-sulfuration. However, premature infants or patients with hepatic failure may require dietary cysteine due to a lack of cystathionine γ-lyase (CTH), a key trans-sulfuration enzyme. Here, we generated CTH-deficient (Cth−/−) mice as an animal model of cystathioninemia/cystathioninuria. Cth−/− mice developed normally in general but displayed hypercystathioninemia/hyperhomocysteinemia though not hypermethioninemia. When fed a low cyst(e)ine diet, Cth−/− mice showed acute skeletal muscle atrophy (myopathy) accompanied by enhanced gene expression of asparagine synthetase and reduced contents of glutathione in livers and skeletal muscles, and intracellular accumulation of LC3 and p62 in skeletal myofibers; they finally died of severe paralysis of the extremities. Cth−/− hepatocytes required cystine in a culture medium and showed greater sensitivity to oxidative stress. Cth−/− mice exhibited systemic vulnerability to oxidative injury, which became more prominent when they were fed the low cyst(e)ine diet. These results reveal novel roles of trans-sulfuration previously unrecognized in mice lacking another trans-sulfuration enzyme cystathionine β-synthase (Cbs−/−). Because Cbs−/− mice display hyperhomocysteinemia and hypermethioninemia, our results raise questions against the homocysteine-based etiology of CBS deficiency and the current newborn screening for homocysteinemia using Guthrie's method, which detects hypermethioninemia.
Intimal and medial contributions to the hydraulic resistance of the arterial wall at different pressures: a combined computational and experimental study

The hydraulic resistances of the intima and media determine water flux and the advection of macromolecules into and across the arterial wall. Despite several experimental and computational studies, these transport processes and their dependence on transmural pressure remain incompletely understood. Here, we use a combination of experimental and computational methods to ascertain how the hydraulic permeability of the rat abdominal aorta depends on these two layers and how it is affected by structural rearrangement of the media under pressure. Ex vivo experiments determined the conductance of the whole wall, the thickness of the media and the geometry of medial smooth muscle cells (SMCs) and extracellular matrix (ECM). Numerical methods were used to compute water flux through the media. Intimal values were obtained by subtraction. A mechanism was identified that modulates pressure-induced changes in medial transport properties: compaction of the ECM leading to spatial reorganization of SMCs. This is summarized in an empirical constitutive law for permeability and volumetric strain. It led to the physiologically interesting observation that, as a consequence of the changes in medial microstructure, the relative contributions of the intima and media to the hydraulic resistance of the wall depend on the applied pressure; medial resistance dominated at pressures above approximately 93 mmHg in this vessel.
The Boston Teacher Questionnaire. 2. Assessments of Validity

We assessed the validity of the Boston Teacher Questionnaire in a sample of 3451 9-year-old children. Those identified by the questionnaire as having a learning difficulty syndrome were compared to those without any characteristic of that syndrome. The validity reference measures were individually administered neuropsychological assessments at age 7 years and a group-administered reading achievement test at age 9 years. Girls and boys with the reading syndrome had much lower reading scores at age 9 years than did their peers. Boys, but not girls, with the arithmetic syndrome were much more likely than their peers to have arithmetic scores more than one grade below the expected level at age 7 years. Girls and boys with the tasks syndrome, characterized by impersistence, dependence, and inflexibility, were more likely than those without any features of the syndrome to be classified as having little or no goal orientation by a neuropsychologist who assessed the children in an office setting. Similarly, the neuropsychologist was much more likely than expected to have classified children with the attention syndrome as having a short attention span, and to have classified boys, but not girls, with the hyperactivity syndrome as having an unusual/extreme level and nature of overactivity. Children with any syndrome were more likely than others to have low scores on components of the Wechsler Intelligence Scale for Children, items of the Bender-Gestalt Test that assessed integration and distortion, and measures of reading comprehension. We conclude that the Boston Teacher Questionnaire validly identifies children with learning problems. (J Child Neurol 1993; 8:54-63).
Application of Activated Sludge Model No. 3 for the Modeling of Organic Matter Biodegradation at Thermophilic Temperatures

The primary aim of our research was to investigate the applicability of activated sludge models (ASM) for aerobic thermophilic processes, especially autothermal thermophilic aerobic digestion (ATAD). The ASM3 model (Gujer et al., 1999) theoretically seems to be the most suitable, because storage plays an important role in a batch‐feed cycle system like ATAD. The ASM3 model was extended with an activation step of the thermophilic organisms. This model was calibrated and verified by independent test results, demonstrating its ability to describe the process. The growth (μH = 26.04 day−1), storage (k STO = 20.39 day−1), hydrolysis (k H = 11.15 day−1) and decay rates (b H,O2 = 1.28 day−1, b STO,O2 = 1.10 day−1) obtained from calibration are significantly higher at 55°C than at mesophilic temperatures, justifying the faster metabolism at higher temperatures. An inert fraction of the biomass (characterized by the model parameter f I = 0.4) was found to be significantly greater than in the mesophilic case. This can be attributed to the lower diversity of the thermophilic species and thus to their narrower substrate spectra.
Epidemiologic and clinical factors associated with Chronic Kidney Disease among Asian Americans and Native Hawaiians

Objective. To examine the association between key susceptibility factors and measures of chronic kidney disease in Asian American and Native Hawaiian participants enrolled in the Hawai‘i site of the national Kidney Early Evaluation Program (KEEP-2) study community screening program. Design. In 2001–2003, 793 participants from five ethnic groups (Japanese, Native Hawaii an, Chinese, Filipino and Caucasian) were enrolled in the Hawai‘i KEEP-2 program. Odds ratios were used as the measure of association and were computed using unconditional logistic regression. Renal susceptibility factors for chronic kidney disease were included in a multivariable model if found to be statistically significant in univariate analysis. The proportion of Hawai‘i KEEP-2 study participants manifesting various clinical characteristics were compared by ethnicity with Japanese as the referent group. Results. Significant ethnic differences in the occurrence of chronic kidney disease were found, with Japanese having the lowest occurrence of chronic kidney disease (18%) and Native Hawaiians the highest (40%). Within each ethnic group, the occurrence of chronic kidney disease was associated with a different ethnic-specific clustering of susceptibility factors. Hypertension was associated with chronic kidney disease among four of the five ethnic groups: Japanese, Caucasian, Native Hawaiian and Filipino. Overweight was associated with a decreased occurrence of chronic kidney disease among Caucasians, while diabetes and lower educational attainment were associated with increased occurrence of chronic kidney disease among Native Hawaiians. For Filipinos, diabetes and age 65 years and older were both associated with an increased occurrence for chronic kidney disease while lower educational attainment was associated with a reduced occurrence of chronic kidney disease. Among Chinese, no factors were significantly associated with chronic kidney disease, although trends for all factors paralleled those of the overall study group. Conclusions. The occurrence of chronic kidney disease in the Hawai‘i KEEP-2 study was nearly fourfold greater compared with the general US population. The clustering of susceptibility factors for chronic kidney disease occurrence was found to differ for all five ethnic groups.
Applications of Copper-Catalyzed Click Chemistry in Activity-Based Protein Profiling

Activity-based protein profiling (ABPP) is a chemical proteomic technique that enables the interrogation of protein activity directly within complex proteomes. Given the dominant role of posttranslational modifications in regulating protein function in vivo, ABPP provides a direct readout of activity that is not attained through traditional proteomic methods. ABPP relies on the design of covalent binding probes that either target a specific enzyme or a class of enzymes with related function. These covalent warheads are coupled to either fluorophores or biotin groups for visualization and enrichment of these active proteins. The advent of bioorthogonal chemistries, in particular, the copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC), has benefitted the field of ABPP by achieving the following: (1) replacing bulky reporter groups with smaller alkyne or azide groups to promote cell permeability; (2) adding modularity to the system such that a single probe can be diversified with a variety of reporter groups without the need to develop new synthetic routes; and (3) enabling the conjugation of complex linkers to facilitate quantitative proteomic analyses. Here, we summarize recent examples of CuAAC in ABPP that serve to illustrate the contribution of bioorthogonal chemistry to advancing discoveries in this field.
Testing a Single Regression Coefficient in High Dimensional Regression Model

In linear regression models with high dimensional data, the classical z-test (or t-test) for testing the significance of each single regression coefficient is no longer applicable. This is mainly because the number of covariates exceeds the sample size. In this paper, we propose a simple and novel alternative by introducing the Correlated Predictors Screening (CPS) method to control for predictors that are highly correlated with the target covariate. Accordingly, the classical ordinary least squares approach can be employed to estimate the regression coefficient associated with the target covariate. In addition, we demonstrate that the resulting estimator is consistent and asymptotically normal even if the random errors are heteroscedastic. This enables us to apply the z-test to assess the significance of each covariate. Based on the p-value obtained from testing the significance of each covariate, we further conduct multiple hypothesis testing by controlling the false discovery rate at the nominal level. Then, we show that the multiple hypothesis testing achieves consistent model selection. Simulation studies and empirical examples are presented to illustrate the finite sample performance and the usefulness of the proposed method, respectively.
Cyclin B and Cyclin A Confer Different Substrate Recognition Properties on CDK2

The transitions of the cell cycle are regulated by the cyclin dependent protein kinases(CDKs). The cyclins activate their respective CDKs and confer substrate recognitionproperties. We report the structure of phospho-CDK2/cyclin B and show that cyclin Bconfers M phase-like properties on CDK2, the kinase that is usually associated with S phase.Cyclin B produces an almost identical activated conformation of CDK2 as that produced bycyclin A. There are differences between cyclin A and cyclin B at the recruitment site, whichin cyclin A is used to recruit substrates containing an RXL motif. Because of sequencedifferences this site in cyclin B binds RXL motifs more weakly than in cyclin A. Despitesimilarity in kinase structures, phospho-CDK2/cyclin B phosphorylates substrates, such asnuclear lamin and a model peptide derived from p107, at sequences SPXX that differ fromthe canonical CDK2/cyclin A substrate recognition motif, SPXK. CDK2/cyclin Bphosphorylation at these non-canonical sites is not dependent on the presence of a RXLrecruitment motif. The p107 peptide contained two SP motifs each followed by a noncanonicalsequence of which only one site (Ser640) is phosphorylated by pCDK2/cyclin Awhile two sites are phosphorylated by pCDK2/cyclin B. The second site is too close to theRXL motif to allow the cyclin A recruitment site to be effective, as previous work has shownthat there must be at least 16 residues between the catalytic site serine and the RXL motif.Thus the cyclins A and B in addition to their role in promoting the activatory conformationalswitch in CDK2, also provide differential substrate specificity.
A metal-organic framework–based splitter for separating propylene from propane

Separating one organic from another Separating closely related organic molecules is a challenge (see the Perspective by Lin). The separation of acetylene from ethylene is needed in high-purity polymer production. Cui et al. developed a copper-based metal-organic framework with hexafluorosilicate and organic linkers designed to have a high affinity for acetylene. These materials, which capture four acetylene molecules in each pore, successfully separated acetylene from mixtures with ethylene. Propane and propylene are both important feedstock chemicals. Their physical and chemical similarity, however, requires energy-intense processes to separate them. Cadiau et al. designed a fluorinated porous metal-organic framework material that selectively adsorbed propylene, with the complete exclusion of propane. Science, this issue pp. 141 and 137; see also p. 121 A tailored metal-organic framework material is able to separate propane from propylene. The chemical industry is dependent on the olefin/paraffin separation, which is mainly accomplished by using energy-intensive processes. We report the use of reticular chemistry for the fabrication of a chemically stable fluorinated metal-organic framework (MOF) material (NbOFFIVE-1-Ni, also referred to as KAUST-7). The bridging of Ni(II)-pyrazine square-grid layers with (NbOF5)2– pillars afforded the construction of a three-dimensional MOF, enclosing a periodic array of fluoride anions in contracted square-shaped channels. The judiciously selected bulkier (NbOF5)2– caused the looked-for hindrance of the previously free-rotating pyrazine moieties, delimiting the pore system and dictating the pore aperture size and its maximum opening. The restricted MOF window resulted in the selective molecular exclusion of propane from propylene at atmospheric pressure, as evidenced through multiple cyclic mixed-gas adsorption and calorimetric studies.
Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation

Yos9p is involved in ER-associated degradation (ERAD) of misfolded glycoproteins. This study shows that Yos9p is required for ER retention of ERAD substrates by targeting them to the Hrd1p E3 ligase. This ER retention is independent of the glycan degradation signal on substrates and is separable from the later degradation step.