bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cvt9/Gsa9 Functions in Sequestering Selective Cytosolic Cargo Destined for the Vacuole
Authors: Kim John , Kamada Yoshiaki , Stromhaug Per E. , Guan Ju , Hefner-Gravink Ann , Baba Misuzu , Scott Sidney V. , Ohsumi Yoshinori , Dunn William A. , Klionsky Daniel J. 
Published: July 2002

Three overlapping pathways mediate the transport of cytoplasmic material to the vacuole in Saccharomyces cerevisiae. The cytoplasm to vacuole targeting (Cvt) pathway transports the vacuolar hydrolase, aminopeptidase I (API), whereas pexophagy mediates the delivery of excess peroxisomes for degradation. Both the Cvt and pexophagy pathways are selective processes that specifically recognize their cargo. In contrast, macroautophagy nonselectively transports bulk cytosol to the vacuole for recycling. Most of the import machinery characterized thus far is required for all three modes of transport. However, unique features of each pathway dictate the requirement for additional components that differentiate these pathways from one another, including at the step of specific cargo selection.
We have identified Cvt9 and its Pichia pastoris counterpart Gsa9. In S. cerevisiae, Cvt9 is required for the selective delivery of precursor API (prAPI) to the vacuole by the Cvt pathway and the targeted degradation of peroxisomes by pexophagy. In P. pastoris, Gsa9 is required for glucose-induced pexophagy. Significantly, neither Cvt9 nor Gsa9 is required for starvation-induced nonselective transport of bulk cytoplasmic cargo by macroautophagy. The deletion of CVT9 destabilizes the binding of prAPI to the membrane and analysis of a cvt9 temperature-sensitive mutant supports a direct role of Cvt9 in transport vesicle formation. Cvt9 oligomers peripherally associate with a novel, perivacuolar membrane compartment and interact with Apg1, a Ser/Thr kinase essential for both the Cvt pathway and autophagy. In P. pastoris Gsa9 is recruited to concentrated regions on the vacuole membrane that contact peroxisomes in the process of being engulfed by pexophagy. These biochemical and morphological results demonstrate that Cvt9 and the P. pastoris homologue Gsa9 may function at the step of selective cargo sequestration.
Notch 1–Deficient Common Lymphoid Precursors Adopt a B Cell Fate in the Thymus
Authors: Wilson Anne , MacDonald H. Robson , Radtke Freddy 
Published: July 2002

We have recently reported that Notch 1, a member of the Notch multigene family, is essential for the development of murine T cells. Using a mouse model in which Notch 1 is inactivated in bone marrow (BM) precursors we have shown that B cells instead of T cells are found in the thymus of BM chimeras. However, it is not clear whether these B cells develop by default from a common lymphoid precursor due to the absence of Notch 1 signaling, or whether they arise as a result of perturbed migration of BM-derived B cells and/or altered homeostasis of normal resident thymic B cells.
In this report we show that Notch 1–deficient thymic B cells resemble BM B cells in phenotype and turnover kinetics and are located predominantly in the medulla and corticomedullary junction. Peripheral blood lymphocyte analysis shows no evidence of recirculating Notch1−/− BM B cells. Furthermore, lack of T cell development is not due to a failure of Notch1−/− precursors to home to the thymus, as even after intrathymic reconstitution with BM cells, B cells instead of T cells develop from Notch 1–deficient precursors. Taken together, these results provide evidence for de novo ectopic B cell development in the thymus, and support the hypothesis that in the absence of Notch 1 common lymphoid precursors adopt the default cell fate and develop into B cells instead.
Analysis of an algorithm for generating locally optimal meshes for 𝐿₂ approximation by discontinuous piecewise polynomials
Authors: Tourigny Y. , Baines M. 
Published: July 2002

This paper discusses the problem of constructing a locally optimal mesh for the best

L
2

L_2

approximation of a given function by discontinuous piecewise polynomials. In the one-dimensional case, it is shown that, under certain assumptions on the approximated function, Baines’ algorithm [M. J. Baines, Math. Comp., 62 (1994), pp. 645-669] for piecewise linear or piecewise constant polynomials produces a mesh sequence which converges to an optimal mesh. The rate of convergence is investigated. A two-dimensional modification of this algorithm is proposed in which both the nodes and the connection between the nodes are self-adjusting. Numerical results in one and two dimensions are presented.
An automated comparative analysis of 17 complete microbial
genomes
Authors: K.Bansal Arvind 
Published: July 2002

Abstract
Motivation: As sequenced genomes become larger and sequencing becomes faster, there is a need to develop accurate automated genome comparison techniques and databases to facilitate derivation of genome functionality; identification of enzymes, putative operons and metabolic pathways; and to derive phylogenetic classification of microbes.
Results: This paper extends an automated pair-wise genome comparison technique (Bansal, Math. Model. Sci. Comput., 9, 1–23, 1998, Bansal and Bork, in First International Workshop of Declarative Languages, Springer, pp. 275–289, 1999) used to identify orthologs and gene groups to derive orthologous genes in a group of genomes and to identify genes with conserved functionality. Seventeen microbial genomes archived at ftp://ncbi.nlm.nih.gov/genbank/genomeshave been compared using the automated technique. Data related to orthologs, gene groups, gene duplication, gene fusion, orthologs with conserved functionality, and genes specifically orthologous to Escherichia coli and pathogens has been presented and analyzed.
Availability: A prototype database is available at ftp://www.mcs.kent.edu/~arvind/intellibio/orthos.html. The software is free for academic research under an academic license. The detailed database for every microbial genome in NCBI is commercially available through intellibio software and consultancy corporation (Web site: http://www.mcs.kent.edu/~arvind/intellibio.html).
Contact: arvind@mcs.kent.edu
Classifying G-protein coupled receptors with support vector
machines
Authors: Karchin Rachel , Karplus Kevin , Haussler David 
Published: July 2002

Abstract
Motivation: The enormous amount of protein sequence data uncovered by genome research has increased the demand for computer software that can automate the recognition of new proteins. We discuss the relative merits of various automated methods for recognizing G-Protein Coupled Receptors (GPCRs), a superfamily of cell membrane proteins. GPCRs are found in a wide range of organisms and are central to a cellular signalling network that regulates many basic physiological processes. They are the focus of a significant amount of current pharmaceutical research because they play a key role in many diseases. However, their tertiary structures remain largely unsolved. The methods described in this paper use only primary sequence information to make their predictions. We compare a simple nearest neighbor approach (BLAST), methods based on multiple alignments generated by a statistical profile Hidden Markov Model (HMM), and methods, including Support Vector Machines (SVMs), that transform protein sequences into fixed-length feature vectors.
Results: The last is the most computationally expensive method, but our experiments show that, for those interested in annotation-quality classification, the results are worth the effort. In two-fold cross-validation experiments testing recognition of GPCR subfamilies that bind a specific ligand (such as a histamine molecule), the errors per sequence at the Minimum Error Point (MEP) were 13.7% for multi-class SVMs, 17.1% for our SVMtree method of hierarchical multi-class SVM classification, 25.5% for BLAST, 30% for profile HMMs, and 49% for classification based on nearest neighbor feature vector Kernel Nearest Neighbor (kernNN). The percentage of true positives recognized before the first false positive was 65% for both SVM methods, 13% for BLAST, 5% for profile HMMs and 4% for kernNN.
Availability: We have set up a web server for GPCR subfamily classification based on hierarchical multi-class SVMs at http://www.soe.ucsc.edu/research/compbio/gpcr-subclass. By scanning predicted peptides found in the human genome with the SVMtree server, we have identified a large number of genes that encode GPCRs. A list of our predictions for human GPCRs is available at http://www.soe.ucsc.edu/research/compbio/gpcr˙hg/class˙results. We also provide suggested subfamily classification for 18 sequences previously identified as unclassified Class A (rhodopsin-like) GPCRs in GPCRDB (Horn et al. , Nucleic Acids Res. , 26, 277–281, 1998), available at http://www.soe.ucsc.edu/research/compbio/gpcr/classA˙unclassified/.
Contact: rachelk@soe.ucsc.edu
* To whom correspondence should be addressed.
Association of nucleotide patterns with gene function classes:
application to human 3′ untranslated sequences
Authors: Conklin Darrell , Jonassen Inge , Aasland Rein , Taylor William R. 
Published: July 2002

Abstract
Motivation: Gene expression is dependent on two main types of signals; one involving transcription factors which initiates gene transcription, and another which regulates the translation of a nascent mRNA. These post-transcriptional events play an important yet incompletely understood role in regulating gene expression and cellular behavior. Many of the identified cis acting elements for translational regulation occur within the 3′untranslated region (3′UTR), and some have been observed to occur with surprising regularity within certain protein function classes.
Results: In this study, we present a new association rule mining method for discovering nucleotide sequence patterns that appear in more sequences than expected within protein function classes. The method is applied to a database of human 3′UTR sequences, and some significant associations between nucleotide patterns and protein function classes are discovered. Among previously identified patterns, the AU-Rich Element (ARE) is found here to occur within the 3′UTR of cytokines, providing statistical validation of an association often reported in the literature. The method has also identified some GC-rich patterns, found to occur within the 3′UTR of homeodomain transcription factors and nuclear proteins. The method should be applicable to many types of regulatory element discovery.
Contact: conklin@zgi.com
* To whom correspondence should be addressed.
TROLL—Tandem Repeat Occurrence Locator
Authors: Castelo Adalberto T. , Martins Wellington , Gao Guang R. 
Published: July 2002

Abstract
Summary: Tandem Repeat Occurrence Locator (TROLL), is a light-weight Simple Sequence Repeat (SSR) finder based on a slight modification of the Aho–Corasick algorithm. It is fast and only requires a standard Personal Computer (PC) to operate. We report running times of 127 s to find all SSRs of length 20 bp or more on the complete Arabdopsis genome—approx. 130 Mbases divided in five chromosomes—using a PC Athlon 650 MHz with 256 MB of RAM.
Availability: TROLL is an open source project and is available at http://finder.sourceforge.net.
Contact: castelo@capsl.udel.edu
Vascular adhesion protein 1 (VAP‐1) functions as a molecular brake during granulocyte rolling and mediates recruitment in vivo
Authors: TOHKA SAMI , LAUKKANEN MARJA‐LEENA , JALKANEN SIRPA , SALMI MARKO 
Published: July 2002

ABSTRACTGranulocyte extravasation from the blood into tissues is a prerequisite for a proper inflammatory response. It is regulated by a multistep adhesion cascade consisting of successive contacts between leukocyte surface receptors and their endothelial ligands on vessels. Vascular adhesion protein 1 (VAP‐1) is an endothelial surface glycoprotein with two functions. It is an enzyme (monoamine oxidase) and an adhesion molecule for lymphocytes. Its function in binding of granulocytes or in leukocyte trafficking into sites of inflammation in vivo has remained unknown. Here we show that treatment of rabbits with anti‐VAP‐1 monoclonal antibodies abrogates ~70% of granulocyte extravasation into a site of an experimental inflammation. Using intravital microscopy, VAP‐1 blockade is shown to increase the velocity of the rolling granulocytes and the frequency of their jerky skippings during the rolling. In addition, the number of firmly bound leukocytes decreased by 44% when VAP‐1 was rendered nonfunctional. Our results suggest that VAP‐1 functions as a molecular brake early in the adhesion cascade and consequently decreases the firm adherence;it may also directly influence the transmigration step. These data elucidate a new interplayer in the granulocyte extravasation process and provide a novel physiological function for a member of the monoamine oxidase family.—Tohka, S., Laukkanen, M.‐L., Jalkanen, S., Salmi, M. Vascular adhesion protein 1 (VAP‐1) functions as a molecular brake during granulocyte rolling and mediates their recruitment in vivo. FASEB J. 15, 373‐382 (2001)
Ca(II)‐ and Tb(III)‐induced stabilization and refolding of anticoagulation factor I from the venom of Agkistrodon acutus
Authors: Xu Xiaolong , Liu Qingliang , Yu Huaming , Xie Yongshu 
Published: July 2002

AbstractAnticoagulation factor I (ACF I) isolated from the venom of Agkistrodon acutus is an activated coagulation factor X‐binding protein in a Ca2+‐dependent fashion with marked anticoagulant activity. The equilibrium unfolding/refolding of apo‐ACF I, holo‐ACF I, and Tb3+‐reconstituted ACF I in guanidine hydrochloride (GdnHCl) solutions was studied by following the fluorescence and circular dichroism. Metal ions were found to increase the structural stability of ACF I against GdnHCl and thermal denaturation and, furthermore, influence its unfolding/refolding behavior. The GdnHCl‐induced unfolding/refolding of both apo‐ACF I and Tb3+‐ACF I is a two‐state process with no detectable intermediate state(s), whereas the GdnHCl‐induced unfolding/refolding of holo‐ACF I in the presence of 1 mM Ca2+ follows a three‐step transition, with intermediate state a (Ia) and intermediate state b (Ib). Ca2+ ions play an important role in the stabilization of the Ia and Ib states. The decalcification of holo‐ACF I shifts the ending zone of unfolding/refolding curve toward lower GdnHCl concentration, whereas the reconstitution of apo‐ACF I with Tb3+ ions shifts the initial zone of denaturation curve toward higher GdnHCl concentration. Therefore, it is possible to find a denaturant concentration (2.0 M GdnHCl) at which refolding from the fully denatured state of apo‐ACF I to the Ib state of holo‐ACF I or to the native state of Tb3+‐ACF I can be initiated merely by adding the 1 mM Ca2+ ions or 10 μM Tb3+ ions to the unfolded state of apo‐ACF I, respectively, without changing the concentration of the denaturant. Using Tb3+ as a fluorescence probe of Ca2+, the kinetic results of metal ions–induced refolding provide evidence that the compact Tb3+‐binding region forms first, and subsequently, the protein undergoes further conformational rearrangements to form the native structure.
Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events
Authors: Zuo Yu , Navaz Sherwin , Liang Wenying , Li Chun , Ayers Colby R. , Rysenga Christine E. , Harbaugh Alyssa , Norman Gary L. , Solow E. Blair , Bermas Bonnie , Akinmolayemi Oludamilola , Rohatgi Anand , Karp David R. , Knight Jason S. , de Lemos James A. 
Published: April 2023

ImportanceThe prevalence of antiphospholipid antibodies (aPL) and their association with future atherosclerotic cardiovascular disease (ASCVD) risk has yet to be thoroughly investigated.ObjectiveTo determine the association between measurements of aPL at a single time point and ASCVD risk in a diverse population.Design, Setting, and ParticipantsThis cohort study measured 8 aPL (anticardiolipin [aCL] IgG/IgM/IgA, anti–beta-2 glycoprotein I [aβ2GPI] IgG/IgM/IgA, and antiphosphatidylserine/prothrombin [aPS/PT] IgG/IgM) by solid-phase assays in plasma from participants of the Dallas Heart Study (DHS) phase 2, a multiethnic, population-based cohort study. Blood samples were collected between 2007 and 2009. The median follow-up was 8 years. Statistical analysis was performed from April 2022 to January 2023.Main Outcomes and MeasuresAssociations of aPL with future ASCVD events (defined as first nonfatal myocardial infarction, first nonfatal stroke, coronary revascularization, or death from cardiovascular cause) were assessed by Cox proportional hazards models, adjusting for known risk factors, medications, and multiple comparisons.ResultsAmong the 2427 participants (mean [SD] age, 50.6 [10.3] years; 1399 [57.6%] female; 1244 [51.3%] Black, 339 [14.0%] Hispanic, and 796 [32.8%] White), the prevalence of any positive aPL tested at a single time point was 14.5% (353 of 2427), with approximately one-third of those detected at a moderate or high titer; aCL IgM had the highest prevalence (156 individuals [6.4%]), followed by aPS/PT IgM (88 [3.4%]), aβ2GPI IgM (63 [2.6%]), and aβ2GPI IgA (62 [2.5%]). The IgA of aCL (adjusted hazard ratio [HR], 4.92; 95% CI, 1.52-15.98) and aβ2GPI (HR, 2.91; 95% CI, 1.32-6.41) were independently associated with future ASCVD events. The risk further increased when applying a positivity threshold of at least 40 units (aCL IgA: HR, 9.01 [95% CI, 2.73-29.72]; aβ2GPI IgA: HR, 4.09 [95% CI, 1.45-11.54]). Levels of aβ2GPI IgA negatively correlated with cholesterol efflux capacity (r = −0.055; P = .009) and positively correlated with circulating oxidized LDL (r = 0.055; P = .007). aβ2GPI IgA–positive plasma was associated with an activated endothelial cell phenotype as evidenced by increased surface expression of surface E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1.Conclusions and RelevanceIn this population-based cohort study, aPL detectable by solid-phase assays were present in a substantial proportion of adults; positive aCL IgA and aβ2GPI IgA at a single time point were independently associated with future ASCVD events. Longitudinal studies with serial aPL measurements are needed to further explore these findings.
Plaque Macrophage‐Targeting Nanosystems with Cooperative Co‐Regulation of ROS and TRAF6 for Stabilization of Atherosclerotic Plaques
Authors: Yang Qian , Jiang Hong , Wang Yue , Leng Xiao , Wang Yantang , Tong Jie , Zhou Yang , Mo Chunfen , Peng Jinrong , Gao Huile 
Published: April 2023

AbstractChronic inflammatory microenvironment is the predominant milieu that promotes the progression of atherosclerosis (AS). However, targeted regulation of the chronic proinflammatory milieu still needs to be improved. In this study, macrophage‐targeting nanosystems composed of 37pA peptide embedded–Pt lipid nanoparticles (37pA‐PtLNP) and tumor necrosis factor‐associated factor 6 (TRAF6) inhibitor (6877002)‐loaded poly(ε‐caprolactone)‐b‐polyethylene glycol‐b‐poly(ε‐caprolactone) (PCEC) are constructed with 37pA peptide embedded–lipid coating (37pA‐LNP/6877002), to stabilize atherosclerotic lesions. The cooperative regulation effects of these nanosystems in achieving reactive oxygen species (ROS) scavenging and inflammatory signaling inhibition are investigated. 37pA‐PtLNP effectively scavenges several ROS, however, also promotes the expression of iNOS. The introduction of 37pA‐LNP/6877002 inhibits the activities of TRAF6, a downstream intracellular factor of the CD40L‐CD40‐TRAF6 axis, to decrease the proportion of the proinflammatory M1 macrophage phenotype, which is further downregulated by combined treatment with 37pA‐PtLNP. The combination of 37pA‐PtLNP and 37pA‐LNP/6877002 not only counteracts 37pA‐PtLNP–induced iNOS upregulation but also alleviates the chronic inflammatory microenvironment by reducing the expression of proinflammatory cytokines and chemokines. The anti‐AS efficacy in vivo on ApoE−/− mice further demonstrates that the combination of 37pA‐PtLNP and 37pA‐LNP/6877002 targetedly modulates the atherosclerotic plaque microenvironment, achieving stabilization of lesions with minimal progression. This study provides a promising strategy for AS management.
Sodium‐Based Concave Metasurfaces for High Performing Plasmonic Optical Filters by Templated Spin‐on‐Sodiophobic‐Glass
Authors: Yang Yuhan , Fu Hanyu , Su Huanhuan , Chen Shuying , Wu Shan , Liang Jie , Wei Tianqi , Wang Yang , Zhu Shining , Zhu Jia , Zhou Lin 
Published: April 2023

AbstractOptical filters have aroused tremendous excitement in advanced photonic instruments and modern digital displays due to their flexible capability of spectrum manipulation. Plasmonic metasurfaces of narrow bandwidth, high spectral contrast, and robust structure tolerance are highly desired for optical filtration (especially in the visible regime) but rather challenging as large spectral broadening from intrinsic ohmic loss and design/fabrication deviations. Here the high‐performing sodium‐based metasurfaces are demonstrated for optical filtration across 450 to 750 nm by unique structure design of spatially decoupled concave surfaces and precise fabrication through templated solidification of liquid metals. Thanks to the distinct suppression of metallic loss as well as fabrication tolerance of interfacial structures, the as‐prepared concave metasurfaces enable a minimum linewidth of ≈15 nm, a maximal optical contrast of ≈93%, and a high measure‐to‐design spectral match ratio ≈1500. These results have for the first time pushed the operation wavelengths of sodium‐based plasmonic devices from infrared to visible which in turn demonstrates the capability of filling the blank of commercial dielectric optical filters thus far.
Polarization‐Tuned Fano Resonances in All‐Dielectric Short‐Wave Infrared Metasurface
Authors: Attiaoui Anis , Daligou Gérard , Assali Simone , Skibitzki Oliver , Schroeder Thomas , Moutanabbir Oussama 
Published: April 2023

AbstractThe short‐wave infrared (SWIR) is an underexploited portion of the electromagnetic spectrum in metasurface‐based nanophotonics despite its strategic importance in sensing and imaging applications. This is mainly attributed to the lack of material systems to tailor light–matter interactions in this range. Herein, this limitation is addressed and an all‐dielectric silicon‐integrated metasurface enabling polarization‐induced Fano resonance control at SWIR frequencies is demonstrated. The platform consists of a 2D Si/Ge0.9Sn0.1 core/shell nanowire array on a silicon wafer. By tuning the light polarization, it is shown that the metasurface reflectance can be efficiently engineered due to Fano resonances emerging from the electric and magnetic dipoles competition. The interference of optically induced dipoles in high‐index nanowire arrays offers additional degrees of freedom to tailor the directional scattering and the flow of light while enabling sharp polarization‐modulated resonances. This tunablity is harnessed in nanosensors yielding an efficient detection of 10−2 changes in the refractive index of the surrounding medium.