Hasil untuk "physics.atm-clus"

Andrey Yachmenev, Guang Yang

We present the first quantum mechanical study of hyperfine effects in the rotational cluster states of a symmetric triatomic molecule H$_2$S. Rotational clusters arise from spontaneous symmetry breaking induced by high-angular-momentum rotational motions in certain rigid molecules, resulting in dynamic enantiomorphism driven by kinetic distortion effects. Hyperfine interactions in the cluster states lead to collision-free breaking of nuclear spin symmetry, with the magnitude of nuclear spin ortho-para mixing significantly exceeding that in other states with same or lower angular momentum. The ortho-para mixing induces nuclear spin polarization in the laboratory frame and gives rise to two sets of enantiomers, that have different energies and oppositely oriented nuclear spin projections. Although hyperfine interactions preserve parity, they lift the degeneracy of opposite-parity cluster states. This phenomenon, previously observed experimentally, is explained as a result of tunneling between rotating enantiomers, facilitated by the Pauli exclusion principle.

T. Lih, Mingming Dong, L. Mangold et al.

Majority of patients with indolent prostate cancer (PCa) can be managed with active surveillance. Therefore, finding biomarkers for classifying patients between indolent and aggressive PCa is essential. In this study, we investigated urinary marker panels composed of urinary glycopeptides and/or urinary prostate-specific antigen (PSA) for their clinical utility in distinguishing non-aggressive (Grade Group 1) from aggressive (Grade Group ≥ 2) PCa. Urinary glycopeptides acquired via data-independent acquisition mass spectrometry (DIA-MS) were quantitatively analyzed, where prostatic acid phosphatase (ACPP), clusterin (CLU), alpha-1-acid glycoprotein 1 (ORM1), and CD antigen 97 (CD97) were selected to be evaluated in various combinations with and without urinary PSA. Targeted parallel reaction monitoring (PRM) assays of the glycopeptides from urinary ACPP and CLU were investigated along with urinary PSA for the ability of aggressive PCa detection. The multi-urinary marker panels, combined via logistic regression, were statistically evaluated using bootstrap resampling and validated by an independent cohort. Majority of the multi-urinary marker panels (e.g., a panel consisted of ACPP, CLU, and Urinary PSA) achieved area under the curve (AUC) ranged from 0.70 to 0.85. Thus, multi-marker panels investigated in this study showed clinically meaningful results on aggressive PCa detection to separate Grade Group 1 from Grade Group 2 and above warranting further evaluation in clinical setting in future.

H. Wijerathna, Kishanthini Nadarajapillai, H. Udayantha et al.

Clusterin (CLU) is a glycoprotein that contains α- and β-chains. CLU exerts multifunctional activities and plays a role in different cell signaling pathways that are associated with various diseases such as proteotoxic and oxidative stress, as well as cell death and survival. However, its role in marine teleost fish remains unclear. Therefore, the present study was carried out to characterize and investigate the immune responses and anti-apoptotic effects of CLU of the big-belly seahorse (Hippocampus abdominalis) (HaCLU) on oxidative stress-induced cell death. The HaCLU open reading frame was 1389 bp long and encoded a protein with 462 amino acids, a molecular weight of 51.28 kDa and an isoelectric point of 5.41. In-silico results demonstrated that HaCLU has a signal peptide in the 1-29 amino acid region, while the α- and β-chains were in the 34-227 and 228-455 amino acid regions, respectively. Multiple sequence alignment clarified the low homology of the α-chain with other orthologs. The highest HaCLU mRNA expression level was observed in the liver, followed by the heart, spleen, and brain tissues of healthy big-belly seahorses. Further, HaCLU mRNA expression level was elevated in the liver in response to different stimuli, including lipopolysaccharides, polyinosinic:polycytidylic acid, Edwardsiella tarda, and Streptococcus iniae. HaCLU potentiates cell viability and weakens chromatin condensation in the nucleus of FHM cells following H2O2-induced oxidative stress and subsequent cell death. HaCLU overexpression resulted in a reduced Bax/Bcl-2 mRNA expression ratio. This study revealed the role of HaCLU in immune regulation against pathogenic infections and its anti-apoptotic effects on oxidative stress-induced cell death.

Ursule Kalvaityte, Csaba Matta, E. Bernotiene et al.

Background Clusterin (CLU; also known as apolipoprotein J) is an ATP-independent holdase chaperone that prevents proteotoxicity as a consequence of protein aggregation. It is a ∼60 kDa disulfide-linked heterodimeric protein involved in the clearance of cellular debris and the regulation of apoptosis. CLU has been proposed to protect cells from cytolysis by complement components and has been implicated in Alzheimer’s disease due to its ability to bind amyloid-β peptides and prevent aggregate formation in the brain. Recent studies suggest that CLU performs moonlighting functions. CLU exists in two major forms: an intracellular form and a secreted extracellular form. The intracellular form of CLU may suppress stress-induced apoptosis by forming complexes with misfolded proteins and facilitates their degradation. The secreted form of CLU functions as an extracellular chaperone that prevents protein aggregation. Methods In this review, we discuss the published literature on the biology of CLU in cartilage, chondrocytes, and other synovial joint tissues. We also review clinical studies that have examined the potential for using this protein as a biomarker in synovial and systemic fluids of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Results Since CLU functions as an extracellular chaperone, we propose that it may be involved in cytoprotective functions in osteoarticular tissues. The secreted form of CLU can be measured in synovial and systemic fluids and may have translational potential as a biomarker of early repair responses in OA. Conclusion There is significant potential for investigating synovial and systemic CLU as biomarkers of OA. Future translational and clinical orthopaedic studies should carefully consider the diverse roles of this protein and its involvement in other comorbidities. Therefore, future biomarker studies should not correlate circulating CLU levels exclusively to the process of OA pathogenesis and progression. Special attention should be paid to CLU levels in synovial fluid. The Translational potential of this article There is significant potential for investigating synovial and systemic CLU as a predictive biomarker of osteoarthritis (OA) progression and response to novel treatments and interventions. Given that CLU plays diverse roles in other comorbidities such as rheumatoid arthritis (RA) and obesity, future translational and clinical orthopaedic biomarker studies should not directly correlate circulating CLU levels to the process of OA pathogenesis and progression. However, special attention should be paid to CLU levels in synovial fluid. The cytoprotective properties of CLU may support the implementation of regenerative strategies and new approaches for developing targeted therapeutics for OA.

R. Burstall, J. Goguen

Megan Torvell, Sarah M Carpanini, Nikoleta Daskoulidou et al.

The presence of complement activation products at sites of pathology in post-mortem Alzheimer’s disease (AD) brains is well known. Recent evidence from genome-wide association studies (GWAS), combined with the demonstration that complement activation is pivotal in synapse loss in AD, strongly implicates complement in disease aetiology. Genetic variations in complement genes are widespread. While most variants individually have only minor effects on complement homeostasis, the combined effects of variants in multiple complement genes, referred to as the “complotype”, can have major effects. In some diseases, the complotype highlights specific parts of the complement pathway involved in disease, thereby pointing towards a mechanism; however, this is not the case with AD. Here we review the complement GWAS hits; CR1 encoding complement receptor 1 (CR1), CLU encoding clusterin, and a suggestive association of C1S encoding the enzyme C1s, and discuss difficulties in attributing the AD association in these genes to complement function. A better understanding of complement genetics in AD might facilitate predictive genetic screening tests and enable the development of simple diagnostic tools and guide the future use of anti-complement drugs, of which several are currently in development for central nervous system disorders.

Juofang Tan, Wei Guo, Su Yang et al.

Worldwide, lung cancer is the most common form of cancer, with an estimated 2.09 million new cases and 1.76 million of death cause in 2018. It is categorized into two subtypes, small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Although platinum-based chemotherapy or molecular targeted drugs is recommended for advanced stages of NSCLC patients, however, resistance to drug and chemotherapy are hindrances for patients to fully beneficial from these treatments. Clusterin (CLU), also known as apolipoprotein J, is a versatile chaperone molecule which produced by a wide array of tissues and found in most biologic fluids. There are studies reported high expression of CLU confers resistance to chemotherapy and radiotherapy in different lung cancer cell lines. By silencing CLU using Custirsen (OGX-011), a second-generation antisense oligonucleotide (ASO) that inhibits CLU production, not only could sensitized cells to chemo- and radiotherapy, also could decreased their metastatic potential. We will review here the extensive literature linking CLU to NSCLC, update the current state of research on CLU for better understanding of this unique protein and the development of more effective anti- CLU treatment.

Benyu Nan, Guo-Feng Xiong, Zi-Rui Zhao et al.

Background Thyroid cancer is the most common endocrine malignancy, with a recent global increase of 20% in age-related incidence. Ultrasonography and ultrasonography-guided fine-needle aspiration biopsy (FNAB) are the most widely used diagnostic tests for thyroid nodules; however, it is estimated that up to 25% of thyroid biopsies are cytologically inconclusive. Molecular markers can help guide patient-oriented and targeted treatment of thyroid nodules and thyroid cancer. Methods Datasets related to papillary thyroid cancer (PTC) or thyroid carcinoma (GSE129562, GSE3678, GSE54958, GSE138042, and GSE124653) were downloaded from the GEO database and analysed using the Limma package of R software. For functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology were applied to differentially expressed genes (DEGs) using the Metascape website. A protein-protein interaction (PPI) network was built from the STRING database. Gene expression, protein expression, immunohistochemistry, and potential functional gene survival were analysed using the GEPIA website, the Human Protein Atlas website, and the UALCAN website. Potential target miRNAs were predicted using the miRDB and Starbase datasets. Results We found 219 upregulated and 310 downregulated DEGs, with a cut-off of p 1.5. The DEGs in papillary thyroid cancer were mainly enriched in extracellular structural organisation. At the intersection of the PPI network and Metascape MCODEs, the hub genes in common were identified as FN1, APOE, CLU, and SDC2. In the targeted regulation network of miRNA-mRNA, the hsa-miR-424-5p was found to synchronously modulate two hub genes. Survival analysis showed that patients with high expression of CLU and APOE had better prognosis. Conclusions CLU and APOE are involved in the molecular mechanism of papillary thyroid cancer. The hsa-miR-424-5p might have the potential to reverse the processes of papillary thyroid cancer by modulating the hub genes. These are potential targets for the treatment of patients with papillary thyroid cancer.

Yuehui Liang, Ningjuan Liang, Yu Ma et al.

Hexavalent chromium [Cr(VI)] and its compounds have caused serious environmental pollution and health damage. Senescent cells can actively change the surrounding environment by secreting some factors, which are called senescence associated secretory phenotype (SASP). Our previous work has confirmed that premature senescent hepatocytes induced by Cr(VI) expressed high level of Clusterin (CLU) and secrete interleukin-6 (IL-6) and IL-8. CLU is involved in the regulation of tumor development and drug resistance, but whether CLU regulates SASP components and participates in Cr(VI)-induced malignant transformation is unclear. In this study we demonstrated that Cr(VI) induced the secretion of tumor promoting components of SASP such as IL-6, IL-8, and granulocyte-macrophage colony stimulating factor (GM-CSF) in senescent L-02 hepatocytes, while the levels of the anti-tumor components of SASP such as chemokine (c-x-c motif) ligand-1 (CXCL-1) and monocyte chemoattractant protein-1 (MCP-1) were not altered. CLU shRNA interference significantly reduced the levels of IL-6, IL-8, and GM-CSF in the culture medium of senescent cells, suggesting CLU may regulate SASP. The NF-κB inhibitor PDTC significantly alleviated Cr(VI)-induced increase of IL-6, IL-8, and GM-CSF, confirming that NF-κB can regulate the tumor promoting components of SASP. CLU shRNA interference aggravated the inhibitory effect of PDTC on SASP secretion, indicating that CLU regulated the secretion of SASP in Cr(VI)-induced senescent hepatocytes through the NF-κB signaling. We speculated that SASP secreted by Cr(VI)-induced premature senescent hepatocytes was tightly related to the carcinogenic effect of Cr(VI). Therefore, elucidation of upstream regulatory mechanism of SASP is of great significance. In addition to further clarifying the carcinogenic mechanisms associated with Cr(VI), we could also seek out new targets for treatment of Cr(VI)-related cancer.

Yan Liu, Yehui Zhou, Xinxing Ma et al.

Triple negative breast cancer (TNBC), with its lack of targeted therapies, shows the worst mortality rate among all breast cancer subtypes. Clusterin (CLU) is implicated to play important oncogenic roles in cancer via promoting various downstream oncogenic pathways. Here, protein kinase D3 (PRKD3) is defined to be a key regulator of CLU in promoting TNBC tumor growth. Mechanically, PRKD3 with kinase activity binding to CLU is critical for CLU protein stability via inhibiting CLU's lysosomal distribution and degradation. CLU and PRKD3 protein level are significantly elevated and positively correlated in collected TNBC tumor samples. CLU silencer (OGX‐011) and PRKDs inhibitor (CRT0066101) can both result in impressive tumor growth suppression in vitro and in vivo, suggesting targeting CLU and its key regulator‐PRKD3 are promisingly efficient against TNBC. Finally, secreted CLU (sCLU) is found to be elevated in serums from TNBC patients and reduced in serum from TNBC murine models post OGX‐011 and/or CRT0066101 treatment, suggesting serum sCLU is a promising blood‐based biomarker for clinical management of TNBC. Taken together, this study provides a thorough molecular basis as well as preclinical evidences for targeting CLU pathway as a new promising strategy against TNBC via revealing PRKD3 as the key regulator of CLU in TNBC.

E. Janiszewska, I. Kokot, Iwona Gilowska et al.

In the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed. Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT). The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively). The concentrations of FUT3 and FUT4, reflecting the expression of Le oligosaccharide structures, were measured using ELISA tests. The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility. Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation. It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression. The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.

Easwaran Ramamurthy, Gwyneth Welch, Jemmie Cheng et al.

We profile genome-wide histone 3 lysine 27 acetylation (H3K27ac) of 3 major brain cell types from hippocampus and dorsolateral prefrontal cortex (dlPFC) of subjects with and without Alzheimer’s Disease (AD). We confirm that single nucleotide polymorphisms (SNPs) associated with late onset AD (LOAD) prefer to reside in the microglial histone acetylome, which varies most strongly with age. We observe acetylation differences associated with AD pathology at 3,598 peaks, predominantly in an oligodendrocyte-enriched population. Strikingly, these differences occur at the promoters of known early onset AD (EOAD) risk genes (APP, PSEN1, PSEN2, BACE1), late onset AD (LOAD) risk genes (BIN1, PICALM, CLU, ADAM10, ADAMTS4, SORL1 and FERMT2), and putative enhancers annotated to other genes associated with AD pathology (MAPT). More broadly, acetylation differences in the oligodendrocyte-enriched population occur near genes in pathways for central nervous system myelination and oxidative phosphorylation. In most cases, these promoter acetylation differences are associated with differences in transcription in oligodendrocytes. Overall, we reveal deregulation of known and novel pathways in AD and highlight genomic regions as therapeutic targets in oligodendrocytes of hippocampus and dlPFC.

Javier F. Troncoso

ClasSOMfier is a software package to classify atoms into a given number of disconnected groups (or clusters) and detect lattice defects, such as vacancies, interstitials, dislocations, voids and grain boundaries. Each cluster is formed by atoms whose atomic environment can be described by a common pattern. Unlike many methods available in the literature, where these patterns are given in advance and are associated with known lattice structures (i.e. fcc, bcc or hcp), this code implements a Kohonen network, which is based on unsupervised learning and where no information about the atomic environment has to be given in advance. ClasSOMfier accelerates the application of machine learning for cluster analysis by providing an efficient and fast code in Fortran with a user-friendly interface in Python.

John C. Mitchell, G. Plotkin

M. Kopczynska, W. Zelek, S. Vespa et al.

PURPOSE To explore whether complement dysregulation occurs in a routinely recruited clinical cohort of epilepsy patients, and whether complement biomarkers have potential to be used as markers of disease severity and seizure control. METHODS Plasma samples from 157 epilepsy cases (106 with focal seizures, 46 generalised seizures, 5 unclassified) and 54 controls were analysed. Concentrations of 10 complement analytes (C1q, C3, C4, factor B [FB], terminal complement complex [TCC], iC3b, factor H [FH], Clusterin [Clu], Properdin, C1 Inhibitor [C1Inh] plus C-reactive protein [CRP]) were measured using enzyme linked immunosorbent assay (ELISA). Univariate and multivariate statistical analysis were used to test whether combinations of complement analytes were predictive of epilepsy diagnoses and seizure occurrence. Correlation between number and type of anti-epileptic drugs (AED) and complement analytes was also performed. RESULTS We found: CONCLUSION: This study adds to evidence implicating complement in pathogenesis of epilepsy and may allow the development of better therapeutics and prognostic markers in the future. Replication in a larger sample set is needed to validate the findings of the study.

E. G. Ilin, A. S. Parshakov, V. G. Yarzhemsky et al.

Using the MALDI-TOF spectroscopy method, clusters of non-stoichiometric tantalum oxychlorides formed as a result of hydrolysis of nanoscale reaction products of tantalum pentachloride with acetylene and of interaction with oxygen and air moisture in the process of sample preparation were studied. The formation of oxychloride clusters containing from 2 to 15 tantalum atoms is shown. Quantum chemical calculations of the structure and relative thermodynamic stability of the possible isomers are carried out. The stability of cage Ta structures connected by oxygen bridges with significant contribution of metal-metal bond is established

Anne D. Müller, Anton N. Artemyev, Philipp V. Demekhin

Angle-resolved multiphoton ionization of fenchone and camphor by short intense laser pulses is computed by the time-dependent Single Center (TDSC) method. Thereby, the photoelectron circular dichroism (PECD) in the three-photon resonance enhanced ionization and four-photon above-threshold ionization of these molecules is investigated in detail. The computational results are in a satisfactory agreement with the available experimental data, measured for randomly-oriented fenchone and camphor molecules at different wavelengths of the exciting pulses. We predict a significant enhancement of the multiphoton PECD for uniaxially-oriented fenchone and camphor.

Sungmi Park, Keisa W. Mathis, I. Lee

M. Shcherbinin, A. C. LaForge, V. Sharma et al.

Interatomic Coulombic decay (ICD) is induced in helium (He) nanodroplets by photoexciting the n=2 excited state of He^+ using XUV synchrotron radiation. By recording multiple coincidence electron and ion images we find that ICD occurs in various locations at the droplet surface, inside the surface region, or in the droplet interior. ICD at the surface gives rise to energetic He^+ ions as previously observed for free He dimers. ICD deeper inside leads to the ejection of slow He^+ ions due to Coulomb explosion delayed by elastic collisions with neighboring He atoms, and to the formation of He_k^+ complexes.

J. Yerbury, Stephen Poon, Sarah Meehan et al.