24 research outputs found

    On Lie Ideals and Generalized Jordan Left Derivations of Prime Rings

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    Let R be a prime ring with characteristic different from 2 and U be a Lie ideal of R. In the paper, we initiate the study of generalized Jordan left derivations on Lie ideals of R and prove that every generalized Jordan left derivation on U is a generalized left derivation on U. Further, it is shown that generalized Jordan left biderivation associated with the left biderivation on U is either U ⊆ Z(R) or a right bicentralizer on U.Нехай R — просте кільцє з характеристикою, відмінною від 2, а U — ідеал Лі цього кільця. У цій статті ми починаємо дослідження узагальнених жорданових лівих похідних на ідеалах Лі кільця R і доводимо, що будь-яка узагальнена жорданова ліва похідна на U є узагальненою лівою похідною на U. Крім того, встановлено, що узагальнена жорданова ліва подвійна похідна, асоційована з лівою подвійною похідною на U, або U ⊆ Z(R), або правим подвійним централайзером на U

    Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

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    The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis

    توزيعات مراكز التشوه Z1 وادمصاص ذرات الهالوجينات على اسطح (001) لبلورات الكلوريدات : حسابات نظرية دالة الكثافة

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    An attempt has been made to examine the relative stabilities of Z, center orientations at the surfaces of Be2+, Mg2+ and Ca2+ doped LiCl, NaCl and KC1 ionic crystals as well as the effects of Z, center on the adsorption of atomic halogens (F, Cl, Br, I and At) using an embedded cluster model and density functional theory calculations. The embedded clusters were terminated by partial ionic charges that make the Coulomb potentials at the central surface sites equal to the Madelung potentials of the host.surfaces. While the linear orientations of the Be2+ doped surfaces were more stable than the non linear orientations, the non linear orientations of Mg2+ and Ca2+ doped surfaces were more stable than the linear orientations. The Z, center is suggested to be an F center strongly perturbed by a neighboring monovalent cation vacancy and almost independent on the position of the divalent cation impurity. The relative stabilities were neither dependent on the type of the divalent cation impurity nor the type of the monovalent hdst cation. The Z, center changes the nature of atomic halogen adsorption from physical adsorption to; chemical adsorption and the adsorption energies are directly proportional to the electronegativity of the halogen and the effec¬ tive nuclear charge of the host cation. The spin pairing mechanism plays the dominant role in the course of adsorbate-substrate interactions, and the surfaces can be made semiconducting by Zt center imperfec¬ tion.تم فحص درجات الاستقرار النسبي لتوزيعات مركز التشوهZ1على أسطح البلورات الايونية kCI, NaCI, LiCI لمطعمة بأيوناتCa2+, Mg2+, Be2+ بالأضافة إلى تأثيراته على ادمصاص الهالوجينات (F, CI, Br, I, At) باستخدام نموذج العناقيد المغمورة وحسابات نظرية دالة الكثافة ثم إحاطة العناقيد المغمورة بشحنات أيونية جزئية لمكافأة جهود كولومب على مركز السطح الأيوني لمضاهاة جهود ماديلونج للسطح العالئلي العائل. بناء على هذه الدراسة وجد أن التوزيعات غير الخطية للأسطح المطعمة بأيونات Ca2+, Mg2+ أكثر استقرارا من مثيلاتها الخطية، كما يقترح أن يكون مركز التشوه Z1 عبارة عن مركزF تحت تأثير فراغ كاتيوني مجاور أحادي التكافؤ بغض النظر عن موقع الشائبة الكاتيونية ثنائية التكافؤ. كما وجد أن درجات الاستقرار النسبي لا تعتمد على نوع الشائبة الكاتيونية ثنائية التكافؤ أو نوع الكاتيون العائل أحادي التكافؤ، وثبت أن مركز Z1 يغير من طبيعة الادمصاص الهالوجيني من فيزيائي إلى كيميائي. وجد أيضأ أن طاقة الادمصاص تتناسب طرديا مع درجة سالبيه الهالوجين المدمص وعلى شحنة النواة المؤثرة للكاتيون العائل.تلعب ميكانيكية الازدواج المغزلي دورا هاما في عملية الادمصاص، كما وجد أن الأسطح العازلة تتحول إلى أسطح شبه موصلة تحت تأثير مركز التشوه Z1

    TFIIH kinase places bivalent marks on the carboxy-terminal domain of RNA polymerase II..

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    Posttranslational modifications of the carboxyterminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) specify a molecular recognition code that is deciphered by proteins involved in RNA biogenesis. The CTD is comprised of a repeating heptapeptide (Y1S2P3T4S5P6S7). Recently, phosphorylation of serine 7 was shown to be important for cotranscriptional processing of two snRNAs in mammalian cells. Here we report that Kin28/Cdk7, a subunit of the evolutionarily conserved TFIIH complex, is a Ser7 kinase. The ability of Kin28/Cdk7 to phosphorylate Ser7 is particularly surprising because this kinase functions at promoters of protein-coding genes, rather than being restricted to promoter-distal regions of snRNA genes. Kin28/Cdk7 is also known to phosphorylate Ser5 residues of the CTD at gene promoters. Taken together, our results implicate the TFIIH kinase in placing bivalent Ser5 and Ser7 marks early in gene transcription. These bivalent CTD marks, in concert with cues within nascent transcripts, specify the cotranscriptional engagement of the relevant RNA processing machinery

    Meteorological Factors and Seasonal Stroke Rates: A Four-year Comprehensive Study

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    Introduction: There is a growing body of evidence suggesting that acute cardiovascular events including stroke are not distributed randomly over time but instead depend on months/season of the year. We report the impact of meteorological variables in extremely hot and arid climate on stroke. Methods: Acute stroke patients admitted from January 2014 to December 2017 were included. The data included demographics, clinical risk factors, temperature, solar radiation, relative humidity, dew point, wind speed, and atmospheric pressure. We calculated stroke rates/100,000/month. Results: There were 3654 cases of stroke (ischemic stroke [IS]: 2956 [80.9%]; and intracerebral hemorrhage [ICH]: 698 [19.1%]) with no difference in hematocrit, creatinine, and blood urea between hot and cold seasons (p > .05). We observed a positive significant correlation of IS with the mean temperature (AOR: 1.023; 95% CI: 1.009-1.036; P = .001) and mean solar radiation (AOR: 1.268; 95% CI: 1.021-1.575; P = .032) showing a 2.3% and 26.8% higher risk relative to ICH respectively, a negative correlation between IS with relative humidity (AOR: 0.99; 95% CI: 0.984-0.997; P = .002), and atmospheric pressure (AOR: 0.977; 95% CI: 0.966-0.989; P < .001) was observed, 1% increase in the relative humidity correlate with 2.4% and 1% lower risk of IS incidence relative to ICH respectively. Conclusion: We demonstrated a distinct seasonal pattern in the incidence of stroke with an increase in IS rates relative to ICH during the summer months with higher solar radiations that cannot be explained by physiological measures suggestive of dehydration or hem-concentration. - 2019 Elsevier Inc.Scopu

    Different phosphoisoforms of RNA polymerase II engage the Rtt103 termination factor in a structurally analogous manner.

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    The carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) orchestrates dynamic recruitment of specific cellular machines during different stages of transcription. Signature phosphorylation patterns of Y1S2P3T4S5P6S7 heptapeptide repeats of the CTD engage specific &quot;readers.&quot; Whereas phospho-Ser5 and phospho-Ser2 marks are ubiquitous, phospho-Thr4 is reported to only impact specific genes. Here, we identify a role for phospho-Thr4 in transcription termination at noncoding small nucleolar RNA (snoRNA) genes. Quantitative proteomics reveals an interactome of known readers as well as protein complexes that were not known to rely on Thr4 for association with Pol II. The data indicate a key role for Thr4 in engaging the machinery used for transcription elongation and termination. We focus on Rtt103, a protein that binds phospho-Ser2 and phospho-Thr4 marks and facilitates transcription termination at protein-coding genes. To elucidate how Rtt103 engages two distinct CTD modifications that are differentially enriched at noncoding genes, we relied on NMR analysis of Rtt103 in complex with phospho-Thr4- or phospho-Ser2-bearing CTD peptides. The structural data reveal that Rtt103 interacts with phospho-Thr4 in a manner analogous to its interaction with phospho-Ser2-modified CTD. The same set of hydrogen bonds involving either the oxygen on phospho-Thr4 and the hydroxyl on Ser2, or the phosphate on Ser2 and the Thr4 hydroxyl, can be formed by rotation of an arginine side chain, leaving the intermolecular interface otherwise unperturbed. This economy of design enables Rtt103 to engage Pol II at distinct sets of genes with differentially enriched CTD marks

    Noncanonical CTD kinases regulate RNA polymerase II in a gene-class-specific manner.

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    Phosphorylation of the carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) governs stage-specific interactions with different cellular machines. The CTD consists of Y1S2P3T4S5P6S7 heptad repeats and sequential phosphorylations of Ser7, Ser5 and Ser2 occur universally at Pol II-transcribed genes. Phosphorylation of Thr4, however, appears to selectively modulate transcription of specific classes of genes. Here, we identify ten new Thr4 kinases from different kinase structural groups. Irreversible chemical inhibition of the most active Thr4 kinase, Hrr25, reveals a novel role for this kinase in transcription termination of specific class of noncoding snoRNA genes. Genome-wide profiles of Hrr25 reveal a selective enrichment at 3&#39; regions of noncoding genes that display termination defects. Importantly, phospho-Thr4 marks placed by Hrr25 are recognized by Rtt103, a key component of the termination machinery. Our results suggest that these uncommon CTD kinases place phospho-Thr4 marks to regulate expression of targeted genes
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