Stimulation of translation by human Unr requires cold shock domains 2 and 4, and correlates with poly(A) binding protein interaction

The RNA binding protein Unr, which contains five cold shock domains, has several specific roles in post-transcriptional control of gene expression. It can act as an activator or inhibitor of translation initiation, promote mRNA turnover, or stabilise mRNA. Its role depends on the mRNA and other proteins to which it binds, which includes cytoplasmic poly(A) binding protein 1 (PABP1). Since PABP1 binds to all polyadenylated mRNAs, and is involved in translation initiation by interaction with eukaryotic translation initiation factor 4G (eIF4G), we investigated whether Unr has a general role in translational control. We found that Unr strongly stimulates translation in vitro, and mutation of cold shock domains 2 or 4 inhibited its translation activity. The ability of Unr and its mutants to stimulate translation correlated with its ability to bind RNA, and to interact with PABP1. We found that Unr stimulated the binding of PABP1 to mRNA, and that Unr was required for the stable interaction of PABP1 and eIF4G in cells. siRNA-mediated knockdown of Unr reduced the overall level of cellular translation in cells, as well as that of cap-dependent and IRES-dependent reporters. These data describe a novel role for Unr in regulating cellular gene expression

Centralizer's applications to the (b, c)-inverses in rings

[EN] We give several conditions in order that the absorption law for one sided (b,c)-inverses in rings holds. Also, by using centralizers, we obtain the absorption law for the (b,c)-inverse and the reverse order law of the (b,c)-inverse in rings. As applications, we obtain the related results for the inverse along an element, Moore-Penrose inverse, Drazin inverse, group inverse and core inverse.This research is supported by the National Natural Science Foundation of China (no. 11771076 and no. 11871301). The first author is grateful to China Scholarship Council for giving him a scholarship for his further study in Universitat Politecnica de Valencia, Spain.Xu, S.; Chen, J.; Benítez López, J.; Wang, D. (2019). Centralizer's applications to the (b, c)-inverses in rings. Revista de la Real Academia de Ciencias Exactas, Físicas y Naturales. 113(3):1739-1746. https://doi.org/10.1007/s13398-018-0574-0S173917461133Baksalary, O.M., Trenkler, G.: Core inverse of matrices. Linear Multilinear Algebra 58(6), 681–697 (2010)Benítez, J., Boasso, E.: The inverse along an element in rings with an involution, Banach algebras and $$C^*$$ C ∗ -algebras. Linear Multilinear Algebra 65(2), 284–299 (2017)Benítez, J., Boasso, E., Jin, H.W.: On one-sided $$(B, C)$$ ( B , C ) -inverses of arbitrary matrices. Electron. J. Linear Algebra 32, 391–422 (2017)Boasso, E., Kantún-Montiel, G.: The $$(b, c)$$ ( b , c ) -inverses in rings and in the Banach context. Mediterr. J. Math. 14, 112 (2017)Chen, Q.G., Wang, D.G.: A class of coquasitriangular Hopf group algebras. Comm. Algebra 44(1), 310–335 (2016)Chen, J.L., Ke, Y.Y., Mosić, D.: The reverse order law of the $$(b, c)$$ ( b , c ) -inverse in semigroups. Acta Math. Hung. 151(1), 181–198 (2017)Deng, C.Y.: Reverse order law for the group inverses. J. Math. Anal. Appl. 382(2), 663–671 (2011)Drazin, M.P.: Pseudo-inverses in associative rings and semigroups. Am. Math. Mon. 65, 506–514 (1958)Drazin, M.P.: A class of outer generalized inverses. Linear Algebra Appl. 436, 1909–1923 (2012)Drazin, M.P.: Left and right generalized inverses. Linear Algebra Appl. 510, 64–78 (2016)Jin, H.W., Benítez, J.: The absorption laws for the generalized inverses in rings. Electron. J. Linear Algebra 30, 827–842 (2015)Johnson, B.E.: An introduction to the theory of centralizers. Proc. Lond. Math. Soc. 14, 299–320 (1964)Ke, Y.Y., Cvetković-Ilić, D.S., Chen, J.L., Višnjić, J.: New results on $$(b, c)$$ ( b , c ) -inverses. Linear Multilinear Algebra 66(3), 447–458 (2018)Ke Y.Y., Višnjić J., Chen J.L.: One sided $$(b,c)$$ ( b , c ) -inverse in rings (2016). arXiv:1607.06230v1Liu, X.J., Jin, H.W., Cvetković-Ilić, D.S.: The absorption laws for the generalized inverses. Appl. Math. Comput. 219, 2053–2059 (2012)Mary, X.: On generalized inverse and Green’s relations. Linear Algebra Appl. 434, 1836–1844 (2011)Mary, X., Patrício, P.: Generalized inverses modulo $$\cal{H}$$ H in semigroups and rings. Linear Multilinear Algebra 61(8), 1130–1135 (2013)Mosić, D., Cvetković-Ilić, D.S.: Reverse order law for the Moore-Penrose inverse in $$C^*$$ C ∗ -algebras. Electron. J. Linear Algebra 22, 92–111 (2011)Rakić, D.S.: A note on Rao and Mitra’s constrained inverse and Drazin’s $$(b, c)$$ ( b , c ) -inverse. Linear Algebra Appl. 523, 102–108 (2017)Rakić, D.S., Dinčić, N.Č., Djordjević, D.S.: Group, Moore–Penrose, core and dual core inverse in rings with involution. Linear Algebra Appl. 463, 115–133 (2014)Wang, L., Castro-González, N., Chen, J.L.: Characterizations of outer generalized inverses. Can. Math. Bull. 60(4), 861–871 (2017)Wei, Y.M.: A characterization and representation of the generalized inverse $$A^{(2)}_{T, S}$$ A T , S ( 2 ) and its applications. Linear Algebra Appl. 280, 87–96 (1998)Xu, S.Z., Benítez, J.: Existence criteria and expressions of the $$(b, c)$$ ( b , c ) -inverse in rings and its applications. Mediterr. J. Math. 15, 14 (2018)Zhu, H.H., Chen, J.L., Patrício, P.: Further results on the inverse along an element in semigroups and rings. Linear Multilinear Algebra 64(3), 393–403 (2016)Zhu, H.H., Chen, J.L., Patrício, P.: Reverse order law for the inverse along an element. Linear Multilinear Algebra 65, 166–177 (2017)Zhu, H.H., Chen, J.L., Patrício, P., Mary, X.: Centralizer’s applications to the inverse along an element. Appl. Math. Comput. 315, 27–33 (2017)Zhu, H.H., Zhang, X.X., Chen, J.L.: Centralizers and their applications to generalized inverses. Linear Algebra Appl. 458, 291–300 (2014

Stem cell factor and its soluble receptor (c-kit) in serum of asthmatic patients- correlation with disease severity

<p>Abstract</p> <p>Background</p> <p>SCF (stem cell factor) is a pleiotropic cytokine exerting its role at different stages of bone marrow development and affecting eosinophil activation, mast cells and basophil chemotaxis and survival. The aim of the study was to assess concentration of SCF and its soluble receptor c-kit (sc-kit) in peripheral blood of patients with asthma referring it to asthma severity and phenotype.</p> <p>Methods</p> <p>The study involved 107 patients with bronchial asthma, well characterized with respect to severity and 21 healthy controls. Concentration of SCF and sc-kit in the patients serum were measured by ELISA method.</p> <p>Results</p> <p>Mean serum SCF level in the group of asthmatics (n = 88) was significantly higher as compared to healthy controls (1010 pg/ml ± 37 vs 799 ± 33; p < 0,001). The level of SCF was higher in patients with severe asthma as compared to patients with non-severe asthma (1054 +/- 41 pg/ml vs 819 +/- 50; p < 0,01) and correlated with dose of inhaled glucocorticosteroids taken by the patients to achieve asthma control (R = 0,28; p < 0,01). The mean sc-kit serum level did not differ between asthmatic patients and healthy controls, however the level of sc-kit in non-severe asthmatics was significantly higher as compared to patients with severe asthma and healthy controls. In asthmatic patients (n = 63) the level of sc-kit correlated positively with FEV1% predicted value (R = 0,45; p < 0,001) and MEF25% predicted value (R = 0,33; p < 0,01). The level of sc-kit inversely correlated with the dose of inhaled glucocorticosteroids taken by the patients (R = -0,26; p < 0,01).</p> <p>Conclusion</p> <p>Serum levels of SCF and its soluble receptor c-kit seem to be reflect asthma severity suggesting a role for these molecules in asthmatic inflammation.</p

Decreased Level of Nurr1 in Heterozygous Young Adult Mice Leads to Exacerbated Acute and Long-Term Toxicity after Repeated Methamphetamine Exposure

The abuse of psychostimulants, such as methamphetamine (METH), is prevalent in young adults and could lead to long-term adaptations in the midbrain dopamine system in abstinent human METH abusers. Nurr1 is a gene that is critical for the survival and maintenance of dopaminergic neurons and has been implicated in dopaminergic neuron related disorders. In this study, we examined the synergistic effects of repeated early exposure to methamphetamine in adolescence and reduction in Nurr1 gene levels. METH binge exposure in adolescence led to greater damage in the nigrostrial dopaminergic system when mice were exposed to METH binge later in life, suggesting a long-term adverse effect on the dopaminergic system. Compared to naïve mice that received METH binge treatment for the first time, mice pretreated with METH in adolescence showed a greater loss of tyrosine hydroxylase (TH) immunoreactivity in striatum, loss of THir fibers in the substantia nigra reticulata (SNr) as well as decreased dopamine transporter (DAT) level and compromised DA clearance in striatum. These effects were further exacerbated in Nurr1 heterozygous mice. Our data suggest that a prolonged adverse effect exists following adolescent METH binge exposure which may lead to greater damage to the dopaminergic system when exposed to repeated METH later in life. Furthermore, our data support that Nurr1 mutations or deficiency could be a potential genetic predisposition which may lead to higher vulnerability in some individuals

Functional characterization of cellulases identified from the cow rumen fungus Neocallimastix patriciarum W5 by transcriptomic and secretomic analyses

<p>Abstract</p> <p>Background</p> <p><it>Neocallimastix patriciarum</it> is one of the common anaerobic fungi in the digestive tracts of ruminants that can actively digest cellulosic materials, and its cellulases have great potential for hydrolyzing cellulosic feedstocks. Due to the difficulty in culture and lack of a genome database, it is not easy to gain a global understanding of the glycosyl hydrolases (<it>GHs</it>) produced by this anaerobic fungus.</p> <p>Results</p> <p>We have developed an efficient platform that uses a combination of transcriptomic and proteomic approaches to <it>N. patriciarum </it>to accelerate gene identification, enzyme classification and application in rice straw degradation. By conducting complementary studies of transcriptome (Roche 454 GS and Illumina GA IIx) and secretome (ESI-Trap LC-MS/MS), we identified 219 putative <it>GH </it>contigs and classified them into 25 <it>GH</it> families. The secretome analysis identified four major enzymes involved in rice straw degradation: β-glucosidase, endo-1,4-β-xylanase, xylanase B and Cel48A exoglucanase. From the sequences of assembled contigs, we cloned 19 putative cellulase genes, including the <it>GH1</it>, <it>GH3</it>, <it>GH5</it>, <it>GH6</it>, <it>GH9</it>, <it>GH18</it>, <it>GH43 </it>and <it>GH48 </it>gene families, which were highly expressed in <it>N. patriciarum </it>cultures grown on different feedstocks.</p> <p>Conclusions</p> <p>These <it>GH </it>genes were expressed in Pichia pastoris and/or Saccharomyces cerevisiae for functional characterization. At least five novel cellulases displayed cellulytic activity for glucose production. One β-glucosidase (W5-16143) and one exocellulase (W5-CAT26) showed strong activities and could potentially be developed into commercial enzymes.</p

Age-Related Changes in the Epithelial and Stromal Compartments of the Mammary Gland in Normocalcemic Mice Lacking the Vitamin D3 Receptor

The vitamin D3 receptor (VDR) serves as a negative growth regulator during mammary gland development via suppression of branching morphogenesis during puberty and modulation of differentiation and apoptosis during pregnancy, lactation and involution. To assess the role of the VDR in the aging mammary gland, we utilized 12, 14, and 16 month old VDR knockout (KO) and wild type (WT) mice for assessment of integrity of the epithelial and stromal compartments, steroid hormone levels and signaling pathways. Our data indicate that VDR ablation is associated with ductal ectasia of the primary mammary ducts, loss of secondary and tertiary ductal branches and atrophy of the mammary fat pad. In association with loss of the white adipose tissue compartment, smooth muscle actin staining is increased in glands from VDR KO mice, suggesting a change in the stromal microenviroment. Activation of caspase-3 and increased Bax expression in mammary tissue of VDR KO mice suggests that enhanced apoptosis may contribute to loss of ductal branching. These morphological changes in the glands of VDR KO mice are associated with ovarian failure and reduced serum 17β-estradiol. VDR KO mice also exhibit progressive loss of adipose tissue stores, hypoleptinemia and increased metabolic rate with age. These developmental studies indicate that, under normocalcemic conditions, loss of VDR signaling is associated with age-related estrogen deficiency, disruption of epithelial ductal branching, abnormal energy expenditure and atrophy of the mammary adipose compartment

Spiritual Well-Being and Depression in Patients with Heart Failure

BACKGROUND: In patients with chronic heart failure, depression is common and associated with poor quality of life, more frequent hospitalizations, and higher mortality. Spiritual well-being is an important, modifiable coping resource in patients with terminal cancer and is associated with less depression, but little is known about the role of spiritual well-being in patients with heart failure. OBJECTIVE: To identify the relationship between spiritual well-being and depression in patients with heart failure. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty patients aged 60 years or older with New York Heart Association class II–IV heart failure. MEASUREMENTS: Spiritual well-being was measured using the total scale and 2 subscales (meaning/peace, faith) of the Functional Assessment of Chronic Illness Therapy—Spiritual Well-being scale, depression using the Geriatric Depression Scale—Short Form (GDS-SF). RESULTS: The median age of participants was 75 years. Nineteen participants (32%) had clinically significant depression (GDS-SF > 4). Greater spiritual well-being was strongly inversely correlated with depression (Spearman’s correlation −0.55, 95% confidence interval −0.70 to −0.35). In particular, greater meaning/peace was strongly associated with less depression (r = −.60, P < .0001), while faith was only modestly associated (r = −.38, P < .01). In a regression analysis accounting for gender, income, and other risk factors for depression (social support, physical symptoms, and health status), greater spiritual well-being continued to be significantly associated with less depression (P = .05). Between the 2 spiritual well-being subscales, only meaning/peace contributed significantly to this effect (P = .02) and accounted for 7% of the variance in depression. CONCLUSIONS: Among outpatients with heart failure, greater spiritual well-being, particularly meaning/peace, was strongly associated with less depression. Enhancement of patients’ sense of spiritual well-being might reduce or prevent depression and thus improve quality of life and other outcomes in this population

Cardiothoracic CT: one-stop-shop procedure? Impact on the management of acute pulmonary embolism

In the treatment of pulmonary embolism (PE) two groups of patients are traditionally identified, namely the hemodynamically stable and instable groups. However, in the large group of normotensive patients with PE, there seems to be a subgroup of patients with an increased risk of an adverse outcome, which might benefit from more aggressive therapy than the current standard therapy with anticoagulants. Risk stratification is a commonly used method to define subgroups of patients with either a high or low risk of an adverse outcome. In this review the clinical parameters and biomarkers of myocardial injury and right ventricular dysfunction (RVD) that have been suggested to play an important role in the risk stratification of PE are described first. Secondly, the use of more direct imaging techniques like echocardiography and CT in the assessment of RVD are discussed, followed by a brief outline of new imaging techniques. Finally, two risk stratification models are proposed, combining the markers of RVD with cardiac biomarkers of ischemia to define whether patients should be admitted to the intensive care unit (ICU) and/or be given thrombolysis, admitted to the medical ward, or be safely treated at home with anticoagulant therapy