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  • 1
    Language: English
    In: The Journal of biological chemistry, 23 February 2018, Vol.293(8), pp.2701-2710
    Description: Mammalian Nod-like receptor (NLR) proteins contribute to the regulation and induction of innate and adaptive immunity in mammals, although the function of about half of the currently identified NLR proteins remains poorly characterized. Here we analyzed the function of the primate-specific gene product. We show that is highly expressed in immune cells, including myeloid cells, B cells, and some B cell lymphoma lines. Overexpression of NLRP11 in human cells did not trigger key innate immune signaling pathways, including NF-κB and type I interferon responses. NLRP11 harbors a pyrin domain, which is responsible for inflammasome formation in related NLR proteins. However, NLRP11 did not interact with the inflammasome adaptor protein ASC, and it did not trigger caspase-1 activation. By contrast, expression of NLRP11 specifically repressed NF-κB and type I interferon responses, two key innate immune pathways involved in inflammation. This effect was independent of the pyrin domain and ATPase...
    Subject(s): B Cell ; Nf-Kappa B (Nf-Kb) ; Nlrp11 ; Nod-Like Receptor (Nlr) ; Anti-Viral ; Immunology ; Inflammasome ; Inflammation ; Innate Immunity ; Interferon ; Lymphoma ; Signaling ; Down-Regulation ; Gene Expression Regulation ; Immunity, Innate ; B-Lymphocytes -- Metabolism ; Intracellular Signaling Peptides and Proteins -- Metabolism ; Myeloid Cells -- Metabolism ; Nlr Proteins -- Metabolism
    ISSN: 0021-9258
    E-ISSN: 1083-351X
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  • 2
    Language: English
    In: FEMS Microbiology Ecology, 01/2012, Vol.79(1), pp.167-175
    Description: B urkholderia is a physiologically and ecologically diverse genus that occurs commonly in assemblages of soil and rhizosphere bacteria. Although B urkholderia is known for its heterotrophic versatility, we demonstrate that 14 distinct environmental isolates oxidized carbon monoxide (CO) and possessed the gene encoding the catalytic subunit of form I CO dehydrogenase ( coxL ). DNA from a B urkholderia isolate obtained from a passalid beetle also contained coxL as do the genomic sequences of species H160 and Ch1-1. Isolates were able to consume CO at concentrations ranging from 100 ppm (vol/vol) to sub-ambient (〈 60 ppb (vol/vol)). High concentrations of pyruvate inhibited CO uptake (〉 2.5 mM), but mixotrophic consumption of CO and pyruvate occurred when initial pyruvate concentrations were lower ( c . 400 μM). With the exception of an isolate most closely related to B urkholderia cepacia , all CO-oxidizing isolates examined were members of a nonpathogenic clade and were most closely related to B urkholderia species, B. caledonica , B. fungorum , B. oxiphila , B. mimosarum , B. nodosa , B. sacchari , B. bryophila , B. ferrariae , B. ginsengesoli , and B. unamae . However, none of these type strains oxidized CO or contained coxL based on results from PCR analyses. Collectively, these results demonstrate that the presence of CO oxidation within members of the B urkholderia genus is variable but it is most commonly found among rhizosphere inhabitants that are not closely related to B . cepacia .
    Subject(s): 〈Kwd〉〈Italic〉B〈/Italic〉〈Italic〉Urkholderia〈/Italic〉〈/Kwd〉 ; Carbon Monoxide ; 〈Kwd〉〈Italic〉Coxl〈/Italic〉〈/Kwd〉;
    ISSN: FEMS Microbiology Ecology
    E-ISSN: 01686496
    E-ISSN: 15746941
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  • 3
    Language: English
    In: Clinical interventions in aging, 2018, Vol.13, pp.1893-1898
    Description: The aim of the study was to assess the myostatin concentration and an improvement in the severity of urinary incontinence (UI) after pelvic floor muscle training (PFMT) in a group of elderly women with stress UI. A total of 74 participants were included in the analysis: 40 participants in the experimental group (EG) and 34 participants in the control group (CG). The EG underwent PFMT, whereas no therapeutic intervention was applied to the CG. Myostatin concentration and UI severity (Revised Urinary Incontinence Scale [RUIS]) were assessed in all women before and after the treatment. By comparing the results before and after the treatment, we have been able to demonstrate a statistically significant decrease in myostatin concentration (〈0.0001) and an improvement in the severity of UI (RUIS) (〈0.0001) in the EG. No statistically significant differences in all measured variables were reported before and after the treatment in the CG. A lower myostatin concentration (=0.0084) and an improvement in the severity of UI (RUIS) (=0.0008) were observed after the treatment in the EG compared to that in the CG. Effective PFMT causes downregulation of myostatin concentration and an improvement in the severity of UI in elderly women with stress UI. Further trials on a larger EG and an assessment of long-term treatment outcomes are required.
    Subject(s): Myostatin ; Pelvic Floor Muscle Training ; Urinary Incontinence ; Urinary Incontinence, Stress ; Exercise Therapy -- Methods ; Myostatin -- Blood ; Pelvic Floor -- Physiopathology
    ISSN: 1176-9092
    E-ISSN: 1178-1998
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  • 4
    Language: English
    In: Journal of education, health and sport, 01 June 2016, Vol.6(6), pp.677-694
    Description: Beck Oliwia, Łakomski Mateusz, Kędziora–Kornatowska Kornelia, Radzimińska Agnieszka, Weber-Rajek Magdalena, Żukow Walery. Otępienia jako choroby cywilizacyjne i społeczne XXI wieku = Dementia as a civilization and social diseases of the 21st century. Journal of Education, Health and Sport. 2016;6(6):677-694. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.101640 http://ojs.ukw.edu.pl/index.php/johs/article/view/3865       The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 755 (23.12.2015). 755 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2016; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s)...
    Subject(s): Starzenie Się, Otępienie, Choroba Alzheimera, Ageing, Dementia, Alzheimer’s Disease
    E-ISSN: 2391-8306
    Source: Directory of Open Access Journals (DOAJ)
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  • 5
    Language: English
    In: Journal of education, health and sport, 01 April 2016, Vol.6(4), pp.515-527
    Description: Beck Oliwia, Łakomski Mateusz, Kędziora–Kornatowska Kornelia, Waśniowski Wojciech, Radzimińska Agnieszka, Weber‑Rajek Magdalena, Żukow Walery. Łagodne zaburzenia poznawcze – aktualny problem geriatryczny = Mild cognitive impairment – current geriatric issue. Journal of Education, Health and Sport. 2016;6(4):515-527. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.154244 http://ojs.ukw.edu.pl/index.php/johs/article/view/3859       The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 755 (23.12.2015). 755 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2016; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original...
    Subject(s): Stopa, Diagnoza, Badanie Statyczne, Badanie Dynamiczne, Foot, Diagnosis, Static Examination, Dynamic Examination
    E-ISSN: 2391-8306
    Source: Directory of Open Access Journals (DOAJ)
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  • 6
    Language: English
    In: Journal of education, health and sport, 01 September 2016, Vol.6(9), pp.471-478
    Description: Beck Oliwia, Łakomski Mateusz, Kędziora–Kornatowska Kornelia, Radzimińska Agnieszka, Weber-Rajek Magdalena, Żukow Walery. Zdrowotne uwarunkowania niepełnosprawności osób starszych = Health determinants of disability in the elderly. Journal of Education, Health and Sport. 2016;6(9):471-478. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.151618 http://ojs.ukw.edu.pl/index.php/johs/article/view/3869       The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 755 (23.12.2015). 755 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2016; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source...
    Subject(s): Zdrowie, Starzenie Się, Niepełnosprawność, Niesamodzielność, Health, Ageing, Disability, Dependency
    E-ISSN: 2391-8306
    Source: Directory of Open Access Journals (DOAJ)
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  • 7
    In: Brain, 2018, Vol. 141(3), pp.688-697
    Description: Brenner et al. show that mutations in a C-terminal hotspot of kinesin-5A ( KIF5A) can cause a classical ALS phenotype. Experiments using patient-derived cell lines suggest haploinsufficiency as the molecular genetic mechanism. This underlines the relevance of intracellular transport processes for ALS, and is important for clinico-genetic diagnosis and counselling. Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A ( KIF5A ) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis. Using whole exome sequencing followed by rare variant analysis of 426 patients with familial amyotrophic lateral sclerosis and 6137 control subjects, we detected an enrichment of KIF5A splice-site mutations in amyotrophic lateral sclerosis (2/426 compared to 0/6137 in controls; P = 4.2 × 10 −3 ), both located in a hot-spot in the C-terminus of the protein and predicted to affect splicing exon 27. We additionally show co-segregation with amyotrophic lateral sclerosis of two canonical splice-site mutations in two families. Investigation of lymphoblast cell lines from patients with KIF5A splice-site mutations revealed the loss of mutant RNA expression and suggested haploinsufficiency as the most probable underlying molecular mechanism. Furthermore, mRNA sequencing of a rare non-synonymous missense mutation (predicting p.Arg1007Gly) located in the C-terminus of the protein shortly upstream of the splice donor of exon 27 revealed defective KIF5A pre-mRNA splicing in respective patient-derived cell lines owing to abrogation of the donor site. Finally, the non-synonymous single nucleotide variant rs113247976 (minor allele frequency = 1.00% in controls, n = 6137), also located in the C-terminal region [p.(Pro986Leu) in exon 26], was significantly enriched in familial amyotrophic lateral sclerosis patients (minor allele frequency = 3.40%; P = 1.28 × 10 −7 ). Our study demonstrates that mutations located specifically in a C-terminal hotspot of KIF5A can cause a classical amyotrophic lateral sclerosis phenotype, and underline the involvement of intracellular transport processes in amyotrophic lateral sclerosis pathogenesis.
    Subject(s): Als ; Kif5a Mutations ; Axonal Transport ; Whole Exome Sequencing
    ISSN: 0006-8950
    E-ISSN: 1460-2156
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  • 8
    Language: English
    In: Clinical interventions in aging, 2018, Vol.13, pp.2473-2480
    Description: Peri- and postmenopausal women frequently suffer from urinary incontinence (UI). Generally, UI becomes more severe with age. It impacts physical, mental, and social functioning as well as the quality of life, often leading to depression. Extracorporeal magnetic innervation (ExMI) is a relatively new conservative treatment method for UI. The aim of the study was to assess the effectiveness of ExMI in the treatment of stress UI in women. A total of 52 women were included in the analysis: 28 participants were allocated to the experimental group (EG) and 24 to the control group (CG). The average age was 65.41 years (±SD 4.08). EG patients completed ExMI therapy. The treatment sessions lasted for 15 minutes, and occurred three times a week, for 4 weeks. No therapeutic intervention was applied to the CG. To objectify the treatment outcomes in both groups before and after the treatment, we measured myostatin concentration and performed the UI severity assessment (The Revised Urinary Incontinence Scale), perceived self-efficacy assessment (General Self-Efficacy Scale), and depression severity assessment (Beck Depression Inventory). The authors compared the EG results at the initial and final assessments and found a statistically significant improvement in severity of UI (=0.001) and depression severity (=0.006), and a decrease in myostatin concentration (0.001). The authors did not find any statistically significant differences between all measured variables for the CG at the initial and final assessments. Furthermore, there were no statistically significant differences between all measured variables for the EG and the CG at the final assessment. Further trials are needed to determine optimal treatment protocols for various UI types and to evaluate long-term outcomes of the ExMI treatment.
    Subject(s): Extracorporeal Magnetic Innervation ; Stress Urinary Incontinence
    ISSN: 1176-9092
    E-ISSN: 1178-1998
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  • 9
    Language: English
    In: Molecular psychiatry, September 2020, Vol.25(9), pp.2047-2057
    Description: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a complex genetic background, hampering identification of underlying genetic risk factors. We hypothesized that combining linkage analysis and whole-exome sequencing (WES) in multi-generation pedigrees with multiple affected individuals can point toward novel ADHD genes. Three families with multiple ADHD-affected members (N = 70) and apparent dominant inheritance pattern were included in this study. Genotyping was performed in 37 family members, and WES was additionally carried out in 10 of those. Linkage analysis was performed using multi-point analysis in Superlink Online SNP 1.1. From prioritized linkage regions with a LOD score ≥ 2, a total of 24 genes harboring rare variants were selected. Those genes were taken forward and were jointly analyzed in gene-set analyses of exome-chip data using the MAGMA software in an independent sample of patients with persistent ADHD and healthy controls (N...
    Subject(s): Risk Factors ; Neurodevelopmental Disorders ; Genotyping ; Attention Deficit Hyperactivity Disorder ; Pedigree ; Single-Nucleotide Polymorphism ; Genes ; Heredity ; Linkage Analysis ; Hyperactivity ; Attention Deficit Hyperactivity Disorder;
    ISSN: 1359-4184
    E-ISSN: 1476-5578
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  • 10
    Language: English
    In: Breast Cancer Research and Treatment, 2016, Vol.157(3), pp.437-446
    Description: The biological subtype of breast cancer influences the selection of systemic therapy. Distinction between luminal A and B cancers depends on consistent assessment of Ki-67, but substantial intra-observer and inter-observer variability exists when immunohistochemistry (IHC) is used. We compared RT-qPCR with IHC in the assessment of Ki-67 and other standard factors used in breast cancer subtyping. RNA was extracted from archival breast tumour tissue of 769 women randomly assigned to the FinHer trial. Cancer ESR1 , PGR , ERBB2 and MKI67 mRNA content was quantitated with an RT-qPCR assay. Local pathologists assessed ER, PgR and Ki-67 expression using IHC. HER2 amplification was identified with chromogenic in situ hybridization (CISH) centrally. The results were correlated with distant disease-free survival (DDFS) and overall survival (OS). qPCR-based and IHC-based assessments of ER and PgR showed good concordance. Both low tumour MKI67 mRNA (RT-qPCR) and Ki-67 protein (IHC) levels were prognostic for favourable DDFS [hazard ratio (HR) 0.42, 95 % CI 0.25–0.71, P  = 0.001; and HR 0.56, 0.37–0.84, P  = 0.005, respectively] and OS. In multivariable analyses, cancer MKI67 mRNA content had independent influence on DDFS (adjusted HR 0.51, 95 % CI 0.29–0.89, P  = 0.019) while Ki-67 protein expression had not any influence ( P  = 0.266) whereas both assessments influenced independently OS. Luminal B patients treated with docetaxel-FEC had more favourable DDFS and OS than those treated with vinorelbine-FEC when the subtype was defined by RT-qPCR (for DDFS, HR 0.52, 95 % CI 0.29–0.94, P  = 0.031), but not when defined using IHC. Breast cancer subtypes approximated with RT-qPCR and IHC show good concordance, but cancer MKI67 mRNA content correlated slightly better with DDFS than Ki-67 expression. The findings based on MKI67 mRNA content suggest that patients with luminal B cancer benefit more from docetaxel-FEC than from vinorelbine-FEC.
    Subject(s): Breast cancer ; Molecular subtypes ; Ki-67 ; Prediction ; Immunohistochemistry ; RT-qPCR
    ISSN: 0167-6806
    E-ISSN: 1573-7217
    Source: Springer Science & Business Media B.V.
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