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  • 1
    Language: English
    In: International Journal of Hygiene and Environmental Health, July 2012, Vol.215(4), pp.482-486
    Description: Influenza viruses are highly contagious. Medical personnel are at risk of occupational exposure to influenza. Data on dental healthcare workers (DHCWs) immunization status has not been published. We conducted a cross-sectional survey of DHCWs and dental students at a German dental university hospital. Surveys, completed between October 2010 and March 2011, focused on reasons of DHCWs for accepting or declining the influenza vaccination. Furthermore, we characterized attitudes towards influenza infection due to the emergence of the H1N1/2009. Compliance rates with the influenza vaccination among DHCWs were low (31.6%). The main reason for not getting vaccinated against the pandemic influenza A/H1N1 virus in the 2009/2010 season was the objection to the AS03-adjuvants (48.5%). Of the DHCWs surveyed, 30.6% (74/242) cited that the H1N1/2009 pandemic influenced their attitudes towards vaccination in general. Our findings confirm the importance of a comprehensive approach to the influenza vaccination, ensuring that DHCWs are correctly informed about the vaccine and that it is convenient to receive it. It could be shown that an immunization campaign at the workplace seems to be capable of improving vaccination rates, one-third of the vaccinees have been vaccinated for the first time.
    Keywords: Dental Health Care Workers ; Influenza ; Influenza A/H1n1 ; Occupational Infections ; Vaccination ; Biology ; Public Health
    ISSN: 1438-4639
    E-ISSN: 1618-131X
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  • 2
    Language: English
    In: Science, Nov 30, 2012, Vol.338(6111), p.1220(6)
    Description: Chronic infections strain the regenerative capacity of antiviral T lymphocyte populations, leading to failure in long-term immunity. The cellular and motecular events controlling this regenerative capacity, however, are unknown. We found that two distinct states of virus-specific [CD8.sup.+] T cells exist in chronically infected mice and humans. Differential expression of the T-box transcription factors T-bet and Eomesodermin (Eomes) facilitated the cooperative maintenance of the pool of antiviral CD[8.sup.+] T cells during chronic viral infection. [T-bet.sup.hi] cells displayed low intrinsic turnover but proliferated in response to persisting antigen, giving rise to [Eomes.sup.hi] terminal progeny. Genetic elimination of either subset resulted in failure to control chronic infection, which suggests that an imbalance in differentiation and renewal could underlie the collapse of immunity in humans with chronic infections. 10.1126/science.1229620
    Keywords: Immunity (Physiology) -- Genetic Aspects ; Cd8 Lymphocytes -- Health Aspects ; Cd8 Lymphocytes -- Genetic Aspects ; Transcription Factors -- Health Aspects
    ISSN: 0036-8075
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  • 3
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 10 November 2015, Vol.112(45), pp.14030-5
    Description: The glycoproteins of herpesviruses and of HIV/SIV are made late in the replication cycle and are derived from transcripts that use an unusual codon usage that is quite different from that of the host cell. Here we show that the actions of natural transinducers from these two different families of persistent viruses (Rev of SIV and ORF57 of the rhesus monkey rhadinovirus) are dependent on the nature of the skewed codon usage. In fact, the transinducibility of expression of these glycoproteins by Rev and by ORF57 can be flipped simply by changing the nature of the codon usage. Even expression of a luciferase reporter could be made Rev dependent or ORF57 dependent by distinctive changes to its codon usage. Our findings point to a new general principle in which different families of persisting viruses use a poor codon usage that is skewed in a distinctive way to temporally regulate late expression of structural gene products.
    Keywords: Rrv Orf57 ; Siv Rev ; Codon Usage ; Glycoprotein Induction ; Temporal Regulation ; Codon -- Genetics ; Gene Expression Regulation, Viral -- Physiology ; Viral Regulatory and Accessory Proteins -- Genetics
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 4
    Language: English
    In: Neuroscience, Oct 10, 2013, Vol.250, p.181(8)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.neuroscience.2013.07.003 Byline: W. Pfeilschifter, S. Kashefiolasl, A. Lauer, H. Steinmetz, C. Foerch Abstract: acents rt-PA treatment does not prolong active bleeding in experimental ICH. acents rt-PA treatment does not increase hematoma volume in experimental ICH. acents 72h observation does not show increased mortality of rt-PA-treated mice. Article History: Accepted 2 July 2013
    Keywords: Tissue Plasminogen Activator ; Hematoma
    ISSN: 0306-4522
    Source: Cengage Learning, Inc.
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  • 5
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 19 May 2015, Vol.112(20), pp.6479-84
    Description: Information processing in the brain requires reliable synaptic transmission. High reliability at specialized auditory nerve synapses in the cochlear nucleus results from many release sites (N), high probability of neurotransmitter release (Pr), and large quantal size (Q). However, high Pr also causes auditory nerve synapses to depress strongly when activated at normal rates for a prolonged period, which reduces fidelity. We studied how synapses are influenced by prolonged activity by exposing mice to constant, nondamaging noise and found that auditory nerve synapses changed to facilitating, reflecting low Pr. For mice returned to quiet, synapses recovered to normal depression, suggesting that these changes are a homeostatic response to activity. Two additional properties, Q and average excitatory postsynaptic current (EPSC) amplitude, were unaffected by noise rearing, suggesting that the number of release sites (N) must increase to compensate for decreased Pr. These changes in N and Pr were confirmed physiologically using the integration method. Furthermore, consistent with increased N, endbulbs in noise-reared animals had larger VGlut1-positive puncta, larger profiles in electron micrographs, and more release sites per profile. In current-clamp recordings, noise-reared BCs had greater spike fidelity even during high rates of synaptic activity. Thus, auditory nerve synapses regulate excitability through an activity-dependent, homeostatic mechanism, which could have major effects on all downstream processing. Our results also suggest that noise-exposed bushy cells would remain hyperexcitable for a period after returning to normal quiet conditions, which could have perceptual consequences.
    Keywords: Cochlear Nucleus ; Homeostasis ; Release Probability ; Auditory Perception -- Physiology ; Brain Stem -- Physiology ; Cochlear Nerve -- Physiology ; Homeostasis -- Physiology ; Neurotransmitter Agents -- Metabolism ; Synapses -- Physiology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 6
    Language: English
    In: Journal of the American Chemical Society, 27 January 2010, Vol.132(3), pp.980-8
    Description: Cell penetrating peptides (CPPs) have attracted recent interest as drug delivery tools, although the mechanisms by which CPPs are internalized by cells are not well-defined. Here, we report a new experimental approach for the detection and secondary structure determination of CPPs in live cells using Raman microscopy with heavy isotope labeling of the peptide. As a first demonstration of principle, penetratin, a 16-residue CPP derived from the Antennapedia homeodomain protein of Drosophila, was measured in single, living melanoma cells. Carbon-13 labeling of the Phe residue of penetratin was used to shift the intense aromatic ring-breathing vibrational mode from 1003 to 967 cm(-1), thereby enabling the peptide to be traced in cells. Difference spectroscopy and principal components analysis (PCA) were used independently to resolve the Raman spectrum of the peptide from the background cellular Raman signals. On the basis of the position of the amide I vibrational band in the Raman spectra, the secondary structure of the peptide was found to be mainly random coil and beta-strand in the cytoplasm, and possibly assembling as beta-sheets in the nucleus. The rapid entry and almost uniform cellular distribution of the peptide, as well as the lack of correlation between peptide and lipid Raman signatures, indicated that the mechanism of internalization under the conditions of study was probably nonendocytotic. This experimental approach can be used to study a wide variety of CPPs as well as other classes of peptides in living cells.
    Keywords: Carrier Proteins -- Chemistry ; Melanoma -- Chemistry
    ISSN: 00027863
    E-ISSN: 1520-5126
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  • 7
    Language: English
    In: The Journal of biological chemistry, 17 October 2014, Vol.289(42), pp.29171-9
    Description: We have recently demonstrated that the transfer of heavy chains (HCs) from inter-α-inhibitor, via the enzyme TSG-6 (tumor necrosis factor-stimulated gene 6), to hyaluronan (HA) oligosaccharides is an irreversible event in which subsequent swapping of HCs between HA molecules does not occur. We now describe our results of HC transfer experiments to chondroitin sulfate A, chemically desulfated chondroitin, chemoenzymatically synthesized chondroitin, unsulfated heparosan, heparan sulfate, and alginate. Of these potential HC acceptors, only chemically desulfated chondroitin and chemoenzymatically synthesized chondroitin were HC acceptors. The kinetics of HC transfer to chondroitin was similar to HA. At earlier time points, HCs were more widely distributed among the different sizes of chondroitin chains. As time progressed, the HCs migrated to lower molecular weight chains of chondroitin. Our interpretation is that TSG-6 swaps the HCs from the larger, reversible sites on chondroitin chains, which function as HC acceptors, onto smaller chondroitin chains, which function as irreversible HC acceptors. HCs transferred to smaller chondroitin chains were unable to be swapped off the smaller chondroitin chains and transferred to HA. HCs transferred to high molecular weight HA were unable to be swapped onto chondroitin. We also present data that although chondroitin was a HC acceptor, HA was the preferred acceptor when chondroitin and HA were in the same reaction mixture.
    Keywords: Chondroitin ; Chondroitin Sulfate ; Glycosaminoglycan ; Heparan Sulfate ; Hyaluronan ; Chondroitin -- Chemistry ; Hyaluronic Acid -- Chemistry ; Oligosaccharides -- Chemistry
    E-ISSN: 1083-351X
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  • 8
    Language: English
    In: Nature, April 28, 2011, Vol.472(7344), p.491(6)
    Description: T-helper cells that produce interleukin-17 ([T.sub.H]17 cells) are a recently identified [CD4.sup.+] T-cell subset with characterized pathological roles in autoimmune diseases (1-3). The nuclear receptors retinoic-acid-receptor-related orphan receptors [alpha] and [gamma]t (ROR[alpha] and ROR[gamma]t, respectively) have indispensible roles in the development of this cell type (4-7). Here we present SR1001, a high-affinity synthetic ligand--the first in a new class of compound--that is specific to both ROR[alpha] and ROR[gamma]t and which inhibits [T.sub.H]17 cell differentiation and function. SR1001 binds specifically to the ligand-binding domains of ROR[alpha] and ROR[gamma]t, inducing a conformational change within the ligand-binding domain that encompasses the repositioning of helix 12 and leads to diminished affinity for co-activators and increased affinity for co-repressors, resulting in suppression of the receptors' transcriptional activity. SR1001 inhibited the development of murine [T.sub.H]17 cells, as demonstrated by inhibition of interleukin-17A gene expression and protein production. Furthermore, SR1001 inhibited the expression of cytokines when added to differentiated murine or human [T.sub.H]17 cells. Finally, SR1001 effectively suppressed the clinical severity of autoimmune disease in mice. Our data demonstrate the feasibility of targeting the orphan receptors ROR[alpha] and ROR[gamma]t to inhibit specifically [T.sub.H]17 cell differentiation and function, and indicate that this novel class of compound has potential utility in the treatment of autoimmune diseases.
    Keywords: Autoimmunity -- Genetic Aspects ; Gene Expression -- Physiological Aspects ; Cell Differentiation -- Genetic Aspects ; Cell Receptors -- Properties ; Protein Binding -- Research
    ISSN: 0028-0836
    E-ISSN: 14764687
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  • 9
    Language: English
    In: The Science of the Total Environment, August 1, 2013, Vol.458-460, p.187(10)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.scitotenv.2013.04.024 Byline: Patrick J. Ferguson, Melody J. Bernot, Jason C. Doll, Thomas E. Lauer Abstract: Pharmaceuticals and personal care products (PPCPs) have been documented throughout the United States freshwaters but research has focused largely on lotic systems. Because PPCPs are designed to have a physiological effect, it is likely that they may also influence aquatic organisms. Thus, PPCPs may negatively impact aquatic ecosystems. The objectives of this research were to quantify PPCP abundance in near-shore habitats of southern Lake Michigan and identify factors related to PPCP abundance. Stratified sampling was conducted seasonally at four southern Lake Michigan sites. All sites and depths had measurable PPCP concentrations, with mean individual compound concentrations of acetaminophen (5.36ng/L), caffeine (31.0ng/L), carbamazepine (2.23ng/L), cotinine (4.03ng/L), gemfibrozil (7.03ng/L), ibuprofen (7.88ng/L), lincomycin (4.28ng/L), naproxen (6.32ng/L), paraxanthine (1,7-dimethylxanthine; 46.2ng/L), sulfadimethoxine (0.94ng/L), sulfamerazine (0.92ng/L), sulfamethazine (0.92ng/L), sulfamethoxazole (26.0ng/L), sulfathiazole (0.92ng/L), triclocarban (5.72ng/L), trimethoprim (5.15ng/L), and tylosin (3.75ng/L). Concentrations of PPCPs varied significantly among sampling times and locations (river mouth vs offshore), with statistical interactions between the main effects of site and time as well as time and location. Concentrations of PPCPs did not differ with site or depth. Temperature, total carbon, total dissolved solids, dissolved oxygen, and ammonium concentrations were related to total pharmaceutical concentrations. These data indicate that PPCPs are ubiquitous and persistent in southern Lake Michigan, potentially posing harmful effects to aquatic organisms. Article History: Received 5 February 2013; Revised 8 April 2013; Accepted 8 April 2013
    Keywords: Toiletries ; Aquatic Ecosystems
    ISSN: 0048-9697
    Source: Cengage Learning, Inc.
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  • 10
    Language: English
    In: Journal of the Neurological Sciences, 15 October 2015, Vol.357, pp.e423-e423
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jns.2015.08.1486 Byline: I. Zinchenko, V. Quenardelle, V. Lauer, C. Marescaux, B. Geny, V. Wolff
    Keywords: Medicine
    ISSN: 0022-510X
    E-ISSN: 1878-5883
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