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101.
Aliaksei Shymanets Prajwal Kirsten Bucher Sandra Beer-Hammer Christian Harteneck Bernd Nürnberg 《The Journal of biological chemistry》2013,288(43):31059-31068
Class IB phosphoinositide 3-kinase γ (PI3Kγ) comprises a single catalytic p110γ subunit, which binds to two non-catalytic subunits, p87 or p101, and controls a plethora of fundamental cellular responses. The non-catalytic subunits are assumed to be redundant adaptors for Gβγ enabling G-protein-coupled receptor-mediated regulation of PI3Kγ. Growing experimental data provide contradictory evidence. To elucidate the roles of the non-catalytic subunits in determining the specificity of PI3Kγ, we tested the impact of p87 and p101 in heterodimeric p87-p110γ and p101-p110γ complexes on the modulation of PI3Kγ activity in vitro and in living cells. RT-PCR, biochemical, and imaging data provide four lines of evidence: (i) specific expression patterns of p87 and p101, (ii) up-regulation of p101, providing the basis to consider p87 as a protein forming a constitutively and p101 as a protein forming an inducibly expressed PI3Kγ, (iii) differences in basal and stimulated enzymatic activities, and (iv) differences in complex stability, all indicating apparent diversity within class IB PI3Kγ. In conclusion, expression and activities of PI3Kγ are modified differently by p87 and p101 in vitro and in living cells, arguing for specific regulatory roles of the non-catalytic subunits in the differentiation of PI3Kγ signaling pathways. 相似文献
102.
103.
Corinne Cayatte Kirsten Schneider-Ohrum Zhaoti Wang Alivelu Irrinki Nga Nguyen Janine Lu Christine Nelson Esteban Servat Lorraine Gemmell Andrzej Citkowicz Yi Liu Gregory Hayes Jennifer Woo Gary Van Nest Hong Jin Gregory Duke A. Louise McCormick 《Journal of virology》2013,87(20):11107-11120
Human cytomegalovirus (HCMV), a betaherpesvirus, can cause severe disease in immunosuppressed patients and following congenital infection. A vaccine that induces both humoral and cellular immunity may be required to prevent congenital infection. Dense bodies (DBs) are complex, noninfectious particles produced by HCMV-infected cells and may represent a vaccine option. As knowledge of the antigenicity and immunogenicity of DB is incomplete, we explored characterization methods and defined DB production methods, followed by systematic evaluation of neutralization and cell-mediated immune responses to the DB material in BALB/c mice. DBs purified from Towne-infected cultures treated with the viral terminase inhibitor 2-bromo-5,6-dichloro-1-beta-d-ribofuranosyl benzimidazole riboside (BDCRB) were characterized by nanoparticle tracking analysis (NTA), two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), immunoblotting, quantitative enzyme-linked immunosorbent assay, and other methods. The humoral and cellular immune responses to DBs were compared to the immunogenicity of glycoprotein B (gB) administered with the adjuvant AddaVax (gB/AddaVax). DBs induced neutralizing antibodies that prevented viral infection of cultured fibroblasts and epithelial cells and robust cell-mediated immune responses to multiple viral proteins, including pp65, gB, and UL48. In contrast, gB/AddaVax failed to induce neutralizing antibodies that prevented infection of epithelial cells, highlighting a critical difference in the humoral responses induced by these vaccine candidates. Our data advance the potential for the DB vaccine approach, demonstrate important immunogenicity properties, and strongly support the further evaluation of DBs as a CMV vaccine candidate. 相似文献
104.
Shipeng Lu Karuna Chourey Marco Reiche Sandor Nietzsche Manesh B. Shah Thomas R. Neu Robert L. Hettich Kirsten Küsel 《Applied and environmental microbiology》2013,79(14):4272-4281
Microbial ferrous iron [Fe(II)] oxidation leads to the formation of iron-rich macroscopic aggregates (“iron snow”) at the redoxcline in a stratified lignite mine lake in east-central Germany. We aimed to identify the abundant Fe-oxidizing and Fe-reducing microorganisms likely to be involved in the formation and transformation of iron snow present in the redoxcline in two basins of the lake that differ in their pH values. Nucleic acid- and lipid-stained microbial cells of various morphologies detected by confocal laser scanning microscopy were homogeneously distributed in all iron snow samples. The dominant iron mineral appeared to be schwertmannite, with shorter needles in the northern than in the central basin samples. Total bacterial 16S rRNA gene copies ranged from 5.0 × 108 copies g (dry weight)−1 in the acidic central lake basin (pH 3.3) to 4.0 × 1010 copies g (dry weight)−1 in the less acidic (pH 5.9) northern basin. Total RNA-based quantitative PCR assigned up to 61% of metabolically active microbial communities to Fe-oxidizing- and Fe-reducing-related bacteria, indicating that iron metabolism was an important metabolic strategy. Molecular identification of abundant groups suggested that iron snow surfaces were formed by chemoautotrophic iron oxidizers, such as Acidimicrobium, Ferrovum, Acidithiobacillus, Thiobacillus, and Chlorobium, in the redoxcline and were rapidly colonized by heterotrophic iron reducers, such as Acidiphilium, Albidiferax-like, and Geobacter-like groups. Metaproteomics yielded 283 different proteins from northern basin iron snow samples, and protein identification provided a glimpse into some of their in situ metabolic processes, such as primary production (CO2 fixation), respiration, motility, and survival strategies. 相似文献
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106.
Sabrina Sacconi Richard?J.L.F. Lemmers Judit Balog Patrick?J. van?der?Vliet Pauline Lahaut Merlijn?P. van?Nieuwenhuizen Kirsten?R. Straasheijm Rashmie?D. Debipersad Marianne Vos-Versteeg Leonardo Salviati Alberto Casarin Elena Pegoraro Rabi Tawil Egbert Bakker Stephen?J. Tapscott Claude Desnuelle Silvère?M. van?der?Maarel 《American journal of human genetics》2013,93(4):744-751
Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array on chromosome 4 to a size of 1–10 units. The residual number of D4Z4 units inversely correlates with clinical severity, but significant clinical variability exists. Each unit contains a copy of the DUX4 retrogene. Repeat contractions are associated with changes in D4Z4 chromatin structure that increase the likelihood of DUX4 expression in skeletal muscle, but only when the repeat resides in a genetic background that contains a DUX4 polyadenylation signal. Mutations in the structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) gene, encoding a chromatin modifier of D4Z4, also result in the increased likelihood of DUX4 expression in individuals with a rare form of FSHD (FSHD2). Because SMCHD1 directly binds to D4Z4 and suppresses somatic expression of DUX4, we hypothesized that SMCHD1 may act as a genetic modifier in FSHD1. We describe three unrelated individuals with FSHD1 presenting an unusual high clinical severity based on their upper-sized FSHD1 repeat array of nine units. Each of these individuals also carries a mutation in the SMCHD1 gene. Familial carriers of the FSHD1 allele without the SMCHD1 mutation were only mildly affected, suggesting a modifier effect of the SMCHD1 mutation. Knocking down SMCHD1 in FSHD1 myotubes increased DUX4 expression, lending molecular support to a modifier role for SMCHD1 in FSHD1. We conclude that FSHD1 and FSHD2 share a common pathophysiological pathway in which the FSHD2 gene can act as modifier for disease severity in families affected by FSHD1. 相似文献
107.
Qiaomei Fu Alissa Mittnik Philip L.F. Johnson Kirsten Bos Martina Lari Ruth Bollongino Chengkai Sun Liane Giemsch Ralf Schmitz Joachim Burger Anna Maria Ronchitelli Fabio Martini Renata G. Cremonesi Jiří Svoboda Peter Bauer David Caramelli Sergi Castellano David Reich Johannes Krause 《Current biology : CB》2013,23(7):553-559
108.
Paula Chappell Kirsten Foley Annette B. Jensen William O. H. Hughes 《Ecology and evolution》2013,3(7):2214-2222
Parasites are thought to be a major driving force shaping genetic variation in their host, and are suggested to be a significant reason for the maintenance of sexual reproduction. A leading hypothesis for the occurrence of multiple mating (polyandry) in social insects is that the genetic diversity generated within‐colonies through this behavior promotes disease resistance. This benefit is likely to be particularly significant when colonies are exposed to multiple species and strains of parasites, but host–parasite genotypic interactions in social insects are little known. We investigated this using honey bees, which are naturally polyandrous and consequently produce genetically diverse colonies containing multiple genotypes (patrilines), and which are also known to host multiple strains of various parasite species. We found that host genotypes differed significantly in their resistance to different strains of the obligate fungal parasite that causes chalkbrood disease, while genotypic variation in resistance to the facultative fungal parasite that causes stonebrood disease was less pronounced. Our results show that genetic variation in disease resistance depends in part on the parasite genotype, as well as species, with the latter most likely relating to differences in parasite life history and host–parasite coevolution. Our results suggest that the selection pressure from genetically diverse parasites might be an important driving force in the evolution of polyandry, a mechanism that generates significant genetic diversity in social insects. 相似文献
109.
Anne-Helene Tauson Dr Rikke Fink Kirsten Bislev Hansen NE Hansen A Chwalibog 《Archives of animal nutrition》2013,67(2):181-194
A total of 36 mink dams and their litters of 3, 6 or 9 kits were used for determination of milk intake of the suckling young by means of deuterium dilution technique, and chemical composition of milk and of kit bodies. Measurements were performed during lactation weeks 1?–?4, each week with 3 dams with each litter size. Milk intake was determined over a 48?h measurement period, and by the end of this milk samples were collected and 2 kits (litters of 6 and 9) or 1 kit per litter (litters of 3) were killed for body chemical composition. Based on the results, different models were applied for calculation of the energetic efficiency of milk. Dam milk yield increased steadily from week 1 until week 3 but only slightly from week 3 to 4. The increase declined with increasing litter size, and for dams suckling 9 kits the increment from week 3 to week 4 was only 2?g. The dry matter content of milk increased significantly as lactation progressed, being reflected in crude protein increasing from 6.9% in lactation week 1 to 8.1% in week 4. Milk fat increased concomitantly from 5.6% to 8.0%. In kit bodies, crude protein content increased from 9.4% in week 1 to about 12% in weeks 3 and 4. Body fat content increased from week 1 (4.1%) to week 3 (8.4%) and then declined in week 4 (7.1%). Animals suckled in litters of 3 kits had the highest milk intake and live weight and kits suckled in litters of 9 had the lowest milk intake, live weight and daily gain. In terms of milk intake per g gain kits in litters of 6 were the most efficient, with 4.1?g milk per g body gain. The metabolizable energy requirement for maintenance (MEm) was estimated to 448 kJ/kg0.75 and the efficiency of utilization of ME for body gain (kg) to 0.67, the estimates being higher (MEm) or in good agreement with previous findings (kg) in suckling mink kits. 相似文献