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61.
Cristina M. Fragoso Gabriela Schumann Burkard Michael Oberle Christina Kunz Renggli Karen Hilzinger Isabel Roditi 《PloS one》2009,4(9)
The coat of Trypanosoma brucei consists mainly of glycosylphosphatidylinositol-anchored proteins that are present in several million copies and are characteristic of defined stages of the life cycle. While these major components of the coats of bloodstream forms and procyclic (insect midgut) forms are well characterised, very little is known about less abundant stage-regulated surface proteins and their roles in infection and transmission. By creating epitope-tagged versions of procyclic-specific surface antigen 2 (PSSA-2) we demonstrated that it is a membrane-spanning protein that is expressed by several different life cycle stages in tsetse flies, but not by parasites in the mammalian bloodstream. In common with other membrane-spanning proteins in T. brucei, PSSA-2 requires its cytoplasmic domain in order to exit the endoplasmic reticulum. Correct localisation of PSSA-2 requires phosphorylation of a cytoplasmic threonine residue (T305), a modification that depends on the presence of TbMAPK4. Mutation of T305 to alanine (T305A) has no effect on the localisation of the protein in cells that express wild type PSSA-2. In contrast, this protein is largely intracellular when expressed in a null mutant background. A variant with a T305D mutation gives strong surface expression in both the wild type and null mutant, but slows growth of the cells, suggesting that it may function as a dominant negative mutant. The PSSA-2 null mutant exhibits no perceptible phenotype in culture and is fully competent at establishing midgut infections in tsetse, but is defective in colonising the salivary glands and the production of infectious metacyclic forms. Given the protein''s structure and the effects of mutation of T305 on proliferation and localisation, we postulate that PSSA-2 might sense and transmit signals that contribute to the parasite''s decision to divide, differentiate or migrate. 相似文献
62.
Christina A. Olson Karen H. Beard David N. Koons William C. Pitt 《Biological invasions》2012,14(4):889-900
Two nonnative Caribbean frogs, the Puerto Rican coqui and the Cuban greenhouse frog, recently invaded Hawaii. Because of its
louder breeding call, management efforts have focused on the coqui, while little has been done to address the more cryptic
greenhouse frog, even though it may be as widespread and have similar ecological impacts. The goal of this research was to
determine the distribution and detection probability of both species on the island of Hawaii. We conducted a breeding call
presence/absence survey at 446 sites every 2 km along major road networks. We re-surveyed 125 sites twice to determine detection
and occupancy probabilities. Greenhouse frog detection probabilities (0.24, 0.29, 0.48, for each of the three visits, respectively)
were lower than coqui detection probabilities (0.58, 0.73, 0.50, respectively) and increased with visits while those of the
coqui did not. Greenhouse frog detection probabilities were lower in the presence of coquis for the first two surveys (0.12,
0.14) than in sites with greenhouse frogs alone (0.41), while greenhouse frogs had no effect on the detection of coquis. Site
occupancy estimates for the greenhouse and coqui frog were 0.35 and 0.31, respectively, suggesting the species are similarly
widespread. Results suggest multiple visits to sites are required to detect the greenhouse frog. Furthermore, results suggest
that accounting for detectability is essential when determining the extent of invasion of cryptic species. 相似文献
63.
David E. Kling Amanda J. Cavicchio Christina A. Sollinger Jay J. Schnitzer T. Bernard Kinane David S. Newburg 《Birth defects research. Part B, Developmental and reproductive toxicology》2010,89(3):223-232
BACKGROUND: Nitrofen is a diphenyl ether that induces congenital diaphragmatic hernia (CDH) in rodents. Its mechanism of action has been hypothesized as inhibition of the retinaldehyde dehydrogenase (RALDH) enzymes with consequent reduced retinoic acid signaling. METHODS: To determine if nitrofen inhibits RALDH enzymes, a reporter gene construct containing a retinoic acid response‐element (RARE) was transfected into HEK‐293 cells and treated with varying concentrations of nitrofen in the presence of retinaldehyde (retinal). Cell death was characterized by caspace‐cleavage microplate assays and terminal deoxynucleotidyl transferase dUTP nick end‐labeling (TUNEL) assays. Ex vivo analyses of cell viability were characterized in fetal rat lung explants using Live/Dead staining. Cell proliferation and apoptosis were assessed using fluorescent immunohistochemistry with phosphorylated histone and activated caspase antibodies on explant tissues. Nile red staining was used to identify intracellular lipid droplets. RESULTS: Nitrofen‐induced dose‐dependent declines in RARE‐reporter gene expression. However, similar reductions were observed in control‐reporter constructs suggesting that nitrofen compromised cell viability. These observed declines in cell viability resulted from increased cell death and were confirmed using two independent assays. Ex vivo analyses showed that mesenchymal cells were particularly susceptible to nitrofen‐induced apoptosis while epithelial cell proliferation was dramatically reduced in fetal rat lung explants. Nitrofen treatment of these explants also showed profound lipid redistribution, primarily to phagocytes. CONCLUSIONS: The observed declines in nitrofen‐associated retinoic acid signaling appear to be independent of RALDH inhibition and likely result from nitrofen induced cell death/apoptosis. These results support a cellular apoptotic mechanism of CDH development, independent of RALDH inhibition. Birth Defects Res (Part B) 89:223–232, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
64.
65.
Said El?Shamieh Marion Neuillé Angélique Terray Elise Orhan Christel Condroyer Vanessa Démontant Christelle Michiels Aline Antonio Fiona Boyard Marie-Elise Lancelot Mélanie Letexier Jean-Paul Saraiva Thierry Léveillard Saddek Mohand-Sa?d Olivier Goureau José-Alain Sahel Christina Zeitz Isabelle Audo 《American journal of human genetics》2014,94(4):625-633
66.
How misfolded proteins are exported from the ER to the cytosol for degradation (ER-associated Degradation, ERAD) and which proteins are participating in this process is not understood. Several studies using a single, leaky mutant indicated that Sec63p might be involved in ERAD. More recently, Sec63p was also found strongly associated with proteasomes attached to the protein-conducting channel in the ER membrane which presumably form part of the export machinery. These observations prompted us to reinvestigate the role of Sec63p in ERAD by generating new mutants which were selected in a screen monitoring the intracellular accumulation of the ERAD substrate CPY*. We show that a mutation in the DnaJ-domain of Sec63p causes a defect in ERAD, whereas mutations in the Brl, acidic, and transmembrane domains only affect protein import into the ER. Unexpectedly, mutations in the acidic domain which mediates interaction of Sec63p with Sec62p also caused defects in cotranslational import. In contrast to mammalian cells where SEC63 expression levels affect steady-state levels of multi-spanning transmembrane proteins, the sec63 J-domain mutant was only defective in ERAD of soluble substrates. 相似文献
67.
Evelyn L. Jensen Christina Tschritter Peter V. C. de Groot Kristen M. Hayward Marsha Branigan Markus Dyck Rute B. G. Clemente‐Carvalho Stephen C. Lougheed 《Ecology and evolution》2020,10(8):3706-3714
Predicting the consequences of environmental changes, including human‐mediated climate change on species, requires that we quantify range‐wide patterns of genetic diversity and identify the ecological, environmental, and historical factors that have contributed to it. Here, we generate baseline data on polar bear population structure across most Canadian subpopulations (n = 358) using 13,488 genome‐wide single nucleotide polymorphisms (SNPs) identified with double‐digest restriction site‐associated DNA sequencing (ddRAD). Our ddRAD dataset showed three genetic clusters in the sampled Canadian range, congruent with previous studies based on microsatellites across the same regions; however, due to a lack of sampling in Norwegian Bay, we were unable to confirm the existence of a unique cluster in that subpopulation. These data on the genetic structure of polar bears using SNPs provide a detailed baseline against which future shifts in population structure can be assessed, and opportunities to develop new noninvasive tools for monitoring polar bears across their range. 相似文献
68.
69.
The synchrony effect refers to the beneficial impact of temporal matching between the timing of cognitive task administration and preferred time-of-day for diurnal activity. Aging is often associated with an advance in sleep-wake timing and concomitant optimal performance levels in the morning. In contrast, young adults often perform better in the evening hours. So far, the synchrony effect has been tested at fixed clock times, neglecting the individual's sleep-wake schedule and thus introducing confounds, such as differences in accumulated sleep pressure or circadian phase, which may exacerbate synchrony effects. To probe this hypothesis, the authors tested older morning and young evening chronotypes with a psychomotor vigilance and a Stroop paradigm once at fixed morning and evening hours and once adapting testing time to their preferred sleep-wake schedule in a within-subject design. The authors observe a persistence of synchrony effects for overall median reaction times during a psychomotor vigilance task, even when testing time is adapted to the specific individual's sleep-wake schedule. However, data analysis also indicates that time-of-day modulations are weakened under those conditions for incongruent trials on Stroop performance and the slowest reaction times on the psychomotor vigilance task. The latter result suggests that the classically observed synchrony effect may be partially mediated by a series of parameters, such as differences in socio-professional timing constraints, the amount of accumulated sleep need, or circadian phase, all leading to differential arousal levels at testing. 相似文献
70.
German Matías Traglia Marisa Almuzara Andrea Karina Merkier Christina Adams Laura Galanternik Carlos Vay Daniela Centrón María Soledad Ramírez 《Current microbiology》2012,65(6):673-678
In the last few years, numerous cases of multidrug-resistant Achromobacter xylosoxidans infections have been documented in immunocompromised and cystic fibrosis patients. To gain insights into the molecular mechanisms and mobile elements related to multidrug resistance in this bacterium, we studied 24 non-epidemiological A. xylosoxidans clinical isolates from Argentina. Specific primers for plasmids, transposons, insertion sequences, bla ampC, intI1, and intI2 genes were used in PCR reactions. The obtained results showed the presence of wide host range IncP plasmids in ten isolates and a high dispersion of class 1 integrons (n?=?10) and class 2 integrons (n?=?3). Four arrays in the variable region (vr) of class 1 integrons were identified carrying different gene cassettes as the aminoglycoside resistance aac(6′)-Ib and aadA1, the trimethoprim resistance dfrA1 and dfrA16, and the β-lactamase bla OXA-2. In only one of the class 2 integrons, a vr was amplified that includes sat2-aadA1. The bla ampC gene was found in all isolates, confirming its ubiquitous nature. Our results show that A. xylosoxidans clinical isolates contain a rich variety of genetic elements commonly associated with resistance genes and their dissemination. This supports the hypothesis that A. xylosoxidans is becoming a reservoir of horizontal genetic transfer elements commonly involved in spreading antibiotic resistance. 相似文献