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1.
Cerebral edema is a common complication following moderate and severe traumatic brain injury (TBI), and a significant risk factor for development of neuronal death and deterioration of neurological outcome. To this date, medical approaches that effectively alleviate cerebral edema and neuronal death after TBI are not available. Glucagon-like peptide-1 (GLP-1) has anti-inflammatory properties on cerebral endothelium and exerts neuroprotective effects. Here, we investigated the effects of GLP-1 on secondary injury after moderate and severe TBI. Male Sprague Dawley rats were subjected either to TBI by Controlled Cortical Impact (CCI) or sham surgery. After surgery, vehicle or a GLP-1 analogue, Liraglutide, were administered subcutaneously twice daily for two days. Treatment with Liraglutide (200 μg/kg) significantly reduced cerebral edema in pericontusional regions and improved sensorimotor function 48 hours after CCI. The integrity of the blood-brain barrier was markedly preserved in Liraglutide treated animals, as determined by cerebral extravasation of Evans blue conjugated albumin. Furthermore, Liraglutide reduced cortical tissue loss, but did not affect tissue loss and delayed neuronal death in the thalamus on day 7 post injury. Together, our data suggest that the GLP-1 pathway might be a promising target in the therapy of cerebral edema and cortical neuronal injury after moderate and severe TBI. 相似文献
2.
Gregor Stiglic Petra Povalej Brzan Nino Fijacko Fei Wang Boris Delibasic Alexandros Kalousis Zoran Obradovic 《PloS one》2015,10(12)
Different studies have demonstrated the importance of comorbidities to better understand the origin and evolution of medical complications. This study focuses on improvement of the predictive model interpretability based on simple logical features representing comorbidities. We use group lasso based feature interaction discovery followed by a post-processing step, where simple logic terms are added. In the final step, we reduce the feature set by applying lasso logistic regression to obtain a compact set of non-zero coefficients that represent a more comprehensible predictive model. The effectiveness of the proposed approach was demonstrated on a pediatric hospital discharge dataset that was used to build a readmission risk estimation model. The evaluation of the proposed method demonstrates a reduction of the initial set of features in a regression model by 72%, with a slight improvement in the Area Under the ROC Curve metric from 0.763 (95% CI: 0.755–0.771) to 0.769 (95% CI: 0.761–0.777). Additionally, our results show improvement in comprehensibility of the final predictive model using simple comorbidity based terms for logistic regression. 相似文献
3.
Andreas Jürgens Gregor Aas Stefan Dötterl 《Botanical journal of the Linnean Society. Linnean Society of London》2014,175(4):624-640
Floral scent, often a complex mixture of several volatile organic compounds (VOCs), has generally been interpreted as an adaptation to attract pollinators. However, not many studies have analysed which VOCs are functionally relevant for the reproductive success of a plant. Here, we show that, in Salix caprea (Salicaceae), temporal changes in floral scent emission during the day and night attract two different types of flower visitor: bees during the day and moths during the evening and night. We analysed the contribution of the two flower visitor groups to the reproductive success of the plant. The differences in scent emitted during the peak activity times of flower visitors (day versus night) were quantified and the response of 13 diurnal/nocturnal pollinator taxa to the floral scents was tested using gas chromatographic and electroantennographic techniques. Many of the c. 40 identified scent compounds were physiologically active, and bees and moths responded to nearly identical sets of compounds, although the response strengths differed. In bioassays, bees preferred the most abundant 1,4‐dimethoxybenzene over lilac aldehyde, a compound with increased emission at night, whereas moths preferred lilac aldehyde over 1,4‐dimethoxybenzene. Pollination by wind plus nocturnal pollinators (mainly moths) or by wind alone contributed less to seed set than pollination by wind plus diurnal pollinators (mainly bees). This suggests that the emission of scent during the night and attracting moths have no significant effect on reproductive success. It is possible that the emission of lilac aldehydes and other compounds at night is s result of phylogenetic constraints. Future studies should investigate whether moths may produce a marginal fitness gain in some years and/or some populations. © 2014 The Linnean Society of London, Botanical Journal of the Linnean Society, 2014, 175 , 624–640. 相似文献
4.
Andrej Meglič Gregor Zupančič 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2011,197(3):301-310
Time courses of mitochondrial responses to illumination-induced physiological loads and to hypoxia, were recorded optically
from eyes of blowflies Calliphora vicina chalky. We isolated changes in redox states of haems a3, a, c, and b. Two types of responses to light stimulation were observed. Haems b and a3 responded with transient oxidation and haems a and c with reduction. The same two groups emerged in response to anoxic exposure.
The onset of reduction of haems a and c had virtually no latency, while haems a3 and b exhibited a transient oxidation followed by reduction only after 10–20 s. The dependence of the steady-state reduction
level on
P\textO2 P_{{{\text{O}}_{2} }} produced the same groups. Haems a and c were significantly reduced at
P\textO2 P_{{{\text{O}}_{2} }} levels around 10 kPa while with haems b and a3 load-induced oxidation was only replaced by reduction below 2 kPa. We propose haems respond to physiological loads in accordance
with their steady-state reduction, which in turn depends largely on barriers for electron transport imposed by the mitochondrial
membrane potential. We also propose it may be possible to assess the values of tissue
P\textO2 P_{{{\text{O}}_{2} }} and O2 consumption by monitoring haems that are highly oxidized at rest such as haem a. 相似文献
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7.
Gregor Hagelueken Hexian Huang Iain L. Mainprize James H. Naismith 《Journal of molecular biology》2009,392(3):678-688
Many Gram-positive and Gram-negative bacteria utilize polysaccharide surface layers called capsules to evade the immune system; consequently, the synthesis and export of the capsule are a potential therapeutic target. In Escherichia coli K-30, the integral membrane tyrosine autokinase Wzc and the cognate phosphatase Wzb have been shown to be key for both synthesis and assembly of capsular polysaccharides. In the Gram-positive bacterium Streptococcus pneumoniae, the CpsCD complex is analogous to Wzc and the phosphatase CpsB is the corresponding cognate phosphatase. The phosphatases are known to dephosphorylate their corresponding autokinases, yet despite their functional equivalence, they share no sequence homology. We present the structure of Wzb in complex with phosphate and high-resolution structures of apo-CpsB and a phosphate-complexed CpsB. We show that both proteins are active toward Wzc and thereby demonstrate that CpsB is not specific for CpsCD. CpsB is a novel enzyme and represents the first solved structure of a tyrosine phosphatase from a Gram-positive bacterium. Wzb and CpsB have completely different structures, suggesting that they must operate by very different mechanisms. Although the mechanism of Wzb can be inferred from previous studies, CpsB appears to have a tyrosine phosphatase mechanism not observed before. We propose a chemical mechanism for CpsB based on site-directed mutagenesis and structural data. 相似文献
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9.
Gregor Reid 《Applied microbiology》1999,65(9):3763-3766
10.
Caliciviruses use reinitiation of translation governed by a ‘termination upstream ribosomal binding site’ (TURBS) for expression of their minor capsid protein VP2. Mutation analysis allowed to identify sequences surrounding the translational start/stop site of the feline calicivirus (FCV) that fine tune reinitiation frequency. A selection of these changes was introduced into the infectious FCV cDNA clone to check the influence of altered VP2 levels on virus replication. In addition, full length constructs were established that displayed a conformation, in which VP2 expression occurred under control of a duplicated subgenomic promoter. Viable viruses recovered from such constructs revealed a rather broad range of VP2 expression levels but comparable growth kinetics showing that caliciviruses can tolerate gross changes of the VP2 expression level. 相似文献