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81.
Mohlopheni J. Marakalala Simon Vautier Joanna Potrykus Louise A. Walker Kelly M. Shepardson Alex Hopke Hector M. Mora-Montes Ann Kerrigan Mihai G. Netea Graeme I. Murray Donna M. MacCallum Robert Wheeler Carol A. Munro Neil A. R. Gow Robert A. Cramer Alistair J. P. Brown Gordon D. Brown 《PLoS pathogens》2013,9(4)
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Joanna Joyner-Matos Kiley A. Hicks Dustin Cousins Michelle Keller Dee R. Denver Charles F. Baer Suzanne Estes 《PloS one》2013,8(6)
We explored the relationship between relaxed selection, oxidative stress, and spontaneous mutation in a set of mutation-accumulation (MA) lines of the nematode Caenorhabditis elegans and in their common ancestor. We measured steady-state levels of free radicals and oxidatively damaged guanosine nucleosides in the somatic tissues of five MA lines for which nuclear genome base substitution and GC-TA transversion frequencies are known. The two markers of oxidative stress are highly correlated and are elevated in the MA lines relative to the ancestor; point estimates of the per-generation rate of mutational decay (ΔM) of these measures of oxidative stress are similar to those reported for fitness-related traits. Conversely, there is no significant relationship between either marker of oxidative stress and the per-generation frequencies of base substitution or GC-TA transversion. Although these results provide no direct evidence for a causative relationship between oxidative damage and base substitution mutations, to the extent that oxidative damage may be weakly mutagenic in the germline, the case for condition-dependent mutation is advanced. 相似文献
85.
Franciszek Burdan Agnieszka Mocarska Marzena Janczarek Robert Klepacz Marek ?osicki Krzysztof Patyra Agnieszka Brodzik Joanna Kiszka Aneta Chru?cicka Iwonna ?elzowska-Cie?lińska El?bieta Staros?awska 《PloS one》2013,8(8)
The spinal perineurial cyst (Tarlov) is a dilatation between the perineurium and endoneurium of spinal nerve roots, located at level of the spinal ganglion and filled with cerebrospinal fluid but without communication with the perineurial subarachnoid space. The aim of the study was to evaluate it incidence among East-European patients. The retrospective data collected during various magnetic resonance spinal examinations and stored on the picture archiving and communication system was analyzed for an incidence of perineurial cysts. From among 842 patients that underwent examination, 75 cases perineurial cysts were revealed. In 22 cases single anomalies were found. In remaining 53 cases, multiple uni- or less frequently bilateral changes were noted. The most common position was the sacral canal, particularly the level of S2 and S3. Occasionally, cysts were also visible on the cervical, thoracic and lumbar level. Incidence of sacral perineurial cysts was significantly higher in females than in males. Similar data was found for single and multiple changes despite of their localization. Insignificant changes were seen for patient age and cyst size. Perineurial spinal cysts were the most frequently observed on the sacral level and such changes were more common in females. 相似文献
86.
Gilles M. Leclerc Guy J. Leclerc Jeffim N. Kuznetsov Joanna DeSalvo Julio C. Barredo 《PloS one》2013,8(8)
The outcome of patients with resistant phenotypes of acute lymphoblastic leukemia (ALL) or those who relapse remains poor. We investigated the mechanism of cell death induced by metformin in Bp- and T-ALL cell models and primary cells, and show that metformin effectively induces apoptosis in ALL cells. Metformin activated AMPK, down-regulated the unfolded protein response (UPR) demonstrated by significant decrease in the main UPR regulator GRP78, and led to UPR-mediated cell death via up-regulation of the ER stress/UPR cell death mediators IRE1α and CHOP. Using shRNA, we demonstrate that metformin-induced apoptosis is AMPK-dependent since AMPK knock-down rescued ALL cells, which correlated with down-regulation of IRE1α and CHOP and restoration of the UPR/GRP78 function. Additionally rapamycin, a known inhibitor of mTOR-dependent protein synthesis, rescued cells from metformin-induced apoptosis and down-regulated CHOP expression. Finally, metformin induced PIM-2 kinase activity and co-treatment of ALL cells with a PIM-1/2 kinase inhibitor plus metformin synergistically increased cell death, suggesting a buffering role for PIM-2 in metformin’s cytotoxicity. Similar synergism was seen with agents targeting Akt in combination with metformin, supporting our original postulate that AMPK and Akt exert opposite regulatory roles on UPR activity in ALL. Taken together, our data indicate that metformin induces ALL cell death by triggering ER and proteotoxic stress and simultaneously down-regulating the physiologic UPR response responsible for effectively buffering proteotoxic stress. Our findings provide evidence for a role of metformin in ALL therapy and support strategies targeting synthetic lethal interactions with Akt and PIM kinases as suitable for future consideration for clinical translation in ALL. 相似文献
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Joanna Szkandera Michael Stotz Florian Eisner Gudrun Absenger Tatjana Stojakovic Hellmut Samonigg Peter Kornprat Renate Schaberl-Moser Wael AlZoughbi Anna Lena Ress Friederike Sophia Seggewies Armin Gerger Gerald Hoefler Martin Pichler 《PloS one》2013,8(11)
Background
With growing evidence on the role of inflammation in cancer biology, the presence of a systemic inflammatory response has been postulated as having prognostic significance in a wide range of cancer types. The derived neutrophil to lymphocyte ratio (dNLR), which represents an easily determinable potential prognostic marker in daily practise and clinical trials, has never been externally validated in pancreatic cancer (PC) patients.Methods
Data from 474 consecutive PC patients, treated between 2004 and 2012 at a single centre, were evaluated retrospectively. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. To evaluate the prognostic relevance of dNLR, univariate and multivariate Cox regression models were applied.Results
We calculated by ROC analysis a cut-off value of 2.3 for the dNLR to be ideal to discriminate between patients’ survival in the whole cohort. Kaplan-Meier curve reveals a dNLR≥2.3 as a factor for decreased CSS in PC patients (p<0.001, log-rank test). An independent significant association between high dNLR≥2.3 and poor clinical outcome in multivariate analysis (HR = 1.24, CI95% = 1.01–1.51, p = 0.041) was identified.Conclusion
In the present study we confirmed elevated pre-treatment dNLR as an independent prognostic factor for clinical outcome in PC patients. Our data encourage independent replication in other series and settings of this easily available parameter as well as stratified analysis according to tumor resectability. 相似文献89.
Mucha Joanna Zadworny Marcin Helmisaari Heljä-Sisko Nihlgård Bengt Repo Tapani Żytkowiak Maciej Małek Stanisław Reich Peter B. Oleksyn Jacek 《Plant and Soil》2020,455(1-2):507-518
Plant and Soil - Any grouping of tree species concerned with SOC sequestration should include trees that are as homogeneous as possible in their carbon sequestration. We propose a classification of... 相似文献
90.
Muszyńska Bożena Kała Katarzyna Włodarczyk Anna Krakowska Agata Ostachowicz Beata Gdula-Argasińska Joanna Suchocki Piotr 《Biological trace element research》2020,194(2):614-615
Biological Trace Element Research - The original version of this article unfortunately contained a mistake. 相似文献