3,041 research outputs found
*PLOS One Fig 1-6 Final.pptx
No full textMinimal dataset for:Webster A, Chintala SK, Kim J, Ngan M, Itakura T, Panjwani N, Argüeso P, Barr JT, Jeong S and Fini ME (2018) Dynasore protects the ocular surface against damaging stress. PLoS ONE 13(10): e0204288. https://doi.org/10.1371/journal.pone.0204288 </div
Indagine archeologica presso il settore M, area foro: dati preliminari
No full textPresentazione dei dati preliminari del settore M localizzato nell'angolo NE dell'area del Foro di Grumentu
Effects of testosterone on the Q-T Interval in older men and older women with chronic heart failure
No full textThe Q-Tc interval duration on the electrocardiogram is recognized to differ between the sexes. In vitro data and data from humans before and after puberty and menopause suggest that sex hormones play a role in the longer Q-Tc intervals in women, or conversely, the shorter Q-Tc intervals in men. Direct investigations of sex hormone effects on the Q-Tc interval in humans, however, are limited and reach conflicting conclusions. Our objective was to determine effects of testosterone on ECG Q-T intervals of older men and older women. ECG's from 84 older men and older women in double-blind placebo-controlled investigations of testosterone supplementation for the treatment of chronic heart failure (CHF) were analysed. Thirty men received 1000mg intramuscular long-acting testosterone undecanoate and 28 men received saline at 0, 6 and 12weeks. ECG's were recorded at baseline and 12weeks. Sixteen women received transdermal testosterone (33μg) and 10 women received matching placebo twice weekly for 24 weeks with ECG's at baseline and after 24weeks. Testosterone, but not placebo, shortened Q-T and Q-Tc intervals without heart rate changes. Q-T intervals decreased from 385±28 (mean±SD) to 382±28 ms (p<0.002) and Q-Tc intervals decreased from 398±26 to 392±27 (p<0.006) in men on testosterone. In women, Q-T intervals decreased from 400±25 to 397±23ms (p=0.06) and Q-Tc intervals from 415±26 to 409±27ms (p=0.3) on testosterone. Q-T intervals were longer in women compared with men under all conditions (p<0.03). The data support a direct effect of testosterone to shorten Q-T intervals in older men and older women in the absence of HR changes or hypogonadal status. Mean decreases are small and unlikely to affect risks of arrhythmic events in patients receiving Q-T prolonging medications
Targeting Wnt/beta-catenin and PI3K/Akt/mTOR pathways in T-cell acute lymphoblastic leukemia.
No full textT‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive hematological disorder
that results from the clonal transformation of T‐cell precursors. Phosphatidylinositol
3‐kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) and canonical
Wnt/β‐catenin signaling pathways play a crucial role in T‐cell development and in
self‐renewal of healthy and leukemic stem cells. Notably, β‐catenin is a transcriptional
regulator of several genes involved in cancer cell proliferation and survival. In this
way, aberrations of components belonging to the aforementioned networks
contribute to T‐ALL pathogenesis. For this reason, inhibition of both pathways could
represent an innovative strategy in this hematological malignancy. Here, we show
that combined targeting of Wnt/β‐catenin pathway through ICG‐001, a CBP/β‐
catenin transcription inhibitor, and of the PI3K/Akt/mTOR axis through ZSTK‐474, a
PI3K inhibitor, downregulated proliferation, survival, and clonogenic activity of T‐ALL
cells. ICG‐001 and ZSTK‐474 displayed cytotoxic effects, and, when combined
together, induced a significant increase in apoptotic cells. This induction of apoptosis
was associated with the downregulation of Wnt/β‐catenin and PI3K/Akt/mTOR
pathways. All these findings were confirmed under hypoxic conditions that mimic the
bone marrow niche where leukemic stem cells are believed to reside. Taken together,
our findings highlight potentially promising treatment consisting of cotargeting
Wnt/β‐catenin and PI3K/Akt/mTOR pathways in T‐ALL settings
Editorial: Plants' Responses to Novel Environmental Pressures
No full textPlants have been exposed to multiple environmental stressors on long-term (seasonal) and short-term (daily) basis since their appearance on land. During the last decades, however, plants have been frequently exposed to sudden changes in their environment (imposed by global change) which indeed involves the acclimation/adaptation syndrome of living organisms. The frequency of these unpredictable ‘stress’ events is expected to increase further in the near future. Such severe, even transient alterations in environmental stimuli (variables) represent new challenges to plants, which do not possess the ‘flight’ strategy usually displayed by other organisms.
Plants have developed, however, a multiplicity of highly integrated adjustments, involving morpho-anatomical, physiological and biochemical traits, to cope with challenges imposed by novel, harsher environments: these constitute the ‘flight strategy of sessile organisms’. Interestingly, several habitats threatened by the novel stresses are biodiversity hotspots. For example, Mediterranean basin, in which high light growing plants face heat waves coupled with the scarcity of rainfall of increasing frequency and severity, represents just 2% of the earth’s land area, but account for 16% of the world’s plant species. This implies that plants have been and are capable to display a wide range of acclimation/adaptation strategies to cope with most unfavorable environments. Nonetheless, the unpreceded rate at which climate changes may exceed the capacity of plants to acclimate and adapt successfully to the novel environmental pressures, further exacerbated by an increase in anthropogenic pressure.
Understanding the mechanisms through which plants respond to new challenges posed by the concurrent effect of different stress agents is crucial, as obvious, to develop strategies of biodiversity conservation and ecosystem functionality. This is exactly the focus of this Research Topic. Review, Opinion as well as Original Research articles are welcome covering basic and applied research on plant functioning under adverse environmental conditions. The frequency of extreme stress events, mostly due to the concurrent effects of different stressors, is increasing particularly in the arid and semi-arid regions, which represent indeed among the most fragile ecosystems worldwide. Papers dealing with the effects of multiple stress agents on plant functioning are, therefore, particularly welcome. We are, however, also interested to receive contributions dissecting response mechanisms (from molecular to organism and whole-plant levels) of plants to a wide range of individual stressors, with a view to a rapidly changing climate, covering plant responses from other regions of the world. These include, but are not limited to drought and heat stress, excess light stress (including UV radiation), cold, ozone and rising CO2 concentration, and their combinations. Theories that predict the plant behavior, acclimation and plant plasticity are also inside the scope of this topi
Fast and Accurate Calculation of Owen's T Function
No full textSee paper for mathematical introduction.
Activity of the Selective IκB kinase Inhibitor BMS-345541 against T-Cell Acute Lymphoblastic Leukemia: involvement of FOXO3a
No full textSeveral lines of evidence suggest that the I kappa B kinase (IKK)/nuclear factor kappa B (NF kappa B) axis is required for viability of leukemic cells and is a predictor of relapse in T-cell acute lymphoblastic leukemia (T-ALL). Moreover, many anticancer agents induce NF kappa B nuclear translocation and activation of its target genes, which counteract cellular resistance to chemotherapeutic drugs. Therefore, the design and the study of IKK-specific drugs is crucial to inhibit tumor cell proliferation and to prevent cancer drug-resistance. Here, we report the anti-proliferative effects induced by BMS-345541 (a highly selective IKK inhibitor) in three Notch1-mutated T-ALL cell lines and in T-ALL primary cells from pediatric patients. BMS-345541 induced apoptosis and an accumulation of cells in the G(2)/M phase of the cell cycle via inhibition of IKK/NF kappa B signaling. We also report that T-ALL cells treated with BMS-345541 displayed nuclear translocation of FOXO3a and restoration of its functions, including control of p21(Cip1) expression levels. We demonstrated that FOXO3a subcellular re-distribution is independent of AKT and ERK 1/2 signaling, speculating that in T-ALL the loss of FOXO3a tumor suppressor function could be due to deregulation of IKK, as has been previously demonstrated in other cancer types
Biomaterials in spinal fixation. An experimental animal study to improve the performance
No full textTargeting Wnt/β-catenin and PI3K/Akt/mTOR pathways in T-cell acute lymphoblastic leukemia
No full textT‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive hematological disorder that results from the clonal transformation of T‐cell precursors. Phosphatidylinositol 3‐kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) and canonical Wnt/β‐catenin signaling pathways play a crucial role in T‐cell development and in self‐renewal of healthy and leukemic stem cells. Notably, β‐catenin is a transcriptional regulator of several genes involved in cancer cell proliferation and survival. In this way, aberrations of components belonging to the aforementioned networks contribute to T‐ALL pathogenesis. For this reason, inhibition of both pathways could represent an innovative strategy in this hematological malignancy. Here, we show that combined targeting of Wnt/β‐catenin pathway through ICG‐001, a CBP/β‐ catenin transcription inhibitor, and of the PI3K/Akt/mTOR axis through ZSTK‐474, a PI3K inhibitor, downregulated proliferation, survival, and clonogenic activity of T‐ALL cells. ICG‐001 and ZSTK‐474 displayed cytotoxic effects, and, when combined together, induced a significant increase in apoptotic cells. This induction of apoptosis was associated with the downregulation of Wnt/β‐catenin and PI3K/Akt/mTOR pathways. All these findings were confirmed under hypoxic conditions that mimic the bone marrow niche where leukemic stem cells are believed to reside. Taken together, our findings highlight potentially promising treatment consisting of cotargeting Wnt/β‐catenin and PI3K/Akt/mTOR pathways in T‐ALL settings
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