755 research outputs found
Targeting the phosphatidylinositol 3-kinase/Akt/mechanistic target of rapamycin signaling pathway in B-lineage acute lymphoblastic leukemia: An update
Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15–20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease. Moreover, activation of this signaling cascade portends a poorer prognosis in both pediatric and adult B-ALL patients. Promising preclinical data on PI3K/Akt/mTOR inhibitors have documented their anticancer activity in B-ALL and some of these novel drugs have entered clinical trials as they could lead to a longer event-free survival and reduce therapy-associated toxicity for patients with B-ALL. This review highlights the current status of PI3K/Akt/mTOR inhibitors in B-ALL, with an emphasis on emerging evidence of the superior efficacy of synergistic combinations involving the use of traditional chemotherapeutics or other novel, targeted agents
Guidelines for the monitoring of Lucanus cervus
Lucanus cervus is one of the most charismatic saproxylic beetles, widely distributed in Europe. The species is typical of mature deciduous forests, especially oak woodlands. Loss and fragmentation of suitable habitats is one of the major threats for this species which is included in Annex II of the Habitats Directive. Despite several studies carried out in the last years for the monitoring methods of the species, an analytical comparison between them is still lacking. The aims of this paper are (i) to review the current knowledge about systematics, ecology and conservation practices on L. cervus and (ii) to present the research carried out during the Life MIPP project, in order to define a standard monitoring method with a suitable protocol to be used for addressing the obligations of the Habitats Directive. Overall, five methods were tested during three years in two different study areas. Based on these results, a suitable standard method for L. cervus is proposed in this paper and, in order to assess the conservation status of populations and to compare them over time, a simple method for the calculation of a reference value is provided
TNF-related apoptosis-inducing ligand (TRAIL): a potential candidate for combined treatment of hematological malignancies.
TRAIL treatment prevents renal morphological changes and TGF-\u3b2-induced mesenchymal transition associated with diabetic nephropathy
BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL) has attracted attention not only as an anti-cancer agent, but also as a potential treatment for diabetes. Animal studies have shown that TRAIL delivery ameliorated glucose control in type 1 and type 2 diabetes. It is currently unknown whether TRAIL positive effects are maintained in more severe forms of type 2 diabetes, and whether they include renoprotection. Our study aimed at evaluating TRAIL effects in a severe form of type 2 diabetes with nephropathy. MATERIALS AND METHODS: A total of 20 db/db mice were treated with saline or TRAIL twice per week for 12 weeks. In parallel, renal tubular epithelial cells were cultured with TGF-\u3b21 in the presence and absence of TRAIL, with and without silencing TRAIL-specific receptor (DR5) and leptin receptor. RESULTS: TRAIL did not improve glucose control, but it significantly reduced circulating interleukin (IL)-6 and resistin. In the kidney, TRAIL treatment significantly ameliorated glomerular and tubular morphology with an improvement in kidney function, but no effect on proteinuria. Our in vitro studies on TGF-\u3b21-treated cells, showed that by binding to DR5, TRAIL rescued normal tubular cell morphology, increasing E-cadherin and reducing \u3b1-smooth muscle actin (SMA) expression, with no effects on cell viability. Interestingly, both in vivo and in vitro, TRAIL reduced the accumulation of the autophagy substrate p62. CONCLUSIONS: Our data confirm TRAIL protective effects against organ damage and shed light on to promising anti-fibrotic actions, which are independent of glucose control. TRAIL anti-fibrotic actions might be due to the rescue of autophagy in diabetes
Improving water use efficiency in vertical farming: Effects of growing systems, far-red radiation and planting density on lettuce cultivation
Vertical farms (VFs) are innovative urban production facilities consisting of multi-level indoor systems equipped with artificial lighting in which all the environmental conditions are controlled independently from the external climate. VFs are generally provided with a closed loop fertigation system to optimize the use of water and nu-trients. The objective of this study, performed within an experimental VF at the University of Bologna, was to quantify the water use efficiency (WUE, ratio between plant fresh weight and the volume of water used) for a lettuce (Lactuca sativa L.) growth cycle obtained in two different growing systems: an ebb-and-flow substrate culture and a high pressure aeroponic system. Considering the total water consumed (water used for irrigation and climate management), WUE of ebb-and-flow and aeroponics was 28.1 and 52.9 g L-1 H2O, respectively. During the growing cycle, the contribution generated by the recovery of internal air moisture from the heating, ventilation and air conditioning (HVAC) system, was quantified. Indeed, by recovering water from the dehu-midifier, water use decreases dramatically (by 67 %), while WUE increased by 206 %. Further improvement of WUE in the ebb-and-flow system was obtained through ameliorated crop management strategies, in particular, by increasing planting densities (e.g., 153, 270 and 733 plants m-2) and by optimizing the light spectrum used for plant growth (e.g., adjusting the amount of far-red radiation in the spectrum). Strategies for efficient use of water in high-tech urban indoor growing systems are therefore proposed
The soluble terminal complement complex (SC5b-9) up-regulates osteoprotegerin expression and release by endothelial cells: Implications in rheumatoid arthritis
Objective. Complement activation products contribute to a large number of inflammatory diseases, including RA. We have investigated whether osteoprotegerin (OPG) may concur with the soluble terminal complement complex (SC5b-9) to the inflammatory cascade characterizing RA. Methods. Levels of SC5b-9 and OPG in the plasma and SF of patients with active RA were determined by ELISA. The presence of SC5b-9 and OPG in RA synovial lesions was analysed by immunohistochemistry. Cultured endothelial cells were used for in vitro leucocyte/endothelial cell adhesion assays. In addition, endothelial cells were exposed to SC5b-9 in order to evaluate the effects on the production of OPG protein, as well as the activation of the OPG promoter. Results. Patients affected by active RA are characterized by elevated levels of both SC5b-9 and OPG in plasma and/or SF. Of note, we have observed a co-localization of SC5b-9 and OPG in endothelial cells of post-capillary venules of RA synovial lesions. Data on endothelial cell cultures showed that exposure to SC5b-9 induced the up-regulation of OPG expression/release, stimulating the transcriptional activity of the OPG promoter, and synergized with TNF-α in up-regulating OPG production. Conclusions. Our findings demonstrate that SC5b-9 induces OPG production by endothelial cells and we propose that the SC5b-9-mediated up-regulation of OPG may be an important mechanism whereby complement contributes in promoting and/or enhancing the inflammation in RA. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved
Aerosol-ozone correlations during dust transport episodes
Its location in the Mediterranean region and its physical characteristics render Mt. Cimone (44°11′ N, 10°42′ E), the highest peak of the Italian northern Apennines (2165 m asl), particularly suitable to study the transport of air masses from the north African desert area to Europe. During these northward transports 12 dust events were registered in measurements of the aerosol concentration at the station during the period June–December 2000, allowing the study of the impact of mineral dust transports on free tropospheric ozone concentrations, which were also measured at Mt. Cimone. Three-dimensional backward trajectories were used to determine the air mass origin, while TOMS Aerosol Index data for the Mt. Cimone area were used to confirm the presence of absorbing aerosol over the measurement site. <P style='line-height: 20px;'> A trajectory statistical analysis allowed identifying the main source areas of ozone and aerosols. The analysis of these back trajectories showed that central Europe and north and central Italy are the major pollution source areas for ozone and fine aerosol, whereas the north African desert regions were the most important source areas for coarse aerosol and low ozone concentrations. During dust events, the Mt. Cimone mean volume concentration for coarse particles was 6.18 µm<sup>3</sup>/cm<sup>3</sup> compared to 0.63 µm<sup>3</sup>/cm<sup>3</sup> in dust-free conditions, while the ozone concentrations were 4% to 21% lower than the monthly mean background values. Our observations show that surface ozone concentrations were lower than the background values in air masses coming from north Africa, and when these air masses were also rich in coarse particles, the lowest ozone values were registered. Moreover, preliminary results on the possible impact of the dust events on PM<sub>10</sub> and ozone values measured in Italian urban and rural areas showed that during the greater number of the considered dust events, significant PM<sub>10</sub> increases and ozone decreases have occurred in the Po valley
BAR-PLUS: the Bologna Annotation Resource Plus for functional and structural annotation of protein sequences
We introduce BAR-PLUS (BAR+), a web server for functional and structural annotation of protein sequences. BAR+ is based on a large-scale genome cross comparison and a non-hierarchical clustering procedure characterized by a metric that ensures a reliable transfer of features within clusters. In this version, the method takes advantage of a large-scale pairwise sequence comparison of 13 495 736 protein chains also including 988 complete proteomes. Available sequence annotation is derived from UniProtKB, GO, Pfam and PDB. When PDB templates are present within a cluster (with or without their SCOP classification), profile Hidden Markov Models (HMMs) are computed on the basis of sequence to structure alignment and are cluster-associated (Cluster-HMM). Therefrom, a library of 10 858 HMMs is made available for aligning even distantly related sequences for structural modelling. The server also provides pairwise query sequence–structural target alignments computed from the correspondent Cluster-HMM. BAR+ in its present version allows three main categories of annotation: PDB [with or without SCOP (*)] and GO and/or Pfam; PDB (*) without GO and/or Pfam; GO and/or Pfam without PDB (*) and no annotation. Each category can further comprise clusters where GO and Pfam functional annotations are or are not statistically significant. BAR+ is available at http://bar.biocomp.unibo.it/bar2.0
Focal lesions induce large-scale percolation of sleep-like intracerebral activity in awake humans.
Focal cortical lesions are known to result in large-scale functional alterations involving distant areas; however, little is known about the electrophysiological mechanisms underlying these network effects. Here, we addressed this issue by analysing the short and long distance intracranial effects of controlled structural lesions in humans. The changes in Stereo-Electroencephalographic (SEEG) activity after Radiofrequency-Thermocoagulation (RFTC) recorded in 21 epileptic subjects were assessed with respect to baseline resting wakefulness and sleep activity. In addition, Cortico-Cortical Evoked Potentials (CCEPs) recorded before the lesion were employed to interpret these changes with respect to individual long-range connectivity patterns. We found that small structural ablations lead to the generation and large-scale propagation of sleep-like slow waves within the awake brain. These slow waves match those recorded in the same subjects during sleep, are prevalent in perilesional areas, but can percolate up to distances of 60 mm through specific long-range connections, as predicted by CCEPs. Given the known impact of slow waves on information processing and cortical plasticity, demonstrating their intrusion and percolation within the awake brain add key elements to our understanding of network dysfunction after cortical injuries
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