ADP Ribosylation Factor Like 2 (Arl2) Regulates Breast Tumor Aggressivity in Immunodeficient Mice

We have previously reported that ADP ribosylation factor like 2 (Arl2), a small GTPase, content influences microtubule dynamics and cell cycle distribution in breast tumor cells, as well as the degree and distribution of phosphorylated P53. Here we show, in two different human breast adenocarcinoma models, that Arl2 content has a major impact on breast tumor cell aggressivity both in vitro and in vivo. Cells with reduced content of Arl2 displayed reduced contact inhibition, increased clonogenic or cluster formation as well as a proliferative advantage over control cells in an in vitro competition assay. These cells also caused larger tumors in SCID mice, a phenotype which was mimicked by the in vivo administration of siRNA directed against Arl2. Cells with increased Arl2 content displayed reduced aggressivity, both in vitro and in vivo, with enhanced necrosis and were also found to contain increased PP2A phosphatase activity. A rt-PCR analysis of fresh human tumor breast samples suggested that low Arl2 expression was associated with larger tumor size and greater risk of lymph node involvement at diagnosis. These data underline the role of Arl2, a small GTPase, as an important regulator of breast tumor cell aggressivity, both in vitro and in vivo

Neurovascular coupling methods in healthy individuals using transcranial doppler ultrasonography: A systematic review and consensus agreement

This is the final version. Available from SAGE Publications via the DOI in this recordData availability. This was a systematic review of existing research studies and no primary research was conducted.Neurovascular coupling (NVC) is the perturbation of cerebral blood flow (CBF) to meet varying metabolic demands induced by various levels of neural activity. NVC may be assessed by Transcranial Doppler ultrasonography (TCD), using task activation protocols, but with significant methodological heterogeneity between studies, hindering cross-study comparisons. Therefore, this review aimed to summarise and compare available methods for TCD-based healthy NVC assessments. Medline (Ovid), Scopus, Web of Science, EMBASE (Ovid) and CINAHL were searched using a predefined search strategy (PROSPERO: CRD42019153228), generating 6006 articles. Included studies contained TCD-based assessments of NVC in healthy adults. Study quality was assessed using a checklist, and findings were synthesised narratively. 76 studies (2697 participants) met the review criteria. There was significant heterogeneity in the participant position used (e.g., seated vs supine), in TCD equipment, and vessel insonated (e.g. middle, posterior, and anterior cerebral arteries). Larger, more significant, TCD-based NVC responses typically included a seated position, baseline durations >one-minute, extraneous light control, and implementation of previously validated protocols. In addition, complementary, combined position, vessel insonated and stimulation type protocols were associated with more significant NVC results. Recommendations are detailed here, but further investigation is required in patient populations, for further optimisation of TCD-based NVC assessments.National Institute for Health and Care Research (NIHR)Stroke AssociationLeicester Biomedical Research Centr

Neurovascular coupling methods in healthy individuals using transcranial Doppler ultrasonography: A systematic review and consensus agreement

Neurovascular coupling (NVC) is the perturbation of cerebral blood flow (CBF) to meet varying metabolic demands induced by various levels of neural activity. NVC may be assessed by Transcranial Doppler ultrasonography (TCD), using task activation protocols, but with significant methodological heterogeneity between studies, hindering cross-study comparisons. Therefore, this review aimed to summarise and compare available methods for TCD-based healthy NVC assessments. Medline (Ovid), Scopus, Web of Science, EMBASE (Ovid) and CINAHL were searched using a predefined search strategy (PROSPERO: CRD42019153228), generating 6006 articles. Included studies contained TCD-based assessments of NVC in healthy adults. Study quality was assessed using a checklist, and findings were synthesised narratively. 76 studies (2697 participants) met the review criteria. There was significant heterogeneity in the participant position used (e.g., seated vs supine), in TCD equipment, and vessel insonated (e.g. middle, posterior, and anterior cerebral arteries). Larger, more significant, TCD-based NVC responses typically included a seated position, baseline durations >one-minute, extraneous light control, and implementation of previously validated protocols. In addition, complementary, combined position, vessel insonated and stimulation type protocols were associated with more significant NVC results. Recommendations are detailed here, but further investigation is required in patient populations, for further optimisation of TCD-based NVC assessments

Effect of teicoplanin and vancomycin on cerebrospinal fluid proteins of non-infected rabbits after suboccipital injection

The IC inoculation of antibiotics into the CSF for therapeutic use could produce biological effects we should consider when analysing samples. To corroborate this assumption, we observed the effect of ICI T and V on the PL of the CSF of non infected rabbits. T and V were ICI as dosage of 1 mg/kg diluted in 0.2 ml of isotonic saline solution (ISS). ISS was also ICI alone. CSF samples were obtained before inoculation from 41 animals (T0) setting the normal PL. Other samples were obtained 2 (T2) and 4 hours (T4) after inoculation. PL were assayed in an Analyser Clinic Automatic (Du Pont). The statistical analysis was performed by the Kolomogorov-Smirnov Test, for comparison of samples from unknown and not necessarily similar distributions. Results were (mg/l) = PL at T0 = 0.20 +/- 0.08. At T2, levels were 0.6 +/- 0.41 (ISS), 0.73 +/- 0.27 (V) and 0.87 +/- 0.44 (T). At T4 they were 0.3 +/- 0.15 (ISS), 0.55 +/- 0.25 (V) and 0.78 +/- (T). Statistical differences (p less than 0.05) were demonstrated at T2 (T, V and ISS vs control at T0), at T4 = V, vs control at T0 but not between the two antibiotics nor between the two antibiotics and ISS, at any time. We conclude that IC inoculation of T and V and ISS increased significantly the CSF PL

Effect of teicoplanin and vancomycin on cerebrospinal fluid proteins of non-infected rabbits after suboccipital injection

The IC inoculation of antibiotics into the CSF for therapeutic use could produce biological effects we should consider when analysing samples. To corroborate this assumption, we observed the effect of ICI T and V on the PL of the CSF of non infected rabbits. T and V were ICI as dosage of 1 mg/kg diluted in 0.2 ml of isotonic saline solution (ISS). ISS was also ICI alone. CSF samples were obtained before inoculation from 41 animals (T0) setting the normal PL. Other samples were obtained 2 (T2) and 4 hours (T4) after inoculation. PL were assayed in an Analyser Clinic Automatic (Du Pont). The statistical analysis was performed by the Kolomogorov-Smirnov Test, for comparison of samples from unknown and not necessarily similar distributions. Results were (mg/l) = PL at T0 = 0.20 +/- 0.08. At T2, levels were 0.6 +/- 0.41 (ISS), 0.73 +/- 0.27 (V) and 0.87 +/- 0.44 (T). At T4 they were 0.3 +/- 0.15 (ISS), 0.55 +/- 0.25 (V) and 0.78 +/- (T). Statistical differences (p less than 0.05) were demonstrated at T2 (T, V and ISS vs control at T0), at T4 = V, vs control at T0 but not between the two antibiotics nor between the two antibiotics and ISS, at any time. We conclude that IC inoculation of T and V and ISS increased significantly the CSF PL

Heat Spreading Packaging Solutions for Hybrid Bonded 3D-ICs

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