Acquiring Metastatic Competence by Oral Squamous Cell Carcinoma Cells Is Associated with Differential Expression of α-Tubulin Isoforms

We performed comparative global proteomics analyses of patient-matched primary (686Tu) and metastatic (686Ln) OSCC cells. The metastatic OSCC 686Ln cells showed greater in vitro migratory/invasive potential and distinct cell shape from their parental primary 686Tu cells. Ettan DIGE analysis revealed 1316 proteins spots in both cell lines with >85% to be quantitatively similar (<2 folds) between the two cell lines. However, two protein spots among four serial spots were highly dominant in 686Ln cells. Mass spectrometry sequencing demonstrated all four spots to be α-tubulin isotypes. Further analysis showed no significant quantitative difference in the α-tubulin between the two cell lines either at mRNA or protein levels. Thus, two distinct isoforms of α-tubulin, probably due to posttranslational modification, were associated with metastatic 686Ln cells. Immunofluorescence demonstrated remarkable differences in the cytosolic α-tubulin distribution patterns between the two cells. In 686Tu cells, α-tubulin proteins formed a normal network composed of filaments. In contrast, α-tubulin in 686Ln cells exhibited only partial cytoskeletal distribution with the majority of the protein diffusely distributed within the cytosol. Since α-tubulin is critical for cell shape and mobility, our finding suggests a role of α-tubulin isoforms in acquisition of metastatic phenotype and represents potential target for therapeutic intervention

Clinical effect of mirikizumab treatment on bowel urgency in patients with moderately to severely active ulcerative colitis and the clinical relevance of bowel urgency improvement for disease remission

Background: Bowel urgency reduces ulcerative colitis patients' quality of life. Mirikizumab, a p19-directed anti-IL-23 antibody, demonstrates ulcerative colitis efficacy. Mirikizumab efficacy to reduce bowel urgency and bowel urgency association with other endpoints were analyzed in 2 Phase 3 trials. Methods: LUCENT-1 (Induction): 1162 patients randomized 3:1 to intravenous 300 mg mirikizumab or placebo every 4 weeks for 12 weeks. LUCENT-2 (Maintenance): 544 mirikizumab responders during induction were re-randomized 2:1 to subcutaneous mirikizumab 200 mg or placebo every 4 weeks for 40 weeks (52 weeks of continuous treatment). Bowel urgency was measured using the Urgency Numeric Rating Scale (0–10); for patients with LUCENT-1 baseline score ≥3, bowel urgency clinically meaningful improvement (≥3-point decrease) and remission (score ≤1) rates in mirikizumab versus placebo groups were compared at Weeks 12 and 52. Associations between bowel urgency and other efficacy endpoints were assessed at Weeks 12 and 52. Results: A significantly higher proportion of mirikizumab patients versus placebo achieved clinically meaningful improvement in bowel urgency and remission at Weeks 12 and 52. Significantly higher percentages of patients achieving bowel urgency clinically meaningful improvement or remission, compared with those who did not, also achieved endpoints for clinical, corticosteroid-free, endoscopic, and symptomatic remission; clinical response; normalized fecal calprotectin and C-reactive protein; and improved quality of life. Conclusions: In patients with ulcerative colitis, bowel urgency improvement was associated with better clinical outcomes than in patients without improvement during induction and maintenance. A greater proportion of mirikizumab patients achieved sustainable bowel urgency improvement and remission compared to placebo patients

Objects, actions, and images: a perspective on early number development

It is the purpose of this article to present a review of research evidence that indicates the existence of qualitatively different thinking in elementary number development. In doing so, the article summarizes empirical evidence obtained over a period of 10 years. This evidence first signaled qualitative differences in numerical processing, and was seminal in the development of the notion of procept. More recently, it examines the role of imagery in elementary number processing. Its conclusions indicate that in the abstraction of numerical concepts from numerical processes qualitatively different outcomes may arise because children concentrate on different objects or different aspects of the objects, which are components of numerical processing

Health-Related Quality of Life Outcomes With Tofacitinib Treatment in Patients With Ulcerative Colitis in the Open-Label Extension Study, OCTAVE Open

BACKGROUND Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We report health-related quality of life (HRQoL) outcomes in patients with ulcerative colitis in the phase 3 open-label, long-term extension study, OCTAVE Open. METHODS The Inflammatory Bowel Disease Questionnaire (IBDQ), EuroQoL-5 Dimensions Health Questionnaire, and 36-Item Short Form Survey scores were analyzed up to month (M) 72 in 4 subpopulations: patients in remission at baseline (maintenance remitters) assigned tofacitinib 5 mg twice daily and patients not in remission at baseline (maintenance nonremitters, maintenance treatment failures, and induction nonresponders [IndNRs]) assigned tofacitinib 10 mg twice daily in OCTAVE Open. Data were analyzed overall and stratified by corticosteroid use at baseline, prior tumor necrosis factor inhibitor failure, and prior immunosuppressant failure. RESULTS Among maintenance remitters and nonremitters, HRQoL outcomes were maintained up to M72: 80.0% and 100.0% of patients had an IBDQ total score ≥170, respectively. At baseline, 7.4% of maintenance treatment failures had an IBDQ total score ≥170, and this increased to 54.3% and 75.0% at M2 and M72, respectively. Corresponding values for IndNRs were 22.6%, 51.0%, and 86.0%. HRQoL outcomes were independent of treatment history. Among patients not in remission at baseline, improvement in EuroQoL-5 Dimensions Health Questionnaire and 36-Item Short Form Survey scores was maintained or achieved by M2, and steady to M72 or M33, with maintenance treatment failures and IndNR subpopulations undergoing the biggest improvements from baseline. CONCLUSIONS A continued favorable impact on HRQoL was revealed with long-term tofacitinib treatment in OCTAVE Open, regardless of baseline remission status or treatment history. (ClinicalTrials.gov; number: NCT01470612)

Seychelles Lagoon Provides Corals with a Refuge from Bleaching

An extensive bleaching event in the summer of the year 1997-1998 affected most reefs along East Africa's shores. In the aftermath of that episode, the reefs of Île Alphonse in the Seychelles were examined and it was found that reefs along the seaward slopes of the island lost >95% of their branching coral colonies, with considerably higher survival of massive species. Île Alphonse features a nearly circular shallow lagoon, with steep seaward slopes. Contrary to our expectations, mortality in the warmer lagoon was far lower than of coral colonies on the surrounding slopes, bathed in deeper and cooler waters. We suggest that corals in the lagoon were protected from UV radiation by leachate stemming from seagrass leaves steeped in the lagoon. Our measurements in the lagoon showed a strong attenuation of ultraviolet radiation, not observed in the waters outside the lagoon, and laboratory examination confirmed that the strong UV absorption of substances leached into seawater from decomposing leaves of the seagrass Thalassodendron (=Cymodocea) testudinaceum. Our findings demonstrate the synergism between elevated seawater temperature and UV radiation in triggering bleaching on shallow reefs

Behavior trees in action: A study of robotics applications

Autonomous robots combine a variety of skills to form increasingly complex behaviors called missions. While the skills are often programmed at a relatively low level of abstraction, their coordination is architecturally separated and often expressed in higher-level languages or frameworks. Recently, the language of Behavior Trees gained attention among roboticists for this reason. Originally designed for computer games to model autonomous actors, Behavior Trees offer an extensible tree-based representation of missions. However, even though, several implementations of the language are in use, little is known about its usage and scope in the real world. How do behavior trees relate to traditional languages for describing behavior? How are behavior tree concepts used in applications? What are the benefits of using them? We present a study of the key language concepts in Behavior Trees and their use in real-world robotic applications. We identify behavior tree languages and compare their semantics to the most well-known behavior modeling languages: state and activity diagrams. We mine open source repositories for robotics applications that use the language and analyze this usage. We find that Behavior Trees are a pragmatic language, not fully specified, allowing projects to extend it even for just one model. Behavior trees clearly resemble the models-at-runtime paradigm. We contribute a dataset of real-world behavior models, hoping to inspire the community to use and further develop this language, associated tools, and analysis techniques.Comment: 14 pages, 5 figures, 13rd ACM SIGPLAN International Conference on Software Language Engineering (SLE) (SLE 2020