184 research outputs found
Improved representation of the diurnal variation of warm season precipitation by an atmospheric general circulation model at a 10 km horizontal resolution
This study investigates the diurnal variation of the warm season precipitation simulated by the Goddard Earth Observing System version 5 atmospheric general circulation model for 2??years (2005???2006) at a horizontal resolution of 10??km. The simulation was validated with the satellite-derived Tropical Rainfall Measuring Mission (TRMM) 3B42 precipitation data and the Modern-Era Retrospective analysis for Research and Applications atmospheric reanalysis for atmospheric winds and moisture. The simulation is compared with the coarse-resolution run in 50??km to examine the impacts driven by resolution change. Overall, the 10??km model tends to reproduce the important features of the observed diurnal variation, such as the amplitude and phase at which precipitation peaks in the evening on land and in the morning over the ocean, despite an excessive amplitude bias over land. The model also reproduces the realistic propagation patterns of precipitation in the vicinity of ocean coasts and major mountains. The regional characteristics of the diurnal precipitation over two regions, the Bay of Bengal and the Great Plains in North America, are examined in detail, where the observed diurnal cycle exhibits a systematic transition in the peak phase due to the development and propagation of regional-scale convective systems. The model is able to reproduce this pattern as well as the diurnal variation of low-level wind and moisture convergence; however, it is less effective at representing the nocturnal peak of precipitation over the Great Plains. The model results suggest that increasing the horizontal resolution of the model to 10??km substantially improves the representation of the diurnal precipitation cycle. However, intrinsic model deficiencies in topographical precipitation and the accurate representation of mesoscale convective systems remain a challenge
The basal epithelial marker P-cadherin associates with breast cancer cell populations harboring a glycolytic and acid-resistant phenotype
"BMC Cancer 2014 14:734"BACKGROUND:
Cancer stem cells are hypoxia-resistant and present a preponderant glycolytic metabolism. These characteristics are also found in basal-like breast carcinomas (BLBC), which show increased expression of cancer stem cell markers.Recently, we demonstrated that P-cadherin, a biomarker of BLBC and a poor prognostic factor in this disease, mediates stem-like properties and resistance to radiation therapy. Thus, the aim of the present study was to evaluate if P-cadherin expression was associated to breast cancer cell populations with an adapted phenotype to hypoxia.
METHODS:
Immunohistochemistry was performed to address the expression of P-cadherin, hypoxic, glycolytic and acid-resistance biomarkers in primary human breast carcinomas. In vitro studies were performed using basal-like breast cancer cell lines. qRT-PCR, FACS analysis, western blotting and confocal microscopy were used to assess the expression of P-cadherin after HIF-1a stabilization, achieved by CoCl2 treatment. siRNA-mediated knockdown was used to silence the expression of several targets and qRT-PCR was employed to evaluate the effects of P-cadherin on HIF-1a signaling. P-cadherin high and low breast cancer cell populations were sorted by FACS and levels of GLUT1 and CAIX were assessed by FACS and western blotting. Mammosphere forming efficiency was used to determine the stem cell activity after specific siRNA-mediated knockdown, further confirmed by western blotting.
RESULTS:
We demonstrated that P-cadherin overexpression was significantly associated with the expression of HIF-1a, GLUT1, CAIX, MCT1 and CD147 in human breast carcinomas. In vitro, we showed that HIF-1a stabilization was accompanied by increased membrane expression of P-cadherin and that P-cadherin silencing led to a decrease of the mRNA levels of GLUT1 and CAIX. We also found that the cell fractions harboring high levels of P-cadherin were the same exhibiting more GLUT1 and CAIX expression. Finally, we showed that P-cadherin silencing significantly decreases the mammosphere forming efficiency in the same range as the silencing of HIF-1a, CAIX or GLUT1, validating that all these markers are being expressed by the same breast cancer stem cell population.
CONCLUSIONS:
Our results establish a link between aberrant P-cadherin expression and hypoxic, glycolytic and acid-resistant breast cancer cells, suggesting a possible role for this marker in cancer cell metabolismo.This work was funded by FEDER funds through the COMPETE Program (Programa Operacional Factores de Competitividade) and by national funds through FCT (Portuguese Foundation for Science and Technology, Portugal), mainly in the context of the scientific project PTDC/SAU-GMG/120049/2010-FCOMP-01-0124-FEDER-021209, and partially by PTDC/SAU-FCF/104347/2008. FCT funded the research grants of BS (SFRH/BD/69353/2010), ASR (SFRH/BPD/75705/2011), ARN (grant from the project PTDC/SAU-GMG/120049/2010), CP (SFRH/BPD/69479/2010), AV (SFRH/BPD/90303/2012), as well as JP, with Programa Ciencia 2007 (Contratacao de Doutorados para o SCTN - financiamento pelo POPH - QREN - Tipologia 4.2 - Promocao do Emprego Cientifico, comparticipado pelo Fundo Social Europeu e por fundos nacionais do MCTES) and Programa IFCT (FCT Investigator). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT
The anti-bacterial iron-restriction defence mechanisms of egg white; the potential role of three lipocalin-like proteins in resistance against Salmonella
Salmonella enterica serovar Enteritidis (SE) is the most frequently-detected Salmonella in foodborne outbreaks in the European Union. Among such outbreaks, egg and egg products were identified as the most common vehicles of infection. Possibly, the major antibacterial property of egg white is iron restriction, which results from the presence of the iron-binding protein, ovotransferrin. To circumvent iron restriction, SE synthesise catecholate siderophores (i.e. enterobactin and salmochelin) that can chelate iron from host iron-binding proteins. Here, we highlight the role of lipocalin-like proteins found in egg white that could enhance egg-white iron restriction through sequestration of certain siderophores, including enterobactin. Indeed, it is now apparent that the egg-white lipocalin, Ex-FABP, can inhibit bacterial growth via its siderophore-binding capacity in vitro. However, it remains unclear whether ex-FABP performs such a function in egg white or during bird infection. Regarding the two other lipocalins of egg white (Cal-γ and α-1-glycoprotein), there is currently no evidence to indicate that they sequester siderophores
Psychometric properties of a prostate cancer radiation late toxicity questionnaire
<p>Abstract</p> <p>Background</p> <p>To construct a short prostate cancer radiation late toxicity (PCRT) questionnaire with health-related quality-of-life (HRQoL) domains.</p> <p>Methods</p> <p>The PCRT was developed by item generation, questionnaire construction (n = 7 experts, n = 8 focus group patients), pilot testing (n = 37), item reduction (n = 100), reliability testing (n = 237), and validity testing (n = 274).</p> <p>Results</p> <p>Reliability of the three item-reduced subscales demonstrated intraclass correlation coefficients (CC) of 0.811 (GU), 0.842 (GI), and 0.740 (sexual). Discriminant validity demonstrated Pearson CC of 0.449 (GU-GI), 0.200 (sexual-GU), and 0.09 (sexual-GI). Content validity correlations between PCRT-PCQoL were 0.35–0.78, PCRT-FACT-G<sup>© </sup>were 0.19–0.39, and PCRT-SF-36<sup>® </sup>were 0.03–0.34.</p> <p>Conclusion</p> <p>We successfully generated a PCRT HRQoL questionnaire including subscales with very good psychometric properties.</p
Connecting Health and Technology (CHAT): protocol of a randomized controlled trial to improve nutrition behaviours using mobile devices and tailored text messaging in young adults
Background: Increasing intakes of fruits and vegetables intake, in tandem with reducing consumption of energy-dense and nutrient poor foods and beverages are dietary priorities to prevent chronic disease. Although most adults do not eat enough fruit and vegetables, teenagers and young adults tend to have the lowest intakes. Young adults typically consume a diet which is inconsistent with the dietary recommendations. Yet little is known about the best approaches to improve dietary intakes and behaviours among this group. This randomised controlled trial aims to evaluate the effectiveness of using a mobile device to assess dietary intake, provide tailored dietary feedback and text messages to motivate changes in fruit, vegetable and junk food consumption among young adults
Cadherin-Dependent Cell Morphology in an Epithelium: Constructing a Quantitative Dynamical Model
Cells in the Drosophila retina have well-defined morphologies that are attained during tissue morphogenesis. We present a computer simulation of the epithelial tissue in which the global interfacial energy between cells is minimized. Experimental data for both normal cells and mutant cells either lacking or misexpressing the adhesion protein N-cadherin can be explained by a simple model incorporating salient features of morphogenesis that include the timing of N-cadherin expression in cells and its temporal relationship to the remodeling of cell-cell contacts. The simulations reproduce the geometries of wild-type and mutant cells, distinguish features of cadherin dynamics, and emphasize the importance of adhesion protein biogenesis and its timing with respect to cell remodeling. The simulations also indicate that N-cadherin protein is recycled from inactive interfaces to active interfaces, thereby modulating adhesion strengths between cells
Connectivity of the Primate Superior Colliculus Mapped by Concurrent Microstimulation and Event-Related fMRI
Background: Neuroanatomical studies investigating the connectivity of brain areas have heretofore employed procedures in which chemical or viral tracers are injected into an area of interest, and connected areas are subsequently identified using histological techniques. Such experiments require the sacrifice of the animals and do not allow for subsequent electrophysiological studies in the same subjects, rendering a direct investigation of the functional properties of anatomically identified areas impossible. Methodology/Principal Findings: Here, we used a combination of microstimulation and fMRI in an anesthetized monkey preparation to study the connectivity of the superior colliculus (SC). Microstimulation of the SC resulted in changes in the blood oxygenation level-dependent (BOLD) signals in the SC and in several cortical and subcortical areas consistent with the known connectivity of the SC in primates. Conclusions/Significance: These findings demonstrates that the concurrent use of microstimulation and fMRI can be used to identify brain networks for further electrophysiological or fMRI investigation
Providing competency-based family medicine residency training in substance abuse in the new millennium: a model curriculum
<p>Abstract</p> <p>Background</p> <p>This article, developed for the Betty Ford Institute Consensus Conference on Graduate Medical Education (December, 2008), presents a model curriculum for Family Medicine residency training in substance abuse.</p> <p>Methods</p> <p>The authors reviewed reports of past Family Medicine curriculum development efforts, previously-identified barriers to education in high risk substance use, approaches to overcoming these barriers, and current training guidelines of the Accreditation Council for Graduate Medical Education (ACGME) and their Family Medicine Residency Review Committee. A proposed eight-module curriculum was developed, based on substance abuse competencies defined by Project MAINSTREAM and linked to core competencies defined by the ACGME. The curriculum provides basic training in high risk substance use to all residents, while also addressing current training challenges presented by U.S. work hour regulations, increasing international diversity of Family Medicine resident trainees, and emerging new primary care practice models.</p> <p>Results</p> <p>This paper offers a core curriculum, focused on screening, brief intervention and referral to treatment, which can be adapted by residency programs to meet their individual needs. The curriculum encourages direct observation of residents to ensure that core skills are learned and trains residents with several "new skills" that will expand the basket of substance abuse services they will be equipped to provide as they enter practice.</p> <p>Conclusions</p> <p>Broad-based implementation of a comprehensive Family Medicine residency curriculum should increase the ability of family physicians to provide basic substance abuse services in a primary care context. Such efforts should be coupled with faculty development initiatives which ensure that sufficient trained faculty are available to teach these concepts and with efforts by major Family Medicine organizations to implement and enforce residency requirements for substance abuse training.</p
‘This In-Between’: How Families Talk about Death in Relation to Severe Brain Injury and Disorders of Consciousness
These comments encapsulate some common themes in how people describe having a severely brain-injured relative in a coma-like condition, medically known as a ‘disorder of consciousness’. In the past it was highly unusual for such individuals to survive very long after the initial trauma that caused their injury. However, the emergence of modern medical technologies, and how they are deployed, has led to the creation of new long-term conditions including the ‘vegetative state’ (in which the patient shows no awareness at all) and the ‘minimally conscious state’ (in which the the patient displays some intermittent and minimal awareness). These conditions are modern phenomena — the vegetative diagnostic category was first created in the early 1970s (Jennett and Plum, 1972) and the ‘minimally conscious state’ [MCS] was only defined in 2002 (Giacino et al., 2002). Patients with disorders of consciousness disrupt previous ways of understanding life. The family may experience their vegetative or minimally conscious relative as ‘present but absent’, ‘living, but dead’, making comments such as ‘this is no life’ and ‘my son is gone’ — and experiencing a sense of loss and grief that may be ‘like a death’, although not a death
Special cases : moons, rings, comets, trojans
Non-planetary bodies provide valuable insight into our current under-
standing of planetary formation and evolution. Although these objects are
challeng- ing to detect and characterize, the potential information to be drawn
from them has motivated various searches through a number of techniques. Here,
we briefly review the current status in the search of moons, rings, comets, and
trojans in exoplanet systems and suggest what future discoveries may occur in
the near future.Comment: Invited review (status August 2017
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