496 research outputs found
Middle Level Preservice Teachers Experience a Natural History Arts-Integrated Interdisciplinary Thematic Unit
Curricular demands and best practices for middle school require interdisciplinary units. Arts integration can provide motivation and a new pathway to learning. This unit focused on inquiry into the natural history of artifacts and rocks recovered from the exposed subsoil of an area near Cedar Falls, Iowa that had been bulldozed as part of subdivision development. The described unit involved preservice teachers in exploration of all subject areas (language arts, mathematics, science, and social studies) with arts-integrated projects (agate watercolor painting, stone tool graphing, acrylic polymer clay agate keyring making, and stone tool drawings). The content area activities for social studies included identification and lifestyle interpretation of stone tools found intermixed with rocks and sand in the subsoil of the site. Science content activities included identification of rocks (igneous and metamorphic rocks; quartz nodules, geodes, and agates; and iron ore specimens) from the site along with interpretation of basalt cobbles that had been ground flat as glacially transported, and interpretation of maps and diagrams of glaciation, iron ore deposits, and agate deposits. Language arts activities involved word study through morpheme analysis of words such as “anthropology” and “artifact” along with matching a set of descriptive adjectives to objects related to agates. Mathematics content activities focused on graphing. Preservice teachers were highly engaged in the activities, remarking that they learned new content and pedagogy. Some expressed lack of confidence regarding artistic ability because of little experience and the desire to complete everything in the correct manner. At the end of the lessons, preservice teachers expressed that teaching the content through themes allowed for a great number of connections between subject areas, increased real-life connections, and deeper understandings of the topics
Modulated contact frequencies at gene-rich loci support a statistical helix model for mammalian chromatin organization
International audienceABSTRACT: BACKGROUND: Despite its critical role for mammalian gene regulation, the basic structural landscape of chromatin in living cells remains largely unknown within chromosomal territories below the megabase scale. RESULTS: Here, using the 3C-qPCR method, we investigate contact frequencies at high resolution within the interphase chromatin at several mouse loci. We find that, at several gene-rich loci, contact frequencies undergo a periodical modulation (every 90-100 kb) that affects chromatin dynamics over large genomic distances (few hundred kb). Interestingly, this modulation appears to be conserved in human cells and bioinformatic analyses of locus-specific, long-range cis-interactions suggest that it may underlie the dynamics of a significant number of gene-rich domains in mammals, thus contributing to genome evolution. Finally, using an original model derived from polymer physics, we show that this modulation can be understood as a fundamental helix shape that chromatin tends to adopt in gene-rich domains when no significant locus-specific interaction takes place. CONCLUSIONS: Altogether, our work unveils a fundamental aspect of chromatin dynamics in mammals and contributes to a better understanding of genome organization within chromosomal territories
A small XY chromosomal region explains sex determination in wild dioecious V. vinifera and the reversal to hermaphroditism in domesticated grapevines
Publis014-agap-029Background In Vitis vinifera L., domestication induced a dramatic change in flower morphology: the wild sylvestris subspecies is dioecious while hermaphroditism is largely predominant in the domesticated subsp. V. v. vinifera. The characterisation of polymorphisms in genes underlying the sex-determining chromosomal region may help clarify the history of domestication in grapevine and the evolution of sex chromosomes in plants. In the genus Vitis, sex determination is putatively controlled by one major locus with three alleles, male M, hermaphrodite H and female F, with an allelic dominance M > H > F. Previous genetic studies located the sex locus on chromosome 2. We used DNA polymorphisms of geographically diverse V. vinifera genotypes to confirm the position of this locus, to characterise the genetic diversity and traces of selection in candidate genes, and to explore the origin of hermaphroditism. Results In V. v. sylvestris, a sex-determining region of 154.8 kb, also present in other Vitis species, spans less than 1% of chromosome 2. It displays haplotype diversity, linkage disequilibrium and differentiation that typically correspond to a small XY sex-determining region with XY males and XX females. In male alleles, traces of purifying selection were found for a trehalose phosphatase, an exostosin and a WRKY transcription factor, with strikingly low polymorphism levels between distant geographic regions. Both diversity and network analysis revealed that H alleles are more closely related to M than to F alleles. Conclusions Hermaphrodite alleles appear to derive from male alleles of wild grapevines, with successive recombination events allowing import of diversity from the X into the Y chromosomal region and slowing down the expansion of the region into a full heteromorphic chromosome. Our data are consistent with multiple domestication events and show traces of introgression from other Asian Vitis species into the cultivated grapevine gene pool. La vigne domestiquée, Vitis vinifera ssp. vinifera, cultivée pour la production de fruit et de vin à travers le monde, dérive de la vigne sauvage, Vitis vinifera ssp. sylvestris, sous-espèce endémique de l'Eurasie. Au cours de la domestication, le système de reproduction a évolué de la diécie à l'hermaphrodisme. Nous montrons que la région du sexe est sous le contrôle d'une région chromosomique qui couvre au maximum 154kpbp, moins de 1% du chromosome 2. La caractérisation de ce locus en terme de diversité haplotypique, de signature de sélection et de déséquilibre de liaison a permis de révéler un système de détermination sexuelle de type XY. La petite taille de cette région chromosomique semble indiquer un stade très précoce dans l'évolution de chromosomes sexuels, malgré que la diécie soit le trait ancestral chez toutes les espèces de Vitis, ayant divergé du sous-genre Muscadinia il y a plusieurs millions d'années. L'analyse des distances génétiques entre haplotypes dans le locus du sexe a révélé que l'hermaphrodisme observé chez la vigne domestiquée résulte de la mutation de l'allèle mâle présent chez la vigne sauvage. Le réseau d'haplotypes a montré qu'en plus de la contribution de V. sylvestris, une autre espèce de Vitis asiatique a pu contribuer à la constitution du génome actuel de la vigne cultivée moderne. Ces travaux résultent d'une collaboration entre l'équipe DAAV d'AGAP et l'UMR CBAE (Montpellier)
Short-Term Changes in Albuminuria and Risk of Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus:A Post Hoc Analysis of the EMPA-REG OUTCOME Trial
Background Early reduction in albuminuria with an SGLT2 (sodium-glucose cotransporter 2) inhibitor may be a positive indicator of long-term cardiovascular and renal benefits. We assessed changes in albuminuria during the first 12 weeks of treatment and subsequent long-term cardiovascular and renal risks associated with the SGLT2 inhibitor, empagliflozin, in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 diabetes Mellitus Patients) trial. Methods and Results We calculated the percentage urinary albumin creatinine ratio (UACR) change from baseline to week 12 in 6820 participants who did not experience a cardiovascular outcome (including 3-point major cardiovascular events and cardiovascular death or hospitalization for heart failure) or renal outcome (defined as 40% decline in estimated glomerular filtration rate from baseline, estimated glomerular filtration rate 30% reduction in UACR (odds ratio, 1.42; 95% CI, 1.27-1.58; P<0.001). During 3.0 years of follow-up, 704 major cardiovascular events, 440 cardiovascular deaths/hospitalizations for heart failure, and 168 renal outcomes were observed. Each 30% decrease in UACR during the first 12 weeks was statistically significantly associated with a lower hazard for major cardiovascular events (HR, 0.96; 95% CI, 0.93-0.99; P=0.012), cardiovascular deaths/hospitalizations for heart failure (HR, 0.94; 95% CI, 0.91-0.98; P=0.003), and renal outcomes (HR, 0.83; 95% CI, 0.78-0.89; P<0.001). Conclusions Short-term reduction in UACR was more common with empagliflozin and was statistically significantly associated with a decreased risk of long-term cardiovascular and renal outcomes. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01131676
Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells.
International audienceExpression of the antimicrobial peptide hCAP18/LL-37 is associated to malignancy in various cancer forms, stimulating cell migration and metastasis. We report that LL-37 induces migration of three cancer cell lines by activating the TRPV2 calcium-permeable channel and recruiting it to pseudopodia through activation of the PI3K/AKT pathway. Ca2+ entry through TRPV2 cooperated with a K+ efflux through the BKCa channel. In a panel of human breast tumors, the expression of TRPV2 and LL-37 was found to be positively correlated. The D-enantiomer of LL-37 showed identical effects as the L-peptide, suggesting that no binding to a specific receptor was involved. LL-37 attached to caveolae and pseudopodia membranes and decreased membrane fluidity, suggesting that a modification of the physical properties of the lipid membrane bilayer was the underlying mechanism of its effects
Characterization and implications of the initial estimated glomerular filtration rate 'dip' upon sodium-glucose cotransporter-2 inhibition with empagliflozin in the EMPA-REG OUTCOME trial
Treatment with sodium-glucose co-transporter-2 inhibitors induces an initial 3-5 ml/min/1.73 m(2) decline in estimated glomerular filtration rate (eGFR). Although considered to be of hemodynamic origin and largely reversible, this 'eGFR dip' may cause concern in clinical practice, which highlights the need to better understand its incidence and clinical implications. In this post hoc analysis of the EMPA-REG OUTCOME trial, 6,668 participants randomized to empagliflozin 10 mg, 25 mg or placebo with eGFR available at baseline and week four were categorized by initial eGFR change into three groups; over 10% decline ('eGFR dipper'), over 0 and up to 10% decline ('eGFR intermediate'), no eGFR decline ('eGFR non-dipper'). Baseline characteristics of 'eGFR intermediate' and 'eGFR non-dipper' were generally comparable. An initial 'eGFR dip' was observed in 28.3% of empagliflozin versus 13.4% of placebo-treated participants; odds ratio 2.7 [95% Confidence Interval 2.3-3.0]. In multivariate logistic regression, diuretic use and higher KDIGO risk category at baseline were independently predictive of an 'eGFR dip' in empagliflozin versus placebo. Safety and beneficial treatment effects with empagliflozin on cardiovascular and kidney outcomes were consistent across subgroups based on these predictive factors. The initial 'eGFR dip' did not have a major impact on the treatment effect of empagliflozin on subsequent cardiovascular death, hospitalization for heart failure, and incident or worsening kidney disease. Thus, patients with type 2 diabetes with more advanced kidney disease and/or on diuretic therapy were more likely to experience an 'eGFR dip' of over 10% with empagliflozin, but reduction in cardiovascular and kidney outcomes was not relevantly modified by such 'eGFR dip.
The French EO high spatial resolution hyperspectral dual mission - an update
More than 25 years of airborne imaging spectroscopy and spaceborne sensors such as Hyperion [1] or HICO [2] have clearly demonstrated the ability of such a remote sensing technique to produce value added information regarding surface composition and physical properties for a large variety of applications [3]. Scheduled missions such as EnMAP [4], HISUI [5] or PRISMA [6] prove the increased interest of the scientific community for such a type of remote sensing data. In France, after gathering a group of Science and Defence users of imaging spectrometry data (Groupe de Synthèse Hyperspectral, GSH [7]) to establish an up-to-date review of possible applications, define instrument specifications required for accurate, quantitative retrieval of diagnostic parameters, and identify fields of application where imaging spectrometry is a major contribution, CNES (French Space Agency) decided a pre-phase A study for an hyperspectral mission concept called HYPXIM (HYPerspectral-X IMagery), the main fields of applications of which were to be vegetation, coastal and inland waters, geosciences, urban environment, atmospheric sciences, cryosphere and Defence. During this pre-phase A, the feasibility of such a platform was evaluated, based on specific studies supported by Defence and a more accurate definition of reference radiances and instrument characteristics. Results also pointed to applications where high spatial resolution was necessary and would not be covered by the other foreseen hyperspectral missions. For example, in the case of ecosystem studies, it is generally agreed that many model variables and processes are not accurately represented and that upcoming sensors with improved spatial and spectral capabilities, such as higher resolution imaging spectrometers, are needed to further improve the quality and accuracy of model variables [8, 9]. The growing interest for urban environment related applications also emphasized the need for an increased spatial resolution [10, 11]. Finally, short revisit time is an issue for security and Defense as well as crisis monitoring. Table 1 summarizes the Science and Defence mission requirements at the end of pre-phase A.
Two instrument designs were proposed by the industry (EADS-Astrium and Thales Alenia Space) based on these new requirements [12]: HYPXIM-Challenging, on a micro-satellite platform, with a 15 m pixel and HYPXIM-Performance, on a mini-satellite platform, with a 8 m pixel, and possible TIR hyperspectral capabilities. Both scenarios included a PAN camera with a 1.85 m pixel. Platform agility would allow for “on-event mode” with a 3-day revisit time. CNES decided to select HYPXIM-Performance, the system providing a higher spatial resolution (pixel ≤ 8 m, [13, 14]), but without TIR capabilities, for a phase A study [15]. This phase A was to start at the beginning of 2013 but is currently stopped due to budget constraints. An important part of the activities has been focusing on getting the French community more involved through various surveys and workshops in preparation for the CNES prospective meeting, an important step for the future of the mission. During this prospective meeting, which took place last March, decision was taken to keep HYPXIM alive as a mid-term (2020-2025) mission. The attendance at the recent workshop organized by the SFPT-GH (Société Française de Photogrammétrie et Télédétection, Groupe Hyperspectral) which gathered more than 90 participants from various field of application, including the industry (see http://www.sfpt.fr/hyperspectral for more details), demonstrates the interest and support of the French scientific community for a high spatial resolution imaging spectrometry mission
Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction : the randomized MARLINA-T2D trial
Aims: The MARLINA-T2D study (ClinicalTrials. gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard-of-care in individuals with type 2 diabetes and albuminuria. Methods: A total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48-86 mmol/ mol), estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m(2) and urinary albumin-tocreatinine ratio (UACR) 30-3000 mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks. The primary and key secondary endpoints were change from baseline in HbA1c at week 24 and time-weighted average of percentage change from baseline in UACR over 24 weeks, respectively. Results: Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8% +/- 0.9% (62.2 +/- 9.6 mmol/mol) and 126 mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24 weeks, the placebo-adjusted mean change in HbA1c from baseline was -0.60% (-6.6 mmol/mol) (95% confidence interval [CI], -0.78 to -0.43 [-8.5 to -4.7 mmol/mol]; P Conclusions: In individuals at early stages of diabetic kidney disease, linagliptin significantly improved glycaemic control but did not significantly lower albuminuria. There was no significant change in placebo-adjusted eGFR. Detection of clinically relevant renal effects of linagliptin may require longer treatment, as its main experimental effects in animal studies have been to reduce interstitial fibrosis rather than alter glomerular haemodynamics.Peer reviewe
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