Developing PCK for Teaching Teachers through a Mentored Internship in Teacher Professional Development

Pedagogical Content Knowledge (PCK), according to Shulman (1987), is what makes possible the transformation of disciplinary content into forms that are accessible and attainable by students. This includes knowledge of how particular subject matter topics, problems, and issues can be organized, represented, and adapted to the diverse interests and abilities of learners and presented for instruction (Magnusson, Krajcik, & Borko, 1999). Recently, researchers have argued that a parallel form of PCK exists for science teacher educators (Abell et al., 2009). Nonetheless, little is known about the process through which teacher educators develop their PCK, and more specifically, how doctoral programs can support prospective teacher educators in this regard. The aim of this study was to understand how a mentored internship experience within a teacher professional development program contributes to the development of doctoral students’ PCK for teaching teachers. Through self study, three graduate students and their faculty mentor documented the development of their PCK throughout the mentorship

Developing PCK for Teaching Teachers through a Mentored Internship in Teacher Professional Development

This conference paper was presented at the annual meeting of the Association for Science Teacher Education in Minneapolis, MN, in January 2011.Pedagogical Content Knowledge (PCK), according to Shulman (1987), is what makes possible the transformation of disciplinary content into forms that are accessible and attainable by students. This includes knowledge of how particular subject matter topics, problems, and issues can be organized, represented, and adapted to the diverse interests and abilities of learners and presented for instruction (Magnusson, Krajcik, & Borko, 1999). Recently, researchers have argued that a parallel form of PCK exists for science teacher educators (Abell et al., 2009). Nonetheless, little is known about the process through which teacher educators develop their PCK, and more specifically, how doctoral programs can support prospective teacher educators in this regard. The aim of this study was to understand how a mentored internship experience within a teacher professional development program contributes to the development of doctoral students' PCK for teaching teachers. Through self‐study, three graduate students and their faculty mentor documented the development of their PCK throughout the mentorship

111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells

Radiolabelled, drug-loaded nanoparticles may combine the theranostic properties of radionuclides, the controlled release of chemotherapy and cancer cell targeting. Here, we report the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface conjugated to DTPA-hEGF (DTPA = diethylenetriaminepentaacetic acid, hEGF = human epidermal growth factor) and encapsulating the ruthenium-based DNA replication inhibitor and radiosensitizer Ru(phen)2(tpphz)2+ (phen = 1,10-phenanthroline, tpphz = tetrapyridophenazine) Ru1. The functionalized PLGA surface incorporates the metal ion chelator DTPA for radiolabelling and the targeting ligand for EGF receptor (EGFR). Nanoparticles radiolabelled with 111In are taken up preferentially by EGFR-overexpressing oesophageal cancer cells, where they exhibit radiotoxicity through the generation of cellular DNA damage. Moreover, nanoparticle co-delivery of Ru1 alongside 111In results in decreased cell survival compared to single-agent formulations; an effect that occurs through DNA damage enhancement and an additive relationship between 111In and Ru1. Substantially decreased uptake and radiotoxicity of nanoparticles towards normal human fibroblasts and oesophageal cancer cells with normal EGFR levels is observed. This work demonstrates nanoparticle co-delivery of a therapeutic radionuclide plus a ruthenium-based radiosensitizer can achieve combinational and targeted therapeutic effects in cancer cells that overexpress EGFR

Penetration Pathways Induced by Low-Frequency Sonophoresis with Physical and Chemical Enhancers: Iron Oxide Nanoparticles versus Lanthanum Nitrates

Low-frequency sonophoresis (LFS) has been shown to disrupt the structure of stratum corneum (SC) lipid bilayers and enhance SC permeability. In this study, we examined the penetration pathway of lanthanum nitrate (LaNO3) tracer in viable epidermis after combined treatment of LFS and tape stripping (TS), as a physical enhancer, or oleic acid (OA) application, as a chemical enhancer, using transmission electron microscopy (TEM). As a positive control, we visualized the passive diffusion pathway of LaNO3 and iron oxide (Fe3O4) nanoparticles after the incision of hairless mouse skin. Next, we applied LFS immediately after TS or OA application and visualized the penetration pathway of LaNO3. Each treatment showed restricted penetration to the SC–stratum granulosum (SG) interface or upper SG layer. However, the additional application of LFS induced diffuse intracellular distribution of LaNO3 throughout the viable epidermis. Quantitative analysis also revealed that combined treatment significantly increases LaNO3 penetration into viable epidermis when compared with each treatment. Our ultrastructural findings show the synergistic effect of LFS and TS or OA application on transdermal drug delivery. We also found that this combined treatment enhances the penetration of LaNO3 through the viable epidermis through an intracellular pathway

Sodium glucose co-transporter 2 inhibition increases epidermal growth factor expression and improves outcomes in patients with type 2 diabetes

Underlying molecular mechanisms of the kidney protective effects of sodium glucose co-transporter 2 (SGLT2) inhibitors are not fully elucidated. Therefore, we studied the association between urinary epidermal growth factor (uEGF), a mitogenic factor involved in kidney repair, and kidney outcomes in patients with type 2 diabetes (T2D). The underlying molecular mechanisms of the SGLT2 inhibitor canagliflozin on EGF using single-cell RNA sequencing from kidney tissue were examined. Urinary EGF-to-creatinine ratio (uEGF/Cr) was measured in 3521 CANagliflozin cardioVascular Assessment Study (CANVAS) participants at baseline and week 52. Associations of uEGF/Cr with kidney outcome were assessed using multivariable-adjusted Cox regression models. Single-cell RNA sequencing was performed using protocol kidney biopsy tissue from ten young patients with T2D on SGLT2i, six patients with T2D on standard care only, and six healthy controls (HCs). In CANVAS, each doubling in baseline uEGF/Cr was associated with a 12% (95% confidence interval 1-22) decreased risk of kidney outcome. uEGF/Cr decreased after 52 weeks with placebo and remained stable with canagliflozin (between-group difference +7.3% (2.0-12.8). In young persons with T2D, EGF mRNA was primarily expressed in the thick ascending loop of Henle. Expression in biopsies from T2D without SGLT2i was significantly lower compared to HCs, whereas treatment with SGLT2i increased EGF levels closer to the healthy state. In young persons with T2D without SGLT2i, endothelin-1 emerged as a key regulator of the EGF co-expression network. SGLT2i treatment was associated with a shift towards normal EGF expression. Thus, decreased uEGF represents increased risk of kidney disease progression in patients with T2D. Canagliflozin increased kidney tissue expression of EGF and was associated with a downstream signaling cascade linked to tubular repair and reversal of tubular injury.</p

Better Few than Hungry: Flexible Feeding Ecology of Collared Lemurs Eulemur collaris in Littoral Forest Fragments

Frugivorous primates are known to encounter many problems to cope with habitat degradation, due to the fluctuating spatial and temporal distribution of their food resources. Since lemur communities evolved strategies to deal with periods of food scarcity, these primates are expected to be naturally adapted to fluctuating ecological conditions and to tolerate a certain degree of habitat changes. However, behavioral and ecological strategies adopted by frugivorous lemurs to survive in secondary habitats have been little investigated. Here, we compared the behavioral ecology of collared lemurs (Eulemur collaris) in a degraded fragment of littoral forest of south-east Madagascar, Mandena, with that of their conspecifics in a more intact habitat, Sainte Luce.Lemur groups in Mandena and in Sainte Luce were censused in 2004/2007 and in 2000, respectively. Data were collected via instantaneous sampling on five lemur groups totaling 1,698 observation hours. The Shannon index was used to determine dietary diversity and nutritional analyses were conducted to assess food quality. All feeding trees were identified and measured, and ranging areas determined via the minimum convex polygon. In the degraded area lemurs were able to modify several aspects of their feeding strategies by decreasing group size and by increasing feeding time, ranging areas, and number of feeding trees. The above strategies were apparently able to counteract a clear reduction in both food quality and size of feeding trees.Our findings indicate that collared lemurs in littoral forest fragments modified their behavior to cope with the pressures of fluctuating resource availability. The observed flexibility is likely to be an adaptation to Malagasy rainforests, which are known to undergo periods of fruit scarcity and low productivity. These results should be carefully considered when relocating lemurs or when selecting suitable areas for their conservation

Negative Autoregulation by Fas Stabilizes Adult Erythropoiesis and Accelerates Its Stress Response

Erythropoiesis maintains a stable hematocrit and tissue oxygenation in the basal state, while mounting a stress response that accelerates red cell production in anemia, blood loss or high altitude. Thus, tissue hypoxia increases secretion of the hormone erythropoietin (Epo), stimulating an increase in erythroid progenitors and erythropoietic rate. Several cell divisions must elapse, however, before Epo-responsive progenitors mature into red cells. This inherent delay is expected to reduce the stability of erythropoiesis and to slow its response to stress. Here we identify a mechanism that helps to offset these effects. We recently showed that splenic early erythroblasts, ‘EryA’, negatively regulate their own survival by co-expressing the death receptor Fas, and its ligand, FasL. Here we studied mice mutant for either Fas or FasL, bred onto an immune-deficient background, in order to avoid an autoimmune syndrome associated with Fas deficiency. Mutant mice had a higher hematocrit, lower serum Epo, and an increased number of splenic erythroid progenitors, suggesting that Fas negatively regulates erythropoiesis at the level of the whole animal. In addition, Fas-mediated autoregulation stabilizes the size of the splenic early erythroblast pool, since mutant mice had a significantly more variable EryA pool than matched control mice. Unexpectedly, in spite of the loss of a negative regulator, the expansion of EryA and ProE progenitors in response to high Epo in vivo, as well as the increase in erythropoietic rate in mice injected with Epo or placed in a hypoxic environment, lagged significantly in the mutant mice. This suggests that Fas-mediated autoregulation accelerates the erythropoietic response to stress. Therefore, Fas-mediated negative autoregulation within splenic erythropoietic tissue optimizes key dynamic features in the operation of the erythropoietic network as a whole, helping to maintain erythroid homeostasis in the basal state, while accelerating the stress response

Tixagevimab–cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial

Background: Tixagevimab–cilgavimab is a neutralising monoclonal antibody combination hypothesised to improve outcomes for patients hospitalised with COVID-19. We aimed to compare tixagevimab–cilgavimab versus placebo, in patients receiving remdesivir and other standard care. Methods: In a randomised, double-blind, phase 3, placebo-controlled trial, adults with symptoms for up to 12 days and hospitalised for COVID-19 at 81 sites in the USA, Europe, Uganda, and Singapore were randomly assigned in a 1:1 ratio to receive intravenous tixagevimab 300 mg–cilgavimab 300 mg or placebo, in addition to remdesivir and other standard care. Patients were excluded if they had acute organ failure including receipt of invasive mechanical ventilation, extracorporeal membrane oxygenation, vasopressor therapy, mechanical circulatory support, or new renal replacement therapy. The study drug was prepared by an unmasked pharmacist; study participants, site study staff, investigators, and clinical providers were masked to study assignment. The primary outcome was time to sustained recovery up to day 90, defined as 14 consecutive days at home after hospital discharge, with co-primary analyses for the full cohort and for participants who were neutralising antibody-negative at baseline. Efficacy and safety analyses were done in the modified intention-to-treat population, defined as participants who received a complete or partial infusion of tixagevimab–cilgavimab or placebo. This study is registered with ClinicalTrials.gov, NCT04501978 and the participant follow-up is ongoing. Findings: From Feb 10 to Sept 30, 2021, 1455 patients were randomly assigned and 1417 in the primary modified intention-to-treat population were infused with tixagevimab–cilgavimab (n=710) or placebo (n=707). The estimated cumulative incidence of sustained recovery was 89% for tixagevimab–cilgavimab and 86% for placebo group participants at day 90 in the full cohort (recovery rate ratio [RRR] 1·08 [95% CI 0·97–1·20]; p=0·21). Results were similar in the seronegative subgroup (RRR 1·14 [0·97–1·34]; p=0·13). Mortality was lower in the tixagevimab–cilgavimab group (61 [9%]) versus placebo group (86 [12%]; hazard ratio [HR] 0·70 [95% CI 0·50–0·97]; p=0·032). The composite safety outcome occurred in 178 (25%) tixagevimab–cilgavimab and 212 (30%) placebo group participants (HR 0·83 [0·68–1·01]; p=0·059). Serious adverse events occurred in 34 (5%) participants in the tixagevimab–cilgavimab group and 38 (5%) in the placebo group. Interpretation: Among patients hospitalised with COVID-19 receiving remdesivir and other standard care, tixagevimab–cilgavimab did not improve the primary outcome of time to sustained recovery but was safe and mortality was lower. Funding: US National Institutes of Health (NIH) and Operation Warp Speed