This study examines the case of an Animal Behavior and Welfare MOOC that specifically targeted attitudinal change in its learners. Attitudinal learning outcomes were evaluated using an ...author-developed survey with questions on perceptions in the four areas of attitudinal learning: General Learning, Cognitive Learning, Affective Learning, and Behavioral Learning. The survey also examined learner goals for enrolling in the course and their perceptions of the instructional methods implemented in the course. Results showed that learners perceived positive learning outcomes across all four areas. Statistically significant differences were found in relation to perceptions of attitudinal learning based on their reason for enrolling in the MOOC and its relation to attitude formation. There were also significant differences in learners' reasons for enrollment based on whether they intended to change animal welfare related behaviors due to their MOOC experience. Learners overwhelming indicated that the instructor videos were the most impactful instructional strategy regardless of whether they had a higher perception of learning, or a lower perception. Finally, learners with higher perceptions primarily enrolled in the MOOC in order to form a viewpoint on animal welfare, while lower perception learners enrolled to earn a formal certificate of completion. Implications are discussed for instructional design for attitude change as well as for the use of MOOCs for learning regarding social topics.
•Examined case of an Animal Behavior and Welfare MOOC targeting attitudinal change.•Learners perceived positive attitudinal learning across all four areas of attitude.•Differences existed in learning based on reason for enrolling in the MOOC.•Differences existed for enrollment based on intent to change related behaviors.•Videos overwhelmingly identified as the most impactful instructional strategy.
Conventional immunization strategies will likely be insufficient for the development of a broadly neutralizing antibody (bnAb) vaccine for HIV or other difficult pathogens because of the ...immunological hurdles posed, including B cell immunodominance and germinal center (GC) quantity and quality. We found that two independent methods of slow delivery immunization of rhesus monkeys (RMs) resulted in more robust T follicular helper (TFH) cell responses and GC B cells with improved Env-binding, tracked by longitudinal fine needle aspirates. Improved GCs correlated with the development of >20-fold higher titers of autologous nAbs. Using a new RM genomic immunoglobulin locus reference, we identified differential IgV gene use between immunization modalities. Ab mapping demonstrated targeting of immunodominant non-neutralizing epitopes by conventional bolus-immunized animals, whereas slow delivery-immunized animals targeted a more diverse set of epitopes. Thus, alternative immunization strategies can enhance nAb development by altering GCs and modulating the immunodominance of non-neutralizing epitopes.
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•Slow delivery immunization enhances HIV neutralizing antibody development in monkeys•Slow delivery immunization alters immunodominance of the responding B cells•Weekly longitudinal germinal center (GC) B and TFH analyses provides new GC insights•High-resolution rhesus immunoglobulin locus genomic reference sequence
An integrated immunological, bioinformatic and imaging approach demonstrates how slow delivery immunization enhances neutralizing antibody and germinal center reactions over conventional strategies in response to HIV Env protein immunization in non-human primates.
Increasing levels of tissue hypoxia have been reported as a natural feature of the aging prostate gland and may be a risk factor for the development of prostate cancer. In this study, we have used ...PwR-1E benign prostate epithelial cells and an equivalently aged hypoxia-adapted PwR-1E sub-line to identify phenotypic and epigenetic consequences of chronic hypoxia in prostate cells. We have identified a significantly altered cellular phenotype in response to chronic hypoxia as characterized by increased receptor-mediated apoptotic resistance, the induction of cellular senescence, increased invasion and the increased secretion of IL-1β, IL6, IL8 and TNFα cytokines. In association with these phenotypic changes and the absence of HIF-1α protein expression, we have demonstrated significant increases in global levels of DNA methylation and H3K9 histone acetylation in these cells, concomitant with the increased expression of DNA methyltransferase DMNT3b and gene-specific changes in DNA methylation at key imprinting loci. In conclusion, we have demonstrated a genome-wide adjustment of DNA methylation and histone acetylation under chronic hypoxic conditions in the prostate. These epigenetic signatures may represent an additional mechanism to promote and maintain a hypoxic-adapted cellular phenotype with a potential role in tumour development.
There is no effective treatment strategy for advanced castration-resistant prostate cancer. Although Docetaxel (Taxotere®) represents the most active chemotherapeutic agent it only gives a modest ...survival advantage with most patients eventually progressing because of inherent or acquired drug resistance. The aims of this study were to further investigate the mechanisms of resistance to Docetaxel. Three Docetaxel resistant sub-lines were generated and confirmed to be resistant to the apoptotic and anti-proliferative effects of increasing concentrations of Docetaxel.
The resistant DU-145 R and 22RV1 R had expression of P-glycoprotein and its inhibition with Elacridar partially and totally reversed the resistant phenotype in the two cell lines respectively, which was not seen in the PC-3 resistant sublines. Resistance was also not mediated in the PC-3 cells by cellular senescence or autophagy but multiple changes in pro- and anti-apoptotic genes and proteins were demonstrated. Even though there were lower basal levels of NF-κB activity in the PC-3 D12 cells compared to the Parental PC-3, docetaxel induced higher NF-κB activity and IκB phosphorylation at 3 and 6 hours with only minor changes in the DU-145 cells. Inhibition of NF-κB with the BAY 11-7082 inhibitor reversed the resistance to Docetaxel.
This study confirms that multiple mechanisms contribute to Docetaxel resistance and the central transcription factor NF-κB plays an immensely important role in determining docetaxel-resistance which may represent an appropriate therapeutic target.
The aims of the study were to investigate learner profiles in a MOOC focused on attitudinal learning, Science of Happiness, based on learner self-assessment of “happiness” and relationships with ...demographics, attitudinal learning gains and preferred instructional activities. A sequential explanatory mixed methods design was used in the attitudinal learning survey. The survey assessed cognitive, affective, and behavioral learning, and was followed by interviews with 12 participants. Latent profile analysis identified two profiles based on the differences in the levels and trends of happiness reported by learners during the 10-week course. Results indicated that MOOC learners described different preferences for exploratory or instructor-directed instructional strategies. Identified implications for the instructional design of MOOCs for attitudinal learning included recognizing that MOOC learners often view MOOCs more as entertainment as opposed to formal education. Therefore, course length, pace, scope, and difficulty should be considered in this light. Furthermore, supporting varied learner goals and interests, and instructional preferences are important. Finally, special consideration must also be paid to the design and facilitation of course discussions.
•Latent profile analysis identified 2 profiles based on happiness levels and trends.•Learners identified different instructional preferences: instructor-led versus self-directed.•Course design should consider views of MOOCs as entertainment.•Design should support varied learner goals and preferences.•MOOC discussion challenges merit focus on design and facilitation.
To develop educational guidelines for the diagnostic confirmation and management of individuals identified by newborn screening, family-based testing after proband identification, or carrier testing ...in at-risk populations, and subsequent prenatal or postnatal testing of those who are presymptomatic for a lysosomal storage disease.
Review of English language literature and discussions in a consensus development panel comprised an international group of experts in the clinical and laboratory diagnosis, treatment and management, newborn screening, and genetic aspects of lysosomal storage diseases.
Although clinical trial and longitudinal data were used when available, the evidence in the literature is limited and consequently the recommendations must be considered as expert opinion. Guidelines were developed for Fabry, Gaucher, and Niemann-Pick A/B diseases, glycogen storage type II (Pompe disease), globoid cell leukodystrophy (Krabbe disease), metachromatic leukodystrophy, and mucopolysaccharidoses types I, II, and VI.
These guidelines serve as an educational resource for confirmatory testing and subsequent clinical management of presymptomatic indivduals suspected to have a lysosomal storage disease; they also help to define a research agenda for longitudinal studies such as the American College of Medical Genetics/National Institutes of Health Newborn Screening Translational Research Network. Genet Med 2011:13(5):457– 484.
In this paper, we present the development and validation of a new measure of attitudinal learning—the Attitudinal Learning Inventory (ALI). While specific scales are available for measuring ...attitudes, they largely focus on established attitudes, not the impact of instruction on those attitudes. We developed the inventory with two explicit objectives: (1) to measure a broad range of attitude constructs representing a holistic view of attitudinal learning and instruction; and (2) to facilitate the measurement of attitudinal learning that can be useful for educational researchers beyond traditional metrics. The ALI was developed and validated across two samples of a total of 1009 participants with diverse demographics. The ALI comprises 15 scale items and exhibited good psychometric properties and conformed to the theoretical four-dimensional structure of attitudinal learning: cognitive, affective, behavioral, and social. The ALI was also shown to correlate with behavioral metrics of class engagement. Future uses of the new measure are discussed. Participants were taken from entirely online populations, and while demographically diverse, implementation of the scale with face-to-face instruction, in varied settings, and across different groups of learners is needed to provide additional evidence of its intended generalizability and consider possible biases.
Docetaxel is the main treatment for advanced castration‐resistant prostate cancer; however, resistance eventually occurs. The development of intratumoral drug‐resistant subpopulations possessing a ...cancer stem cell (CSC) morphology is an emerging mechanism of docetaxel resistance, a process driven by epithelial–mesenchymal transition (EMT). This study characterised EMT in docetaxel‐resistant sublines through increased invasion, MMP‐1 production and ZEB1 and ZEB2 expression. We also present evidence for differential EMT across PC‐3 and DU145 in vitro resistance models as characterised by differential migration, cell colony scattering and susceptibility to the CSC inhibitor salinomycin. siRNA manipulation of ZEB1 and ZEB2 in PC‐3 and DU145 docetaxel‐resistant sublines identified ZEB1, through its transcriptional repression of E‐cadherin, to be a driver of both EMT and docetaxel resistance. The clinical relevance of ZEB1 was also determined through immunohistochemical tissue microarray assessment, revealing significantly increased ZEB1 expression in prostate tumours following docetaxel treatment. This study presents evidence for a role of ZEB1, through its transcriptional repression of E‐cadherin to be a driver of both EMT and docetaxel resistance in docetaxel‐resistant prostate cancer. In addition, this study highlights the heterogeneity of prostate cancer and in turn emphasises the complexity of the clinical management of docetaxel‐resistant prostate cancer.
This study investigated both ZEB1 and ZEB2 in docetaxel‐resistant prostate cancer and provides strong evidence for ZEB1, through its transcriptional repression of E‐cadherin to be a driver of EMT and docetaxel resistance. This was clinically validated, with patients treated with docetaxel exhibiting increased ZEB1 tumour expression. We also identified differential EMT across resistance models, thereby highlighting the heterogeneity of docetaxel‐resistant prostate cancer.
The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa ...to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum
-glycan profiling was carried out on 117 prostate cancer patients' serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of
-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.
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