Examine race and personal exposure to Alzheimer's Disease (AD) on projected memory failure attributions and medical help-seeking thresholds of pre-morbid adults. The goal is to better understand race ...discrepancies in help-seeking for those potentially at risk for early-onset AD.
498 adults aged 40 to 65 (M = 52.27), screened for current memory failure, completed an online questionnaire exploring their help-seeking intentions and threshold, attributions of hypothetical memory failures, and level of AD concern.
Non-Hispanic Whites (n = 248) were significantly more concerned about AD than African Americans (n = 250) (p =.027). Personal exposure to AD moderated the impact of race on memory failure attributions (p =.036), so that personal exposure was more influential for African Americans. Those who were more likely to attribute hypothetical memory failures to AD had lower projected thresholds for seeking a medical evaluation (p =.010). Memory failure attribution emerged as a potential mediator of the impact of race on projected help-seeking behaviors (p =.057).
African Americans were more influenced by personal experience when considering the causes of hypothetical memory failures.
Healthcare providers should emphasize to African American families the value of early AD detection and treatment in terms of quality of life for both patient and caregiver.
This thesis examines the narratival influence of Perrault’s “Bluebeard” fairy tale regarding women’s sexual agency and empowerment. Over time, the villainous serial killer Bluebeard has been ...transformed into a romantic figure, a transformation which has troubled some critics. However, I argue that this transformation when viewed through the Marquis de Sade’s philosophy instead serves to help women, as becomes apparent when contextualizing Sadeian philosophy with Thomas Harris’s The Silence of the Lambs and Hannibal.
Hematopoietic development and cell fate choices are regulated by signals from the extracellular environment. This study focuses on two developmental checkpoints in the hematopoietic system that are ...characterized by unique proliferative stages: (1) The DN3 (double negative 3) to DP (double positive) transition, otherwise known as β-selection, in T cell development and (2) The regulation of self-renewal in long-term hematopoietic stem cells. This thesis tests the hypothesis that Akt, a serine/threonine kinase, is required for both of these proliferative stages of hematopoietic development. The first set of experiments test whether a constitutively active Akt molecule is sufficient to rescue survival, proliferation, and differentiation in a mouse model that fails to generate mature T cells due to a block at the DN3 stage. In the second set of experiments, we ask if Akt is necessary for T cell development, specifically at the DN3 to DP transition. After defining the biological role for Akt signaling in thymocyte development, we next determine whether Akt also has a similar role in the development of other hematopoietic lineages. The hematopoietic stem cell pool is another exquisitely regulated developmental stage in hematopoiesis that is dependent on cell survival and proliferation. In the last set of experiments, we test the hypothesis that Akt would also be required for maintenance of the most primitive hematopoietic stem cell. In summary, we found that Akt is sufficient to promote differentiation to the DP stage in the absence of signals from the pre-TCR, and that Akt1 and Akt2 are also required for differentiation at the same pre-TCR mediated checkpoint. The biological role of Akt in T cell development is similar to its function in long-term hematopoietic stem cells (LT-HSCs). LT-HSCs require Akt signals to maintain self-renewal and survival of more mature progenitor cells. In conclusion, these studies provide evidence that Akt is required in proliferating hematopoietic cells during development, but is not required at the more quiescent stage of hematopoiesis.
This is my review of Jes Battis's book Thinking Queerly: Medievalism, Wizardry, and Neurodiversity in Young Adult Texts. Battis's book reads beautifully and easily, even if you are not well-versed in ...disability studies or queer theory, and I imagine that even a reader who is not especially knowledgeable about either medievalisms or YA literature could also follow along well. This book is written in an uncommonly accessible, even conversational style, that is utterly enthralling, and yet Battis's work still shows impressive scholarly rigor and scope. If I were to describe the book in a single sentence, it would be this one: Jes Battis thoughtfully and successfully navigates a broad array of texts, both medieval and modern, to paint a compelling portrait of the traditional wizard figure, adolescence, neurodiversity, and pedagogical concerns in the field of medieval studies.
Leiomyosarcoma is a malignant neoplasm with smooth muscle differentiation. Little is known about its molecular heterogeneity and no targeted therapy currently exists for leiomyosarcoma. Recognition ...of different molecular subtypes is necessary to evaluate novel therapeutic options. In a previous study on 51 leiomyosarcomas, we identified three molecular subtypes in leiomyosarcoma. The current study was performed to determine whether the existence of these subtypes could be confirmed in independent cohorts.
Ninety-nine cases of leiomyosarcoma were expression profiled with 3'end RNA-Sequencing (3SEQ). Consensus clustering was conducted to determine the optimal number of subtypes.
We identified 3 leiomyosarcoma molecular subtypes and confirmed this finding by analyzing publically available data on 82 leiomyosarcoma from The Cancer Genome Atlas (TCGA). We identified two new formalin-fixed, paraffin-embedded tissue-compatible diagnostic immunohistochemical markers; LMOD1 for subtype I leiomyosarcoma and ARL4C for subtype II leiomyosarcoma. A leiomyosarcoma tissue microarray with known clinical outcome was used to show that subtype I leiomyosarcoma is associated with good outcome in extrauterine leiomyosarcoma while subtype II leiomyosarcoma is associated with poor prognosis in both uterine and extrauterine leiomyosarcoma. The leiomyosarcoma subtypes showed significant differences in expression levels for genes for which novel targeted therapies are being developed, suggesting that leiomyosarcoma subtypes may respond differentially to these targeted therapies.
We confirm the existence of 3 molecular subtypes in leiomyosarcoma using two independent datasets and show that the different molecular subtypes are associated with distinct clinical outcomes. The findings offer an opportunity for treating leiomyosarcoma in a subtype-specific targeted approach.
Abstract
Sin or public health taxes are excise taxes imposed on the consumption of potentially harmful goods for health sugar-sweetened beverages (SSBs), tobacco, alcohol, among others, aiming to ...reduce consumption, raise additional revenue and/or improve population health. This paper assesses the extent to which sin taxes (a) can reduce consumption of potentially harmful goods, (b) raise revenue for national health systems and (c) contribute to population health in Latin America. A systematic literature review was conducted on peer-reviewed and grey literature; endpoints included: impact of raising sin taxes on consumption, ability to raise revenue for health and the possibility of population health improvements. Risk of bias for each study was assessed. The synthesis of the literature on sin tax implementation showed improvements in all three endpoints across the study countries. Following the introduction of sin taxes or by simulating their potential impact, nearly all studies explicitly reported that consumption of potentially harmful goods (mainly SSBs and tobacco) declined; revenue was found to have increased in almost all countries, suggesting that there may be additional scope for further tax increase. Simulated improvements in population health have also been shown, by demonstrating a relationship between sin tax increases and reduction in prevalence of diabetes, stroke, heart attacks and associated deaths. However, sin tax effects on health would be better quantified over the long-term. Data quality and availability challenges did place some limitations on sin tax impact assessment. Sin taxes can be effective in reducing consumption of potentially harmful goods, improve population health and generate additional revenue. Promoting further research on this topic should be a priority.
The self-assembled layer-by-layer technique has attracted a great deal of attention as a method for engineering bio-functional surfaces under mild chemical conditions. The production of multilayer ...films, starting from newly designed building blocks, may be laborious, considering the inherent limitations for anticipating how minimal changes in the macromolecular composition may impact both film deposition and performance. This paper presents an automated, high-throughput approach to depositing polyelectrolyte multilayers (PEMs) in multiwell plates, enabling the screening of nearly 100 film formulations in the same process. This high-throughput layer-by-layer (HT-LbL) method runs in an affordable, fully commercial platform using Python-coded routines that can be easily adapted for the materials science lab settings. The HT-LbL system was validated by investigating the deposition of polysaccharide-based films in multiwell plates, probing the absorbance signal of ionically stained polyelectrolyte multilayers (PEMs) prepared in one single batch. The HT-LbL method was also used to investigate the deposition of PEMs with a small library of genetically engineered elastin-like polypeptides (ELPs) with different levels of ionizable and hydrophobic amino acid residues. The deposition of ELP/chitosan films was assessed based on the signal of fluorescently labeled species (chitosan or ELP-mCherry), demonstrating that both electrostatic and hydrophobic residues are essential for film buildup. The growth and surface properties of ELP-mCherry/chitosan films also seemed susceptible to the assembly pH, forming a higher film growth and a rougher and more hydrophobic surface for both polyelectrolytes deposited under a low ionization degree. Overall, this study illustrates the challenge of predicting the growth and properties of multilayer films and how the HT-LbL can accelerate the development of multilayer films that demand high levels of testing and optimization.
Diamond Blackfan Anemia (DBA) is an inherited bone marrow failure syndrome with clinical features of red cell aplasia and variable developmental abnormalities. Most affected patients have ...heterozygous loss of function mutations in ribosomal protein genes but the pathogenic mechanism is still unknown. We generated induced pluripotent stem cells from DBA patients carrying RPS19 or RPL5 mutations. Transcriptome analysis revealed the striking dysregulation of the transforming growth factor β (TGFβ) signaling pathway in DBA lines. Expression of TGFβ target genes, such as TGFBI, BAMBI, COL3A1 and SERPINE1 was significantly increased in the DBA iPSCs. We quantified intermediates in canonical and non-canonical TGFβ pathways and observed a significant increase in the levels of the non-canonical pathway mediator p-JNK in the DBA iPSCs. Moreover, when the mutant cells were corrected by ectopic expression of WT RPS19 or RPL5, levels of p-JNK returned to normal. Surprisingly, nuclear levels of SMAD4, a mediator of canonical TGFβ signaling, were decreased in DBA cells due to increased proteolytic turnover. We also observed the up-regulation of TGFβ1R, TGFβ2, CDKN1A and SERPINE1 mRNA, and the significant decrease of GATA1 mRNA in the primitive multilineage progenitors. In summary our observations identify for the first time a dysregulation of the TGFβ pathway in the pathobiology of DBA.
Diamond Blackfan anemia (DBA) is a congenital disorder with erythroid (Ery) hypoplasia and tissue morphogenic abnormalities. Most DBA cases are caused by heterozygous null mutations in genes encoding ...ribosomal proteins. Understanding how haploinsufficiency of these ubiquitous proteins causes DBA is hampered by limited availability of tissues from affected patients. We generated induced pluripotent stem cells (iPSCs) from fibroblasts of DBA patients carrying mutations in RPS19 and RPL5. Compared with controls, DBA fibroblasts formed iPSCs inefficiently, although we obtained 1 stable clone from each fibroblast line. RPS19-mutated iPSCs exhibited defects in 40S (small) ribosomal subunit assembly and production of 18S ribosomal RNA (rRNA). Upon induced differentiation, the mutant clone exhibited globally impaired hematopoiesis, with the Ery lineage affected most profoundly. RPL5-mutated iPSCs exhibited defective 60S (large) ribosomal subunit assembly, accumulation of 12S pre-rRNA, and impaired erythropoiesis. In both mutant iPSC lines, genetic correction of ribosomal protein deficiency via complementary DNA transfer into the “safe harbor” AAVS1 locus alleviated abnormalities in ribosome biogenesis and hematopoiesis. Our studies show that pathological features of DBA are recapitulated by iPSCs, provide a renewable source of cells to model various tissue defects, and demonstrate proof of principle for genetic correction strategies in patient stem cells.
•Ribosome biogenesis and hematopoiesis are impaired in iPSCs from DBA patients.•The abnormalities of DBA iPSCs are ameliorated by genetic restoration of the defective ribosomal protein genes.
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