244 research outputs found
Do You Know What You Owe? Students\u27 Understanding of Their Student Loans
Using a data set that augments a student survey with administrative data from the Iowa State University Office of Financial Aid, the authors posed two questions: Do students know whether they have student loans? Do students know how much they owe on outstanding student loans? We used logistic and ordered logit regressions to answer these questions. Results suggest that although the majority of students are aware that they owe on student loans, many underestimate the amount they owe. One eighth of students in the current study reported no student debt when, in fact, they had a loan. Over a quarter of the students underestimated the amount they owed by less than 10,000. This article discusses the roles that counselors, educators, and policy makers can play in improving students’ understanding of their student loan debt
An Orally Active Galectin-3 Antagonist Inhibits Lung Adenocarcinoma Growth and Augments Response to PD-L1 Blockade
A combination therapy approach is required to improve tumor immune infiltration and patient response to immune checkpoint inhibitors that target negative regulatory receptors. Galectin-3 is a β-galactoside-binding lectin that is highly expressed within the tumor microenvironment of aggressive cancers and whose expression correlates with poor survival particularly in patients with non-small cell lung cancer (NSCLC). To examine the role of galectin-3 inhibition in NSCLC, we tested the effects of galectin-3 depletion using genetic and pharmacologic approaches on syngeneic mouse lung adenocarcinoma and human lung adenocarcinoma xenografts. Galectin-3-/- mice developed significantly smaller and fewer tumors and metastases than syngeneic C57/ Bl6 wild-type mice. Macrophage ablation retarded tumor growth, whereas reconstitution with galectin-3-positive bone marrow restored tumor growth in galectin-3-/- mice, indicating that macrophages were a major driver of the antitumor response. Oral administration of a novel small molecule galectin-3 inhibitor GB1107 reduced human and mouse lung adenocarcinoma growth and blocked metastasis in the syngeneic model. Treatment with GB1107 increased tumor M1 macrophage polarization and CD8 + T-cell infiltration. Moreover, GB1107 potentiated the effects of a PD-L1 immune checkpoint inhibitor to increase expression of cytotoxic (IFNγ, granzyme B, perforin-1, Fas ligand) and apoptotic (cleaved caspase-3) effector molecules. In summary, galectin-3 is an important regulator of lung adenocarcinoma progression. The novel galectin-3 inhibitor presented could provide an effective, nontoxic monotherapy or be used in combination with immune checkpoint inhibitors to boost immune infiltration and responses in lung adenocarcinoma and potentially other aggressive cancers. Significance: A novel and orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and metastasis and augments response to PD-L1 blockade
Aptamer-based multiplexed proteomic technology for biomarker discovery
Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine
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Large contribution of supercooled liquid clouds to the solar radiation budget of the Southern Ocean
The Southern Ocean is a critical region for global climate, yet large cloud and solar radiation biases over the Southern Ocean are a long-standing problem in climate models and are poorly understood, leading to biases in simulated sea surface temperatures. This study shows that supercooled liquid clouds are central to understanding and simulating the Southern Ocean environment. A combination of satellite observational data and detailed radiative transfer calculations is used to quantify the impact of cloud phase and cloud vertical structure on the reflected solar radiation in the Southern Hemisphere summer. It is found that clouds with supercooled liquid tops dominate the population of liquid clouds. The observations show that clouds with supercooled liquid tops contribute between 27% and 38% to the total reflected solar radiation between 40° and 70°S, and climate models are found to poorly simulate these clouds. The results quantify the importance of supercooled liquid clouds in the Southern Ocean environment and highlight the need to improve understanding of the physical processes that control these clouds in order to improve their simulation in numerical models. This is not only important for improving the simulation of present-day climate and climate variability, but also relevant for increasing confidence in climate feedback processes and future climate projections
Exosome signalling in the kidney
Urine contains exosomes originating from the circulation and all cells lining the
urinary tract. Exosomes are a route of inter-cellular communication along the
nephron potentially able to transfer of protein and/or RNA. It is not known whether
this is a regulated process analogous to other cell-to-cell signalling systems. The
aims of this study were to develop nanoparticle tracking analysis (NTA) as a
technique to quantify exosomes in urine. Secondly, the hormonal regulation of
exosome uptake in vitro and in vivo was investigated. Thirdly, exosome excretion in
a central diabetes insipidus (DI) patient and a patient group after radiocontrast
exposure was measured to investigate exosome excretion along the kidney in injury.
Using the fluorescent capabilities of NTA, urinary exosomes were quantified in urine
samples. NTA was able to detect changes in aquaporin 2 levels in vitro and in vivo.
Storage conditions for human urinary exosomes were also optimised using NTA. A
kidney cortical collecting duct cell line (CCDs) was used to model regulation of
exosome uptake in vitro. CCDs were stimulated with desmopressin, a vasopressin
analogue, and uptake of fluorescently-loaded or microRNA-loaded exosomes was
measured. Desmopressin stimulated exosome uptake into collecting duct cells via V2
receptor stimulation. Intra-cellular uptake of exosomes was confirmed by microRNA
specific mRNA down-regulation. Mechanistically, exosome uptake in response to
desmopressin required cyclic AMP production, was mediated by clathrin-dependent
endocytosis and was selective for exosomes from kidney tubular cells. In mice,
fluorescently-loaded exosomes were systemically injected before and after
administration of the V2 antagonist, tolvaptan, and urinary exosome excretion was
measured. Basally, 2.5% of injected exosomes were recovered in urine; tolvaptan
treatment resulted in a 5-fold increase. By combining antibodies to nephron segment-specific
proteins with NTA we measured human urinary exosome excretion in
central diabetes insipidus (DI) and after radiocontrast exposure (n=37). In DI,
desmopressin reduced the excretion of exosomes derived from upstream glomerular
and proximal tubule cells. In patients exposed to radiocontrast, urinary exosomes
from the glomerulus were positively correlated with the tubular injury markers KIM-
1 and NGAL.
These findings therefore show that tubular exosome uptake is a specific, hormonally
regulated process that is reduced with injury. Physiologically, exosomes are a
mechanism of inter-cellular communication; therapeutically, exosomes represent a
novel vehicle by which RNA therapy could be targeted for the treatment of kidney
disease
Self-Reported Time in Bed and Sleep Quality in Association with Internalizing and Externalizing Symptoms in School-Age Youth
This study investigated the relationship between self-reported time in bed and sleep quality in association with self-reported internalizing and externalizing symptoms in a sample of 285 elementary school students (52% female) recruited from a rural Midwestern elementary school. Path models were used to estimate proposed associations, controlling for grade level and gender. Curvilinear associations were found between time in bed and anxiety, depressive symptoms, and irritability. Marginal curvilinear trends were found between time in bed and emotion dysregulation, reactive aggression, and proactive aggression. Sleep quality was negatively associated with anxiety, depressive symptoms, irritability, reactive aggression, and delinquency engagement. Gender and grade differences were found across models. Findings suggest that examining self-reported time in bed (both linear and quadratic) and sleep quality is important for understanding internalizing and externalizing symptoms associated with sleep in school-age youth. Incorporating self-reported sleep assessments into clinical practice and school-based evaluations may have implications for a child’s adjustment
R/Avr gene expression study of Rpi-vnt1.1 transgenic potato resistant to the Phytophthora infestans clonal lineage EC-1
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