3,245 research outputs found
Competition and adverse selection in the small-dollar loan market: Overdraft versus payday credit
We find that competition from payday lenders leads depository institutions to raise overdraft fees and reduce the availability of 'free' checking accounts. We attribute this rise in prices partly to adverse selection created by banks' practice of charging a flat fee regardless of the overdraft amount - pricing that favors depositors prone to large overdrafts. Payday credit is priced per dollar borrowed, so when that option is available, depositors prone to small overdrafts switch. That selection works against banks; large overdrafts cost more to supply and, if depositors default, banks lose more, so prices rise. Consistent with this adverse selection hypothesis, we document that the average dollar amount per returned check at banks and other depository institutions increases when depositors have access to payday credit. Our findings illuminate competition and pricing frictions in the large, yet largely unstudied, small-dollar loan market
FRESH VEGETABLE PRICE LINKAGE BETWEEN GROWER/SHIPPERS, WHOLESALERS AND RETAILERS
This study focused on the transmission of price adjustments between grower/shippers and wholesalers and between wholesale handlers and retailers of nine fresh vegetables (only the results associated with bell peppers are reported in this paper). Results among the nine vegetable products were not consistent with respect to the magnitude of adjustments or the time periods involved in the adjustments. In response to wholesale price changes, upward price adjustments at the retail level occur more quickly than do downward price adjustments. Price transmission relationships also varied among the vegetable products between the wholesaler and grower. Overall, the results indicate that factors in addition to changes in upstream prices are impacting retailers' and wholesalers' pricing decisions.Demand and Price Analysis,
Infection of neuronal cells by Chlamydia pneumoniae and Herpes simplex virus type 1 alters expression of genes associated with Alzheimer’s disease
Several studies have suggested an infectious etiology for Alzheimer’s disease (AD). We have been investigating a potential role for both Chlamydia pneumoniae and Herpes simplex virus type 1 (HSV1) in the initiation of sporadic late-onset AD. Our current study focuses on investigation of gene expression using Alzheimer-specific Real-Time PCR microarrays on RNA derived from SKNMC human neuronal cells infected with C. pneumoniae and/or HSV1. There are distinct differences in the patterns of gene regulation by the two pathogens. For example, C. pneumoniae induces expression of genes involved in amyloid production and processing, such as β-amyloid precursor protein (APP), β-site APP-cleaving enzyme 1 (BACE1), a γ-secretase complex protein (nicastrin [NCSTN]), NEDD8 activating enzyme E1 (NAE1), as well as a mitochondria-associated protein (hydroxysteroid (17-β) dehydrogenase 10 [HSD17B10]), α-2-macroglobulin (A2M) and the metallopeptidase ADAM9. Conversely, HSV1 tends to down-regulate expression of many genes, including those encoding a component of the γ-secretase complex (anterior pharynx defective 1 homolog A [APH1A]), low density lipoprotein related proteins (LRP1, LRP6, and LRP8), β-synuclein (SNCB) and ubiquinols (UQCRC1, UQCRC2). Co-infection with C. pneumoniae and HSV-1 produced a greater down-regulation of gene expression than that seen with HSV1 alone for several genes, including APP-like proteins (APLP1, APLP2) and kinases (cell division cycle 2 protein [CDC2], cyclin-dependent kinase [CDK5] and CDC2-related kinase [CDKL1]). Our data indicate that both C. pneumoniae and HSV1 can modulate expression of genes associated with AD, and thus could contribute to AD pathology, however these two pathogens likely act via different pathways. Furthermore, for several genes, co-infection with both C. pneumoniae and HSV1 appears to exacerbate the changes in gene expression seen with HSV1 alone.https://digitalcommons.pcom.edu/posters/1007/thumbnail.jp
Biomechanical, ultrastructural, and electrophysiological characterization of the non-human primate experimental glaucoma model.
Laser-induced experimental glaucoma (ExGl) in non-human primates (NHPs) is a common animal model for ocular drug development. While many features of human hypertensive glaucoma are replicated in this model, structural and functional changes in the unlasered portions of trabecular meshwork (TM) of laser-treated primate eyes are understudied. We studied NHPs with ExGl of several years duration. As expected, ExGl eyes exhibited selective reductions of the retinal nerve fiber layer that correlate with electrophysiologic measures documenting a link between morphologic and elctrophysiologic endpoints. Softening of unlasered TM in ExGl eyes compared to untreated controls was observed. The degree of TM softening was consistent, regardless of pre-mortem clinical findings including severity of IOP elevation, retinal nerve fiber layer thinning, or electrodiagnostic findings. Importantly, this softening is contrary to TM stiffening reported in glaucomatous human eyes. Furthermore, microscopic analysis of unlasered TM from eyes with ExGl demonstrated TM thinning with collapse of Schlemm's canal; and proteomic analysis confirmed downregulation of metabolic and structural proteins. These data demonstrate unexpected and compensatory changes involving the TM in the NHP model of ExGl. The data suggest that compensatory mechanisms exist in normal animals and respond to elevated IOP through softening of the meshwork to increase outflow
Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics
The 30S ribosomal subunit has two primary functions in protein synthesis. It discriminates against aminoacyl transfer RNAs that do not match the codon of messenger RNA, thereby ensuring accuracy in translation of the genetic message in a process called decoding. Also, it works with the 50S subunit to move the tRNAs and associated mRNA by precisely one codon, in a process called translocation. Here we describe the functional implications of the high-resolution 30S crystal structure presented in the accompanying paper, and infer details of the interactions between the 30S subunit and its tRNA and mRNA ligands. We also describe the crystal structure of the 30S subunit complexed with the antibiotics paromomycin, streptomycin and spectinomycin, which interfere with decoding and translocation. This work reveals the structural basis for the action of these antibiotics, and leads to a model for the role of the universally conserved 16S RNA residues A1492 and A1493 in the decoding process
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Prevalence and diversity of TAL effector-like proteins in fungal endosymbiotic Mycetohabitans spp.
Endofungal Mycetohabitans (formerly Burkholderia) spp. rely on a type III secretion system to deliver mostly unidentified effector proteins when colonizing their host fungus, Rhizopus microsporus. The one known secreted effector family from Mycetohabitans consists of homologues of transcription activator-like (TAL) effectors, which are used by plant pathogenic Xanthomonas and Ralstonia spp. to activate host genes that promote disease. These 'Burkholderia TAL-like (Btl)' proteins bind corresponding specific DNA sequences in a predictable manner, but their genomic target(s) and impact on transcription in the fungus are unknown. Recent phenotyping of Btl mutants of two Mycetohabitans strains revealed that the single Btl in one Mycetohabitans endofungorum strain enhances fungal membrane stress tolerance, while others in a Mycetohabitans rhizoxinica strain promote bacterial colonization of the fungus. The phenotypic diversity underscores the need to assess the sequence diversity and, given that sequence diversity translates to DNA targeting specificity, the functional diversity of Btl proteins. Using a dual approach to maximize capture of Btl protein sequences for our analysis, we sequenced and assembled nine Mycetohabitans spp. genomes using long-read PacBio technology and also mined available short-read Illumina fungal-bacterial metagenomes. We show that btl genes are present across diverse Mycetohabitans strains from Mucoromycota fungal hosts yet vary in sequences and predicted DNA binding specificity. Phylogenetic analysis revealed distinct clades of Btl proteins and suggested that Mycetohabitans might contain more species than previously recognized. Within our data set, Btl proteins were more conserved across M. rhizoxinica strains than across M. endofungorum, but there was also evidence of greater overall strain diversity within the latter clade. Overall, the results suggest that Btl proteins contribute to bacterial-fungal symbioses in myriad ways
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Multivariate Models of Adult Pacific Salmon Returns
Most modeling and statistical approaches encourage simplicity, yet ecological processes are often complex, as they are influenced by numerous dynamic environmental and biological factors. Pacific salmon abundance has been highly variable over the last few decades and most forecasting models have proven inadequate, primarily because of a lack of understanding of the processes affecting variability in survival. Better methods and data for predicting the abundance of returning adults are therefore required to effectively manage the species. We combined 31 distinct indicators of the marine environment collected over an 11-year period into a multivariate analysis to summarize and predict adult spring Chinook salmon returns to the Columbia River in 2012. In addition to forecasts, this tool quantifies the strength of the relationship between various ecological indicators and salmon returns, allowing interpretation of ecosystem processes. The relative importance of indicators varied, but a few trends emerged. Adult returns of spring Chinook salmon were best described using indicators of bottom-up ecological processes such as composition and abundance of zooplankton and fish prey as well as measures of individual fish, such as growth and condition. Local indicators of temperature or coastal upwelling did not contribute as much as large-scale indicators of temperature variability, matching the spatial scale over which salmon spend the majority of their ocean residence. Results suggest that effective management of Pacific salmon requires multiple types of data and that no single indicator can represent the complex early-ocean ecology of salmon
NR4A Nuclear Receptors Support Memory Enhancement by Histone Deacetylase Inhibitors
The formation of a long-lasting memory requires a transcription-dependent consolidation period that converts a short-term memory into a long-term memory. Nuclear receptors compose a class of transcription factors that regulate diverse biological processes, and several nuclear receptors have been implicated in memory formation. Here, we examined the potential contribution of nuclear receptors to memory consolidation by measuring the expression of all 49 murine nuclear receptors after learning. We identified 13 nuclear receptors with increased expression after learning, including all 3 members of the Nr4a subfamily. These CREB-regulated Nr4a genes encode ligand-independent “orphan” nuclear receptors. We found that blocking NR4A activity in memory-supporting brain regions impaired long-term memory but did not impact short-term memory in mice. Further, expression of Nr4a genes increased following the memory-enhancing effects of histone deacetylase (HDAC) inhibitors. Blocking NR4A signaling interfered with the ability of HDAC inhibitors to enhance memory. These results demonstrate that the Nr4a gene family contributes to memory formation and is a promising target for improving cognitive function
Diminished Bone Formation During Diabetic Fracture Healing Is Related to the Premature Resorption of Cartilage Associated with Increased Osteoclast Activity
Histological and molecular analysis of fracture healing in normal and diabetic animals showed significantly enhanced removal of cartilage in diabetic animals. Increased cartilage turnover was associated with elevated osteoclast numbers, a higher expression of genes that promote osteoclastogenesis, and diminished primary bone formation. Introduction Diminished bone formation, an increased incidence of nonunions, and delayed fracture healing have been observed in animal models and in patients with diabetes. Fracture healing is characterized by the formation of a stabilizing callus in which cartilage is formed and then resorbed and replaced by bone. To gain insight into how diabetes affects fracture healing, studies were carried out focusing on the impact of diabetes on the transition from cartilage to bone. Materials and Methods A low-dose treatment protocol of streptozotocin in CD-1 mice was used to induce a type 1 diabetic condition. After mice were hyperglycemic for 3 weeks, controlled closed simple transverse fractures of the tibia were induced and fixed by intramedullary pins. Histomorphometric analysis of the tibias obtained 12, 16, and 22 days after fracture was performed across the fracture callus at 0.5 mm proximal and distal increments using computer-assisted image analysis. Another group of 16-day samples were examined by μCT. RNA was isolated from a separate set of animals, and the expression of genes that reflect the formation and removal of cartilage and bone was measured by real-time PCR. Results Molecular analysis of collagen types II and X mRNA expression showed that cartilage formation was the same during the initial period of callus formation. Histomorphometric analysis of day 12 fracture calluses showed that callus size and cartilage area were also similar in normoglycemic and diabetic mice. In contrast, on day 16, callus size, cartilage tissue, and new bone area were 2.0-, 4.4-, and 1.5-fold larger, respectively, in the normoglycemic compared with the diabetic group (p \u3c 0.05). Analysis of μCT images indicated that the bone volume in the normoglycemic animals was 38% larger than in diabetic animals. There were 78% more osteoclasts in the diabetic group compared with the normoglycemic group (p \u3c 0.05) on day 16, consistent with the reduction in cartilage. Real-time PCR showed significantly elevated levels of mRNA expression for TNF-α, macrophage-colony stimulating factor, RANKL, and vascular endothelial growth factor-A in the diabetic group. Similarly, the mRNA encoding ADAMTS 4 and 5, major aggrecanases that degrade cartilage, was also elevated in diabetic animals. Conclusions These results suggest that impaired fracture healing in diabetes is characterized by increased rates of cartilage resorption. This premature loss of cartilage leads to a reduction in callus size and contributes to decreased bone formation and mechanical strength frequently reported in diabetic fracture healing
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