An Investigation of Some Changes in the Chemical composition of Arterial Tissue Which Correlate With the Development of Arteriosclerosis

Arteriosclerosis is one of the major health problems confronting people of middle and advanced age. The disorder, commonly called hardening of the arteries , is a contributing factor in more deaths than any other ailment. The profound alteration in the physical properties of arteries which comes about as a result of the sclerotic process suggests that equally important changes may take place in the chemical composition of the arterial tissue

The Case for Counting Cases

Reliable, consistent statistics on the number of cases with self-represented litigants do not exist. To address this knowledge gap, the National Center for State Courts, supported by a grant from the State Justice Institute, recently designed a reporting framework for state courts to count cases with self-represented litigants. At the most basic level, the framework includes two ways of counting cases: (1) a snapshot of current or last-known representation status at the time of disposition and (2) a retrospective analysis of representation status by party over the life of the case. The snapshot approach can be used by courts whose case-management systems overwrite the representation status of a party each time it changes, while the retrospective approach can be used by courts whose case-management systems keep a record of changes to the representation status of each party throughout the case. Preliminary data provided by five states show wide variation in the percentage of cases with self-represented litigants (SRLs), underlining the need for more states to report these statistics so that an accurate national picture can be developed. Consistent with anecdotal reports, the data show that domestic-relations cases are more likely than civil cases to have self-represented litigants

Do COX-2 inhibitors worsen renal function?

No, COX-2 inhibitors, as a class, do not worsen renal function for those without renal disease. Celecoxib is the only COX-2 inhibitor available, and it is associated with a lower risk of renal dysfunction and hypertension when compared with controls. Available data do not allow for adjusted risk assessment for patients with preexisting renal disease on COX-2 inhibitors (strength of recommendation [SOR]: A, based on meta-analysis)

Abnormal microglia and enhanced inflammation-related gene transcription in mice with conditional deletion of Ctcf in Camk2a-Cre-expressing neurons

CCCTC-binding factor (CTCF) is an 11 zinc finger DNA-binding domain protein that regulates gene expression by modifying 3D chromatin structure. Human mutations inCTCFcause intellectual disability and autistic features. Knocking outCtcfin mouse embryonic neurons is lethal by neonatal age, but the effects of CTCF deficiency in postnatal neurons are less well studied. We knocked outCtcfpostnatally in glutamatergic forebrain neurons under the control ofCamk2a-Cre. CtcfloxP/loxP;Camk2a-Cre+(CtcfCKO) mice of both sexes were viable and exhibited profound deficits in spatial learning/memory, impaired motor coordination, and decreased sociability by 4 months of age.CtcfCKO mice also had reduced dendritic spine density in the hippocampus and cerebral cortex. Microarray analysis of mRNA fromCtcfCKO mouse hippocampus identified increased transcription of inflammation-related genes linked to microglia. Separate microarray analysis of mRNA isolated specifically fromCtcfCKO mouse hippocampal neurons by ribosomal affinity purification identified upregulation of chemokine signaling genes, suggesting crosstalk between neurons and microglia inCtcfCKO hippocampus. Finally, we found that microglia inCtcfCKO mouse hippocampus had abnormal morphology by Sholl analysis and increased immunostaining for CD68, a marker of microglial activation. Our findings confirm thatCtcfKO in postnatal neurons causes a neurobehavioral phenotype in mice and provide novel evidence that CTCF depletion leads to overexpression of inflammation-related genes and microglial dysfunction.SIGNIFICANCE STATEMENTCCCTC-binding factor (CTCF) is a DNA-binding protein that organizes nuclear chromatin topology. Mutations inCTCFcause intellectual disability and autistic features in humans. CTCF deficiency in embryonic neurons is lethal in mice, but mice with postnatal CTCF depletion are less well studied. We find that mice lackingCtcfinCamk2a-expressing neurons (CtcfCKO mice) have spatial learning/memory deficits, impaired fine motor skills, subtly altered social interactions, and decreased dendritic spine density. We demonstrate thatCtcfCKO mice overexpress inflammation-related genes in the brain and have microglia with abnormal morphology that label positive for CD68, a marker of microglial activation. Our findings suggest that inflammation and dysfunctional neuron–microglia interactions are factors in the pathology of CTCF deficiency.</jats:p

Tissue plasminogen activator mRNA in murine tissues

AbstractThe urokinase-type and tissue-type plasminogen activators are the two enzymes found in mammals, which specifically convert the zymogen plasminogen to plasmin. Using cDNA probes, we have assayed for the presence of the two types of plasminogen activator mRNAs in murine tissues. We demonstrate that tissue-type plasminogen activator mRNA can be detected in a wide variety of tissues. In contrast, the accumulation of urokinase-type plasminogen activator mRNA is observed in only a few of the tissues analyzed. Using an S1 nuclease assay, we demonstrate that the tPA mRNA detected contains the complete sequences encoding the non-protease finger, growth-factor and kringle domains

Atrazine Transport Within a Coastal Zone in Southeastern Puerto Rico: a Sensitivity Analysis of an Agricultural Field Model and Riparian Zone Management Model

Agrichemical runoff from farmland may adversely impact coastal water quality. Two models, the Agricultural Policy/Environmental eXtender (APEX) and the Riparian Ecosystem Management Model (REMM), were used to evaluate the movement of the herbicide atrazine to the Jobos Bay National Estuarine Research Reserve from adjacent fields. The reserve is located on Puerto Rico’s southeast coast. Edge-of-field atrazine outputs simulated with the APEX were routed through a grass-forest buffer using the REMM. Atrazine DT50 (half-life) values measured in both field and buffer soils indicated that accelerated degradation conditions had developed in the field soil due to repeated atrazine application. APEX simulations examined both the measured field and buffer soil atrazine DT50 and the model’s default value. The use of the measured field soil atrazine degradation rate in the APEX resulted in 33 % lower atrazine transport from the field. REMMsimulations indicated that the buffer system had the potential to reduce dissolved atrazine transport in surface runoff by 77%during non-tropical stormevents by increasing infiltration, slowing transport, and increasing time for pesticide degradation. During a large runoff event due to a tropical stormthat occurred close to the time of an atrazine application, the REMM simulated only a 37 % reduction in atrazine transport. The results indicate that large storm events soon after herbicide application likely dominate herbicide transport to coastal waters in the region. These results agree with water quality measurements in the reserve. This study demonstrated the sensitivity of these models to variations in DT50 values in evaluating atrazine fate and transport in the region and emphasizes that the use of measured DT50 values can improve model accuracy

Topographic, Bioclimatic, and Vegetation Characteristics of Three Ecoregion Classification Systems in North America: Comparisons Along Continent-wide Transects

Ecoregion classification systems are increasingly used for policy and management decisions, particularly among conservation and natural resource managers. A number of ecoregion classification systems are currently available, with each system defining ecoregions using different classification methods and different types of data. As a result, each classification system describes a unique set of ecoregions. To help potential users choose the most appropriate ecoregion system for their particular application, we used three latitudinal transects across North America to compare the boundaries and environmental characteristics of three ecoregion classification systems [Küchler, World Wildlife Fund (WWF), and Bailey]. A variety of variables were used to evaluate the three systems, including woody plant species richness, normalized difference in vegetation index (NDVI), and bioclimatic variables (e.g., mean temperature of the coldest month) along each transect. Our results are dominated by geographic patterns in temperature, which are generally aligned north–south, and in moisture, which are generally aligned east–west. In the west, the dramatic changes in physiography, climate, and vegetation impose stronger controls on ecoregion boundaries than in the east. The Küchler system has the greatest number of ecoregions on all three transects, but does not necessarily have the highest degree of internal consistency within its ecoregions with regard to the bioclimatic and species richness data. In general, the WWF system appears to track climatic and floristic variables the best of the three systems, but not in all regions on all transects

Large scale variation in DNA copy number in chicken breeds

Background Detecting genetic variation is a critical step in elucidating the molecular mechanisms underlying phenotypic diversity. Until recently, such detection has mostly focused on single nucleotide polymorphisms (SNPs) because of the ease in screening complete genomes. Another type of variant, copy number variation (CNV), is emerging as a significant contributor to phenotypic variation in many species. Here we describe a genome-wide CNV study using array comparative genomic hybridization (aCGH) in a wide variety of chicken breeds. Results We identified 3,154 CNVs, grouped into 1,556 CNV regions (CNVRs). Thirty percent of the CNVs were detected in at least 2 individuals. The average size of the CNVs detected was 46.3 kb with the largest CNV, located on GGAZ, being 4.3 Mb. Approximately 75% of the CNVs are copy number losses relatively to the Red Jungle Fowl reference genome. The genome coverage of CNVRs in this study is 60 Mb, which represents almost 5.4% of the chicken genome. In particular large gene families such as the keratin gene family and the MHC show extensive CNV. Conclusions A relative large group of the CNVs are line-specific, several of which were previously shown to be related to the causative mutation for a number of phenotypic variants. The chance that inter-specific CNVs fall into CNVRs detected in chicken is related to the evolutionary distance between the species. Our results provide a valuable resource for the study of genetic and phenotypic variation in this phenotypically diverse species

Aberrant Schwann Cell Lipid Metabolism Linked to Mitochondrial Deficits Leads to Axon Degeneration and Neuropathy

SummaryMitochondrial dysfunction is a common cause of peripheral neuropathy. Much effort has been devoted to examining the role played by neuronal/axonal mitochondria, but how mitochondrial deficits in peripheral nerve glia (Schwann cells [SCs]) contribute to peripheral nerve diseases remains unclear. Here, we investigate a mouse model of peripheral neuropathy secondary to SC mitochondrial dysfunction (Tfam-SCKOs). We show that disruption of SC mitochondria activates a maladaptive integrated stress response (ISR) through the actions of heme-regulated inhibitor (HRI) kinase, and causes a shift in lipid metabolism away from fatty acid synthesis toward oxidation. These alterations in SC lipid metabolism result in depletion of important myelin lipid components as well as in accumulation of acylcarnitines (ACs), an intermediate of fatty acid β-oxidation. Importantly, we show that ACs are released from SCs and induce axonal degeneration. A maladaptive ISR as well as altered SC lipid metabolism are thus underlying pathological mechanisms in mitochondria-related peripheral neuropathies