1,331 research outputs found

    Preemption in the Rehnquist and Roberts Courts: An Empirical Analysis

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    This article presents an empirical analysis of the Rehnquist Court’s and the Roberts Court’s decisions on the federal (statutory) preemption of state law. In addition to raw outcomes for or against preemption, we examine cases by subject-matter, level of judicial consensus, tort versus regulatory preemption, party constellation, and origin in state or federal court. We present additional data and analysis on the role of state amici and of the U.S. Solicitor General in preemption cases, and we examine individual justices’ voting records. Among our findings, one stands out: over time and especially under the Roberts Court, lawyerly preemption questions have assumed a distinctly ideological flavor. Preemption cases are much more likely to be contested than they were in earlier decades; and in those cases, once-rare judicial bloc voting has become common

    Analyzing the Effects of Body Mass Index in Total Hip Arthroplasty Cases. Does it Influence Patient Characteristics, Operative Planning, and Postoperative Outcomes?

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    Background: Total hip arthroplasty (THA) is one of the most performed orthopaedic procedures commonly used for the treatment of osteoarthritis (OA). There are several underlying factors that lead to the formation of this condition. Not only is obesity one of the main contributors, but it is also a modifiable risk factor and one of the leading causes of end-stage arthrosis of the hip. Though there have been advancements in agricultural and health technologies, rates of obesity continue to rise causing similar increases in the demands for hip replacement surgeries. Therefore, we sought to investigate the effects of BMI on THA procedures and determine if it plays any influential role in patient characteristics, operative planning, and postoperative outcomes. Methods: A prospectively collected database from a single institution was queried from January 2018 to December 2021, to identify 66 THA patients (mean age 69.5) included in this study. Patient’s BMI were recorded preoperatively and separated into five classes in accordance with the World Health Organization classification of Normal (18.5-24.9), Pre-Obesity (25.0-29.9), Obesity Class I (30.0-34.9), Obesity Class II (35.0-39.9), and Obesity Class III (BMI ≥ 40). Patient attributes, operative characteristics, and postoperative outcomes were then stratified and grouped into the different BMI classes. All patients had radiograph imaging obtained preoperatively and at a minimum 9-month interval to observe for the presence of any radiolucent lines which would be plotted using the hip regions set forth by De Lee and Charnley. Results: The mean BMI of our patient population was 30.5 which overall characterizes it as Obesity Class I. However, the classification that contained the most of our population was Pre-Obesity (n = 26, 39.4%). There were no males in our entire population that had a BMI considered normal, but 13 females did fall into this classification. There was a significant number of patients who underwent a direct anterior approach within the Pre-Obesity classification than those who underwent a posterolateral approach (21 vs 5 patients, P value = 0.047). However, for subjects meeting Obesity Class II and Class III criteria, a significant number of posterolateral approaches were performed than the direct anterior approach. In analyzing the radiographs, only 2 patients were discovered to have radiolucent lines, but no related symptoms or physical complications were reported. Conclusion: Our investigation demonstrates that having a higher BMI only significantly affects the surgical approach to THA but can conclude that it is an excellent surgical option for the treatment of OA in obese patients

    Co-delivery of free vancomycin and transcription factor decoy-nanostructured lipid carriers can enhance inhibition of methicillin resistant Staphylococcus aureus (MRSA)

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    Bacterial resistance to antibiotics is widely regarded as a major public health concern with last resort MRSA treatments like vancomycin now encountering resistant strains. TFDs (Transcription Factor Decoys) are oligonucleotide copies of the DNA-binding sites for transcription factors. They bind to and sequester the targeted transcription factor, thus inhibiting transcription of many genes. By developing TFDs with sequences aimed at inhibiting transcription factors controlling the expression of highly conserved bacterial cell wall proteins, TFDs present as a potential method for inhibiting microbial growth without encountering typical resistance mechanisms. However, the efficient protection and delivery of the TFDs inside the bacterial cells is a critical step for the success of this technology. Therefore, in our study, specific TFDs against S. aureus were complexed with two different types of nanocarriers: cationic nanostructured lipid carriers (cNLCs) and chitosan-based nanoparticles (CS-NCs). These TFD-carrier nanocomplexes were characterized for size, zeta potential and TFD complexation or loading efficiency in a variety of buffers. In vitro activity of the nanocomplexes was examined alone and in combination with vancomycin, first in methicillin susceptible strains of S. aureus with the lead candidate advancing to tests against MRSA cultures. Results found that both cNLCs and chitosan-based carriers were adept at complexing and protecting TFDs in a range of physiological and microbiological buffers up to 72 hours. From initial testing, chitosan-TFD particles demonstrated no visible improvements in effect when co-administered with vancomycin. However, co-delivery of cNLC-TFD with vancomycin reduced the MIC of vancomycin by over 50% in MSSA and resulted in significant decreases in viability compared with vancomycin alone in MRSA cultures. Furthermore, these TFD-loaded particles demonstrated very low levels of cytotoxicity and haemolysis in vitro. To our knowledge, this is the first attempt at a combined antibiotic/oligonucleotide-TFD approach to combatting MRSA and, as such, highlights a new avenue of MRSA treatment combining traditional small molecules drugs and bacterial gene inhibition

    Thermally Induced Oxidation of [FeII(tacn)2](OTf)2 (tacn = 1,4,7‐triazacyclononane)

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141624/1/ejic201701190_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141624/2/ejic201701190-sup-0001-SupMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141624/3/ejic201701190.pd

    Identity-by-descent filtering as a tool for the identification of disease alleles in exome sequence data from distant relatives

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    Large-scale, deep resequencing may be the next logical step in the genetic investigation of common complex diseases. Because each individual is likely to carry many thousands of variants, the identification of causal alleles requires an efficient strategy to reduce the number of candidate variants. Under many genetic models, causal alleles can be expected to reside within identity-by-descent (IBD) regions shared by affected relatives. In distant relatives, IBD regions constitute a small portion of the genome and can thus greatly reduce the search space for causal alleles. However, the effectiveness of this strategy is unknown. We test the simulated mini-exome data set in extended pedigrees provided by Genetic Analysis Workshop 17. At the fourth- and fifth-degree level of relatedness, case-case pairs shared between 1% and 9% of the genome identical by descent. As expected, no genes were shared identical by descent by all case subjects, but 43 genes were shared by many case subjects across at least 50 replicates. We filtered variants in these genes based on population frequency, function, informativeness, and evidence of association using the family-based association test. This analysis highlighted five genes previously implicated in triglyceride, lipid, and cholesterol metabolism. Comparison with the list of true risk alleles revealed that strict IBD filtering followed by association testing of the rarest alleles was the most sensitive strategy. IBD filtering may be a useful strategy for narrowing down the list of candidate variants in exome data, but the optimal degree of relatedness of affected pairs will depend on the genetic architecture of the disease under study

    Allelic Variation of MYB10 Is the Major Force Controlling Natural Variation in Skin and Flesh Color in Strawberry (Fragaria spp.) Fruit

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    Independent mutations in the transcription factor MYB10 cause most of the anthocyanin variation observed in diploid woodland strawberry (Fragaria vesca) and octoploid cultivated strawberry (Fragaria x ananassa). The fruits of diploid and octoploid strawberry (Fragaria spp) show substantial natural variation in color due to distinct anthocyanin accumulation and distribution patterns. Anthocyanin biosynthesis is controlled by a clade of R2R3 MYB transcription factors, among which MYB10 is the main activator in strawberry fruit. Here, we show that mutations in MYB10 cause most of the variation in anthocyanin accumulation and distribution observed in diploid woodland strawberry (F. vesca) and octoploid cultivated strawberry (F. xananassa). Using a mapping-by-sequencing approach, we identified a gypsy-transposon in MYB10 that truncates the protein and knocks out anthocyanin biosynthesis in a white-fruited F. vesca ecotype. Two additional loss-of-function mutations in MYB10 were identified among geographically diverse white-fruited F. vesca ecotypes. Genetic and transcriptomic analyses of octoploid Fragaria spp revealed that FaMYB10-2, one of three MYB10 homoeologs identified, regulates anthocyanin biosynthesis in developing fruit. Furthermore, independent mutations in MYB10-2 are the underlying cause of natural variation in fruit skin and flesh color in octoploid strawberry. We identified a CACTA-like transposon (FaEnSpm-2) insertion in the MYB10-2 promoter of red-fleshed accessions that was associated with enhanced expression. Our findings suggest that cis-regulatory elements in FaEnSpm-2 are responsible for enhanced MYB10-2 expression and anthocyanin biosynthesis in strawberry fruit flesh.Peer reviewe

    Allelic Variation of MYB10 is the Major Force Controlling Natural Variation of Skin and Flesh Color in Strawberry (Fragaria spp.) fruit

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    Anthocyanins are the principal color-producing compounds synthesized in developing fruits of strawberry (Fragaria spp.). Substantial natural variation in color have been observed in fruits of diploid and octoploid accessions, resulting from distinct accumulation and distribution of anthocyanins in fruits. Anthocyanin biosynthesis is controlled by a clade of R2R3 MYB transcription factors, among which MYB10 has been shown as the main activator in strawberry fruit. Here, we show that MYB10 mutations cause most of the anthocyanin variation observed in diploid woodland strawberry (F. vesca) and octoploid cultivated strawberry (F. ×ananassa). Using a mapping-by-sequencing approach, we identified a gypsytransposon insertion in MYB10 that truncates the protein and knocks out anthocyanin biosynthesis in a white-fruited F. vesca ecotype. Two additional lossof-function MYB10 mutations were identified among geographically diverse whitefruited F. vesca ecotypes. Genetic and transcriptomic analyses in octoploid Fragaria spp. revealed that FaMYB10-2, one of three MYB10 homoeologs identified, residing in the F. iinumae-derived subgenome, regulates the biosynthesis of anthocyanins in developing fruit. Furthermore, independent mutations in MYB10-2 are the underlying cause of natural variation in fruit skin and flesh color in octoploid strawberry. We identified a CACTA-like transposon (FaEnSpm-2) insertion in the MYB10-2 promoter of red-fleshed accessions that was associated with enhanced expression and anthocyanin accumulation. Our findings suggest that putative cis regulatory elements provided by FaEnSpm-2 are required for high and ectopic MYB10-2 expression and induction of anthocyanin biosynthesis in fruit flesh. We developed MYB10-2 (sub-genome) specific DNA markers for marker-assisted selection that accurately predicted anthocyanin phenotypes in octoploid segregating populations
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