595 research outputs found
Children in Immigrant Families - The U.S. and 50 States: Economic Need Beyond the Official Poverty Measure
Analyzes gaps between child poverty rates in immigrant families and native-born families based on two alternative measures that take into account the costs of housing, food, other basic necessities, transportation, taxes, child care, and early education
Children in Immigrant Families -- The U.S. and 50 States: National Origins, Language, and Early Education
Draws on new results of U.S. Census 2000 data to focus on children in immigrant families, highlighting the proportion, dispersion, national origins, language, and early education of children in newcomer families nationwide and in various states
Carbonates replacing plagioclase glass in the Martian meteorite ALH84001
No abstract available
Prevalence of baseline polymorphisms for potential resistance to NS5A inhibitors in drug-naive individuals infected with hepatitis C genotypes 1–4
Background: The non-structural 5A (NS5A) protein of HCV is a multifunctional phosphoprotein involved in regulation of viral replication and virion assembly. NS5A inhibitors targeting domain I of NS5A protein have demonstrated high potency and pan-genotypic antiviral activity, however they possess a low genetic barrier to resistance. At present, only genotype 1, the most prevalent HCV genotype has been studied in detail for resistant variants.
Methods: Utilising a panel of genotypic-specific resistance assays, population sequencing was performed on plasma derived viral RNA isolated from 138 patients infected with HCV genotypes 1-4 and not treated with directly acting anti-viral agents (DAAs). Amino acid changes in HCV NS5A domain I at codon positions 28, 30, 31, 32 and 93, reported to confer reduced susceptibility to certain NS5A inhibitors were examined. Additionally, genotypic outcome based on NS5A sequences were compared with LiPA and Abbott® real time.
Results: Amino acid substitutions associated with moderate to high level resistance to NS5A inhibitors were detected in 2/42 (4.76%) HCV-1a, 3/23 (13.04%) HCV-1b, 4/26 ( 15.38% ) HCV-2, 1/24 (4.17%) HCV-3 and 1/23 (4.35%) HCV-4 infected patients who had not been treated with NS5A inhibitors. Genotype prediction based on NS5A sequences were concordant with LiPA and/or Abbott® real-time for 97.10% of cases.
Conclusion: Primary resistance mutations associated with resistance to first generation NS5A inhibitors such as Daclatasvir (DCV) were observed in all genotypes, albeit at low frequencies. An excellent correlation based on NS5A genotyping and LiPA or Abbott® real-time was achieved
Synthesis of a [2]rotaxane through first- and second-sphere coordination
In an effort to expand the application of a new template from interpenetrated to interlocked molecular species, we report the synthesis of a new [2]rotaxane by means of both first- and second-sphere coordination of a palladium(II) dichloride subunit
USP15 targets ALK3/BMPR1A for deubiquitylation to enhance bone morphogenetic protein signalling
Protein kinase ALK3/BMPR1A mediates bone morphogenetic protein (BMP) signalling through phosphorylation and activation of SMADs 1/5/8. SMAD6, a transcriptional target of BMP, negatively regulates the BMP pathway by recruiting E3 ubiquitin ligases and targeting ALK3 for ubiquitin-mediated degradation. Here, we identify a deubiquitylating enzyme USP15 as an interactor of SMAD6 and ALK3. We show that USP15 enhances BMP-induced phosphorylation of SMAD1 by interacting with and deubiquitylating ALK3. RNAi-mediated depletion of USP15 increases ALK3 K48-linked polyubiquitylation, and reduces both BMP-induced SMAD1 phosphorylation and transcription of BMP target genes. We also show that loss of USP15 expression from mouse myoblast cells inhibits BMP-induced osteoblast differentiation. Furthermore, USP15 modulates BMP-induced phosphorylation of SMAD1 and transcription during Xenopus embryogenesis
Liposomal Encapsulation of Amoxicillin via Microfluidics with Subsequent Investigation of the Significance of PEGylated Therapeutics
With an increasing concern of global antimicrobial resistance, the efforts to improve the formulation of a narrowing library of therapeutic antibiotics must be confronted. The liposomal encapsulation of antibiotics using a novel and sustainable microfluidic method has been employed in this study to address this pressing issue, via a targeted, lower-dose medical approach. The study focusses upon microfluidic parameter optimisation, formulation stability, cytotoxicity, and future applications. Particle sizes of circa. 130 nm, with viable short-term (28-day) physical stability were obtained, using two different non-cytotoxic liposomal formulations, both of which displayed suitable antibacterial efficacy. The microfluidic method allowed for high encapsulation efficiencies (≈77 %) and the subsequent in vitro release profile suggested high limits of antibiotic dissociation from the nanovessels, achieving 90% release within 72 h. In addition to the experimental data, the growing use of poly(ethylene) glycol (PEG) within lipid-based formulations is discussed in relation to anti-PEG antibodies, highlighting the key pharmacological differences between PEGylated and non-PEGylated formulations and their respective advantages and drawbacks. It's surmised that in the case of the formulations used in this study, the addition of PEG upon the liposomal membrane would still be a beneficial feature to possess owing to beneficial features such as stability, antibiotic efficacy and the capacity to further modify the liposomal membrane.</p
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