The quantity of each protein in a cell only is only partially correlated with its gene transcription rate. Independent influences on protein synthesis levels include mRNA sequence motifs, amino acyl-tRNA synthesis levels, elongation factor action, and protein susceptibility to degradation. Here we report that the amino acid composition of a protein can also influence its expression level in two distinct ways.
View Article and Find Full Text PDFBackground: Increased HIV testing is essential to ending the HIV epidemic. People who inject drugs (PWID) are among the highest risk for HIV infection. Previous research at Tufts Medical Center identified low HIV testing rates in hospitalized PWID.
View Article and Find Full Text PDFDecision makers need to know the drivers of surface water phosphorus (P) concentrations, the environmental factors that mediate P loading in freshwater systems, and where pollution sources and mediating factors are co-located to inform water quality restoration efforts. To provide this information, publicly available spatial data sets of P pollution sources and relevant environmental variables, like temperature, precipitation, and agricultural soil erodibility, were matched with >7,000 stream and lake total P observations throughout the conterminous United States. Using three statistical approaches, consisting of (a) correlation, (b) regression, and (c) machine learning techniques, we identified likely drivers of P concentrations.
View Article and Find Full Text PDFPDA J Pharm Sci Technol
November 2023
The use of amplified adenosine trisphosphate (ATP) bioluminescence has been established within AstraZeneca as a technique for assessing the sterility of drug product formulations. A platform validation was generated that challenged the technology with a range of organisms and inoculum levels, and the approach to onboarding additional drug products has been designed to maximize the understanding of the drug product behavior when samples may be limited during the development phases of the life cycle of a drug product. Many activities to support sterility assurance take place during product development.
View Article and Find Full Text PDFBackground: Despite national guidelines on infectious disease testing and vaccination in prisons, there is heterogeneity on the implementation of these practices in jails. We sought to better understand perspectives on the implementation of opt-out vaccination for infectious diseases in jails by interviewing a broad group of stakeholders involved in infectious diseases vaccination, testing, and treatment in Massachusetts jails.
Methods: The research team conducted semistructured interviews with people incarcerated in Hampden County Jail (Ludlow, Massachusetts), clinicians working in jail and community settings, corrections administrators, and representatives from public health, government, and industry between July 2021 and March 2022.
Background: COVID-19 shut down trial courts across the country, prolonging case resolution of charged, detained, and incarcerated people. We report on the implementation of rapid COVID-19 testing at Trial Courts in Massachusetts (MA), focusing on the outcomes of adoption and acceptability.
Methods: Guided by the Expert Recommendations in Implementing Change (ERIC) framework, we chose six strategies to guide implementation.
Headwater streams and inland wetlands provide essential functions that support healthy watersheds and downstream waters. However, scientists and aquatic resource managers lack a comprehensive synthesis of national and state stream and wetland geospatial datasets and emerging technologies that can further improve these data. We conducted a review of existing United States (US) federal and state stream and wetland geospatial datasets, focusing on their spatial extent, permanence classifications, and current limitations.
View Article and Find Full Text PDFAcoustic transduction by plants has been proposed as a mechanism to enable just-in-time up-regulation of metabolically expensive defensive compounds. Although the mechanisms by which this "hearing" occurs are unknown, mechanosensation by elongated plant hair cells known as trichomes is suspected. To evaluate this possibility, we developed a theoretical model to evaluate the acoustic radiation force that an elongated cylinder can receive in response to sounds emitted by animals, including insect herbivores, and applied it to the long, cylindrical stem trichomes of the tomato plant Solanum lycopersicum.
View Article and Find Full Text PDFOngoing and potential future changes in precipitation will affect water management infrastructure. Urban drainage systems are particularly vulnerable. Design standards for many stormwater practices rely on precipitation intensity-duration-frequency (IDF) curves based on extreme value analysis.
View Article and Find Full Text PDFTo understand the environmental and anthropogenic drivers of stream nitrogen (N) concentrations across the conterminous US, we combined summer low-flow data from 4997 streams with watershed information across three survey periods (2000-2014) of the US EPA's National Rivers and Streams Assessment. Watershed N inputs explained 51% of the variation in log-transformed stream total N (TN) concentrations. Both N source and input rates influenced stream NO/TN ratios and N concentrations.
View Article and Find Full Text PDFAlzheimer's disease is an irreversible neurodegenerative disease, which accounts for most dementia cases. Neuroinflammation is increasingly recognised for its roles in Alzheimer's disease pathogenesis which, in part, links amyloid-beta to neuronal death. Neuroinflammatory signalling can be exhibited by neurons themselves, potentially leading to widespread neuronal cell death, although neuroinflammation is commonly associated with glial cells.
View Article and Find Full Text PDFThe innate immune system and inflammatory response in the brain have critical impacts on the pathogenesis of many neurodegenerative diseases including Alzheimer's disease (AD). In the central nervous system (CNS), the innate immune response is primarily mediated by microglia. However, non-glial cells such as neurons could also partake in inflammatory response independently through inflammasome signalling.
View Article and Find Full Text PDFDiaminobutyric polypropylenimine (DAB) dendrimers have been shown to be highly efficient non-viral gene delivery systems for cancer therapy. However, their cytotoxicity currently limits their applications. To overcome this issue, PEGylation of DAB dendrimer, using various PEG molecular weights and dendrimer generations, has been attempted to decrease the cytotoxicity and enhance the DNA condensation, size and zeta potential, cellular uptake and transfection efficacy of these dendriplexes.
View Article and Find Full Text PDFThe much studied plant Arabidopsis thaliana has been reported recently to react to the sounds of caterpillars of Pieris rapae chewing on its leaves by promoting synthesis of toxins that can deter herbivory. Identifying participating receptor cells-potential "ears"-of Arabidopsis is critical to understanding and harnessing this response. Motivated in part by other recent observations that Arabidopsis trichomes (hair cells) respond to mechanical stimuli such as pressing or brushing by initiating potential signaling factors in themselves and in the neighboring skirt of cells, we analyzed the vibrational responses of Arabidopsis trichomes to test the hypothesis that trichomes can respond acoustically to vibrations associated with feeding caterpillars.
View Article and Find Full Text PDFLithium is the most successful mood stabilizer treatment for bipolar disorder. However, unlike conventional drugs that are designed to interact with a specific molecular target, the actions of lithium are distributed across many biological processes and pathways. Treatment response is subject to genetic variation between individuals and similar genetic variation may dictate susceptibility to side effects.
View Article and Find Full Text PDFAlthough there is considerable genetic and pathologic evidence for an association between neuregulin 1 (NRG1) dysregulation and schizophrenia, the underlying molecular and cellular mechanisms remain unclear. Mutant mice containing disruption of the transmembrane (TM) domain of the NRG1 gene constitute a heuristic model for dysregulation of NRG1-ErbB4 signaling in schizophrenia. The present study focused on hitherto uncharacterized information processing phenotypes in this mutant line.
View Article and Find Full Text PDFLandsc Urban Plan
February 2017
Costs of repairing and expanding aging infrastructure and competing demands for water from other sectors such as industry and agriculture are stretching water managers' abilities to meet essential domestic drinking water needs for future generations. Using Bayesian statistical modeling on past and present water use, we project domestic water demand in the context of four climate scenarios developed by the Intergovernmental Panel on Climate Change as part of the their Special Report on Emission Scenarios (SRES). We compare 2010 demand to projections of domestic water demand for the years 2030, 2060 and 2090 for the four SRES scenarios.
View Article and Find Full Text PDFRobust statistical, genetic and functional evidence supports a role for in the aetiology of major mental illness. Furthermore, many of its protein-binding partners show evidence for involvement in the pathophysiology of a range of neurodevelopmental and psychiatric disorders. Copy number variants (CNVs) are suspected to play an important causal role in these disorders.
View Article and Find Full Text PDFHuman aging is associated with epigenetic modification of the genome. DNA methylation at cytosines appears currently as the best characterised modification that occurs during the mammalian lifetime. Such methylation changes at regulatory region can provide insights to track contributor age for criminal investigation.
View Article and Find Full Text PDFMetabolomic profiling was carried out on 53 post-mortem brain samples from subjects diagnosed with schizophrenia, depression, bipolar disorder (SDB), diabetes, and controls. Chromatography on a ZICpHILIC column was used with detection by Orbitrap mass spectrometry. Data extraction was carried out with m/z Mine 2.
View Article and Find Full Text PDFTrichomes ('hair cells') on Arabidopsis thaliana stem and leaf surfaces provide a range of benefits arising from their shape and disposition. These include tempting herbivores to sample constitutive toxins before they reach the bulk of the tissue. We asked whether, in addition, small mechanical disturbances such as an insect can make elicit signals that might help the plant respond to herbivory.
View Article and Find Full Text PDFMammalian ageing features biological attrition evident at cellular, genetic and epigenetic levels. Mutation of mitochondrial DNA, and nuclear DNA methylation changes are well established correlates of ageing. The methylation of mitochondrial DNA (mtDNA) is a new and incompletely described phenomenon with unknown biological control and significance.
View Article and Find Full Text PDFThe possibility of using gene therapy for the treatment of brain diseases such as brain cancer, Alzheimer's and Parkinson's diseases, is currently hampered by the lack of gene delivery systems able to cross the blood-brain barrier and deliver DNA to the brain following intravenous administration. On the basis that lactoferrin can effectively reach the brain by using specific receptors for crossing the blood-brain barrier, we propose to investigate if a lactoferrin-bearing generation 3-diaminobutyric polypropylenimine (DAB) dendrimer would allow the transport of plasmid DNA to the brain after intravenous administration. In this work, we demonstrated that the conjugation of lactoferrin to the dendrimer led to an enhanced DNA uptake by 2.
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