231 research outputs found

    Induction of secretory pathway components in yeast is associated with increased stability of their mRNA

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    The overexpression of certain membrane proteins is accompanied by a striking proliferation of intracellular membranes. One of the best characterized inducers of membrane proliferation is the 180-kD mammalian ribosome receptor (p180), whose expression in yeast results in increases in levels of mRNAs encoding proteins that function in the secretory pathway, and an elevation in the cell's ability to secrete proteins. In this study we demonstrate that neither the unfolded protein response nor increased transcription accounts for membrane proliferation or the observed increase in secretory pathway mRNAs. Rather, p180-induced up-regulation of certain secretory pathway transcripts is due to a p180-mediated increase in the longevity of these mRNA species, as determined by measurements of transcriptional activity and specific mRNA turnover. Moreover, we show that the longevity of mRNA in general is substantially promoted through the process of its targeting to the membrane of the endoplasmic reticulum. With respect to the terminal differentiation of secretory tissues, results from this model system provide insights into how the expression of a single protein, p180, could result in substantial morphological and functional changes

    PROTOCOL: The Effects of Medical Cannabis on Pain and Quality of Life in Individuals with Parkinson’s Disease and/or Chronic Pain

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    Background: The opioid epidemic has led medical professionals to research alternative methods of pain reduction. There is limited evidence concerning the usage of medical cannabis and its effect on the symptoms associated with Parkinson’s disease and/or reduction of chronic pain. Pain is subjective and neurologically derived, therefore, an association of quality of life differentiation upon individuals with chronic illnesses such as Parkinson’s disease and chronic pain can add to the research of whether medical cannabis is an appropriate alternative treatment to influence pain perception. Objective: The aim of this study is to identify a correlation between medical cannabis and Parkinson’s disease and/or Chronic pain. Design: This is a descriptive design study carried out through means of an electronic survey. Paper copies of the survey will also be made available for participants who prefer a paper copy. Setting: The participants will be obtained from customers that shop at Ethos Cannabis Dispensary in Wilkes Barre, Pennsylvania. Analysis will be performed at Misericordia University in Dallas, Pennsylvania. Participants: We hope to obtain 100 participants to complete our survey that are current prescription medical cannabis users and have been diagnosed with Parkinson’s disease and/or Chronic pain. Measurements: The primary outcome measures included in our survey are the LISAT-11 and the Wong-Baker Pain Faces Scale. The LISAT-11 is a quality of life questionnaire and the Wong-Baker Pain Faces Scale is a pain questionnaire. Participants will be asked to rank their current quality of life using medical cannabis as well as their pain perceptions both before and after medical cannabis usage. Limitations: Limitations include a small sample size of participants to complete the survey and knowledge of any other means of pain reduction the individual may be utilizing paired with Medical Cannabis. Conclusion: This study will describe differences in quality of life and pain perceived by medical cannabis users with Parkinson’s disease and/or Chronic pain at Ethos Dispensary before and after they started using medical cannabis.https://digitalcommons.misericordia.edu/research_posters2021/1008/thumbnail.jp

    Extensions of operator algebras I

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    We transcribe a portion of the theory of extensions of C*-algebras to general operator algebras. We also include several new general facts about approximately unital ideals in operator algebras and the C*-algebras which they generate

    Clinically relevant aberrant Filip1l DNA methylation detected in a murine model of cutaneous squamous cell carcinoma

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    Background: Cutaneous squamous cell carcinomas (cSCC) are among the most common and highly mutated human malignancies. Understanding the impact of DNA methylation in cSCC may provide avenues for new therapeutic strategies. Methods: We used reduced-representation bisulfite sequencing for DNA methylation analysis of murine cSCC. Differential methylation was assessed at the CpG level using limma. Next, we compared with human cSCC Infinium HumanMethylation BeadArray data. Genes were considered to be of major relevance when they featured at least one significantly differentially methylated CpGs (RRBS) / probes (Infinium) with at least a 30% difference between tumour vs. control in both a murine gene and its human orthologue. The human EPIC Infinium data were used to distinguish two cSCC subtypes, stem-cell-like and keratinocyte-like tumours. Findings: We found increased average methylation in mouse cSCC (by 12.8%, p = 0.0011) as well as in stem-cell like (by 3.1%, p=0.002), but not keratinocyte-like (0.2%, p = 0.98), human cSCC. Comparison of differentially methylated genes revealed striking similarities between human and mouse cSCC. Locus specific methylation changes in mouse cSCC often occurred in regions of potential regulatory function, including enhancers and promoters. A key differentially methylated region was located in a potential enhancer of the tumour suppressor gene Filip1l and its expression was reduced in mouse tumours. Moreover, the FILIP1L, locus showed hypermethylation in human cSCC and lower expression in human cSCC cell lines. Interpretation: Deregulation of DNA methylation is an important feature of murine and human cSCC that likely contributes to silencing of tumour suppressor genes, as shown for Filip1l. 2021 The Author(s). Published by Elsevier B.V

    Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution

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    Ex situ dual hypothermic oxygenated machine perfusion (DHOPE) and normothermic machine perfusion (NMP) of donor livers may have a complementary effect when applied sequentially. While DHOPE resuscitates the mitochondria and increases hepatic adenosine triphosphate (ATP) content, NMP enables hepatobiliary viability assessment prior to transplantation. In contrast to DHOPE, NMP requires a perfusion solution with an oxygen carrier, for which red blood cells (RBC) have been used in most series. RBC, however, have limitations and cannot be used cold. We, therefore, established a protocol of sequential DHOPE, controlled oxygenated rewarming (COR), and NMP using a new hemoglobin-based oxygen carrier (HBOC)-based perfusion fluid (DHOPE-COR-NMP trial, NTR5972). Seven livers from donation after circulatory death (DCD) donors, which were initially declined for transplantation nationwide, underwent DHOPE-COR-NMP. Livers were considered transplantable if perfusate pH and lactate normalized, bile production was >= 10 mL and biliary pH > 7.45 within 150 minutes of NMP. Based on these criteria five livers were transplanted. The primary endpoint, 3-month graft survival, was a 100%. In conclusion, sequential DHOPE-COR-NMP using an HBOC-based perfusion fluid offers a novel method of liver machine perfusion for combined resuscitation and viability testing of suboptimal livers prior to transplantation
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