The Location of NF-kB and AKAP-95 in Lipopolysaccharide Treated RT4-D6P2T Schwannoma Cells

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Simulation of an Inflammatory Model Using Schwann Cells

Schwann cells are a type of glial cell in the peripheral nervous system that produce the myelin sheath surrounding neuronal axons. This myelin insulates the neurons and promotes the rapid conduction of electrical impulses throughout the body. Schwann cells have also been found to play a critical role in neuron repair following nerve injury. During nerve injury, the myelin sheath is damaged, stimulating Schwann cells to release cytokines, or inflammatory mediators, that recruit immune cells to the site of injury so that the myelin debris can be cleared, and repair can take place.1 Then neuronal growth is facilitated by heregulin and an unknown growth factor that stimulates the cyclic adenosine monophosphate (cAMP) pathway.2,3 There is still yet to be known regarding the exact mechanisms by which Schwann cells mediate nerve repair. Two pathways of interest are the nuclear factor kappa B (NK-κB) and cAMP pathways. The NF-κB pathway plays a major role in inflammation through the production of cytokines like tumor necrosis factor alpha (TNF-α) and can be stimulated in vitro by treating cells with lipopolysaccharide (LPS), a cell wall immunostimulatory component of Gram-negative bacteria.1 The cAMP pathway is a key regulator of cell division2,4 and can be stimulated by treating cells with an artificial plant extract called forskolin.2 This study aims to examine proteins of the NF-κB pathway when stimulated with cAMP-activating growth factors. It was hypothesized that cells treated with LPS and growth factors express less NF-κB and TNF-α than cells treated with LPS only. A better understanding of the mechanisms underlying nerve injury and Schwann cell-mediated repair will hopefully shed light on a potential therapeutic target in the treatment of nerve injury and inflammation.https://digitalcommons.misericordia.edu/surf2022/1001/thumbnail.jp

Abandoned, lost and discarded fishing gear ‘ghost nets’ are increasing through time in Northern Australia

The remote Gulf of Carpentaria (GoC) represents 10% of Australia’s coastline. This large, shallow sea supports high value fishing activities and habitat for threatened species, and is a sink for abandoned, lost and discarded fishing gear (ALDFG) ‘ghost nets’, most originating from fishing activities outside of Australia’s Exclusive Economic Zone. With growing concerns about the plastic waste along the world’s coastlines, we retrospectively analyzed ghost net sighting information from four aerial surveys across 15 years, to investigate whether densities of ghost nets are changing through time or in space. We found an increase in ghost nets, despite more than a decade of illegal fishing countermeasure and clean-up efforts in the broader region. This demonstrates that the input of ALDFG into the system currently overwhelms the substantial net removal activities. We make recommendations for improving monitoring and consider the underlying drivers of nets being lost to improve ghost gear management on land and at sea

High prevalence of subclass-specific binding and neutralizing antibodies against Clostridium difficile toxins in adult cystic fibrosis sera: possible mode of immunoprotection against symptomatic C. difficile infection

Objectives: Despite multiple risk factors and a high rate of colonization for Clostridium difficile, the occurrence of C. difficile infection in patients with cystic fibrosis is rare. The aim of this study was to compare the prevalence of binding C. difficile toxin-specific immunoglobulin (Ig)A, IgG and anti-toxin neutralizing antibodies in the sera of adults with cystic fibrosis, symptomatic C. difficile infection (without cystic fibrosis) and healthy controls. Methods: Subclass-specific IgA and IgG responses to highly purified whole C. difficile toxins A and B (toxinotype 0, strain VPI 10463, ribotype 087), toxin B from a C. difficile toxin-B only expressing strain (CCUG 20309) and precursor form of B fragment of binary toxin, pCDTb, were determined by protein microarray. Neutralizing antibodies to C. difficile toxins A and B were evaluated using a Caco-2 cell-based neutralization assay. Results: Serum IgA anti-toxin A and B levels and neutralizing antibodies against toxin A were significantly higher in adult cystic fibrosis patients (n=16) compared with healthy controls (n=17) and patients with symptomatic C. difficile infection (n=16); p≤0.05. The same pattern of response prevailed for IgG, except that there was no difference in anti-toxin A IgG levels between the groups. Compared with healthy controls (toxins A and B) and patients with C. difficile infection (toxin A), sera from cystic fibrosis patients exhibited significantly stronger protective anti-toxin neutralizing antibody responses. Conclusion: A superior ability to generate robust humoral immunity to C. difficile toxins in the cystic fibrosis population is likely to confer protection against symptomatic C. difficile infection. This protection may be lost in the post-transplantation setting, where sera-monitoring of anti-C. difficile toxin antibody titers may be of clinical value

Interannual differences in larval haddock survival : hypothesis testing with a 3D biophysical model of Georges Bank

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Fisheries Oceanography 23 (2014): 521–553, doi:10.1111/fog.12087.The ultimate goal of early life studies of fish over the past century has been to better understand recruitment variability. As evident in the Georges Bank haddock (Melanogrammus aeglefinus) population, there is a strong relationship between recruitment success and processes occurring during the planktonic larval stage. This research sought new insights into the mechanisms controlling the recruitment process in fish populations by using biological-physical modeling methods together with laboratory and field data sets. We created the first three-dimensional model of larval haddock on Georges Bank by coupling models of hydrodynamics, lower trophic levels, a single copepod species, and larval haddock. Interactions between feeding, metabolism, growth, vertical behavior, advection, predation, and the physical environment of larval haddock were quantitatively investigated using the coupled models. Particularly, the model was used to compare survival over the larval period and the sources of mortality in 1995 and 1998, two years of disparate haddock recruitment. The results of model simulations suggest that the increased egg hatching rates and higher food availability, which reduced starvation and predation, in 1998 contributed to its larger year-class. Additionally, the inclusion of temperature-dependent predation rates produced model results that better agreed with observations of the mean hatch date of survivors. The results from this biophysical model imply that food-limitation and its related losses to starvation and predation, especially from hatch to 7 mm, may be responsible for interannual variability in recruitment and larval survival outside of the years studied.Financial support was provided by a WHOI Watson Fellowship, a WHOI Coastal Ocean Institute Student Research Proposal Award, and GLOBEC grants NA17RJ1223 (NOAA) and OCE0815838 (NSF).2015-11-1

Patient advocate involvement in the design and conduct of breast cancer clinical trials requiring the collection of multiple biopsies.

Plain english summary Breast cancer is a diverse and varied disease. Recent research has shown that the collection of multiple biopsies before surgery can help researchers determine how the cancer is responding to treatment and can predict for long-term outcomes. However biopsies can be uncomfortable, and sometimes clinicians and research teams in hospitals may be reluctant to offer clinical trials requiring several biopsies to patients who have been recently diagnosed with breast cancer. The Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU) oversees a large number of breast cancer clinical trials where multiple biopsies are required. ICR-CTSU recognises that patient advocates (patients who have previously had, or cared for someone with, cancer) are key members of the trial design group and should be involved in the clinical trial throughout its lifespan. Patient advocates can provide reassurance regarding the acceptability of trial designs involving multiple biopsies from a patient perspective. This paper summarises patient advocate involvement in ICR-CTSU breast cancer trials activity and how this has benefited our research.Abstract The importance of collecting tissue samples in breast cancer has become increasingly recognised, as the diversity of the disease has become better known. It has been documented in recent research that tumours may change in response to treatment prior to surgery (the neoadjuvant treatment setting). The collection of sequential biopsies over time can identify changes within tumours and potentially predict how the tumour may respond to certain treatments. However, the acceptability of multiple biopsies amongst patients, clinicians and other research staff in hospitals is variable and recruitment into clinical trials requiring multiple biopsies may be challenging.The Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU) is responsible for a portfolio of breast cancer trials where multiple biopsies are key to the trial design. Patient advocate involvement has been essential in helping us to design and deliver complex and innovative cancer trials which require multiple invasive tissue biopsies, often without any direct benefit to the trial participants. The views expressed by patient advocates involved in ICR-CTSU trials supports the published evidence that patients are willing to donate additional tissue for research and that clinicians' concerns about approaching patients for trials involving multiple biopsies are often unfounded.Patient advocate involvement in ICR-CTSU trials activity takes various forms, from membership on protocol development groups and trial management groups, attendance at focus groups and forums, and presentations at trial development and launch meetings. This involvement has provided reassurance to research teams within the NHS and research ethics committees of the importance and acceptability of our trials from a patient perspective. Patient advocate involvement throughout the lifetime of our trials ensures that the patient remains central to our research considerations

Protective antibodies against Clostridium difficile are present in intravenous immunoglobulin and are retained in humans following its administration

The prevalence of serum antibodies against Clostridium difficile (CD) toxins A and B in healthy populations have prompted interest in evaluating the therapeutic activity of intravenous immunoglobulin (IVIg) in individuals experiencing severe or recurrent C. difficile infection (CDI). Despite some promising case reports, a definitive clinical role for IVIg in CDI remains unclear. Contradictory results may be attributed to a lack of consensus regarding optimal dose, timing of administration and patient selection as well as variability in specific antibody content between commercial preparations. The purpose of this study was to investigate retrospectively the efficacy of three commercial preparations of IVIg for treating severe or recurrent CDI. In subsequent mechanistic studies using protein microarray and toxin neutralization assays, all IVIg preparations were analysed for specific binding and neutralizing antibodies (NAb) to CD antigens in vitro and the presence of anti-toxin NAbs in vivo following IVIg infusion. A therapeutic response to IVIg was observed in 41% (10 of 17) of the CDI patients. Significant variability in multi-isotype specific antibodies to a 7-plex panel of CD antigens and toxin neutralization efficacies were observed between IVIg preparations and also in patient sera before and after IVIg administration. These results extend our current understanding of population immunity to CD and support the inclusion of surface layer proteins and binary toxin antigens in CD vaccines. Future strategies could enhance IVIg treatment response rates by using protein microarray to preselect donor plasma/serum with the highest levels of anti-CD antibodies and/or anti-toxin neutralizing capacities prior to fractionation

Tracking genomic cancer evolution for precision medicine: The Lung TRACERx Study

The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types