Nuclear Localized LSR: A Novel Regulator of Breast Cancer Behavior and Tumorigenesis

Lipolysis Stimulated Lipoprotein Receptor (LSR) has been found in the plasma membrane and is believed to function in lipoprotein endocytosis and tight junctions. Given the impact of cellular metabolism and junction signaling pathways on tumor phenotypes and patient outcome, it is important to understand how LSR cellular localization mediates its functions. We conducted localization studies, evaluated DNA binding, and examined the effects of nuclear LSR in cells, xenografts, and clinical specimens. We found LSR within the membrane, cytoplasm, and the nucleus of breast cancer cells representing multiple intrinsic subtypes. Chromatin immunoprecipitation (ChIP) showed direct binding of LSR to DNA, and sequence analysis identified putative functional motifs and post-translational modifications of the LSR protein. While neither overexpression of transcript variants, nor pharmacological manipulation of post-translational modification significantly altered localization, inhibition of nuclear export enhanced nuclear localization, suggesting a mechanism for nuclear retention. Co-immunoprecipitation and proximal ligation assays indicated LSR-pericentrin interactions, presenting potential mechanisms for nuclear-localized LSR. The clinical significance of LSR was evaluated using data from over 1,100 primary breast tumors, which showed high LSR levels in basal-like tumors and tumors from African-Americans. In tumors histosections, nuclear localization was significantly associated with poor outcomes. Finally, in vivo xenograft studies revealed that basal-like breast cancer cells that over-express LSR exhibited both membrane and nuclear localization, and developed tumors with 100% penetrance, while control cells lacking LSR developed no tumors. These results show that nuclear LSR alters gene expression and may promote aggressive cancer phenotypes

Educating Dairy and Beef Producers on Environmental Issues and Regulatory Concerns for Smaller Farms

Livestock producers in Iowa have seen a progression of regulations and compliance enforcement throughout the past two decades. Awareness through Extension meetings and information put out by commodity groups has played a substantial role in bringing confinement feeding operations and large CAFO feedlots into compliance. For small to medium-sized feedlots and dairies that may or may not be classified as CAFOs, the education and outreach was not formalized prior to the EPA beginning their recent compliance reviews. This issue surfaced because of EPA interpretation of regulations and the subsequent impact on livestock producers. The message from EPA was not well defined and still remains a challenge for livestock producers, extension personnel, and agribusiness (advisers) and agency staff

Furthering patient adherence: A position paper of the international expert forum on patient adherence based on an internet forum discussion

<p>Abstract</p> <p>Background</p> <p>As the problem of patient non-adherence persists and a solution appears hard to be found, it continues to be important to look for new ways to further the issue. We recently conducted a meta-review of adherence intervention studies which yielded a preliminary agenda for future research, practice and theory development in patient adherence. The objective of the present project was to find out to what extent adherence experts consider this agenda relevant and feasible.</p> <p>Methods</p> <p>The thirty-five corresponding authors of the review studies included in the meta-review were invited to join the International Expert Forum on Patient Adherence and to participate in a four-week web-based focus group discussion. The discussion was triggered by the points on the preliminary agenda presented as propositions to which forum members could react. Two researchers analysed the transcripts and selected relevant phrases.</p> <p>Results</p> <p>Twenty adherence experts participated. Various ideas and viewpoints were raised. After the closure of the web-site, the expert forum was asked to authorize the synthesis of the discussion, to list the propositions in order of priority and to answer a few questions on the use of the web-based focus group as a tool to obtain expert opinions. Their ranking showed that the development of simple interventions is the most promising step to take in fostering patient adherence, preferably within a multidisciplinary setting of medical, pharmaceutical, social and technical science and, not in the least, by incorporating patients' perspectives.</p> <p>Conclusion</p> <p>For enhancing adherence, the development of simple interventions originating from a multidisciplinary perspective including patients' input, appears most promising. Disclosing patients' perspectives requires open communication about patients' expectations, needs and experiences in taking medication and about what might help them to become and remain adherent.</p

Development of A Method To Quantify The DNA Content in Cationic Peptide-DNA Nanoparticles

Gene therapy has the potential to provide safe and targeted therapies for a variety of diseases. A range of intracellular gene delivery vehicles have been proposed for this purpose. Non-viral vectors are a particularly attractive option and among them cationic peptides have emerged as promising candidates. For the pharmaceutical formulation and application to clinical studies it is necessary to quantify the amount of pDNA condensed with the delivery system. There is a severe deficiency in this area, thus far no methods have been reported specifically for pDNA condensed with cationic peptide to form nanoparticles. The current study seeks to address this and describes the evaluation of a range of disruption agents to extract DNA from nanoparticles formed by condensation with cationic fusogenic peptides RALA and KALA. Only proteinase K exhibited efficient and reproducible results and compatibility with the PicoGreen reagent based quantification assay. Thus we report for the first time a simple and reliable method that can quantify the pDNA content in pDNA cationic peptide nanoparticles

Elentári: a massive proto-supercluster at z ∼ 3.3 in the COSMOS field

Motivated by spectroscopic confirmation of three overdense regions in the COSMOS field at z similar to 3.35, we analyse the uniquely deep multiwavelength photometry and extensive spectroscopy available in the field to identify any further related structure. We construct a three-dimensional density map using the Voronoi tesselation Monte Carlo method and find additional regions of significant overdensity. Here, we present and examine a set of six overdense structures at 3.20 &lt; z &lt; 3.45 in the COSMOS field, the most well-characterized of which, PCl J0959 + 0235, has 80 spectroscopically confirmed members and an estimated mass of 1.35 x 10(15) M-circle dot, and is modelled to virialize at z similar to 1.5-2.0. These structures contain 10 overdense peaks with &gt;5 sigma overdensity separated by up to 70 cMpc, suggestive of a proto-supercluster similar to the Hyperion system at z similar to 2.45. Upcoming photometric surveys with JWST such as COSMOS-Web, and further spectroscopic follow-up will enable more extensive analysis of the evolutionary effects that such an environment may have on its component galaxies at these early times

Risk Factors for SARS Transmission from Patients Requiring Intubation: A Multicentre Investigation in Toronto, Canada

In the 2003 Toronto SARS outbreak, SARS-CoV was transmitted in hospitals despite adherence to infection control procedures. Considerable controversy resulted regarding which procedures and behaviours were associated with the greatest risk of SARS-CoV transmission.A retrospective cohort study was conducted to identify risk factors for transmission of SARS-CoV during intubation from laboratory confirmed SARS patients to HCWs involved in their care. All SARS patients requiring intubation during the Toronto outbreak were identified. All HCWs who provided care to intubated SARS patients during treatment or transportation and who entered a patient room or had direct patient contact from 24 hours before to 4 hours after intubation were eligible for this study. Data was collected on patients by chart review and on HCWs by interviewer-administered questionnaire. Generalized estimating equation (GEE) logistic regression models and classification and regression trees (CART) were used to identify risk factors for SARS transmission. ratio ≤59 (OR = 8.65, p = .001) were associated with increased risk of transmission of SARS-CoV. In CART analyses, the four covariates which explained the greatest amount of variation in SARS-CoV transmission were covariates representing individual patients.Close contact with the airway of severely ill patients and failure of infection control practices to prevent exposure to respiratory secretions were associated with transmission of SARS-CoV. Rates of transmission of SARS-CoV varied widely among patients

Climate change implications for tidal marshes and food web linkages to estuarine and coastal nekton

Climate change is altering naturally fluctuating environmental conditions in coastal and estuarine ecosystems across the globe. Departures from long-term averages and ranges of environmental variables are increasingly being observed as directional changes [e.g., rising sea levels, sea surface temperatures (SST)] and less predictable periodic cycles (e.g., Atlantic or Pacific decadal oscillations) and extremes (e.g., coastal flooding, marine heatwaves). Quantifying the short- and long-term impacts of climate change on tidal marsh seascape structure and function for nekton is a critical step toward fisheries conservation and management. The multiple stressor framework provides a promising approach for advancing integrative, cross-disciplinary research on tidal marshes and food web dynamics. It can be used to quantify climate change effects on and interactions between coastal oceans (e.g., SST, ocean currents, waves) and watersheds (e.g., precipitation, river flows), tidal marsh geomorphology (e.g., vegetation structure, elevation capital, sedimentation), and estuarine and coastal nekton (e.g., species distributions, life history adaptations, predator-prey dynamics). However, disentangling the cumulative impacts of multiple interacting stressors on tidal marshes, whether the effects are additive, synergistic, or antagonistic, and the time scales at which they occur, poses a significant research challenge. This perspective highlights the key physical and ecological processes affecting tidal marshes, with an emphasis on the trophic linkages between marsh production and estuarine and coastal nekton, recommended for consideration in future climate change studies. Such studies are urgently needed to understand climate change effects on tidal marshes now and into the future

Secondary fibrosarcoma of the brain stem treated with cyclophosphamide and Imatinib

Radiation-induced midbrain fibrosarcoma is a rare, highly aggressive tumor, which is associated with poor prognosis. We present the case of a 48-year old man with brainstem fibrosarcoma 20 years following radiation therapy received for a pituitary tumor. We discuss this case in the context of the diagnostic criteria for these tumors, and previous reports of secondary and primary sarcomas of the central nervous system