Search for: All records

It is a major clinical challenge to ensure the long-term function of transplanted kidneys. Specifically, the injury associated with cold storage of kidneys compromises the long-term function of the grafts after transplantation. Therefore, the molecular mechanisms underlying cold-storage–related kidney injury are attractive therapeutic targets to prevent injury and improve long-term graft function. Previously, we found that constitutive proteasome function was compromised in rat kidneys after cold storage followed by transplantation. Here, we evaluated the role of the immunoproteasome (iproteasome), a proteasome variant, during cold storage (CS) followed by transplantation.

Established in vivo rat kidney transplant model with or without CS containing vehicle or iproteasome inhibitor (ONX 0914) was used in this study. Theiproteasome function was performed using rat kidney homogenates and fluorescent-based peptide substrate specific to β5i subunit. Western blotting and quantitative RT-PCR were used to assess the subunit expression/level of theiproteasome (β5i) subunit.

We demonstrated a decrease in the abundance of the β5i subunit of theiproteasome in kidneys during CS, but β5i levels increased in kidneys after CS and transplant. Despite the increase in β5i levels and its peptidase activity within kidneys, inhibiting β5i during CS did not improve graft function after transplantation.

These results suggest that the pharmacological inhibition of immunoproteasome function during CS does not improve graft function or outcome. In light of these findings, future studies targeting immunoproteasomes during both CS and transplantation may define the role of immunoproteasomes on short- and long-term kidney transplant outcomes.

 

Glioblastoma ranks among the most lethal of primary brain malignancies, with glioblastoma stem cells (GSCs) at the apex of tumor cellular hierarchies. Here, to discover novel therapeutic GSC targets, we interrogated gene expression profiles from GSCs, differentiated glioblastoma cells (DGCs), and neural stem cells (NSCs), revealing EYA2 as preferentially expressed by GSCs. Targeting EYA2 impaired GSC maintenance and induced cell cycle arrest, apoptosis, and loss of self-renewal. EYA2 displayed novel localization to centrosomes in GSCs, and EYA2 tyrosine (Tyr) phosphatase activity was essential for proper mitotic spindle assembly and survival of GSCs. Inhibition of the EYA2 Tyr phosphatase activity, via genetic or pharmacological means, mimicked EYA2 loss in GSCs in vitro and extended the survival of tumor-bearing mice. Supporting the clinical relevance of these findings, EYA2 portends poor patient prognosis in glioblastoma. Collectively, our data indicate that EYA2 phosphatase function plays selective critical roles in the growth and survival of GSCs, potentially offering a high therapeutic index for EYA2 inhibitors. 

Effective data management plays a key role in oceanographic research as cruise-based data, collected from different laboratories and expeditions, are commonly compiled to investigate regional to global oceanographic processes. Here we describe new and updated best practice data standards for discrete chemical oceanographic observations, specifically those dealing with column header abbreviations, quality control flags, missing value indicators, and standardized calculation of certain properties. These data standards have been developed with the goals of improving the current practices of the scientific community and promoting their international usage. These guidelines are intended to standardize data files for data sharing and submission into permanent archives. They will facilitate future quality control and synthesis efforts and lead to better data interpretation. In turn, this will promote research in ocean biogeochemistry, such as studies of carbon cycling and ocean acidification, on regional to global scales. These best practice standards are not mandatory. Agencies, institutes, universities, or research vessels can continue using different data standards if it is important for them to maintain historical consistency. However, it is hoped that they will be adopted as widely as possible to facilitate consistency and to achieve the goals stated above. 

Abstract. Internally consistent, quality-controlled (QC) data products play animportant role in promoting regional-to-global research efforts tounderstand societal vulnerabilities to ocean acidification (OA). However,there are currently no such data products for the coastal ocean, where mostof the OA-susceptible commercial and recreational fisheries and aquacultureindustries are located. In this collaborative effort, we compiled, quality-controlled, and synthesized 2 decades of discrete measurements ofinorganic carbon system parameters, oxygen, and nutrient chemistry data fromthe North American continental shelves to generate a data product calledthe Coastal Ocean Data Analysis Product in North America (CODAP-NA). Thereare few deep-water (> 1500 m) sampling locations in the currentdata product. As a result, crossover analyses, which rely on comparisonsbetween measurements on different cruises in the stable deep ocean, couldnot form the basis for cruise-to-cruise adjustments. For this reason, carewas taken in the selection of data sets to include in this initial releaseof CODAP-NA, and only data sets from laboratories with known qualityassurance practices were included. New consistency checks and outlierdetections were used to QC the data. Future releases of this CODAP-NAproduct will use this core data product as the basis for cruise-to-cruisecomparisons. We worked closely with the investigators who collected andmeasured these data during the QC process. This version (v2021) of theCODAP-NA is comprised of 3391 oceanographic profiles from 61 researchcruises covering all continental shelves of North America, from Alaska toMexico in the west and from Canada to the Caribbean in the east. Data for 14variables (temperature; salinity; dissolved oxygen content; dissolvedinorganic carbon content; total alkalinity; pH on total scale; carbonateion content; fugacity of carbon dioxide; and substance contents of silicate,phosphate, nitrate, nitrite, nitrate plus nitrite, and ammonium) have beensubjected to extensive QC. CODAP-NA is available as a merged data product(Excel, CSV, MATLAB, and NetCDF; https://doi.org/10.25921/531n-c230,https://www.ncei.noaa.gov/data/oceans/ncei/ocads/metadata/0219960.html, last access: 15 May 2021)(Jiang et al., 2021a). The original cruise data have also been updated withdata providers' consent and summarized in a table with links to NOAA'sNational Centers for Environmental Information (NCEI) archives(https://www.ncei.noaa.gov/access/ocean-acidification-data-stewardship-oads/synthesis/NAcruises.html).