Age-related calcium dysregulation linked with tau pathology and impaired cognition in non-human primates.

Introduction: The etiology of sporadic Alzheimer's disease (AD) requires non-genetically modified animal models.

Methods: The relationship of tau phosphorylation to calcium-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) dysregulation was analyzed in aging rhesus macaque dorsolateral prefrontal cortex (dlPFC) and rat primary cortical neurons using biochemistry and immuno-electron microscopy. The influence of calcium leak from ryanodine receptors (RyRs) on neuronal firing and cognitive performance was examined in aged macaques.

Hydrogel-based 3D bioprints repair rat small intestine injuries and integrate into native intestinal tissue.

3D Printing has become a mainstay of industry, with several applications in the medical field. One area that could benefit from 3D printing is intestinal failure due to injury or genetic malformations. We bioprinted cylindrical tubes from rat vascular cells that were sized to form biopatches.

Immunolocalization of anion transporter Slc26a7 in mouse kidney.

Previous studies have indicated that a major fraction of the filtered Cl(-) is reabsorbed via apical membrane Cl(-)/base exchange in the proximal tubule. Recent studies in Slc26a6 null mice have suggested that this transporter mediates only a portion of proximal tubule Cl(-)/base exchange, raising the possibility that one or more unidentified apical membrane transporters may additionally contribute. Recent studies have identified Slc26a7 as another Cl(-)/base exchanger expressed in the kidney.

Role of PDZK1 in membrane expression of renal brush border ion exchangers.

Na-H exchanger NHE3 and Cl-anion exchanger CFEX (SLC26A6, PAT1) play principal roles in the reabsorption of Na and Cl in the proximal tubule of the mammalian kidney. The mechanisms by which NHE3 and CFEX are localized to and maintained in the brush border of the proximal tubule are largely unknown. To investigate the possible interaction of NHE3 and CFEX with the PDZ-domain-containing scaffolding protein PDZK1, we performed a series of in vitro interaction assays with GST-fusion proteins and native brush border membrane proteins.

Immunolocalization of NHE8 in rat kidney.

In situ hybridization studies demonstrated that Na+/H+ exchanger NHE8 is expressed in kidney proximal tubules. Although membrane fractionation studies suggested apical brush-border localization, precise membrane localization could not be definitively established. The goal of the present study was to develop isoform-specific NHE8 antibodies as a tool to directly establish the localization of NHE8 protein in the kidney by immunocytochemistry.

Histopathological analysis of renal cystic epithelia in the Pkd2WS25/- mouse model of ADPKD.

It has been proposed that autosomal dominant polycystic kidney disease (ADPKD)affected renal epithelial cells undergo a phenotypic transition from a highly differentiated absorptive state to a much less differentiated secretory state during cystogenesis and that this transition is accompanied by loss of epithelial cell polarity and mistargeting of specific membrane proteins. We conducted a detailed evaluation of this hypothesis in the Pkd2WS25/- mouse model of ADPKD. Ultrastructural analysis of Pkd2WS25/- cysts by electron microscopy confirmed that cystic epithelial cells progressively dedifferentiate with cyst enlargement.

Expression of myosin VI within the early endocytic pathway in adult and developing proximal tubules.

Myosin VI is a reverse-direction molecular motor implicated in membrane transport events. Because myosin VI is most highly expressed in the kidney, we investigated its renal localization by using high-resolution immunocytochemical and biochemical methods. Indirect immunofluorescence microscopy revealed myosin VI at the base of the brush border in proximal tubule cells.