103 research outputs found
USDA CSREES\u27 Role in Broadening Support for an Aging Nation
The aging of America is of major public concern and has far-reaching implications for the nation and for rural communities. In particular, older Americans in rural areas face a wide array of challenges that negatively affect their health and quality of life. Working with its land-grant university and the Cooperative Extension System partners, USDA CSREES is strategically directed and uniquely positioned to address many of these challenges through effective research, education, and Extension activities
Gibberellin and abscisic acid transporters facilitate endodermal suberin formation in Arabidopsis
The plant hormone gibberellin (GA) regulates multiple developmental processes. It accumulates in the root elongating endodermis, but how it moves into this cell file and the significance of this accumulation are unclear. Here we identify three NITRATE TRANSPORTER1/PEPTIDE TRANSPORTER (NPF) transporters required for GA and abscisic acid (ABA) translocation. We demonstrate that NPF2.14 is a subcellular GA/ABA transporter, presumably the first to be identified in plants, facilitating GA and ABA accumulation in the root endodermis to regulate suberization. Further, NPF2.12 and NPF2.13, closely related proteins, are plasma membrane-localized GA and ABA importers that facilitate shoot-to-root GA translocation, regulating endodermal hormone accumulation. This work reveals that GA is required for root suberization and that GA and ABA can act non-antagonistically. We demonstrate how the clade of transporters mediates hormone flow with cell-file-specific vacuolar storage at the phloem unloading zone, and slow release of hormone to induce suberin formation in the maturation zone
Two Isoforms of the mRNA Binding Protein IGF2BP2 Are Generated by Alternative Translational Initiation
IGF2BP2 is a member of a family of mRNA binding proteins that, collectively, have been shown to bind to several different mRNAs in mammalian cells, including one of the mRNAs encoding insulin-like growth factor-2. Polymorphisms in the Igf2bp2 gene are associated with risk of developing type 2 diabetes, but detailed functional characterisation of IGF2BP2 protein is lacking. By immunoblotting with C-terminally reactive antibodies we identified a novel IGF2BP2 isoform with a molecular weight of 58 kDa in both human and rodents, that is expressed at somewhat lower levels than the full-length 65 kDa protein. We demonstrated by mutagenesis that this isoform is generated by alternative translation initiation at the internal Met69. It lacks a conserved N-terminal RNA Recognition Motif (RRM) and would be predicted to differ functionally from the canonical full length isoform. We further investigated IGF2BP2 mRNA transcripts by amplification of cDNA using 5′-RACE. We identified multiple transcription start sites of the human, mouse and rat Igf2bp2 genes in a highly conserved region only 50–90 nts upstream of the major translation start site, ruling out the existence of N-terminally extended isoforms. We conclude that structural heterogeneity of IGF2BP2 protein should be taken into account when considering cellular function
Androgen receptor signalling in the male adrenal facilitates X-zone regression, cell turnover and protects against adrenal degeneration during ageing
Androgens are known to be an essential regulator of male health. Androgen receptor (AR) is widely expressed throughout the adrenal cortex, yet the wider role for androgen signalling in the adrenal remains underexplored. To investigate AR-dependent and AR-independent androgen signalling in the adrenal, we used a novel mouse model with a specific ablation of androgen receptor in the adrenal cortex with or without reduction of circulating androgen levels by castration. Our results describe AR expression in the human and mouse adrenal and highlight that the mouse is a viable model to investigate androgen signalling in the adrenal cortex. We show androgen signalling via AR is required for X-zone regression during puberty. Furthermore, cortex measurements define differences in X-zone morphology depending on whether circulating androgens or AR have been removed. We show androgens promote both cortical cell differentiation and apoptosis but are dispensable for the formation of the definitive cortex. Additionally, investigation of aged mice with AR ablation reveals severe cortex disruption, spindle cell hyperplasia and X-zone expansion. The data described herein demonstrates AR-signalling is required to facilitate X-zone regression, cell clearance and to protect against adrenal degeneration during ageing.Full Tex
CarboCell G/C offers high and prolonged concentrations of gentamicin and clindamycin in bone tissue following intraosseous injection
Objectives: The novel local antibiotic-eluting depot technology CarboCell G/C has shown great promise in terms of efficacy in an osteomyelitis pig model. The present study aimed to investigate the initial release kinetics of gentamicin and clindamycin from CarboCell G/C in trabecular bone after a thin-needle intraosseous injection. Methods: In the tibial metaphysis of four pigs (both hind legs, n=8), microdialysis catheters were placed 5 and 10 mm from an intraosseous injected CarboCell G/C depot of 1.5 mL comprising gentamicin (25 mg) and clindamycin (95 mg). Sampling was performed for 12 consecutive hours to evaluate gentamicin and clindamycin concentrations in trabecular bone and subcutaneous tissue adjacent to the knee joint. Plasma samples were taken to determine systemic spillover. Results: Across trabecular bone locations, the mean peak drug concentrations ranged from 471–524 µg mL−1 for gentamicin and from 681–788 µg mL−1 for clindamycin. The mean concentrations at 12 h ranged from 126–321 µg mL−1 for gentamicin and from 255–594 µg mL−1 for clindamycin. Low concentrations of both drugs were found in subcutaneous tissue adjacent to the knee joint (<1 µg mL−1) and plasma (<0.2 µg mL−1). Conclusions: CarboCell G/C can maintain high local concentrations of gentamicin and clindamycin for at least 12 h after intraosseous injection with negligible systemic spillover. The data bolster the potential benefit of improved local antibiotic delivery systems with flexible administration in target tissues for future therapeutic strategies addressing orthopaedic infections.</p
The Epidemiology, Genetics and Future Management of Syndactyly
Syndactyly is a condition well documented in current literature due to it being the most common congenital hand defect, with a large aesthetic and functional significance
USDA CSREES\u27 Role in Broadening Support for an Aging Nation
The aging of America is of major public concern and has far-reaching implications for the nation and for rural communities. In particular, older Americans in rural areas face a wide array of challenges that negatively affect their health and quality of life. Working with its land-grant university and the Cooperative Extension System partners, USDA CSREES is strategically directed and uniquely positioned to address many of these challenges through effective research, education, and Extension activities
Androgen receptor mRNA expression during mouse embryogenesis is confined to distinct sites but indistinguishable between males and females in its spatio-temporal pattern
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