Research networking and the role of the medical librarian.

Medical librarians work collaboratively across all units and missions of academic medical centers. One area where librarians can provide key expertise is in the building and maintenance of Research Information Management Systems (RIMS). At Penn State, the RIMS implementation team has included a medical librarian, research administrators and marketing staff from the College of Medicine (CoM) since its inception in 2016.

How Does a Junior Faculty Development Program Affect Burnout? A Mixed Methods Assessment.

Objectives: Burnout is common among junior faculty. Professional development has been proposed as a method to improve engagement and reduce burnout among academic physicians. The Penn State College of Medicine Junior Faculty Development Program (JFDP) is a well-established, interdisciplinary program.

Podocyte-specific chemokine (C-C motif) receptor 2 overexpression mediates diabetic renal injury in mice.

Inflammation is a central pathophysiologic mechanism that contributes to diabetes mellitus and diabetic nephropathy. Recently, we showed that macrophages directly contribute to diabetic renal injury and that pharmacological blockade or genetic deficiency of chemokine (C-C motif) receptor 2 (CCR2) confers kidney protection in diabetic nephropathy. However, the direct role of CCR2 in kidney-derived cells such as podocytes in diabetic nephropathy remains unclear.

Insulin treatment normalizes retinal neuroinflammation but not markers of synapse loss in diabetic rats.

Diabetic retinopathy is one of the leading causes of blindness in developed countries, and a majority of patients with type I and type II diabetes will develop some degree of vision loss despite blood glucose control regimens. The effects of different insulin therapy regimens on early metabolic, inflammatory and neuronal retinal disease processes such as retinal neuroinflammation and synapse loss have not been extensively investigated. This study compared 3 months non-diabetic and streptozotocin (STZ)-induced diabetic Sprague Dawley rats.

Nanoliposomal minocycline for ocular drug delivery.

Unlabelled: Nanoliposomal technology is a promising drug delivery system that could be employed to improve the pharmacokinetic properties of clearance and distribution in ocular drug delivery to the retina. We developed a nanoscale version of an anionic, cholesterol-fusing liposome that can encapsulate therapeutic levels of minocycline capable of drug delivery. We demonstrate that size extrusion followed by size-exclusion chromatography can form a stable 80-nm liposome that encapsulates minocycline at a concentration of 450 ± 30 μM, which is 2% to 3% of loading material.

Hyperglycemia-induced O-GlcNAcylation and truncation of 4E-BP1 protein in liver of a mouse model of type 1 diabetes.

4E-BP1 is a protein that, in its hypophosphorylated state, binds the mRNA cap-binding protein eIF4E and represses cap-dependent mRNA translation. By doing so, it plays a major role in the regulation of gene expression by controlling the overall rate of mRNA translation as well as the selection of mRNAs for translation. Phosphorylation of 4E-BP1 causes it to release eIF4E to function in mRNA translation.

Chronic insulin treatment of diabetes does not fully normalize alterations in the retinal transcriptome.

Background: Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. Approximately 95% of patients with Type 1 diabetes develop some degree of retinopathy within 25 years of diagnosis despite normalization of blood glucose by insulin therapy. The goal of this study was to identify molecular changes in the rodent retina induced by diabetes that are not normalized by insulin replacement and restoration of euglycemia.

Multi-modal proteomic analysis of retinal protein expression alterations in a rat model of diabetic retinopathy.

Background: As a leading cause of adult blindness, diabetic retinopathy is a prevalent and profound complication of diabetes. We have previously reported duration-dependent changes in retinal vascular permeability, apoptosis, and mRNA expression with diabetes in a rat model system. The aim of this study was to identify retinal proteomic alterations associated with functional dysregulation of the diabetic retina to better understand diabetic retinopathy pathogenesis and that could be used as surrogate endpoints in preclinical drug testing studies.

Circulating sphingolipid biomarkers in models of type 1 diabetes.

Alterations in lipid metabolism may contribute to diabetic complications. Sphingolipids are essential components of cell membranes and have essential roles in homeostasis and in the initiation and progression of disease. However, the role of sphingolipids in type 1 diabetes remains largely unexplored.

Skeletal muscle protein balance in mTOR heterozygous mice in response to inflammation and leucine.

Sepsis and lipopolysaccharide (LPS) may decrease skeletal muscle protein synthesis by impairing mTOR (mammalian target of rapamycin) activity. The role of mTOR in regulating muscle protein synthesis was assessed in wild-type (WT) and mTOR heterozygous (+/-) mice under basal conditions and in response to LPS and/or leucine stimulation. No difference in body weight of mTOR(+/-) mice was observed compared with WT mice; whereas whole body lean body mass was reduced.

Transcriptomic comparison of the retina in two mouse models of diabetes.

Mouse models of type I diabetes offer the potential to combine genetic approaches with other pharmacological or physiological manipulations to investigate the pathophysiology and treatment of diabetic retinopathy. Type I diabetes is induced in mice through chemical toxins or can arise spontaneously from genetic mutations. Both models are associated with retinal vascular and neuronal changes.

Dendrite remodeling and other abnormalities in the retinal ganglion cells of Ins2 Akita diabetic mice.

Purpose: To determine the extent of retinal ganglion cell loss and morphologic abnormalities in surviving ganglion cells in Ins2 Akita/+ diabetic mice.

Methods: Mice that expressed cyan fluorescent protein (CFP) or yellow fluorescent protein (YFP) reporter genes under the transcriptional control of the Thy1 promoter were crossed with Ins2 Akita/+ mice. After 3 months of diabetes, the number and morphology of retinal ganglion cells was analyzed by confocal microscopy.

Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling.

Although insulin resistance has been traditionally associated with type 2 diabetes, recent evidence in humans and animal models indicates that insulin resistance may also develop in type 1 diabetes. A point mutation of insulin 2 gene in Ins2(Akita) mice leads to pancreatic beta-cell apoptosis and hyperglycemia, and these mice are commonly used to investigate type 1 diabetes and complications. Since insulin resistance plays an important role in diabetic complications, we performed hyperinsulinemic-euglycemic clamps in awake Ins2(Akita) and wild-type mice to measure insulin action and glucose metabolism in vivo.

Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle.

Leucine is recognized as a nutrient signal; however, the long-term in vivo consequences of leucine signaling and the role of branched-chain amino acid (BCAA) metabolism in this signaling remain unclear. To investigate these questions, we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism. BCATm(-/-) mice exhibited elevated plasma BCAAs and decreased adiposity and body weight, despite eating more food, along with increased energy expenditure, remarkable improvements in glucose and insulin tolerance, and protection from diet-induced obesity.

Osteogenic nodule formation from single embryonic stem cell-derived progenitors.

The process of bone formation can be approximated in vitro in the form of a mineralized nodule. Osteoprogenitors and mesenchymal stem cells (MSCs), the immediate precursors of the osteoprogenitor, proliferate and differentiate into osteoblasts when placed into culture. These osteoblasts secrete and mineralize a matrix during a period of 3-4 weeks.

Diabetic retinopathy: seeing beyond glucose-induced microvascular disease.

Diabetic retinopathy remains a frightening prospect to patients and frustrates physicians. Destruction of damaged retina by photocoagulation remains the primary treatment nearly 50 years after its introduction. The diabetes pandemic requires new approaches to understand the pathophysiology and improve the detection, prevention, and treatment of retinopathy.

Artificial chromosome-based transgenes in the study of genome function.

The transfer of large DNA fragments to the mouse genome in the form of bacterial, yeast or phage artificial chromosomes is an important process in the definition of transcription units, the modeling of inherited disease states, the dissection of candidate regions identified by linkage analysis and the construction of in vivo reporter genes. However, as with small recombinant transgenes, the transferred sequences are usually integrated randomly often with accompanying genomic alterations and variable expression of the introduced genes due to the site of integration and/or copy number. Therefore, alternative methods of integrating large genomic transgenes into the genome have been developed to avoid the variables associated with random integration.

Analysis of embryonic stem cell-derived osteogenic cultures.

The process of bone formation can be approximated in vitro in the form of a mineralized nodule. Osteoprogenitors and mesenchymal stem cells, the immediate precursors to the osteoprogenitor, when placed into culture proliferate and differentiate into osteoblasts. These osteoblasts secrete and mineralize a matrix during a period of 3-4 wk.

The Ins2Akita mouse as a model of early retinal complications in diabetes.

Purpose: This study tested the Ins2(Akita) mouse as an animal model of retinal complications in diabetes. The Ins2(Akita) mutation results in a single amino acid substitution in the insulin 2 gene that causes misfolding of the insulin protein. The mutation arose and is maintained on the C57BL/6J background.

Mice with deficiency of G protein gamma3 are lean and have seizures.

Emerging evidence suggests that the gamma subunit composition of an individual G protein contributes to the specificity of the hundreds of known receptor signaling pathways. Among the twelve gamma subtypes, gamma3 is abundantly and widely expressed in the brain. To identify specific functions and associations for gamma3, a gene-targeting approach was used to produce mice lacking the Gng3 gene (Gng3-/-).

Tissue-specific expression of a BAC transgene targeted to the Hprt locus in mouse embryonic stem cells.

The hypoxanthine phosphoribosyltransferase (Hprt) locus has been shown to have minimal influence on transgene expression when used as a surrogate site in the mouse genome. We have developed a method to transfer bacterial artificial chromosomes (BACs) as a single copy into the partially deleted Hprt locus of embryonic stem cells. BACs were modified by Cre/loxP recombination to contain the sequences necessary for homologous recombination into and complementation of the partially deleted Hprt locus.

Transgenic bcl-2 is not sufficient to rescue all hematolymphoid defects in STAT5A/5B-deficient mice.

Objective: Cytokines bind high-affinity receptors expressed on hematopoietic cells to initiate signaling cascades that regulate differentiation, proliferation, and survival. Previous studies have established a role for STAT5 in transducing survival signals for hematopoietic progenitor cells in response to cytokines.

Materials And Methods: To determine if constitutive expression of a member of the bcl-2 family of anti-apoptotic proteins could compensate for the loss of STAT5, we utilized combinatorial genetics to generate STAT5A/5B-deficient mice expressing a bcl-2 transgene.