A functional genomics screen identifying blood cell development genes in Drosophila by undergraduates participating in a course-based research experience.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.

A systematic review of non-pharmacological interventions used for pain relief after orthopedic surgical procedures.

The purpose of the present review was to evaluate the available evidence on the efficacy of various non-pharmacological interventions to relieve pain after orthopedic surgical procedures. An electronic search of the PubMed, Embase and Cochrane library databases was performed to retrieve studies of all types assessing the role of non-pharmacological interventions for pain relief after orthopedic surgical procedures. The included studies were required to assess pain outcomes using a validated measurement index, such as the Visual Analog Scale. The quality of randomized control trials (RCTs) was assessed using the Cochrane tool, while the ROBINS-I tool was used for non-RCTs. A total of five studies were included, namely three RCTs and two non-RCTs. The included studies used relaxation therapy, guided imagery, music and audio-visual distraction for pain management. There was considerable heterogeneity concerning study participants and types of intervention, which precluded a meta-analysis. Overall, all studies reported a significant beneficial effect of non-pharmacological interventions for pain relief. To conclude, current evidence from a limited number of studies indicates there may be a potential role of non-pharmacological interventions, including relaxation therapy, guided imagery, music and audio-visual distraction, in pain management of patients after orthopedic surgery. Owing to considerable heterogeneity and risk of bias in the included studies, strong conclusions cannot be drawn. Further high-quality RCTs assessing the role of such non-pharmacological techniques of pain management are required to strengthen the current evidence.

Combined therapy with GABA and proinsulin/alum acts synergistically to restore long-term normoglycemia by modulating T-cell autoimmunity and promoting ß-cell replication in newly diabetic NOD mice.

Antigen-based therapies (ABTs) fail to restore normoglycemia in newly diabetic NOD mice, perhaps because too few ß-cells remain by the time that ABT-induced regulatory responses arise and spread. We hypothesized that combining a fast-acting anti-inflammatory agent with an ABT could limit pathogenic responses while ABT-induced regulatory responses arose and spread. γ-Aminobutyric acid (GABA) administration can inhibit inflammation, enhance regulatory T-cell (Treg) responses, and promote ß-cell replication in mice. We examined the effect of combining a prototypic ABT, proinsulin/alum, with GABA treatment in newly diabetic NOD mice. Proinsulin/alum monotherapy failed to correct hyperglycemia, while GABA monotherapy restored normoglycemia for a short period. Combined treatment restored normoglycemia in the long term with apparent permanent remission in some mice. Proinsulin/alum monotherapy induced interleukin (IL)-4- and IL-10-secreting T-cell responses that spread to other ß-cell autoantigens. GABA monotherapy induced moderate IL-10 (but not IL-4) responses to ß-cell autoantigens. Combined treatment synergistically reduced spontaneous type 1 T-helper cell responses to autoantigens, ABT-induced IL-4 and humoral responses, and insulitis, but enhanced IL-10 and Treg responses and promoted ß-cell replication in the islets. Thus, combining ABT with GABA can inhibit pathogenic T-cell responses, induce Treg responses, promote ß-cell replication, and effectively restore normoglycemia in newly diabetic NOD mice. Since these treatments appear safe for humans, they hold promise for type 1 diabetes intervention.

γ-Aminobutyric acid regulates both the survival and replication of human ß-cells.

γ-Aminobutyric acid (GABA) has been shown to inhibit apoptosis of rodent ß-cells in vitro. In this study, we show that activation of GABAA receptors (GABAA-Rs) or GABAB-Rs significantly inhibits oxidative stress-related ß-cell apoptosis and preserves pancreatic ß-cells in streptozotocin-rendered hyperglycemic mice. Moreover, treatment with GABA, or a GABAA-R- or GABAB-R-specific agonist, inhibited human ß-cell apoptosis following islet transplantation into NOD/scid mice. Accordingly, activation of GABAA-Rs and/or GABAB-Rs may be a useful adjunct therapy for human islet transplantation. GABA-R agonists also promoted ß-cell replication in hyperglycemic mice. While a number of agents can promote rodent ß-cell replication, most fail to provide similar activities with human ß-cells. In this study, we show that GABA administration promotes ß-cell replication and functional recovery in human islets following implantation into NOD/scid mice. Human ß-cell replication was induced by both GABAA-R and GABAB-R activation. Hence, GABA regulates both the survival and replication of human ß-cells. These actions, together with the anti-inflammatory properties of GABA, suggest that modulation of peripheral GABA-Rs may represent a promising new therapeutic strategy for improving ß-cell survival following human islet transplantation and increasing ß-cells in patients with diabetes.