Baseline Characteristics of the 2015-2019 First Year Student Cohorts of the NIH Building Infrastructure Leading to Diversity (BUILD) Program.

Objective: The biomedical/behavioral sciences lag in the recruitment and advancement of students from historically underrepresented backgrounds. In 2014 the NIH created the Diversity Program Consortium (DPC), a prospective, multi-site study comprising 10 Building Infrastructure Leading to Diversity (BUILD) institutional grantees, the National Research Mentoring Network (NRMN) and a Coordination and Evaluation Center (CEC). This article describes baseline characteristics of four incoming, first-year student cohorts at the primary BUILD institutions who completed the Higher Education Research Institute, The Freshmen Survey between 2015-2019. These freshmen are the primary student cohorts for longitudinal analyses comparing outcomes of BUILD program participants and non-participants. Design: Baseline description of first-year students entering college at BUILD institutions during 2015-2019. Setting: Ten colleges/universities that each received <$7.5mil/yr in NIH Research Project Grants and have high proportions of low-income students. Participants: First-year undergraduate students who participated in BUILD-sponsored activities and a sample of non-BUILD students at the same BUILD institutions. A total of 32,963 first-year students were enrolled in the project; 64% were female, 18% Hispanic/Latinx, 19% African American/Black, 2% American Indian/Alaska Native and Native Hawaiian/Pacific Islander, 17% Asian, and 29% White. Twenty-seven percent were from families with an income <$30,000/yr and 25% were their family's first generation in college. Planned Outcomes: Primary student outcomes to be evaluated over time include undergraduate biomedical degree completion, entry into/completion of a graduate biomedical degree program, and evidence of excelling in biomedical research and scholarship. Conclusions: The DPC national evaluation has identified a large, longitudinal cohort of students with many from groups historically underrepresented in the biomedical sciences that will inform institutional/national policy level initiatives to help diversify the biomedical workforce.

IMPACT OF OPEN ENROLLMENT IN COURSE-BASED UNDERGRADUATE RESEARCH EXPERIENCES WITH AT-RISK STUDENT POPULATIONS.

Participation in authentic research activities, particularly mentored undergraduate research experiences, at the University of Texas at El Paso has long been associated with student success measures such as graduation and matriculation to strong graduate programs in STEM. However, these opportunities typically are available to upper division students, despite evidence suggesting that the first (Freshman) year at university is determinant for individuals to complete STEM degrees. To expand the number of research opportunities and to extend them preferentially to new, entering students, we established the Freshman Year Research Intensive Sequence (FYRIS) in 2015, a course sequence consisting of a research foundations course and one or two laboratory courses redesigned by faculty into small, special topic Course-based Undergraduate Research Experiences (CUREs). CUREs provide authentic research experiences with similar early-, middle-, and late-term benefits to those found in traditional mentored experiences. Several of these benefits can be conceptualized as "hubs", which derive from earlier benefits, while facilitating later positive outcomes. Self-efficacy is one such hub, while retention and persistence in science enrollment represent late-phase positive outcomes. In this report, we examined self-efficacy of FYRIS participants in surveys administered at the start and end of each course to assess their confidence in conducting fundamental and specific research activities in the foundations and research driven courses, respectively. Specific items from a validated survey were used in addition to items developed for each course based on specific learning objectives. Retention was measured across three years of assessment of participants and non-participants, controlling for key scholastic characteristics. Results on retention rates after FYRIS vary depending on whether students fully or partially participated in the course-sequence. Results will be presented for three cohorts of students: 2015-16, 2016-17, and 2017-18.

BUILDing SCHOLARS: enhancing diversity among U.S. biomedical researchers in the Southwest.

BACKGROUND AND PURPOSE: With funding from the National Institutes of Health, BUILDing SCHOLARS was established at The University of Texas at El Paso with the goal of implementing, evaluating and sustaining a suite of institutional, faculty and student development interventions in order to train the next generation of biomedical researchers from the U.S. Southwest region, where the need is dire among underserved communities. The focus is on supporting the infrastructure necessary to train and mentor students so they persist on pathways across a range of biomedical research fields. The purpose of this article is to highlight the design and implementation of BUILDing SCHOLARS' key interventions, which offer a systemic student training model for the U.S. Southwest. In-depth reporting of evaluation results is reserved for other technical publications. PROGRAM AND KEY HIGHLIGHTS: BUILDing SCHOLARS uses a comprehensive regional approach to undergraduate training through a multi-institution consortium that includes 12 research partners and various pipeline partners across Texas, New Mexico, and Arizona. Through faculty collaborations and undergraduate research training, the program integrates social and behavioral sciences and biomedical engineering while emphasizing seven transdisciplinary nodes of biomedical research excellence that are common across partner institutions: addiction, cancer, degenerative and chronic diseases, environmental health, health disparities, infectious diseases, and translational biomedicine. Key interventions aim to: (1) improve institutional capacities by expanding undergraduate research training infrastructures; (2) develop an intra- and cross-institutional mentoring-driven "community of practice" to support undergraduate student researchers; (3) broaden the pool of student participants, improve retention, and increase matriculation into competitive graduate programs; and (4) support faculty and postdoctoral personnel by training them in research pedagogy and mentoring techniques and providing them with resources for increasing their research productivity. Student training activities focus on early interventions to maximize retention and on enabling students to overcome common barriers by addressing their educational endowments, science socialization, network development, family expectations, and material resources. Over the long term, BUILDing SCHOLARS will help increase the diversity of the biomedical research workforce in the U.S. by meeting the needs of students from the Southwest region and by serving as a model for other institutions.

Lipidomic analysis reveals that phosphatidylglycerol and phosphatidylethanolamine are newly generated phospholipids in an early-divergent protozoan, Giardia lamblia.

The pathogenic protozoan Giardia lamblia is known to not synthesize membrane lipids de novo. Therefore, it is possible that lipids in the small intestine, where trophozoites colonize, play key roles in regulating the growth and differentiation of this important pathogen. The focus of the current study is to conduct a complete lipidomic analysis and to test the hypothesis that Giardia has some ability to generate new phospholipids (PLs). Using mass spectrometry, now we show that phosphatidylglycerols (PGs) are major PLs followed by phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) in non-encysting and encysting trophozoites, as well in cysts. The fatty acids attached to these PLs consist mostly of palmitate, palmitoleate, oleate, and linoleate. Results also indicate that PGs and PEs, unlike PCs, are not present in bovine bile and serum, the major sources of lipids of the culture medium, and that they could therefore be produced by fatty acid and headgroup remodeling reactions, circumventing the synthesis of entirely new PLs via de novo pathways. Genomic and transcriptional analyses show the presence of giardial phosphatidylglycerolphosphate synthase (gpgps) and phosphatidylserine decarboxylase (gpsd) genes, which are expressed throughout the life cycle. Bioinformatic and phylogenetic analyses further indicated that both genes are of prokaryotic origin and that they have undergone duplication in the course of evolution. Our studies suggest that the abundance of PG in Giardia is unique among eukaryotes and that its synthesis thus could serve as a potential target for developing new therapies against this waterborne parasite.

Genomic minimalism in the early diverging intestinal parasite Giardia lamblia.

The genome of the eukaryotic protist Giardia lamblia, an important human intestinal parasite, is compact in structure and content, contains few introns or mitochondrial relics, and has simplified machinery for DNA replication, transcription, RNA processing, and most metabolic pathways. Protein kinases comprise the single largest protein class and reflect Giardia's requirement for a complex signal transduction network for coordinating differentiation. Lateral gene transfer from bacterial and archaeal donors has shaped Giardia's genome, and previously unknown gene families, for example, cysteine-rich structural proteins, have been discovered. Unexpectedly, the genome shows little evidence of heterozygosity, supporting recent speculations that this organism is sexual. This genome sequence will not only be valuable for investigating the evolution of eukaryotes, but will also be applied to the search for new therapeutics for this parasite.

Transcriptional analysis of three major putative phosphatidylinositol kinase genes in a parasitic protozoan, Giardia lamblia.

The current investigation evaluates the expression of phosphatidylinositol kinase (PIK) genes in the parasitic protozoan, Giardia lamblia. The G. lamblia Genome Database revealed the presence of two putative phosphatidylinositol-3-kinase (gPI3K) and one phosphatidylinositol-4-kinase (gPI4K) genes resembling the catalytic subunit of eukaryotic PIKs. Primers, designed to amplify mRNA of these three genes, were used to measure transcription by quantitative reverse-transcriptase polymerase chain reactions. Results suggest that all three PIK genes are expressed in non-encysting and encysting trophozoites. The relative levels of the mRNA were highest in parasites cultured in pre-encysting medium that contained no bile. Two inhibitors of PI3K, LY 294002 and wortmannin were found to inhibit the growth of the trophozoite in culture. However, wortmannin was more effective than LY294002. Altogether, the present study indicates that Giardia is capable of expressing PIKs that are necessary for the growth and differentiation of this pathogen.

Clathrin-dependent pathways and the cytoskeleton network are involved in ceramide endocytosis by a parasitic protozoan, Giardia lamblia.

Although identified as an early-diverged protozoan, Giardia lamblia shares many similarities with higher eukaryotic cells, including an internal membrane system and cytoskeleton, as well as secretory pathways. However, unlike many other eukaryotes, Giardia does not synthesize lipids de novo, but rather depends on exogenous sources for both energy production and organelle or membrane biogenesis. It is not known how lipid molecules are taken up by this parasite and if endocytic pathways are involved in this process. In this investigation, we tested the hypothesis that highly regulated and selective lipid transport machinery is present in Giardia and necessary for the efficient internalization and intracellular targeting of ceramide molecules, the major sphingolipid precursor. Using metabolic and pathway inhibitors, we demonstrate that ceramide is internalized through endocytic pathways and is primarily targeted into perinuclear/endoplasmic reticulum membranes. Further investigations suggested that Giardia uses both clathrin-dependent pathways and the actin cytoskeleton for ceramide uptake, as well as microtubule filaments for intracellular localization and targeting. We speculate that this parasitic protozoan has evolved cytoskeletal and clathrin-dependent endocytic mechanisms for importing ceramide molecules from the cell exterior for the synthesis of membranes and vesicles during growth and differentiation.