DESEGREGATION IN AN ERA OF RESEGREGATION: HOW HETEROGENEOUS SECONDARY SCIENCE CLASSES INCREASE STUDENT ACHIEVEMENT AND ENTRANCE INTO THE STEM PIPELINE

African American students are underrepresented in high-level secondary science courses that preclude them from pursuing post-secondary science, technology, engineering, and mathematics (STEM) degrees and careers. A significant factor associated with this problem is the institutionalized organization of secondary curriculum and instruction that disproportionately tracks or groups students of color into lower-level courses. African American students are disproportionately placed into lower-level science courses where they receive an inequitable opportunity to learn. A mixed methods design was used in which both qualitative and quantitative data were embedded within a major design intervention trial to address the negative effects caused by ability grouping in science by measuring the effect of heterogeneous chemistry classes on student achievement, self-efficacy, engagement, and interest in science. Findings revealed that regardless of course recommendation, initial achievement levels, and race, initially lower and higher achieving students enrolled in high-level heterogeneous science classes outperform their peers in traditionally grouped course levels and have higher levels of self-efficacy. Findings suggest that teacher professional development in the areas of differentiated instruction, mindset, and self-efficacy are important factors contributing to the success of students in heterogeneous classes

Implication of Mitochondrial Cytoprotection in Human Islet Isolation and Transplantation

Islet transplantation is a promising therapy for type 1 diabetes mellitus; however, success rates in achieving both short- and long-term insulin independence are not consistent, due in part to inconsistent islet quality and quantity caused by the complex nature and multistep process of islet isolation and transplantation. Since the introduction of the Edmonton Protocol in 2000, more attention has been placed on preserving mitochondrial function as increasing evidences suggest that impaired mitochondrial integrity can adversely affect clinical outcomes. Some recent studies have demonstrated that it is possible to achieve islet cytoprotection by maintaining mitochondrial function and subsequently to improve islet transplantation outcomes. However, the benefits of mitoprotection in many cases are controversial and the underlying mechanisms are unclear. This article summarizes the recent progress associated with mitochondrial cytoprotection in each step of the islet isolation and transplantation process, as well as islet potency and viability assays based on the measurement of mitochondrial integrity. In addition, we briefly discuss immunosuppression side effects on islet graft function and how transplant site selection affects islet engraftment and clinical outcomes

Implication of Mitochondrial Cytoprotection in Human Islet Isolation and Transplantation

Islet transplantation is a promising therapy for type 1 diabetes mellitus; however, success rates in achieving both short-and longterm insulin independence are not consistent, due in part to inconsistent islet quality and quantity caused by the complex nature and multistep process of islet isolation and transplantation. Since the introduction of the Edmonton Protocol in 2000, more attention has been placed on preserving mitochondrial function as increasing evidences suggest that impaired mitochondrial integrity can adversely affect clinical outcomes. Some recent studies have demonstrated that it is possible to achieve islet cytoprotection by maintaining mitochondrial function and subsequently to improve islet transplantation outcomes. However, the benefits of mitoprotection in many cases are controversial and the underlying mechanisms are unclear. This article summarizes the recent progress associated with mitochondrial cytoprotection in each step of the islet isolation and transplantation process, as well as islet potency and viability assays based on the measurement of mitochondrial integrity. In addition, we briefly discuss immunosuppression side effects on islet graft function and how transplant site selection affects islet engraftment and clinical outcomes

The roles of progranulin and TMEM106B in lysosomal physiology and neurodegenerative disease

Frontotemporal lobar degeneration (FTLD) is a devastating, clinically heterogeneous neurodegenerative disease that results in the progressive atrophy of the frontal and temporal lobes of the brain. Most often presenting with drastic alterations in personality and behavior, as well as a gradual decline in language capabilities, FTLD is the second leading cause of early-onset dementia only after Alzheimer’s disease. One of the major causes of familial FTLD is haploinsufficiency of the protein, progranulin (PGRN), resulting from mutation in the granulin (GRN) gene. Interestingly, PGRN shows a dosage-dependent disease correlation, and GRN mutation resulting in complete loss of PGRN causes the lysosomal storage disease (LSD), neuronal ceroid lipofuscinosis (NCL). In this text, my co-workers and I demonstrate that PGRN is proteolytically processed in the lysosome into discrete granulin peptides, which may possess distinct functions. We have independently found interactions between PGRN or granulin peptides and three lysosomal hydrolases: Cathepsin D (CTSD), glucocerebrosidase (GBA), and ɑ-N-acetylgalactosaminidase (NAGA). The activity of each of these enzymes was found to be reduced in Grn-/- mice, indicating that a potential mechanism of PGRN-related disease may be dysfunction of multiple lysosomal hydrolases. In addition to possessing an indeterminate lysosomal function, PGRN has also been shown to be a neurotrophic factor. Completion of a high-throughput screen searching for the receptor that mediates this function identified cluster of differentiation 68 (CD68) and neuropilin 2 (NRP2) as putative PGRN receptors. A second protein that has become of interest to the study of FTLD is TMEM106B. Variants of TMEM106B have been associated with an increased risk of developing FTLD, especially in cases of GRN mutation (FTLD-GRN). Although TMEM106B is known to be an endolysosomal transmembrane protein that regulates lysosomal morphology and degradative capacity, its exact function is unclear. Our current findings suggest that TMEM106B may regulate cellular levels of the phosphoinositide, PI(3,5)P2. In summary, our work supports a lysosomal role of the FTLD- and NCL-related protein, PGRN, and identifies a novel function of the FTLD risk factor, TMEM106B