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Lysosomes play important roles in catabolism, nutrient sensing, metabolic signaling, and homeostasis. NPC1 deficiency disrupts lysosomal function by inducing cholesterol accumulation that leads to early neurodegeneration in Niemann-Pick type C (NPC) disease. Mitochondria pathology and deficits in NPC1 deficient cells are associated with impaired lysosomal proteolysis and metabolic signaling. It is thought that activation of the transcription factor TFEB, an inducer of lysosome biogenesis, restores lysosomal-autophagy activity in lysosomal storage disorders. Here, we investigated the effect of trehalose, a TFEB activator, in the mitochondria pathology of NPC1 mutant fibroblastsin vitroand in mouse developmental Purkinje cellsex vivo. We found that in NPC1 mutant fibroblasts, serum starvation or/and trehalose treatment, both activators of TFEB, reversed mitochondria fragmentation to a more tubular mitochondrion. Trehalose treatment also decreased the accumulation of Filipin⁺cholesterol in NPC1 mutant fibroblasts. However, trehalose treatment in cerebellar organotypic slices (COSCs) from wild-type andNpc1^nmf164mice caused mitochondria fragmentation and lack of dendritic growth and degeneration in developmental Purkinje cells. Our data suggest, that although trehalose successfully restores mitochondria length and decreases cholesterol accumulation in NPC1 mutant fibroblasts, in COSCs, Purkinje cells mitochondria and dendritic growth are negatively affected possibly through the overactivation of the TFEB-lysosomal-autophagy pathway. 

Abstract Though much is known about children's sexual abuse disclosure, less attention has been directed towards disclosure in other types of youthful victims, especially those who may be reluctant to tell due to either normative development or victims' specific experiences. Trafficked youth, particularly those who are adolescents, represent one such group. Understanding how suspected youth trafficking victims are questioned by authorities, especially with respect to establishing rapport and trust, is important for informing professionals how to effectively question this unique population of victims to overcome their reluctance. We examined transcripts of interviews conducted by federal interviewers (n = 12,653 question‐answer turns across 33 interviews) and police (n = 4,972 question‐answer turns across 14 interviews) with trafficked youth between the ages of 12 and 18. Interviews were reliably coded for the length of pre‐substantive questioning, provision of instructions and ground rules, and use of rapport building and supportive strategies. Federal interviewers used pre‐substantive instructions and built rapport with potential victims more often than police did. Also, and although infrequently used overall, supportive interviewing strategies were evident more often by federal interviewers than police. Results provide much‐needed knowledge about how law enforcement investigators interview and elicit disclosures from vulnerable populations of adolescent victims. 

Abstract Purkinje cell (PC) loss occurs at an early age in patients and animal models of Niemann-Pick Type C (NPC), a lysosomal storage disease caused by mutations in theNpc1orNpc2genes. Although degeneration of PCs occurs early in NPC, little is known about how NPC1 deficiency affects the postnatal development of PCs. Using theNpc1^nmf164mouse model, we found that NPC1 deficiency significantly affected the postnatal development of PC dendrites and synapses. The developing dendrites of Npc1^nmf164PCs were significantly deficient in mitochondria and lysosomes. Furthermore, anabolic (mTORC1) and catabolic (TFEB) signaling pathways were not only perturbed but simultaneously activated in NPC1-deficient PCs, suggesting a loss of metabolic balance. We also found that mice with conditional heterozygous deletion of the Phosphatase and Tensin Homolog Deleted on Chromosome 10 gene (Pten-cHet), an inhibitor of mTORC1, showed similar early dendritic alterations in PCs to those found inNpc1-deficient mice. However, in contrast toNpc1^nmf164mice,Pten-cHet mice exhibited the overactivation of the mTORC1 pathway but with a strong inhibition of TFEB signaling, along with no dendritic mitochondrial reductions by the end of their postnatal development. Our data suggest that disruption of the lysosomal-metabolic signaling in PCs causes dendritic and synaptic developmental deficits that precede and promote their early degeneration in NPC. 

Abstract Cognitive flexibility, the adaptation of representations and responses to new task demands, improves dramatically in early childhood. It is unclear, however, whether flexibility is a coherent, unitary cognitive trait, or is an emergent dimension of task-specific performance that varies across populations with divergent experiences. Three- to 5-year-old English-speaking U.S. children and Tswana-speaking South African children completed two distinct language-processing cognitive flexibility tests: the FIM-Animates, a word-learning test, and the 3DCCS, a rule-switching test. U.S. and South African children did not differ in word-learning flexibility but showed similar age-related increases. In contrast, U.S. preschoolers showed an age-related increase in rule-switching flexibility but South African children did not. Verbal recall explained additional variance in both tests but did not modulate the interaction between population sample (i.e., country) and task. We hypothesize that rule-switching flexibility might be more dependent upon particular kinds of cultural experiences, whereas word-learning flexibility is less cross-culturally variable.