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Lauren Smith

Publications and source records attributed to Lauren Smith.

7 recordsLinked to original sources
PubMed2006

Context-dependent dysregulation of transcription by mutant huntingtin.

Huntington disease (HD) is an adult-onset neurodegenerative disease caused by expansion of a polyglutamine (poly(Q) tract in the N-terminal region of huntingtin (htt). Although the precise mechanisms leading to neurodegeneration in HD have not been fully elucidated, transcriptional dysregulation has been implicated in disease pathogenesis. In HD, multiple N-terminal mutant htt fragments smaller than the first 500 amino acids have been found to accumulate in the nucleus and adversely affect gene transcription. It is unknown whether different htt fragments in the nucleus can differentially bind transcription factors and affect transcription. Here, we report that shorter N-terminal htt fragments, which are more prone to misfolding and aggregation, are more competent to bind Sp1 and inhibit its activity. These effects can be reversed by Hsp40, a molecular chaperone that reduces the misfolding of mutant htt. Our results provide insight into the beneficial effects of molecular chaperones and suggest that context dependent transcriptional dysregulation may contribute to differential toxicity of various N-terminal htt fragments.

Animals↗
PubMed2006

Blue digits.

Explore the source record for details and available documents.

Cyanosis↗
PubMed2004

Nociception and antinociception during the first week of life in mice: sex differences and test dependence.

UNLABELLED: This study demonstrates that reliable sex differences in nociceptive and antinociceptive mechanisms are present in even very young subjects. Sex differences were observed in mice tested either on the day of birth or 1 week later on basal tail-flick latency and morphine analgesic magnitude. Female mice had longer tail-withdrawal latencies; male mice demonstrated stronger analgesic responses to morphine. In addition, basal pain behavior and analgesic responsiveness differed between day-old and week-old animals on the hot plate, with day-old mice showing enhanced pain behavior and reduced morphine antinociception compared to week-old subjects. These findings further support the competence of pain processing circuitry in even very young subjects and highlight the early development of nociceptive and antinociceptive mechanisms. PERSPECTIVE: This study highlights the competence of nociceptive circuitry and the analgesic efficacy of morphine as early as the day of birth in mice, reinforcing the importance of evaluating and treating pain in even the youngest subjects. Sex differences were present, suggesting infant sex as one of several potential factors that predict the experience of procedural or pathological pain and analgesic requirement.

Analgesics↗
PubMed2004

Why pediatricians need lawyers to keep children healthy.

Pediatricians recognize that social and nonmedical factors influence child health and that there are many government programs and laws designed to provide for children's basic needs. However, gaps in implementation result in denials of services, leading to preventable poor health outcomes. Physician advocacy in these arenas is often limited by lack of knowledge, experience, and resources to intervene. The incorporation of on-site lawyers into the health care team facilitates the provision of crucial legal services to vulnerable families. Although social workers and case managers play a critical role in assessing family stability and finding appropriate resources for families, lawyers are trained to identify violations of rights and to take the appropriate legal steps to hold agencies, landlords, schools, and others accountable on behalf of families. The incorporation of lawyers in the clinical setting originated at an urban academic medical center and is being replicated at >30 sites across the country. Lawyers can help enhance a culture of advocacy in pediatrics by providing direct legal assistance and case consultation for providers, as well as jointly addressing systemic issues affecting children and families. Until laws to promote health and safety are consistently applied and enforced, pediatricians will need lawyers to effectively care for vulnerable children.

Child↗
PubMed2002

Comorbidity of bipolar disorder and substance abuse in Costa Rica: pedigree- and population-based studies.

BACKGROUND: The purpose of this study was to determine the prevalence of substance use disorders (substance abuse or substance dependence: SA/SD) in a large sample of Bipolar Type I (BPI) patients drawn from the Costa Rican population and to describe the effects of SA/SD on the course of their bipolar disorder. METHOD: 110 subjects from two high-risk (for BPI) Costa Rican pedigrees and 205 unrelated Costa Rican BPI subjects were assessed using structured interviews and a best estimate process. Chi(2) and survival analyses were performed to assess the effect of gender on comorbidity risk, and the effect of comorbidity on the clinical course of BPI. RESULTS: SA/SD (primarily alcohol dependence) occurred in 17% of the BPI patients from the population sample and 35% of the BPI patients from the pedigree sample. Comorbid SA/SD was strongly associated with gender chi(2) = 16.84, P = 0.00004). In comorbid subjects, alcohol dependence tended to predate the first manic episode (chi(2) = 6.54, P < 0.025). History of SA/SD did not significantly alter the prevalence of psychosis or age of onset of mania in BPI subjects. CONCLUSIONS: These results suggest that SA/SD comorbidity rates are lower in this type of population than in BPI patient populations in the US. Gender is a strong predictor of comorbidity prevalence in BPI patients from this population. Although SA/SD may be a risk factor for precipitating BPI in those at risk, in this population comorbid BPI subjects do not have a different onset or course of BPI in comparison to BPI patients without comorbidity.

Bipolar Disorder↗
PubMedDate not supplied

Conduit properties and karstification in the unconfined Floridan aquifer.

Exchange of water between conduits and matrix is an important control on regional chemical compositions, karstification, and quality of ground water resources in karst aquifers. A sinking stream (Santa Fe River Sink) and its resurgence (River Rise) in the unconfined portion of the Floridan Aquifer provide the opportunity to monitor conduit inflow and outflow. The use of temperature as a tracer allows determination of residence times and velocities through the conduit system. Based on temperature records from two high water events, flow is reasonably represented as pipe flow with a cross-sectional area of 380 m2, although this model may be complicated by losses of water from the conduit system at higher discharge rates. Over the course of the study year, the River Rise discharged a total of 1.9 x 10(7) m3 more water than entered the River Sink, reflecting net contribution of ground water from the matrix into the conduit system. However, as River Sink discharge rates peaked following three rainfall events during the study period, the conduit system lost water, presumably into the matrix. Surface water in high flow events is typically undersaturated with respect to calcite and thus may lead to dissolution, depending on its residence time in the matrix. A calculation of local denudation is larger than other regional estimates, perhaps reflecting return of water to conduits before calcite equilibrium is reached. The exchange of matrix and conduit water is an important variable in karst hydrology that should be considered in management of these water resources.

Environmental Monitoring↗