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In JoVE (1)
Other Publications (19)
- American Journal of Public Health
- Genetics
- Journal of Gerontological Nursing
- Sexually Transmitted Diseases
- Frontiers in Bioscience : a Journal and Virtual Library
- AIDS and Behavior
- Substance Use & Misuse
- Endocrinology
- Journal of Substance Abuse Treatment
- Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses
- Endocrinology
- Environmental Health Perspectives
- Neurotoxicology and Teratology
- Women's Health Issues : Official Publication of the Jacobs Institute of Women's Health
- Journal of Prevention & Intervention in the Community
- Neurotoxicology and Teratology
- Reproductive Toxicology (Elmsford, N.Y.)
- Toxicological Sciences : an Official Journal of the Society of Toxicology
- Neurotoxicology
Articles by Mary Gilbert in JoVE
JoVE General
Visualizing the Live Drosophila Glial-neuromuscular Junction with Fluorescent Dyes
Department of Zoology, University of British Columbia - UBC
We described structural features of the Glia-neuromuscular synapses in a novel Inside-out tissue preparation of live fly larvae using fluorescent dyes with confocal microscopy. We labeled live neuron terminals with fluorescent primary antibodies to HRP, and also visualized the perisynaptic space with fluorescent Dextrans.
Other articles by Mary Gilbert on PubMed
Role of Black Churches in Health Promotion Programs: Lessons from the Los Angeles Mammography Promotion in Churches Program
This article assesses pastor-level factors that affect the successful recruitment and implementation of community-based health promotion programs in Black churches.
DIM-1, a Novel Immunoglobulin Superfamily Protein in Caenorhabditis Elegans, is Necessary for Maintaining Bodywall Muscle Integrity
The UNC-112 protein is required during initial muscle assembly in C. elegans to form dense bodies and M-lines. Loss of this protein results in arrest at the twofold stage of embryogenesis. In contrast, a missense mutation in unc-112 results in viable animals that have disorganized bodywall muscle and are paralyzed as adults. Loss or reduction of dim-1 gene function can suppress the severe muscle disruption and paralysis exhibited by these mutant hermaphrodites. The overall muscle structure in hermaphrodites lacking a functional dim-1 gene is slightly disorganized, and the myofilament lattice is not as strongly anchored to the muscle cell membrane as it is in wild-type muscle. The dim-1 gene encodes two polypeptides that contain three Ig-like repeats. The short DIM-1 protein isoform consists entirely of three Ig repeats and is sufficient for wild-type bodywall muscle structure and stability. DIM-1(S) localizes to the region of the muscle cell membrane around and between the dense bodies, which are the structures that anchor the actin filaments and may play a role in stabilizing the thin rather than the thick filament components of the sarcomere.
Sexual Risk Among Injection Drug Users Recruited from Syringe Exchange Programs in California
The objective of this study was to examine correlates of sexual risk among injection drug users (IDUs).
Evolution of Clams (cholinesterase-like Adhesion Molecules): Structure and Function During Development
The protein family known as CLAMS (cholinesterase-like adhesion molecules) forms a novel class of heterophilic cell adhesion proteins. Family members are found through a wide range of metazoans and play a role during the development of multiple tissues. The majority of members of this family are transmembrane proteins with an extracellular domain that is conserved with cholinesterases including acetylcholinesterase. Yet all family members lack one or more of the residues that make up the catalytic triad necessary for enzymatic function. Therefore the conserved cholinesterase-like domain is not necessary for enzymatic function but does appear to play a role in heterophilic binding. CLAMS are expressed in a wide array of tissues and most family members appear to play a role in cell adhesion and junction formation. The development of junctions including septate junctions and synaptic junctions require CLAM family members such as Gliotactin and Neuroligins respectively. Modeling of the cholinesterase-like domain reveals that evolutionary changes to the binding pocket of the cholinesterase domain may produce a range of different ligand binding partners for CLAM family members. In this vein, previous chimera experiments and recent work has identified mutations in CLAM family members that affect the structure of the cholinesterase-like domain. These mutant forms affect protein function during the development of specialized junctions and confirm the role of the cholinesterase domain in mediating heterophilic binding.
Condom Attitudes and Behaviors Among Injection Drug Users Participating in California Syringe Exchange Programs
This study examined condom attitudes, preferences, barriers, and use among a sample of 550 injection drug using clients of syringe exchange programs in California. In multivariate analyses, positive attitudes toward condoms were significantly associated with consistent condom use for vaginal, anal, and oral sex in the past six months, beyond the effects of confounding socio-demographic and HIV risk variables. Participants commonly cited partner-related barriers to condom use, such as reluctance to use condoms with steady partners (34%). Almost a quarter of the sample cited dislike of condoms (e.g., because of pleasure reduction). In addition, a third of respondents stated specific preferences regarding condom brands, sensitivity, sizes, and textures. Interventions that increase awareness about positive aspects of condom use and sexual risk from steady partners may be successful in increasing condom use among injection drug users.
Secondary Syringe Exchange Among Users of 23 California Syringe Exchange Programs
This article describes the secondary syringe exchange (SSE) practices of injection drug users (IDUs) attending 23 syringe exchange programs (SEPs) in the state of California during 2002 (n=539). The sample was primarily heroin injecting, about two thirds male, half White and half other racial/ethnic groups. Participants were interviewed with a structured questionnaire that included items on sociodemographic factors, drug use practices, sexual practices, use of SEP and other social services, and satisfaction with SEP services. Interviews lasted about 30 minutes. SSE was highly prevalent: 75% of IDUs reported participating in SSE in the 6 months before interview. Program characteristics, such as legal status, SSE policy, and exchange policy, did not affect the prevalence of SSE among SEP clients. Infectious disease risk behaviors were significantly more common among SSE participants than nonparticipants. SSE participants were more likely to share syringes (p<.001) and cookers (p<.001) in the previous 6 months. SSE was significantly associated with being stuck with another person's syringe (needle-stick), a little-discussed "occupational hazard" of this practice. In multivariate analysis, the adjusted odds ratio of needle-stick among SSE participants was 2.8 (95% confidence interval, 1.3, 6.0). The high prevalence of SSE and the infectious disease risk associated with it warrant additional research to determine the causality of these associations. In the interim, SEPs should consider reinforcing HIV prevention education messages and training IDUs who engage in SSE in safe handling of biohazardous materials.
Modest Thyroid Hormone Insufficiency During Development Induces a Cellular Malformation in the Corpus Callosum: a Model of Cortical Dysplasia
There is a growing body of evidence that subtle decreases in maternal thyroid hormone during gestation can impact fetal brain development. The present study examined the impact of graded levels of thyroid hormone insufficiency on brain development in rodents. Maternal thyroid hormone insufficiency was induced by exposing timed-pregnant dams to propylthiouracil (PTU) at doses of 0, 1, 2, 3, and 10 ppm in the drinking water from gestational d 6 through weaning on postnatal d 30. An examination of Nissl-stained sections of the brains from developmentally hypothyroid offspring killed on postnatal d 23 revealed the presence of a heretofore unreported bilateral cellular malformation, a heterotopia, positioned within the white matter of the corpus callosum of both hemispheres. Immunohistochemical techniques were used to determine that this heterotopia primarily consists of neurons born between gestational d 17-19 and exhibits a dose-dependent increase in size with decreases in thyroid hormone levels. Importantly, this structural abnormality is evident at modest levels of maternal thyroid hormone insufficiency ( approximately 45% reductions in T(4) with no change in T(3)), persists in adult offspring despite a return to normal hormonal status, and is dramatically reduced in size with prenatal thyroid hormone replacement. Developmental exposure to methimazole, another goitrogen, also induced formation of this heterotopia. Whereas the long-term consequence of this cortical malformation on brain function remains to be determined, the presence of the heterotopia underscores the critical role thyroid hormone plays in brain development during the prenatal period and provides a new model in which to study mechanisms of cortical development and cortical dysplasia.
Human Immunodeficiency Virus and Hepatitis C Virus Testing Services at Syringe Exchange Programs: Availability and Outcomes
We described the availability and outcomes of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) testing services at syringe exchange programs throughout California, using interviews with 24 syringe exchange program directors and 560 syringe exchange clients. Both HIV and HCV testing services were available in 62% of programs, 21% had HIV testing only, and 17% had neither. Programs administered by health care/social service providers were more likely than independent syringe exchange programs to have HIV and HCV testing services available. Among clients of programs with testing available, clients of illegal programs were significantly less likely than clients of legal programs to have used syringe exchange HIV and HCV testing services. The availability of HIV and HCV testing services at syringe exchange programs varies, and the use of existing testing services by clients is not universal. Efforts to increase both the availability of HIV and HCV testing services at syringe exchange programs and the use of existing testing services are needed.
Religiosity and Coping in Mothers of Children Diagnosed with Cancer: an Exploratory Analysis
Although several factors related to coping in parents of children diagnosed with cancer have been explored, little is known about their religious beliefs and behavior and its relationship to coping. The purpose of this study was to provide preliminary data on the religious beliefs and behaviors of mothers of children with cancer and the relation to their psychological adjustment. Twenty-seven mothers of children diagnosed with cancer completed several measures of religious beliefs and behaviors as well as the Beck Depression Inventory-II. The sample was highly religious and specifically Christian. Thirty percent of the mothers reported elevated levels of depressive symptoms, and these mothers reported lower levels of religious belief and behavior than the mothers who denied depressive symptoms. These data suggest a relationship between religiosity and positive coping behavior that should continue to be explored.
The Balance Between Oligodendrocyte and Astrocyte Production in Major White Matter Tracts is Linearly Related to Serum Total Thyroxine
Thyroid hormone (TH) may control the ratio of oligodendrocytes to astrocytes in white matter by acting on a common precursor of these two cell types. If so, then TH should produce an equal but opposite effect on the density of these two cells types across all TH levels. To test this, we induced graded TH insufficiency by treating pregnant rats with increasing doses of propylthiouracil. Propylthiouracil induced a dose-dependent decrease in serum T(4) in postnatal d 15 pups, a dose-dependent decrease in the density of MAG-positive oligodendrocytes, and an equal increase in the density of glial fibrillary acidic protein-positive astrocytes in both the corpus callosum and anterior commissure. Linear regression analyses demonstrated a strong correlation between glial densities and serum T(4); this correlation was positive for astrocytes and negative for oligodendrocytes. Surprisingly, oligodendrocyte density in the corpus callosum was more sensitive to changes in TH than in the anterior commissure, as indicated by the slope of the regressions. Furthermore, we measured an overall reduction in the cellular density that was independent of changes in myelin-associated glycoprotein and glial fibrillary acidic protein-positive cells. These data strongly support the interpretation that TH controls the balance of production of oligodendrocytes and astrocytes in major white matter tracts of the developing brain by acting on a common precursor of these cell types. Moreover, these findings indicate that major white matter tracts may differ in their sensitivity to TH insufficiency.
Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat
Perchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development.
A Pilot of a Tripartite Prevention Program for Homeless Young Women in the Transition to Adulthood
Among young women who are impoverished and homeless, the transition to adulthood (ages 18-25) is associated with alcohol and drug use, risky sexual activity, and increased risk of being victimized by intimate partner violence.
Developing a Tripartite Prevention Program for Impoverished Young Women Transitioning to Young Adulthood: Addressing Substance Use, HIV Risk, and Victimization by Intimate Partners
Little is known about the transition to adulthood for adolescent females and young women who are impoverished and homeless. Co-occurrence of drug use and abuse, HIV risk, and victimization is notable among homeless women, highlighting the need for comprehensive interventions. Unfortunately, evidence-based prevention approaches addressing these inter-related problems among impoverished women transitioning into adulthood are lacking. To address this gap, we designed an innovative prevention program by utilizing open- and closed-ended interview data from impoverished women (n = 20), focus groups with community experts and providers (2 groups; n = 9), and a theoretical framework to direct the research. Information provided by our focus groups and interviews with women supported our theoretical framework and highlighted the importance of addressing normative information, providing skills training, and utilizing a non-confrontational approach when discussing these sensitive issues.
Behavioral Effects of Subchronic Inhalation of Toluene in Adult Rats
Whereas the acute neurobehavioral effects of toluene are robust and well characterized, evidence for persistent effects of repeated exposure to this industrial solvent is less compelling. The present experiment sought to determine whether subchronic inhalation of toluene caused persistent behavioral changes in rats. Adult male Long-Evans rats inhaled toluene vapor (0, 10, 100, or 1000 ppm) for 6h/day, 5 days/week for 13 weeks and were evaluated on a series of behavioral tests beginning 3 days after the end of exposure. Toluene delayed appetitively-motivated acquisition of a lever-press response, but did not affect motor activity, anxiety-related behavior in the elevated plus maze, trace fear conditioning, acquisition of an appetitively-motivated visual discrimination, or performance of a visual signal detection task. Challenges with acute inhalation of toluene vapor (1200-2400 ppm for 1 h) and injections of quinpirole (0.01-0.03 mg/kg) and raclopride (0.03-0.10 mg/kg) revealed no toluene-induced latent impairments in visual signal detection. These results are consistent with a pattern of subtle and inconsistent long-term effects of daily exposure to toluene vapor, in contrast to robust and reliable effects of acute inhalation of the solvent.
Akt1 Protects Against Germ Cell Apoptosis in the Postnatal Mouse Testis Following Lactational Exposure to 6-N-propylthiouracil
Exposure to 6-propyl-2-thio-uracil (PTU), a neonatal goitrogen, leads to increased testis size and sperm production in rodents. Akt1, a gene involved in cell survival and proliferation is also phosphorylated by thyroxine (T(4)). Therefore, we examined the requirement for Akt1 in germ cell survival following PTU-induced hypothyroidism. Experiments were performed using Akt1+/+, Akt1+/-, and Akt1-/- mice. PTU was administered (0.01% w/v) via the drinking water of dams from birth to PND21. At PND15, T(4) serum levels were similar in all control groups, and significantly lower in all exposed groups with a dramatic decrease in Akt1-/- mice. PTU-exposed Akt1-/- testes displayed smaller tubules, increased apoptosis, delayed lumen formation, and increased inhibin B and AMH mRNA. Relative adult testis weights were similar in all exposure groups; however, no increase in daily sperm production was observed in PTU-exposed Akt1-/- mice. In conclusion, Akt1 contributes to the effects of thyroid hormone on postnatal testis development.
Impact of Low-level Thyroid Hormone Disruption Induced by Propylthiouracil on Brain Development and Function
The critical role of thyroid hormone (TH) in brain development is well-established. Evidence shows that severe deficiencies lead to significant neurological dysfunction. Much less information is available on more modest perturbations of TH on brain function. The present study induced varying degrees of developmental hypothyroidism by administration of low doses of the TH synthesis inhibitor, propylthiouracil (PTU 0, 1, 2, and 3 ppm) to the drinking water of pregnant rats. This regimen produced dose-dependent reductions in circulating levels of T4 in dams and offspring on postnatal days (PN) 15 and 22, with return to control levels in adulthood upon termination of treatment at weaning. Modest reductions in T3 were observed in the high-dose group on PN15. Synaptic function in the dentate gyrus was examined in adult euthyroid offspring using in vivo field potentials. Excitatory synaptic transmission (excitatory postsynaptic potential [EPSP] slope amplitude) was significantly reduced at 2 and 3 ppm PTU, with no statistically reliable effect detected in the population spike. Paired-pulse functions estimating the integrity of inhibitory synaptic processing were modestly reduced by 3 ppm PTU. Long-term potentiation (LTP) of the EPSP slope was impaired at all dose levels. Trace fear conditioning to context and to cue was impaired at the highest dose level when a distractor stimulus was present, whereas conditioning in a standard trace fear paradigm paradoxically revealed "enhanced" performance at the intermediate dose and a return to control values in the high-dose group. Biphasic dose-response profiles were evident in some measures (trace fear conditioning and LTP) but not others and serve to exemplify the complexity of the role of TH in brain development and its consequences for brain function.
Developmental Thyroid Hormone Disruption: Prevalence, Environmental Contaminants and Neurodevelopmental Consequences
Thyroid hormones (TH) are critical for growth and development and particularly brain development. There are numerous environmental agents that lead to marginal reductions of circulating TH. Although it is clear that severe developmental hypothyroidism is profoundly detrimental to neurodevelopment, there is less information regarding the consequences of modest degrees of thyroid. The impact of low level TH disruptions induced by environmental contaminants has not been defined. This paper is a synopsis from four invited speakers who presented at the 13th International Neurotoxicology Association meeting held in Xi'an, China during the summer of 2011. An overview of the role of TH in brain development and a review of human and animal data on the neurological sequelae of disruption of the thyroid axis in the pre- and early post-natal periods were presented by Mary Gilbert and Joanne Rovet. Iodine deficiency, a common cause of TH insufficiency and mental retardation in many countries, including China, was addressed by Zupei Chen. In this presentation the current incidence of iodine deficiency and neurological outcome in China and the efficacy of recently implemented iodinization programs to eliminate this cause of mental retardation were reviewed. Joanne Rovet described the impact of TH disruption during pregnancy and under conditions of congenital hypothyroidism. Children born with normal thyroid function, but who experienced TH insufficiency in the womb, display subtle cognitive impairments and abnormalities in brain imaging. Despite early detection and treatment, deficiencies also exist in children born with thyroid disorders. Different patterns of cognitive effects result from prenatal versus postnatal TH insufficiency. Mary Gilbert reported on the effects of environmental contaminants with thyroid disrupting action on brain development in animals. Results of neurophysiological, behavioral, structural and molecular alterations that accompany modest perturbations of the thyroid axis were reviewed. Noriyuki Koibuchi described molecular targets of TH-mediated signalling accompanying exposure to persistent organic pollutants. Both polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are prevalent environmental contaminants that disrupt TH signalling at the receptor level. This action by these chemical classes could contribute to the negative impact of these chemicals on brain function. In summary, epidemiological, preclinical and animal research has clearly identified the critical role of TH in brain development. Additional work is required to understand the impact of low level perturbations of the thyroid axis to evaluate the risk associated with environmental contaminants with thyroid action.
