Bioprocess exploitation of microaerobic auto-induction using the example of rhamnolipid biosynthesis in Pseudomonas putida KT2440.

Background: In biomanufacturing of surface-active agents, such as rhamnolipids, excessive foaming is a significant obstacle for the development of high-performing bioprocesses. The exploitation of the inherent tolerance of Pseudomonas putida KT2440, an obligate aerobic bacterium, to microaerobic conditions has received little attention so far. Here low-oxygen inducible promoters were characterized in biosensor strains and exploited for process control under reduction of foam formation by low aeration and stirring rates during biosynthesis of rhamnolipids.

Engineering Material Properties of Transcription Factor Condensates to Control Gene Expression in Mammalian Cells and Mice.

Phase separation of biomolecules into condensates is a key mechanism in the spatiotemporal organization of biochemical processes in cells. However, the impact of the material properties of biomolecular condensates on important processes, such as the control of gene expression, remains largely elusive. Here, the material properties of optogenetically induced transcription factor condensates are systematically tuned, and probed for their impact on the activation of target promoters.

Prenatal and Newborn Immunoglobulin Levels from Mother-Child Pairs and Risk of Autism Spectrum Disorders.

Background: An etiological role for immune factors operating during early brain development in children with autism spectrum disorders (ASD) has not yet been established. A major obstacle has been the lack of early biologic specimens that can be linked to later diagnosis. In a prior study, we found lower risk of ASD associated with higher levels of maternally-derived total IgG and Toxoplasmosis gondii (Toxo) IgG in newborn blood spot specimens from children later diagnosed with ASD compared to population controls.

Prenatal and neonatal peripheral blood mercury levels and autism spectrum disorders.

Background: Prenatal and early-life exposures to mercury have been hypothesized to be associated with increased risk of autism spectrum disorders (ASDs).

Objectives: This study investigated the association between ASDs and levels of total mercury measured in maternal serum from mid-pregnancy and infant blood shortly after birth.

Methods: The study sample was drawn from the Early Markers for Autism (EMA) Study.

Familial recurrence of autism spectrum disorder: evaluating genetic and environmental contributions.

Objective: This study was designed to examine the pattern of familial recurrence of autism spectrum disorder (ASD) in terms of genetic and environmental contributions related to timing of birth.

Method: The authors linked California Department of Developmental Services records with state birth certificates to identify all siblings and half siblings of individuals affected with ASD born between 1990 and 2003. A total of 6,616 full siblings, 644 maternal half siblings, and 299 paternal half siblings born after ASD index cases were used to calculate recurrence risks.

Neonatal cytokines and chemokines and risk of Autism Spectrum Disorder: the Early Markers for Autism (EMA) study: a case-control study.

Background: Biologic markers of infection and inflammation have been associated with Autism Spectrum Disorders (ASD) but prior studies have largely relied on specimens taken after clinical diagnosis. Research on potential biologic markers early in neurodevelopment is required to evaluate possible causal pathways and screening profiles.

Objective: To investigate levels of cytokines and chemokines in newborn blood specimens as possible early biologic markers for autism.

Evidence of reproductive stoppage in families with autism spectrum disorder: a large, population-based cohort study.

Importance: Few studies have examined the curtailment of reproduction (ie, stoppage) after the diagnosis of a child with autism spectrum disorder (ASD).

Objective: To examine stoppage in a large, population-based cohort of families in which a child has received a diagnosis of ASD.

Design, Setting, And Participants: Individuals with ASD born from January 1, 1990, through December 31, 2003, were identified in the California Department of Developmental Services records, which were then linked to state birth certificates to identify full sibs and half-sibs and to obtain information on birth order and demographics.

Prenatal and perinatal risk factors in a twin study of autism spectrum disorders.

Introduction: Multiple studies associate prenatal and perinatal complications with increased risks for autism spectrum disorders (ASDs). The objectives of this study were to utilize a twin study design to 1) Investigate whether shared gestational and perinatal factors increase concordance for ASDs in twins, 2) Determine whether individual neonatal factors are associated with the presence of ASDs in twins, and 3) Explore whether associated factors may influence males and females differently.

Methods: Data from medical records and parent response questionnaires from 194 twin pairs, in which at least one twin had an ASD, were analyzed.

Autism and developmental screening in a public, primary care setting primarily serving Hispanics: challenges and results.

We implemented screening of children 16-30 months of age (n = 1,760) from a typically under-served, primarily Hispanic, population, at routine pediatric appointments using the modified checklist for autism in toddlers (M-CHAT) and Ages and Stages Questionnaire. Screen positive rates of 26 and 39%, respectively, were higher than previous reports. Hispanics were more likely to score M-CHAT positive than non-Hispanics (adjusted OR 1.

Maternal Infection During Pregnancy and Autism Spectrum Disorders.

We conducted a nested case-control study including 407 cases and 2,075 frequency matched controls to investigate the association between maternal infections during pregnancy and risk of autism spectrum disorders (ASD). Cases, controls, and maternal infections were ascertained from Kaiser Permanente Northern California clinical databases. No overall association between diagnoses of any maternal infection during pregnancy and ASD was observed [adjusted odds ratio (ORadj) = 1.

Adaptation of the "ten questions" to screen for autism and other neurodevelopmental disorders in Uganda.

Neurodevelopmental disorders are recognized to be relatively common in developing countries but little data exist for planning effective prevention and intervention strategies. In particular, data on autism spectrum disorders are lacking. For application in Uganda, we developed a 23-question screener (23Q) that includes the Ten Questions screener and additional questions on autism spectrum disorder behaviors.

Use of birth certificates to examine maternal occupational exposures and autism spectrum disorders in offspring.

The continuing rise in the prevalence of autism spectrum disorders has led to heightened interest in the role of nongenetic factors, including exogenous exposures, but little research has been conducted. To explore a possible role in autism etiology, we used data available from our prior studies to examine potential occupational exposures, as these may occur at higher levels than environmental exposures. Parental occupation was obtained from birth certificates for 284 children with autism and 659 controls, born in 1994 in the San Francisco Bay Area.

Head circumferences in twins with and without Autism Spectrum Disorders.

To determine the genetic relationship between head circumference (HC) and Autism Spectrum Disorders (ASDs). Twin pairs with at least one twin with an ASD were assessed. HCs in affected and unaffected individuals were compared, as were HC correlations in monozygotic and dizygotic pairs.

Is infertility associated with childhood autism?

Concerns persist about a possible link between infertility and risk of autism spectrum disorders (ASD). Interpretation of existing studies is limited by racial/ethnic homogeneity of study populations and other factors. Using a case-control design, we evaluated infertility history and treatment documented in medical records of members of Kaiser Permanente Northern California.

"Communities" in community engagement: lessons learned from autism research in South Korea and South Africa.

Little research has been conducted on behavioral characteristics of children with autism spectrum disorder (ASD) from diverse cultures within the US, or from countries outside of the US or Europe, with little reliable information yet reported from developing countries. We describe the process used to engage diverse communities in ASD research in two community-based research projects-an epidemiologic investigation of 7- to 12-year olds in South Korea and the Early Autism Project, an ASD detection program for 18- to 36-month-old Zulu-speaking children in South Africa. Despite the differences in wealth between these communities, ASD is underdiagnosed in both settings, and generally not reported in clinical or educational records.

The Study to Explore Early Development (SEED): a multisite epidemiologic study of autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) network.

The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal, gastrointestinal, and sociodemographic characteristics. SEED uses a case-control design with population-based ascertainment of children aged 2-5 years with an autism spectrum disorder (ASD) and children in two control groups-one from the general population and one with non-ASD developmental problems. Data from parent-completed questionnaires, interviews, clinical evaluations, biospecimen sampling, and medical record abstraction focus on the prenatal and early postnatal periods.

Are thyroid hormone concentrations at birth associated with subsequent autism diagnosis?

Thyroid hormones substantially influence central nervous system development during gestation. We hypothesized that perturbations of early thyroid profiles may contribute to the development of autism spectrum disorders (ASD). Thyroid pathways could provide a mechanism by which environmental factors that affect the thyroid system may impact autism occurrence or phenotypic expression.

Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: A case-control study.

Background: Immune anomalies have been documented in individuals with autism spectrum disorders (ASDs) and their family members. It is unknown whether the maternal immune profile during pregnancy is associated with the risk of bearing a child with ASD or other neurodevelopmental disorders.

Methods: Using Luminex technology, levels of 17 cytokines and chemokines were measured in banked serum collected from women at 15 to 19 weeks of gestation who gave birth to a child ultimately diagnosed with (1) ASD (n = 84), (2) a developmental delay (DD) but not autism (n = 49) or (3) no known developmental disability (general population (GP); n = 159).

Genetic heritability and shared environmental factors among twin pairs with autism.

Context: Autism is considered the most heritable of neurodevelopmental disorders, mainly because of the large difference in concordance rates between monozygotic and dizygotic twins.

Objective: To provide rigorous quantitative estimates of genetic heritability of autism and the effects of shared environment.

Design, Setting, And Participants: Twin pairs with at least 1 twin with an autism spectrum disorder (ASD) born between 1987 and 2004 were identified through the California Department of Developmental Services.

Antidepressant use during pregnancy and childhood autism spectrum disorders.

Context: The prevalence of autism spectrum disorders (ASDs) has increased over recent years. Use of antidepressant medications during pregnancy also shows a secular increase in recent decades, prompting concerns that prenatal exposure may contribute to increased risk of ASD.

Objective: To systematically evaluate whether prenatal exposure to antidepressant medications is associated with increased risk of ASD.

Birth prevalence of autism spectrum disorders in the San Francisco Bay area by demographic and ascertainment source characteristics.

Using standardized methods for multi-source surveillance, we calculated the prevalence of autism spectrum disorders (ASD) among children born in a racially diverse region in 1994 or 1996 as 4.7/1000 live births. Children with ASD before age 9 were identified through chart abstraction at health-related sources; three-quarters were being served by the state-wide Department of Developmental Services.

Neonatally measured immunoglobulins and risk of autism.

Previous studies indicate that prenatal exposure to infections is a possible pathway through which autism spectrum disorders (ASD) could be initiated. We investigated whether immunoglobulin levels in archived specimens obtained from newborns subsequently diagnosed with ASD are different from levels in newborn specimens from controls. Children with ASD born in six California counties in 1994 were ascertained through records of the California Department of Developmental Services (DDS) and Kaiser Permanente; controls were randomly selected using birth certificates.

Interleukin-6 genotype and risk for cerebral palsy in term and near-term infants.

Objective: Chorioamnionitis is associated with increased risk for cerebral palsy (CP) in term infants. A functional polymorphism in the interleukin-6 (IL-6) gene has been implicated in newborn brain injury. We studied whether the IL-6 -174 G/C polymorphism confers increased risk for CP in term infants.

Risk of autism and increasing maternal and paternal age in a large north American population.

Previous studies are inconsistent regarding whether there are independent effects of maternal and paternal age on the risk of autism. Different biologic mechanisms are suggested by maternal and paternal age effects. The study population included all California singletons born in 1989-2002 (n = 7,550,026).

Antenatal ultrasound and risk of autism spectrum disorders.

We evaluated antenatal ultrasound (U/S) exposure as a risk factor for autism spectrum disorders (ASD), comparing affected singleton children and control children born 1995-1999 and enrolled in the Kaiser Permanente health care system. Among children with ASD (n = 362) and controls (n = 393), 13% had no antenatal exposure to U/S examinations; case-control differences in number of exposures during the entire gestation or by trimester were small and not statistically significant. In analyses adjusted for covariates, cases were generally similar to controls with regard to the number of U/S scans throughout gestation and during each trimester.