Biology subjects

Kaiser, A.

Publications and source records attributed to Kaiser, A..

3 recordsLinked to original sources

bioRxiv2020

Longitudinal alterations in fronto-striatal glutamate are associated with functioning during inhibitory control in autism spectrum disorder and obsessive compulsive disorder

BackgroundAutism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) are neurodevelopmental disorders with overlapping symptomatology. Both show deficits in inhibitory control, which are associated with altered functioning and glutamate concentrations in the fronto-striatal circuitry. These parameters have never been examined together. Here we, for the first time, used a multi-center, longitudinal approach to investigate fronto-striatal functioning during an inhibitory control task and its association with fronto-striatal glutamate concentrations across these two disorders. Methods74 adolescents with ASD (24) or OCD (15) and controls (35) aged 8-17 were recruited across three sites of the European TACTICS consortium. They underwent two magnetic resonance imaging (MRI) sessions with a one-year interval. This included proton magnetic resonance spectroscopy (1H-MRS; n=74) and functional MRI during an inhibitory control task (n=57). We used linear mixed effects models to investigate, over time, the relationship between fronto-striatal functioning and glutamate concentrations across these groups and continuous measures of overlapping compulsivity symptoms. ResultsDuring failed inhibitory control, in OCD increased striatal glutamate was associated with increased neural activation of ACC, an effect that decreased over time. During successful inhibitory control, higher ACC glutamate was positively associated with striatal activation in OCD and compulsivity across time. ACC glutamate levels decreased over time in the ASD group compared to controls, while striatal glutamate decreased over time, independent of diagnosis. ConclusionsSignificant differences in fronto-striatal glutamate were observed in ASD and OCD, affecting functional activity during failed- and successful inhibitory control differently, especially in OCD, with effects changing over time.

neuroscience↗

bioRxiv2020

The Development of Cognitive Control in Children with Autism Spectrum Disorders or Obsessive-Compulsive Disorder: A Longitudinal fMRI study

Repetitive behavior is a core symptom of Autism Spectrum Disorder (ASD) and Obsessive-Compulsive Disorder (OCD), and has been associated with impairments in cognitive control. However, it is unclear how cognitive control and associated neural circuitry relate to the development of repetitive behavior in children with these disorders. In a multicenter, longitudinal study (TACTICS; Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes), the development of cognitive control was assessed during late childhood using a longitudinal fMRI design with a modified stop-signal task in children with ASD or OCD, and typically developing (TD) children (baseline: N=122 (8-12y), follow-up: N=72 (10-14y), average interval: 1.2y). Stop-signal reaction time (SSRT) decreased over development, regardless of diagnosis. Repetitive behavior in children with ASD and OCD was not associated with performance on the stop-signal task. There were no whole-brain between-group differences in brain activity, but ROI-analyses showed increases in activity in right precentral gyrus over development for children with OCD. In sum, even though subtle differences were observed in the development of brain activity in children with OCD, the findings overall suggest that the development of cognitive control, as assessed by the stop signal task, is similar in children with and without ASD or OCD.

neuroscience↗

bioRxiv2020

Controlling the Growth of the Skin Commensal Staphylococcus epidermidis Using D-Alanine Auxotrophy

Using live microbes as therapeutic candidates is a strategy that has gained traction across multiple therapeutic areas. In the skin, commensal microorganisms play a crucial role in maintaining skin barrier function, homeostasis, and cutaneous immunity. Alterations of the homeostatic skin microbiome are associated with a number of skin diseases. Here, we present the design of an engineered commensal organism, Staphylococcus epidermidis, for use as a live biotherapeutic product (LBP) candidate for skin diseases. The development of novel bacterial strains whose growth can be controlled without the use of antibiotics, or genetic elements conferring antibiotic resistance, enables modulation of therapeutic exposure and improves safety. We therefore constructed an auxotrophic strain of S. epidermidis that requires exogenously supplied D-alanine. The S. epidermidis strain, NRRL B-4268 {Delta}alr1{Delta}alr2{Delta}dat (SE{Delta}{Delta}{Delta}) contains deletions of three biosynthetic genes: two alanine racemase genes, alr1 and alr2 (SE1674 and SE1079), and the D-alanine aminotransferase gene, dat (SE1423). These three deletions restricted growth in D-alanine deficient media, pooled human blood, and skin. In the presence of D-alanine, SE{Delta}{Delta}{Delta} colonized and increased expression of human {beta}-defensin 2 in cultured human skin models in vitro. SE{Delta}{Delta}{Delta}, showed a low propensity to revert to D-alanine prototrophy, and did not form biofilms on plastic in vitro. These studies support the potential safety and utility of SE{Delta}{Delta}{Delta} as a live biotherapeutic strain whose growth can be controlled by D-alanine.

microbiology↗