Gamma-Aminobutyric Acid and Glutamate Concentrations in the Striatum and Anterior Cingulate Cortex Not Found to Be Associated with Cognitive Flexibility

Behavioral flexibility and goal-directed behavior heavily depend on fronto-striatal networks. Within these circuits, gamma-aminobutyric acid (GABA) and glutamate play an important role in (motor) response inhibition, but it has remained largely unclear whether they are also relevant for cognitive inhibition. We hence investigated the functional role of these transmitters for cognitive inhibition during cognitive flexibility. Healthy young adults performed two paradigms assessing different aspects of cognitive flexibility. Magnetic resonance spectroscopy (MRS) was used to quantify GABA+ and total glutamate/glutamine (Glx) levels in the striatum and anterior cingulate cortex (ACC) referenced to N-acetylaspartate (NAA). We observed typical task switching and backward inhibition effects, but striatal and ACC concentrations of GABA+/NAA and Glx/NAA were not associated with cognitive flexibility in a functionally relevant manner. The assumption of null effects was underpinned by Bayesian testing. These findings suggest that behavioral and cognitive inhibition are functionally distinct faculties, that depend on (at least partly) different brain structures and neurotransmitter systems. While previous studies consistently demonstrated that motor response inhibition is modulated by ACC and striatal GABA levels, our results suggest that the functionally distinct cognitive inhibition required for successful switching is not, or at least to a much lesser degree, modulated by these factors

Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy

Background Nephronophthisis associated ciliopathies (NPHP-AC) comprise a group of autosomal recessive cystic kidney diseases that includes nephronophthisis (NPHP), Senior-Loken syndrome (SLS), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). To date, causative mutations in NPHP-AC have been described for 18 different genes, rendering mutation analysis tedious and expensive. To overcome the broad genetic locus heterogeneity, a strategy of DNA pooling with consecutive massively parallel resequencing (MPR) was devised.Methods In 120 patients with severe NPHP-AC phenotypes, five pools of genomic DNA with 24 patients each were prepared which were used as templates in order to PCR amplify all 376 exons of 18 NPHP-AC genes (NPHP1, INVS, NPHP3, NPHP4, IQCB1, CEP290, GLIS2, RPGRIP1L, NEK8, TMEM67, INPP5E, TMEM216, AHI1, ARL13B, CC2D2A, TTC21B, MKS1, and XPNPEP3). PCR products were then subjected to MPR on an Illumina Genome-Analyser and mutations were subsequently assigned to their respective mutation carrier via CEL I endonuclease based heteroduplex screening and confirmed by Sanger sequencing.Results For proof of principle, DNA from patients with known mutations was used and detection of 22 out of 24 different alleles (92% sensitivity) was demonstrated. MPR led to the molecular diagnosis in 30/120 patients (25%) and 54 pathogenic mutations (27 novel) were identified in seven different NPHP-AC genes. Additionally, in 24 patients only single heterozygous variants of unknown significance were found.Conclusions The combined approach of DNA pooling followed by MPR strongly facilitates mutation analysis in broadly heterogeneous single gene disorders. The lack of mutations in 75% of patients in this cohort indicates further extensive heterogeneity in NPHP-AC

TRCP-6 Mutation Causing FSGS in Childhood

WOS: 00038208260034

Atypical hemolytic uremic syndrome in infancy

Ozcakar, Zeynep/0000-0002-6376-9189; Cakar, Nilgun/0000-0002-1853-0101WOS: 000382082600487

Hysterosalpingography prior to the gonadotropin stimulated intrauterine insemination improves clinical pregnancy rates in women with unexplained infertility

Purpose of investigation: Gonadotropin stimulated intrauterine insemination (IUI) cycles performed following one month after hysterosalpingography (HSG) are associated with improvement in clinical pregnancy rates in unexplained infertile couples. Materials and Methods: A retrospective cohort study was performed between 2008 and 2014. A total of 92 unexplained infertile couples undergoing their first cycle IUI stimulated by gonadotropins were included in the analysis. Participants were classified into two groups according to IUI cycles performed one month (Group A, n = 25 cycles) or longer than one month (Group B, n = 67 cycles) after the HSG procedure. Result: The overall clinical pregnancy rate was found as 25% (23 clinical pregnancies/92 cycles). Clinical pregnancy rate was 44 % (11/25) for Group A and 17.9 % (12/67) for Group B. In Group A, there were significantly higher clinical pregnancy rates compared to Group B (OR: 3.6, 95% CI, 1.3-9.8;p = 0.012). Conclusions: It has been demonstrated that fertility improving effect of HSG was most prominent in the first six months after procedure. Likewise, in gonadotropin stimulated IUI cycles performed following one month after HSG, there seems to be an improvement in pregnancy rates in unexplained couples. In unexplained cases, it may be a reasonable approach to plan IUI cycles in the first month after HSG in clinical practice

Gamma-Aminobutyric Acid and Glutamate Concentrations in the Striatum and Anterior Cingulate Cortex Not Found to Be Associated with Cognitive Flexibility

Behavioral flexibility and goal-directed behavior heavily depend on fronto-striatal networks. Within these circuits, gamma-aminobutyric acid (GABA) and glutamate play an important role in (motor) response inhibition, but it has remained largely unclear whether they are also relevant for cognitive inhibition. We hence investigated the functional role of these transmitters for cognitive inhibition during cognitive flexibility. Healthy young adults performed two paradigms assessing different aspects of cognitive flexibility. Magnetic resonance spectroscopy (MRS) was used to quantify GABA+ and total glutamate/glutamine (Glx) levels in the striatum and anterior cingulate cortex (ACC) referenced to N-acetylaspartate (NAA). We observed typical task switching and backward inhibition effects, but striatal and ACC concentrations of GABA+/NAA and Glx/NAA were not associated with cognitive flexibility in a functionally relevant manner. The assumption of null effects was underpinned by Bayesian testing. These findings suggest that behavioral and cognitive inhibition are functionally distinct faculties, that depend on (at least partly) different brain structures and neurotransmitter systems. While previous studies consistently demonstrated that motor response inhibition is modulated by ACC and striatal GABA levels, our results suggest that the functionally distinct cognitive inhibition required for successful switching is not, or at least to a much lesser degree, modulated by these factors.ISSN:2076-342