Delayed and asynchronous ganglionic maturation during cephalopod neurogenesis as evidenced by Sof‐elav1 expression in embryos of Sepia officinalis (Mollusca,Cephalopoda)

Among the Lophotrochozoa, centralization of the nervous system reaches an exceptional level of complexity in cephalopods, where the typical molluscan ganglia become highly developed and fuse into hierarchized lobes. It is known that ganglionic primordia initially emerge early and simultaneously during cephalopod embryogenesis but no data exist on the process of neuron differentiation in this group. We searched for members of the elav/hu family in the cuttlefish Sepia officinalis, since they are one of the first genetic markers of postmitotic neural cells. Two paralogs were identified and the expression of the most neural‐specific gene, Sof‐elav1, was characterized during embryogenesis. Sof‐elav1 is expressed in all ganglia at one time of development, which provides the first genetic map of neurogenesis in a cephalopod. Our results unexpectedly revealed that Sof‐elav1 expression is not similar and not coordinated in all the prospective ganglia. Both palliovisceral ganglia show extensive Sof‐elav1 expression soon after emergence, showing that most of their cells differentiate into neurons at an early stage. On the contrary, other ganglia, and especially both cerebral ganglia that contribute to the main parts of the brain learning centers, show a late extensive Sof‐elav1 expression. These delayed expressions in ganglia suggest that most ganglionic cells retain their proliferative capacities and postpone differentiation. In other molluscs, where a larval nervous system predates the development of the definitive adult nervous system, cerebral ganglia are among the first to mature. Thus, such a difference may constitute a cue in understanding the peculiar brain evolution in cephalopods. J. Comp. Neurol. 521:1482–1496, 2013. © 2012 Wiley Periodicals, Inc.     

The use of endoscopic ultrasonography and other imaging modalities in the preoperative staging of rectal villous tumours: A case of overstaging by magnetic resonance imaging

A case of a 60-year-old man with recurrent rectal villous adenoma is described. Preoperative staging with endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) revealed very discordant results. EUS showed a tumour present in the mucosa with no submucosal invasion, while MRI revealed invasion of the muscularis propria consistent with an invasive stage T2 carcinoma. Based on the MRI findings, the patient underwent a low anterior resection of the tumour. The surgical pathology specimen revealed a villous adenoma with low-grade dysplasia but no carcinoma and no extension into the muscularis propria. The present case highlights the uncertainty that currently exists as to which imaging modality provides the greatest accuracy in the staging of rectal cancer and in guiding the type of surgical procedure performed. Two recent meta-analyses and a systematic review of the literature point to EUS as the imaging modality of choice for determining muscularis propria and perirectal tissue invasion, as well as nodal involvement.     

The Prevalence of Gestational Diabetes Mellitus and Glucose Abnormalities in Pregnant Women With Hepatitis C Virus Infection in British Columbia

ObjectiveThere is evidence to support an association between diabetes mellitus (DM) and hepatitis C virus (HCV) infection. The insulin resistant state of pregnancy suggests a predisposition to developing gestational diabetes mellitus (GDM) in women infected with HCV. The aim of this study was to compare the prevalence of GDM and impaired glucose tolerance (IGT) of pregnancy between women infected with HCV and the general population of British Columbia screened for GDM.MethodsThe HCV cohort was drawn from a population-based prospective cohort of 148 pregnant women infected with HCV in British Columbia. GDM screening tests were completed in 84 women. The prevalence of GDM and IGT of pregnancy in the general population of British Columbia was estimated by acquiring 24 321 GDM screening tests performed by the two major laboratories in the province.ResultsNon-compliance was the primary reason for incomplete screening. The prevalence of GDM was 9.5% in the HCV cohort and 6.8% in the screened general population (χ² test P = 0.33). Similarly, there was no difference in IGT of pregnancy between the two cohorts (2.4% vs. 3.5%; χ² test P = 0.57).ConclusionA difference in the prevalence of either GDM or IGT of pregnancy was not detected between HCV-infected patients who were screened for GDM and those screened in the general population. Further studies are required to assess whether HCV infection is an independent risk factor for GDM.     

GABA receptor 1 polymorphism (G1465A) and temporal lobe epilepsy

PURPOSE: To reevaluate the genetic contribution of the polymorphism G1465A of the gene coding for gamma-aminobutyric acid (GABA)(B) receptor 1 subunit [GABA(B)(1)] in a sample of French patients with temporal lobe epilepsy (TLE) and to perform an exploratory analysis in other phenotypic subgroups. METHODS: The 134 patients were genotyped for the polymorphism G1465A. This sample was divided in two groups. The first one had patients with nonlesional TLE, and the second one, with lesional TLE. Then these two groups were compared with a sample of 145 healthy individuals. RESULTS: The genotype and allele distributions for the polymorphism G1465A showed no difference between patients and controls. CONCLUSIONS: The association between the variant G1465A and the sample of patients could not be replicated, so these results exclude a major effect of this polymorphism in the susceptibility to nonlesional TLE. Larger samples should be tested to determine whether the G1465A in exon 7 of the GABA(B)(1) receptor gene is a susceptibility factor for nonlesional TLE.     

Identification and analysis of new sequence variants in the human tryptophan hydroxylase (TpH) gene

The tryptophan hydroxylase (TpH) gene codes for the rate-limiting enzyme in serotonin biosynthesis. It is one of the major candidate genes for psychiatric and behavioral disorders. A polymorphism in TpH intron 7 has been shown to be associated with suicidal attempts, aggressive behavior and psychiatric illnesses. By systematically screening the TpH genomic sequence, we identified and confirmed an earlier report of four variants in the promoter region and localized six new sequence variants, ie two in intron 1b, one in exon 1c, one in intron 8, one in intron 9 and a microsatellite in the 3' region, 5687 bp downstream of the last exon 11. We analyzed these polymorphisms, as well as the one in intron 7, by Single Strand Conformation Analysis, microsatellite or restriction analysis in a collection of 175 West European Caucasian healthy subjects. The four variants in the promoter region are in complete linkage disequilibrium (frequencies of G-T-G-T and T-C-A-G haplotypes are 0. 41 and 0.59, respectively). Deletion of GTT in intron 1b is rare (0. 7%) and so not informative. The rarer allele T of intron 1b polymorphism T3792A has a frequency of 0.34 and is in partial linkage disequilibrium with the more common alleles of intron 7, 8 and 9. The polymorphisms of these three introns are in complete linkage disequilibrium and the frequencies of haplotypes A-T-C and C-C-T are 0.36 and 0.64 respectively. We detected 10 different alleles in the microsatellite localized in the 3' region; allele '194' is in partial linkage disequilibrium with haplotype A-T-C of introns 7, 8, and 9. Analysis of these different polymorphisms will constitute an important tool for future studies between the TpH gene and psychiatric disorders. Molecular Psychiatry (2000) 5, 49-55.     

Study of the voltage-gated sodium channel beta 1 subunit gene (SCN1B) in the benign familial infantile convulsions syndrome (BFIC)

Benign familial infantile convulsions (BFIC) is a rare autosomal dominant epilepsy syndrome. This syndrome has been recently described in Italian and French pedigrees. Patients present with partial, then generalized seizures, with onset at age three months. The seizures usually spontaneously cease after one year without treatment, leaving no neurological abnormalities. We have mapped BFIC to chromosome 19q in five Italian pedigrees. The sodium channel beta1 subunit gene (SCN1B) maps to this candidate region and has been shown to be involved in one Australian pedigree with generalized epilepsy and febrile seizures "plus" (GEFS +). In this family, a missense mutation in SCN1B cosegregates with the GEFS+ phenotype. BFIC and GEFS+ have clinical features in common, therefore SCN1B is a candidate gene for BFIC. We studied SCN1B exons 1, 2, 3, 4, and 5, using four SSCP methods in 10 Caucasian BFIC probands of Western Europe. We found no exon variants. One variant was identified in intron 5 (IVS5-10C>G), which did not segregate with BFIC and was observed in 9.2% controls. A second variant in intron 5 was identified (IVS5+30G>A). It was rare, as not observed in controls, but not segregating with the BFIC phenotype.     

The influence of four serotonin-related genes on decision-making in suicide attempters.

Genetic factors have been associated with the vulnerability to suicidal behavior. We previously reported decision-making impairment in suicide attempters and hypothesized that these cognitive alterations may represent an endophenotype of suicidal behavior. In this study, we aimed to investigate the influence of four serotonin-related genes relevant to suicidal behavior on decision-making, in a large population of suicide attempters. The Iowa Gambling Task was used to assess decision-making in 168 patients with a personal history of attempted suicide. Patients were genotyped for four serotonergic polymorphisms: 5HTTLPR, TPH1 A218C, MAOA u-VNTR, and TPH2 rs1118997. Patients carrying the 5HTTLPR-ll and -sl, TPH1-CC and -AC, MAOA-HH (in women) and TPH2-AA genotypes significantly improved their performance during the task, suggesting a genetic modulation of the learning process required for advantageous decision-making. In contrast, genotypes previously associated with a higher risk of suicidal behavior, a greater sensitivity to the environment and a higher propensity to negative feelings are those conferring poorer learning abilities. We hypothesize that the influence of genetic factors on the vulnerability to suicidal behavior may partly be achieved through their modulation of decision-making and particularly its learning component.