Hippocampal GABA enables inhibitory control over unwanted thoughts.

Intrusive memories, images, and hallucinations are hallmark symptoms of psychiatric disorders. Although often attributed to deficient inhibitory control by the prefrontal cortex, difficulty in controlling intrusive thoughts is also associated with hippocampal hyperactivity, arising from dysfunctional GABAergic interneurons. How hippocampal GABA contributes to stopping unwanted thoughts is unknown. Here we show that GABAergic inhibition of hippocampal retrieval activity forms a key link in a fronto-hippocampal inhibitory control pathway underlying thought suppression. Subjects viewed reminders of unwanted thoughts and tried to suppress retrieval while being scanned with functional magnetic resonance imaging. Suppression reduced hippocampal activity and memory for suppressed content. 1H magnetic resonance spectroscopy revealed that greater resting concentrations of hippocampal GABA predicted better mnemonic control. Higher hippocampal, but not prefrontal GABA, predicted stronger fronto-hippocampal coupling during suppression, suggesting that interneurons local to the hippocampus implement control over intrusive thoughts. Stopping actions did not engage this pathway. These findings specify a multi-level mechanistic model of how the content of awareness is voluntarily controlled

Excitatory neurotransmitters in brain regions in interictal migraine patients

<p>Abstract</p> <p>Objective</p> <p>To examine biochemical differences in the anterior cingulate cortex (ACC) and insula during the interictal phase of migraine patients. We hypothesized that there may be differences in levels of excitatory amino acid neurotransmitters and/or their derivatives in migraine group based on their increased sensitivity to pain.</p> <p>Methods</p> <p>2D <it>J</it>-resolved proton magnetic resonance spectroscopy (¹H-MRS) data were acquired at 4.0 Tesla (T) from the ACC and insula in 10 migraine patients (7 women, 3 men, age 43 ± 11 years) and 8 age gender matched controls (7 women, 3 men, age 41 ± 9 years).</p> <p>Results</p> <p>Standard statistical analyses including analysis of variance (ANOVA) showed no significant metabolite differences between the two subject cohorts in the ACC nor the insula. However, linear discriminant analysis (LDA) introduced a clear separation between subject cohorts based on N-acetyl aspartylglutamate (NAAG) and glutamine (Gln) in the ACC and insula.</p> <p>Conclusion</p> <p>These results are consistent with glutamatergic abnormalities in the ACC and insula in migraine patients during their interictal period compared to healthy controls. An alteration in excitatory amino acid neurotransmitters and their derivatives may be a contributing factor for migraineurs for a decrease in sensitivity for migraine or a consequence of the chronic migraine state. Such findings, if extrapolated to other regions of the brain would offer new opportunities to modulate central system as interictal or preemptive medications in these patients.</p

Hadronic Structure in the Decay τ−→ντπ−π0π0\tau^{-}\to \nu_{\tau}\pi^{-}\pi^{0}\pi^{0} and the Sign of the Tau Neutrino Helicity

Based on a sample corresponding to 4.3 million produced tau-pair events, we have studied hadronic dynamics in the decay tau- --> nu_tau pi- pi0 pi0 in data recorded by the CLEO II detector operating at the CESR e+e- collider. The decay is dominated by the process tau --> nu_tau a_1(1260), with the a_1 meson decaying to three pions predominantly via the lowest dimensional (mainly S-wave) a_1 --> rho pi Born amplitude. From fits to the Dalitz plot and angular observables, we find significant additional contributions from amplitudes for a_1 decay to sigma pi, f_0(1370) pi and f_2(1270) pi, as well as higher dimensional a_1 --> rho pi and rho' pi amplitudes. The squared sigma pi amplitude accounts for ~15% of the total tau- --> nu_tau pi- pi0 pi0 rate in the models considered. We have searched for additional contributions from tau --> nu_tau pi'(1300). We place 90% confidence level upper limits on the branching fraction for this channel of between 1.0*10^{-4} and 1.9*10^{-4}, depending on the pi' decay mode. The pi- pi0 pi0 mass spectrum is parametrized by a Breit-Wigner form with a mass-dependent width which is specified according to the results of the Dalitz plot fits plus a coupling to an a_1 --> K* K amplitude. From a chi^2 fit, we extract the pole mass and width of the a_1, as well as the magnitude of the K* K coupling. We have also investigated the impact of a possible contribution from the a_1'(1700) meson on this spectrum. Finally, exploiting the parity-violating angular asymmetry in a_1 --> 3pi decay, we determine the signed value of the tau neutrino helicity to be h_{\nu_\tau} = -1.02 +- 0.13(stat.) +- 0.03(syst.+model), confirming the left-handedness of the tau neutrino.Comment: 44 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Quais as principais características organizacionais das empresas dos diferentes segmentos da construção civil?

Resumo Neste artigo os autores se propõem a identificar os fatores que definem as principais características organizacionais de empresas do subsetor da construção civil, localizadas em Curitiba e região metropolitana, assim como verificar as diferenças existentes entre os cinco segmentos de atividade mais relevantes desse mercado: residencial, industrial e comercial, infraestrutura, serviços especializados e construção industrializada. Para tanto, foi desenvolvida uma pesquisa exploratória e de natureza quantitativa, em nível de mestrado. O método survey foi escolhido como procedimento principal para este estudo, permitindo a obtenção de dados primários por meio da aplicação de um questionário em um grupo de 118 empresas. Esse questionário procurou identificar o perfil da organização e as características organizacionais das empresas avaliadas. Os dados foram analisados com a aplicação de técnicas multivariadas de análise fatorial e análise discriminante. A análise fatorial evidenciou as estratégias de melhoria, o comportamento do indivíduo no trabalho, a estrutura de funcionamento, a dinâmica de crescimento, o estilo de gestão, as relações interpessoais e o posicionamento da empresa perante o mercado como fatores determinantes. A análise discriminante apontou significativa homogeneidade no desenvolvimento organizacional das empresas que representam os diferentes segmentos de atividade

Microbiology

xiii, 992 p. : ilus. ; 27 cm

Molecular features assisting in diagnosis, surgery, and treatment decision making in low-grade gliomas

The preferred management of suspected low-grade gliomas (LGGs) has been disputed, and the implications of molecular changes for medical and surgical management of LGGs are important to consider. Current strategies that make use of molecular markers and imaging techniques and therapeutic considerations offer additional options for management of LGGs. Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes suggest a role for this abnormal metabolic pathway in the pathogenesis and progression of these primary brain tumors. Use of magnetic resonance spectroscopy can provide preoperative detection of IDH-mutated gliomas and affect surgical planning. In addition, IDH1 and IDH2 mutation status may have an effect on surgical resectability of gliomas. The IDH-mutated tumors exhibit better prognosis throughout every grade of glioma, and mutation may be an early genetic event, preceding lineage-specific secondary and tertiary alterations that transform LGGs into secondary glioblastomas. The O6-methylguanine-DNAmethyltransferase (MGMT) promoter methylation and 1p19q codeletion status can predict sensitivity to chemotherapy and radiation in low- and intermediate-grade gliomas. Thus, these recent advances, which have led to a better understanding of how molecular, genetic, and epigenetic alterations influence the pathogenicity of the different histological grades of gliomas, can lead to better prognostication and may lead to specific targeted surgical interventions and medical therapies

Biallelic ANGPT2 loss-of-function causes severe early-onset non-immune hydrops fetalis

Abstract Background: Hydrops fetalis, a pathological fluid accumulation in two or more body compartments, is aetiologically heterogeneous. We investigated a consanguineous family with recurrent pregnancy loss due to severe early-onset non-immune hydrops fetalis. Methods and results: Whole exome sequencing in four fetuses with hydrops fetalis revealed that they were homozygous for the angiopoietin-2 (ANGPT2) variant Chr8 (GRCh37/Hg19): 6385085T>C, NM_001147.2:c.557A>G. The substitution introduces a cryptic, exonic splice site predicted to result in loss of 10 nucleotides with subsequent shift in reading frame, leading to a premature stop codon. RNA analysis in the heterozygous parents demonstrated loss of detectable mutant allele, indicative of loss-of-function via nonsense-mediated mRNA decay. Serum ANGPT2 levels were reduced in the parents. In a pregnancy with a healthy, heterozygous child, transiently increased fetal nuchal translucency was noted. Conclusion: Pathogenic heterozygous ANGPT2 missense variants were recently shown to cause autosomal dominant primary lymphoedema. ANGPT2 is a ligand of the TIE1-TIE2 (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and 2) pathway. It is critical to the formation and remodelling of blood and lymphatic vessels and is involved in vessel maintenance. ANGPT2 knockout mice die from generalised lymphatic dysfunction. We show here that a homozygous pathogenic variant causes loss-of-function and results in severe early-onset hydrops fetalis. This is the first report of an autosomal recessive ANGPT2-related disorder in humans