Detaching from the negative by reappraisal: the role of right superior frontal gyrus (BA9/32)

The ability to reappraise the emotional impact of events is related to long-term mental health. Self-focused reappraisal (REAPPself), i.e., reducing the personal relevance of the negative events, has been previously associated with neural activity in regions near right medial prefrontal cortex, but rarely investigated among brain-damaged individuals. Thus, we aimed to examine the REAPPself ability of brain-damaged patients and healthy controls considering structural atrophies and gray matter intensities, respectively. Twenty patients with well-defined cortex lesions due to an acquired circumscribed tumor or cyst and 23 healthy controls performed a REAPPself task, in which they had to either observe negative stimuli or decrease emotional responding by REAPPself. Next, they rated the impact of negative arousal and valence. REAPPself ability scores were calculated by subtracting the negative picture ratings after applying REAPPself from the ratings of the observing condition. The scores of the patients were included in a voxel-based lesion-symptom mapping (VLSM) analysis to identify deficit related areas (ROI). Then, a ROI group-wise comparison was performed. Additionally, a whole-brain voxel-based-morphometry (VBM) analysis was run, in which healthy participant's REAPPself ability scores were correlated with gray matter intensities. Results showed that (1) regions in the right superior frontal gyrus (SFG), comprising the right dorsolateral prefrontal cortex (BA9) and the right dorsal anterior cingulate cortex (BA32), were associated with patient's impaired down-regulation of arousal, (2) a lesion in the depicted ROI occasioned significant REAPPself impairments, (3) REAPPself ability of controls was linked with increased gray matter intensities in the ROI regions. Our findings show for the first time that the neural integrity and the structural volume of right SFG regions (BA9/32) might be indispensable for REAPPself. Implications for neurofeedback research are discussed.Fil: Falquez, Rosalux. University of Heidelberg; AlemaniaFil: Couto, Juan Blas Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Ibáñez Barassi, Agustín Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Freitag, Martin T.. German Cancer Research Center; AlemaniaFil: Berger, Moritz. German Cancer Research Center; AlemaniaFil: Arens, Elisabeth A.. University of Heidelberg; AlemaniaFil: Lang, Simone. University of Heidelberg; AlemaniaFil: Barnow, Sven. University of Heidelberg; Alemani

Integration of CT urography improves diagnostic confidence of 68Ga-PSMA-11 PET/CT in prostate cancer patients

Background: To prove the feasibility of integrating CT urography (CTU) into 68Ga-PSMA-11 PET/CT and to analyze the impact of CTU on assigning focal tracer accumulation in the ureteric space to either ureteric excretion or metastatic disease concerning topographic attribution and diagnostic confidence. Methods: Ten prostate cancer patients who underwent 68Ga-PSMA-11 PET/CT including CTU because of biochemical relapse or known metastatic disease were retrospectively analyzed. CTU consisted of an excretory phase 10 min after injection of 80 mL iodinated contrast material. Ureter opacification at CTU was evaluated using the following score: 0, 0% opacification; 1, < 50%; 2, 50–99%; 3, 100%. Topographic attribution and confidence of topographic attribution of focal tracer accumulation in the ureteric space were separately assessed for 68Ga-PSMA-11 PET/CT without and with CTU. Diagnostic confidence was evaluated using the following score: 0, < 25% confidence; 1, 26–50%; 2, 51–75%; 3, 76–100%. Results: At CTU, mean ureter opacification score was 2.6 ± 0.7. At 68Ga-PSMA-11 PET/CT without CTU, mean confidence of topographic attribution of focal tracer accumulation was 2.5 ± 0.7 in total and 2.6 ± 0.7 for metastatic disease. At 68Ga-PSMA-11 PET/CT with CTU, mean confidence of topographic attribution of focal areas of tracer accumulation was significantly higher with 2.9 ± 0.2 in total and 2.7 ± 0.9 for metastatic disease (p < 0.001). In 4 of 34 findings (12%) attribution to either ureteric excretion or metastatic disease was discrepant between 68Ga-PSMA-11 PET/CT without and with CTU (n.s). Conclusions: Integration of CTU into 68Ga-PSMA-11 PET/CT is feasible and increases diagnostic confidence of assigning focal areas of tracer accumulation in the ureteric space to either metastatic disease or ureteric excretion

A Novel Heat Shock Transcription Factor Family in <i>Entamoeba histolytica</i>

The HSTF is a master molecule involved in the transcriptional control of several genes during different types of stress. This transcription factor is a very conserved protein identified in different organisms from bacterial to human. <i>Entamoeba histolytica</i> is the protozoan responsible for the human amoebiasis. This parasite is exposed to different kind of stress as changes in the pH, temperature, drugs, all that situations in where the parasite needs survive. Here we identified and isolated a novel gene family of HSTFs in the protozoan parasite <i>E. histolytica</i>. Three members that we called <i>Ehhstf1</i>, <i>Ehhstf2</i> and <i>Ehhstf3</i> compose this family. Amino acid alignments and domain architecture analysis revealed that the EhHSTFs presents a conserved DNA-binding domain composed of approximately 25 residues. Interestingly this domain is shorter than the domain of the human, mouse and yeast HSTFs. Heterologous antibodies recognized four peptides of 73, 66, 47 and 23 kDa in total extracts from trophozoites growth under normal conditions. The 73, 47 and 23 kDa peptides increased their intensity when the cells were growth at 42°C by 2 h. All results together demonstrate that the amoeba present HSTFs, which may be, controlled the gene expression of this parasite under different stress situations

68Ga-PSMA-11 Dynamic PET/CT Imaging in Primary Prostate Cancer.

PURPOSE The aim of our study is to assess the pharmacokinetics and biodistribution of Ga-PSMA-11 in patients suffering from primary prostate cancer (PC) by means of dynamic and whole-body PET/CT. MATERIALS AND METHODS Twenty-four patients with primary, previously untreated PC were enrolled in the study. All patients underwent dynamic PET/CT (dPET/CT) scanning of the pelvis and whole-body PET/CT studies with Ga-PSMA-11. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on two-tissue compartment modeling and a noncompartmental approach leading to the extraction of fractal dimension (FD). RESULTS A total of 23/24 patients (95.8%) were Ga-PSMA-11 positive. In 9/24 patients (37.5%), metastatic lesions were detected. PC-associated lesions demonstrated the following mean values: SUVaverage = 14.3, SUVmax = 23.4, K1 = 0.24 (1/min), k3 = 0.34 (1/min), influx = 0.15 (1/min), and FD = 1.27. The parameters SUVaverage, SUVmax, k3, influx, and FD derived from PC-associated lesions were significantly higher than respective values derived from reference prostate tissue. Time-activity curves derived from PC-associated lesions revealed an increasing Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate but significant correlation between PSA levels and SUVaverage (r = 0.60) and SUVmax (r = 0.57), and a weak but significant correlation between Gleason score and SUVaverage (r = 0.33) and SUVmax (r = 0.28). CONCLUSION Ga-PSMA-11 PET/CT confirmed its capacity in detecting primary PC with a detection rate of 95.8%. Dynamic PET/CT studies of the pelvis revealed an increase in tracer uptake in PC-associated lesions during the 60 minutes of dynamic PET acquisition, a finding with potential applications in anti-PSMA approaches

High loading of polygenic risk for ADHD in children with comorbid aggression

Objective: Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. Method: Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. Results: Polygenic risk for ADD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by,the aggression items. Conclusions: Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Constitutive Activation of PrfA Tilts the Balance of Listeria monocytogenes Fitness Towards Life within the Host versus Environmental Survival

PrfA is a key regulator of Listeria monocytogenes pathogenesis and induces the expression of multiple virulence factors within the infected host. PrfA is post-translationally regulated such that the protein becomes activated upon bacterial entry into the cell cytosol. The signal that triggers PrfA activation remains unknown, however mutations have been identified (prfA* mutations) that lock the protein into a high activity state. In this report we examine the consequences of constitutive PrfA activation on L. monocytogenes fitness both in vitro and in vivo. Whereas prfA* mutants were hyper-virulent during animal infection, the mutants were compromised for fitness in broth culture and under conditions of stress. Broth culture prfA*-associated fitness defects were alleviated when glycerol was provided as the principal carbon source; under these conditions prfA* mutants exhibited a competitive advantage over wild type strains. Glycerol and other three carbon sugars have been reported to serve as primary carbon sources for L. monocytogenes during cytosolic growth, thus prfA* mutants are metabolically-primed for replication within eukaryotic cells. These results indicate the critical need for environment-appropriate regulation of PrfA activity to enable L. monocytogenes to optimize bacterial fitness inside and outside of host cells

Intracellular Vesicles as Reproduction Elements in Cell Wall-Deficient L-Form Bacteria

Cell wall-deficient bacteria, or L-forms, represent an extreme example of bacterial plasticity. Stable L-forms can multiply and propagate indefinitely in the absence of a cell wall. Data presented here are consistent with the model that intracellular vesicles in Listeria monocytogenes L-form cells represent the actual viable reproductive elements. First, small intracellular vesicles are formed along the mother cell cytoplasmic membrane, originating from local phospholipid accumulation. During growth, daughter vesicles incorporate a small volume of the cellular cytoplasm, and accumulate within volume-expanding mother cells. Confocal Raman microspectroscopy demonstrated the presence of nucleic acids and proteins in all intracellular vesicles, but only a fraction of which reveals metabolic activity. Following collapse of the mother cell and release of the daughter vesicles, they can establish their own membrane potential required for respiratory and metabolic processes. Premature depolarization of the surrounding membrane promotes activation of daughter cell metabolism prior to release. Based on genome resequencing of L-forms and comparison to the parental strain, we found no evidence for predisposing mutations that might be required for L-form transition. Further investigations revealed that propagation by intracellular budding not only occurs in Listeria species, but also in L-form cells generated from different Enterococcus species. From a more general viewpoint, this type of multiplication mechanism seems reminiscent of the physicochemical self-reproducing properties of abiotic lipid vesicles used to study the primordial reproduction pathways of putative prokaryotic precursor cells

Depression and anxiety in relation to catechol-O-methyltransferase Val158Met genotype in the general population: The Nord-Trøndelag Health Study (HUNT)

<p>Abstract</p> <p>Background</p> <p>The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, which has been linked to anxiety and depression, but previous results are not conclusive. The aim of the present study was to examine the relationship between the Val158Met COMT gene polymorphism and anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS) in the general adult population.</p> <p>Methods</p> <p>In the Nord-Trøndelag Health Study (HUNT) the association between the Val158Met polymorphism and anxiety and depression was evaluated in a random sample of 5531 individuals. Two different cut off scores (≥ 8 and ≥ 11) were used to identify cases with anxiety (HADS-A) and depression (HADS-D), whereas controls had HADS-A <8 and HADS-D <8.</p> <p>Results</p> <p>The COMT genotype distribution was similar between controls and individuals in the groups with anxiety and depression using cut-off scores of ≥ 8. When utilizing the alternative cut-off score HADS-D ≥ 11, Met/Met genotype and Met allele were less common among men with depression compared to the controls (genotype: p = 0.017, allele: p = 0.006). In the multivariate analysis, adjusting for age and heart disease, depression (HADS-D ≥ 11) was less likely among men with the Met/Met genotype than among men with the Val/Val genotype (OR = 0.37, 95% CI = 0.18–0.76).</p> <p>Conclusion</p> <p>In this population-based study, no clear association between the Val158Met polymorphism and depression and anxiety was revealed. The Met/Met genotype was less likely among men with depression defined as HADS-D ≥ 11, but this may be an incidental finding.</p