Emotion processing, reappraisal and craving in alcohol dependence: A functional Magnetic Resonance Imaging study

FdR – Publicaties niet-programma gebonde

The MLL recombinome of acute leukemias in 2017

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes

Autonomic failure in Parkinson's disease is associated with striatal dopamine deficiencies

Contains fulltext : 220829.pdf (Publisher’s version ) (Open Access)Autonomic dysfunction is a common non-motor symptom in Parkinson's disease (PD). Dopamine and serotonin are known to play a role in autonomic regulation, and, therefore, PD-related degeneration of serotonergic and dopaminergic neurons in these regions may be associated with autonomic dysfunction. We sought to clarify the association between extrastriatal serotonergic and striatal dopaminergic degeneration and the severity of autonomic symptoms, including gastrointestinal, pupillomotor, thermoregulatory, cardiovascular, and urinary dysfunction. We performed hierarchical multiple regression analyses to determine the relationships between (extra)striatal serotonergic and dopaminergic degeneration and autonomic dysfunction in 310 patients with PD. We used [(123)I]FP-CIT SPECT binding to presynaptic serotonin (SERT) and dopamine (DAT) transporters as a measure of the integrity of these neurotransmitter systems, and the SCOPA-AUT (Scales for Outcomes in Parkinson's Disease-Autonomic) questionnaire to evaluate the perceived severity of autonomic dysfunction. Motor symptom severity, medication status, and sex were added to the model as covariates. Additional analyses were also performed using five subdomains of the SCOPA-AUT: cardiovascular, gastrointestinal, urinary, thermoregulatory, and pupillomotor symptoms. We found that autonomic symptoms were most significantly related to lower [(123)I]FP-CIT binding ratios in the right caudate nucleus and were mainly driven by gastrointestinal and cardiovascular dysfunction. These results provide a first look into the modest role of dopaminergic projections towards the caudate nucleus in the pathophysiology of autonomic dysfunction in PD, but the underlying mechanism warrants further investigation