Targeting Neuronal Populations of the Striatum

The striatum is critically involved in motor and motivational functions. The dorsal striatum, caudate–putamen, is primarily implicated in motor control and the learning of habits and skills, whereas the ventral striatum, the nucleus accumbens, is essential for motivation and drug reinforcement. The GABA medium-sized spiny neurons (MSNs, about 95% of striatal neurons), which are targets of the cerebral cortex and the midbrain dopaminergic neurons, form two pathways. The dopamine D1 receptor-positive (D1R) striatonigral MSNs project to the medial globus pallidus and substantia nigra pars reticulata (direct pathway) and co-express D1R and substance P, whereas dopamine D2 receptor-positive (D2R) striatopallidal MSNs project to the lateral globus pallidus (indirect pathway) and co-express D2R, adenosine A2A receptor (A2AR) and enkephalin (Enk). The specific role of the two efferent pathways in motor and motivational control remained poorly understood until recently. Indeed, D1R striatonigral and D2R striatopallidal neurons, are intermingled and morphologically indistinguishable, and, hence, cannot be functionally dissociated with techniques such as chemical lesions or surgery. In view of the still debated respective functions of projection D2R striatopallidal and D1R striatonigral neurons and striatal interneurons, both in motor control and learning but also in more cognitive processes such as motivation, the present review sum up the development of new models and techniques (bacterial artificial chromosome transgenesis, optogenetic, viral transgenesis) allowing the selective targeting of these striatal neuronal populations in adult animal brain to understand their specific roles

The monitoring of seismic activity at Nyiragongo volcano through telemetered seismic network Goma Volcano Observatory (Democratic Republic of the Congo)

The eruption, in January 2002, of Mount Nyiragongo in eastern Congo, and the humanitarian disaster that followed in its wake, underlined the critical importance of accurate seismology to predict when such events will take place. Thus, a seismic telemeterd network, with centre in Goma Observatory, was built across Virunga area to help the moniotring of Volcano. Mount Nyiragongo is a volcano in the Virunga Mountains associated with the Great Rift Valley. The most prominent feature of the Democratic Republic of Congo's geology is the Western Rift Zone (WRZ), which runs through its eastern border regions and neighbouring countries (e.g. Uganda, Rwanda, Burundi, Tanzania) between 28°E to 32°E and 4°N to 12°S. The WRZ extends over a 1600 km arc, including lakes Albert, Eduard, Kivu and Tanganyika, until it joins the eastern branch. The Western Rift Valley of Africa has experienced severe earthquakes and volcanic eruptions in recent historical times. Earthquakes with magnitude >=6 are not frequent, but may cause significant destruction. They occur mostly in DRC and neighbouring countries (e.g. Uganda and Tanzania). In 1991, IAVCEI selected the Nyiragongo volcano as the ‘African decade volcano’ for the International Decade of Natural Disaster Reduction (IDNDR) program. Nyiragongo is located about 20 km north of Lake Kivu and 15 km north of Goma, a city of about 500,000 inhabitants. Goma is twinned to Gisenyi in Rwanda, which has a population of about 100,000. Several small villages are also located on the flank of the volcano. Population growth and poor or non-existent planning has led to relatively uncontrolled use of land for building, and the development of sites vulnerable to earthquake and/or volcanic risk.EUROPEAN CENTER FOR GEODYNAMICS AND SEISMOLOGY Royal Museum for Central Africa, B National Museum of Nat. History, LUnpublishedLuxembourg1.4. TTC - Sorveglianza sismologica delle aree vulcaniche attiveope

Virtual signatures of dark sectors in Higgs couplings

Where collider searches for resonant invisible particles loose steam, dark sectors might leave their trace as virtual effects in precision observables. Here we explore this option in the framework of Higgs portal models, where a sector of dark fermions interacts with the standard model through a strong renormalizable coupling to the Higgs boson. We show that precise measurements of Higgs-gauge and triple Higgs interactions can probe dark fermions up to the TeV scale through virtual corrections. Observation prospects at the LHC and future lepton colliders are discussed for the so-called singlet-doublet model of Majorana fermions, a generalization of the bino-higgsino scenario in supersymmetry. We advocate a two-fold search strategy for dark sectors through direct and indirect observables.Comment: 20 pages, 7 figures, 1 tabl

Effect of maternal obesity and preconceptional weight loss on male and female offspring metabolism and olfactory performance in mice

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. According to the “developmental origins of health and disease” (DOHaD) concept, maternal obesity predisposes the offspring to non-communicable diseases in adulthood. While a preconceptional weight loss (WL) is recommended for obese women, its benefits on the offspring have been poorly addressed. We evaluated whether preconceptional WL was able to reverse the adverse effects of maternal obesity in a mouse model, exhibiting a modification of foetal growth and of the expression of genes encoding epigenetic modifiers in liver and placenta. We tracked metabolic and olfactory behavioural trajectories of offspring born to control, obese or WL mothers. After weaning, the offspring were either put on a control diet (CD) or a high-fat (HFD). After only few weeks of HFD, the offspring developed obesity, metabolic alterations and olfactory impairments, independently of maternal context. However, male offspring born to obese mother gained even more weight under HFD than their counterparts born to lean mothers. Preconceptional WL normalized the offspring metabolic phenotypes but had unexpected effects on olfactory performance: a reduction in olfactory sensitivity, along with a lack of fasting-induced, olfactory-based motivation. Our results confirm the benefits of maternal preconceptional WL for male offspring metabolic health but highlight some possible adverse outcomes on olfactory-based behaviours

Novel diagnostic cerebrospinal fluid biomarkers for pathologic subtypes of frontotemporal dementia identified by proteomics

Introduction: Reliable cerebrospinal fluid (CSF) biomarkers enabling identification of frontotemporal dementia (FTD) and its pathologic subtypes are lacking. Methods: Unbiased high-resolution mass spectrometry-based proteomics was applied on CSF of FTD patients with TAR DNA-binding protein 43 (TDP-43, FTD-TDP, n = 12) or tau pathology (FTD-tau, n = 8), and individuals with subjective memory complaints (SMC, n = 10). Validation was performed by applying enzyme-linked immunosorbent assay (ELISA) or enzymatic assays, when available, in a larger cohort (FTLD-TDP, n = 21, FTLD-tau, n = 10, SMC, n = 23) and in Alzheimer's disease (n = 20), dementia with Lewy bodies (DLB, n = 20), and vascular dementia (VaD, n = 18). Results: Of 1914 identified CSF proteins, 56 proteins were differentially regulated (fold change >1.2, P <.05) between the different patient groups: either between the two pathologic subtypes (10 proteins), or between at least one of these FTD subtypes and SMC (47 proteins). We confirmed the differential expression of YKL-40 by ELISA in a partly independent cohort. Furthermore, enzyme activity of catalase was decreased in FTD subtypes compared with SMC. Further validation in a larger cohort showed that the level of YKL-40 was twofold increased in both FTD pathologic subtypes compared with SMC and that the levels in FTLD-tau were higher compared to Alzheimer's dementia (AD), DLB, and VaD patients. Clinical validation furthermore showed that the catalase enzyme activity was decreased in the FTD subtypes compared to SMC, AD and DLB. Discussion: We identified promising CSF biomarkers for both FTD differential diagnosis and pathologic subtyping. YKL-40 and catalase enzyme activity should be validated further in similar pathology defined patient cohorts for their use for FTD diagnosis or treatment development

Truncation, validity, uncertainties

The truncation of the standard-model effective field theory, its validity andthe associated uncertainties have been discussed in meetings of the LHC EFT WG.Proposals were made by participants to address these issues. No consensus wasreached and no formal recommendation is therefore put forward at this time.None of the proposals has been approved or validated and further work is neededto establish a prescription. This note aims at summarizing the proposals andpoints of debate.<br

Truncation, validity, uncertainties

The truncation of the standard-model effective field theory, its validity andthe associated uncertainties have been discussed in meetings of the LHC EFT WG.Proposals were made by participants to address these issues. No consensus wasreached and no formal recommendation is therefore put forward at this time.None of the proposals has been approved or validated and further work is neededto establish a prescription. This note aims at summarizing the proposals andpoints of debate.<br

Investigation of attentional bias in obsessive compulsive disorder with and without depression in visual search

Copyright: © 2013 Morein-Zamir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedWhether Obsessive Compulsive Disorder (OCD) is associated with an increased attentional bias to emotive stimuli remains controversial. Additionally, it is unclear whether comorbid depression modulates abnormal emotional processing in OCD. This study examined attentional bias to OC-relevant scenes using a visual search task. Controls, non-depressed and depressed OCD patients searched for their personally selected positive images amongst their negative distractors, and vice versa. Whilst the OCD groups were slower than healthy individuals in rating the images, there were no group differences in the magnitude of negative bias to concern-related scenes. A second experiment employing a common set of images replicated the results on an additional sample of OCD patients. Although there was a larger bias to negative OC-related images without pre-exposure overall, no group differences in attentional bias were observed. However, OCD patients subsequently rated the images more slowly and more negatively, again suggesting post-attentional processing abnormalities. The results argue against a robust attentional bias in OCD patients, regardless of their depression status and speak to generalized difficulties disengaging from negative valence stimuli. Rather, post-attentional processing abnormalities may account for differences in emotional processing in OCD.Peer reviewedFinal Published versio

Effective implementation of research into practice: an overview of systematic reviews of the health literature

<p>Abstract</p> <p>Background</p> <p>The gap between research findings and clinical practice is well documented and a range of interventions has been developed to increase the implementation of research into clinical practice.</p> <p>Findings</p> <p>A review of systematic reviews of the effectiveness of interventions designed to increase the use of research in clinical practice. A search for relevant systematic reviews was conducted of Medline and the Cochrane Database of Reviews 1998-2009. 13 systematic reviews containing 313 primary studies were included. Four strategy types are identified: audit and feedback; computerised decision support; opinion leaders; and multifaceted interventions. Nine of the reviews reported on multifaceted interventions. This review highlights the small effects of single interventions such as audit and feedback, computerised decision support and opinion leaders. Systematic reviews of multifaceted interventions claim an improvement in effectiveness over single interventions, with effect sizes ranging from small to moderate. This review found that a number of published systematic reviews fail to state whether the recommended practice change is based on the best available research evidence.</p> <p>Conclusions</p> <p>This overview of systematic reviews updates the body of knowledge relating to the effectiveness of key mechanisms for improving clinical practice and service development. Multifaceted interventions are more likely to improve practice than single interventions such as audit and feedback. This review identified a small literature focusing explicitly on getting research evidence into clinical practice. It emphasizes the importance of ensuring that primary studies and systematic reviews are precise about the extent to which the reported interventions focus on changing practice based on research evidence (as opposed to other information codified in guidelines and education materials).</p