Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I: wet lab procedure

Metagenomic high-throughput sequencing (mHTS) is a hypothesis-free, universal pathogen detection technique for determination of the DNA/RNA sequences in a variety of sample types and infectious syndromes. mHTS is still in its early stages of translating into clinical application. To support the development, implementation and standardization of mHTS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mHTS for viral diagnostics to share methodologies and experiences, and to develop application recommendations. This manuscript aims to provide practical recommendations for the wet lab procedures necessary for implementation of mHTS for virus diagnostics and to give recommendations for development and validation of laboratory methods, including mHTS quality assurance, control and quality assessment protocols.Molecular basis of virus replication, viral pathogenesis and antiviral strategie

Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I: Wet lab procedure

Metagenomic high-throughput sequencing (mHTS) is a hypothesis-free, universal pathogen detection technique for determination of the DNA/RNA sequences in a variety of sample types and infectious syndromes. mHTS is still in its early stages of translating into clinical application. To support the development, implementation and standardization of mHTS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mHTS for viral diagnostics to share methodologies and experiences, and to develop application recommendations. This manuscript aims to provide practical recommendations for the wet lab procedures necessary for i

Roles of the amygdala and basal forebrain in defense: A Reply to Lucyk et al. and implications for defensive action

Contains fulltext : 204116.pdf (publisher's version ) (Open Access)The commentary by Luyck and colleagues on our paper provides many stimulating viewpoints and interpretations of our original study on dissociable responses in the amygdala and bed nucleus of the stria terminalis in threat processing. Here, we reply to some of the points raised and while agreeing with most of the comments also provide some alternative viewpoints. We end by putting forward a research agenda for how to further investigate the roles of these regions in threat processing, with an emphasis on studying their roles in defensive action.4 p

Altering memories for emotional experiences

Contains fulltext : 115716.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 05 september 2013Promotores : Fernandez, G.S.E., Strange, B.A. Co-promotor : Wingen, G.A. va

Episodic memory and Pavlovian conditioning: ships passing in the night

Contains fulltext : 204811.pdf (publisher's version ) (Closed access)Research on emotional learning and memory is traditionally approached from one of two directions: episodic memory and classical conditioning. These approaches differ substantially in methodology and intellectual tradition. Here, we offer a new approach to the study of emotional memory in humans that involves integrating theoretical knowledge and experimental techniques from these seemingly distinct fields. Specifically, we describe how subtle modifications to traditional Pavlovian conditioning procedures have provided new insight into how emotional experiences are selectively prioritized in long-term episodic memory. We also speculate on future directions and undeveloped lines of research where some of the knowledge and principles of classical conditioning might advance our understanding of how emotion modifies episodic memory, and vice versa

Dynamic neural systems enable adaptive, flexible memories.

Item does not contain fulltextAlmost all studies on memory formation have implicitly put forward a rather static view on memory. However, memories are not stable but sensitive to changes over time. Here we argue that memory alterations arise from the inherent predictive function of memory. Within this framework, we draw an analogy between the lateral temporal-lateral prefrontal system that supports prediction based on simple stimulus-response associations and propose that a similar system centring on the hippocampus and medial prefrontal cortex (mPFC) exists for complex episodic memories. We consider the hippocampus to be elementary for regularity detection and the mPFC for regularity storage together with response options, which form the basis of abstract knowledge. As such, abstract knowledge can come to guide behaviour in novel situations that only share partial overlap with episodic experiences that have given rise to the formation of abstract knowledge. Furthermore, we suggest that systems consolidation and sleep contribute to the formation of abstract knowledge, and that abstract knowledge can function as pre-existing schemas to the encoding of novel memories. Finally, we discuss that reconsolidation supports the updating of memories to optimize prediction. We accentuate that memory formation requires dynamic interactions between brain regions, and that rapid formation of detailed memories depends on synaptic weight changes, whereas rather stable abstract knowledge is supported by cortico-cortical rewiring. Together, we attempt explaining that apparent memory alterations and distortions are adaptive.1 augustus 201

A reminder before extinction strengthens episodic memory via reconsolidation but fails to disrupt generalized threat responses

Contains fulltext : 177015.pdf (publisher's version ) (Open Access)A reminder can temporarily renew flexibility of consolidated memories, referred to as reconsolidation. Pavlovian threat-conditioning studies suggest that a reminder can renew flexibility of threat responses but that episodic memories remain stable. In contrast, outside the threat-conditioning domain, studies testing memory for word lists or stories find that a reminder can renew flexibility of episodic memory. This discrepancy in findings leaves it unclear if episodic memories reconsolidate, or only Pavlovian responses. Here we unite the different approaches in the field and show that a reminder can retroactively strengthen episodic memory for Pavlovian threat-conditioned events, but that, in contrast to threat-conditioning studies with simple sensory stimuli, extinction after a reminder fails to prevent recovery of generalized threat responses. Our results indicate the episodic memories also reconsolidate, allowing strengthening of relevant memories. These findings also suggest that generalized threat responses and episodic memories are less susceptible to be modified by reminder-interventions procedures

Association between flashbacks and structural brain abnormalities in posttraumatic stress disorder

Item does not contain fulltextOBJECTIVE: Posttraumatic stress disorder (PTSD) is reliably associated with reduced brain volume relative to healthy controls, in areas similar to those found in depression. We investigated whether in a PTSD sample brain volumes in these areas were related to reporting specific symptoms of PTSD or to overall symptom severity. METHOD: Structural MRI scans were obtained from 28 participants diagnosed with PTSD according to DSM-IV-TR. Participants reported the extent of individual PTSD symptoms using the Posttraumatic Diagnostic Scale. Voxel-based morphometry applying the Dartel algorithm implemented within SPM5 was used to identify volumetric changes, related to PTSD total, symptom cluster, and individual symptom scores. RESULTS: Brain volume was unrelated to overall PTSD severity, but greater reexperiencing scores predicted reduced volumes in the middle temporal and inferior occipital cortices. Increased reports of flashbacks predicted reduced volume in the insula/parietal operculum and in the inferior temporal gyrus. CONCLUSION: The data illustrate the value of analyses at the symptom level within a patient population to supplement group comparisons of patients and healthy controls. Areas identified were consistent with a neurobiological account of flashbacks implicating specific abnormalities in the ventral visual stream

How human amygdala and bed nucleus of the stria terminalis may drive distinct defensive responses

The ability to adaptively regulate responses to the proximity of potential danger is critical to survival and imbalance in this system may contribute to psychopathology. The bed nucleus of the stria terminalis (BNST) is implicated in defensive responding during uncertain threat anticipation whereas the amygdala may drive responding upon more acute danger. This functional dissociation between the BNST and amygdala is however controversial, and human evidence scarce. Here we utilized data from two independent functional magnetic resonance imaging studies (N=108 males & N=70 (45 females)) to probe how coordination between the BNST and amygdala may regulate responses during shock anticipation and actual shock confrontation. In a subset of participants from sample 2 (N=48) we demonstrate that anticipation and confrontation evoke bradycardic and tachycardic responses respectively. Further, we show that in each sample when going from shock anticipation to the moment of shock confrontation neural activity shifted from a region anatomically consistent with the BNST towards the amygdala. Comparisons of functional connectivity during threat processing showed overlapping yet also consistently divergent functional connectivity profiles for the BNST and amygdala. Finally, childhood maltreatment levels predicted amygdala, but not BNST, hyperactivity during shock anticipation. Our results support an evolutionary conserved, defensive distance-dependent dynamic balance between BNST and amygdala activity. Shifts in this balance may enable shifts in defensive reactions via the demonstrated differential functional connectivity. Our results indicate that early life stress may tip the neural balance towards acute threat responding and via that route predispose for affective disorder

How human amygdala and BNST may drive distinct defensive responses

Supplementary material to the paper:How human amygdala and BNST may drive distinct defensive response