rudyvdbrink/CitationDatabase huggingface dataset:
Overexpression of parkin rescues the defective mitochondrial phenotype and the increased apoptosis of Cockayne Syndrome A cells.
Oncotarget, 2017

The ERCC8/CSA gene encodes a WD-40 repeat protein (CSA) that is part of a E3-ubiquitin ligase/COP9 signalosome complex. When mutated, CSA causes the Cockayne Syndrome group A (CS-A), a rare recessive progeroid disorder characterized by sun sensitivity and neurodevelopmental abnormalities. CS-A cells features include ROS hyperproduction, accumulation of oxidative genome damage, mitochondrial dysfunction and increased apoptosis that may contribute to the neurodegenerative process. In this study, we show that CSA localizes to mitochondria and specifically interacts with the mitochondrial fission protein dynamin-related protein (DRP1) that is hyperactivated when CSA is defective. Increased fission is not counterbalanced by increased mitophagy in CS-A cells thus leading to accumulation of fragmented mitochondria. However, when mitochondria are challenged with the mitochondrial toxin carbonyl cyanide m-chloro phenyl hydrazine, CS-A fibroblasts undergo mitophagy as efficiently as normal fibroblasts, suggesting that this process remains targetable to get rid of damaged mitochondria. Indeed, when basal mitophagy was potentiated by overexpressing Parkin in CSA deficient cells, a significant rescue of the dysfunctional mitochondrial phenotype was observed. Importantly, Parkin overexpression not only reactivates basal mitophagy, but plays also an anti-apoptotic role by significantly reducing the translocation of Bax at mitochondria in CS-A cells. These findings provide new mechanistic insights into the role of CSA in mitochondrial maintenance and might open new perspectives for therapeutic approaches.
Behavioral testing affects the phenotypic expression of APOE ε3 and APOE ε4 in targeted replacement mice and reduces the differences between them.
Alzheimer's & dementia (Amsterdam, Netherlands), 2015

Apolipoprotein E4 (APOE ε4) is the most prevalent genetic risk factor for Alzheimer's disease (AD). Targeted replacement mice that express either APOE ε4 or its AD benign isoform, APOE ε3, are used extensively in behavioral, biochemical, and physiological studies directed at assessing the phenotypic effects of APOE ε4 and at unraveling the mechanisms underlying them. Such experiments often involve pursuing biochemical and behavioral measurements on the same cohort of mice. In view of the possible cross-talk interactions between brain parameters and cognitive performance, we presently investigated the extent to which the phenotypic expression of APOE ε4 and APOE ε4 in targeted replacement mice is affected by behavioral testing. This was performed using young, naïve APOE ε4 and APOE ε3 mice in which the levels of distinct brain parameters are affected by the APOE genotype (e.g., elevated levels of amyloid beta [Aβ] and hyperphosphorylated tau and reduced levels of vesicular glutamate transporter (VGLUT) in hippocampal neurons of APOE ε4 mice). These mice were exposed to a fear-conditioning paradigm, and the resulting effects on the brain parameters were examined. The results obtained revealed that the levels of Aβ, hyperphosphorylated tau, VGluT, and doublecortin of the APOE ε4 and APOE ε3 mice were markedly affected following the exposure of APOE ε4 and APOE ε3 mice to the fear-conditioning paradigm such that the isoform-specific effects of APOE ε4 on these parameters were greatly diminished. The finding that behavioral testing affects the APOE ε3 and APOE ε4 phenotypes and masks the differences between them has important theoretical and practical implications and suggests that the assessment of brain and behavioral parameters should be performed using different cohorts.
Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures.
Nature communications, 2015

The potassium-chloride co-transporter KCC2, encoded by SLC12A5, plays a fundamental role in fast synaptic inhibition by maintaining a hyperpolarizing gradient for chloride ions. KCC2 dysfunction has been implicated in human epilepsy, but to date, no monogenic KCC2-related epilepsy disorders have been described. Here we show recessive loss-of-function SLC12A5 mutations in patients with a severe infantile-onset pharmacoresistant epilepsy syndrome, epilepsy of infancy with migrating focal seizures (EIMFS). Decreased KCC2 surface expression, reduced protein glycosylation and impaired chloride extrusion contribute to loss of KCC2 activity, thereby impairing normal synaptic inhibition and promoting neuronal excitability in this early-onset epileptic encephalopathy.
Short and Long Term Clinical and Immunologic Follow up after Bone Marrow Mesenchymal Stromal Cell Therapy in Progressive Multiple Sclerosis-A Phase I Study.
Journal of clinical medicine, 2019

Bone marrow derived mesenchymal stromal cells (BM-MSCs) have emerged as a possible new therapy for Multiple Sclerosis (MS), however studies regarding efficacy and in vivo immune response have been limited and inconclusive. We conducted a phase I clinical study assessing safety and clinical and peripheral immune responses after MSC therapy in MS. Seven patients with progressive MS were intravenously infused with a single dose of autologous MSC (1-2 × 10
Two routes for remembering the past.
Cell, 2011

Which brain circuits underlie retrieval of distant memories? Goshen et al. (2011) use a powerful optogenetic-based approach to reveal the critical contribution of the hippocampus to remote memory retrieval. In so doing, they provide new evidence toward resolving a long-standing debate in cognitive neuroscience.
Case report: the unexpected culprit for multiple shunt revisions.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2019

Silicone allergy in patients with ventricular shunts is uncommon hence easily missed. However, there are clinical features that could assist in identifying and diagnosing this condition. We discuss a case where a patient with a ventriculoperitoneal (VP) shunt presented to us with features suggestive of silicone allergy.
Efficacy of Systemic Treatments of Psoriasis on Pruritus: A Systemic Literature Review and Meta-Analysis.
The Journal of investigative dermatology, 2018

In the course of the last 30 years, several studies have clearly documented that pruritus is a very frequent symptom of psoriasis and its impact on the patients' quality of life. The variety of available systemic treatments for psoriasis is increasing rapidly. Our objective was to assess their efficacy on pruritus based on a systematic literature review. A systematic literature search was performed using PubMed and Trip Database (from January 1990 to September 2016) to find published clinical trials for the treatments of psoriasis, and then a meta-analysis was performed. Among 516 articles identified, 35 studies were retained in the systematic review. At baseline, the high prevalence of pruritus (80-100%) was confirmed. The meta-analysis included 13 trials using a 0 to 10 itch scale and highlighted that all treatments evaluated reduced pruritus. Anti-IL-17, JAK inhibitors, adalimumab, and apremilast were all shown to be effective in reducing pruritus in psoriasis with variable effect size magnitudes. Our systematic review highlights that systemic treatments, including UVB phototherapy, improve pruritus in psoriasis but that it is not necessarily correlated with lesion recovering. Nonetheless, these results must be displayed carefully because there are so many variable endpoints in different studies.
Roles of Category, Shape, and Spatial Frequency in Shaping Animal and Tool Selectivity in the Occipitotemporal Cortex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Does the nature of representation in the category-selective regions in the occipitotemporal cortex reflect visual or conceptual properties? Previous research showed that natural variability in visual features across categories, quantified by image gist statistics, is highly correlated with the different neural responses observed in the occipitotemporal cortex. Using fMRI, we examined whether category selectivity for animals and tools would remain, when image gist statistics were comparable across categories. Critically, we investigated how category, shape, and spatial frequency may contribute to the category selectivity in the animal- and tool-selective regions. Female and male human observers viewed low- or high-passed images of round or elongated animals and tools that shared comparable gist statistics in the main experiment, and animal and tool images of naturally varied gist statistics in a separate localizer. Univariate analysis revealed robust category-selective responses for images with comparable gist statistics across categories. Successful classification for category (animals/tools), shape (round/elongated), and spatial frequency (low/high) was also observed, with highest classification accuracy for category. Representational similarity analyses further revealed that the activation patterns in the animal-selective regions were most correlated with a model that represents only animal information, whereas the activation patterns in the tool-selective regions were most correlated with a model that represents only tool information, suggesting that these regions selectively represent information of only animals or tools. Together, in addition to visual features, the distinction between animal and tool representations in the occipitotemporal cortex is likely shaped by higher-level conceptual influences such as categorization or interpretation of visual inputs.
Beyond conformity: Social influences on pain reports and physiology.
Emotion (Washington, D.C.), 2016

Social information can profoundly influence behavior, but its effects are often explained in terms of "conformity," implying effects on decision-making and communication rather than deeper sensory modulation. We examined whether information about other people's pain reports affected both participants' pain experience and skin conductance responses (SCR) during pain. Sixty volunteers experienced painful heat stimulation preceded by 2 kinds of informational cues: (a) nonreinforced social information indicating low or high pain ratings from previous participants; and (b) reinforced conditioned stimuli (CSlow, CShigh). Both high-pain social information and CShigh cues enhanced pain and SCRs relative to their respective controls, with particularly robust effects of social information. Effects of both manipulations on both pain and SCRs were mediated by trial-by-trial pain expectancies. These results demonstrate strong social influences on pain and autonomic responses, and suggest that expectations from multiple sources can influence pain physiology independent of reinforcement.
History of abuse and neglect and their associations with mental health in rescued child labourers in Nepal.
The Australian and New Zealand journal of psychiatry, 2019

Little is known about rates of childhood maltreatment in low-income countries, particularly among marginalised sectors of society. Economic hardships mean that in such countries, many children and young people are exploited in the labour force and/or are trafficked, placing them at greater risk for being exposed to other forms of maltreatment. Cultural norms endorsing the use of physical and emotional acts to discipline children further exacerbate this risk. Here, we assessed the rates of childhood victimisation experiences and associated mental health problems in Nepalese youth rescued from illegal child labour including trafficking.
Different dorsal striatum circuits mediate action discrimination and action generalization.
The European journal of neuroscience, 2012

Generalization is an important process that allows animals to extract rules from regularities of past experience and apply them to analogous situations. In particular, the generalization of previously learned actions to novel instruments allows animals to use past experience to act faster and more efficiently in an ever-changing environment. However, generalization of actions to a dissimilar instrument or situation may also be detrimental. In this study, we investigated the neural bases of action generalization and discrimination in mice trained on a lever-pressing task. Using specific schedules of reinforcement known to bias animals towards habitual or goal-directed behaviors, we confirmed that action generalization is more prominent in animals using habitual rather than goal-directed strategies. We discovered that selective excitotoxic lesions of the dorsolateral and dorsomedial striatum have opposite effects on the generalization of a previously learned action to a novel lever. Whereas lesions of the dorsolateral striatum impair action generalization, dorsomedial striatum lesions affect action discrimination and bias subjects towards action generalization. Importantly, these lesions do not affect the ability of animals to explore or match their lever-pressing rate to the reinforcement rate, or the ability to distinguish between different levers. The data presented here reveal that dorsolateral and dorsomedial striatal circuits have opposing roles in the generalization of previously learned actions to novel instruments, and suggest that these circuits compete for the expression of generalization in novel situations.
Concerns about pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PK-PD) studies in the new therapeutic area of COVID-19 infection.
Antiviral research, 2020

In the context of the COVID-19 pandemic, several drugs have been repurposed as potential candidates for the treatment of COVID-19 infection. While preliminary choices were essentially based on in vitro potency, clinical translation into effective therapies may be challenging due to unfavorable in vivo pharmacokinetic properties at the doses chosen for this new indication of COVID-19 infection. However, available pharmacokinetic and pharmacokinetic-pharmacodynamic studies suffer from severe limitations leading to unreliable conclusions, especially in term of dosing optimization. In this paper we propose to highlight these limitations and to identify some of the major requirements that need to be addressed in designing PK and PK-PD studies in this era of COVID. A special attention should be paid to pre-analytical and analytical requirements and to the proper collection of covariates affecting dose-exposure relationships (co-medications, use of specific organ support techniques and other clinical and para-clinical data). We also promote the development of population PK and PK-PD models specifically dedicated to COVID-19 patients since those previously developed for other diseases (SEL, malaria, HIV) and clinical situations (steady-state, non-ICU patients) are not representative of severe patients. Therefore, implementation of well-designed PK and PD studies targeted to COVID-19 patients is urgently needed. For that purpose we call for multi-institutional collaborative work and involvement of clinical pharmacologists in multidisciplinary research consortia.
Levodopa/carbidopa intestinal gel therapy for advanced Parkinson Disease: AN early toxic effect for small nerve fibers?
Muscle & nerve, 2016

Peripheral neuropathy related to levodopa/carbidopa intestinal gel (LCIG) therapy for advanced Parkinson disease (PD) is under investigation and is debated in the literature. The purpose of the study was to detect whether small nerve fibers are damaged during LCIG infusion.
Spasmodic dysphonia: a laryngeal control disorder specific to speech.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Spasmodic dysphonia (SD) is a rare neurological disorder that emerges in middle age, is usually sporadic, and affects intrinsic laryngeal muscle control only during speech. Spasmodic bursts in particular laryngeal muscles disrupt voluntary control during vowel sounds in adductor SD and interfere with voice onset after voiceless consonants in abductor SD. Little is known about its origins; it is classified as a focal dystonia secondary to an unknown neurobiological mechanism that produces a chronic abnormality of laryngeal motor neuron regulation during speech. It develops primarily in females and does not interfere with breathing, crying, laughter, and shouting. Recent postmortem studies have implicated the accumulation of clusters in the parenchyma and perivascular regions with inflammatory changes in the brainstem in one to two cases. A few cases with single mutations in THAP1, a gene involved in transcription regulation, suggest that a weak genetic predisposition may contribute to mechanisms causing a nonprogressive abnormality in laryngeal motor neuron control for speech but not for vocal emotional expression. Research is needed to address the basic cellular and proteomic mechanisms that produce this disorder to provide intervention that could target the pathogenesis of the disorder rather than only providing temporary symptom relief.
Inflammatory cell recruitment after experimental thromboembolic stroke in rats.
Neuroscience, 2014

Inflammatory mechanisms were recently identified as contributors to delayed neuronal damage after ischemic stroke. However, therapeutic strategies are still lacking, probably related to the outstanding standardization on inflammatory cell recruitment emerging from predominantly artificial stroke models, and the uncertainty on functional properties of distinct subpopulations. Using a rodent model of stroke that closely reflects human embolic ischemia, this study was focused on the local recruitment of immunoreactive cells as well as their functional and regional characterization. Wistar rats underwent thromboembolic middle cerebral artery occlusion, followed by intravenous injection of the blood-brain barrier permeability marker fluorescein-conjugated albumin at 24h. One hour later, brain tissue was subjected to multi-parameter flow cytometry and Pappenheim staining to characterize cells invaded into the ischemia-affected hemisphere, compared to the contralateral side. Immunofluorescence labeling was applied to explore the distribution patterns of recruited cells and their spatial relationships with the vasculature. One day after ischemia onset, a 6.12-fold increase of neutrophils and a 5.43-fold increase of monocytes/macrophages was found in affected hemispheres, while these cells exhibited enhanced major histocompatibility complex class II expression and allocation with vessels exhibiting impaired blood-brain barrier integrity. Microglia remained numerically unaltered in ischemic hemispheres, but shifted to an activated phenotype indicated by CD45/CD86 expression and morphological changes toward an ameboid appearance in the bordering zone. Ischemia caused an increase of lymphoid cells in close vicinity to the affected vasculature, while further analyses allowed separation into natural killer cells, natural killer T cells, T cells (added by an unconventional CD11b(+)/CD3(+) population) and two subpopulations of B cells. Taken together, our study provides novel data on the local inflammatory response to experimental thromboembolic stroke. As concomitantly present neutrophils, monocytes/macrophages and lymphoid cells in the early stage after ischemia induction correspond to changes seen in human stroke, future stroke research should preferably use animal models with relevance for clinical translation.
Postsynaptic integrative properties of dorsal CA1 pyramidal neuron subpopulations.
Journal of neurophysiology, 2020

The population activity of CA1 pyramidal neurons (PNs) segregates along anatomical axes with different behaviors, suggesting that CA1 PNs are functionally subspecialized based on somatic location. In dorsal CA1, spatial encoding is biased toward CA2 (CA1c) and in deep layers of the radial axis. In contrast, nonspatial coding peaks toward subiculum (CA1a) and in superficial layers. While preferential innervation by spatial vs. nonspatial input from entorhinal cortex (EC) may contribute to this specialization, it cannot fully explain the range of in vivo responses. Differences in intrinsic properties thus may play a critical role in modulating such synaptic input differences. In this study we examined the postsynaptic integrative properties of dorsal CA1 PNs in six subpopulations along the transverse (CA1c, CA1b, CA1a) and radial (deep, superficial) axes. Our results suggest that active and passive properties of deep and superficial neurons evolve over the transverse axis to promote the functional specialization of CA1c vs. CA1a as dictated by their cortical input. We also find that CA1b is not merely an intermediate mix of its neighbors, but uniquely balances low excitability with superior input integration of its mixed input, as may be required for its proposed role in sequence encoding. Thus synaptic input and intrinsic properties combine to functionally compartmentalize CA1 processing into at least three transverse axis regions defined by the processing schemes of their composite radial axis subpopulations.
Polysomnographic measures of sleep in cocaine dependence and alcohol dependence: Implications for age-related loss of slow wave, stage 3 sleep.
Addiction (Abingdon, England), 2016

Sleep disturbance is a prominent complaint in cocaine and alcohol dependence. This controlled study evaluated differences of polysomnographic (PSG) sleep in cocaine- and alcohol-dependent subjects, and examined whether substance dependence interacts with age to alter slow wave sleep and rapid eye movement (REM) sleep.
Training peers to treat Ebola centre workers with anxiety and depression in Sierra Leone.
The International journal of social psychiatry, 2018

Following the 2014 Ebola virus disease (EVD) outbreak in West Africa, the UK Department for International Development funded South London and Maudsley National Health Service (NHS) to develop a psychological intervention that ex-Ebola Treatment Centre (ETC) staff could be trained to deliver to their peers to improve mental health in Sierra Leone.
Internally coupled middle ears enhance the range of interaural time differences heard by the chicken.
The Journal of experimental biology, 2019

Interaural time differences (ITDs) are one of several principal cues for localizing sounds. However, ITDs are in the sub-millisecond range for most animals. Because the neural processing of such small ITDs pushes the limit of temporal resolution, the precise ITD range for a given species and its usefulness - relative to other localization cues - has been a powerful selective force in the evolution of the neural circuits involved. Birds and other non-mammals have internally coupled middle ears working as pressure-difference receivers that may significantly enhance ITDs, depending on the precise properties of the interaural connection. Here, the extent of this internal coupling was investigated in chickens, specifically under the same experimental conditions as typically used in investigations of the neurophysiology of ITD-coding circuits, i.e. with headphone stimulation and skull openings. Cochlear microphonics (CM) were recorded simultaneously from both ears of anesthetized chickens under monaural and binaural stimulation, using pure tones from 0.1 to 3 kHz. Interaural transmission peaked at 1.5 kHz at a loss of only -5.5 dB; the mean interaural delay was 264 µs. CM amplitude was strongly modulated as a function of ITD, confirming significant interaural coupling. The 'ITD heard' derived from the CM phases in both ears showed enhancement, compared with the acoustic stimuli, by a factor of up to 1.8. However, the experimental conditions impaired interaural transmission at low frequencies (<1 kHz). I identify factors that need to be considered when interpreting neurophysiological data obtained under these conditions and relating them to the natural free-field condition.