rudyvdbrink/CitationDatabase huggingface dataset:
Redundancy in synaptic connections enables neurons to learn optimally.
Proceedings of the National Academy of Sciences of the United States of America, 2018

Recent experimental studies suggest that, in cortical microcircuits of the mammalian brain, the majority of neuron-to-neuron connections are realized by multiple synapses. However, it is not known whether such redundant synaptic connections provide any functional benefit. Here, we show that redundant synaptic connections enable near-optimal learning in cooperation with synaptic rewiring. By constructing a simple dendritic neuron model, we demonstrate that with multisynaptic connections synaptic plasticity approximates a sample-based Bayesian filtering algorithm known as particle filtering, and wiring plasticity implements its resampling process. Extending the proposed framework to a detailed single-neuron model of perceptual learning in the primary visual cortex, we show that the model accounts for many experimental observations. In particular, the proposed model reproduces the dendritic position dependence of spike-timing-dependent plasticity and the functional synaptic organization on the dendritic tree based on the stimulus selectivity of presynaptic neurons. Our study provides a conceptual framework for synaptic plasticity and rewiring.
Serum 25-hydroxyvitamin D levels and psychological distress symptoms in patients with affective disorders during the COVID-19 pandemic.
Psychoneuroendocrinology, 2020

The COVID-19 pandemic has given rise to stress worldwide, especially in vulnerable people like those suffering from mental illness. This study aims to investigate the psychological distress perceived by a cohort of patients with Major Depressive Disorder (MDD) or Bipolar Disorder (BD) after a seven-week period of lockdown measures, and to analyze serum 25-hydroxyvitamin D [25(OH)D] levels as a potential predictor of distress severity.
Linking data on women in public family law court proceedings concerning their children to mental health service records in South London.
International journal of population data science, 2021

Maternal mental health problems and substance misuse are key risk factors for child neglect or abuse and court-mandated placement into care. Linkage between mental health records and family court data could raise awareness about parent mental health needs and inform approaches to address them.
Dissociating cholinergic influence on alertness and temporal attention in primates in a simple reaction time paradigm.
The European journal of neuroscience, 2020

The ability to promptly respond to behaviourally relevant events depends on both general alertness and phasic changes in attentional state driven by temporal expectations. Using a variable foreperiod simple reaction time (RT) task in four adult male rhesus macaques, we investigated the role of the cholinergic system in alertness and temporal expectation. Foreperiod effects on RT reflect temporal expectation, while alertness is quantified as overall response speed. We measured these RT parameters under vehicle treatment and systemic administration of the muscarinic receptor antagonist scopolamine. We also investigated whether and to what extent the effects of scopolamine were reversed by donepezil, a cholinesterase inhibitor widely used for the treatment of dementia. In the control condition, RT showed a continuous decrease as the foreperiod duration increased, which clearly indicated the effect of temporal expectation on RT. This foreperiod effect was mainly detectable on the faster tail of the RT distribution and was eliminated by scopolamine. Furthermore, scopolamine treatment slowed down the average RT. Donepezil treatment was efficient on the slower tail of the RT distribution and improved scopolamine-induced impairments only on the average RT reflecting a general beneficial effect on alertness without any improvement in temporal expectation. The present results highlight the role of the cholinergic system in temporal expectation and alertness in primates and help delineate the efficacy and scope of donepezil and other cholinomimetic agents as cognitive enhancers in present and future clinical practice.
Swāsthya, an integrated chronic condition management programme for families of patients with hypertension and diabetes mellitus: a study protocol for a randomised controlled trial.
BMC family practice, 2021

Kerala is known as the diabetes mellitus (DM) and hypertension (HTN) capital of the world, thus compelling health professionals to model strategies, addressing their social, behavioural, and cognitive risk factors and eliminating various barriers to management. This paper describes the protocol of our study that aims to examine the effectiveness and sustainability of an integrated care model for the management of chronic conditions and their risk factors through a family-based intervention. The proposed care model targets to modify systems and processes that predispose to chronic conditions by enhancing social cohesion and social networks, preventing lifestyle risks, developing iterative cognitive interventions, and engaging the family into customised treatment adherence strategies navigated by community health social workers (CHSWs).
Astrocytes mediate the effect of oxytocin in the central amygdala on neuronal activity and affective states in rodents.
Nature neuroscience, 2021

Oxytocin (OT) orchestrates social and emotional behaviors through modulation of neural circuits. In the central amygdala, the release of OT modulates inhibitory circuits and, thereby, suppresses fear responses and decreases anxiety levels. Using astrocyte-specific gain and loss of function and pharmacological approaches, we demonstrate that a morphologically distinct subpopulation of astrocytes expresses OT receptors and mediates anxiolytic and positive reinforcement effects of OT in the central amygdala of mice and rats. The involvement of astrocytes in OT signaling challenges the long-held dogma that OT acts exclusively on neurons and highlights astrocytes as essential components for modulation of emotional states under normal and chronic pain conditions.
Is COVID-19 associated thrombosis caused by overactivation of the complement cascade? A literature review.
Thrombosis research, 2020

Severe acute respiratory syndrome coronavirus 2 is responsible for the current COVID-19 pandemic resulting in an escalating number of cases and fatalities worldwide. Preliminary evidence from these patients, as well as past coronavirus epidemics, indicates that those infected suffer from disproportionate complement activation as well as excessive coagulation, leading to thrombotic complications and poor outcome. In non-coronavirus cohorts, evidence has accumulated of an interaction between the complement and coagulation systems, with one amplifying activation of the other. A pressing question is therefore if COVID-19 associated thrombosis could be caused by overactivation of the complement cascade? In this review, we summarize the literature on thrombotic complications in COVID-19, complement activation in coronavirus infections, and the crosstalk between the complement and coagulation systems. We demonstrate how the complement system is able to activate the coagulation cascade and platelets, inhibit fibrinolysis and stimulate endothelial cells. We also describe how these interactions see clinical relevance in several disorders where overactive complement results in a prothrombotic clinical presentation, and how it could be clinically relevant in COVID-19.
[Sarcoid Neuropathy].
Brain and nerve = Shinkei kenkyu no shinpo, 2020

Sarcoid neuropathy has a broader spectrum of clinical features than previously expected. It is typically characterized by multiple mononeuropathy but often shows a polyneuropathy pattern, making it difficult to be differentiated from other neuropathies. In the diagnostic process, several clinical features, including laterality and proximal-predominance of symptoms at extremities, sensory deficits in the territory of the branch of the peripheral nerve trunk, and positive neuropathic sensory symptoms typically accompanied by pain, could be the cues to evaluate the probability of sarcoid neuropathy. Axonal disturbance with a patchy distribution is a rule in nerve conduction studies; however, abnormalities suggestive of demyelination are also seen, imitating the clinical picture of chronic inflammatory demyelinating polyneuropathy.
Axonal swellings are related to type 2 diabetes, but not to distal diabetic sensorimotor polyneuropathy.
Diabetologia, 2021

Distal diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes with many patients showing a reduction of intraepidermal nerve fibre density (IENFD) from skin biopsy, a validated and sensitive diagnostic tool for the assessment of DSP. Axonal swelling ratio is a morphological quantification altered in DSP. It is, however, unclear if axonal swellings are related to diabetes or DSP. The aim of this study was to investigate how axonal swellings in cutaneous nerve fibres are related to type 2 diabetes mellitus, DSP and neuropathic pain in a well-defined cohort of patients diagnosed with type 2 diabetes.
Pediatric Neurology Research in the Twenty-First Century: Status, Challenges, and Future Directions Post-COVID-19.
Pediatric neurology, 2020

The year 2020 marked a fundamental shift in the pediatric neurology field. An impressive positive trajectory of advances in patient care and research faced sudden global disruptions by the coronavirus disease 2019 pandemic and by an international movement protesting racial, socioeconomic, and health disparities. The disruptions revealed obstacles and fragility within the pediatric neurology research mission. However, renewed commitment offers unique opportunities for the pediatric neurology research community to enhance and prioritize research directions for the coming decades.
CHRNA5 belongs to the secondary estrogen signaling network exhibiting prognostic significance in breast cancer.
Cellular oncology (Dordrecht, Netherlands), 2021

Cholinergic signals can be important modulators of cellular signaling in cancer. We recently have shown that knockdown of nicotinic acetylcholine receptor subunit alpha 5, CHRNA5, diminishes the proliferative potential of breast cancer cells. However, modulation of CHRNA5 expression in the context of estrogen signaling and its prognostic implications in breast cancer remained unexplored.
Seeing motion of controlled object improves grip timing in adults with autism spectrum condition: evidence for use of inverse dynamics in motor control.
Experimental brain research, 2021

Previous studies (Haswell et al. in Nat Neurosci 12:970-972, 2009; Marko et al. in Brain J Neurol 138:784-797, 2015) reported that people with autism rely less on vision for learning to reach in a force field. This suggested a possibility that they have difficulties in extracting force information from visual motion signals, a process called inverse dynamics computation. Our recent study (Takamuku et al. in J Int Soc Autism Res 11:1062-1075, 2018) examined the ability of inverse computation with two perceptual tasks and found similar performances in typical and autistic adults. However, this tested the computation only in the context of sensory perception while it was possible that the suspected disability is specific to the motor domain. Here, in order to address the concern, we tested the use of inverse dynamics computation in the context of motor control by measuring changes in grip timing caused by seeing/not seeing a controlled object. The motion of the object was informative of its inertial force and typical participants improved their grip timing based on the visual feedback. Our interest was on whether the autism participants show the same improvement. While some autism participants showed atypical hand slowing when seeing the controlled object, we found no evidence of abnormalities in the inverse computation in our grip timing task or in a replication of the perceptual task. This suggests that the ability of inverse dynamics computation is preserved not only for sensory perception but also for motor control in adults with autism.
Inflammation in Bipolar Disorder (BD): Identification of new therapeutic targets.
Pharmacological research, 2021

Bipolar disorder (BD) is a chronic and cyclic mental disorder, characterized by unusual mood swings between mania/hypomania and depression, raising concern in both scientific and medical communities due to its deleterious social and economic impact. Polypharmacy is the rule due to the partial effectiveness of available drugs. Disease course is often unremitting, resulting in frequent cognitive deficits over time. Despite all research efforts in identifying BD-associated molecular mechanisms, current knowledge remains limited. However, the involvement of inflammation in BD pathophysiology is increasingly consensual, with the immune system and neuroinflammation playing a key role in disease course. Evidence includes altered levels of cytokines and acute-phase proteins, pathological microglial activation, deregulation of Nrf2-Keap1 system and changes in biogenic amines neurotransmitters, whose expression is regulated by TNF-α, a pro-inflammatory cytokine highly involved in BD, pointing out inflammation as a novel and attractive therapeutic target for BD. As result, new therapeutic agents including non-steroidal anti-inflammatory drugs, N-acetylcysteine and GSK3 inhibitors have been incorporated in BD treatment. Taking into consideration the latest pre-clinical and clinical trials, in this review we discuss recent data regarding inflammation in BD, unveiling potential therapeutic approaches through direct or indirect modulation of inflammatory response.
The concept of cerebral chemical dominance.
The International journal of neuroscience, 2003

The study assessed the biochemical differences between right hemispheric dominant and left hemispheric dominant individuals detected by handedness and the dichotic listening test. The isoprenoid metabolites--digoxin, dolichol, and ubiquinone, glycoconjugate metabolism, free radical metabolism, and the RBC membrane composition were studied in individuals with differing hemispheric dominance. The results showed that all right hemispheric dominant individuals and 50% of left hemispheric dominant individuals had increased HMG CoA reductase activity, elevated digoxin and dolichol levels. The serum magnesium, RBC membrane Na+-K+ ATPase activity and serum ubiquinone levels were reduced in all right hemispheric dominant individuals and 50% of left hemispheric dominant individuals. The tryptophan-derived neurotransmitters--serotonin, quinolinic acid, strychnine, and nicotine--were increased while the tyrosine derived neurotransmitters--dopamine, noradrenaline, and morphine--were reduced in all right hemispheric dominant individuals and 50% of left hemispheric dominant individuals. The other 50% of left hemispheric dominant individuals had decreased HMG CoA reductase activity, reduced digoxin, and dolichol levels. The serum magnesium, RBC membrane Na+-K+ ATPase activity, and serum ubiquinone levels were increased in this group. The tryptophan derived neurotransmitters--serotonin, quinolinic acid, strychnine, and nicotine were reduced, while the tyrosine-derived neurotransmitters--dopamine, noradrenaline, and morphine-- were increased in the rest (50% of left hemispheric dominant individuals). Hemispheric dominance detected by the dichotic listening test and handedness has no correlation with cerebral chemical dominance.
Inflammation-driven glial alterations in the cuprizone mouse model probed with diffusion-weighted magnetic resonance spectroscopy at 11.7 T.
NMR in biomedicine, 2021

Inflammation of brain tissue is a complex response of the immune system to the presence of toxic compounds or to cell injury, leading to a cascade of pathological processes that include glial cell activation. Noninvasive MRI markers of glial reactivity would be very useful for in vivo detection and monitoring of inflammation processes in the brain, as well as for evaluating the efficacy of personalized treatments. Due to their specific location in glial cells, myo-inositol (mIns) and choline compounds (tCho) seem to be the best candidates for probing glial-specific intra-cellular compartments. However, their concentrations quantified using conventional proton MRS are not specific for inflammation. In contrast, it has been recently suggested that mIns intra-cellular diffusion, measured using diffusion-weighted MRS (DW-MRS) in a mouse model of reactive astrocytes, could be a specific marker of astrocytic hypertrophy. In order to evaluate the specificity of both mIns and tCho diffusion to inflammation-driven glial alterations, we performed DW-MRS in a volume of interest containing the corpus callosum and surrounding tissue of cuprizone-fed mice after 6 weeks of intoxication, and evaluated the extent of astrocytic and microglial alterations using immunohistochemistry. Both mIns and tCho apparent diffusion coefficients were significantly elevated in cuprizone-fed mice compared with control mice, and histologic evaluation confirmed the presence of severe inflammation. Additionally, mIns and tCho diffusion showed, respectively, strong and moderate correlations with histological measures of astrocytic and microglial area fractions, confirming DW-MRS as a promising tool for specific detection of glial changes under pathological conditions.
Acinus: a nuclear regulator of autophagy and endocytic trafficking.
Autophagy, 2010

Fusion with lysosomes is the common last step of endocytic trafficking and autophagy. Accordingly, several proteins are required in both pathways for cargoes to reach their destinations. Among these proteins, Drosophila Acinus stands out, as it exerts opposite effects on these two pathways, and thus establishes a new paradigm. Loss of Acinus function destabilizes early endosomes, thereby promoting the delivery of their cargo to lysosomes. By contrast, the maturation of autophagosomes to autolysosomes is inhibited in acn mutant cells. The increase in autophagy upon Acinus overexpression and its location to the nucleus are consistent with Acinus being a novel regulator of autophagy.
The 11th Zebrafish Disease Models Conference in Leiden, 2018.
Zebrafish, 2019

In July 2018, the 11th Zebrafish Disease Models Conference (ZDM11) was held at Leiden University, The Netherlands, providing an excellent international opportunity for scientific presentations and collaborative discussion regarding the modeling of disease using zebrafish. Much like the original ZDM1, which was also hosted in Leiden in 2007, immunology and cancer had a strong presence at ZDM11, with zebrafish still proving an invaluable tool to interrogate their disease genetics and progression
Can memory exist outside of brain and be transferred? Historical review, issues & ways forward.
Medical hypotheses, 2017

Learning and memory are among the executive functions attributed to intelligent forms of life. Unfortunately, there is a lack of clear understanding regarding the underlying mechanisms governing these functions. Most of the modern day scientists attribute these functions solely to brain. However, in the latter half of last century, a number of reports suggested existence of extra-cranial memory and potential of its transfer between animals. Some have linked this phenomenon to RNA while others believed that peptides were responsible. The terms like "educated RNA" and "scotophobin" were coined. This atypical work involving flatworms, yeast RNA and scotophobin was received with deep skepticism and ultimately disregarded. However, the recent reproduction of some of this earlier work by scientists at Tufts University has reignited the debate on the mechanisms of learning and memory. Keeping this in view, we believe it is high time to summarize this historical work and discuss the possibilities to delineate these atypical claims. The objective is to incite the present day researchers to explore this opportunity under the perspective of newer advancements in science.
Verbal and physical client aggression - A longitudinal analysis of professional caregivers' psychophysiological stress response and burnout.
Psychoneuroendocrinology, 2018

We investigated the impact of verbal and physical client aggression on risk of developing high hair cortisol concentration (HCC) as an indicator of chronic stress exposure and burnout in a Swiss population of professional caregivers working in youth residential care.
Action at a distance: Long-distance rate adaptation in event perception.
Quarterly journal of experimental psychology (2006), 2021

Viewers' perception of actions is coloured by the context in which those actions are found. An action that seems uncomfortably sudden in one context might seem expeditious in another. In this study, we examined the influence of one type of context: the rate at which an action is being performed. Based on parallel findings in other modalities, we anticipated that viewers would adapt to the rate at which actions were displayed at. Viewers watched a series of actions performed on a touchscreen that could end in actions that were ambiguous to their number (e.g., two separate "tap" actions versus a single "double tap" action) or identity (e.g., a "swipe" action versus a slower "drag"). In Experiment 1, the rate of actions themselves was manipulated; participants used the rate of the actions to distinguish between two similar, related actions. In Experiment 2, the rate of the actions that preceded the ambiguous one was sped up or slowed down. In line with our hypotheses, viewers perceived the identity of those final actions with reference to the rate of the preceding actions. This was true even in Experiment 3, when the action immediately before the ambiguous one was left unmodified. Ambiguous actions embedded in a fast context were seen as relatively long, while ambiguous actions embedded in a slow context were seen as relatively short. This shows that viewers adapt to the rate of actions when perceiving visual events.
Liver iron is a major regulator of hepcidin gene expression via BMP/SMAD pathway in a rat model of chronic renal failure under treatment with high rHuEPO doses.
BioFactors (Oxford, England), 2016

Hepcidin is the major central regulator of iron metabolism, controlling iron absorption and mobilization. Considering its interaction with several factors that are altered in chronic kidney disease (CKD), particularly in hyporesponsive CKD patients under therapy with high recombinant human erythropoietin (rHuEPO) doses, it was aimed to study the impact of increasing rHuEPO doses on the regulation of iron-hepcidin metabolism. The blood, cellular, and tissue studies, using the remnant kidney rat model of CKD induced by 5/6 nephrectomy, under rHuEPO (100, 200, 400, and 600 IU/Kg body weight [BW]/week) treatment during 3 weeks were performed. It was found that the rHuEPO stimulus triggered a first wave to achieve correction of anemia, by inhibiting hepcidin synthesis, favoring erythropoiesis and iron absorption; this continuous stimulus enhanced iron absorption leading to iron overload, as showed by the hepatic iron deposits found in rats treated with higher rHuEPO dose that seems to trigger the upregulation of hepcidin synthesis through the activation of the BMP6/SMAD pathway. The data suggested that liver iron overload was an important stimuli for hepcidin synthesis, stronger than the inhibitory effect of high rHuEPO doses; moreover, the findings raised the hypothesis that when high inflammation (triggering hepcidin expression) was associated with increased iron stores in hemodialysis patients, hepcidin expression was also upregulated via BMP6, enhancing hepcidin synthesis, leading, therefore, to worsening of anemia and, eventually, to a hyporesponse/resistance to rHuEPO therapy. © 2016 BioFactors, 42(3):296-306, 2016.