rudyvdbrink/CitationDatabase huggingface dataset:
TGF-β1 is critical for Wallerian degeneration after rat sciatic nerve injury.
Neuroscience, 2015

Wallerian degeneration (WD) is a process of axonal degeneration distal to the injury site followed by a robust regenerative response. It involves degeneration and regeneration which can be directly induced by nerve injury and activated by transcription factors. Although WD has been studied extensively, the precise mechanisms of transcription factors regulating WD are still elusive. In this study, we reported the effect of transforming growth factor-β1 (TGF-β1) on WD after rat sciatic nerve injury. The data showed that TGF-β1 may express in injured rat sciatic nerve and cultured Schwann cells (SCs). Knock down of TGF-β1 expressions resulted in the reduction of SC proliferation and apoptosis, up regulation of cytokines and Smad2, 4. Enhanced expression of TGF-β1 could promote SC proliferation and apoptosis, down regulation of cytokines and Smad2, 4. Altered expressions of TGF-β1 may affect Smad and AKT but not c-Jun and extracellular regulated protein kinase (ERK) pathways. Our results revealed the role of TGF-β1 on WD and provided the basis for the molecular mechanisms of TGF-β1-regulated nerve degeneration and/or regeneration.
The anorexic hormone Peptide YY3-36 is rapidly metabolized to inactive Peptide YY3-34 in vivo.
Physiological reports, 2015

Peptide YY (PYY) is a 36 amino acid peptide hormone released from enteroendocrine cells. An N-terminally degraded metabolite, PYY3-36, has anorexigenic effects, which makes the PYY system a target for obesity treatment. However, little is known about the kinetics and degradation products of PYY. A related peptide, Neuropeptide Y (NPY), may be degraded from the C-terminus. We therefore investigated PYY degradation after in vitro incubations in porcine plasma and blood and in vivo by infusing PYY3-36 into multicatheterized pigs (n = 7) (2 pmol/kg/min). Plasma samples were analyzed by region-specific radioimmunoassays (RIA) and HPLC analysis. A metabolite, corresponding to PYY3-34 was formed after incubation in plasma and blood and during the infusion study. When taking the C-terminal degradation into account, the half-life (T½) of PYY in blood and plasma amounted to 3.4 ± 0.2 and 6.2 ± 0.2 h, respectively. After PYY3-36 infusion in pigs, the peptide was degraded with a T½ of 3.6 ± 0.5 min. Significant extraction (20.5 ± 8.0%) compatible with glomerular filtration was observed across the kidneys and significant C-terminal degradation (26.5 ± 4.8%) was observed across the liver. Net balances across the hind limb, splanchnic bed, and lungs were not significantly different from zero. PYY3-34 was unable to activate the Y2 receptor in a transfected cell line. In conclusion, PYY3-36 is extensively degraded to PYY3-34 in the pig, a degradation that renders the peptide inactive on the Y2 receptor. Currently used assays are unlikely to be able to detect this degradation and therefore measure falsely elevated levels of PYY3-36, leading to underestimation of its physiological effects.
Targeting brain functions from the scalp: Transcranial brain atlas based on large-scale fMRI data synthesis.
NeuroImage, 2020

Transcranial brain mapping techniques, such as functional near-infrared spectroscopy (fNIRS) and transcranial magnetic stimulation (TMS), have been playing an increasingly important role in studies of human brain functions. Given a brain function of interest, fNIRS probes and TMS coils should be properly placed on the scalp to ensure that the function is effectively measured or modulated. However, since brain activity is inside the skull and invisible to the researcher during placement, this blind targeting may cause the device to partially or completely miss the functional target, resulting in inconsistent experimental results and divergent clinical outcomes, especially when participants' structural MRI data are not available. To address this issue, we propose here a framework for targeting a designated function directly from the scalp. First, a functional brain atlas for the targeted brain function is constructed via a meta-analysis of large-scale functional magnetic resonance imaging datasets. Second, the functional brain atlas is presented on the scalp surface by using a transcranial mapping previously established from an structural MRI dataset (n ​= ​114), resulting in a novel functional transcranial brain atlas (fTBA). Finally, a low-cost, portable scalp-navigation system is used to localize the transcranial device on the individual's scalp with the guidance of the fTBA. To demonstrate the feasibility of the targeting framework, both fNIRS and TMS mapping experiments were conducted. The results show that fTBA-guided fNIRS positioning can detect functional activity with high sensitivity and specificity for working memory and motor systems; Moreover, compared with traditional TMS targeting approaches (e.g. the International 10-20 System and the conventional 5-cm rule), the fTBA suggested motor stimulation site is closesr to both the motor hotspot and the center of gravity of motor evoked potentials (MEP-COG). In summary, the proposed method unblinds the transcranial function targeting process using prior information, providing an effective and straightforward approach to transcranial brain mapping studies, especially those without participants' structural MRI data.
Age-related changes in cortical connectivity influence the neuromodulatory effects of transcranial electrical stimulation.
Neurobiology of aging, 2019

Transcranial electrical stimulation (tES) is a potentially viable tool for boosting cognitive performance in aging. However, most knowledge on tES effects is based on studies involving young adults. Here, we applied tES (transcranial random noise stimulation [tRNS] as an effective stimulation and anodal transcranial direct current stimulation [atDCS] as a "control" stimulation) to the visual cortex during visual perceptual learning (VPL) in healthy young and older individuals. Moreover, we measured transcranial magnetic stimulation-evoked potentials to investigate the neurophysiological underpinnings of tES effects. We found that only the tRNS in the young, but not in the older, subjects modulated VPL, by decreasing performance. Transcranial magnetic stimulation-evoked potentials revealed age-related changes in connectivity, that is, a stronger activation of the prefrontal cortex after visual cortex stimulation, and a stronger modulation of the prefrontal cortex after VPL in the older subjects. These results may indicate that task performance in older adults relies on the recruitment of a wider network and a crucial contribution of the anterior portion of the brain, which may dramatically influence tES effects in aging.
PKMζ, but not PKCλ, is rapidly synthesized and degraded at the neuronal synapse.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

Synthesizing, localizing, and stabilizing new protein copies at synapses are crucial factors in maintaining the synaptic changes required for storing long-term memories. PKMζ recently emerged as a molecule putatively responsible for maintaining encoded memories over time because its presence correlates with late LTP and because its inhibition disrupts LTP in vitro and long-term memory storage in vivo. Here we investigated PKMζ stability in rat neurons to better understand its role during information encoding and storage. We used TimeSTAMP reporters to track the synthesis and degradation of PKMζ as well as a related atypical PKC, PKCλ. These reporters revealed that both PKMζ and PKCλ were upregulated after chemical LTP induction; however, these new PKMζ copies exhibited more rapid turnover than basally produced PKMζ, particularly in dendritic spines. In contrast to PKMζ, new PKCλ copies exhibited elevated stability. Stable information storage over long periods of time is more challenging the shorter the metabolic lifetime of the candidate molecules.
Behavioural therapies versus other psychological therapies for depression.
The Cochrane database of systematic reviews, 2013

Behavioural therapies represent one of several categories of psychological therapies that are currently used in the treatment of depression. However, the effectiveness and acceptability of behavioural therapies for depression compared with other psychological therapies remain unclear.
Calcineurin inhibition eliminates the normal inverted U curve, enhances acquisition and prolongs memory in a mammalian 3'-5'-cyclic AMP-dependent learning paradigm.
Neuroscience, 2009

The role protein phosphatase 2B (calcineurin, CaN) plays in learning and memory has received a significant amount of attention due to its promotion of the dephosphorylation of 3'-5'-cyclic AMP response element binding protein (CREB). Researchers have ascertained that overexpression of CaN is associated with memory retention deficits [Foster TC, Sharrow KM, Masse JR, Norris CM, Kumar A (2001) Calcineurin links Ca(2+) dysregulation with brain aging. J Neurosci 21:4066-4073; Mansuy IM, Mayford M, Jacob B, Kandel ER, Bach ME (1998) Restricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory. Cell 92:39-49], while CaN inhibition enhances learning and memory [Gerdjikov TV, Beninger RJ (2005) Differential effects of calcineurin inhibition and protein kinase A activation on nucleus accumbens amphetamine-produced conditioned place preference in rats. Eur J Neurosci 22:697-705; Ikegami S, Inokuchi K (2000) Antisense DNA against calcineurin facilitates memory in contextual fear conditioning by lowering the threshold for hippocampal long-term potentiation induction. Neuroscience 98:637-646]. The present study hypothesized that infusion of a CaN inhibitor (FK506) bilaterally into the olfactory bulbs of postnatal day 6 Sprague Dawley rat pups would prolong the duration of a conditioned odor preference and retard cyclic AMP response element binding protein dephosphorylation. A 2 mg/kg s.c. injection of isoproterenol (ISO, beta-adrenoceptor agonist) was paired with a 10 min exposure to peppermint and subsequently an infusion of FK506. Immunohistochemistry for phosphorylated 3'-5'-cyclic AMP response element binding protein (pCREB) revealed that unilateral infusion of FK506 resulted in an amplification of phosphorylated CREB in the olfactory bulb 40 min after training compared with saline-infused bulbs. Pups infused bilaterally with FK506 maintained a learned preference for peppermint 48, 72 and 96 h after training. CaN inhibition also modified the conventional inverted U curve obtained when ISO is used to replace stroking, as the unconditioned stimulus. When pups were infused with FK506, learning occurred with sub- and supra-optimal doses of ISO indicating that CaN overcomes non-optimal effects ISO may have on learning. We demonstrate that CaN inhibition can extend the duration of conditioned olfactory memory and may provide a target for memory prolongation that is superior to even phosphodiesterase inhibition observed in previous studies.
Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene.
Archives of neurology, 2011

To perform an extensive screening for mutations of amyotrophic lateral sclerosis (ALS)-related genes in a consecutive cohort of Sardinian patients, a genetic isolate phylogenically distinct from other European populations.
The effects of sympathetic outflow on upregulation of vanilloid receptors TRPV(1) in primary afferent neurons evoked by intradermal capsaicin.
Experimental neurology, 2010

The vanilloid receptor TRPV(1) is a key nociceptive molecule located in primary afferent nociceptive neurons in dorsal root ganglia (DRG) for initiating neurogenic inflammation and pain. Our recent study demonstrates that up-regulation of TRPV(1) receptors by intradermal injection of capsaicin is modulated by activation of the protein kinase C (PKC) cascade. Neurogenic inflammation and pain resulting from capsaicin injection are sympathetically dependent, responding to norepinephrine, adenosine 5'-triphosphate (ATP) and/or neuropeptide Y released from sympathetic efferents. In a rat model of acute neurogenic inflammatory pain produced by capsaicin injection, we used immunofluorescence and Western blots combined with pharmacology and surgical sympathectomies to analyze whether the capsaicin-evoked up-regulation of TRPV(1) in DRG neurons is affected by sympathetic outflow by way of activating the PKC cascade. Sympathetic denervation reduced significantly the capsaicin-evoked expressions of TRPV(1), calcitonin gene-related peptide and/or phosphorylated PKC and their co-expression. These reductions could be restored by exogenous pretreatment with an analog of ATP, alpha,beta-methylene ATP. Inhibition of PKC with chelerythrine chloride prevented the ATP effect. Consistent results were obtained from experiments in which capsaicin-evoked changes in cutaneous inflammation (vasodilation and edema) were examined after sympathetic denervation, and the effects of the above pharmacological manipulations were evaluated. Our findings suggest that the capsaicin-evoked up-regulation of TRPV(1) receptors in DRG neurons is modulated sympathetically by the action of ATP released from sympathetic efferents to activate the PKC cascade. Thus, this study proposes a potential new mechanism of sympathetic modulation of neurogenic inflammation.
Metacognitive training in patients recovering from a first psychosis: an experience sampling study testing treatment effects.
European archives of psychiatry and clinical neuroscience, 2018

Cognitive biases, negative affect and negative self-esteem are associated with paranoia in people with psychotic disorders. Metacognitive group training (MCT) aims to target these biases although research has shown mixed results. Our objective was to establish the effect of MCT on paranoid ideation in patients with recent onset psychosis in a powerful experience sampling design. 50 patients between the age of 18 and 35 were included in a single-blind, parallel group RCT comparing MCT with occupational therapy (OT) as an active control condition. We assessed via questionnaires and experience sampling treatment effects on paranoid ideation, delusional conviction, the cognitive bias jumping to conclusion (JTC), and cognitive insight, as well as treatment effects on associations between negative affect, negative self-esteem and paranoid ideation. Patients in the MCT group did not show a decrease in paranoid ideation, delusional conviction, JTC-bias or an increase in cognitive insight compared with OT. However, negative affect showed a weaker association with paranoid ideation post-treatment in the MCT condition. In the OT condition, this association was stronger post-treatment. We tentatively suggest that patients with an early psychosis seemed to benefit from MCT in emotional learning compared with the OT condition. Despite the fact that the group training is well-received by patients, subsequent individual MCT (MCT+) may be indicated for stronger favorable effects on paranoid ideation.
A prospective study of focal brain atrophy, mobility and fitness.
Journal of internal medicine, 2019

The parallel decline of mobility and cognition with ageing is explained in part by shared brain structural changes that are related to fitness. However, the temporal sequence between fitness, brain structural changes and mobility loss has not been fully evaluated.
Does Infant-Directed Speech Help Phonetic Learning? A Machine Learning Investigation.
Cognitive science, 2021

A prominent hypothesis holds that by speaking to infants in infant-directed speech (IDS) as opposed to adult-directed speech (ADS), parents help them learn phonetic categories. Specifically, two characteristics of IDS have been claimed to facilitate learning: hyperarticulation, which makes the categories more separable, and variability, which makes the generalization more robust. Here, we test the separability and robustness of vowel category learning on acoustic representations of speech uttered by Japanese adults in ADS, IDS (addressed to 18- to 24-month olds), or read speech (RS). Separability is determined by means of a distance measure computed between the five short vowel categories of Japanese, while robustness is assessed by testing the ability of six different machine learning algorithms trained to classify vowels to generalize on stimuli spoken by a novel speaker in ADS. Using two different speech representations, we find that hyperarticulated speech, in the case of RS, can yield better separability, and that increased between-speaker variability in ADS can yield, for some algorithms, more robust categories. However, these conclusions do not apply to IDS, which turned out to yield neither more separable nor more robust categories compared to ADS inputs. We discuss the usefulness of machine learning algorithms run on real data to test hypotheses about the functional role of IDS.
Veterinary surgeons and suicide: a structured review of possible influences on increased risk.
The Veterinary record, 2010

Veterinary surgeons are known to be at a higher risk of suicide compared with the general population. There has been much speculation regarding possible mechanisms underlying the increased suicide risk in the profession, but little empirical research. A computerised search of published literature on the suicide risk and influences on suicide among veterinarians, with comparison to the risk and influences in other occupational groups and in the general population, was used to develop a structured review. Veterinary surgeons have a proportional mortality ratio (PMR) for suicide approximately four times that of the general population and around twice that of other healthcare professions. A complex interaction of possible mechanisms may occur across the course of a veterinary career to increase the risk of suicide. Possible factors include the characteristics of individuals entering the profession, negative effects during undergraduate training, work-related stressors, ready access to and knowledge of means, stigma associated with mental illness, professional and social isolation, and alcohol or drug misuse (mainly prescription drugs to which the profession has ready access). Contextual effects such as attitudes to death and euthanasia, formed through the profession's routine involvement with euthanasia of companion animals and slaughter of farm animals, and suicide 'contagion' due to direct or indirect exposure to suicide of peers within this small profession are other possible influences.
An intrinsic DFF40/CAD endonuclease deficiency impairs oligonucleosomal DNA hydrolysis during caspase-dependent cell death: a common trait in human glioblastoma cells.
Neuro-oncology, 2016

Glioblastoma (GBM) or grade IV astrocytoma is one of the most devastating human cancers. The loss of DFF40/CAD, the key endonuclease that triggers oligonucleosomal DNA fragmentation during apoptosis, has been linked to genomic instability and cell survival after radiation. Despite the near inevitability of GBM tumor recurrence after treatment, the relationship between DFF40/CAD and GBM remains unexplored.
Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats I: Magnetic resonance imaging.
Epilepsia, 2016

The mammalian target of rapamycin (mTOR) pathway has received increasing attention as a potential antiepileptogenic target. Treatment with the mTOR inhibitor rapamycin after status epilepticus reduces the development of epilepsy in a rat model. To study whether rapamycin mediates this effect via restoration of blood-brain barrier (BBB) dysfunction, contrast-enhanced magnetic resonance imaging (CE-MRI) was used to determine BBB permeability throughout epileptogenesis.
A functional role for Anopheles gambiae Arrestin1 in olfactory signal transduction.
Journal of insect physiology, 2008

Insect sensory arrestins act to desensitize visual and olfactory signal transduction pathways, as evidenced by the phenotypic effects of mutations in the genes encoding both Arr1 and Arr2 in Drosophila melanogaster. To assess whether such arrestins play similar roles in other, more medically relevant dipterans, we examined the ability of Anopheles gambiae sensory arrestin homologs AgArr1 and AgArr2 to rescue phenotypes associated with an olfactory deficit observed in D. melanogaster arrestin mutants. Of these, only AgArr1 facilitated significant phenotypic rescue of the corresponding Drosophila arr mutant olfactory phenotype, consistent with the view that functional orthology is shared by these Arr1 homologs. These results represent the first step in the functional characterization of AgArr1, which is highly expressed in olfactory appendages of An. gambiae in which it is likely to play an essential role in olfactory signal transduction. In addition to providing insight into the common elements of the peripheral olfactory system of dipterans, this work validates the importance of AgArr1 as a potential target for novel anti-malaria strategies that focus on olfactory-based behaviors in An. gambiae.
Intracerebral hemorrhage in Intensive Care Unit: early prognostication fallacies. A single center retrospective study.
Minerva anestesiologica, 2018

Intracerebral hemorrhage (ICH) admitted to Intensive Care is deem of poor prognosis. The aim of this study was to compare observed and predicted 30-day mortality and to evaluate long term functional outcome in a consecutive ICH cohort.
Internet interventions: Past, present and future.
Internet interventions, 2018

Internet interventions have been around now for about 20 years. While the field still suffers from a scattered terminology a large number of programs and studies exist. In the present paper I present an overview of my experiences of studying internet-supported cognitive-behaviour therapy (ICBT), but also mention other approaches including the use of smartphones. The paper covers the history of ICBT, short-term effects in controlled trials for a range of conditions, long-term effects, comparisons against face-to-face therapy, effectiveness studies, prediction studies, how the treatment is perceived, critique, and finally future directions. I conclude that we have now reached a stage in which we have numerous evidence-based treatments and procedures, and increasingly internet interventions including ICBT are disseminated.