rudyvdbrink/CitationDatabase huggingface dataset:
Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity.
Nature, 2016

The Rho GTPase proteins Rac1, RhoA and Cdc42 have a central role in regulating the actin cytoskeleton in dendritic spines, thereby exerting control over the structural and functional plasticity of spines and, ultimately, learning and memory. Although previous work has shown that precise spatiotemporal coordination of these GTPases is crucial for some forms of cell morphogenesis, the nature of such coordination during structural spine plasticity is unclear. Here we describe a three-molecule model of structural long-term potentiation (sLTP) of murine dendritic spines, implicating the localized, coincident activation of Rac1, RhoA and Cdc42 as a causal signal of sLTP. This model posits that complete tripartite signal overlap in spines confers sLTP, but that partial overlap primes spines for structural plasticity. By monitoring the spatiotemporal activation patterns of these GTPases during sLTP, we find that such spatiotemporal signal complementation simultaneously explains three integral features of plasticity: the facilitation of plasticity by brain-derived neurotrophic factor (BDNF), the postsynaptic source of which activates Cdc42 and Rac1, but not RhoA; heterosynaptic facilitation of sLTP, which is conveyed by diffusive Rac1 and RhoA activity; and input specificity, which is afforded by spine-restricted Cdc42 activity. Thus, we present a form of biochemical computation in dendrites involving the controlled complementation of three molecules that simultaneously ensures signal specificity and primes the system for plasticity.
Expression of Pituitary Adenylate Cyclase-activating Peptide, Calcitonin Gene-related Peptide and Headache Targets in the Trigeminal Ganglia of Rats and Humans.
Neuroscience, 2018

Neurotransmitter and headache target localization in the trigeminal ganglia (TG) might increase the understanding of sites of action, and mechanisms related to headache therapy. The overall aim of the study was to investigate the presence of migraine targets in the TG with particular emphasis on pituitary adenylate cyclase-activating peptide (PACAP) and calcitonin gene-related peptide (CGRP), known to be involved in cranial pain processing, and selected headache targets. Rat- and human TG were processed for immunohistochemistry. PACAP-38, CGRP and the headache targets were expressed in rat and human TG. PACAP receptors were confined to neurons and satellite glial cells (SGCs), however with variability between the receptor subtypes PACAP type I receptor (PAC
Dysregulation of astrocyte extracellular signaling in Costello syndrome.
Science translational medicine, 2015

Astrocytes produce an assortment of signals that promote neuronal maturation according to a precise developmental timeline. Is this orchestrated timing and signaling altered in human neurodevelopmental disorders? To address this question, the astroglial lineage was investigated in two model systems of a developmental disorder with intellectual disability caused by mutant Harvey rat sarcoma viral oncogene homolog (HRAS) termed Costello syndrome: mutant HRAS human induced pluripotent stem cells (iPSCs) and transgenic mice. Human iPSCs derived from patients with Costello syndrome differentiated to astroglia more rapidly in vitro than those derived from wild-type cell lines with normal HRAS, exhibited hyperplasia, and also generated an abundance of extracellular matrix remodeling factors and proteoglycans. Acute treatment with a farnesyl transferase inhibitor and knockdown of the transcription factor SNAI2 reduced expression of several proteoglycans in Costello syndrome iPSC-derived astrocytes. Similarly, mice in which mutant HRAS was expressed selectively in astrocytes exhibited experience-independent increased accumulation of perineuronal net proteoglycans in cortex, as well as increased parvalbumin expression in interneurons, when compared to wild-type mice. Our data indicate that astrocytes expressing mutant HRAS dysregulate cortical maturation during development as shown by abnormal extracellular matrix remodeling and implicate excessive astrocyte-to-neuron signaling as a possible drug target for treating mental impairment and enhancing neuroplasticity.
Design of the ExCersion-VCI study: The effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment.
Alzheimer's & dementia (New York, N. Y.), 2017

There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination ≥22 and Clinical Dementia Rating ≤0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status.
Presbyphagia Diagnostics Using M-Mode Ultrasound: Changes in the Tongue Movement Pattern.
Dysphagia, 2020

Age-related physiological changes of the swallowing act impair particularly the oral phase and the tongue function, which is very important for bolus preparation and transfer. At present, there are no easily applicable methods for measurement of this phase of swallowing. This study was designed to investigate the deglutitive tongue movement by M-mode ultrasound and to compare the collected parameters of different age groups. In this exploratory prospective study, the tongue and its movements of 20 younger and 30 older women were examined during swallowing by B-mode and M-mode ultrasound. Preexisting dysphagia or malnutrition as well as psychic or neurological deficits were excluded by clinical examination and screening with the Mini Nutritional Assessment-Short Form (MNA-SF), the Gugging Swallowing Screen (GUSS), the Mini-Mental State Examination (MMSE) and the Barthel Index. The data were compared with each other and statistically analyzed. With increasing age, a change in the tongue movement pattern becomes apparent. In the group of older women, the vertical lingual movement had a smaller amplitude (p < 0.001) and a shorter time to the maximum amplitude (p < 0.03) than in the group of younger women. However, there were no differences in the tongue diameter (p > 0.4). The tongue movement pattern appears to be subject to age-specific changes, in contrast to anatomy. The use of M-mode ultrasonography is an easy, radiation-free and cost-effective method for the assessment of the oral phase of swallowing. Limitations are the widely scattered values of the ultrasound findings. Further studies are needed for validation and definition of standard values for this promising method.
Activity-dependent ubiquitination of the AMPA receptor subunit GluA2.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

AMPA receptors (AMPARs) are postsynaptic glutamate-gated ion channels that mediate fast excitatory neurotransmission in the mammalian brain. Synaptic activity modulates the density of synaptic AMPARs, thereby affecting synaptic function, learning, and memory. Consequently, there is intense interest in defining the molecular mechanisms regulating AMPAR trafficking. Protein expression in the postsynaptic density of excitatory synapses is tightly regulated by ubiquitination, a posttranslational modification that dynamically regulates protein trafficking and degradation in response to synaptic activity. In this study, we demonstrate that increasing synaptic activity, via treatment with the GABA(A) receptor antagonist bicuculline, rapidly and robustly induces ubiquitination of the GluA2 AMPAR subunit. Similarly, treatment with AMPAR agonists results in GluA2 ubiquitination, which suggests that ligand binding plays a critical role. Finally, we find that clathrin- and dynamin-dependent endocytosis of AMPARs is required for activity-dependent GluA2 ubiquitination. Our finding that GluA2 undergoes activity-dependent ubiquitination expands our understanding of how ubiquitination regulates synaptic plasticity.
Hierarchical model of natural images and the origin of scale invariance.
Proceedings of the National Academy of Sciences of the United States of America, 2013

The study of natural images and how our brain processes them has been an area of intense research in neuroscience, psychology, and computer science. We introduced a unique approach to studying natural images by decomposing images into a hierarchy of layers at different logarithmic intensity scales and mapping them to a quasi-2D magnet. The layers were in different phases: "cold" and ordered at large-intensity scales, "hot" and disordered at small-intensity scales, and going through a second-order phase transition at intermediate scales. There was a single "critical" layer in the hierarchy that exhibited long-range correlation similar to that found in the 2D Ising model of ferromagnetism at the critical temperature. We also determined the interactions between layers mapped from natural images and found mutual inhibition that generated locally "frustrated" antiferromagnetic states. Almost all information in natural images was concentrated in a few layers near the phase transition, which has biological implications and also points to the hierarchical origin of scale invariance in natural images.
Proteomics studies in inner ear disorders: pathophysiology and biomarkers.
Expert review of proteomics, 2015

Although proteomics has been exploited in a wide range of diseases for identification of biomarkers and pathophysiological mechanisms, there are still biomedical disciplines such as otology where proteomics platforms are underused due to technical challenges and/or complex features of the disease. Thus, in the past few years, healthcare and scientific agencies have advocated the development and adoption of proteomic technologies in otological research. However, few studies have been conducted and limited literature is available in this area. Here, we present the state of the art of proteomics in otology, discussing the substantial evidence from recent experimental models and clinical studies in inner-ear conditions. We also delineate a series of critical issues including minute size of the inner ear, delicacy and poor accessibility of tissue that researchers face while undertaking otology proteomics research. Furthermore, we provide perspective to enhance the impact and lead to the clinical implementation of these proteomics-based strategies.
Cortical responses before 6 months of life associate with later autism.
The European journal of neuroscience, 2018

Autism spectrum disorder (ASD) is a common, highly heritable, developmental disorder and later-born siblings of diagnosed children are at higher risk of developing ASD than the general population. Although the emergence of behavioural symptoms of ASD in toddlerhood is well characterized, far less is known about development during the first months of life of infants at familial risk. In a prospective longitudinal study of infants at familial risk followed to 36 months, we measured functional near-infrared spectroscopy (fNIRS) brain responses to social videos of people (i.e. peek-a-boo) compared to non-social images (vehicles) and human vocalizations compared to non-vocal sounds. At 4-6 months, infants who went on to develop ASD at 3 years (N = 5) evidenced-reduced activation to visual social stimuli relative to low-risk infants (N = 16) across inferior frontal (IFG) and posterior temporal (pSTS-TPJ) regions of the cortex. Furthermore, these infants also showed reduced activation to vocal sounds and enhanced activation to non-vocal sounds within left lateralized temporal (aMTG-STG/pSTS-TPJ) regions compared with low-risk infants and high-risk infants who did not develop ASD (N = 15). The degree of activation to both the visual and auditory stimuli correlated with parent-reported ASD symptomology in toddlerhood. These preliminary findings are consistent with later atypical social brain responses seen in children and adults with ASD, and highlight the need for further work interrogating atypical processing in early infancy and how it may relate to later social interaction and communication difficulties characteristic of ASD.
Cien Años de Microglía: Milestones in a Century of Microglial Research.
Trends in neurosciences, 2019

The year 2019 marks the 100-year anniversary of the discovery of microglia by Pío del Río-Hortega. We will recount the state of neuroscience research at the beginning of the 20th century and the heated scientific dispute regarding microglial identity. We will then walk through some of the milestones of microglial research in the decades since then. In the last 20 years, the field has grown exponentially. Researchers have shown that microglia are unlike any other resident macrophages: they have a unique origin and distinguishing features. Microglia are extraordinarily motile cells and constantly survey their environment, interacting with neurons, astrocytes, oligodendrocytes, neural stem cells, and infiltrating immune cells. We finally highlight some open questions for future research regarding microglia's identity, population dynamics, and dual (beneficial and detrimental) role in pathology.
Acute stress affects free recall and recognition of pictures differently depending on age and sex.
Behavioural brain research, 2015

Little is known about age differences in the effects of stress on memory retrieval. Our aim was to perform an in-depth examination of acute psychosocial stress effects on memory retrieval, depending on age and sex. For this purpose, data from 52 older subjects (27 men and 25 women) were reanalyzed along with data from a novel group of 50 young subjects (26 men and 24 women). Participants were exposed to an acute psychosocial stress task (Trier Social Stress Test) or a control task. After the experimental manipulation, the retrieval of positive, negative and neutral pictures learned the previous day was tested. As expected, there was a significant response to the exposure to the stress task, but the older participants had a lower cortisol response to TSST than the younger ones. Stress impaired free recall of emotional (positive and negative) and neutral pictures only in the group of young men. Also in this group, correlation analyses showed a marginally significant association between cortisol and free recall. However, exploratory analyses revealed only a negative relationship between the stress-induced cortisol response and free recall of negative pictures. Moreover, stress impaired recognition memory of positive pictures in all participants, although this effect was not related to the cortisol or alpha-amylase response. These results indicate that both age and sex are critical factors in acute stress effects on specific aspects of long-term memory retrieval of emotional and neutral material. They also point out that more research is needed to better understand their specific role.
Extracellular Matrix: A Treasure Trove in Ovarian Cancer Dissemination and Chemotherapeutic Resistance.
Cureus, 2021

Late presentation and resistance to chemotherapeutic agents make a deadly combination for ovarian cancer patients. The treatment of these patients is thus challenging. This study explores the possible molecular mechanisms by which tumor cells interact with the extracellular matrix (ECM) constituents, forming metastatic implants and enhancing patients' sensitivity to drugs. For the literature review, PubMed was used as a database. The standard search was done using keywords "collagen, ovarian cancer, extracellular matrix, drug resistance" in different combinations, which finally yielded 32 studies meeting the inclusion/exclusion criteria. The studies included were published in the English language in the past seven years. After analyzing, we found all of them to be histopathological studies. Nine studies also used murine cell lines besides human cell lines and tissue samples from ovarian cancer patients. One study has a retrospective analysis done. Eight studies demonstrate the role of hypoxia and matrix remodeling enzymes in ovarian cancer dissemination. Genetics playing a crucial role in cancer metastasis is demonstrated in eight studies. Ten studies included shows receptors, enzymes, and spheroid organization in disease progression. Six studies address chemotherapeutic resistance. Intraperitoneal dissemination of ovarian cancer and the development of chemotherapeutic resistance depends on certain molecular interactions, and they can be targeted to improve patients' overall survival.
Comparing glycaemic benefits of Active Versus passive lifestyle Intervention in kidney Allograft Recipients (CAVIAR): study protocol for a randomised controlled trial.
Trials, 2016

Lifestyle modification is widely recommended to kidney allograft recipients post transplantation due to the cardiometabolic risks associated with immunosuppression including new-onset diabetes, weight gain and cardiovascular events. However, we have no actual evidence that undertaking lifestyle modification protects from any adverse outcomes post transplantation. The aim of this study is to compare whether a more proactive versus passive interventional approach to modify lifestyle is associated with superior outcomes post kidney transplantation.
Saponin 6 derived from Anemone taipaiensis induces U87 human malignant glioblastoma cell apoptosis via regulation of Fas and Bcl‑2 family proteins.
Molecular medicine reports, 2016

Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor, and is associated with a poor prognosis. Saponin 6, derived from Anemone taipaiensis, exerts potent cytotoxic effects against the human hepatocellular carcinoma HepG2 cell line and the human promyelocytic leukemia HL‑60 cell line; however, the effects of saponin 6 on glioblastoma remain unknown. The present study aimed to evaluate the effects of saponin 6 on human U87 malignant glioblastoma (U87 MG) cells. The current study revealed that saponin 6 induced U87 MG cell death in a dose‑ and time‑dependent manner, with a half maximal inhibitory concentration (IC50) value of 2.83 µM after treatment for 48 h. However, saponin 6 was needed to be used at a lesser potency in HT‑22 cells, with an IC50 value of 6.24 µM. Cell apoptosis was assessed by flow cytometry using Annexin V‑fluorescein isothiocyanate/propidium iodide double staining. DNA fragmentation and alterations in nuclear morphology were examined by terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling and transmission electron microscopy, respectively. The present study demonstrated that treatment with saponin 6 induced cell apoptosis in U87 MG cells, and resulted in DNA fragmentation and nuclear morphological alterations typical of apoptosis. In addition, flow cytometric analysis revealed that saponin 6 was able to induce cell cycle arrest. The present study also demonstrated that saponin 6‑induced apoptosis of U87 MG cells was attributed to increases in the protein expression levels of Fas, Fas ligand, and cleaved caspase‑3, ‑8 and ‑9, and decreases in the levels of B‑cell lymphoma 2. The current study indicated that saponin 6 may exhibit selective cytotoxicity toward U87 MG cells by activating apoptosis via the extrinsic and intrinsic pathways. Therefore, saponin 6 derived from A. taipaiensis may possess therapeutic potential for the treatment of GBM.
Simultaneous contrast and gamut relativity in achromatic color perception.
Vision research, 2012

Simultaneous contrast refers to the respective whitening or blackening of physically identical image regions surrounded by regions of low or high luminance, respectively. A common method of measuring the strength of this effect is achromatic color matching, in which subjects adjust the luminance of a target region to achieve an achromatic color match with another region. Here I present psychophysical data questioning the assumption--built into many models of achromatic color perception--that achromatic colors are represented as points in a one-dimensional (1D) perceptual space, or an absolute achromatic color gamut. I present an alternative model in which the achromatic color gamut corresponding to a target region is defined relatively, with respect to surround luminance. Different achromatic color gamuts in this model correspond to different 1D lines through a 2D perceptual space composed of blackness and whiteness dimensions. Each such line represents a unique gamut of achromatic colors ranging from black to white. I term this concept gamut relativity. Achromatic color matches made between targets surrounded by regions of different luminance are shown to reflect the relative perceptual distances between points lying on different gamut lines. The model suggests a novel geometrical approach to simultaneous contrast and achromatic color matching in terms of the vector summation of local luminance and contrast components, and sets the stage for a unified computational theory of achromatic color perception.
The ATXN1 and TRIM31 genes are related to intelligence in an ADHD background: evidence from a large collaborative study totaling 4,963 subjects.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2011

Intelligence is a highly heritable trait for which it has proven difficult to identify the actual genes. In the past decade, five whole-genome linkage scans have suggested genomic regions important to human intelligence; however, so far none of the responsible genes or variants in those regions have been identified. Apart from these regions, a handful of candidate genes have been identified, although most of these are in need of replication. The recent growth in publicly available data sets that contain both whole genome association data and a wealth of phenotypic data, serves as an excellent resource for fine mapping and candidate gene replication. We used the publicly available data of 947 families participating in the International Multi-Centre ADHD Genetics (IMAGE) study to conduct an in silico fine mapping study of previously associated genomic locations, and to attempt replication of previously reported candidate genes for intelligence. Although this sample was ascertained for attention deficit/hyperactivity disorder (ADHD), intelligence quotient (IQ) scores were distributed normally. We tested 667 single nucleotide polymorphisms (SNPs) within 15 previously reported candidate genes for intelligence and 29451 SNPs in five genomic loci previously identified through whole genome linkage and association analyses. Significant SNPs were tested in four independent samples (4,357 subjects), one ascertained for ADHD, and three population-based samples. Associations between intelligence and SNPs in the ATXN1 and TRIM31 genes and in three genomic locations showed replicated association, but only in the samples ascertained for ADHD, suggesting that these genetic variants become particularly relevant to IQ on the background of a psychiatric disorder.