rudyvdbrink/CitationDatabase huggingface dataset:
The calcium-binding type III repeats domain of thrombospondin-2 binds to fibroblast growth factor 2 (FGF2).
Angiogenesis, 2019

Thrombospondin (TSP)-1 and TSP-2 share similar structures and functions, including a remarkable antiangiogenic activity. We have previously demonstrated that a mechanism of the antiangiogenic activity of TSP-1 is the interaction of its type III repeats domain with fibroblast growth factor-2 (FGF2), affecting the growth factor bioavailability and angiogenic activity. Since the type III repeats domain is conserved in TSP-2, this study aimed at investigating whether also TSP-2 retained the ability to interact with FGF2. The FGF2 binding properties of TSP-1 and TSP-2 and their recombinant domains were analyzed by solid-phase binding and surface plasmon resonance assays. TSP-2 bound FGF2 with high affinity (Kd = 1.3 nM). TSP-2/FGF2 binding was inhibited by calcium and heparin. The FGF2-binding domain of TSP-2 was located in the type III repeats and the minimal interacting sequence was identified as the GVTDEKD peptide in repeat 3C, corresponding to KIPDDRD, the active sequence of TSP-1. A second putative FGF2 binding sequence was also identified in repeat 11C of both TSPs. Computational docking analysis predicted that both the TSP-2 and TSP-1-derived heptapeptides interacted with FGF2 with comparable binding properties. Accordingly, small molecules based on the TSP-1 active sequence blocked TSP-2/FGF2 interaction. Binding of TSP-2 to FGF2 impaired the growth factor ability to interact with its cellular receptors, since TSP-2-derived fragments prevented the binding of FGF2 to both heparin (used as a structural analog of heparan sulfate proteoglycans) and FGFR-1. These findings identify TSP-2 as a new FGF2 ligand that shares with TSP-1 the same molecular requirements for interaction with the growth factor and a comparable capacity to block FGF2 interaction with proangiogenic receptors. These features likely contribute to TSP-2 antiangiogenic and antineoplastic activity, providing the rationale for future therapeutic applications.
The medial nucleus of the trapezoid body: comparative physiology.
Neuroscience, 2008

Principal cells of the medial nucleus of the trapezoid body (MNTB) receive their excitatory input through large somatic terminals, the calyces of Held, which arise from axons of globular bushy cells located in the contralateral ventral cochlear nucleus. Discharges of MNTB neurons are characterized by high stimulus evoked firing rates, temporally precise onset responses, and a high degree of phase-locking to either pure tones or stimulus envelopes. Since the calyx of Held synapse is accessible to in vitro and to in vivo recordings, it serves as one of the most elaborate models for studying synaptic transmission in the mammalian brain. Although in such studies, the major emphasis is on synaptic physiology, the interpretation of the data will benefit from an understanding of the MNTB's contribution to auditory signal processing, including possible functional differences in different species. This implies the consideration of possible functional differences in different species. Here, we compare single unit recordings from MNTB principal cells in vivo in three different rodent species: gerbil, mouse and rat. Because of their good low-frequency hearing gerbils are often used in in vivo preparations, while mice and rats are predominantly used in slice preparations. We show that MNTB units in all three species exhibit high firing rates and precise onset-timing. Still there are species-specific specializations that might suggest the preferential use of one species over the others, depending on the scope of the respective investigation.
Disinhibition of the rat prelimbic cortex promotes serotonergic activation of the dorsal raphe nucleus and panicolytic-like behavioral effects.
Journal of psychopharmacology (Oxford, England), 2017

Several studies have shown that serotonin plays a dual role in the modulation of defensive behaviors related to anxiety and panic. A major source of serotonergic projections to limbic structures responsible for this modulation is the dorsal raphe nucleus (DR). Anatomical studies indicate that the prelimbic (PL) cortex sends dense glutamatergic projections to the DR, leading to stimulation or inhibition of serotonin release in structures innervated by the DR. The objective of the present study was to investigate if GABAergic disinhibition of the PL by means of local administration of picrotoxin (PIC), a chloride channel blocker, can affect serotonergic tone and the expression of defensive behaviors related to anxiety and panic. We used the elevated T-maze model and Vogel conflict test to evaluate defensive responses associated with anxiety or panic. The results showed that intra-PL PIC caused an increase in c-Fos activation in serotonergic cells in DR subregions. Furthermore, the intra-PL injection of PIC induced a panicolytic-like effect without affecting behaviors associated with anxiety. Our findings suggest that the PL-DR pathway, through DR serotonergic stimulation, is involved in the control of panic-related behaviors by control of serotonin release in structures that modulate panic responses, such as the dorsal periaqueductal gray.
Peripheral and central mechanisms of cough hypersensitivity.
Journal of thoracic disease, 2020

Chronic cough is a difficult to treat symptom of many respiratory and some non-respiratory diseases, indicating that varied pathologies can underpin the development of chronic cough. However, clinically and experimentally it has been useful to collate these different pathological processes into the single unifying concept of cough hypersensitivity. Cough hypersensitivity syndrome is reflected by troublesome cough often precipitated by levels of stimuli that ordinarily don't cause cough in healthy people, and this appears to be a hallmark feature in many patients with chronic cough. Accordingly, a strong argument has emerged that changes in the excitability and/or normal regulation of the peripheral and central neural circuits responsible for cough are instrumental in establishing cough hypersensitivity and for causing excessive cough in disease. In this review, we explore the current peripheral and central neural mechanisms that are believed to be involved in altered cough sensitivity and present possible links to the mechanism of action of novel therapies that are currently undergoing clinical trials for chronic cough.
Signals governing the trafficking and mistrafficking of a ciliary GPCR, rhodopsin.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Rhodopsin is a cilia-specific GPCR essential for vision. Rhodopsin mislocalization is associated with blinding diseases called retinal ciliopathies. The mechanism by which rhodopsin mislocalizes in rod photoreceptor neurons is not well understood. Therefore, we investigated the roles of trafficking signals in rhodopsin mislocalization. Rhodopsin and its truncation mutants were fused to a photoconvertible fluorescent protein, Dendra2, and expressed in Xenopus laevis rod photoreceptors. Photoconversion of Dendra2 causes a color change from green to red, enabling visualization of the dynamic events associated with rhodopsin trafficking and renewal. We found that rhodopsin mislocalization is a facilitated process for which a signal located within 322-326 aa (CCGKN) is essential. An additional signal within 327-336 aa further facilitated the mislocalization. This collective mistrafficking signal confers toxicity to rhodopsin and causes mislocalization when the VXPX cilia-targeting motif is absent. We also determined that the VXPX motif neutralizes this mistrafficking signal, enhances ciliary targeting at least 10-fold, and accelerates trafficking of post-Golgi vesicular structures. In the absence of the VXPX motif, mislocalized rhodopsin is actively cleared through secretion of vesicles into the extracellular milieu. Therefore, this study unveiled the multiple roles of trafficking signals in rhodopsin localization and renewal.
Publisher Correction: Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease.
Nature neuroscience, 2019

In the version of this article initially published, the legends for Supplementary Figs. 4-8 and 10-14 contained errors. The Supplementary Figure legends have been corrected in the HTML and PDF versions of the article.
A.R. Luria's Approach to Neuropsychological Assessment and Rehabilitation.
Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists, 2019

Luria is one of the most influential authors in cognitive neuroscience, and in particular neuropsychology. New scientific achievements and clinical observations have significantly supported many of his suggestions and hypotheses. The article describes the basic concepts of neuropsychological evaluation and rehabilitation, associated with the method of syndrome analysis developed by Luria for diagnosis mental function and focus in the qualitative interpretation of the results neuropsychological diagnosis. Luria is regarded as a pioneer in cognitive rehabilitation. His ideas have maintained relevance and have continued to be developed and analyzed. Luria is presented as one of the major founders of contemporary neuropsychology from the fundamental point of view and the clinical perspective. His influence has continued significantly during the 21st century.
Laquinimod in the treatment of relapsing remitting multiple sclerosis.
Expert opinion on drug metabolism & toxicology, 2016

Laquinimod is a new once-daily oral administrable agent, which is under investigation in a phase 3 clinical trial for relapsing remitting multiple sclerosis (RRMS) and in a phase 2 clinical trial for primary progressive MS (PPMS).
Individual cognitive remediation therapy benefits for patients with anorexia nervosa and high autistic features.
European eating disorders review : the journal of the Eating Disorders Association, 2020

Cognitive remediation therapy (CRT) is an increasingly implemented intervention in psychiatric conditions. The majority of randomized treatment trials in psychiatry reports cognitive improvements resulting in better functional outcomes in CRT groups. This brief report from the national inpatient treatment programme for eating disorders demonstrates cognitive performance task-based improvements in patients with high and low autistic characteristics. This preliminary study shows feasibility and benefits of individual CRT in patients who have autism spectrum disorder features.
Ontogeny of odor liking during childhood and its relation to language development.
Chemical senses, 2011

One important aspect of odor hedonics is its plasticity during human development. The present study set out to probe the modulators of such olfactory change during that period by testing the hypothesis that language and semantic representations of objects are strong organizers of odor liking. To this end, 15 three-year-old children were tested in a longitudinal study. Participants were exposed to exactly the same 12 odorants once a year over a 3-year period. At each experimental session, they were asked to answer 2 questions: 1) "Do you like or dislike this odor?" and 2) "Can you tell me what it is?" The level of language production was assessed on a standardized test. The 3-year-old children were found to categorize the same number of odorants as liked and as disliked. The follow-up study, in contrast, showed that at 5 years of age they categorized more of these odors as liked and that the shift was significant only in the children with higher language production skills. Taken as a whole, these findings suggest that the 3- to 5-year age range, when children begin to master language, is a turning point in the construction of olfactory hedonic categories during childhood.
SLC13A5 is the second gene associated with Kohlschütter-Tönz syndrome.
Journal of medical genetics, 2017

Kohlschütter-Tönz syndrome (KTZS) is a rare autosomal-recessive disease characterised by epileptic encephalopathy, intellectual disability and amelogenesis imperfecta (AI). It is frequently caused by biallelic mutations in ROGDI. Here, we report on individuals with ROGDI-negative KTZS carrying biallelic SLC13A5 mutations.
The analgesic effect of low dose focal irradiation in a mouse model of bone cancer is associated with spinal changes in neuro-mediators of nociception.
Pain, 2006

Despite the widespread use of radiotherapy to treat painful bone metastases, the mechanism underlying the analgesic effect of low dose ionizing radiation is unknown. Bone cancer pain is mostly associated with an inflammatory response dominated by local activation of osteoclasts and by astrogliosis in the spinal cord. We determined the effects of a 6 Gy irradiation given focally on osteolytic sarcoma cells inoculated in humeri of mice. Pain behavior was assessed using the rota-rod and the grip force test. Seven days post-irradiation (day 17 post-tumor implantation) the performance of mice markedly improved on the rotarod (non-irradiated, 67+/-16s vs irradiated, 223 +/- 22 s; P = 0.0005), and the grip force test (non-irradiated, 34 +/- 4 g vs irradiated, 55 +/- 2 g; P = 0.001). This improvement was similar to the analgesia achieved with 30 mg/kg of the cyclooxygenase (COX) inhibitor ketorolac (Rota-rod, 67 +/- 16 s vs 178 +/- 35 s; P = 0.01: grip force test, 34 +/- 4 g, vs 60 +/- 5 g; P = 0.003). Following irradiation, the tumor mass and the number of osteoclasts did not decrease while the expression of two pro-inflammatory cytokines (monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-alpha) increased. Tumor irradiation led to clear differences in the spinal cord. These include a decrease in glial activity (astrocytes and microglial cells) as well as pain mediators such as dynorphin, COX-2 and chemotactic cytokine receptor (CCR2). We conclude that the analgesic effect of low dose irradiation of bone cancer is associated with the alteration of nociceptive transmission in the central nervous system.
TMEM106B protects C9ORF72 expansion carriers against frontotemporal dementia.
Acta neuropathologica, 2014

Variants in transmembrane protein 106 B (TMEM106B) modify the disease penetrance of frontotemporal dementia (FTD) in carriers of progranulin (GRN) mutations. We investigated whether TMEM106B is also a genetic modifier of disease in carriers of chromosome 9 open reading frame 72 (C9ORF72) expansions. We assessed the genotype of 325 C9ORF72 expansion carriers (cohort 1), 586 FTD patients lacking C9ORF72 expansions [with or without motor neuron disease (MND); cohort 2], and a total of 1,302 controls for TMEM106B variants (rs3173615 and rs1990622) using MassArray iPLEX and Taqman genotyping assays. For our primary analysis, we focused on functional variant rs3173615, and employed a recessive genotypic model. In cohort 1, patients with C9ORF72 expansions showed a significantly reduced frequency of carriers homozygous for the minor allele as compared to controls [11.9 vs. 19.1 %, odds ratio (OR) 0.57, p = 0.014; same direction as carriers of GRN mutations]. The strongest evidence was provided by FTD patients (OR 0.33, p = 0.009) followed by FTD/MND patients (OR 0.38, p = 0.017), whereas no significant difference was observed in MND patients (OR 0.85, p = 0.55). In cohort 2, the frequency of carriers homozygous for the minor allele was not significantly reduced in patients as compared to controls (OR 0.77, p = 0.079); however, a significant reduction was observed when focusing on those patients with frontotemporal lobar degeneration and TAR DNA-binding protein 43 inclusions (FTLD-TDP; OR 0.26, p < 0.001). Our study identifies TMEM106B as the first genetic factor modifying disease presentation in C9ORF72 expansion carriers. Homozygosity for the minor allele protects carriers from developing FTD, but not from developing MND; similar effects are seen in FTLD-TDP patients with yet unknown genetic causes. These new findings show that the protective effects of TMEM106B are not confined to carriers of GRN mutations and might be relevant for prognostic testing, and as a promising therapeutic target for the entire spectrum of FTLD-TDP.
Effects of Medial Orbitofrontal Cortex Lesions on Self-Control in Intertemporal Choice.
Current biology : CB, 2016

Many decisions involve a trade-off between the temporal proximity of a reward and its magnitude. A range of clinical conditions are associated with poor self-control during such intertemporal choices, such that smaller rewards that are received sooner are preferred over larger rewards that are received later to a greater extent [1, 2]. According to a prominent neural model of self-control [3-6], subjective reward values are represented in the medial orbitofrontal cortex (mOFC) at the time of choice [7-9]. Successful self-control in this model is then thought to depend on a modulation of these mOFC value representations via the lateral prefrontal cortex (lPFC) [3, 6]. Here we directly tested three key predictions of this model in patients with lesions to the mOFC (n = 9) and matched controls (n = 19). First, we show that mOFC lesions disrupt choice-free valuation ratings. This finding provides causal evidence for a role of the mOFC in reward valuation and contrasts with the effects of lPFC disruption [6]. Second, we show that mOFC damage indeed decreases self-control during intertemporal choice, replicating previous findings [10]. Third, extending these previous observations, we show that the effect of mOFC damage on intertemporal choice depends on the actual self-control demands of the task. Our findings thus provide causal evidence for a role of mOFC in reward valuation and are compatible with the idea that mOFC damage affects self-control specifically under conditions that might normally require a modulation of mOFC value representations, e.g., by the lPFC.
A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication.
Nature microbiology, 2018

The endoplasmic reticulum (ER) is an architecturally diverse organelle that serves as a membrane source for the replication of multiple viruses. Flaviviruses, including yellow fever virus, West Nile virus, dengue virus and Zika virus, induce unique single-membrane ER invaginations that house the viral replication machinery
Systemic vesicular stomatitis virus selectively destroys multifocal glioma and metastatic carcinoma in brain.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Metastatic tumors and malignant gliomas make up the majority of cancers in the brain. They are invariably fatal and there is currently no cure. From in vitro comparisons of a number of viruses, we selected one that appeared the best in selectively killing glioblastoma cells. This replication-competent virus, the glioma-adapted vesicular stomatis virus strain VSVrp30a, was used for in vivo tests with the underlying view that infection of tumor cells will lead to an increase in the number of viruses subsequently released to kill additional tumor cells. Intravenous injection of VSVrp30a expressing a green fluorescent protein reporter, rapidly targeted and destroyed multiple types of human and mouse tumors implanted in the mouse brain, including glioblastoma and mammary tumors. When tumors were implanted both in the brain and peripherally, emulating systemic cancer metastasis, tumors inside and outside the brain were simultaneously infected. Intranasal inoculation, leading to olfactory nerve transport of the virus into the brain, selectively infected and killed olfactory bulb tumors. Neither control cortical wounds nor transplanted normal mouse or human cells were targeted, indicating viral tumor selectivity. Control viruses, including pseudorabies, adeno-associated, or replication-deficient VSV, did not infect the brain tumor. Confocal laser time-lapse imaging through a cranial window showed that intravenous VSV infects the tumor at multiple sites and kills migrating tumor cells. Disrupted tumor vasculature, suggested by dye leakage, may be the port of entry for intravenously delivered VSV. Quantitative PCR analysis of how VSVrp30a selectively infected tumor cells suggested multiple mechanisms, including cell surface binding and internalization.
Evidence-based mental health interventions for traumatized youth: a statewide dissemination project.
Behaviour research and therapy, 2011

Psychological trauma in childhood has been shown to increase a variety of psychological disturbances and psychiatric disorders. Although evidence-based treatments for children who have been traumatized exist, they are infrequently used by clinicians treating children. The present paper describes the creation of the Treatment Collaborative for Traumatized Youth (TCTY) which is a statewide partnership in North Dakota designed to disseminate efficacious treatments for traumatized children and monitor outcomes across a broad, rural, geographic expanse. The paper reviews the dissemination strategy developed by the TCTY, reports outcomes regarding both clinicians and child participants, and highlights problems identified in the project and solutions that were generated.
Memory deficits of British dementia knock-in mice are prevented by Aβ-precursor protein haploinsufficiency.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Familial British Dementia (FBD) is caused by an autosomal dominant mutation in the BRI2/ITM2B gene (Vidal et al., 1999). FBD(KI) mice are a model of FBD that is genetically congruous to the human disease, because they carry one mutant and one wild-type Bri2/Itm2b allele. Analysis of these mice has shown that the British mutation causes memory impairments due to loss of Bri2 function (Tamayev et al., 2010b). BRI2 is a physiologic inhibitor of processing of the Aβ-precursor protein (APP; Matsuda et al., 2008), a gene associated with Alzheimer's disease (Bertram et al., 2010). Here we show that APP haploinsufficiency prevents memory dysfunctions seen in FBD(KI) mice. This genetic suppression is consistent with a role for APP in the pathogenesis of memory deficits. Moreover, it provides compelling evidence that the memory dysfunctions caused by the British BRI2 mutant are dependent on endogenous APP and that BRI2 and APP functionally interact. This evidence establishes a mechanistic connection between Familial British and Alzheimer's dementias.
Prefrontal cortex and impulsive decision making.
Biological psychiatry, 2011

Impulsivity refers to a set of heterogeneous behaviors that are tuned suboptimally along certain temporal dimensions. Impulsive intertemporal choice refers to the tendency to forego a large but delayed reward and to seek an inferior but more immediate reward, whereas impulsive motor responses also result when the subjects fail to suppress inappropriate automatic behaviors. In addition, impulsive actions can be produced when too much emphasis is placed on speed rather than accuracy in a wide range of behaviors, including perceptual decision making. Despite this heterogeneous nature, the prefrontal cortex and its connected areas, such as the basal ganglia, play an important role in gating impulsive actions in a variety of behavioral tasks. Here, we describe key features of computations necessary for optimal decision making and how their failures can lead to impulsive behaviors. We also review the recent findings from neuroimaging and single-neuron recording studies on the neural mechanisms related to impulsive behaviors. Converging approaches in economics, psychology, and neuroscience provide a unique vista for better understanding the nature of behavioral impairments associated with impulsivity.