rudyvdbrink/CitationDatabase huggingface dataset:
A second wind for the cholinergic system in Alzheimer's therapy.
Behavioural pharmacology, 2017

Notwithstanding tremendous research efforts, the cause of Alzheimer's disease (AD) remains elusive and there is no curative treatment. The cholinergic hypothesis presented 35 years ago was the first major evidence-based hypothesis on the etiology of AD. It proposed that the depletion of brain acetylcholine was a primary cause of cognitive decline in advanced age and AD. It relied on a series of observations obtained in aged animals, elderly, and AD patients that pointed to dysfunctions of cholinergic basal forebrain, similarities between cognitive impairments induced by anticholinergic drugs and those found in advanced age and AD, and beneficial effects of drugs stimulating cholinergic activity. This review revisits these major results to show how this hypothesis provided the drive for the development of anticholinesterase inhibitor-based therapies of AD, the almost exclusively approved treatment in use despite transient and modest efficacy. New ideas for improving cholinergic therapies are also compared and discussed in light of the current revival of the cholinergic hypothesis on the basis of two sets of evidence from new animal models and refined imagery techniques in humans. First, human and animal studies agree in detecting signs of cholinergic dysfunctions much earlier than initially believed. Second, alterations of the cholinergic system are deeply intertwined with its reactive responses, providing the brain with efficient compensatory mechanisms to delay the conversion into AD. Active research in this field should provide new insight into development of multitherapies incorporating cholinergic manipulation, as well as early biomarkers of AD enabling earlier diagnostics. This is of prime importance to counteract a disease that is now recognized to start early in adult life.
Functional integration across oscillation frequencies by cross-frequency phase synchronization.
The European journal of neuroscience, 2018

Neuronal oscillations and their inter-areal synchronization may be instrumental in regulating neuronal communication in distributed networks. Several lines of research have, however, shown that cognitive tasks engage neuronal oscillations simultaneously in multiple frequency bands that have distinct functional roles in cognitive processing. Gamma oscillations (30-120 Hz) are associated with bottom-up processing, while slower oscillations in delta (1-4 Hz), theta (4-7 Hz), alpha (8-14 Hz) and beta (14-30 Hz) frequency bands may have roles in executive or top-down controlling functions, although also other distinctions have been made. Identification of the mechanisms that integrate such spectrally distributed processing and govern neuronal communication among these networks is crucial for understanding how cognitive functions are achieved in neuronal circuits. Cross-frequency interactions among oscillations have been recognized as a likely candidate mechanism for such integration. We advance here the hypothesis that phase-phase synchronization of neuronal oscillations in two different frequency bands, cross-frequency phase synchrony (CFS), could serve to integrate, coordinate and regulate neuronal processing distributed into neuronal assemblies concurrently in multiple frequency bands. A trail of studies over the past decade has revealed the presence of CFS among cortical oscillations and linked CFS with roles in cognitive integration. We propose that CFS could connect fast and slow oscillatory networks and thereby integrate distributed cognitive functions such as representation of sensory information with attentional and executive functions.
GPR40 activation leads to CREB and ERK phosphorylation in primary cultures of neurons from the mouse CNS and in human neuroblastoma cells.
Hippocampus, 2014

GPR40, the free fatty acid receptor 1, is expressed strongly in the primate pancreas and brain. While the role of pancreatic GPR40 in glucose homeostasis has been extensively studied, the absence of this G-protein-coupled receptor from the brain of rodents has hampered studies into its role in the central nervous system. However, we found intense GPR40 mRNA expression by in situ hybridization in mouse hippocampal and motor cortex neurons. Furthermore, in a neuroblastoma cell GPR40 was activated by docosahexaenoic acid and selective agonists, yet not by palmitic acid. Significantly, the activation of GPR40 provoked the phosphorylation of the cAMP response element-binding protein, CREB. The receptor was also functional in primary cultures of murine neurons, in which its activation by a selective agonist produced the phosphorylation of CREB and of extracellular signal-regulated kinases, ERK1/2. These results suggest that mice represent a suitable model for elucidating the role of GPR40 in brain function.
Recurring sequences of multimodal non-verbal and verbal communication during a human psycho-social stress test: A temporal pattern analysis.
Physiology & behavior, 2020

The Trier Social Stress Test (TSST) is a widely used protocol to study human psycho-social stress responses. Quantitative reports of non-verbal behaviors have been carried out by means of the Ethological Coding System for Interviews (ECSI). However, no data have described whether and how non-verbal and verbal behaviors take part in the composition of multimodal sequences of communication during the test.
A Hospital Level Analysis of 30-Day Readmission Performance for Heart Failure Patients and Long-Term Survival: Findings from Get With The Guidelines-Heart Failure.
American heart journal, 2018

Medicare utilizes 30-day risk-standardized readmission rates (RSRR) as a measure of hospital quality and applies penalties based on this measure. The objective of this study was to identify the relationship between hospital performance on 30-day RSRR in heart failure (HF) patients and long-term patient survival.
The Importance of Keeping Time in the Liver.
Endocrinology, 2021

The liver is a "front line" in the homeostatic defenses against variation in nutrient intake. It orchestrates metabolic responses to feeding by secreting factors essential for maintaining metabolic homeostasis, converting carbohydrates to triglycerides for storage, and releasing lipids packaged as lipoproteins for distribution to other tissues. Between meals, it provides fuel to the body by releasing glucose produced from glucogenic precursors and ketones from fatty acids and ketogenic amino acids. Modern diets enriched in sugars and saturated fats increase lipid accumulation in hepatocytes (nonalcoholic fatty liver disease). If untreated, this can progress to liver inflammation (nonalcoholic steatohepatitis), fibrosis, cirrhosis, and hepatocellular carcinoma. Dysregulation of liver metabolism is also relatively common in modern societies. Increased hepatic glucose production underlies fasting hyperglycemia that defines type 2 diabetes, while increased production of atherogenic, large, triglyceride-rich, very low-density lipoproteins raises the risk of cardiovascular disease. Evidence has accrued of a strong connection between meal timing, the liver clock, and metabolic homeostasis. Metabolic programming of the liver transcriptome and posttranslation modifications of proteins is strongly influenced by the daily rhythms in nutrient intake governed by the circadian clock. Importantly, whereas cell-autonomous clocks have been identified in the liver, the complete circadian programing of the liver transcriptome and posttranslational modifications of essential metabolic proteins is strongly dependent on nutrient flux and circadian signals from outside the liver. The purpose of this review is to provide a basic understanding of liver circadian physiology, drawing attention to recent research on the relationships between circadian biology and liver function.
De novo exonic duplication of ATP1A2 in Italian patient with hemiplegic migraine: a case report.
The journal of headache and pain, 2017

Sporadic Hemiplegic Migraine is a rare form of migraine headache. Mutations in three different genes, two ion-channel genes and one encoding an ATP exchanger, CACNA1A, ATP1A2 and SCN1A are all responsible for the FHM phenotype, thus indicating a genetic heterogeneity for this disorder. Here, we described a de novo exonic duplication of ATP1A2 in an Italian patient with Hemiplegic Migraine.
Entrained neuronal activity to periodic visual stimuli in the primate striatum compared with the cerebellum.
eLife, 2019

Rhythmic events recruit neuronal activity in the basal ganglia and cerebellum, but their roles remain elusive. In monkeys attempting to detect a single omission of isochronous visual stimulus, we found that neurons in the caudate nucleus showed increased activity for each stimulus in sequence, while those in the cerebellar dentate nucleus showed decreased activity. Firing modulation in the majority of caudate neurons and all cerebellar neurons was proportional to the stimulus interval, but a quarter of caudate neurons displayed a clear duration tuning. Furthermore, the time course of population activity in the cerebellum well predicted stimulus timing, whereas that in the caudate reflected stochastic variation of response latency. Electrical stimulation to the respective recording sites confirmed a causal role in the detection of stimulus omission. These results suggest that striatal neurons might represent periodic response preparation while cerebellar nuclear neurons may play a role in temporal prediction of periodic events.
Inferences about mental states.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2009

Human social cognition relies on an ability to predict what others will think, feel or do in novel situations. Research in social neuroscience has consistently observed several brain regions that contribute ubiquitously to these abilities, including medial prefrontal cortex and aspects of lateral and medial parietal cortex. Interestingly, parallel work has suggested that this same network of regions subserves several seemingly distinct phenomena-notably, the abilities to remember the past, imagine the future and visualize spatial layouts-suggesting the existence of a common set of cognitive processes devoted to projecting oneself into worlds that differ mentally, temporally or physically from one's current experience. This use of self-projection to understand others' minds requires perceivers to solve three distinct cognitive challenges: (i) generating a simulated facsimile of one's own hypothetical mental states in a given situation, (ii) suppressing one's own current mental states, and (iii) deciding on the appropriateness of simulated states for understanding a particular other person. The present paper reviews recent psychology and neuroscience research aimed at understanding the underlying mechanisms that allow humans to solve each of these cognitive challenges to use self-projection to predict and understand the mental states of others.
On the specificity of sequential congruency effects in implicit learning of motor and perceptual sequences.
Journal of experimental psychology. Learning, memory, and cognition, 2013

Individuals experience less interference from conflicting information following events that contain conflicting information. Recently, Jiménez, Lupiáñez, and Vaquero (2009) demonstrated that such adaptations to conflict occur even when the source of conflict arises from implicit knowledge of sequences. There is accumulating evidence that momentary changes in adaptations made in response to conflicting information are conflict-type specific (e.g., Funes, Lupiáñez, & Humphreys, 2010a), suggesting that there are multiple modes of control. The current study examined whether conflict-specific sequential congruency effects occur when the 2 sources of conflict are implicitly learned. Participants implicitly learned a motor sequence while simultaneously learning a perceptual sequence. In a first experiment, after learning the 2 orthogonal sequences, participants expressed knowledge of the 2 sequences independently of each other in a transfer phase. In Experiments 2 and 3, within each sequence, the presence of a single control trial disrupted the expression of this specific type of learning on the following trial. There was no evidence of cross-conflict modulations in the expression of sequence learning. The results suggest that the mechanisms involved in transient shifts in conflict-specific control, as reflected in sequential congruency effects, are also engaged when the source of conflict is implicit.
The acuity of pediatric neuroscience nursing using the Inpatient Complexity Assessment and Monitoring to Ensure Optimal Outcomes (CAMEO
Journal for specialists in pediatric nursing : JSPN, 2021

The neuroscience nurse must possess advanced knowledge and skills to care for a wide range of unique congenital and acquired neurological diagnoses. For each of these clinical scenarios, the measurement of complexity and acuity of patient care is key to informing staffing models and patient assignments. The Inpatient Complexity Assessment and Monitoring to Ensure Optimal Outcomes (CAMEO
beta-Phorbol ester-induced enhancement of exocytosis in large mossy fiber boutons of mouse hippocampus.
The journal of physiological sciences : JPS, 2009

beta-Phorbol esters (BPE), synthetic analogues of diacylglycerol (DAG), induce the potentiation of transmission in many kinds of synapses through activating the C(1) domain-containing receptors. However, their effects on synaptic vesicle exocytosis have not yet been investigated. Here, we evaluated the vesicular exocytosis directly from individual large mossy fiber boutons (LMFBs) in hippocampal slices from transgenic mice that selectively express synaptopHluorin (SpH). We found that the activity-dependent increment of SpH fluorescence (DeltaSpH) was enhanced by 4beta-phorbol 12,13-diacetate (PDAc), one of the BPEs, without influencing the recycled component of SpH. These PDAc effects on DeltaSpH were almost completely inhibited by staurosporine, a non-selective antagonist of protein kinases. However, intermittent synaptic transmission was still potentiated through a staurosporine-resistant mechanism. The staurosporine-sensitive cascade may facilitate the vesicle replenishment, thus maintaining the fidelity of transmission at a high level during repetitive firing of the presynaptic neuron.
Asynchronous, contagious and digital aging.
Nature aging, 2021

Aging has largely been defined by analog measures of organ and organismal dysfunction. This has led to the characterization of aging processes at the molecular and cellular levels that underlie these gradual changes. However, current knowledge does not fully explain the growing body of data emerging from large epidemiological, systems biology, and single cell studies of entire organisms pointing to varied rates of aging between individuals (different functionality and lifespan), across lifespan (asynchronous aging), and within an organism at the tissue and organ levels (aging mosaicism). Here we consider these inhomogeneities in the broader context of the rate of aging and from the perspective of underlying cellular changes. These changes reflect genetic, environmental, and stochastic factors that cells integrate to adopt new homeostatic, albeit less functional, states, such as cellular senescence. In this sense, cellular aging can be viewed, at least in part, as a quantal process we refer to as "digital aging". Nevertheless, analog declines of tissue dysfunction and organ failure with age could be the sum of underlying digital events. Importantly, cellular aging, digital or otherwise, is not uniform across time or space within the organism or between organisms of the same species. Certain tissues may exhibit earliest signs of cellular aging, acting as drivers for organismal aging as signals from those driver cells within those tissues may accelerate the aging of other cells locally or even systemically. Advanced methodologies at the systems level and at the single cell level are likely to continue to refine our understanding to the processes of how cells and tissues age and how the integration of those processes leads to the complexities of individual, organismal aging.
Sparse but highly efficient Kv3 outpace BKCa channels in action potential repolarization at hippocampal mossy fiber boutons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Presynaptic elements of axons, in which action potentials (APs) cause release of neurotransmitter, are sites of high densities and complex interactions of proteins. We report that the presence of K(v)3 channels in addition to K(v)1 at glutamatergic mossy fiber boutons (MFBs) in rat hippocampal slices considerably limits the number of fast, voltage-activated potassium channels necessary to achieve basal presynaptic AP repolarization. The ∼ 10-fold higher repolarization efficacy per K(v)3 channel compared with presynaptic K(v)1 results from a higher steady-state availability at rest, a better recruitment by the presynaptic AP as a result of faster activation kinetics, and a larger single-channel conductance. Large-conductance calcium- and voltage-activated potassium channels (BK(Ca)) at MFBs give rise to a fast activating/fast inactivating and a slowly activating/sustained K(+) current component during long depolarizations. However, BK(Ca) contribute to MFB-AP repolarization only after presynaptic K(v)3 have been disabled. The calcium chelators EGTA and BAPTA are equally effective in preventing BK(Ca) activation, suggesting that BK(Ca) are not organized in nanodomain complexes with presynaptic voltage-gated calcium channels. Thus, the functional properties of K(v)3 channels at MFBs are tuned to both promote brevity of presynaptic APs limiting glutamate release and at the same time keep surface protein density of potassium channels low. Presynaptic BK(Ca) channels are restricted to limit additional increases of the AP half-duration in case of K(v)3 hypofunction, because rapid membrane repolarization by K(v)3 combined with distant calcium sources prevent BK(Ca) activation during basal APs.
AMPK agonist AICAR improves cognition and motor coordination in young and aged mice.
Learning & memory (Cold Spring Harbor, N.Y.), 2014

Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging-associated frailty can preclude physical activity. In young sedentary animals, pharmacological activation of AMP-activated protein kinase (AMPK), a transcriptional regulator important for muscle physiology, enhanced spatial memory function, and endurance. In the present study we investigated effects of AMPK agonist 5-aminoimidazole-4-carboxamide riboside (AICAR) on memory and motor function in young (5- to 7-wk-old) and aged (23-mo-old) female C57Bl/6 mice, and in young (4- to 6-wk-old) transgenic mice with muscle-specific mutated AMPK α2-subunit (AMPK-DN). Mice were injected with AICAR (500 mg/kg) for 3-14 d. Two weeks thereafter animals were tested in the Morris water maze, rotarod, and open field. Improved water maze performance and motor function were observed, albeit at longer duration of administration, in aged (14-d AICAR) than in young (3-d AICAR) mice. In the AMPK-DN mice, the compound did not enhance behavior, providing support for a muscle-mediated mechanism. In addition, microarray analysis of muscle and hippocampal tissue derived from aged mice treated with AICAR revealed changes in gene expression in both tissues, which correlated with behavioral effects in a dose-dependent manner. Pronounced up-regulation of mitochondrial genes in muscle was observed. In the hippocampus, genes relevant to neuronal development and plasticity were enriched. Altogether, endurance-related factors may mediate both muscle and brain health in aging, and could play a role in new therapeutic interventions.
Sex-specific effects of cytotoxic chemotherapy agents cyclophosphamide and mitomycin C on gene expression, oxidative DNA damage, and epigenetic alterations in the prefrontal cortex and hippocampus - an aging connection.
Aging, 2016

Recent research shows that chemotherapy agents can be more toxic to healthy brain cells than to the target cancer cells. They cause a range of side effects, including memory loss and cognitive dysfunction that can persist long after the completion of treatment. This condition is known as chemo brain. The molecular and cellular mechanisms of chemo brain remain obscure. Here, we analyzed the effects of two cytotoxic chemotherapy drugs-cyclophosphamide (CPP) and mitomycin C (MMC) - on transcriptomic and epigenetic changes in the murine prefrontal cortex (PFC) and hippocampal regions. We for the first time showed that CPP and MMC treatments led to profound sex- and brain region-specific alterations in gene expression profiles. Gene expression changes were most prominent in the PFC tissues of female mice 3 weeks after MMC treatment, and the gene expression response was much greater for MCC than CPP exposure. MMC exposure resulted in oxidative DNA damage, evidenced by accumulation of 8-oxo-2'-deoxyguanosine (8-oxodG) and a decrease in the level of 8-oxodG repair protein OGG1 in the PFC of female animals 3 weeks after treatment. MMC treatment decreased global DNA methylation and increased DNA hydroxymethylation in the PFC tissues of female mice. The majority of the changes induced by chemotherapy in the PFC tissues of female mice resembled those that occur during the brain's aging processes. Therefore, our study suggests a link between chemotherapy-induced chemo brain and brain aging, and provides an important roadmap for future analysis.
Season of treatment initiation with antidepressants and suicidal behavior: A population-based cohort study in Sweden.
Journal of affective disorders, 2017

Decreased binding capacity of SERT in the prefrontal cortex has been observed in both suicide victims and suicide attempters. Moreover, some studies have shown that SERT has a seasonal variation with lower binding capacity in the spring and summer, which coincides with a seasonal peak of suicides. Our aim was to explore whether the season of treatment initiation with antidepressants is associated with suicide or suicide attempt and compare it with the underlying suicide seasonality in the general population.
Outcomes of cranioplasty with synthetic materials and autologous bone grafts.
World neurosurgery, 2015

Using current surgical methods, cranioplasty is associated with a high complication rate. We analyzed if there are preexisting medical conditions associated with complications and compared the effect of different implant materials on the degree of complications.
A Cross Talk between Neuronal Urokinase-type Plasminogen Activator (uPA) and Astrocytic uPA Receptor (uPAR) Promotes Astrocytic Activation and Synaptic Recovery in the Ischemic Brain.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017

Urokinase-type plasminogen activator (uPA) is a serine proteinase that, upon binding to its receptor (uPAR), catalyzes the conversion of plasminogen into plasmin on the cell surface. Our previous studies indicate that uPA and uPAR expression increase in the ischemic brain during the recovery phase from an acute ischemic injury and that uPA binding to uPAR promotes neurological recovery after an acute ischemic stroke. Here, we used male mice genetically deficient on either uPA (uPA