rudyvdbrink/CitationDatabase huggingface dataset:
The role of focal epilepsy in the development of jacksonian localization.
Journal of the history of the neurosciences, 2009

In the 1860s John Hughlings Jackson (1835-1911) reasoned on theoretical grounds that voluntary movements probably were represented in the human cerebral cortex. He then studied the clinical phenomenologies and pathological associations of human focal motor epileptic seizures, post-epileptic hemiplegia and aphasia, and also chorea. From these various lines of evidence he concluded by 1870 that voluntary movement of the face and upper limb on the opposite side were represented in a localized area of the human cerebral cortex overlying the corpus striatum. He recognized this shortly before the physiologists demonstrated such cortical localization of function in experimental animals. Over the following three decades, Jackson analyzed the spread of focal motor epileptic seizure activity, and the phenomenology of other types of epileptic seizure in humans, and related this knowledge to the sites of the brain pathology that appeared responsible for these events. This enabled him to locate cerebral cortical sites for the representation of foot movement, consciousness, and various aspects of special sensory function, as well as for certain psychic phenomena that arose from temporal lobe paroxysmal disturbance.
Nonpeptidic Amphiphilic Xanthone Derivatives: Structure-Activity Relationship and Membrane-Targeting Properties.
Journal of medicinal chemistry, 2016

We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more potent compounds with lower hemolytic activity and greater membrane selectivity. Forty-six amphiphilic xanthone derivatives were analyzed in this study and structurally classified into four groups based on spacer length, cationic moieties, lipophilic chains, and triarm functionalization. We evaluated and explored the effects of the structures on their membrane-targeting properties. The SAR analysis successfully identified 3a with potent MICs (1.56-3.125 μ/mL) and lower hemolytic activity (80.2 μg/mL for 3a versus 19.7 μg/mL for 2c). Compound 3a displayed a membrane selectivity of 25.7-50.4. Thus, 3a with improved HC50 value and promising selectivity could be used as a lead compound for further structural optimization for the treatment of MRSA infection.
T-box transcription regulator Tbr2 is essential for the formation and maintenance of Opn4/melanopsin-expressing intrinsically photosensitive retinal ganglion cells.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Opsin 4 (Opn4)/melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) play a major role in non-image-forming visual system. Although advances have been made in understanding their morphological features and functions, the molecular mechanisms that regulate their formation and survival remain unknown. Previously, we found that mouse T-box brain 2 (Tbr2) (also known as Eomes), a T-box-containing transcription factor, was expressed in a subset of newborn RGCs, suggesting that it is involved in the formation of specific RGC subtypes. In this in vivo study, we used complex mouse genetics, single-cell dye tracing, and behavioral analyses to determine whether Tbr2 regulates ipRGC formation and survival. Our results show the following: (1) Opn4 is expressed exclusively in Tbr2-positive RGCs; (2) no ipRGCs are detected when Tbr2 is genetically ablated before RGC specification; and (3) most ipRGCs are eliminated when Tbr2 is deleted in established ipRGCs. The few remaining ipRGCs display abnormal dendritic morphological features and functions. In addition, some Tbr2-expressing RGCs can activate Opn4 expression on the loss of native ipRGCs, suggesting that Tbr2-expressing RGCs may serve as a reservoir of ipRGCs to regulate the number of ipRGCs and the expression levels of Opn4.
Regulation of peroxisome proliferator-activated receptors (PPAR) α and -γ of rat brain astrocytes in the course of activation by toll-like receptor agonists.
Journal of neurochemistry, 2015

Peroxisome proliferator-activated receptors (PPAR)-α and -γ in astrocytes play important roles in inflammatory brain pathologies. Understanding the regulation of both activity and expression levels of PPARs is an important neuroscience issue. Toll-like receptor (TLR) agonists are inflammatory stimuli that could modulate PPAR, but the mechanisms of their control in astrocytes are poorly understood. In the present study, we report that lipopolysaccharide, peptidoglycan, and flagellin, which are agonists of TLR4, TLR1/2, and TLR5, respectively, exert time- and nuclear factor kappa-light-chain-enhancer of activated B cells-dependent suppression of mRNA, protein and activity of PPARα and PPARγ. In naïve astrocytes, PPARα and PPARγ mRNA have short turnover time (half-life about 30 min for PPARα, 75 min for PPARγ) with a nearly two-fold stabilization after TLR-activation. p38 inhibition abolished TLR-induced stabilization. The levels of PPARα and PPARγ mRNA, and protein and DNA-binding activity could be modified using c-Jun N-terminal Kinase and p38 inhibitors. In addition, the expression levels of both PPARα and PPARγ isotypes were induced after inhibition of protein synthesis. This induction signifies participation of additional regulatory proteins with short life-time. They are p38-sensitive for PPARα and c-Jun N-terminal Kinase-sensitive for PPARγ. Thus, PPARα and PPARγ are regulated in astrocytes on mRNA and protein levels, mRNA stability, and DNA-binding activity during TLR-mediated responses. Astrocytes have the triad of PPARα, PPARβ/δ, and PPARγ in regulation of proinflammatory responses. Activation of Toll-like receptors (TLR) leads to PPARβ/δ overexpression, PPARα and PPARγ suppression via TLR/NF-κB pathway on mRNA, protein and activity levels. Mitogen-activated protein kinases (MAPK) p38 and JNK are involved in regulation of PPAR expression. p38 MAPK plays a special role in stabilization of PPAR mRNA.
Is Stevia rebaudiana Bertoni a Non Cariogenic Sweetener? A Review.
Molecules (Basel, Switzerland), 2015

Stevia rebaudiana Bertoni is a small perennial shrub of the Asteraceae (Compositae) family that is native to South America, particularly Brazil and Paraguay, where it is known as "stevia" or "honey leaf" for its powerful sweetness. Several studies have suggested that in addition to their sweetness, steviosides and their related compounds, including rebaudioside A and isosteviol, may offer additional therapeutic benefits. These benefits include anti-hyperglycaemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions. Additionally, critical analysis of the literature supports the anti-bacterial role of steviosides on oral bacteria flora. The aim of this review is to show the emerging results regarding the anti-cariogenic properties of S. rebaudiana Bertoni. Data shown in the present paper provide evidence that stevioside extracts from S. rebaudiana are not cariogenic. Future research should be focused on in vivo studies to evaluate the effects on dental caries of regular consumption of S. rebaudiana extract-based products.
Rhythm and interpersonal synchrony in early social development.
Annals of the New York Academy of Sciences, 2015

Adults who engage in synchronous movement to music later report liking each other better, remembering more about each other, trusting each other more, and are more likely to cooperate with each other compared to adults who engage in asynchronous movements. Although poor motor coordination limits infants' ability to entrain to a musical beat, they perceive metrical structure in auditory rhythm patterns, their movements are affected by the tempo of music they hear, and if they are bounced by an adult to a rhythm pattern, the manner of this bouncing can affect their auditory interpretation of the meter of that pattern. In this paper, we review studies showing that by 14 months of age, infants who are bounced in synchrony with an adult subsequently show more altruistic behavior toward that adult in the form of handing back objects "accidentally" dropped by the adult compared to infants who are bounced asynchronously with the adult. Furthermore, increased helpfulness is directed at the synchronized bounce partner, but not at a neutral stranger. Interestingly, however, helpfulness does generalize to a "friend" of the synchronized bounce partner. In sum, synchronous movement between infants and adults has a powerful effect on infants' expression of directed prosocial behavior.
The neural network for face recognition: Insights from an fMRI study on developmental prosopagnosia.
NeuroImage, 2018

Face recognition is supported by collaborative work of multiple face-responsive regions in the brain. Based on findings from individuals with normal face recognition ability, a neural model has been proposed with the occipital face area (OFA), fusiform face area (FFA), and face-selective posterior superior temporal sulcus (pSTS) as the core face network (CFN) and the rest of the face-responsive regions as the extended face network (EFN). However, little is known about how these regions work collaboratively for face recognition in our daily life. Here we focused on individuals suffering developmental prosopagnosia (DP), a neurodevelopmental disorder specifically impairing face recognition, to shed light on the infrastructure of the neural model of face recognition. Specifically, we used a variant of global brain connectivity method to comprehensively explore resting-state functional connectivity (FC) among face-responsive regions in a large sample of DPs (N = 64). We found that both the FCs within the CFN and those between the CFN and EFN were largely reduced in DP. Importantly, the right OFA and FFA served as the dysconnectivity hubs within the CFN, i.e., FCs concerning these two regions within the CFN were largely disrupted. In addition, DPs' right FFA also showed reduced FCs with the EFN. Moreover, these disrupted FCs were related to DP's behavioral deficit in face recognition, with the FCs from the FFA to the anterior temporal lobe (ATL) and pSTS the most predictive. Based on these findings, we proposed a revised neural model of face recognition demonstrating the relatedness of interactions among face-responsive regions to face recognition.
White matter changes in primary dystonia determined by 2D distribution analysis of diffusion tensor images.
Journal of magnetic resonance imaging : JMRI, 2013

To determine brain tissue affected by dystonia by making group comparison of parameter-based diffusion tensor imaging (DTI) distributions of patients with control subjects. A 2D distribution analysis of mean diffusivity and fractional anisotropy index was used for modeling brain tissues according to the inherent diffusion characteristics.
Network-based gene expression analysis of intracranial aneurysm tissue reveals role of antigen presenting cells.
Neuroscience, 2008

Little is known about the pathology and pathogenesis of the rupture of intracranial aneurysms. For a better understanding of the molecular processes involved in intracranial aneurysm (IA) formation we performed a gene expression analysis comparing ruptured and unruptured aneurysm tissue to a control artery. Tissue samples of six ruptured and four unruptured aneurysms, and four cerebral arteries serving as controls, were profiled using oligonucleotide microarrays. Gene ontology classification of the differentially expressed genes was analyzed and regulatory functional networks and canonical pathways were identified with a network-based computational pathway analysis tool. Real time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining were performed as confirmation. Analysis of aneurysmal and control tissue revealed 521 differentially expressed genes. The most significantly associated gene ontology term was antigen processing (P=1.64E-16). Further network-based analysis showed the top scoring regulatory functional network to be built around overexpressed major histocompatibility class (MHC) I and II complex related genes and confirmed the canonical pathway "Antigen Presentation" to have the highest upregulation in IA tissue (P=7.3E-10). Real time RT-PCR showed significant overexpression of MHC class II genes. Immunohistochemical staining showed strong positivity for MHC II molecule specific antibody (HLA II), for CD68 (macrophages, monocytes), for CD45RO (T-cells) and HLA I antibody. Our results offer strong evidence for MHC class II gene overexpression in human IA tissue and that antigen presenting cells (macrophages, monocytes) play a key role in IA formation.
Remodelin Is a Cryptic Assay Interference Chemotype That Does Not Inhibit NAT10-Dependent Cytidine Acetylation.
ACS medicinal chemistry letters, 2021

Remodelin is a putative small molecule inhibitor of the RNA acetyltransferase NAT10 which has shown preclinical efficacy in models of the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS). Here we evaluate remodelin's assay interference characteristics and effects on NAT10-catalyzed RNA cytidine acetylation. We find the remodelin chemotype constitutes a cryptic assay interference compound, which does not react with small molecule thiols but demonstrates protein reactivity in ALARM NMR and proteome-wide affinity profiling assays. Biophysical analyses find no direct evidence for interaction of remodelin with the NAT10 acetyltransferase active site. Cellular studies verify that N4-acetylcytidine (ac4C) is a nonredundant target of NAT10 activity in human cell lines and find that this RNA modification is not affected by remodelin treatment in several orthogonal assays. These studies display the potential for remodelin's chemotype to interact with multiple protein targets in cells and indicate remodelin should not be applied as a specific chemical inhibitor of NAT10-catalyzed RNA acetylation.
Women and Men who Committed Murder: Male/Female Psychopathic Homicides.
Journal of forensic sciences, 2020

The present study was designed to compare gender differences in psychiatric diagnosis with the dimension of psychopathy in women and men who had attempted or committed homicide. The study samples consisted of 39 homicidal females and 48 homicidal males who were confined in one of Italy's REMS or prison facilities in two southern provinces of Italy (Puglia and Basilicata). Assessment instruments included the SCID-5, the PID-5 IRF, and the PCL-R. Each gender group was stratified according to the level of criminal responsibility for the homicidal offense (full, partial, absent), and after assessments, according to the degree of the psychopathic dimension. There were clear gender differences in homicidal individuals. Female offenders were less likely to have had a record of criminal charges/convictions or imprisonment, and their homicides were more often intrafamilial, victimizing especially of their children, whereas males targeted intimate partners and extrafamilial victims. In the entire group, there was an inverse relationship between the level of psychopathy and the personality disorder on one side, and the psychotic disturbance on the other. Factor 2 (lifestyle/antisocial dimension) of the PCL-R was higher among the homicidal males, whereas females tended to score higher on Factor 1 (the interpersonal/affective dimension). Finally, if the psychopathic dimension is a qualifier for antisocial personality disorder, as indicated in DSM-5, this appears to be less true for females who tend to have other personality disorders.
White matter injury in the preterm infant: pathology and mechanisms.
Acta neuropathologica, 2017

The human preterm brain is particularly susceptible to cerebral white matter injury (WMI) that disrupts the normal progression of developmental myelination. Advances in the care of preterm infants have resulted in a sustained reduction in the severity of WMI that has shifted from more severe focal necrotic lesions to milder diffuse WMI. Nevertheless, WMI remains a global health problem and the most common cause of chronic neurological morbidity from cerebral palsy and diverse neurobehavioral disabilities. Diffuse WMI involves maturation-dependent vulnerability of the oligodendrocyte (OL) lineage with selective degeneration of late oligodendrocyte progenitors (preOLs) triggered by oxidative stress and other insults. The magnitude and distribution of diffuse WMI are related to both the timing of appearance and regional distribution of susceptible preOLs. Diffuse WMI disrupts the normal progression of OL lineage maturation and myelination through aberrant mechanisms of regeneration and repair. PreOL degeneration is accompanied by early robust proliferation of OL progenitors that regenerate and augment the preOL pool available to generate myelinating OLs. However, newly generated preOLs fail to differentiate and initiate myelination along their normal developmental trajectory despite the presence of numerous intact-appearing axons. Disrupted preOL maturation is accompanied by diffuse gliosis and disturbances in the composition of the extracellular matrix and is mediated in part by inhibitory factors derived from reactive astrocytes. Signaling pathways implicated in disrupted myelination include those mediated by Notch, WNT-beta catenin, and hyaluronan. Hence, there exists a potentially broad but still poorly defined developmental window for interventions to promote white matter repair and myelination and potentially reverses the widespread disturbances in cerebral gray matter growth that accompanies WMI.
Nectin-3 links CRHR1 signaling to stress-induced memory deficits and spine loss.
Nature neuroscience, 2013

Stress impairs cognition via corticotropin-releasing hormone receptor 1 (CRHR1), but the molecular link between abnormal CRHR1 signaling and stress-induced cognitive impairments remains unclear. We investigated whether the cell adhesion molecule nectin-3 is required for the effects of CRHR1 on cognition and structural remodeling after early-life stress exposure. Postnatally stressed adult mice had decreased hippocampal nectin-3 levels, which could be attenuated by CRHR1 inactivation and mimicked by corticotropin-releasing hormone (CRH) overexpression in forebrain neurons. Acute stress dynamically reduced hippocampal nectin-3 levels, which involved CRH-CRHR1, but not glucocorticoid receptor, signaling. Suppression of hippocampal nectin-3 caused spatial memory deficits and dendritic spine loss, whereas enhancing hippocampal nectin-3 expression rescued the detrimental effects of early-life stress on memory and spine density in adulthood. Our findings suggest that hippocampal nectin-3 is necessary for the effects of stress on memory and structural plasticity and indicate that the CRH-CRHR1 system interacts with the nectin-afadin complex to mediate such effects.
Nicotine exposure during adolescence induces a depression-like state in adulthood.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009

There is a strong link between tobacco consumption and mood disorders. It has been suggested that afflicted individuals smoke to manage mood, however, there is evidence indicating that tobacco consumption can induce negative mood. This study was designed to investigate whether nicotine exposure during adolescence influences emotionality/behavioral functioning later in life. Adolescent (postnatal days, PD 30-44) male rats were treated with twice-daily injections of nicotine (0, 0.16, 0.32, or 0.64 mg/kg) for 15 consecutive days, and their behavioral reactivity to various behavioral paradigms (the elevated plus maze (EPM), sucrose preference, locomotor activity in the open field, and forced swim test (FST) was assessed 24 h (short term) or 1-month (long term) after exposure. Separate groups of adult rats received nicotine (0.32 mg/kg) to control for age-dependent effects. We report that nicotine exposure during adolescence-but not adulthood-leads to a depression-like state manifested in decreased sensitivity to natural reward (sucrose), and enhanced sensitivity to stress- (FST) and anxiety-eliciting situations (EPM) later in life. Our data show that behavioral dysregulation can emerge 1 week after drug cessation, and that a single day of nicotine exposure during adolescence can be sufficient to precipitate a depression-like state in adulthood. We further demonstrate that these deficits can be normalized by subsequent nicotine (0.32 mg/kg) or antidepressant (ie fluoxetine or bupropion; 10 mg/kg) treatment in adulthood. These data suggest that adolescent exposure to nicotine results in a negative emotional state rendering the organism significantly more vulnerable to the adverse effects of stress. Within this context, our findings, together with others indicating that nicotine exposure during adolescence enhances risk for addiction later in life, could serve as a potential model of comorbidity.
Using paired pulse TMS to facilitate contralateral and ipsilateral MEPs in upper extremity muscles of chronic hemiparetic stroke patients.
Journal of neuroscience methods, 2011

In moderate to severely impaired stroke patients, single pulse TMS, with or without background facilitation, may not be able to evoke a motor response in muscles of the upper extremity, thereby hindering potential studies of stroke patients using TMS. Paired pulse TMS has been shown to facilitate responses in distal muscles of healthy subjects. In this study, our aim was to investigate thirteen muscles of the upper extremity in moderate to severely impaired stroke patients and determine the paired pulse interstimulus interval (ISI) that was optimal for facilitation of the TMS response.
Eye movement tracking in pediatric obsessive compulsive disorder.
Asian journal of psychiatry, 2019

Till date researchers have elucidated the neurobiological substrates in OCD using methods like neuroimaging. However, a potential biomarker is still elusive. The present study is an attempt to identify a potential biomarker in pediatric OCD using eye tracking. The present study measured pro-saccade and anti-saccade parameters in 36 cases of pediatric OCD and 31 healthy controls. There was no significant difference between cases and controls in the error rate, peak velocity, position gain and latency measures in both pro-saccade and anti-saccade eye tracking tasks. With age, anti-saccades become slower in velocity, faster in response and more accurate irrespective of disorder status of the child. Pro-saccades also show a similar effect that is less prominent than anti-saccades. Gain measures more significantly vary with age in children with OCD than the controls, whereas latency measures positively correlated with age in children with OCD as opposed to being negatively correlated in the controls. Findings of this study do not support any of the eye tracking measures as putative diagnostic bio-markers in OCD. However, latency and gain parameters across different age groups in anti-saccade tasks need to be explored in future studies.