rudyvdbrink/CitationDatabase huggingface dataset:
Mechanism of translation inhibition by type II GNAT toxin AtaT2.
Nucleic acids research, 2020

Type II toxin-antitoxins systems are widespread in prokaryotic genomes. Typically, they comprise two proteins, a toxin, and an antitoxin, encoded by adjacent genes and forming a complex in which the enzymatic activity of the toxin is inhibited. Under stress conditions, the antitoxin is degraded liberating the active toxin. Though thousands of various toxin-antitoxins pairs have been predicted bioinformatically, only a handful has been thoroughly characterized. Here, we describe the AtaT2 toxin from a toxin-antitoxin system from Escherichia coli O157:H7. We show that AtaT2 is the first GNAT (Gcn5-related N-acetyltransferase) toxin that specifically targets charged glycyl tRNA. In vivo, the AtaT2 activity induces ribosome stalling at all four glycyl codons but does not evoke a stringent response. In vitro, AtaT2 acetylates the aminoacyl moiety of isoaccepting glycyl tRNAs, thus precluding their participation in translation. Our study broadens the known target specificity of GNAT toxins beyond the earlier described isoleucine and formyl methionine tRNAs, and suggest that various GNAT toxins may have evolved to specificaly target other if not all individual aminoacyl tRNAs.
Individuals With Autism Have No Detectable Deficit in Neural Markers of Prediction Error When Presented With Auditory Rhythms of Varied Temporal Complexity.
Autism research : official journal of the International Society for Autism Research, 2020

The brain's ability to encode temporal patterns and predict upcoming events is critical for speech perception and other aspects of social communication. Deficits in predictive coding may contribute to difficulties with social communication and overreliance on repetitive predictable environments in individuals with autism spectrum disorder (ASD). Using a mismatch negativity (MMN) task involving rhythmic tone sequences of varying complexity, we tested the hypotheses that (1) individuals with ASD have reduced MMN response to auditory stimuli that deviate in presentation timing from expected patterns, particularly as pattern complexity increases and (2) amplitude of MMN signal is inversely correlated with level of impairment in social communication and repetitive behaviors. Electroencephalography was acquired as individuals (age 6-21 years) listened to repeated five-rhythm tones that varied in the Shannon entropy of the rhythm across three conditions (zero, medium-1 bit, and high-2 bit entropy). The majority of the tones conformed to the established rhythm (standard tones); occasionally the fourth tone was temporally shifted relative to its expected time of occurrence (deviant tones). Social communication and repetitive behaviors were measured using the Social Responsiveness Scale and Repetitive Behavior Scale-Revised. Both neurotypical controls (n = 19) and individuals with ASD (n = 21) show stepwise decreases in MMN as a function of increasing entropy. Contrary to the result forecasted by a predictive coding hypothesis, individuals with ASD do not differ from controls in these neural mechanisms of prediction error to auditory rhythms of varied temporal complexity, and there is no relationship between these signals and social communication or repetitive behavior measures. LAY SUMMARY: We tested the idea that the brain's ability to use previous experience to influence processing of sounds is weaker in individuals with autism spectrum disorder (ASD) than in neurotypical individuals. We found no difference between individuals with ASD and neurotypical controls in brain wave responses to sounds that occurred earlier than expected in either simple or complex rhythms. There was also no relationship between these brain waves and social communication or repetitive behavior scores.
[Study on precise localization of intraoperative matrix electrode].
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi, 2017

In order to accurately localize the image coordinates and serial numbers of intraoperative subdural matrix electrodes, a matrix electrode localization algorithm for image processing is proposed in this paper. Firstly, by using point-by-point extended electrode location algorithm, the electrode is expanded point-by-point vertically and horizontally, and the initial coordinates and serial numbers of each electrode are determined. Secondly, the single electrode coordinate region extraction algorithm is used to determine the best coordinates of each electrode, so that the image coordinates and serial numbers of all electrodes are determined point-by-point. The results show that the positioning accuracy of electrode serial number is 100%, and the electrode coordinate positioning error is less than 2 mm. The algorithms in this paper can accurately localize the image coordinates and the serial numbers of a matrix electrode arranged in an arc, which could aid drawing of cortical function mapping, and achieve precise positioning of brain functional areas, so that it can be widely used in neuroscience research and clinical application based on electrocorticogram analysis.
Unmasking the dichoptic mask.
Journal of vision, 2019

Previously, it has been shown that dichoptic color-contrast masking can be dramatically reduced by the introduction of task-irrelevant binocular features. It is unclear, however, whether or not the task-irrelevant features need to be matched in the two eyes in order to reduce dichoptic masking. We measured dichoptic masking between target and mask luminance decrement patches and between target and mask isoluminant violet patches. The stimuli were surrounded by a task-irrelevant feature that consisted of a ring of various widths: either a luminance decrement, an isoluminant violet, or an isoluminant red. When the ring was presented to just the target eye-that is, the eye opposite to that of the mask-dichoptic masking was reduced just as much as when the ring was binocular-that is, presented to both eyes. A model that incorporated the combined influence of interocular inhibition from all stimulus components-that is, mask, target, and rings-was found to give a good account of the pattern of dichoptic masking across the full range of conditions.
A scalable, high resolution strain sensing matrix suitable for tactile transduction.
Journal of biomechanics, 2016

The integration of tactile information, such as contact area, displacement magnitude, velocity, and acceleration, is paramount to the optimization of robotics in human-centric environments. Cost effective embeddable sensors with scalable receptive field size and strain sensitivity are not readily commercially available and would benefit investigations of in situ tissue mechanics. We describe the design and performance of a scalable sensor matrix that transduces fine parameters of strain and is made of combinable "modules". The sensors transduce static and dynamic strains of both uniaxial and multi-dimensional nature. Modules consist of three silicon wafers placed on top of and three on the bottom of a hexagonal collar, wafers are thus positioned 120° to one another to facilitate force vector extrapolation. Analog signals from each sensor can be easily compared to neighboring sensor output to determine mechanical phenomena such as slip or shear. The smallest of our prototype multiunit matrices consisted of seven hexes in a honeycomb orientation of 4.1mm diameter (containing 42 silicon gauges). Unamplified, unshielded output from this embodiment (3 Vexc button cell) yielded 1 mV from 5 μm displacement. Transduction linearity was high (R>0.99 nearest displacement) and exhibited nominal hysteresis. Modules may be placed upon or embedded into a multitude of materials and the size of individual hexagons may be scaled for favorable stiffness to strain ratio and to scale receptive field. Given the scalability of matrix size and resolution, we believe the sensor matrices could benefit the fields of prosthetics, robotics, and physiologic investigation of tissue mechanics.
Experiences and lessons learned as a Chair of anatomy-An 18-year journey.
Anatomical record (Hoboken, N.J. : 2007), 2020

In 1998, I was appointed Chair of the Department of Anatomy at Monash University in Melbourne, Australia. On commencing as Chair, I had three main goals: (a) to maintain and extend the high quality of anatomy teaching in the medical program; (b) to introduce significantly more developmental biology, cell biology, and neuroscience into our existing Bachelor of Science major in human anatomy; and (c) to establish an active research program in the department. Over the next 18 years, I worked with staff and students at all levels of the university to turn this vision into a reality, with the Monash Department of Anatomy and Developmental Biology now arguably the top ranked anatomy department in Australia. During my tenure, countless challenges were faced and while some errors were made, and a good number of goals were never realized the general outcome was a vibrant scholarly environment where that rich nexus of research and teaching was realized. This personal account provides some insights into that 18-year journey, which I hope may prove useful for current and future Chairs of anatomy. For me personally, it was definitely a journey worth taking.
Country-Level Structural Stigma, School-Based and Adulthood Victimization, and Life Satisfaction Among Sexual Minority Adults: A Life Course Approach.
Journal of youth and adolescence, 2021

Country-level structural stigma, defined as prejudiced population attitudes and discriminatory legislation and policies, has been suggested to compromise the wellbeing of sexual minority adults. This study explores whether and how structural stigma might be associated with sexual minorities' school-based and adulthood experiences of victimization and adulthood life satisfaction. Using a sample of 55,263 sexual minority individuals (22% female; 53% 18-29 years old; 85% lesbian/gay, 15% bisexual) living across 28 European countries and a country-level index of structural stigma, results show that sexual minorities, especially men, reported school bullying in both higher- and lower-stigma countries. Higher rates of school bullying were found among sexual minorities living in higher-stigma countries when open about their identity at school. Past exposure to school bullying was associated with lower adulthood life satisfaction, an association partially explained by an increased risk of adulthood victimization. These findings suggest that sexual minorities living in higher-stigma countries might benefit from not being open about their sexual identity at school, despite previously established mental health costs of identity concealment, because of the reduced risk of school bullying and adverse adulthood experiences. These results provide one of the first indications that structural stigma is associated with sexual minority adults' wellbeing through both contemporaneous and historical experiences of victimization.
Examining the value of body gestures in social reward contexts.
NeuroImage, 2020

Brain regions associated with the processing of tangible rewards (such as money, food, or sex) are also involved in anticipating social rewards and avoiding social punishment. To date, studies investigating the neural underpinnings of social reward have presented feedback via static or dynamic displays of faces to participants. However, research demonstrates that participants find another type of social stimulus, namely, biological motion, rewarding as well, and exert effort to engage with this type of stimulus. Here we examine whether feedback presented via body gestures in the absence of facial cues also acts as a rewarding stimulus and recruits reward-related brain regions. To achieve this, we investigated the neural underpinnings of anticipating social reward and avoiding social disapproval presented via gestures alone, using a social incentive delay task. As predicted, the anticipation of social reward and avoidance of social disapproval engaged reward-related brain regions, including the nucleus accumbens, in a manner similar to previous studies' reports of feedback presented via faces and money. This study provides the first evidence that human body motion alone engages brain regions associated with reward processing in a similar manner to other social (i.e. faces) and non-social (i.e. money) rewards. The findings advance our understanding of social motivation in human perception and behavior.
"Practice makes perfect?" white matter microstructural characteristic predicts the degree of improvement in within-trial conflict processing across two weeks.
Brain imaging and behavior, 2019

Several studies have investigated the trait-like characteristics of conflict processing at different levels. Our study extends these findings by reporting a practice-based improvement in within-trial conflict processing across two sessions. Eighty-three participants performed the same flanker task on two occasions 2 weeks apart. A subset of 37 subjects also underwent diffusion tensor imaging (DTI) scanning the day before the first behavioral task. Despite the trait-like characteristics of conflict processing, within-trial conflict processing in the second behavioral session was significantly shorter than that in the first session, indicating a practice-based improvement in conflict processing. Furthermore, changes in within-trial conflict processing across the two sessions exhibited significant individual differences. Tract-based spatial statistics revealed that the improvement across two sessions was related to the axial diffusivity values in white matter regions, including the body and splenium of the corpus callosum, right superior and posterior corona radiate, and right superior longitudinal fasciculus. Subsequently, lasso regression with leave-one-out cross validation was used to assess the predictive ability of white matter microstructural characteristics in significant regions. The results showed that 61% of individual variability in the improvement in the within-trial conflict processing could be explained by variations in the axial diffusivity values in the four significant regions and the within-trial conflict processing in the first session. These results suggest that axonal morphology in the white tracts connecting conflict-related regions predicts the degree of within-trial conflict processing improvement across two sessions.
Painful trigeminal neuropathy associated with anti-Plexin D1 antibody.
Neurology(R) neuroimmunology & neuroinflammation, 2020

To determine whether anti-Plexin D1 antibody (Plexin D1-immunoglobulin G [IgG]), which is associated with limb and trunk neuropathic pain (NP) and binds to pain-conducting small unmyelinated dorsal root ganglion (DRG) neurons, exists in patients with idiopathic painful trigeminal neuropathy (IPTN) and whether Plexin D1-IgG binds to trigeminal ganglion (TG) neurons.
Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial.
The Lancet. Neurology, 2020

There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort.
A conserved PI(4,5)P2-binding domain is critical for immune regulatory function of DOCK8.
Life science alliance, 2021

DOCK8 is a Cdc42-specific guanine-nucleotide exchange factor that is essential for development and functions of various subsets of leukocytes in innate and acquired immune responses. Although DOCK8 plays a critical role in spatial control of Cdc42 activity during interstitial leukocyte migration, the mechanism remains unclear. We show that the DOCK homology region (DHR)-1 domain of DOCK8 binds specifically to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and is required for its recruitment to the plasma membrane. Structural and biochemical analyses reveal that DOCK8 DHR-1 domain consists of a C2 domain-like core with loops creating the upper surface pocket, where three basic residues are located for stereospecific recognition of phosphoinositides. Substitution of the two basic residues, K576 and R581, with alanine abolished PI(4,5)P2 binding in vitro, ablated the ability of DOCK8 to activate Cdc42 and support leukocyte migration in three-dimensional collagen gels. Dendritic cells carrying the mutation exhibited defective interstitial migration in vivo. Thus, our study uncovers a critical role of DOCK8 in coupling PI(4,5)P2 signaling with Cdc42 activation for immune regulation.
Automated brainstem volumetry can aid in the diagnostics of parkinsonian disorders.
Parkinsonism & related disorders, 2020

Separating progressive supranuclear palsy (PSP) from Parkinson's disease (PD) and multiple system atrophy (MSA) is often challenging in early disease but is important for appropriate management. Magnetic resonance imaging (MRI) can aid the diagnostics and manual 2D measurements are often used. However, new fully automatic brainstem volumetry could potentially be more accurate and increase availability of brainstem metrics.
Meta-analysis of generalized additive models in neuroimaging studies.
NeuroImage, 2021

Analyzing data from multiple neuroimaging studies has great potential in terms of increasing statistical power, enabling detection of effects of smaller magnitude than would be possible when analyzing each study separately and also allowing to systematically investigate between-study differences. Restrictions due to privacy or proprietary data as well as more practical concerns can make it hard to share neuroimaging datasets, such that analyzing all data in a common location might be impractical or impossible. Meta-analytic methods provide a way to overcome this issue, by combining aggregated quantities like model parameters or risk ratios. Most meta-analytic tools focus on parametric statistical models, and methods for meta-analyzing semi-parametric models like generalized additive models have not been well developed. Parametric models are often not appropriate in neuroimaging, where for instance age-brain relationships may take forms that are difficult to accurately describe using such models. In this paper we introduce meta-GAM, a method for meta-analysis of generalized additive models which does not require individual participant data, and hence is suitable for increasing statistical power while upholding privacy and other regulatory concerns. We extend previous works by enabling the analysis of multiple model terms as well as multivariate smooth functions. In addition, we show how meta-analytic p-values can be computed for smooth terms. The proposed methods are shown to perform well in simulation experiments, and are demonstrated in a real data analysis on hippocampal volume and self-reported sleep quality data from the Lifebrain consortium. We argue that application of meta-GAM is especially beneficial in lifespan neuroscience and imaging genetics. The methods are implemented in an accompanying R package metagam, which is also demonstrated.
Role for fatty acid amide hydrolase (FAAH) in the leptin-mediated effects on feeding and energy balance.
Proceedings of the National Academy of Sciences of the United States of America, 2018

Endocannabinoid signaling regulates feeding and metabolic processes and has been linked to obesity development. Several hormonal signals, such as glucocorticoids and ghrelin, regulate feeding and metabolism by engaging the endocannabinoid system. Similarly, studies have suggested that leptin interacts with the endocannabinoid system, yet the mechanism and functional relevance of this interaction remain elusive. Therefore, we explored the interaction between leptin and endocannabinoid signaling with a focus on fatty acid amide hydrolase (FAAH), the primary degradative enzyme for the endocannabinoid
Carbamazepine modulates the spatiotemporal activity in the dentate gyrus of rats and pharmacoresistant humans in vitro.
Brain and behavior, 2016

Human hippocampal tissue resected from pharmacoresistant epilepsy patients was investigated to study the effect of the antiepileptic drug CBZ (carbamazepine) and was compared to similar experiments in the hippocampus of control rats.
Experimental Therapeutic Trial Design for Pediatric Brain Tumors.
Journal of child neurology, 2016

Pediatric brain tumors are the leading cause of cancer-related death during childhood. Since the first pediatric brain tumor clinical trials, the field has seen improved outcomes in some, but not all tumor types. In the past few decades, a number of promising new therapeutic agents have emerged, yet only a few of these agents have been incorporated into clinical trials for pediatric brain tumors. In this review, the authors discuss the process of and challenges in pediatric clinical trial design; this will allow for highly efficient and effective clinical trials with appropriate endpoints to ensure rapid and safe investigation of novel therapeutics for children with brain tumors.
Dissecting the contribution of host genetics and the microbiome in complex behaviors.
Cell, 2021

The core symptoms of many neurological disorders have traditionally been thought to be caused by genetic variants affecting brain development and function. However, the gut microbiome, another important source of variation, can also influence specific behaviors. Thus, it is critical to unravel the contributions of host genetic variation, the microbiome, and their interactions to complex behaviors. Unexpectedly, we discovered that different maladaptive behaviors are interdependently regulated by the microbiome and host genes in the Cntnap2
An improved and simplified protocol to combine Golgi-Cox staining with immunofluorescence and transmission electron microscopy techniques.
Neurochemistry international, 2021

Approaches utilizing multiple analysis techniques on a single sample are highly desirable in research, especially to reduce the number of animals and obtain the maximum information. Golgi-Cox staining is a widely used method for characterizing axon and dendritic morphology and several attempts to combine this technique with immunofluorescence and transmission electron microscopy have been proposed. With few exceptions, most of the protocols were characterized by a high degree of complexity and low reproducibility. Here we show a simplified procedure of perfusion, fixation and staining of brain tissues that allows Golgi-Cox staining, immunofluorescence and transmission electron microscopy in the same sample, to obtain high-quality images with a low-cost procedure. The main novelty in this protocol is the possibility of performing Golgi-Cox staining after the perfusion and post-fixation of brain tissue with a buffered solution containing, not only formaldehyde, but also glutaraldehyde. This renders the tissue suitable for electron microscopy, but it is also compatible with immunofluorescence staining. This combined protocol can be used in most neuroscience laboratories as it does not require special equipment and skills. This protocol will be useful in a broad range of neuroscience topics to study morphological changes during brain development and plasticity in physiological and pathological conditions.