rudyvdbrink/CitationDatabase huggingface dataset:
Anatomy of an iron-sulfur cluster scaffold protein: Understanding the determinants of [2Fe-2S] cluster stability on IscU.
Biochimica et biophysica acta, 2015

Protein-bound iron sulfur clusters are prosthetic groups involved in several metabolic pathways. Understanding how they interact with the host protein and which factors influence their stability is therefore an important goal in biology. Here, we have addressed this question by studying the determinants of the 2Fe-2S cluster stability in the IscU/Isu protein scaffold. Through a detailed computational study based on a mixed quantum and classical mechanics approach, we predict that the simultaneous presence of two conserved residues, D39 and H105, has a conflicting role in cluster coordination which results in destabilizing cluster-loaded IscU/Isu according to a 'tug-of-war' mechanism. The effect is absent in the D39A mutant already known to host the cluster more stably. Our theoretical conclusions are directly supported by experimental data, also obtained from the H105A mutant, which has properties intermediate between the wild-type and the D39A mutant. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases.
Evaluation of enzymatic and non-enzymatic antioxidants in seminal plasma of men with genitourinary infections, varicocele and idiopathic infertility.
Andrology, 2016

This study was aimed to assess the antioxidant enzymatic and non-enzymatic compounds in semen of infertile men. Seventy-four infertile patients were grouped according to their clinical diagnosis: genitourinary infection, varicocele, idiopathic infertility. Semen samples of fertile men represent the control. Semen characteristics were evaluated by light and transmission electron microscopy (TEM). TEM data was quantified with a mathematical formula, which provides numerical scores. Spectrophotometric and HPLC methods were used to measure the amount of reduced (GSH), oxidised glutathione (GSSG), ascorbic acid (AA) and malondialdehyde (MDA, marker of lipid peroxidation) and the activity of glutathione reductase, catalase (CAT), glutathione peroxidase. Infertile groups showed significantly decreased values of sperm parameters vs.
Neuroprotective effects of mitochondria-targeted curcumin against rotenone-induced oxidative damage in cerebellum of mice.
Journal of biochemical and molecular toxicology, 2020

The present study investigated the protective effect of curcumin and mitochondrial-targeted curcumin (MTC) in rotenone-induced cerebellar toxicity in mice. Treatment of rotenone in mice significantly shortened the stride length for both forelimb and hind-limb and increased fore-paws and hind-limb base width. Co-treatment of curcumin and MTC with rotenone improved the walking pattern. A significant increase in lipid peroxidation, nitric oxide and decreased activity of AChE, reduced glutathione, superoxide dismutase and catalase were observed in rotenone-treated mice while co-treatment of curcumin and MTC with rotenone significantly increased AChE activity and protected against rotenone-induced oxidative damage. Rotenone exposed mice showed irregular, damaged Purkinje cells and perineuronal vacuolation while co-treatment of curcumin and MTC with rotenone protected against rotenone-induced cellular damage in these cells. The result exhibits that both curcumin and MTC showed protective effects against rotenone-induced cerebellar toxicity in mice and MTC is more effective than curcumin.
Serial order working memory and numerical ordinal processing share common processes and predict arithmetic abilities.
The British journal of developmental psychology, 2018

Recent studies have demonstrated that both ordinal number processing and serial order working memory (WM) abilities predict calculation achievement. This raises the question of shared ordinal processes operating in both numerical and WM domains. We explored this question by assessing the interrelations between numerical ordinal, serial order WM, and arithmetic abilities in 102 7- to 9-year-old children. We replicated previous studies showing that ordinal numerical judgement and serial order WM predict arithmetic abilities. Furthermore, we showed that ordinal numerical judgement abilities predict arithmetic abilities after controlling for serial order WM abilities while the relationship between serial order WM and arithmetic abilities was mediated by numerical ordinal judgement performance. We discuss these results in the light of recent theoretical frameworks considering that numerical ordinal codes support the coding of order information in verbal WM. Statement of contribution What is already known on this subject? Numerical ordinal processes predict mathematical achievement in adults. Order WM processing predicts first mathematical abilities. What the present study adds? Numerical ordinal processes predict mathematical achievement in children and independently of order WM. The link between order WM and mathematical abilities was mediated by long-term ordinal processes.
Interleaved lexical and audiovisual information can retune phoneme boundaries.
Attention, perception & psychophysics, 2020

To adapt to situations in which speech perception is difficult, listeners can adjust boundaries between phoneme categories using perceptual learning. Such adjustments can draw on lexical information in surrounding speech, or on visual cues via speech-reading. In the present study, listeners proved they were able to flexibly adjust the boundary between two plosive/stop consonants, /p/-/t/, using both lexical and speech-reading information and given the same experimental design for both cue types. Videos of a speaker pronouncing pseudo-words and audio recordings of Dutch words were presented in alternating blocks of either stimulus type. Listeners were able to switch between cues to adjust phoneme boundaries, and resulting effects were comparable to results from listeners receiving only a single source of information. Overall, audiovisual cues (i.e., the videos) produced the stronger effects, commensurate with their applicability for adapting to noisy environments. Lexical cues were able to induce effects with fewer exposure stimuli and a changing phoneme bias, in a design unlike most prior studies of lexical retuning. While lexical retuning effects were relatively weaker compared to audiovisual recalibration, this discrepancy could reflect how lexical retuning may be more suitable for adapting to speakers than to environments. Nonetheless, the presence of the lexical retuning effects suggests that it may be invoked at a faster rate than previously seen. In general, this technique has further illuminated the robustness of adaptability in speech perception, and offers the potential to enable further comparisons across differing forms of perceptual learning.
Corollary discharge in precerebellar nuclei of sleeping infant rats.
eLife, 2018

In week-old rats, somatosensory input arises predominantly from external stimuli or from sensory feedback (reafference) associated with myoclonic twitches during active sleep. A previous study suggested that the brainstem motor structures that produce twitches also send motor copies (or corollary discharge, CD) to the cerebellum. We tested this possibility by recording from two precerebellar nuclei-the inferior olive (IO) and lateral reticular nucleus (LRN). In most IO and LRN neurons, twitch-related activity peaked sharply around twitch onset, consistent with CD. Next, we identified twitch-production areas in the midbrain that project independently to the IO and LRN. Finally, we blocked calcium-activated slow potassium (SK) channels in the IO to explain how broadly tuned brainstem motor signals can be transformed into precise CD signals. We conclude that the precerebellar nuclei convey a diversity of sleep-related neural activity to the developing cerebellum to enable processing of convergent input from CD and reafferent signals.
Brain bioenergetics during resting wakefulness are related to neurobehavioral deficits in severe obstructive sleep apnea: a 31P magnetic resonance spectroscopy study.
Sleep, 2018

Obstructive sleep apnea (OSA) is a well-established cause of impaired daytime functioning. However, there is a complex inter-individual variability in neurobehavioral performance in OSA patients. We previously reported compromised brain bioenergetics during apneic sleep in severe OSA. In this study, we investigate whether brain bioenergetics during resting wakefulness are related to neurobehavioral performance.
MRI-compatible pneumatic stimulator for sensorimotor mapping.
Journal of neuroscience methods, 2019

Two major concerns with respect to task-based motor functional magnetic resonance imaging (fMRI) are inadequate participants' performance as well as intra- and inter-subject variability in execution of the motor action.
NPY modulates PYY function in the regulation of energy balance and glucose homeostasis.
Diabetes, obesity & metabolism, 2012

Both the neuronal-derived neuropeptide Y (NPY) and the gut hormone peptide YY (PYY) have been implicated in the regulation of energy balance and glucose homeostasis. However, despite similar affinities for the same Y receptors, the co-ordinated actions of these two peptides in energy and glucose homeostasis remain largely unknown.
What is a gesture? A meaning-based approach to defining gestural repertoires.
Neuroscience and biobehavioral reviews, 2017

Current systems of categorising ape gestures are typically subjective, relying on human intuition. We have systematised the features on which categorization depends (movement; body part; one/both limbs; use of detached object; rhythmic repetition; contact with recipient), showing that a potential repertoire of over 1000 gestures is physically possible, as large as the lexicon of some languages. In contrast, little more than a tenth of these gestures is used in chimpanzee communication. The striking overlaps in repertoire found between populations and even species of great ape are evidently not a result of a restricted set of possible gestures. Using the reactions of signallers to identify which gestures are intended to be different by the apes themselves, we revised the current classification, making some new distinctions and abolishing others previously considered important, giving a final repertoire of 81. A small number of gestures are used deictically, such that the recipient must pay attention to specific locations to satisfy the signaller; raising the possibility of a stepping-stone to the evolution of reference.
Disease-specific databases: why we need them and some recommendations from the Human Variome Project Meeting, May 28, 2011.
American journal of medical genetics. Part A, 2012

The need for Locus-Specific Databases, with disease-specific experts and curators, is an essential ingredient in a process to enable the benefits of the advances in sequencing and mutational analysis to be realized across the genome. Next generation sequencing provides both astounding opportunities and challenges, especially for genetic counsellors. An approach coordinated at a genome wide, international level, supported by well-organized disease-specific respected organizations is a model most likely to be successful, but committed resourceful professionals working in local poorly resourced environments can make valuable contributions that can grow. Bioinformatic tools to sift and integrate multiple domains of information are being developed, and play a major part in meeting the challenges. Regulation of providers, including a requirement for them to submit mutational information to central databases, also should assist to reach the goals needed to realize the opportunities. There is also a need to agree on governance of Locus-Specific Databases (LSDBs) at an international level, and for adequate international funding to support this need, to ensure humanity reaps the benefits of the current molecular genetic revolution. The Human Variome Project offers this, working also with the other major initiatives with similar objectives. This report concludes with Recommendations for the Human Variome Project stemming from the presentations and discussions at the meeting.
Central Activation of Alpha7 Nicotinic Signaling Attenuates LPS-Induced Neuroinflammation and Sickness Behavior in Adult but Not in Aged Animals.
Molecules (Basel, Switzerland), 2021

We previously reported that lipopolysaccharide (LPS) challenge caused microglial-mediated neuroinflammation and sickness behavior that was amplified in aged mice. As α7 nAChRs are implicated in the "Cholinergic anti-inflammatory pathway", we aimed to determine how α7 nAChR stimulation modulates microglial phenotype in an LPS-induced neuroinflammation model in adult and aged mice. For this, BALB/c mice were injected intraperitoneally with LPS (0.33 mg/kg) and treated with the α7 nAChR agonist PNU282987, using different administration protocols. LPS challenge reduced body weight and induced lethargy and social withdrawal in adult mice. Peripheral (intraperitoneal) co-administration of the α7 nAChR agonist PNU282987 with LPS, attenuated body weight loss and sickness behavior associated with LPS challenge in adult mice, and reduced microglial activation with suppression of IL-1β and TNFα mRNA levels. Furthermore, central (intracerebroventricular) administration of the α7 nAChR agonist, even 2 h after LPS injection, attenuated the decrease in social exploratory behavior and microglial activation induced by peripheral administration of LPS, although this recovery was not achieved if activation of α7 nAChRs was performed peripherally. Finally, we observed that the positive results of central activation of α7 nAChRs were lost in aged mice. In conclusion, we provide evidence that stimulation of α7 nAChR signaling reduces microglial activation in an in vivo LPS-based model, but this cholinergic-dependent regulation seems to be dysfunctional in microglia of aged mice.
Intracerebral Hemorrhage: A Common yet Disproportionately Deadly Stroke Subtype.
Mayo Clinic proceedings, 2021

Spontaneous intracerebral hemorrhage (ICH) is a medical emergency and is disproportionately associated with higher mortality and long-term disability compared with ischemic stroke. The phrase "time is brain" was derived for patients with large vessel occlusion ischemic stroke in which approximately 1.9 million neurons are lost every minute. Similarly, this statement holds true for ICH patients due to a high volume of neurons that are damaged at initial onset and during hematoma expansion. Most cases of spontaneous ICH pathophysiologically stem from chronic hypertension and rupture of small perforating vessels off of larger cerebral arteries supplying deep brain structures, with cerebral amyloid angiopathy being another cause for lobar hemorrhages in older patients. Optimal ICH medical management strategies include timely diagnosis, aggressive blood pressure control, correction of underlying coagulopathy defects if present, treatment of cerebral edema, and continuous assessment for possible surgical intervention. Current strategies in the surgical management of ICH include newly developed minimally invasive techniques for hematoma evacuation, with the goal of mitigating injury to fiber tracts while accessing the clot. We review evidence-based medical and surgical management of spontaneous ICH with the overall goal of reducing neurologic injury and optimizing functional outcome.
Decoding the Information Contained in Fluorophore Radiation Patterns.
ACS nano, 2018

Dipole radiation patterns change when a fluorescent molecule comes close to the boundary between media of different refractive indices. Near-interface molecules emit mostly into the higher-index medium, predominantly around the critical angle. The radiation pattern encodes information about the emitter distance, orientation, and the refractive index of the embedding medium. Analyses of the supercritical angle fluorescence on pupil plane images can retrieve this information and have been applied both for refractometry with subcellular resolution and for the detection of metabolically active cancerous cells. In this issue of ACS Nano, Ferdman et al. employ this strategy in a label-free assay for detecting single bacteria, based on measuring the refractive-index change produced by bacterial growth in a fluorophore-coated microfluidic channel.
Insulin regulates POMC neuronal plasticity to control glucose metabolism.
eLife, 2018

Hypothalamic neurons respond to nutritional cues by altering gene expression and neuronal excitability. The mechanisms that control such adaptive processes remain unclear. Here we define populations of POMC neurons in mice that are activated or inhibited by insulin and thereby repress or inhibit hepatic glucose production (HGP). The proportion of POMC neurons activated by insulin was dependent on the regulation of insulin receptor signaling by the phosphatase TCPTP, which is increased by fasting, degraded after feeding and elevated in diet-induced obesity. TCPTP-deficiency enhanced insulin signaling and the proportion of POMC neurons activated by insulin to repress HGP. Elevated TCPTP in POMC neurons in obesity and/or after fasting repressed insulin signaling, the activation of POMC neurons by insulin and the insulin-induced and POMC-mediated repression of HGP. Our findings define a molecular mechanism for integrating POMC neural responses with feeding to control glucose metabolism.
It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis.
Stroke and vascular neurology, 2019

There is concern that blood pressure (BP) lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis. We assessed the effect of glyceryl trinitrate (GTN) in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke (ENOS) Trial.
TBCE Mutations Cause Early-Onset Progressive Encephalopathy with Distal Spinal Muscular Atrophy.
American journal of human genetics, 2016

Tubulinopathies constitute a family of neurodevelopmental/neurodegenerative disorders caused by mutations in several genes encoding tubulin isoforms. Loss-of-function mutations in TBCE, encoding one of the five tubulin-specific chaperones involved in tubulin folding and polymerization, cause two rare neurodevelopmental syndromes, hypoparathyroidism-retardation-dysmorphism and Kenny-Caffey syndrome. Although a missense mutation in Tbce has been associated with progressive distal motor neuronopathy in the pmn/pmn mice, no similar degenerative phenotype has been recognized in humans. We report on the identification of an early-onset and progressive neurodegenerative encephalopathy with distal spinal muscular atrophy resembling the phenotype of pmn/pmn mice and caused by biallelic TBCE mutations, with the c.464T>A (p.Ile155Asn) change occurring at the heterozygous/homozygous state in six affected subjects from four unrelated families originated from the same geographical area in Southern Italy. Western blot analysis of patient fibroblasts documented a reduced amount of TBCE, suggestive of rapid degradation of the mutant protein, similarly to what was observed in pmn/pmn fibroblasts. The impact of TBCE mutations on microtubule polymerization was determined using biochemical fractionation and analyzing the nucleation and growth of microtubules at the centrosome and extracentrosomal sites after treatment with nocodazole. Primary fibroblasts obtained from affected subjects displayed a reduced level of polymerized α-tubulin, similarly to tail fibroblasts of pmn/pmn mice. Moreover, markedly delayed microtubule re-polymerization and abnormal mitotic spindles with disorganized microtubule arrangement were also documented. Although loss of function of TBCE has been documented to impact multiple developmental processes, the present findings provide evidence that hypomorphic TBCE mutations primarily drive neurodegeneration.
Functional Connectivity Changes of Key Regions for Motor Initiation in Parkinson's Disease.
Cerebral cortex (New York, N.Y. : 1991), 2019

Akinesia, a cardinal symptom of Parkinson's disease, has been linked to abnormal activation in putamen and posterior medial frontal cortex (pMFC). However, little is known whether clinical severity of akinesia is linked to dysfunctional connectivity of these regions. Using a seed-based approach, we here investigated resting-state functional connectivity (RSFC) of putamen, pMFC and primary motor cortex (M1) in 60 patients with Parkinson's disease on regular medication and 72 healthy controls. We found that in patients putamen featured decreases of connectivity for a number of cortical and subcortical areas engaged in sensorimotor and cognitive processing. In contrast, the pMFC showed reduced connectivity with a more focal cortical network involved in higher-level motor-cognition. Finally, M1 featured a selective disruption of connectivity in a network specifically connected with M1. Correlating clinical impairment with connectivity changes revealed a relationship between akinesia and reduced RSFC between pMFC and left intraparietal lobule (IPL). Together, the present study demonstrated RSFC decreases in networks for motor initiation and execution in Parkinson's disease. Moreover, results suggest a relationship between pMFC-IPL decoupling and the manifestation of akinetic symptoms.
Sperm-associated antigen 16 is a novel target of the humoral autoimmune response in multiple sclerosis.
Journal of immunology (Baltimore, Md. : 1950), 2014

We have previously identified eight novel autoantibody targets in the cerebrospinal fluid of multiple sclerosis (MS) patients, including sperm-associated Ag 16 (SPAG16). In the current study, we further investigated the autoantibody response against SPAG16-a protein with unknown function in the CNS-and its expression in MS pathology. Using isoelectric focusing, we detected SPAG16-specific oligoclonal bands in the cerebrospinal fluid of 5 of 23 MS patients (22%). Analysis of the anti-SPAG16 Ab reactivity in the plasma of a total of 531 donors using ELISA demonstrated significantly elevated anti-SPAG16 Ab levels (p = 0.002) in 32 of 153 MS patients (21%) compared with all other control groups with 95% specificity for the disease. To investigate the pathologic relevance of anti-SPAG16 Abs in vivo, anti-SPAG16 Abs were injected in mice with experimental autoimmune encephalomyelitis, resulting in a significant disease exacerbation. Finally, we demonstrated a consistent upregulation of SPAG16 in MS brain and experimental autoimmune encephalomyelitis spinal cord lesions, more specifically in reactive astrocytes. We conclude that SPAG16 is a novel autoantibody target in a subgroup of MS patients and in combination with other diagnostic criteria, elevated levels of anti-SPAG16 Abs could be used as a biomarker for diagnosis. Furthermore, the pathologic relevance of anti-SPAG16 Abs was shown in vivo.