rudyvdbrink/CitationDatabase huggingface dataset:
Does infrared or ultraviolet light damage the lens?
Eye (London, England), 2016

In daylight, the human eye is exposed to long wavelength ultraviolet radiation (UVR), visible radiation and short wavelength infrared radiation (IRR). Almost all the UVR and a fraction of the IRR waveband, respectively, left over after attenuation in the cornea, is absorbed in the lens. The time delay between exposure and onset of biological response in the lens varies from immediate-to-short-to-late. After exposure to sunlight or artificial sources, generating irradiances of the same order of magnitude or slightly higher, biological damage may occur photochemically or thermally. Epidemiological studies suggest a dose-dependent association between short wavelength UVR and cortical cataract. Experimental data infer that repeated daily in vivo exposures to short wavelength UVR generate photochemically induced damage in the lens, and that short delay onset cataract after UVR exposure is photochemically induced. Epidemiology suggests that daily high-intensity short wavelength IRR exposure of workers, is associated with a higher prevalence of age-related cataract. It cannot be excluded that this effect is owing to a thermally induced higher denaturation rate. Recent experimental data rule out a photochemical effect of 1090 nm in the lens but other wavelengths in the near IRR should be investigated.
Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells.
Chembiochem : a European journal of chemical biology, 2018

The aberrant misfolding and subsequent conversion of monomeric protein into amyloid aggregates characterises many neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. These aggregates are highly heterogeneous in structure, generally of low abundance and typically smaller than the diffraction limit of light (≈250 nm). To overcome the challenges these characteristics pose to the study of endogenous aggregates formed in cells, we have developed a method to characterise them at the nanometre scale without the need for a conjugated fluorophore. Using a combination of DNA PAINT and an amyloid-specific aptamer, we demonstrate that this technique is able to detect and super-resolve a range of aggregated species, including those formed by α-synuclein and amyloid-β. Additionally, this method enables endogenous protein aggregates within cells to be characterised. We found that neuronal cells derived from patients with Parkinson's disease contain a larger number of protein aggregates than those from healthy controls.
The relationship between lamotrigine concentration and change in resting motor threshold in a rodent model of motor cortex stimulation.
Epilepsy research, 2009

The anticonvulsant sodium channel blocker lamotrigine (LTG) increases resting motor threshold (RMT) measured using transcranial magnetic stimulation (TMS) of the motor cortex in humans. However, studies suggest a weak relationship between LTG plasma concentration and increase in RMT. This undermines the possibility to use the technique to investigate the dose-efficacy relationship of lamotrigine or novel sodium channel blocking drugs. In order to investigate this relationship further, we have examined blood and brain concentrations of LTG in parallel with the drugs effects on RMT in a model in which electrical-stimulation is used to activate the motor cortex of propofol-anaesthetised rats. LTG (3-20 mg/kg s.c.) significantly increased RMT (P<0.001). There was a significant (P<0.01) positive correlation between LTG blood and brain concentration and increase in RMT; however correlation-coefficients were low (brain: r(2)=0.26 and blood r(2)=0.25), with evidence for non-responders, similar to human studies. The results show that the variation in RMT response is unlikely to be due to pharmacokinetic differences between subjects, and suggest that biological differences may underpin the variability. Understanding the source of this variability will be an important goal and, assuming some relationship between the effects of LTG on motor pathway excitability and the drugs anticonvulsant efficacy, could lead to a means to identify epilepsy patients that may be more likely to respond to treatment.
Rapid Head Movements in Common Marmoset Monkeys.
iScience, 2020

Gaze shifts, the directing of the eyes to an approaching predator, preferred food source, or potential mate, have universal biological significance for the survival of a species. Our knowledge of gaze behavior is based primarily on visually triggered responses, whereas head orientation triggered by auditory stimuli remains poorly characterized. Common marmoset (Callithrix jacchus) is a diurnal, small-bodied (∼350 g), New World monkey species, known for its rich behavioral repertoires during social interactions. We used a lightweight head tracking system to measure marmosets' reflexive head orientations toward a natural stimulus presented from behind. We found that marmoset could rotate its head at angular velocities above 1,000°/s and maintained target accuracy for a wide range of rotation amplitudes (up to 250°). This unusual, saccadic head orienting behavior offers opportunities for understanding the many biological factors that have shaped the evolution of sensorimotor controls of gaze orientation by the primate brain.
Risk Factors of Caregiver Burden Evolution, for Patients With Subjective Cognitive Decline or Neurocognitive Disorders: A Longitudinal Analysis.
Journal of the American Medical Directors Association, 2016

The identification of factors used to predict caregiver burden may help preventive care. This study aimed to assess the relationship between evolution of patients with subjective cognitive decline (SCD) or progressive neurocognitive disorder (NCD) and evolution of caregiver burden.
Targeting ATM ameliorates mutant Huntingtin toxicity in cell and animal models of Huntington's disease.
Science translational medicine, 2014

Age-related neurodegenerative disorders including Alzheimer's disease and Huntington's disease (HD) consistently show elevated DNA damage, but the relevant molecular pathways in disease pathogenesis remain unclear. One attractive gene is that encoding the ataxia-telangiectasia mutated (ATM) protein, a kinase involved in the DNA damage response, apoptosis, and cellular homeostasis. Loss-of-function mutations in both alleles of ATM cause ataxia-telangiectasia in children, but heterozygous mutation carriers are disease-free. Persistently elevated ATM signaling has been demonstrated in Alzheimer's disease and in mouse models of other neurodegenerative diseases. We show that ATM signaling was consistently elevated in cells derived from HD mice and in brain tissue from HD mice and patients. ATM knockdown protected from toxicities induced by mutant Huntingtin (mHTT) fragments in mammalian cells and in transgenic Drosophila models. By crossing the murine Atm heterozygous null allele onto BACHD mice expressing full-length human mHTT, we show that genetic reduction of Atm gene dosage by one copy ameliorated multiple behavioral deficits and partially improved neuropathology. Small-molecule ATM inhibitors reduced mHTT-induced death of rat striatal neurons and induced pluripotent stem cells derived from HD patients. Our study provides converging genetic and pharmacological evidence that reduction of ATM signaling could ameliorate mHTT toxicity in cellular and animal models of HD, suggesting that ATM may be a useful therapeutic target for HD.
Multifunctional Theranostic Graphene Oxide Nanoflakes as MR Imaging Agents with Enhanced Photothermal and Radiosensitizing Properties.
ACS applied bio materials, 2021

The integration of multiple therapeutic and diagnostic functions into a single nanoplatform for image-guided cancer therapy has been an emerging trend in nanomedicine. We show here that multifunctional theranostic nanostructures consisting of superparamagnetic iron oxide (SPIO) and gold nanoparticles (AuNPs) scaffolded within graphene oxide nanoflakes (GO-SPIO-Au NFs) can be used for dual photo/radiotherapy by virtue of the near-infrared (NIR) absorbance of GO for photothermal therapy (PTT) and the Z element radiosensitization of AuNPs for enhanced radiation therapy (RT). At the same time, this nanoplatform can also be detected by magnetic resonance (MR) imaging because of the presence of SPIO NPs. Using a mouse carcinoma model, GO-SPIO-Au NF-mediated combined PTT/RT exhibited a 1.85-fold and 1.44-fold higher therapeutic efficacy compared to either NF-mediated PTT or RT alone, respectively, resulting in a complete eradication of tumors. As a sensitive multifunctional theranostic platform, GO-SPIO-Au NFs appear to be a promising nanomaterial for enhanced cancer imaging and therapy.
The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice.
Journal of neurology, neurosurgery, and psychiatry, 2017

Cerebral amyloid angiopathy (CAA) has never been more relevant. The last 5 years have seen a rapid increase in publications and research in the field, with the development of new biomarkers for the disease, thanks to advances in MRI, amyloid positron emission tomography and cerebrospinal fluid biomarker analysis. The inadvertent development of CAA-like pathology in patients treated with amyloid-beta immunotherapy for Alzheimer's disease has highlighted the importance of establishing how and why CAA develops; without this information, the use of these treatments may be unnecessarily restricted. Our understanding of the clinical and radiological spectrum of CAA has continued to evolve, and there are new insights into the independent impact that CAA has on cognition in the context of ageing and intracerebral haemorrhage, as well as in Alzheimer's and other dementias. While the association between CAA and lobar intracerebral haemorrhage (with its high recurrence risk) is now well recognised, a number of management dilemmas remain, particularly when considering the use of antithrombotics, anticoagulants and statins. The Boston criteria for CAA, in use in one form or another for the last 20 years, are now being reviewed to reflect these new wide-ranging clinical and radiological findings. This review aims to provide a 5-year update on these recent advances, as well as a look towards future directions for CAA research and clinical practice.
A role for Bicaudal-D2 in radial cerebellar granule cell migration.
Nature communications, 2014

Bicaudal-D (BICD) belongs to an evolutionary conserved family of dynein adaptor proteins. It was first described in Drosophila as an essential factor in fly oogenesis and embryogenesis. Missense mutations in a human BICD homologue, BICD2, have been linked to a dominant mild early onset form of spinal muscular atrophy. Here we further examine the in vivo function of BICD2 in Bicd2 knockout mice. BICD2-deficient mice develop disrupted laminar organization of cerebral cortex and the cerebellum, pointing to impaired radial neuronal migration. Using astrocyte and granule cell specific inactivation of BICD2, we show that the cerebellar migration defect is entirely dependent upon BICD2 expression in Bergmann glia cells. Proteomics analysis reveals that Bicd2 mutant mice have an altered composition of extracellular matrix proteins produced by glia cells. These findings demonstrate an essential non-cell-autonomous role of BICD2 in neuronal cell migration, which might be connected to cargo trafficking pathways in glia cells.
Spiking Noise and Information Density of Neurons in Visual Area V2 of Infant Monkeys.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019

Encoding of visual information requires precisely timed spiking activity in the network of cortical neurons; irregular spiking can interfere with information processing especially for low-contrast images. The vision of newborn infants is impoverished. An infant's contrast sensitivity is low and the ability to discriminate complex stimuli is poor. The neural mechanisms that limit the visual capacities of infants are a matter of debate. Here we asked whether noisy spiking and/or crude information processing in visual cortex limit infant vision. Since neurons beyond the primary visual cortex (V1) have rarely been studied in neonates or infants, we focused on the firing pattern of neurons in visual area V2, the earliest extrastriate visual area of both male and female macaque monkeys (
Testosterone and sexual desire in healthy women and men.
Archives of sexual behavior, 2012

Sexual desire is typically higher in men than in women, with testosterone (T) thought to account for this difference as well as within-sex variation in desire in both women and men. However, few studies have incorporated both hormonal and social or psychological factors in studies of sexual desire. The present study addressed how three psychological domains (sexual-relational, stress-mood, body-embodiment) were related to links between T and sexual desire in healthy adults and whether dyadic and solitary desire showed associations with T. Participants (n = 196) were recruited as part of the Partnering, Physiology, and Health study, which had 105 men and 91 women who completed questionnaires and provided saliva for cortisol and T assays. T was positively linked to solitary desire in women, with masturbation frequency influencing this link. In contrast, T was negatively correlated with dyadic desire in women, but only when cortisol and perceived social stress were controlled. Replicating past findings, no significant correlations between T and desire in men were apparent, but these analyses showed that the null association remained even when psychological and confound variables were controlled. Men showed higher desire than women, but masturbation frequency rather than T influenced this difference. Results were discussed in terms of challenges to assumptions of clear links between T and desire, gendered approaches to T, and the unitarity of desire.
An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype.
Biological psychiatry, 2017

The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.
Diffusion magnetic resonance imaging-derived free water detects neurodegenerative pattern induced by interferon-γ.
Brain structure & function, 2020

Imaging biomarkers for immune activation may be valuable for early-stage detection, therapeutic testing, and research on neurodegenerative conditions. In the present study, we determined whether diffusion magnetic resonance imaging-derived free water signal is a sensitive marker for neuroinflammatory effects of interferon-gamma (Ifn-γ). Neonatal wild-type mice were injected in the cerebral ventricles with recombinant adeno-associated viruses expressing the inflammatory cytokine Ifn-γ. Groups of mice expressing Ifn-γ and age-matched controls were imaged at 1, 5 and 8 months. Mice deficient in Ifngr1
Growth and elongation of axons through mechanical tension mediated by fluorescent-magnetic bifunctional Fe
Journal of nanobiotechnology, 2020

The primary strategy to repair peripheral nerve injuries is to bridge the lesions by promoting axon regeneration. Thus, the ability to direct and manipulate neuronal cell axon regeneration has been one of the top priorities in the field of neuroscience. A recent innovative approach for remotely guiding neuronal regeneration is to incorporate magnetic nanoparticles (MNPs) into cells and transfer the resulting MNP-loaded cells into a magnetically sensitive environment to respond to an external magnetic field. To realize this intention, the synthesis and preparation of ideal MNPs is an important challenge to overcome.
Anorexigenic effects of estradiol in the medial preoptic area occur through membrane-associated estrogen receptors and metabotropic glutamate receptors.
Hormones and behavior, 2019

Activation of membrane-associated estrogen receptors (mER) decreases food and water intake in female rats. Additional studies suggest these effects are mediated, at least in part, by membrane-associated estrogen receptor alpha (ERα). Nevertheless, the critical site of action and the intracellular signaling required for the ingestive effects of ERα remain unclear. Estradiol given to the medial preoptic area (mPOA) decreases ingestive behaviors, and membrane-associated ERα has been shown to affect intracellular signaling through interactions with metabotropic glutamate receptor (mGluR) subtypes, but an involvement of this signaling pathway, in the mPOA, in ingestive behavior remains untested. To address these open questions, we first showed that activation of mER in the mPOA decreased both overnight food and water intake, and did so in a time course consistent with a genomic mechanism of action. Next, we tested the requirement of mGluR1a signaling in the mPOA for the anorexigenic and anti-dipsogenic effects of estradiol. As expected, estradiol in the mPOA decreased food intake, but only in the absence of an mGluR1a antagonist. The same was not true for estradiol effects on water intake, which were unaffected by an mGluR1a antagonist. These results suggest that estrogens require mGluR activation for at least some of their effects on ingestive behaviors, and indicate that the mPOA is a critical site of action. The results also reveal an interesting divergence in the estrogenic control of ingestive behavior by which mGluR signaling in the mPOA plays a role in the control of food intake, but not water intake.
Recent insights into the molecular genetics of dementia.
Trends in neurosciences, 2009

Our understanding of the molecular genetic basis of two common neurodegenerative dementias, Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), has greatly advanced in recent years. Progranulin mutations were identified as a major cause of FTLD and a potential susceptibility factor for other forms of dementia. In addition, through copy-number analyses of previously identified disease genes and the study of microRNA regulation in dementia, new evidence emerged to support the view that subtle variability in the expression of known disease proteins could increase the risk for sporadic forms of dementia. Finally, in late-onset AD populations, the first genome-wide association studies were performed and novel potential AD susceptibility genes reported. These exciting findings provide novel insights into the disease mechanisms underlying dementia and hold promise for the development of potential treatments.
The Reciprocity between Radiotherapy and Cancer Immunotherapy.
Clinical cancer research : an official journal of the American Association for Cancer Research, 2019

The clinical success of immune checkpoint inhibitors in treating metastatic and refractory cancers has generated significant interest in investigating their role in treating locally advanced diseases, thus requiring them to be combined with standard treatments in the hope of producing synergistic antitumor responses. Radiotherapy, in particular, has long been hypothesized to have actions complementary to those of immune checkpoint blockade, and a growing body of evidence indicates that cancer immunotherapy may also have radiosensitizing effects, which would provide unique benefit for locoregional treatments. Recent studies have demonstrated that when immune cells are activated by immunotherapeutics, they can reprogram the tumor microenvironment in ways that may potentially increase the radiosensitivity of the tumor. In this review, we highlight the evidence that supports reciprocal interactions between cancer immunotherapy and radiotherapy, where in addition to the traditional notion that radiation serves to enhance the activation of antitumor immunity, an alternative scenario also exists in which T-cell activation by cancer immunotherapy may sensitize tumors to radiation treatment through mechanisms that include normalization of the tumor vasculature and tissue hypoxia. We describe the empirical observations from preclinical models that support such effects and discuss their implications for future research and trial design.
DPYSL2 is a novel regulator for neural stem cell differentiation in rats: revealed by Panax notoginseng saponin administration.
Stem cell research & therapy, 2020

The limited neuronal differentiation of the endogenous or grafted neural stem cells (NSCs) after brain injury hampers the clinic usage of NSCs. Panax notoginseng saponins (PNS) were extensively used for their clinical value, such as in controlling blood pressure, blood glucose, and inhibiting neuronal apoptosis and enhancing neuronal protection, but whether or not it exerts an effect in promoting neuronal differentiation of the endogenous NSCs is completely unclear and the potential underlying mechanism requires further exploration.
Dietary, environmental, and genetic risk factors of Extensive Macular Atrophy with Pseudodrusen, a severe bilateral macular atrophy of middle-aged patients.
Scientific reports, 2018

EMAP (Extensive Macular Atrophy with Pseudodrusen) is a maculopathy we recently described that shares pseudodrusen and geographic atrophy with Age-related Macular Disease (AMD). EMAP differs from AMD by an earlier age of onset (50-55 years) and a characteristic natural history comprising a night blindness followed by a severe visual loss. In a prospective case-control study, ten referral centers included 115 EMAP (70 women, 45 men) patients and 345 matched controls to appraise dietary, environmental, and genetic risk factors. The incidence of EMAP (mean 2.95/1.10
A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers.
Neurology, 2016

Biomarkers have become an essential component of Alzheimer disease (AD) research and because of the pervasiveness of AD pathology in the elderly, the same biomarkers are used in cognitive aging research. A number of current issues suggest that an unbiased descriptive classification scheme for these biomarkers would be useful. We propose the "A/T/N" system in which 7 major AD biomarkers are divided into 3 binary categories based on the nature of the pathophysiology that each measures. "A" refers to the value of a β-amyloid biomarker (amyloid PET or CSF Aβ42); "T," the value of a tau biomarker (CSF phospho tau, or tau PET); and "N," biomarkers of neurodegeneration or neuronal injury ([(18)F]-fluorodeoxyglucose-PET, structural MRI, or CSF total tau). Each biomarker category is rated as positive or negative. An individual score might appear as A+/T+/N-, or A+/T-/N-, etc. The A/T/N system includes the new modality tau PET. It is agnostic to the temporal ordering of mechanisms underlying AD pathogenesis. It includes all individuals in any population regardless of the mix of biomarker findings and therefore is suited to population studies of cognitive aging. It does not specify disease labels and thus is not a diagnostic classification system. It is a descriptive system for categorizing multidomain biomarker findings at the individual person level in a format that is easy to understand and use. Given the present lack of consensus among AD specialists on terminology across the clinically normal to dementia spectrum, a biomarker classification scheme will have broadest acceptance if it is independent from any one clinically defined diagnostic scheme.