rudyvdbrink/CitationDatabase huggingface dataset:
Hyperactivated PTP1B phosphatase in parvalbumin neurons alters anterior cingulate inhibitory circuits and induces autism-like behaviors.
Nature communications, 2020

Individuals with autism spectrum disorder (ASD) have social interaction deficits and difficulty filtering information. Inhibitory interneurons filter information at pyramidal neurons of the anterior cingulate cortex (ACC), an integration hub for higher-order thalamic inputs important for social interaction. Humans with deletions including LMO4, an endogenous inhibitor of PTP1B, display intellectual disabilities and occasionally autism. PV-Lmo4KO mice ablate Lmo4 in PV interneurons and display ASD-like repetitive behaviors and social interaction deficits. Surprisingly, increased PV neuron-mediated peri-somatic feedforward inhibition to the pyramidal neurons causes a compensatory reduction in (somatostatin neuron-mediated) dendritic inhibition. These homeostatic changes increase filtering of mediodorsal-thalamocortical inputs but reduce filtering of cortico-cortical inputs and narrow the range of stimuli ACC pyramidal neurons can distinguish. Simultaneous ablation of PTP1B in PV-Lmo4KO neurons prevents these deficits, indicating that PTP1B activation in PV interneurons contributes to ASD-like characteristics and homeostatic maladaptation of inhibitory circuits may contribute to deficient information filtering in ASD.
Luminal polyethylene glycol solution delays the onset of preservation injury in the human intestine.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2021

The organ damage incurred during the cold storage (CS) of intestinal grafts has short and long-term consequences. Animal studies suggest that additional luminal preservation (LP) with polyethylene glycol (PEG) may alleviate this damage. This study aims to validate these findings using human intestines. Ileal segments, perfused intravascularly with IGL-1 solution, were procured from 32 multiorgan donors and divided into two parts: one containing a PEG 3350-based solution introduced luminally (LP group) and another one without luminal treatment (control). Sampling was performed after 4 h, 8 h, 14 h, and 24 h of CS. Histology was assessed using the Chiu/Park score. Tight junctions (TJ), several inflammatory markers, and transcription factors were examined by immunofluorescence, ddPCR, and western blot. Tissue water content (edema) was also measured. Apoptotic activity was assessed with caspase -2, -3, and -9 assays. LP significantly lowered mucosal injury at all time points. Redistribution of TJ proteins occurred earlier and more severely in the control group. After 24 h of CS, LP intestines showed an emerging unfolding protein response. Increased caspase-3 and -9 activity was found in the control group. The current results indicate that luminal PEG is safe and effective in reducing damage to the intestinal epithelium during CS.
Training and plasticity of working memory.
Trends in cognitive sciences, 2010

Working memory (WM) capacity predicts performance in a wide range of cognitive tasks. Although WM capacity has been viewed as a constant trait, recent studies suggest that it can be improved by adaptive and extended training. This training is associated with changes in brain activity in frontal and parietal cortex and basal ganglia, as well as changes in dopamine receptor density. Transfer of the training effects to non-trained WM tasks is consistent with the notion of training-induced plasticity in a common neural network for WM. The observed training effects suggest that WM training could be used as a remediating intervention for individuals for whom low WM capacity is a limiting factor for academic performance or in everyday life.
mGlu5-mediated signalling in developing astrocyte and the pathogenesis of autism spectrum disorders.
Current opinion in neurobiology, 2018

Astrocytes, the largest glial population in human and murine brains, are crucial to the regulation of synaptic connectivity. During the first three weeks of postnatal development, immature astrocytes express mGlu5 and expands several fold while undergoing a transition towards their mature phase. Although mGlu5-mediated signalling in astrocyte functions has been extensively studied in the last decades, whether this signalling is implicated in the mechanisms governing their development, as well as the effects of dysregulated astrocytic development on neurodevelopmental disorders, are still unclear. The aim of this review is to examine what is known about the mGlu5-mediated signalling in the developing astrocytes and its possible contribution to the pathophysiology of autism spectrum disorders.
Recipe for a Healthy Gut: Intake of Unpasteurised Milk Is Associated with Increased 
Nutrients, 2020

The gut microbiota plays a role in gut-brain communication and can influence psychological functioning. Diet is one of the major determinants of gut microbiota composition. The impact of unpasteurised dairy products on the microbiota is unknown. In this observational study, we investigated the effect of a dietary change involving intake of unpasteurised dairy on gut microbiome composition and psychological status in participants undertaking a residential 12-week cookery course on an organic farm.
Slowly progressive anti-neutrophil cytoplasmic antibody-associated renal vasculitis: clinico-pathological characterization and outcome.
Clinical kidney journal, 2021

Although rapidly progressive glomerulonephritis is the main renal phenotype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), slow renal disease progression is sometimes observed. These forms have been rarely discussed; we analysed their prevalence, clinico-pathological characteristics and outcome.
Microglia and sexual differentiation of the developing brain: A focus on extrinsic factors.
Glia, 2020

Microglia, the innate immune cells of the brain, have recently been removed from the position of mere sentinels and promoted to the role of active sculptors of developing circuits and cells. Alongside their functions in normal brain development, microglia coordinate sexual differentiation of the brain, a set of processes which vary by region and endpoint like that of microglia function itself. In this review, we highlight the ways microglia are both targets and drivers of brain sexual differentiation. We examine the factors that may drive sex differences in microglia, with a special focus on how changing microenvironments in the developing brain dictate microglia phenotypes and discuss how their diverse functions sculpt lasting sex-specific changes in the brain. Finally, we consider how sex-specific early life environments contribute to epigenetic programming and lasting sex differences in microglia identity.
Cocaine-elicited imbalances in ventromedial prefrontal cortex Homer1 versus Homer2 expression: implications for relapse.
Addiction biology, 2015

Withdrawal from a history of extended access to self-administered cocaine produces a time-dependent intensification of drug seeking, which might relate to a cocaine-induced imbalance in the relative expression of constitutively expressed Homer1 versus Homer2 isoforms within the ventromedial aspect of the prefrontal cortex (vmPFC). Thus, we employed immunoblotting to examine the relation between cue-reinforced lever pressing at 3- versus 30-day withdrawal from a 10-day history of extended access (6 hours/day) to intravenous cocaine (0.25 mg/infusion) or saline (Sal6h), and the expression of Homer1b/c and Homer2a/b within the vmPFC versus the more dorsomedial aspect of this structure (dmPFC). Behavioral studies employed adeno-associated virus (AAV) vectors to reverse cocaine-elicited changes in the relative expression of Homer1 versus Homer2 isoforms and tested animals for cocaine prime-, and cue-induced responding following extinction training. Cocaine self-administration elevated both Homer1b/c and Homer2a/b levels within the vmPFC at 3-day withdrawal, and the rise in Homer2a/b persisted for at least 30 days. dmPFC Homer levels did not change as a function of self-administration history. Reversing the relative increase in Homer2 versus Homer1 expression via Homer1c overexpression or Homer2b knockdown failed to influence cue-reinforced lever pressing when animals were tested in a drug-free state, but both AAV treatments prevented cocaine-primed reinstatement of lever-pressing behavior. These data suggest that a cocaine-elicited imbalance in the relative expression of constitutively expressed Homer2 versus Homer1 within the vmPFC is necessary for the capacity of cocaine to reinstate drug-seeking behavior, posing drug-induced changes in vmPFC Homer expression as a molecular trigger contributing to drug-elicited relapse.
Discovering the Italian phenotype of cerebral amyloid angiopathy (CAA): the SENECA project.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2020

Cerebral amyloid angiopathy (CAA) is one of the major types of cerebral small vessel disease, and a leading cause of spontaneous intracerebral hemorrhage and cognitive decline in elderly patients. Although increasingly detected, a number of aspects including the pathophysiology, the clinical and neuroradiological phenotype, and the disease course are still under investigation. The incomplete knowledge of the disease limits the implementation of evidence-based guidelines on patient's clinical management and the development of treatments able to prevent or reduce disease progression. The SENECA (SEarchiNg biomarkErs of Cerebral Angiopathy) project is the first Italian multicenter cohort study aimed at better defining the disease natural history and identifying clinical and neuroradiological markers of disease progression. By a multidisciplinary approach and the collection of a large and well-phenotyped series and biorepository of CAA patients, the study is ultimately expected to improve the diagnosis and the knowledge of CAA pathophysiological mechanisms.
Allosteric inhibitor of β-catenin selectively targets oncogenic Wnt signaling in colon cancer.
Scientific reports, 2020

Abnormal regulation of β-catenin initiates an oncogenic program that serves as a main driver of many cancers. Albeit challenging, β-catenin is an attractive drug target due to its role in maintenance of cancer stem cells and potential to eliminate cancer relapse. We have identified C2, a novel β-catenin inhibitor, which is a small molecule that binds to a novel allosteric site on the surface of β-catenin. C2 selectively inhibits β-catenin, lowers its cellular load and significantly reduces viability of β-catenin-driven cancer cells. Through direct binding to β-catenin, C2 renders the target inactive that eventually activates proteasome system for its removal. Here we report a novel pharmacologic approach for selective inhibition of β-catenin via targeting a cryptic allosteric modulation site. Our findings may provide a new perspective for therapeutic targeting of β-catenin.
Efficacy and acceptability of transcranial direct current stimulation (tDCS) for major depressive disorder: An individual patient data meta-analysis.
Progress in neuro-psychopharmacology & biological psychiatry, 2020

We evaluated the efficacy and acceptability of transcranial direct current stimulation (tDCS) for treating acute depressive episodes using individual patient data that provide more precise estimates than aggregate data meta-analysis. A systematic review of placebo-controlled trials on tDCS as only intervention was conducted until December-2018. Data from each study was collated to estimate odds ratio (OR) and number needed to treat (NNT) of response and remission, and depression improvement. Endpoints were pre-determined. Nine eligible studies (572 participants), presenting moderate/high certainty of evidence, were included. Active tDCS was significantly superior to sham for response (30.9% vs. 18.9% respectively; OR = 1.96, 95%CI [1.30-2.95], NNT = 9), remission (19.9% vs. 11.7%, OR = 1.94 [1.19-3.16], NNT = 13) and depression improvement (effect size of β = 0.31, [0.15-0.47]). Moreover, continuous clinical improvement was observed even after the end of acute tDCS treatment. There were no differences in all-cause discontinuation rates and no predictors of response were identified. To conclude, active tDCS was statistically superior to sham in all outcomes, although its clinical effects were moderate.
Generation and Characterization of Novel Monoclonal Antibodies Targeting p62/sequestosome-1 Across Human Neurodegenerative Diseases.
Journal of neuropathology and experimental neurology, 2020

Human neurodegenerative diseases can be characterized as disorders of protein aggregation. As a key player in cellular autophagy and the ubiquitin proteasome system, p62 may represent an effective immunohistochemical target, as well as mechanistic operator, across neurodegenerative proteinopathies. In this study, 2 novel mouse-derived monoclonal antibodies 5G3 and 2A5 raised against residues 360-380 of human p62/sequestosome-1 were characterized via immunohistochemical application upon human tissues derived from cases of C9orf72-expansion spectrum diseases, Alzheimer disease, progressive supranuclear palsy, Lewy body disease, and multiple system atrophy. 5G3 and 2A5 reliably highlighted neuronal dipeptide repeat, tau, and α-synuclein inclusions in a distribution similar to a polyclonal antibody to p62, phospho-tau antibodies 7F2 and AT8, and phospho-α-synuclein antibody 81A. However, antibodies 5G3 and 2A5 consistently stained less neuropil structures, such as tau neuropil threads and Lewy neurites, while 2A5 marked fewer glial inclusions in progressive supranuclear palsy. Both 5G3 and 2A5 revealed incidental astrocytic tau immunoreactivity in cases of Alzheimer disease and Lewy body disease with resolution superior to 7F2. Through their unique ability to highlight specific types of pathological deposits in neurodegenerative brain tissue, these novel monoclonal p62 antibodies may provide utility in both research and diagnostic efforts.
Flunarizine in migraine-related headache prevention: results from 200 patients treated in the UK.
European journal of neurology, 2018

For over 20 years, as a group we have been using flunarizine in primary headache disorders. Flunarizine is widely used in Europe, but not licensed in the UK. In September 2014, the National Institute for Clinical Excellence published supportive guidelines for flunarizine use in migraine, based on randomized controlled evidence that it is as effective as propranolol and topiramate in adults.
Ki-67 index as a predictor of vestibular schwannoma regrowth or recurrence.
The Journal of laryngology and otology, 2019

Ki-67 is a monoclonal antibody that provides a means of evaluating the growth fraction of normal and neoplastic human cell populations. A Ki-67 index of less than 3 per cent is expected for a typical schwannoma. Vestibular schwannomas with an index of greater than 3 per cent are presumed to be actively proliferating and pose a theoretically higher risk for regrowth or recurrence.
Differing causal roles for lateral occipital cortex and occipital face area in invariant shape recognition.
The European journal of neuroscience, 2010

The human extrastriate visual cortex contains functionally distinct regions where neuronal populations exhibit signals that are selective for objects. How such regions might play a causal role in underpinning our ability to recognize objects across different viewpoints remains uncertain. Here, we tested whether two extrastriate areas, the lateral occipital (LO) region and occipital face area (OFA), contained neuronal populations that play a causal role in recognizing two-dimensional shapes across different rotations. We used visual priming to modulate the rotation-sensitive activity of neuronal populations in these areas. State-dependent transcranial magnetic stimulation (TMS) was applied after the presentation of a shape and immediately before a subsequent probe shape to which participants had to respond. We found that TMS applied to both the LO region and OFA modulated rotation-invariant shape priming but, whereas the LO region was modulated by TMS for small rotations, the OFA was modulated for larger rotations. Importantly, our results demonstrate that a node in the face-sensitive network, the OFA, participates in causally relevant encoding of non-face stimuli.
Association and heterogeneity at the GAPDH locus in Alzheimer's disease.
Neurobiology of aging, 2012

Glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) and its paralogs were implicated in late-onset Alzheimer's disease (LOAD), although the strength and direction of association have not been consistent. We genotyped 3 previously reported single nucleotide polymorphisms (SNPs; rs3741916-GAPDH 5' UTR, rs2029721-pGAPD, and rs4806173-GAPDHS) in 3 case-control series (2112 cases and 3808 controls). Rs3741916 showed the strongest LOAD association (p = 0.003). The minor allele of rs3741916 showed a protective effect in our combined series (odds ratio [OR] = 0.87%, 95% confidence interval [CI] = 0.79-0.96). This is consistent with results from the 2 published follow-up studies and in opposite direction of the original report. Meta-analysis of the published series with ours suggests presence of heterogeneity (Breslow-Day p < 0.0001). Meta-analysis of only the follow-up series including ours revealed a significant protective effect for the minor allele of rs3741916 (OR = 0.85%, 95% CI = 0.76-0.96, p = 0.009). Our results support the presence of LOAD variants and heterogeneity at the GAPDH locus. The most promising rs3741916 variant is unlikely to be functional given opposing effects in different series. Identification of functional variant(s) in this region likely awaits deep sequencing.
Blocking the Thrombin Receptor Promotes Repair of Demyelinated Lesions in the Adult Brain.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Myelin loss limits neurological recovery and myelin regeneration and is critical for restoration of function. We recently discovered that global knock-out of the thrombin receptor, also known as Protease Activated Receptor 1 (PAR1), accelerates myelin development. Here we demonstrate that knocking out PAR1 also promotes myelin regeneration. Outcomes in two unique models of myelin injury and repair, that is lysolecithin or cuprizone-mediated demyelination, showed that PAR1 knock-out in male mice improves replenishment of myelinating cells and remyelinated nerve fibers and slows early axon damage. Improvements in myelin regeneration in PAR1 knock-out mice occurred in tandem with a skewing of reactive astrocyte signatures toward a prorepair phenotype. In cell culture, the promyelinating effects of PAR1 loss of function are consistent with possible direct effects on the myelinating potential of oligodendrocyte progenitor cells (OPCs), in addition to OPC-indirect effects involving enhanced astrocyte expression of promyelinating factors, such as BDNF. These findings highlight previously unrecognized roles of PAR1 in myelin regeneration, including integrated actions across the oligodendrocyte and astroglial compartments that are at least partially mechanistically linked to the powerful BDNF-TrkB neurotrophic signaling system. Altogether, findings suggest PAR1 may be a therapeutically tractable target for demyelinating disorders of the CNS.
Early human visual cortex encodes surface brightness induced by dynamic context.
Journal of cognitive neuroscience, 2012

Visual scene perception owes greatly to surface features such as color and brightness. Yet, early visual cortical areas predominantly encode surface boundaries rather than surface interiors. Whether human early visual cortex may nevertheless carry a small signal relevant for surface perception is a topic of debate. We induced brightness changes in a physically constant surface by temporally modulating the luminance of surrounding surfaces in seven human participants. We found that fMRI activity in the V2 representation of the constant surface was in antiphase to luminance changes of surrounding surfaces (i.e., activity was in-phase with perceived brightness changes). Moreover, the amplitude of the antiphase fMRI activity in V2 predicted the strength of illusory brightness perception. We interpret our findings as evidence for a surface-related signal in early visual cortex and discuss the neural mechanisms that may underlie that signal in concurrence with its possible interaction with the properties of the fMRI signal.
Differential stroke-induced proliferative response of distinct precursor cell subpopulations in the young and aged dentate gyrus.
Neuroscience, 2010

The capability of the adult brain to generate new hippocampal neurons after brain insults like stroke is decreasing during the aging process. Recent evidence further indicates that the proliferative properties of the precursor cells change in the aged brain. We therefore analyzed the early proliferative response of distinct precursor cell populations in the subgranular zone of the dentate gyrus in 3 and 16 months old transgenic nestin-green-fluorescent protein mice 4 days after ischemic cortical infarcts. A detailed immunocytochemical analysis of proliferating precursors revealed a significant infarct-induced activation of the earliest radial glia-like precursor cells (type 1 cells) and the more differentiated precursor cell subtypes (type 2b cells) in young mice. In contrast the proliferation of early neuronal precursor cells (type 2a cells) was stimulated in the aged brain. Additional long-term experiments further demonstrated that this differential proliferative response of distinct precursor cells is associated with an enhanced number of newborn neurons in the young DG after stroke whereas this increase in neurogenesis was absent in the aged brain. However, our study demonstrates that even precursor cells in the aged hippocampus possess the ability to respond to remote cortical infarcts.
Considerations for the Use of Polyphenols as Therapies in Neurodegenerative Diseases.
International journal of molecular sciences, 2019

Over the last two decades, the increase in the incidence of neurodegenerative diseases due to the increasingly ageing population has resulted in a major social and economic burden. At present, a large body of literature supports the potential use of functional nutrients, which exhibit potential neuroprotective properties to mitigate these diseases. Among the most studied dietary molecules, polyphenols stand out because of their multiple and often overlapping reported modes of action. However, ambiguity still exists as to the significance of their influence on human health. This review discusses the characteristics and functions of polyphenols that shape their potential therapeutic actions in neurodegenerative diseases while the less-explored gaps in knowledge of these nutrients will also be highlighted.
Feasibility of mHealth interventions for depressive symptoms in Latin America: a systematic review.
International review of psychiatry (Abingdon, England), 2021

Depression is a prevalent disorder and leading cause of disability in Latin America, where the mental health treatment gap is still above 50%. We sought to synthesise and assess the quality of the evidence on the feasibility of mHealth-based interventions for depression in Latin America. We conducted a literature search of studies published in 2007 and after using four electronic databases. We included peer-reviewed articles, in English, Spanish or Portuguese, that evaluated interventions for depressive symptoms. Two authors independently extracted data using forms developed a priori. We assessed appropriateness of reporting utilising the CONSORT checklist for feasibility trials. Eight manuscripts were included for full data extraction. Appropriate reporting varied greatly. Most (