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https://www.readbyqxmd.com/read/29342245/structure-function-relationships-of-olfactory-and-taste-receptors
#1
Maik Behrens, Loïc Briand, Claire A de March, Hiroaki Matsunami, Atsuko Yamashita, Wolfgang Meyerhof, Simone Weyand
The field of chemical senses has made major progress in understanding the cellular mechanisms of olfaction and taste in the past two decades. However, the molecular understanding of odour and taste recognition is still lagging far behind and will require solving multiple structures of the relevant full-length receptors in complex with native ligands to achieve this goal. However, the development of multiple complimentary strategies for the structure determination of G protein-coupled receptors (GPCRs) makes this goal realistic...
January 12, 2018: Chemical Senses
https://www.readbyqxmd.com/read/29342244/gli2-rescues-delays-in-brain-development-induced-by-kif3a-dysfunction
#2
Jia-Long Chen, Chia-Hsiang Chang, Jin-Wu Tsai
The primary cilium in neural stem cells plays distinct roles in different stages during cortical development. Ciliary dysfunctions in human (i.e., ciliopathy) cause developmental defects in multiple organs, including brain developmental delays, which lead to intellectual disabilities and cognitive deficits. However, effective treatment to this devastating developmental disorder is still lacking. Here, we first investigated the effects of ciliopathy on neural stem cells by knocking down Kif3a, a kinesin II motor required for ciliogenesis, in the neurogenic stage of cortical development by in utero electroporation of mouse embryos...
January 12, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29342227/brain-cytosolic-phospholipase-a2%C3%AE-mediates-angiotensin-ii-induced-hypertension-and-reactive-oxygen-species-production-in-male-mice
#3
Chi Young Song, Nayaab S Khan, Francesca-Fang Liao, Bin Wang, Ji Soo Shin, Joseph V Bonventre, Kafait U Malik
Background: Recently we reported that angiotensin II (Ang II)-induced hypertension is mediated by group IV cytosolic phospholipase A2α (cPLA2α) via production of pro-hypertensive eicosanoids. Since Ang II increases blood pressure via its action in the subfornical organ (SFO), it led us to investigate the expression and possible contribution of cPLA2α to oxidative stress and development of hypertension in this brain area. Methods: Adenovirus (Ad)-green fluorescence protein (GFP) cPLA2α short hairpin (sh) RNA (Ad-cPLA2α shRNA) and its control Ad-scrambled shRNA (Ad-Scr shRNA) or Ad-enhanced cyan fluorescence protein cPLA2α DNA (Ad-cPLA2α DNA) and its control Ad-GFP DNA were transduced into SFO of cPLA2α+/+ and cPLA2α-/- male mice, respectively...
January 12, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29342116/vegf-signaling-in-neurological-disorders
#4
REVIEW
Joon W Shim, Joseph R Madsen
Vascular endothelial growth factor (VEGF) is a potent growth factor playing diverse roles in vasculogenesis and angiogenesis. In the brain, VEGF mediates angiogenesis, neural migration and neuroprotection. As a permeability factor, excessive VEGF disrupts intracellular barriers, increases leakage of the choroid plexus endothelia, evokes edema, and activates the inflammatory pathway. Recently, we discovered that a heparin binding epidermal growth factor like growth factor (HB-EGF)-a class of EGF receptor (EGFR) family ligands-contributes to the development of hydrocephalus with subarachnoid hemorrhage through activation of VEGF signaling...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342085/development-of-a-region-specific-physiologically-based-pharmacokinetic-brain-model-to-assess-hippocampus-and-frontal-cortex-pharmacokinetics
#5
Zaril Zakaria, Raj Badhan
Central nervous system drug discovery and development is hindered by the impermeable nature of the blood-brain barrier. Pharmacokinetic modeling can provide a novel approach to estimate CNS drug exposure; however, existing models do not predict temporal drug concentrations in distinct brain regions. A rat CNS physiologically based pharmacokinetic (PBPK) model was developed, incorporating brain compartments for the frontal cortex (FC), hippocampus (HC), "rest-of-brain" (ROB), and cerebrospinal fluid (CSF). Model predictions of FC and HC Cmax, tmax and AUC were within 2-fold of that reported for carbamazepine and phenytoin...
January 17, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29341901/a-small-peptide-derived-from-bmp-9-can-increase-the-effect-of-bfgf-and-ngf-on-sh-sy5y-cells-differentiation
#6
Marc-Antoine Lauzon, Nathalie Faucheux
The current aging of the world population will increase the number of people suffering from brain degenerative diseases such as Alzheimer's disease (AD). There are evidence showing that the use of growth factors such as BMP-9 could restored cognitive function as it acts on many AD hallmarks at the same time. However, BMP-9 is a big protein expensive to produce that can hardly access the central nervous system. We have therefore developed a small peptide, SpBMP-9, derived from the knuckle epitope of BMP-9 and showed its therapeutic potential in a previous study...
January 13, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29341803/licorice-pretreatment-protects-against-brain-damage-induced-by-middle-cerebral-artery-occlusion-in-mice
#7
Chiyeon Lim, Sehyun Lim, Byoungho Lee, Buyeo Kim, Suin Cho
Licorice is extracted from the roots of plants in the Glycyrrhiza genus, especially Glycyrrhiza uralensis in China and Korea. It has several pharmacological activities, including neuro-protective, anti-fungal, and anti-cariogenic effects. Ischemia/reperfusion-induced brain injury is a leading cause of adult disability and death; thus, the identification of anti-apoptotic, neuro-protective therapeutic agents is viewed as an attractive drug development strategy. Infarct volumes and the expression of several apoptosis-related proteins, including Bcl-xL, Bcl-2, caspase-8, and caspase-9, were evaluated by western blotting in the brains of mice subjected to middle cerebral artery occlusion (MCAO)...
January 17, 2018: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29341341/prediction-of-activation-patterns-preceding-hallucinations-in-patients-with-schizophrenia-using-machine-learning-with-structured-sparsity
#8
Amicie de Pierrefeu, Thomas Fovet, Fouad Hadj-Selem, Tommy Löfstedt, Philippe Ciuciu, Stephanie Lefebvre, Pierre Thomas, Renaud Lopes, Renaud Jardri, Edouard Duchesnay
Despite significant progress in the field, the detection of fMRI signal changes during hallucinatory events remains difficult and time-consuming. This article first proposes a machine-learning algorithm to automatically identify resting-state fMRI periods that precede hallucinations versus periods that do not. When applied to whole-brain fMRI data, state-of-the-art classification methods, such as support vector machines (SVM), yield dense solutions that are difficult to interpret. We proposed to extend the existing sparse classification methods by taking the spatial structure of brain images into account with structured sparsity using the total variation penalty...
January 16, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29341331/the-relationship-between-thalamic-gaba-content-and-resting-cortical-rhythm-in-neuropathic-pain
#9
Flavia Di Pietro, Paul M Macey, Caroline D Rae, Zeynab Alshelh, Vaughan G Macefield, E Russell Vickers, Luke A Henderson
Recurrent thalamocortical connections are integral to the generation of brain rhythms and it is thought that the inhibitory action of the thalamic reticular nucleus is critical in setting these rhythms. Our work and others' has suggested that chronic pain that develops following nerve injury, that is, neuropathic pain, results from altered thalamocortical rhythm, although whether this dysrhythmia is associated with thalamic inhibitory function remains unknown. In this investigation, we used electroencephalography and magnetic resonance spectroscopy to investigate cortical power and thalamic GABAergic concentration in 20 patients with neuropathic pain and 20 pain-free controls...
January 17, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29341330/real-time-and-high-resolution-bioimaging-with-bright-aggregation-induced-emission-dots-in-short-wave-infrared-region
#10
Ji Qi, Chaowei Sun, Abudureheman Zebibula, Hequn Zhang, Ryan T K Kwok, Xinyuan Zhao, Wang Xi, Jacky W Y Lam, Jun Qian, Ben Zhong Tang
Fluorescence imaging in the spectral region beyond the conventional near-infrared biological window (700-900 nm) can theoretically afford high resolution and deep tissue penetration. Although some efforts have been devoted to developing a short-wave infrared (SWIR; 900-1700 nm) imaging modality in the past decade, long-wavelength biomedical imaging is still suboptimal owing to the unsatisfactory materials properties of SWIR fluorophores. Taking advantage of organic dots based on an aggregation-induced emission luminogen (AIEgen), herein microscopic vasculature imaging of brain and tumor is reported in living mice in the SWIR spectral region...
January 17, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29341323/test-retest-reliability-and-longitudinal-analysis-of-automated-hippocampal-subregion-volumes-in-healthy-ageing-and-alzheimer-s-disease-populations
#11
Amanda Worker, Danai Dima, Anna Combes, William R Crum, Johannes Streffer, Steven Einstein, Mitul A Mehta, Gareth J Barker, Steve C R Williams, Owen O'daly
The hippocampal formation is a complex brain structure that is important in cognitive processes such as memory, mood, reward processing and other executive functions. Histological and neuroimaging studies have implicated the hippocampal region in neuropsychiatric disorders as well as in neurodegenerative diseases. This highly plastic limbic region is made up of several subregions that are believed to have different functional roles. Therefore, there is a growing interest in imaging the subregions of the hippocampal formation rather than modelling the hippocampus as a homogenous structure, driving the development of new automated analysis tools...
January 16, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29341299/autonomous-purkinje-cell-axonal-dystrophy-causes-ataxia-in-peroxisomal-multifunctional-protein-2-deficiency
#12
Stephanie De Munter, Dorien Bamps, Ana Rita Malheiro, Ritesh Kumar Baboota, Pedro Brites, Myriam Baes
BACKGROUND: Peroxisomes play a crucial role in normal neurodevelopment and in the maintenance of the adult brain. This depends largely on intact peroxisomal β-oxidation given the similarities in pathologies between peroxisome biogenesis disorders and deficiency of multifunctional protein-2 (MFP2), the central enzyme of this pathway. Recently, adult patients diagnosed with cerebellar ataxia were shown to have mild mutations in the MFP2 gene, hydroxy-steroid dehydrogenase (17 beta) type 4 (HSD17B4)...
January 17, 2018: Brain Pathology
https://www.readbyqxmd.com/read/29341271/review-shows-that-early-fetal-alcohol-exposure-may-cause-adverse-effects-even-when-the-mother-consumes-low-levels
#13
Ihsan Sarman
AIM: Studies are increasingly focusing on the effects of prenatal alcohol exposure (PAE) on child health. The aim of this review was to provide paediatricians with new insights to help them communicate key messages about avoiding alcohol during pregnancy. METHODS: Inspired by the 7th International Conference on Fetal Alcohol Spectrum Disorder, which focused on integrating research, policy and practice, we studied English language papers published since 2010 on how early PAE triggered epigenetic mechanisms that had an impact on the development of some chronic diseases...
January 17, 2018: Acta Paediatrica
https://www.readbyqxmd.com/read/29341130/mitochondrial-function-and-autophagy-integrating-proteotoxic-redox-and-metabolic-stress-in-parkinson-s-disease
#14
REVIEW
Jianhua Zhang, M Lillian Culp, Jason G Craver, Victor Darley-Usmar
Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration in the brain. Significant oxidative, reductive, metabolic, and proteotoxic alterations have been observed in PD postmortem brains. The alterations of mitochondrial function resulting in decreased bioenergetic health is important and needs to be further examined to help develop biomarkers for PD severity and prognosis. It is now becoming clear that multiple hits on metabolic and signaling pathways are likely to exacerbate PD pathogenesis...
January 17, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29341120/trajectories-of-infants-biobehavioral-development-timing-and-rate-of-a-not-b-performance-gains-and-eeg-maturation
#15
Leigha A MacNeill, Nilam Ram, Martha Ann Bell, Nathan A Fox, Koraly Pérez-Edgar
This study examined how timing (i.e., relative maturity) and rate (i.e., how quickly infants attain proficiency) of A-not-B performance were related to changes in brain activity from age 6 to 12 months. A-not-B performance and resting EEG (electroencephalography) were measured monthly from age 6 to 12 months in 28 infants and were modeled using logistic and linear growth curve models. Infants with faster performance rates reached performance milestones earlier. Infants with faster rates of increase in A-not-B performance had lower occipital power at 6 months and greater linear increases in occipital power...
January 17, 2018: Child Development
https://www.readbyqxmd.com/read/29341112/conditionally-reprogrammed-cells-crc-methodology-does-not-allow-the-in-vitro-expansion-of-patient-derived-primary-and-metastatic-lung-cancer-cells
#16
Giovanni Sette, Valentina Salvati, Ilenia Giordani, Emanuela Pillozzi, Denise Quacquarini, Enrico Duranti, Francesca De Nicola, Matteo Pallocca, Maurizio Fanciulli, Mario Falchi, Roberto Pallini, Ruggero De Maria, Adriana Eramo
Availability of tumor and non-tumor patient-derived models would promote the development of more effective therapeutics for Non Small Cell Lung Cancer (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology demonstrated exceptional potential for the expansion of epithelial cells from patient tissues. However, the possibility to expand patient-derived lung cancer cells using CRC protocols is controversial. Here, we used CRC approach to expand cells from non-tumoral and tumor biopsies of patients with primary or metastatic NSCLC as well as pulmonary metastases of colorectal or breast cancers...
January 17, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29341020/mri-in-the-study-of-animal-models-of-stroke
#17
Pedro Ramos-Cabrer, Daniel Padro
Stroke consists of the loss of cerebral functions resulting from the interruption of blood supply to a region of the brain, and represents the second cause of death and the leading cause of major disability in adults in Europe. Stroke is a very active field of research at preclinical and clinical levels, and Magnetic Resonance Imaging (MRI) is one of the most powerful tools that scientist and clinicians have for the study of the onset, evolution and consequences of this devastating disease, as well as for the monitoring of the success of available treatments, or for the development of novel therapeutic strategies...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29341015/in-utero-mri-of-mouse-embryos
#18
Jiangyang Zhang, Dan Wu, Daniel H Turnbull
Genetically engineered mouse models are used extensively as models of human development and developmental diseases. Conventional histological approaches are static and two-dimensional, and do not provide a full understanding of the dynamic, spatiotemporal changes in developing mouse embryos. Magnetic resonance imaging (MRI) offers a noninvasive and longitudinal approach for three-dimensional in utero imaging of normal and mutant mouse embryos. In this chapter, we describe MRI approaches that have been developed for imaging the living embryonic mouse brain and vasculature...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29341001/dynamic-susceptibility-contrast-mri-in-small-animals
#19
Pilar López-Larrubia
The use of magnetic resonance imaging (MRI) for studying the cerebral perfusion mechanisms is well proved and contrasted in the clinical and research setups. This methodology is a promising tool in assessing numerous brain diseases like intracranial tumors, neurodegeneration processes, mental disorders, injuries and so on. In the preclinical environment, perfusion MRI offers a powerful resource for characterizing pathological models and specially identifying biomarkers to monitor the illness and validate the efficacy of therapeutical approaches...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29340594/keratan-sulphate-a-complex-glycosaminoglycan-with-unique-functional-capability
#20
Bruce Caterson, James Melrose
From an evolutionary perspective keratan sulphate (KS) is the newest glycosaminoglycan (GAG) but the least understood. KS is a sophisticated molecule with a diverse structure, and unique functional roles continue to be uncovered for this GAG. The cornea is the richest tissue source of KS in the human body but the central and peripheral nervous systems also contain significant levels of KS and a diverse range of KS-proteoglycans with essential functional roles. KS also displays important cell regulatory properties in epithelial and mesenchymal tissues and in bone and in tumour development of diagnostic and prognostic utility...
January 11, 2018: Glycobiology
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