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https://www.readbyqxmd.com/read/28734822/icotinib-versus-whole-brain-irradiation-in-patients-with-egfr-mutant-non-small-cell-lung-cancer-and-multiple-brain-metastases-brain-a-multicentre-phase-3-open-label-parallel-randomised-controlled-trial
#1
Jin-Ji Yang, Caicun Zhou, Yisheng Huang, Jifeng Feng, Sun Lu, Yong Song, Cheng Huang, Gang Wu, Li Zhang, Ying Cheng, Chengping Hu, Gongyan Chen, Li Zhang, Xiaoqing Liu, Hong Hong Yan, Fen Lai Tan, Wenzhao Zhong, Yi-Long Wu
BACKGROUND: For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. METHODS: We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China...
July 19, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28714010/ptprq-as-a-potential-biomarker-for-idiopathic-normal-pressure-hydrocephalus
#2
Yuki Nagata, Masahiko Bundo, Saiko Sugiura, Masahiro Kamita, Masaya Ono, Kotaro Hattori, Sumiko Yoshida, Yu-Ichi Goto, Katsuya Urakami, Shumpei Niida
Idiopathic normal pressure hydrocephalus (iNPH) is caused by the accumulation of cerebrospinal fluid (CSF) and is characterized by gait disturbance, urinary incontinence, and dementia. iNPH dementia is treatable by shunt operation; however, since the cognitive symptoms of iNPH are often similar to those of other dementias, including Alzheimer's disease (AD), accurate diagnosis of iNPH is difficult. To overcome this problem, the identification of novel diagnostic markers to distinguish iNPH and AD is warranted...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712060/abnormal-social-behavior-in-mice-with-tyrosinemia-type-i-is-associated-with-an-increase-of-myelin-in-the-cerebral-cortex
#3
Marissa E Moore, Ashton E Koenig, Megan A Hillgartner, Christopher C Otap, Elizabeth Barnby, Gordon G MacGregor
Hereditary tyrosinemia type I (HT1) is caused by mutations in the fumarylacetoacetate hydrolase (FAH) gene, the template for the final enzyme in the tyrosine catabolism pathway. If left untreated this deficiency of functional FAH leads to a buildup of toxic metabolites that can cause liver disease, kidney dysfunction and high mortality. The current treatment with the drug NTBC prevents the production of these metabolites and has consequently increased the survival rate in HT1 children. As a result of this increased survival, long term complications of HT1 are now being observed, including slower learning, impaired cognition and altered social behavior...
July 15, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28711564/role-of-estrogen-and-levodopa-in-1-methyl-4-pheny-l-1-2-3-6-tetrahydropyridine-mptp-induced-cognitive-deficit-in-parkinsonian-ovariectomized-mice-model-a-comparative-study
#4
Satyndra Kumar Yadav, Shivani Pandey, Babita Singh
Parkinson's disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In this study, the neuroprotective effects of estrogen was evaluated in the 1-methyl-4-phe-nyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD with cognitive deficit and compared to Levodopa (LD), a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+LD and MPTP+estrogen...
July 12, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28705440/inhibition-of-trkb-at-the-nucleus-accumbens-using-ana-12-regulates-basal-and-stress-induced-orexin-a-expression-within-the-mesolimbic-system-and-affects-anxiety-sociability-and-motivation
#5
Idu Azogu, Helene Plamondon
Repeated stress exposure can lead to the development of anxiety and mood disorders. An emerging biological substrate of depression and associated pathology is the nucleus accumbens (NAc), which through interactions with limbic, cognitive and motor circuits can regulate a variety of stress responses. Within these circuits, orexin neurons are involved in arousal and stress adaptability, effects proposed mediated via brain-derived neurotrophic factor signaling. This study tested the hypotheses that 1) repeated exposure to heterotypic stress alters social ability and preference and passive avoidant behaviors, 2) TrkB receptors at the NAc shell regulates stress-induced behavioral responses and orexin expression within the mesocorticolimbic system...
July 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28702436/paternal-physical-exercise-improves-spatial-learning-ability-by-enhancing-hippocampal-neuroplasticity-in-male-pups-born-from-obese-maternal-rats
#6
Hye-Sang Park, Tae-Woon Kim
Maternal obesity exerts negative effects on cognitive function and behavior of the offspring. In the present study, we assessed the effects of paternal physical exercise on spatial learning ability in relation with hippocampal neuroplasticity in the rat pups born from the obese maternal rats. There were four experimental groups: paternal nonexercised male pups from normal maternal rats, paternal exercised male pups from normal maternal rats, paternal nonexercised male pups from obese maternal rats, and paternal exercised male pups from obese maternal rats...
June 2017: Journal of Exercise Rehabilitation
https://www.readbyqxmd.com/read/28684271/ablating-erbb4-in-pv-neurons-attenuates-synaptic-and-cognitive-deficits-in-an-animal-model-of-alzheimer-s-disease
#7
Heng Zhang, Ling Zhang, Dongming Zhou, Xiao He, Dongpi Wang, Hongyu Pan, Xiaoqin Zhang, Yufei Mei, Qi Qian, Tingting Zheng, Frank E Jones, Binggui Sun
Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aβ-induced suppression of long term potentiation (LTP)...
July 4, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28665013/epigenetic-regulation-by-g9a-glp-complex-ameliorates-amyloid-beta-1-42-induced-deficits-in-long-term-plasticity-and-synaptic-tagging-capture-in-hippocampal-pyramidal-neurons
#8
Mahima Sharma, Tobias Dierkes, Sreedharan Sajikumar
Altered epigenetic mechanisms are implicated in the cognitive decline associated with neurodegenerative diseases such as in Alzheimer's disease (AD). AD is the most prevalent form of dementia worldwide; amyloid plaques and neurofibrillary tangles are the histopathological hallmarks of AD. We have recently reported that the inhibition of G9a/GLP complex promotes long-term potentiation (LTP) and its associative mechanisms such as synaptic tagging and capture (STC). However, the role of this complex in plasticity impairments remains elusive...
June 30, 2017: Aging Cell
https://www.readbyqxmd.com/read/28647555/normalizing-the-gene-dosage-of-dyrk1a-in-a-mouse-model-of-down-syndrome-rescues-several-alzheimer-s-disease-phenotypes
#9
Susana García-Cerro, Noemí Rueda, Verónica Vidal, Sara Lantigua, Carmen Martínez-Cué
The intellectual disability that characterizes Down syndrome (DS) is primarily caused by prenatal changes in central nervous system growth and differentiation. However, in later life stages, the cognitive abilities of DS individuals progressively decline due to accelerated aging and the development of Alzheimer's disease (AD) neuropathology. The AD neuropathology in DS has been related to the overexpression of several genes encoded by Hsa21 including DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which encodes a protein kinase that performs crucial functions in the regulation of multiple signaling pathways that contribute to normal brain development and adult brain physiology...
June 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28641491/nicotine-and-cigarette-smoke-modulate-nrf2-bdnf-dopaminergic-signal-and-neurobehavioral-disorders-in-adult-rat-cerebral-cortex
#10
Nibedita Naha, D N Gandhi, A K Gautam, J Ravi Prakash
BACKGROUND: Nicotine and cigarette smoking (CS) are associated with addiction behavior, drug-seeking, and abuse. However, the mechanisms that mediate this association especially, the role of brain-derived neurotrophic factor (BDNF), dopamine (DA), and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in the cerebral cortex, are not fully known. Therefore, we hypothesized that overexpression of BDNF and DA, and suppression of Nrf2 contribute to several pathological and behavioral alterations in adult cerebral cortex...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28631188/role-of-clu-picalm-and-tnk1-genotypes-in-aging-with-and-without-alzheimer-s-disease
#11
Davide Seripa, Francesco Panza, Giulia Paroni, Grazia D'Onofrio, Paola Bisceglia, Carolina Gravina, Maria Urbano, Madia Lozupone, Vincenzo Solfrizzi, Alessandra Bizzarro, Virginia Boccardi, Chiara Piccininni, Antonio Daniele, Giancarlo Logroscino, Patrizia Mecocci, Carlo Masullo, Antonio Greco
Healthy and impaired cognitive aging may be associated to different prevalences of single-nucleotide polymorphisms (SNPs). In a multicenter case-control association study, we studied the SNPs rs11136000 (clusterin, CLU), rs541458 (phosphatidylinositol binding clatrin assembly protein, PICALM), and rs1554948 (transcription factor A, and tyrosine kinase, non-receptor, 1, TNK1) according to the three age groups 50-65 years (group 1), 66-80 years (group 2), and 80+ years (group 3) in 569 older subjects without cognitive impairment (NoCI) and 520 Alzheimer's disease (AD) patients...
June 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28607064/impact-of-nutrition-on-social-decision-making
#12
Sabrina Strang, Christina Hoeber, Olaf Uhl, Berthold Koletzko, Thomas F Münte, Hendrik Lehnert, Raymond J Dolan, Sebastian M Schmid, Soyoung Q Park
Food intake is essential for maintaining homeostasis, which is necessary for survival in all species. However, food intake also impacts multiple biochemical processes that influence our behavior. Here, we investigate the causal relationship between macronutrient composition, its bodily biochemical impact, and a modulation of human social decision making. Across two studies, we show that breakfasts with different macronutrient compositions modulated human social behavior. Breakfasts with a high-carbohydrate/protein ratio increased social punishment behavior in response to norm violations compared with that in response to a low carbohydrate/protein meal...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28591103/treatment-of-acute-lymphoblastic-leukemia-in-older-adults-now-and-the-future
#13
Musa Yilmaz, Hagop Kantarjian, Elias Jabbour
Acute lymphoblastic leukemia (ALL) is an uncommon disease with poor outcomes in older patients. Although intensive chemotherapy can induce complete responses in older patients, the mortality rate is unacceptably high. The 5-year survival rate for patients achieving a remission ranges from 17% to 23%. ALL is usually more aggressive in older patients, and these patients' reduced functional capacity renders them less able to tolerate treatment. The need for less-intensive, more-efficient treatment modalities in this population of frail and high-risk patients is evident...
April 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28556830/adolescence-is-the-starting-point-of-sex-dichotomous-comt-genetic-effects
#14
S Sannino, M C Padula, F Managò, M Schaer, M Schneider, M Armando, E Scariati, F Sloan-Bena, M Mereu, M Pontillo, S Vicari, G Contarini, C Chiabrera, M Pagani, A Gozzi, S Eliez, F Papaleo
The catechol-o-methyltransferase (COMT) genetic variations produce pleiotropic behavioral/neuroanatomical effects. Some of these effects may vary among sexes. However, the developmental trajectories of COMT-by-sex interactions are unclear. Here we found that extreme COMT reduction, in both humans (22q11.2 deletion syndrome COMT Met) and mice (COMT-/-), was associated to cortical thinning only after puberty and only in females. Molecular biomarkers, such as tyrosine hydroxylase, Akt and neuronal/cellular counting, confirmed that COMT-by-sex divergent effects started to appear at the cortical level during puberty...
May 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28555636/pyk2-modulates-hippocampal-excitatory-synapses-and-contributes-to-cognitive-deficits-in-a-huntington-s-disease-model
#15
Albert Giralt, Veronica Brito, Quentin Chevy, Clémence Simonnet, Yo Otsu, Carmen Cifuentes-Díaz, Benoit de Pins, Renata Coura, Jordi Alberch, Sílvia Ginés, Jean-Christophe Poncer, Jean-Antoine Girault
The structure and function of spines and excitatory synapses are under the dynamic control of multiple signalling networks. Although tyrosine phosphorylation is involved, its regulation and importance are not well understood. Here we study the role of Pyk2, a non-receptor calcium-dependent protein-tyrosine kinase highly expressed in the hippocampus. Hippocampal-related learning and CA1 long-term potentiation are severely impaired in Pyk2-deficient mice and are associated with alterations in NMDA receptors, PSD-95 and dendritic spines...
May 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28552082/cerebral-dopamine-deficiency-plasma-monoamine-alterations-and-neurocognitive-deficits-in-adults-with-phenylketonuria
#16
E Boot, C E M Hollak, S C J Huijbregts, R Jahja, D van Vliet, A J Nederveen, D H Nieman, A M Bosch, L J Bour, A J Bakermans, N G G M Abeling, A S Bassett, T A M J van Amelsvoort, F J van Spronsen, J Booij
BACKGROUND: Phenylketonuria (PKU), a genetic metabolic disorder that is characterized by the inability to convert phenylalanine to tyrosine, leads to severe intellectual disability and other cerebral complications if left untreated. Dietary treatment, initiated soon after birth, prevents most brain-related complications. A leading hypothesis postulates that a shortage of brain monoamines may be associated with neurocognitive deficits that are observable even in early-treated PKU. However, there is a paucity of evidence as yet for this hypothesis...
May 29, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28529699/evolution-immunity-and-the-emergence-of-brain-superautoantigens
#17
Serge Nataf
While some autoimmune disorders remain extremely rare, others largely predominate the epidemiology of human autoimmunity. Notably, these include psoriasis, diabetes, vitiligo, thyroiditis, rheumatoid arthritis and multiple sclerosis. Thus, despite the quasi-infinite number of "self" antigens that could theoretically trigger autoimmune responses, only a limited set of antigens, referred here as superautoantigens, induce pathogenic adaptive responses. Several lines of evidence reviewed in this paper indicate that, irrespective of the targeted organ (e...
2017: F1000Research
https://www.readbyqxmd.com/read/28504493/neuropsychological-assessment-among-children-and-adolescents-with-phenylketonuria-and-hyperphenylalaninemia-and-its-relationship-with-plasma-phenylalanine-levels
#18
María B González García, Pablo Conde-Guzon, Carlos Alcalde Martín, María J Conde-Guzon, Roberto Velasco Zúñiga
Although with early treatment phenylketonuria patients may have average intelligence levels, it is important to optimize the nutritional management to maintain adequate phenylalanine levels, so that patients can develop their intellectal potential free of abnormalities in their daily activities due to deficits of cognitive executive functions. This study presents a series of 26 patients, diagnosed and treated early, who underwent a psychometric evaluation together with phenylalanine determinations along their lives, and at the time of doing the tests...
June 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28487222/neuroprotective-effects-of-ceftriaxone-treatment-on-cognitive-and-neuronal-deficits-in-a-rat-model-of-accelerated-senescence
#19
Maria A Tikhonova, Shih-Chun Ho, Anna A Akopyan, Nataliya G Kolosova, Jun-Cheng Weng, Wan-Yun Meng, Chih-Li Lin, Tamara G Amstislavskaya, Ying-Jui Ho
Rats of OXYS strain are characterized by genetically defined accelerated senescence. Ceftriaxone (CEF) exerts neuroprotective effects by decreasing the excitotoxicity and activation of antioxidant system. Here, we studied the effects of CEF (50 or 100mg/kg/day, i.p., 36 days) on cognitive and neuronal deficits in 5-month-old OXYS rats. Chronic CEF administration in a dose of 100mg/kg partially inhibited impairments of movement and restored the deficit in the novel object recognition in OXYS rats. Neuromorphologically, control OXYS rats exhibited a lowered neuronal density in the hippocampal CA1 area and there was a tendency to decrease in the substantia nigra pars compacta compared to Wistar controls...
May 6, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28466270/synaptic-nmda-receptor-activation-induces-ubiquitination-and-degradation-of-step61
#20
Jian Xu, Pradeep Kurup, Angus C Nairn, Paul J Lombroso
NMDA receptor signaling is critical for the development of synaptic plasticity, learning, and memory, and dysregulation of NMDAR signaling is implicated in a number of neurological disorders including schizophrenia (SZ). Previous work has demonstrated that the STriatal-Enriched protein tyrosine Phosphatase 61 kDa (STEP61) is elevated in human SZ postmortem cortical samples and after administration of psychotomimetics to cultures or mice. Here, we report that activation of synaptic NMDAR by bicuculline or D-serine results in the ubiquitination and proteasomal degradation of STEP61, and increased surface localization of GluN1/GluN2B receptors...
May 2, 2017: Molecular Neurobiology
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