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https://www.readbyqxmd.com/read/29346368/mechanical-feedback-coordinates-cell-wall-expansion-and-assembly-in-yeast-mating-morphogenesis
#1
Samhita P Banavar, Carlos Gomez, Michael Trogdon, Linda R Petzold, Tau-Mu Yi, Otger Campàs
The shaping of individual cells requires a tight coordination of cell mechanics and growth. However, it is unclear how information about the mechanical state of the wall is relayed to the molecular processes building it, thereby enabling the coordination of cell wall expansion and assembly during morphogenesis. Combining theoretical and experimental approaches, we show that a mechanical feedback coordinating cell wall assembly and expansion is essential to sustain mating projection growth in budding yeast (Saccharomyces cerevisiae)...
January 18, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29346315/dietary-total-prenylflavonoids-from-the-fruits-of-psoralea-corylifolia-l-prevents-age-related-cognitive-deficits-and-down-regulates-alzheimer-s-markers-in-samp8-mice
#2
Zhi-Jing Chen, Yan-Fang Yang, Ying-Tao Zhang, Dong-Hui Yang
Alzheimer's disease (AD) is a serious threat for the aging society. In this study, we examined the preventive effect of the total prenylflavonoids (TPFB) prepared from the dried fruits of Psoralea corylifolia L., using an age-related AD mouse model SAMP8. We found that long-term dietary TPFB at 50 mg/kg·day significantly improved cognitive performance of the SAMP8 mice in Morris water maze tests, similar to 150 mg/kg·day of resveratrol, a popular neuro-protective compound. Furthermore, TPFB treatment showed significant improvements in various AD markers in SAMP8 brains, which were restored to near control levels of the normal mice, SAMR1...
January 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29346139/blood-biomarkers-for-evaluation-of-perinatal-encephalopathy-state-of-the-art
#3
Ernest M Graham, Allen D Everett, Jean-Christophe Delpech, Frances J Northington
PURPOSE OF REVIEW: The rapid progress in biomarker science is on the threshold of significantly changing clinical care for infants in the neonatal ICU. Infants with neonatal brain injuries will likely be the first group whose management is dramatically altered with point-of-care, rapidly available brain biomarker analysis. Providing an interim update on progress in this area is the purpose of this review. RECENT FINDINGS: Highlighted findings from the past 18 months of publications on biomarkers in neonatal brain injury include; Specific nonbrain markers of cardiac health and global asphyxia continue to provide information on brain injury after hypoxic-ischemic encephalopathy (HIE)...
January 17, 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29346009/automation-on-an-open-access-platform-of-alzheimer-s-disease-biomarker-immunoassays
#4
Benjamin Gille, Lieselot Dedeene, Erik Stoops, Leentje Demeyer, Cindy Francois, Stefanie Lefever, Maxim De Schaepdryver, Britta Brix, Rik Vandenberghe, Jos Tournoy, Hugo Vanderstichele, Koen Poesen
The lack of (inter-)laboratory standardization has hampered the application of universal cutoff values for Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers and their transfer to general clinical practice. The automation of the AD biomarker immunoassays is suggested to generate more robust results than using manual testing. Open-access platforms will facilitate the integration of automation for novel biomarkers, allowing the introduction of the protein profiling concept. A feasibility study was performed on an automated open-access platform of the commercial immunoassays for the 42-amino-acid isoform of amyloid-β (Aβ1-42), Aβ1-40, and total tau in CSF...
January 1, 2018: SLAS Technology
https://www.readbyqxmd.com/read/29345897/design-synthesis-and-biological-evaluation-of-1-benzylamino-2-hydroxyalkyl-derivatives-as-new-potential-disease-modifying-multifunctional-anti-alzheimer-s-agents
#5
Dawid Panek, Anna Więckowska, Jakub Jończyk, Justyna Godyń, Marek W Bajda, Tomasz Wichur, Anna Pasieka, Damijan Knez, Anja Pislar, Jan Korabecny, Ondrej Soukup, Vendula Sepsova, Raimon Sabaté, Janko Kos, Stanislav Gobec, Barbara Malawska
The multitarget approach is a promising paradigm in drug discovery, potentially leading to new treatment options for complex disorders, such as Alzheimer's disease. Herein, we present the discovery of a unique series of 1-benzylamino-2-hydroxyalkyl derivatives combining inhibitory activity against butyrylcholinesterase, β-secretase, β-amyloid and tau protein aggregation, all related to mechanisms which underpin Alzheimer's disease. Notably, diphenylpropylamine derivative 10 showed balanced activity against both disease-modifying targets - inhibition of β-secretase (IC50 hBACE-1 = 41...
January 18, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29345054/isoflurane-anesthesia-in-aged-mice-and-effects-of-a1-adenosine-receptors-on-cognitive-impairment
#6
Chun-Long Zuo, Chun-Man Wang, Jin Liu, Ting Shen, Jiang-Ping Zhou, Xin-Rui Hao, Yi-Zhao Pan, Hua-Cheng Liu, Qing-Quan Lian, Han Lin
AIMS: Isoflurane may not only accelerate the process of Alzheimer's disease (AD), but increase the risk of incidence of postoperative cognitive dysfunction (POCD). However, the underlying mechanisms remain unknown. This study was designed to investigate whether isoflurane contributed to the POCD occurrence through A1 adenosine receptor (A1AR) in aged mice. METHODS: We assessed cognitive function of mice with Morris water maze (MWM) and then measured expression level of two AD biomarkers (P-tau and Aβ) and a subtype of the NMDA receptor (NR2B) in aged wild-type (WT) and homozygous A1 adenosine receptor (A1AR) knockout (KO) mice at baseline and after they were exposed to isoflurane (1...
January 17, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29341269/characterization-of-a-3xtg-ad-mouse-model-of-alzheimer-s-disease-with-the-senescence-accelerated-mouse-prone-8-samp8-background
#7
Jessica Virgili, Meryem Lebbadi, Cyntia Tremblay, Isabelle St-Amour, Caroline Pierrisnard, Audrey Faucher-Genest, Vincent Emond, Carl Julien, Frédéric Calon
No model fully recapitulates the neuropathology of Alzheimer's disease (AD). Although the triple-transgenic mouse model of AD (3xTg-AD) expresses Aβ plaques and tau-laden neurofibrillary tangles, as well as synaptic and behavioral deficits, it does not display frank neuronal loss. Since old age is the most important risk factor in AD, senescence-related interactions might be lacking to truly establish an AD-like environment. To investigate this hypothesis, we bred the 3xTg-AD mouse with the senescence-accelerated mouse prone 8 (SAMP8), a model of accelerated aging...
January 17, 2018: Synapse
https://www.readbyqxmd.com/read/29341130/mitochondrial-function-and-autophagy-integrating-proteotoxic-redox-and-metabolic-stress-in-parkinson-s-disease
#8
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/29339765/mutations-in-bassoon-in-individuals-with-familial-and-sporadic-progressive-supranuclear-palsy-like-syndrome
#9
Ichiro Yabe, Hiroaki Yaguchi, Yasutaka Kato, Yasuo Miki, Hidehisa Takahashi, Satoshi Tanikawa, Shinichi Shirai, Ikuko Takahashi, Mari Kimura, Yuka Hama, Masaaki Matsushima, Shinsuke Fujioka, Takahiro Kano, Masashi Watanabe, Shin Nakagawa, Yasuyuki Kunieda, Yoshio Ikeda, Masato Hasegawa, Hiroshi Nishihara, Toshihisa Ohtsuka, Shinya Tanaka, Yoshio Tsuboi, Shigetsugu Hatakeyama, Koichi Wakabayashi, Hidenao Sasaki
Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult because various phenotypes have been identified. Here, we report a mutation in the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical features resembled not only those of PSP patients but also those of individuals with multiple system atrophy and Alzheimer's disease. The neuropathological findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral degeneration and hippocampal sclerosis...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339255/design-synthesis-and-biological-evaluation-of-lx2343-derivatives-as-neuroprotective-agents-for-the-treatment-of-alzheimer-s-disease
#10
Guanglong Sun, Junwei Wang, Xiaodan Guo, Min Lei, Yinan Zhang, Xiachang Wang, Xu Shen, Lihong Hu
A series of LX2343 derivatives were designed, synthesized and evaluated as neuroprotective agents for Alzheimer's disease (AD) in vitro. Most of the compounds displayed potent neuroprotective activities. Especially for compound A6, exhibited a remarkable EC50 value of 0.22 μM. Further investigation demonstrated that compound A6 can significantly reduce Aβ production and increase Aβ clearance, and alleviate Tau hyperphosphorylation. Most importantly, compound A6 could ameliorate learning and memory impairments in APP/PS1 transgenic mice...
January 2, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29338754/molecular-and-functional-signatures-in-a-novel-alzheimer-s-disease-mouse-model-assessed-by-quantitative-proteomics
#11
Dong Kyu Kim, Joonho Park, Dohyun Han, Jinhee Yang, Ahbin Kim, Jongmin Woo, Youngsoo Kim, Inhee Mook-Jung
BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. To understand the pathological mechanisms underlying AD, developing animal models that completely encompass the main features of AD pathologies is indispensable. Although mouse models that display pathological hallmarks of AD (amyloid plaques, neurofibrillary tangles, or both) have been developed and investigated, a systematic approach for understanding the molecular characteristics of AD mouse models is lacking...
January 16, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29338678/supplementation-with-curcuma-longa-reverses-neurotoxic-and-behavioral-damage-in-models-of-alzheimer-s-disease-a-systematic-review
#12
Ianara Mendonca da Costa, Marco Aurelio de Moura Freire, Jose Rodolfo Lopes de Paiva Cavalcanti, Dayane Pessoa de Araujo, Bianca Norrara, Isleania Maria Marques Moreira Rosa, Eduardo Pereira de Azevedo, Amalia Cinthia Meneses do Rego, Irami Araujo Filho, Fausto Pierdona Guzen
BACKGROUND: The formation of senile plaques and neurofibrillary tangles of the tau protein are the main pathological mechanism of Alzheimer's disease (AD). Current therapies for AD offer discrete benefits to the clinical symptoms and do not prevent the continuing degeneration of neuronal cells. Therefore, novel therapeutic strategies have long been investigated, where curcumin (Curcuma longa) has shown some properties that can prevent the deleterious processes involved in neurodegenerative diseases...
January 16, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29338612/gene-profiling-of-nucleus-basalis-tau-containing-neurons-in-chronic-traumatic-encephalopathy-a-chronic-effects-of-neurotrauma-consortium-study
#13
Elliott Jay Mufson, Bin He, Stephen D Ginsberg, Benjamin A Carper, Gayle S Bieler, Fiona C Crawford, Victor E Alverez, Bernard R Huber, Thor D Stein, Ann C McKee, Sylvia E Perez
Military personnel and athletes exposed to traumatic brain injury may develop chronic traumatic encephalopathy (CTE). Brain pathology in CTE includes intracellular accumulation of abnormally phosphorylated tau proteins (p-tau), the main constituent of neurofibrillary tangles (NFTs). Recently, we found that cholinergic basal forebrain (CBF) neurons within the nucleus basalis of Meynert (nbM), which provide the major cholinergic innervation to the cortex, display an increasing number of NFTs across the pathological stages of CTE...
January 16, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29338452/an-update-on-diagnostic-and-prognostic-biomarkers-for-traumatic-brain-injury
#14
Kevin K Wang, Zhihui Yang, Tian Zhu, Yuan Shi, Richard Rubenstein, J Adrian Tyndall, Geoff T Manley
Traumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encouragingly, there are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome. Area covered: The authors provide an update on the current knowledge of TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH-L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non-protein biomarkers...
January 17, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29337233/tau-deficiency-down-regulated-transcription-factor-orthodenticle-homeobox-2-expression-in-the-dopaminergic-neurons-in-ventral-tegmental-area-and-caused-no-obvious-motor-deficits-in-mice
#15
Xiaolu Tang, Luyan Jiao, Meige Zheng, Yan Yan, Qi Nie, Ting Wu, Xiaomei Wan, Guofeng Zhang, Yonglin Li, Song Wu, Bin Jiang, Huaibin Cai, Pingyi Xu, Jinhai Duan, Xian Lin
Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes are controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau+/+, tau+/-, tau-/- mice. We found tau deficiency could not induce significant motor disorders...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29334921/a-pilot-feasibility-randomised-controlled-trial-of-an-adjunct-brief-social-network-intervention-in-opiate-substitution-treatment-services
#16
Ed Day, Alex Copello, Jennifer L Seddon, Marilyn Christie, Deborah Bamber, Charlotte Powell, Carmel Bennett, Shabana Akhtar, Sanju George, Andrew Ball, Emma Frew, Ilias Goranitis, Nick Freemantle
BACKGROUND: Approximately 3% of people receiving opioid substitution therapy (OST) in the UK manage to achieve abstinence from prescribed and illicit drugs within three years of commencing treatment. Involvement of families and wider social networks in supporting psychological treatment may be an effective strategy in facilitating recovery, and this pilot study aimed to evaluate the impact of a social network-focused intervention for patients receiving OST. METHODS: A two-site, open feasibility trial randomised patients receiving OST for at least 12 months but still reporting illicit opiate use in the past 28 days to one of three treatments: 1) treatment as usual (TAU), 2) Brief Social Behaviour and Network Therapy (B-SBNT) + TAU, or 3) Personal Goal Setting (PGS) + TAU...
January 15, 2018: BMC Psychiatry
https://www.readbyqxmd.com/read/29332046/a-novel-antibody-targeting-tau-phosphorylated-at-serine-235-detects-neurofibrillary-tangles
#17
David Brici, Jürgen Götz, Rebecca M Nisbet
Alzheimer's disease is characterized by two main pathological hallmarks in the human brain: the extracellular deposition of amyloid-β as plaques and the intracellular accumulation of the hyperphosphorylated protein tau as neurofibrillary tangles (NFTs). Phosphorylated tau (p-tau) specific-antibodies and silver staining have been used to reveal three morphological stages of NFT formation: pre-NFTs, intraneuronal NFTs (iNFTs), and extraneuronal NFTs (eNFTs). Here we characterize a novel monoclonal antibody, RN235, which is specific for tau phosphorylated at serine 235, and detects iNFTs and eNFTs in brain tissue, suggesting that phosphorylation at this site is indicative of late stage changes in tau...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332041/in-vivo-visualization-of-tau-accumulation-microglial-activation-and-brain-atrophy-in-a-mouse-model-of-tauopathy-rtg4510
#18
Ai Ishikawa, Masaki Tokunaga, Jun Maeda, Takeharu Minamihisamatsu, Masafumi Shimojo, Hiroyuki Takuwa, Maiko Ono, Ruiqing Ni, Shigeki Hirano, Satoshi Kuwabara, Bin Ji, Ming-Rong Zhang, Ichio Aoki, Tetsuya Suhara, Makoto Higuchi, Naruhiko Sahara
BACKGROUND: Tau imaging using PET is a promising tool for the diagnosis and evaluation of tau-related neurodegenerative disorders, but the relationship among PET-detectable tau, neuroinflammation, and neurodegeneration is not yet fully understood. OBJECTIVE: We aimed to elucidate sequential changes in tau accumulation, neuroinflammation, and brain atrophy by PET and MRI in a tauopathy mouse model. METHODS: rTg4510 transgenic (tg) mice expressing P301L mutated tau and non-tg mice were examined with brain MRI and PET imaging (analyzed numbers: tg = 17, non-tg = 13; age 2...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332037/increased-vulnerability-of-the-hippocampus-in-transgenic-mice-overexpressing-app-and-triple-repeat-tau
#19
Andrew Arner, Edward Rockenstein, Michael Mante, Jazmin Florio, Deborah Masliah, Bahar Salehi, Anthony Adame, Cassia Overk, Eliezer Masliah, Robert A Rissman
 Alzheimer's disease (AD) is the most common tauopathy, characterized by progressive accumulation of amyloid-β (Aβ) and hyperphosphorylated tau. While pathology associated with the 4-repeat (4R) tau isoform is more abundant in corticobasal degeneration and progressive supranuclear palsy, both 3R and 4R tau isoforms accumulate in AD. Many studies have investigated interactions between Aβ and 4R tau in double transgenic mice, but few, if any, have examined the effects of Aβ with 3R tau. To examine this relationship, we crossed our APP751 mutant line with our recently characterized 3R tau mutant model to create a bigenic line (hAPP-3RTau) to model AD neuropathology...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29331877/cerebral-changes-and-disrupted-gray-matter-cortical-networks-in-asymptomatic-older-adults-at-risk-for-alzheimer-s-disease
#20
Jose L Cantero, Mercedes Atienza, Pascual Sanchez-Juan, Eloy Rodriguez-Rodriguez, Jose Luis Vazquez-Higuera, Ana Pozueta, Andrea Gonzalez-Suarez, Eduard Vilaplana, Jordi Pegueroles, Victor Montal, Rafael Blesa, Daniel Alcolea, Alberto Lleo, Juan Fortea
The diagnostic value of cerebrospinal fluid (CSF) biomarkers is well established in Alzheimer's disease, but our current knowledge about how abnormal CSF levels affect cerebral integrity, at local and network levels, is incomplete in asymptomatic older adults. Here, we have collected CSF samples and performed structural magnetic resonance imaging scans in cognitively normal elderly as part of a cross-sectional multicenter study (SIGNAL project). To identify group differences in cortical thickness, white matter volume, and properties of structural networks, participants were split into controls (N = 20), positive amyloid-β (Aβ1-42+) (N = 19), and positive phosphorylated tau (N = 18)...
December 20, 2017: Neurobiology of Aging
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