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https://www.readbyqxmd.com/read/27911312/increased-transforming-growth-factor-%C3%AE-2-in-the-neocortex-of-alzheimer-s-disease-and-dementia-with-lewy-bodies-is%C3%A2-correlated-with-disease-severity-and%C3%A2-soluble-a%C3%AE-42-load
#1
Joyce R Chong, Yuek Ling Chai, Jasinda H Lee, David Howlett, Johannes Attems, Clive G Ballard, Dag Aarsland, Paul T Francis, Christopher P Chen, Mitchell K P Lai
BACKGROUND: Of the three transforming growth factor (TGF)-β isoforms known, TGFβ1 deficits have been widely reported in Alzheimer's disease (AD) and studied as a potential therapeutic target. In contrast, the status of TGFβ2, which has been shown to mediate amyloid-β (Aβ)-mediated neuronal death, are unclear both in AD and in Lewy body dementias (LBD) with differential neuritic plaque and neurofibrillary tangle burden. OBJECTIVE: To measure neocortical TGFβ2 levels and their correlations with neuropathological and clinical markers of disease severity in a well-characterized cohort of AD as well as two clinical subtypes of LBD, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), known to manifest relatively high and low Aβ plaque burden, respectively...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27903893/identification-of-a-novel-k311-ubiquitination-site-critical-for-androgen-receptor-transcriptional-activity
#2
Urszula L McClurg, David M W Cork, Steven Darby, Claudia A Ryan-Munden, Sirintra Nakjang, Leticia Mendes Côrtes, Achim Treumann, Luke Gaughan, Craig N Robson
The androgen receptor (AR) is the main driver of prostate cancer (PC) development and progression, and the primary therapeutic target in PC. To date, two functional ubiquitination sites have been identified on AR, both located in its C-terminal ligand binding domain (LBD). Recent reports highlight the emergence of AR splice variants lacking the LBD that can arise during disease progression and contribute to castrate resistance. Here, we report a novel N-terminal ubiquitination site at lysine 311. Ubiquitination of this site plays a role in AR stability and is critical for its transcriptional activity...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895202/the-lbd12-1-transcription-factor-suppresses-apical-meristem-size-by-repressing-argonaute-10-expression
#3
Weiwei Ma, Fuqing Wu, Peike Sheng, Xiaole Wang, Zhe Zhang, Kunneng Zhou, Huan Zhang, Jinlong Hu, Qibing Lin, Zhijun Cheng, Jiulin Wang, Shanshan Zhu, Xin Zhang, Xiuping Guo, Haiyang Wang, Chuanyin Wu, Jianmin Wan
The shoot apical meristem (SAM) consists of a population of multipotent cells that generate all aerial structures and regenerates itself. SAM maintenance and lateral organ development are regulated by several complex signaling pathways, in which the Argonaute gene mediated pathway plays a key role. One Argonaute gene, AGO10, functions as a miRNA locker that attenuates miR165/166 activity and positively regulates shoot apical meristem development, but little is known about when and how AGO10 is regulated at the transcriptional level...
November 28, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27890717/ecdysone-receptor-ecr-and-ultraspiracle-usp-genes-from-the-cyclopoid-copepod-paracyclopina-nana-identification-and-expression-in-response-to-water-accommodated-fractions-wafs
#4
Jayesh Puthumana, Min-Chul Lee, Jeonghoon Han, Hui-Su Kim, Dae-Sik Hwang, Jae-Seong Lee
Ecdysteroid hormones are pivotal in the development, growth, and molting of arthropods, and the hormone pathway is triggered by binding ecdysteroid to a heterodimer of the two nuclear receptors; ecdysone receptors (EcR) and ultraspiracle (USP). We have characterized EcR and USP genes, and their 5'-untranslated region (5'-UTR) from the copepod Paracyclopina nana, and studied mRNA transcription levels in post-embryonic stages and in response to water accommodated fractions (WAFs) of crude oil. The open reading frames (ORF) of EcR and USP were 1470 and 1287bp that encoded 490 and 429 amino acids with molecular weight of 121...
November 23, 2016: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/27890450/src2-3-binds-to-vitamin-d-receptor-with-high-sensitivity-and-strong-affinity
#5
Daichi Egawa, Toshimasa Itoh, Akira Kato, Saori Kataoka, Yasuaki Anami, Keiko Yamamoto
Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily and regulates the expression of target genes through ligand binding. To express the target gene, coactivator binding to the VDR/ligand complex is essential. Although there are many coactivators in living cells, precise interactions between coactivators and VDR have not been clarified. Here, we synthesized two coactivator peptides, DRIP205-2 and SRC2-3, evaluated their affinity for the ligand-binding domain (LBD) of VDR using 1α,25-dihydroxyvitamin D3, partial agonist 1, and antagonist 2 by surface plasmon resonance (SPR), and assessed their interaction modes with VDR-LBD using X-ray crystallographic analysis...
November 14, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27870939/mixed-neuropathologies-and-estimated-rates-of-clinical-progression-in-a-large-autopsy-sample
#6
Willa D Brenowitz, Rebecca A Hubbard, C Dirk Keene, Stephen E Hawes, W T Longstreth, Randy L Woltjer, Walter A Kukull
INTRODUCTION: Whether co-occurring neuropathologies interact or independently affect clinical disease progression is uncertain. We estimated rates of clinical progression and tested whether associations between clinical progression and Alzheimer's disease neuropathology (ADNP) were modified by co-occurring Lewy body disease (LBD) or vascular brain injury (VBI). METHODS: Linear mixed effects models evaluated longitudinal trends in the Clinical Dementia Rating Sum of Boxes on 2046 autopsied participants seen at a U...
November 18, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27868177/-early-use-of-memantine-in-the-treatment-of-lewy-body-dementia
#7
H Vanhaute, P Persoons
Early use of memantine in the treatment of Lewy body dementia (LBD) is a common type of major neurocognitive disorder (NCD), which is difficult to treat. The use of memantine can be an early treatment strategy. This is illustrated by a case of an 80-year-old patient whose cognition, motor skills and perception disorders reacted favourably to treatment with memantine. The beneficial effect, however, was soon lost after the treatment was discontinued, but reappeared after the medication was reintroduced.
2016: Tijdschrift Voor Psychiatrie
https://www.readbyqxmd.com/read/27864003/novel-screening-system-for-high-affinity-ligand-of-heredity-vitamin-d-resistant-rickets-associated-vitamin-d-receptor-mutant-r274l-using-bioluminescent-sensor
#8
Hiroki Mano, Miyu Nishikawa, Kaori Yasuda, Shinichi Ikushiro, Nozomi Saito, Daisuke Sawada, Shinobu Honzawa, Masashi Takano, Atsushi Kittaka, Toshiyuki Sakaki
Hereditary vitamin D-resistant rickets (HVDRR) is caused by mutations in the vitamin D receptor (VDR) gene. Arg274 located in the ligand binding domain (LBD) of VDR is responsible for anchoring 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) by forming a hydrogen bond with the 1α-hydroxyl group of 1α,25(OH)2D3. The Arg274Leu (R274L) mutation identified in patients with HVDRR causes a 1000-fold decrease in the affinity for 1α,25(OH)2D3, and dramatically reduces vitamin D- related gene expression. Recently, we successfully constructed fusion proteins consisting of split-luciferase and LBD of the VDR...
November 15, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27860026/medical-specialists-care-and-hospital-costs-for-low-back-pain-in-the-netherlands
#9
C J Itz, B L T Ramaekers, M van Kleef, C D Dirksen
BACKGROUND: To examine the organization of medical specialist care and hospital costs for low back pain (LBP) in the Netherlands. METHODS: Aggregated health insurance claims data were provided on all diagnosis treatment combination (DTC) declarations for LBP patients first referred to the hospital in the 2nd half of 2008 and retrieved from Vektis, an organization that collects health insurance claims data. Data were available up to 1 January 2012. The data included patient characteristics, DTC-specific information including: neurology, neurosurgery, orthopaedic surgery, anaesthesiology and radiology...
November 8, 2016: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/27849622/novel-mutations-of-the-srd5a2-and-ar-genes-in-thai-patients-with-46-xy-disorders-of-sex-development
#10
Chupong Ittiwut, Jaturong Pratuangdejkul, Vichit Supornsilchai, Sasipa Muensri, Yodporn Hiranras, Taninee Sahakitrungruang, Suttipong Watcharasindhu, Kanya Suphapeetiporn, Vorasuk Shotelersuk
BACKGROUND: Abnormalities of dihydrotestosterone conversion [5α-reductase deficiency: online Mendelian inheritance in man (OMIM) 607306] or actions of androgens [partial androgen insensitivity syndrome (PAIS): OMIM 312300] during the 8th-12th weeks of gestation cause varying degrees of undervirilized external genitalia in 46, XY disorders of sex development (DSD) with increased testosterone production. The objective of the study was to determine clinical and genetic characteristics of Thai patients with 46, XY DSD...
November 16, 2016: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/27848066/molecular-mechanism-of-r-bicalutamide-switching-from-androgen-receptor-antagonist-to-agonist-induced-by-amino-acid-mutations-using-molecular-dynamics-simulations-and-free-energy-calculation
#11
Hongli Liu, Rui Han, Jiazhong Li, Huanxiang Liu, Lifang Zheng
R-bicalutamide, a first generation antiandrogen, was used to treat prostate cancer for decades. Although it is very effective at the beginning, resistance appears after 2-3 years of treatment. Mutation of androgen receptor (AR) is considered a main reason for drug resistance. It is reported that AR W741C, W741L, W741C_T877A, T877A, F876L, F876L_T877A and L701H mutations can convert R-bicalutamide from AR antagonist to agonist, but the switching mechanisms are not clear. In this study, molecular dynamics simulations and molecular mechanics generalized Born surface area (MM-GBSA) calculations were performed to analyze the interaction mechanisms between R-bicalutamide and wild type/mutant ARs...
November 15, 2016: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/27843674/granulovacuolar-degeneration-in-hippocampus-of-neurodegenerative-diseases-quantitative-study
#12
Maher Kurdi, Esther Chin, Lee Cyn Ang
Background. Granulovacuolar degeneration (GVD) is one of the pathological features long associated with Alzheimer's disease (AD) and normal aging. Aim. We investigate the frequency of GVDs in AD, other neurodegenerative diseases, and normal aging, with attempt to determine whether the GVD has preponderance in any particular neurodegenerative disease other than AD. Materials and Methods. A retrospective review of 111 autopsied cases with a variety of neurodegenerative diseases and 70 control cases without pathological evidence of neurodegeneration was evaluated quantitatively...
2016: Journal of Neurodegenerative Diseases
https://www.readbyqxmd.com/read/27832947/sensitive-detection-of-estradiol-based-on-ligand-binding-domain-of-estrogen-receptor-and-gold-nanoparticles
#13
Pimchanok Busayapongchai, Sineenat Siri
With increasing concerns of estrogenic effects of endocrine disrupting compounds, the development of simple detection assay for these compounds is an ongoing need. Herein, a simple, rapid, and highly sensitive assay for estradiol (E2) detection was developed using the ligand binding domain of estrogen receptor α (LBD-ERα), the receptor interacting domain of steroid receptor co-activator 1 (RID-SRC1), and gold nanoparticles (AuNPs). The colloidal AuNPs could be stabilized against a salt-induced aggregation by adding LBD-ERα protein...
November 8, 2016: Analytical Biochemistry
https://www.readbyqxmd.com/read/27824891/exploring-flexibility-of-progesterone-receptor-ligand-binding-domain-using-molecular-dynamics
#14
Liangzhen Zheng, Valerie Chunling Lin, Yuguang Mu
Progesterone receptor (PR), a member of nuclear receptor (NR) superfamily, plays a vital role for female reproductive tissue development, differentiation and maintenance. PR ligand, such as progesterone, induces conformation changes in PR ligand binding domain (LBD), thus mediates subsequent gene regulation cascades. PR LBD may adopt different conformations upon an agonist or an antagonist binding. These different conformations would trigger distinct transcription events. Therefore, the dynamics of PR LBD would be of general interest to biologists for a deep understanding of its structure-function relationship...
2016: PloS One
https://www.readbyqxmd.com/read/27824503/nestorone%C3%A2-nes-a-novel-progestin-for-non-oral-contraception-structure-activity-relationships-and-brain-metabolism-studies
#15
Narender Kumar, Jerôme Fagart, Philippe Liere, Scott J Mitchell, Alanah R Knibb, Isabelle Petit-Topin, Marion Rame, Martine El-Etr, Michael Schumacher, Jeremy J Lambert, Marie-Edith Rafestin-Oblin, Regine Sitruk-Ware
Nestorone® (NES) is a highly potent non-androgenic progestin being developed for contraception. NES is a synthetic progestin that may possess neuroprotective and myelin regenerative potential as an added health benefits. In receptor transactivation experiments, NES displayed greater potency than progesterone to transactivate the human progesterone receptor (hPR). This was confirmed by docking experiments which revealed that NES adopts the same docking position within the PR ligand-binding domain (LBD) as progesterone and forms additional stabilizing contacts between 17α-acetoxy and 16-methylene groups and PR LBD supporting its higher potency than progesterone...
November 8, 2016: Endocrinology
https://www.readbyqxmd.com/read/27801938/causes-of-death-according-to-death-certificates-in-individuals-with-dementia-a-cohort-from-the-swedish-dementia-registry
#16
Sara Garcia-Ptacek, Ingemar Kåreholt, Pavla Cermakova, Debora Rizzuto, Dorota Religa, Maria Eriksdotter
OBJECTIVES: The causes of death in dementia are not established, particularly in rarer dementias. The aim of this study is to calculate risk of death from specific causes for a broader spectrum of dementia diagnoses. DESIGN: Cohort study. SETTING: Swedish Dementia Registry (SveDem), 2007-2012. PARTICIPANTS: Individuals with incident dementia registered in SveDem (N = 28,609); median follow-up 741 days. Observed deaths were 5,368 (19%)...
November 2016: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/27791085/molecular-lock-regulates-binding-of-glycine-to-a-primitive-nmda-receptor
#17
Alvin Yu, Robert Alberstein, Alecia Thomas, Austin Zimmet, Richard Grey, Mark L Mayer, Albert Y Lau
The earliest metazoan ancestors of humans include the ctenophore Mnemiopsis leidyi The genome of this comb jelly encodes homologs of vertebrate ionotropic glutamate receptors (iGluRs) that are distantly related to glycine-activated NMDA receptors and that bind glycine with unusually high affinity. Using ligand-binding domain (LBD) mutants for electrophysiological analysis, we demonstrate that perturbing a ctenophore-specific interdomain Arg-Glu salt bridge that is notably absent from vertebrate AMPA, kainate, and NMDA iGluRs greatly increases the rate of recovery from desensitization, while biochemical analysis reveals a large decrease in affinity for glycine...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27786277/the-conformational-dynamics-of-h2-h3n-and-s2-h6-in-gating-ligand-entry-into-the-buried-binding-cavity-of-vitamin-d-receptor
#18
Wei-Ven Tee, Adiratna Mat Ripen, Saharuddin Bin Mohamad
Crystal structures of holo vitamin D receptor (VDR) revealed a canonical conformation in which the ligand is entrapped in a hydrophobic cavity buried in the ligand-binding domain (LBD). The mousetrap model postulates that helix 12 is positioned away from the domain to expose the interior cavity. However, the extended form of helix 12 is likely due to artifacts during crystallization. In this study, we set out to investigate conformational dynamics of apo VDR using molecular dynamics simulation on microsecond timescale...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27768859/4-hydroxyalkenal-activated-ppar%C3%AE-mediates-hormetic-interactions-in-diabetes
#19
Shlomo Sasson
Activated peroxisome proliferator-activated receptor-δ (PPARδ) induces the expression of genes encoding enzymes that metabolize fatty acids and carbohydrate. Attempts to identify cellular activators of PPARδ produced large lists of various fatty acids and their metabolic derivatives; however, there is no consensus on specific and selective binding interactions of natural ligands with PPARδ. Most models on binding interactions within the ligand binding domain (LBD) of PPARδ have been derived from analyses of PPARδ-LBD crystals formed with synthetic low molecular weight ligands...
October 18, 2016: Biochimie
https://www.readbyqxmd.com/read/27762328/nuclear-receptor-nhr-48-is-required-for-pathogenicity-of-the-second-stage-j2-of-the-plant-parasite-meloidogyne-incognita
#20
Chao-Jun Lu, Bao-Yu Tian, Yi Cao, Cheng-Gang Zou, Ke-Qin Zhang
Nuclear receptors (NRs) are a diverse class of transcription factors, which are involved in regulating a large number of physiological events in metazoans. However, the function of NRs is poorly understood in plant-parasitic nematodes. Here, members of the NR1J+K group of NRs in nematodes, including the free-living and plant parasites, were examined and phylogenetically analyzed. We found that the number of members of the NR1J+K group in plant-parasitic nematodes was less than that in the free-living nematodes, suggesting this reduction of NR1J+K group members in plant parasites maybe arose during the separation of the free-living and intermediately plant parasitic nematodes (Bursaphelenchus xylophilus)...
October 20, 2016: Scientific Reports
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