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https://www.readbyqxmd.com/read/29161441/contributions-of-function-altering-variants-in-genes-implicated-in-pubertal-timing-and-body-mass-for-self-limited-delayed-puberty
#1
Sasha R Howard, Leonardo Guasti, Ariel Poliandri, Alessia David, Claudia P Cabrera, Michael R Barnes, Karoliina Wehkalampi, Stephen O'Rahilly, Catherine E Aiken, Anthony P Coll, Marcella Ma, Debra Rimmington, Giles S H Yeo, Leo Dunkel
Context: Self-limited delayed puberty (DP) is often associated with delay in physical maturation, but whilst highly heritable the causal genetic factors remain elusive. Genome-wide association studies of the timing of puberty have identified multiple loci for age of menarche (AAM) in females and voice break in males, particularly in pathways controlling energy balance. Objective/Main outcome measures: We aimed to assess the contribution of rare variants in such genes to the phenotype of familial DP...
November 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29160901/dietary-advanced-glycation-end-products-have-sex-and-age-dependent-effects-on-vertebral-bone-microstructure-and-mechanical-function-in-mice
#2
Svenja Illien-Jünger, Paolo Palacio-Mancheno, William F Kindschuh, Xue Chen, Grazyna E Sroga, Deepak Vashishth, James C Iatridis
Back pain is a leading cause of global disability that can arise from vertebral fracture and osteoporosis. While poor general health and obesity are among the strongest risk factors for back pain, there is remarkably little known about how diet influences spinal diseases. Advanced glycation endproducts (AGEs) are implicated in increased fracture risk, yet no studies investigated how dietary AGEs affect spinal health. We tested the hypothesis that high dietary AGE ingestion will diminish vertebral structure and function in a sex- and age-dependent manner...
November 21, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29160844/altered-aconitase-2-activity-in-huntington-s-disease-peripheral-blood-cells-and-mouse-model-striatum
#3
Chiung-Mei Chen, Yih-Ru Wu, Kuo-Hsuan Chang
Huntington's disease (HD) is caused by an unstable cytosine adenine guanine (CAG) trinucleotide repeat expansion encoding a polyglutamine tract in the huntingtin protein. Previously, we identified several up- and down-regulated protein molecules in the striatum of the Hdh((CAG)150) knock-in mice at 16 months of age, a mouse model which is modeling the early human HD stage. Among those molecules, aconitase 2 (Aco2) located in the mitochondrial matrix is involved in the energy generation and susceptible to increased oxidative stress that would lead to inactivation of Aco2 activity...
November 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29160796/role-of-galectin-3-in-bone-cell-differentiation-bone-pathophysiology-and-vascular-osteogenesis
#4
REVIEW
Carla Iacobini, Claudia Blasetti Fantauzzi, Giuseppe Pugliese, Stefano Menini
Galectin-3 is expressed in various tissues, including the bone, where it is considered a marker of chondrogenic and osteogenic cell lineages. Galectin-3 protein was found to be increased in the differentiated chondrocytes of the metaphyseal plate cartilage, where it favors chondrocyte survival and cartilage matrix mineralization. It was also shown to be highly expressed in differentiating osteoblasts and osteoclasts, in concomitance with expression of osteogenic markers and Runt-related transcription factor 2 and with the appearance of a mature phenotype...
November 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29160692/s100a9-protein-aggregates-boost-hippocampal-glutamate-modifying-monoaminergic-neurochemistry-a-glutamate-antibody-sensitive-outcome-on-alzheimer-like-memory-decline
#5
Marina A Gruden, Tatiana V Davydova, Vladimir S Kudrin, Chao Wang, Victor B Narkevich, Ludmilla A Morozova-Roche, Robert D E Sewell
Alzheimer's disease (AD) involves dementia conceivably arising from integrated inflammatory processes, amyloidogenesis and neuronal apoptosis. Glutamate can also cause neuronal death via excitotoxicity and this is similarly implicated in some neurological diseases. The aim was to examine treatment with in vitro generated pro-inflammatory protein S100A9 aggregate species alone or with glutamate antibodies (Glu-Abs) on Morris water maze (MWM) spatial learning and memory performance in 12-month old mice. Amino acid and monoamine cerebral neurotransmitter metabolic changes were concurrently monitored...
November 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29160110/peroxiredoxin6-a-multitask-antioxidant-enzyme-involved-in-the-pathophysiology-of-chronic-non-communicable-diseases
#6
Francesca Pacifici, David Della-Morte, Barbara Capuani, Donatella Pastore, Alfonso Bellia, Paolo Sbraccia, Nicola Di Daniele, Renato Lauro, Davide Lauro
SIGNIFICANCE: Chronic Non-Communicable Diseases (NCDs) are the leading causes of disability and death worldwide. NCDs mainly comprise diabetes mellitus, cardiovascular diseases, chronic obstructive pulmonary disease (COPD), cancer, and neurological degenerative diseases, which kill more than 80% of population, especially elderlies, worldwide. Recent Advances: Several recent theories established NCDs as multifactorial diseases, where a combination of genetic, epigenetic and environmental factors contributes to their pathogenesis...
November 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29159318/young-donor-white-blood-cell-immunotherapy-induces-extensive-tumor-necrosis-in-advanced-stage-solid-tumors
#7
Dipnarine Maharaj, Pedro G Vianna, Wendy Ward, Anthony J Messina, Trevor Rayborn, Jacqueline V Gouvea, Richard D Hammer, Zheng Cui
Background: In the past decade, a variety of immunotherapy approaches focused predominantly on the adaptive immune system have shown unprecedented responses in patients with advanced-stage malignancies. However, studies in spontaneous regression/complete resistance (SR/CR) mice and humans have shown a novel innate cancer-killing activity mediated by granulocytes, which is completely transferable for prevention or therapy against established malignancies. Methods: Three patients with advanced, relapsed or refractory solid tumors for which no standard therapy was available or was refused were enrolled into this ongoing combined phase I/II open label clinical trial testing the safety, dose tolerance, and possible antineoplastic efficacy of sequential infusions of HLA-mismatched non-irradiated allogeneic white cells (68-91% granulocytes) collected by leukapheresis from young, healthy donors (age 18-35) following mobilization with granulocyte colony stimulating factor (G-CSF) and dexamethasone...
October 2017: Heliyon
https://www.readbyqxmd.com/read/29158587/analysis-of-the-gut-microbiome-and-plasma-short-chain-fatty-acid-profiles-in-a-spontaneous-mouse-model-of-metabolic-syndrome
#8
Kazuchika Nishitsuji, Jinzhong Xiao, Ryosuke Nagatomo, Hitomi Umemoto, Yuki Morimoto, Hiroyasu Akatsu, Koichi Inoue, Koichi Tsuneyama
Male Tsumura Suzuki obese diabetes (TSOD) mice spontaneously develop obesity and obesity-related metabolic syndrome. Gut dysbiosis, an imbalance of gut microbiota, has been implicated in the pathogenesis of metabolic syndrome, but its mechanisms are unknown. Short-chain fatty acids (SCFAs) are the main fermentation products of gut microbiota and a link between the gut microbiota and the host's physiology. Here, we investigated a correlation among gut dysbiosis, SCFAs, and metabolic syndrome in TSOD mice. We detected enriched levels of Gram-positive bacteria and corresponding decreases in Gram-negative bacteria in 24-wk-old metabolic syndrome-affected TSOD mice compared with age-matched controls...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158586/insights-into-gene-expression-profiles-induced-by-socs3-depletion-in-keratinocytes
#9
Archana Bajpai, Takashi Ishii, Kosuke Miyauchi, Vipul Gupta, Yuka Nishio-Masaike, Yuki Shimizu-Yoshida, Masato Kubo, Hiroaki Kitano
Specific deletion of suppressor of cytokine signaling 3 (Socs3) in keratinocytes can cause severe skin inflammation with infiltration of immune cells. The molecular mechanisms and key regulatory pathways involved in these processes remain elusive. To investigate the role of Socs3 in keratinocytes, we generated and analyzed global RNA-Seq profiles from Socs3 conditional knockout (cKO) mice of two different ages (2 and 10 weeks). Over 400 genes were significantly regulated at both time points. Samples from 2-week-old mice exhibited down-regulation of genes involved in keratin-related functions and up-regulation of genes involved in lipid metabolism...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158260/the-actin-organizing-formin-protein-fhod3-is-required-for-postnatal-development-and-functional-maintenance-of-the-adult-heart-in-mice
#10
Tomoki Ushijima, Noriko Fujimoto, Sho Matsuyama, Meikun Kan-O, Hiroshi Kiyonari, Go Shioi, Yohko Kage, Sho Yamasaki, Ryu Takeya, Hideki Sumimoto
Cardiac development and function require actin-myosin interactions in the sarcomere, a highly organized contractile structure. Sarcomere assembly mediated by formin homology 2 domain-containing 3 (Fhod3), a member of formins that direct formation of straight actin filaments, is essential for embryonic cardiogenesis. However, the role of Fhod3 in the neonatal and adult stages has remained unknown. Here we generated floxed Fhod3 mice to bypass the embryonic lethality of an Fhod3 knockout (KO). Perinatal KO of Fhod3 in the heart caused juvenile lethality at around day 10 after birth with enlarged hearts composed of severely impaired myofibrils, indicating that Fhod3 is crucial for postnatal heart development...
November 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29158112/subtle-behavioral-changes-and-increased-prefrontal-hippocampal-network-synchronicity-in-app-nl-g-f-mice-before-prominent-plaque-deposition
#11
Amira Latif Hernandez, Disha Shah, Kathleen Craessaerts, Takaomi Saido, Takashi Saito, Bart De Strooper, Annemie Van der Linden, Rudi D'Hooge
Amyloid-β (Aβ) peptides occur in the brains of patients with Alzheimer's disease (AD), but their role in functional impairment is still debated. High levels of APP and APP fragments in mice that overexpress APP might confound their use in preclinical research. We examined the occurrence of behavioral, cognitive and neuroimaging changes in APP(NL-G-F) knock-in mice that display Aβ42 amyloidosis in the absence of APP overexpression. Female APP(NL-G-F) mice (carrying Swedish, Iberian and Arctic APP mutations) were compared to APP(NL) mice (APP Swedish) at 3, 7 and 10 months...
November 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29158108/signaling-by-synaptic-zinc-is-required-for-whisker-mediated-fine-texture-discrimination
#12
Hsia-Pai Patrick Wu, Richard H Dyck
Zinc-containing terminals are found throughout the neocortex, concentrated predominantly in layers II/III, V, and VI. Synaptic zinc is a potent neurotransmitter/modulator and, therefore, may mediate inter- or intra-cortical integration of sensory information. We have previously shown that levels of synaptic zinc are rapidly modulated in somatosensory (barrel) cortex, in an experience- and activity-dependent manner. Zinc Transporter 3 (ZnT3) knockout (KO) mice lack synaptic zinc and provide us with a good model to examine the contribution of synaptic zinc to barrel cortex-dependent behavior...
November 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/29157601/modulation-of-cognition-and-anxiety-like-behavior-by-bone-remodeling
#13
Lori Khrimian, Arnaud Obri, Gerard Karsenty
OBJECTIVE: That the bone-derived hormone osteocalcin is necessary to promote normal brain development and function, along with its recently described sufficiency in reversing cognitive manifestations of aging, raises novel questions. One of these is to assess whether bone health, which deteriorates rapidly with aging, is a significant determinant of cognition and anxiety-like behavior. METHODS: To begin addressing this question, we used mice haploinsufficient for Runx2, the master gene of osteoblast differentiation and the main regulator of Osteocalcin expression...
December 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29157127/modulation-of-the-gut-microbiota-by-metformin-improves-metabolic-profiles-in-aged-obese-mice
#14
Heetae Lee, Youngjoo Lee, Jiyeon Kim, Jinho An, Sungwon Lee, Hyunseok Kong, Youngcheon Song, Chong-Kil Lee, Kyungjae Kim
The gut microbiota is a contributing factor in obesity-related metabolic disorders. The effect of metformin on the gut microbiota has been reported; however, the relationship between the gut microbiota and the mechanism of action of metformin in elderly individuals is unclear. In this study, the effect of metformin on the gut microbiota was investigated in aged obese mice. The abundance of the genera Akkermansia, Bacteroides, Butyricimonas, and Parabacteroides was significantly increased by metformin in mice fed a high-fat diet...
November 20, 2017: Gut Microbes
https://www.readbyqxmd.com/read/29157116/perinatal-exposure-to-high-dietary-advanced-glycation-end-products-in-transgenic-nod8-3-mice-leads-to-pancreatic-beta-cell-dysfunction
#15
Danielle J Borg, Felicia Y T Yap, Sahar Keshvari, David G Simmons, Linda A Gallo, Amelia K Fotheringham, Aowen Zhuang, Robyn M Slattery, Sumaira Z Hasnain, Melinda T Coughlan, Phillip Kantharidis, Josephine M Forbes
The contribution of environmental factors to pancreatic islet damage in type 1 diabetes remains poorly understood. In this study, we crossed mice susceptible to type 1 diabetes, where parental male (CD8(+) T cells specific for IGRP206-214; NOD8.3) and female (NOD/ShiLt) mice were randomized to a diet either low or high in AGE content and maintained on this diet throughout pregnancy and lactation. After weaning, NOD8.3(+) female offspring were identified and maintained on the same parental feeding regimen for until day 28 of life...
November 20, 2017: Islets
https://www.readbyqxmd.com/read/29156156/effects-of-arachidonic-acid-eicosapentaenoic-acid-and-docosahexaenoic-acid-on-brain-development-using-artificial-rearing-of-delta-6-desaturase-knockout-mice
#16
Akiko Harauma, Erisa Hatanaka, Hidemi Yasuda, Manabu T Nakamura, Norman Salem, Toru Moriguchi
This study focused on the effect of polyunsaturated fatty acids (PUFAs) during the lactation period of delta-6-desaturase knockout (D6D-KO) mice using an artificial rearing method. Newborn pups of D6D-KO male mice were separated from their dams within 48h and were fed artificial milk. Six formulations of milk were used: Control (Cont) milk (3.9% α-linolenic acid and 18% linoleic acid), + 1.3% arachidonic acid (ARA), + 1.2% docosahexaenoic acid (DHA), + 1.3% eicosapentaenoic acid (EPA), + 1.1% ARA + 1.3% DHA, and + 1...
December 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/29155983/meox1-accelerates-myocardial-hypertrophic-decompensation-through-gata4
#17
Dan Lu, Jizheng Wang, Jing Li, Feifei Guan, Xu Zhang, Wei Dong, Ning Liu, Shan Gao, Lianfeng Zhang
Aims: Pathological hypertrophy is the result of gene network regulation, which ultimately leads to adverse cardiac remodelling and heart failure (HF), and is accompanied by the reactivation of a 'foetal gene programme'. The Mesenchyme homeobox 1 (Meox1) gene is one of the foetal programme genes. Meox1 may play a role in embryonic development, but its regulation of pathological hypertrophy is not known. Therefore, this study investigated the effect of Meox1 on pathological hypertrophy, including familial and pressure overload-induced hypertrophy, and its potential mechanism of action...
November 16, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29155979/epigenetic-editing-of-the-dlg4-psd95-gene-improves-cognition-in-aged-and-alzheimer-s-disease-mice
#18
Fernando J Bustos, Estibaliz Ampuero, Nur Jury, Rodrigo Aguilar, Fahimeh Falahi, Jorge Toledo, Juan Ahumada, Jaclyn Lata, Paula Cubillos, Berta Henríquez, Miguel V Guerra, Jimmy Stehberg, Rachael L Neve, Nibaldo C Inestrosa, Ursula Wyneken, Marco Fuenzalida, Steffen Härtel, Miguel Sena-Esteves, Lorena Varela-Nallar, Marianne G Rots, Martin Montecino, Brigitte van Zundert
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9)...
November 16, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29155004/variability-and-temporal-dynamics-of-novel-object-recognition-in-aging-male-c57bl-6-mice
#19
Andreas Traschütz, Markus P Kummer, Stephanie Schwartz, Michael T Heneka
No abstract text is available yet for this article.
November 15, 2017: Behavioural Processes
https://www.readbyqxmd.com/read/29154859/expression-of-cgrp-neurotransmitter-and-vascular-genesis-marker-mrna-is-age-dependent-in-superior-cervical-ganglia-of-senescence-accelerated-prone-mice
#20
Kazuyuki Mitsuoka, Takeshi Kikutani, Yoko Miwa, Iwao Sato
Calcitonin gene-related peptide (CGRP) is a neurotransmitter that is released from the superior cervical ganglion (SCG) and causes head and neck pain. The morphological properties of human SCG neurons, including neurotransmitter content, are altered during aging. However, morphological changes in CGRP in the SCG during aging are not known. Therefore, we investigated CGRP and other markers in the SCG during aging in an aging model of senescence-accelerated prone mouse (SAMP8) and senescence-accelerated resistant mice (SAMR1) using real-time RT-PCR mRNA analyses and in situ hybridization...
November 14, 2017: Neuroscience Letters
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