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https://www.readbyqxmd.com/read/28729213/physical-exercise-increases-sestrin-2-protein-levels-and-induces-autophagy-in-the-skeletal-muscle-of-old-mice
#1
Luciene Lenhare, Barbara M Crisol, Vagner R R Silva, Carlos K Katashima, André V Cordeiro, Karina D Pereira, Augusto D Luchessi, Adelino S R da Silva, Dennys E Cintra, Leandro P Moura, José R Pauli, Eduardo R Ropelle
Sestrins and autophagy deficiencies are associated with several aging-related organic dysfunctions and metabolic disorders. Here we evaluate the effects of acute exercise on Sestrin 2 (Sesn2) protein content and autophagy markers in the skeletal muscle of experimental models of aging. Twenty-four months-old C57BL/6J male mice were submitted to a single bout of swimming exercise and the gastrocnemius muscle was evaluated by Western blot. Transcriptomic and phenotypic analysis were also performed by using strains of genetically-diverse BXD mice...
July 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28724767/integrity-of-the-linker-of-nucleoskeleton-and-cytoskeleton-is-required-for-efficient-herpesvirus-nuclear-egress
#2
Barbara G Klupp, Teresa Hellberg, Harald Granzow, Kati Franzke, Beatriz Dominguez Gonzalez, Rose Goodchild, Thomas C Mettenleiter
Herpesvirus capsids assemble in the nucleus while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28716951/a-calcium-diacylglycerol-stimulated-protein-kinase-c-c-elegans-pkc-2-links-thermal-signals-to-learned-behavior-by-acting-in-a-sensory-neuron-and-intestinal-cells
#3
Marianne Land, Charles S Rubin
Ca(2+) and diacylglycerol (DAG) activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a C. elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc) and migrates along Tc within a 17-25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2(-/-) animals...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28708816/determination-of-the-minimal-clinically-important-difference-of-the-university-of-north-carolina-dry-eye-management-scale
#4
Christopher J Hwang, Reeves Ellis, Richard M Davis, Sue Tolleson-Rinehart
PURPOSE: To establish an initial estimation of the MCID of the University of North Carolina Dry Eye Management Scale (UNC DEMS) and assess its association with patient perceptions of symptom change. METHODS: Thirty-three patients (33.3% men, 67.7% women, mean age 60.5 yrs) with previous DEMS scores were recruited from a UNC ophthalmology clinic in spring 2014. We used anchor-based methods, categorizing important symptom change, to compare the change in the DEMS scores across visits to patient assessments of change; linear regression coefficients estimated the MCID...
July 13, 2017: Cornea
https://www.readbyqxmd.com/read/28699918/ampk-activation-dependent-autophagy-compromises-oleanolic-acid-induced-cytotoxicity-in-human-bladder-cancer-cells
#5
Yarong Song, Peng Zhang, Yadong Sun, Xuechao Li, Lifeng Chen, Yajun Xiao, Yifei Xing
Autophagy is an evolutionarily conserved catabolic process in eukaryotic cells, which allows cells to overcome a wide array of of stresses and has recently been shown to result in drug resistance. This study examined the effect of autophagy on oleanolic acid (OA)-induced cytotoxicity against bladder cancer cells. Our study demonstrated that OA inhibited cell viability, proliferation, and induced apoptosis in bladder cancer lines T24 and EJ. Furthermore, OA induced autophagy in both cell lines by activating AMP-activated protein kinase (AMPK), inhibiting mechanistic target of rapamycin (mTOR) and promoting unc-51 like autophagy activating kinase 1 (ULK1)...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28694018/the-enu-3-protein-family-members-function-in-the-wnt-pathway-parallel-to-unc-6-netrin-to-promote-motor-neuron-axon-outgrowth-in-c-elegans
#6
Roxana Oriana Florica, Victoria Hipolito, Stephen Bautista, Homa Anvari, Chloe Rapp, Suzan El-Rass, Alimohammad Asgharian, Costin N Antonescu, Marie T Killeen
The axons of the DA and DB classes of motor neurons fail to reach the dorsal cord in the absence of the guidance cue UNC-6/Netrin or its receptor UNC-5 in C. elegans. However, the axonal processes usually exit their cell bodies in the ventral cord in the absence of both molecules. Strains lacking functional versions of UNC-6 or UNC-5 have a low level of DA and DB motor neuron axon outgrowth defects. We found that mutations in the genes for all six of the ENU-3 proteins function to enhance the outgrowth defects of the DA and DB axons in strains lacking either UNC-6 or UNC-5...
July 7, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28686223/regulation-of-autophagy-through-torc1-and-mtorc1
#7
REVIEW
Takeshi Noda
Autophagy is an intracellular protein-degradation process that is conserved across eukaryotes including yeast and humans. Under nutrient starvation conditions, intracellular proteins are transported to lysosomes and vacuoles via membranous structures known as autophagosomes, and are degraded. The various steps of autophagy are regulated by the target of rapamycin complex 1 (TORC1/mTORC1). In this review, a history of this regulation and recent advances in such regulation both in yeast and mammals will be discussed...
July 7, 2017: Biomolecules
https://www.readbyqxmd.com/read/28685860/exercise-mediated-modulation-of-autophagy-in-skeletal-muscle
#8
REVIEW
Marcos Martin-Rincon, David Morales-Alamo, Jose A L Calbet
Although exercise exerts multiple beneficial health effects, it may also damage cellular structures. Damaged elements are continuously degraded and its constituents recycled to produce renovated structures through a process called autophagy, which is essential for the adaptation to training. Autophagy is particularly active in skeletal muscle, where it can be evaluated by using specific molecular markers of activation (unc-51-like kinase 1 (ULK1) phosphorylation) and specific proteins indicating increased autophagosome content (increased total LC3, LC3-II, LC3-II/LC3-I ratio)...
July 7, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28678595/the-unc-53-gene-negatively-regulates-rac-gtpases-to-inhibit-unc-5-activity-during-distal-tip-cell-migrations-in-c-elegans
#9
Amita Pandey, Vipul Yadav, Aditi Sharma, Jitendra P Khurana, Girdhar K Pandey
The unc-53/NAV2 gene encodes for an adaptor protein required for cell migrations along the anteroposterior (AP) axes of C. elegans. This study identifies unc-53 as a novel component of signaling pathways regulating distal tip cell (DTC) migrations along the AP and dorsoventral (DV) axes. unc-53 negatively regulates and functions downstream of ced-10/Rac pathway genes; ced-10/Rac and mig-2/RhoG, which are required for proper DTC migration. Moreover, unc-53 exhibits genetic interaction with abl-1 and unc-5, the two known negative regulators of ced-10/Rac signaling...
July 5, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28677525/an-intersectional-gene-regulatory-strategy-defines-subclass-diversity-of-c-elegans-motor-neurons
#10
Paschalis Kratsios, Sze Yen Kerk, Catarina Catela, Joseph Liang, Berta Vidal, Emily A Bayer, Weidong Feng, Estanisla Daniel De La Cruz, Laura Croci, G Giacomo Consalez, Kota Mizumoto, Oliver Hobert
A core principle of nervous system organization is the diversification of neuron classes into subclasses that share large sets of features but differ in select traits. We describe here a molecular mechanism necessary for motor neurons to acquire subclass-specific traits in the nematode Caenorhabditis elegans. Cholinergic motor neuron classes of the ventral nerve cord can be subdivided into subclasses along the anterior-posterior (A-P) axis based on synaptic connectivity patterns and molecular features. The conserved COE-type terminal selector UNC-3 not only controls the expression of traits shared by all members of a neuron class, but is also required for subclass-specific traits expressed along the A-P axis...
July 5, 2017: ELife
https://www.readbyqxmd.com/read/28673505/the-first-sign-of-loss-of-consciousness
#11
B S Typ Whinnery, Estrella M Forster
The first clinically observable sign of an unconsciousness episode (UNCE) serves as the temporal sequence (kinetics) onset point for neurological events occurring during the loss of consciousness, unconsciousness and recovery of consciousness phases of the UNCE. The initial neurologic signs of 212 individuals exposed to gradual (N=114) and rapid (N=98) onset +Gz acceleration stress, inducing the ischemic LOC phase in 83.3±18.6s and 8.89±1.52s; p<0.001respectively, were determined. The duration of the unconscious phase (considered absolute incapacitation) was 10...
June 30, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28673312/reduced-nicotine-content-cigarettes-in-smokers-of-low-socioeconomic-status-study-protocol-for-a-randomized-control-trial
#12
Nicolle M Krebs, Sophia I Allen, Susan Veldheer, Diane J Martinez, Kimberly Horn, Craig Livelsberger, Jennifer Modesto, Robin Kuprewicz, Ashley Wilhelm, Shari Hrabovsky, Abid Kazi, Alyse Fazzi, Jason Liao, Junjia Zhu, Emily Wasserman, Samantha M Reilly, Lisa Reinhart, Neil Trushin, Robinn E Moyer, Rebecca Bascom, Jonathan Foulds, John P Richie, Joshua E Muscat
BACKGROUND: The Family Smoking Prevention and Tobacco Control Act gave the Food and Drug Administration jurisdiction over the regulation of all tobacco products, including their nicotine content. Under this act, a major strategy to reduce harm from cigarette tobacco is lowering the nicotine content without causing unintended adverse consequences. Initial research on reduced nicotine content (RNC) cigarettes has shown that smokers of these cigarettes gradually decrease their smoking frequency and biomarkers of exposure...
July 3, 2017: Trials
https://www.readbyqxmd.com/read/28669597/local-intra-articular-injection-of-resveratrol-delays-cartilage-degeneration-in-c57bl-6-mice-by-inducing-autophagy-via-ampk-mtor-pathway
#13
Na Qin, Liwei Wei, Wuyin Li, Wei Yang, Litao Cai, Zhuang Qian, Shufang Wu
Autophagy is an essential cellular homeostasis mechanism that was found to be compromised in aging and osteoarthritis (OA) cartilage. Previous studies showed that resveratrol can effectively regulate autophagy in other cells. The purpose of this study was to determine whether the chondroprotective effect of resveratrol was related to chondrocyte autophagy and to elucidate underlying mechanisms. OA model was induced by destabilization of the medial meniscus (DMM) in 10-week-old male mice. OA mice were treated with resveratrol with/without 3-MA for 8 weeks beginning 4 weeks after surgery...
June 15, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28669545/retrograde-synaptic-inhibition-is-mediated-by-%C3%AE-neurexin-binding-to-the-%C3%AE-2%C3%AE-subunits-of-n-type-calcium-channels
#14
Xia-Jing Tong, Eduardo Javier López-Soto, Lei Li, Haowen Liu, Daniel Nedelcu, Diane Lipscombe, Zhitao Hu, Joshua M Kaplan
The synaptic adhesion molecules Neurexin and Neuroligin alter the development and function of synapses and are linked to autism in humans. In C. elegans, post-synaptic Neurexin (NRX-1) and pre-synaptic Neuroligin (NLG-1) mediate a retrograde synaptic signal that inhibits acetylcholine (ACh) release at neuromuscular junctions. Here, we show that the retrograde signal decreases ACh release by inhibiting the function of pre-synaptic UNC-2/CaV2 calcium channels. Post-synaptic NRX-1 binds to an auxiliary subunit of pre-synaptic UNC-2/CaV2 channels (UNC-36/α2δ), decreasing UNC-36 abundance at pre-synaptic elements...
July 19, 2017: Neuron
https://www.readbyqxmd.com/read/28652764/sun1-silencing-inhibits-cell-growth-through-g0-g1-phase-arrest-in-lung-adenocarcinoma
#15
Weiyi Huang, Haihua Huang, Lei Wang, Jiong Hu, Weifeng Song
PURPOSE: Cytoskeleton is critical for carcinoma cell proliferation, migration, and invasion. Sad-1 and UNC-84 domain containing 1 (SUN1) is one of the core linkers of nucleoskeleton and cytoskeleton. However, the functions of SUN1 in lung adenocarcinoma are largely unknown. METHODS: In this study, we first transduced the lentivirus delivering the short hairpin RNA (shRNA) against SUN1 to lung adenocarcinoma cells (A549 and 95D cells) with high efficiency. After lentivirus infection, quantitative real-time polymerase chain reaction and Western blotting were used to detect the expressions of SUN1 mRNA and protein...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28642249/unc-cancer-center-director-to-lead-nci
#16
(no author information available yet)
President Donald Trump has selected Norman "Ned" Sharpless, MD, director of the University of North Carolina Lineberger Comprehensive Cancer Center, to lead the NCI. The news was met with widespread approval among cancer researchers, who view Sharpless as a strong communicator who can ably represent the needs of the cancer community in the face of proposed funding cuts.
June 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28628528/increased-persistence-of-initial-treatment-for-hiv-infection-with-modern-antiretroviral-therapy
#17
Thibaut Davy-Mendez, Joseph J Eron, Oksana Zakharova, David A Wohl, Sonia Napravnik
BACKGROUND: Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic response to initial ART according to the class of anchor agent used. SETTING: An observational clinical cohort study in the Southeastern United States. METHODS: All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included...
June 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28624033/house-staff-led-interdisciplinary-morbidity-and-mortality-conference-promotes-systematic-improvement
#18
Christopher J Tignanelli, Genevieve G R Embree, Amir Barzin
BACKGROUND: Improvements in patient safety are critical to improving clinical outcomes. We present a resident-led interdisciplinary morbidity and mortality (M&M) conference utilizing postconference task forces to identify unique system issues, classify key contributors to interdisciplinary complications, and implement systems solutions. The conference also served to facilitate resident involvement in quality improvement projects. MATERIALS AND METHODS: Members of the UNC Housestaff Council designed and implemented a hospital-wide M&M conference...
June 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28617448/diminishing-effectiveness-of-long-term-maintenance-topical-steroid-therapy-in-ppi-non-responsive-eosinophilic-esophagitis
#19
Swathi Eluri, Thomas M Runge, Jason Hansen, Bharati Kochar, Craig C Reed, Benjamin S Robey, John T Woosley, Nicholas J Shaheen, Evan S Dellon
OBJECTIVES: While topical corticosteroids are first-line therapy for eosinophilic esophagitis (EoE), the data regarding long-term effectiveness are lacking. We aimed to determine long-term histologic and endoscopic outcomes of maintenance therapy in EoE steroid responders. METHODS: We performed a retrospective study of adults with EoE at UNC Hospitals who had initial histologic response (<15 eos/hpf) after 8 weeks of topical steroids, and maintained on therapy...
June 15, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28596978/multiple-roles-of-ulk4-in-neurogenesis-and-brain-function
#20
Min Liu, Ping Xu, Timothy O'Brien, Sanbing Shen
Neurogenesis is essential for proper brain formation and function, and abnormal neural proliferation is an underlying neuropathology of many brain disorders. Recent advances on adult neurogenesis demonstrate that neural stem cells (NSCs) at the subventricular zone (SVZ) are largely derived during mid-embryonic neurogenesis from a subset of cells, which slow down in their pace of cell division,(1) become quiescent cells and can be reactivated in need.(2) The NSCs at birth constitute the stem cell pool for both postnatal oligodendrogenesis(3) and adult neurogenesis...
2017: Neurogenesis (Austin, Tex.)
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