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https://www.readbyqxmd.com/read/28351053/macular-edema-rationale-for-therapy
#1
Thomas J Wolfensberger
Macular edema represents the end-stage of multiple pathophysiological pathways in a multitude of ocular vascular, inflammatory, and other diseases. The rationale for clinical treatment of macular edema is based on the understanding and the inhibition of these pathophysiological mechanisms. When macular edema is caused by a generalized health problem such as diabetes, high blood pressure, or generalized inflammatory conditions, treatment of these generalized diseases can in many cases cure macular edema directly...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28350976/neuroendocrine-tumor-of-the-common-bile-duct-case-report
#2
C Raspanti, N Falco, V Silvestri, G Rotolo, S Bonventre, G Gulotta
Neuroendocrine tumors (NET) are a very heterogeneous group of neoplasms; in recent years we have seen an increase in their incidence (3.65 /100.000/year). They can be associated with hereditary endocrine syndromes (MEN, Von Hippel Lindau); they can occur at any age and the incidence is slightly higher in men than women. The aetiology of the neuroendocrine tumors is unclear; in most cases, inflammation of the bile ducts may be the underlying cause and for this reason, the initial patient's evaluation should be focused on the different aspects concerning the oncological one and the possible sequelae of the biliary obstructions that can evolve in biliary sepsis...
November 2016: Il Giornale di Chirurgia
https://www.readbyqxmd.com/read/28350885/glutamate-dependent-ectodomain-shedding-of-neuregulin-1-type-ii-precursors-in-rat-forebrain-neurons
#3
Yuriko Iwakura, Ran Wang, Naoko Inamura, Kazuaki Araki, Shigeki Higashiyama, Nobuyuki Takei, Hiroyuki Nawa
The neurotrophic factor neuregulin 1 (NRG1) regulates neuronal development, glial differentiation, and excitatory synapse maturation. NRG1 is synthesized as a membrane-anchored precursor and is then liberated by proteolytic processing or exocytosis. Mature NRG1 then binds to its receptors expressed by neighboring neurons or glial cells. However, the molecular mechanisms that govern this process in the nervous system are not defined in detail. Here we prepared neuron-enriched and glia-enriched cultures from embryonic rat neocortex to investigate the role of neurotransmitters that regulate the liberation/release of NRG1 from the membrane of neurons or glial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28350856/a-fat-derived-metabolite-regulates-a-peptidergic-feeding-circuit-in-drosophila
#4
Do-Hyoung Kim, Minjung Shin, Sung-Hwan Jung, Young-Joon Kim, Walton D Jones
Here, we show that the enzymatic cofactor tetrahydrobiopterin (BH4) inhibits feeding in Drosophila. BH4 biosynthesis requires the sequential action of the conserved enzymes Punch, Purple, and Sepiapterin Reductase (Sptr). Although we observe increased feeding upon loss of Punch and Purple in the adult fat body, loss of Sptr must occur in the brain. We found Sptr expression is required in four adult neurons that express neuropeptide F (NPF), the fly homologue of the vertebrate appetite regulator neuropeptide Y (NPY)...
March 2017: PLoS Biology
https://www.readbyqxmd.com/read/28350795/fine-mapping-of-the-human-leukocyte-antigen-locus-as-a-risk-factor-for-alzheimer-disease-a-case-control-study
#5
Natasha Z R Steele, Jessie S Carr, Luke W Bonham, Ethan G Geier, Vincent Damotte, Zachary A Miller, Rahul S Desikan, Kevin L Boehme, Shubhabrata Mukherjee, Paul K Crane, John S K Kauwe, Joel H Kramer, Bruce L Miller, Giovanni Coppola, Jill A Hollenbach, Yadong Huang, Jennifer S Yokoyama
BACKGROUND: Alzheimer disease (AD) is a progressive disorder that affects cognitive function. There is increasing support for the role of neuroinflammation and aberrant immune regulation in the pathophysiology of AD. The immunoregulatory human leukocyte antigen (HLA) complex has been linked to susceptibility for a number of neurodegenerative diseases, including AD; however, studies to date have failed to consistently identify a risk HLA haplotype for AD. Contributing to this difficulty are the complex genetic organization of the HLA region, differences in sequencing and allelic imputation methods, and diversity across ethnic populations...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28350532/urethral-proteomic-analysis-in-ovariectomized-mice-administered-17%C3%AE-oestradiol-replacement-therapy
#6
Huey-Yi Chen, Yu-Ning Lin, Wen-Chi Chen, Shih-Jing Wang, Chao-Jung Chen, Yung-Hsiang Chen
The molecular mechanism by which 17β-oestradiol (E2) increases urethral tone is unclear. As human tissue is limited in availability, we explored changes in the urethras of ovariectomized (OVX) mice. Twenty-four virgin female mice were randomised into three groups: mice with a sham operation only (control), OVX mice without E2 replacement (OVX), and OVX mice with E2 replacement (OVX + E2). Two weeks after the ovariectomy, mice received either E2 or placebo for 4 weeks. Leak point pressure (LPP) and maximum urethral closure pressure (MUCP) were assessed in these mice at 6 weeks after OVX, under anaesthesia...
March 28, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28350524/an-atf4-atg5-signaling-in-hypothalamic-pomc-neurons-regulates-obesity
#7
Yuzhong Xiao, Yalan Deng, Feixiang Yuan, Tingting Xia, Hao Liu, Zhigang Li, Shanghai Chen, Zhixue Liu, Hao Ying, Yi Liu, Qiwei Zhai, Feifan Guo
ATF4 (activating transcription factor 4) is an important transcription factor that has many biological functions, while its role in hypothalamic POMC (pro-opiomelanocortin-alpha) neurons in the regulation of energy homeostasis has not been explored. We recently discovered that mice with an Atf4 deletion specific to POMC neurons (PAKO mice) are lean and have higher energy expenditure. Furthermore, these mice are resistant to high-fat diet (HFD)-induced obesity and obesity-related metabolic disorders. Mechanistically, we found the expression of ATG5 (autophagy related 5) is upregulated in POMC neurons of PAKO mice, and ATF4 regulates ATG5 expression by binding directly to its promoter...
March 28, 2017: Autophagy
https://www.readbyqxmd.com/read/28350445/structural-changes-in-an-anion-channelrhodopsin-formation-of-the-k-and-l-intermediates-at-80-k
#8
Adrian Yi, Hai Li, Natalia V Mamaeva, Roberto F de Cordoba, Johan Lugtenburg, Willem J DeGrip, John L Spudich, Kenneth J Rothschild
A recently discovered natural family of light-gated anion channelrhodopsins (ACRs) from cryptophyte algae provides an effective means of optogenetically silencing neurons. The most extensively studied ACR is from Guillardia theta (GtACR1). Earlier studies of GtACR1 have established a correlation between formation of a blue-shifted L-like intermediate and the anion channel "open" state. To study structural changes of GtACR1 in the K and L intermediates of the photocycle, a combination of low-temperature FTIR and UV-visible absorption difference spectroscopy was used along with stable-isotope retinal labeling and site-directed mutagenesis...
March 28, 2017: Biochemistry
https://www.readbyqxmd.com/read/28346814/nicotinamide-riboside-a-form-of-vitamin-b3-and-nad-precursor-relieves-the-nociceptive-and-aversive-dimensions-of-paclitaxel-induced-peripheral-neuropathy-in-female-rats
#9
Marta V Hamity, Stephanie R White, Roxanne Y Walder, Mark S Schmidt, Charles Brenner, Donna L Hammond
Injury to sensory afferents may contribute to the peripheral neuropathies that develop after administration of chemotherapeutic agents. Manipulations that increase levels of nicotinamide adenine dinucleotide (NAD) can protect against neuronal injury. This study examined whether nicotinamide riboside (NR), a third form of vitamin B3 and precursor of NAD, diminishes tactile hypersensitivity and place escape-avoidance behaviors in a rodent model of paclitaxel-induced peripheral neuropathy. Female Sprague-Dawley rats received 3 intravenous injections of 6...
January 30, 2017: Pain
https://www.readbyqxmd.com/read/28346718/modulation-of-the-rat-micturition-reflex-with-transcutaneous-ultrasound
#10
Daniel P Casella, Anne G Dudley, Douglass B Clayton, John C Pope, Stacy T Tanaka, John Thomas, Mark C Adams, John W Brock, Charles F Caskey
INTRODUCTION: Low intensity focused ultrasound has recently been identified as a novel method of stimulating targeted neurons. We hypothesized that ultrasound stimulation of the posterior tibial nerve would inhibit bladder contractions in an established rat model of rhythmic bladder contractions. METHODS: Cyclical detrusor contractions were initiated by placing a transurethral catheter in female rats and infusing saline into the bladder. Transcutaneous ultrasound pulses were then delivered to the lower extremity of a rat (overlying the posterior tibial nerve) using a single element spherically focused 250 kHz transducer...
March 27, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28346578/association-of-plasma-neurofilament-light-with-neurodegeneration-in-patients-with-alzheimer-disease
#11
Niklas Mattsson, Ulf Andreasson, Henrik Zetterberg, Kaj Blennow
Importance: Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias. Objective: To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration...
March 27, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28346493/aberrant-neuronal-activity-induced-signaling-and-gene-expression-in-a-mouse-model-of-rasopathy
#12
Franziska Altmüller, Santosh Pothula, Anil Annamneedi, Saeideh Nakhei-Rad, Carolina Montenegro-Venegas, Eneko Pina-Fernández, Claudia Marini, Monica Santos, Denny Schanze, Dirk Montag, Mohammad R Ahmadian, Oliver Stork, Martin Zenker, Anna Fejtova
Noonan syndrome (NS) is characterized by reduced growth, craniofacial abnormalities, congenital heart defects, and variable cognitive deficits. NS belongs to the RASopathies, genetic conditions linked to mutations in components and regulators of the Ras signaling pathway. Approximately 50% of NS cases are caused by mutations in PTPN11. However, the molecular mechanisms underlying cognitive impairments in NS patients are still poorly understood. Here, we report the generation and characterization of a new conditional mouse strain that expresses the overactive Ptpn11D61Y allele only in the forebrain...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346482/24s-hydroxycholesterol-and-25-hydroxycholesterol-differentially-impact-hippocampal-neuronal-survival-following-oxygen-glucose-deprivation
#13
Min-Yu Sun, Amanda Taylor, Charles F Zorumski, Steven Mennerick
N-methyl-D-aspartate receptors (NMDARs), a major subtype of glutamate receptor mediating excitatory transmission throughout the CNS, participate in ischemia-induced neuronal death. Unfortunately, undesired side effects have limited the strategy of inhibiting/blocking NMDARs as therapy. Targeting endogenous positive allosteric modulators of NMDAR function may offer a strategy with fewer downsides. Here, we explored whether 24S-hydroxycholesterol (24S-HC), an endogenous positive NMDAR modulator characterized recently by our group, participates in NMDAR-mediated excitotoxicity following oxygen-glucose deprivation (OGD) in primary neuron cultures...
2017: PloS One
https://www.readbyqxmd.com/read/28346481/edaravone-protects-against-hyperosmolarity-induced-oxidative-stress-and-apoptosis-in-primary-human-corneal-epithelial-cells
#14
Yanwei Li, Haifeng Liu, Wei Zeng, Jing Wei
An increase in the osmolarity of tears induced by excessive evaporation of the aqueous tear phase is a major pathological mechanism behind dry eye. Exposure of epithelial cells on the surface of the human eye to hyperosmolarity leads to oxidative stress, mitochondrial dysfunction, and apoptosis. Edaravone, a hydroxyl radical scavenging agent, is clinically used to reduce neuronal damage following ischemic stroke. In this study, we found that treatment with hyperosmotic media at 400 and 450 mOsM increased the levels of ROS and mitochondrial oxidative damage, which were ameliorated by edaravone treatment in a dose-dependent manner...
2017: PloS One
https://www.readbyqxmd.com/read/28346453/activity-induced-histone-modifications-govern-neurexin-1-mrna-splicing-and-memory-preservation
#15
Xinlu Ding, Sanxiong Liu, Miaomiao Tian, Wenhao Zhang, Tao Zhu, Dongdong Li, Jiawei Wu, HaiTeng Deng, Yichang Jia, Wei Xie, Hong Xie, Ji-Song Guan
Epigenetic mechanisms regulate the formation, consolidation and reconsolidation of memories. However, the signaling path from neuronal activation to epigenetic modifications within the memory-related brain circuit remains unknown. We report that learning induces long-lasting histone modifications in hippocampal memory-activated neurons to regulate memory stability. Neuronal activity triggers a late-onset shift in Nrxn1 splice isoform choice at splicing site 4 by accumulating a repressive histone marker, H3K9me3, to modulate the splicing process...
March 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28346452/purine-synthesis-promotes-maintenance-of-brain-tumor-initiating-cells-in-glioma
#16
Xiuxing Wang, Kailin Yang, Qi Xie, Qiulian Wu, Stephen C Mack, Yu Shi, Leo J Y Kim, Briana C Prager, William A Flavahan, Xiaojing Liu, Meromit Singer, Christopher G Hubert, Tyler E Miller, Wenchao Zhou, Zhi Huang, Xiaoguang Fang, Aviv Regev, Mario L Suvà, Tae Hyun Hwang, Jason W Locasale, Shideng Bao, Jeremy N Rich
Brain tumor initiating cells (BTICs), also known as cancer stem cells, hijack high-affinity glucose uptake active normally in neurons to maintain energy demands. Here we link metabolic dysregulation in human BTICs to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility...
March 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28346321/growth-arrest-and-dna-damage-inducible-protein-45%C3%AE-mediated-dna-demethylation-of-voltage-dependent-t-type-calcium-channel-3-2-subunit-enhances-neuropathic-allodynia-after-nerve-injury-in-rats
#17
Cheng-Yuan Lai, Ming-Chun Hsieh, Yu-Cheng Ho, An-Sheng Lee, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
BACKGROUND: Growth arrest and DNA-damage-inducible protein 45β reactivates methylation-silenced neural plasticity-associated genes through DNA demethylation. However, growth arrest and DNA-damage-inducible protein 45β-dependent demethylation contributes to neuropathic allodynia-associated spinal plasticity remains unclear. METHODS: Adult male Sprague-Dawley rats (654 out of 659) received a spinal nerve ligation or a sham operation with or without intrathecal application of one of the following: growth arrest and DNA-damage-inducible protein 45β messenger RNA-targeted small interfering RNA, lentiviral vector expressing growth arrest and DNA-damage-inducible protein 45β, Ro 25-6981 (an NR2B-bearing N-methyl-D-aspartate receptor antagonist), or KN-93 (a calmodulin-dependent protein kinase II antagonist) were used for behavioral measurements, Western blotting, immunofluorescence, dot blots, detection of unmodified cytosine enrichment at cytosine-phosphate-guanine site, chromatin immunoprecipitation quantitative polymerase chain reaction analysis, and slice recordings...
March 27, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28346294/diagnosis-and-treatment-of-vestibular-neuritis-neuronitis-or-peripheral-vestibulopathy-pvp-open-questions-and-possible-answers
#18
Stefan C A Hegemann, Angela Wenzel
The acute vestibular syndrome is a clinically defined entity consisting of vertigo or dizziness that develops acutely over minutes to hours and is accompanied by nausea/vomiting, gait instability, head motion intolerance, and nystagmus, while persisting over a day or more. When it is caused by a peripheral vestibular lesion and is not associated with clinically manifest auditory deficits, it is mostly labeled vestibular neuritis/neuronitis/neuropathy or sometimes peripheral vestibulopathy. Here, we propose hypotheses and discuss current research advances on viral or vascular factors in the pathogenesis, the recurrence, the site of lesion, old and new treatment options, contraindicated measures, the differential diagnosis, and the prognosis of vestibular neuritis/neuronitis/neuropathy or vestibulopathy...
March 24, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28346227/reducing-expression-of-synapse-restricting-protein-ephexin5-ameliorates-alzheimer-s-like-impairment-in-mice
#19
Gabrielle L Sell, Thomas B Schaffer, Seth S Margolis
Accumulation of amyloid-β (Aβ) protein may cause synapse degeneration and cognitive impairment in Alzheimer's disease (AD) by reactivating expression of the developmental synapse repressor protein Ephexin5 (also known as ARHGEF15). Here, we have reported that Aβ is sufficient to acutely promote the production of Ephexin5 in mature hippocampal neurons and in mice expressing human amyloid precursor protein (hAPP mice), a model for familial AD that produces high brain levels of Aβ. Ephexin5 expression was highly elevated in the hippocampi of human AD patients, indicating its potential relevance to AD...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346224/mutant-%C3%AE-2-chimaerin-signals-via-bidirectional-ephrin-pathways-in-duane-retraction-syndrome
#20
Alicia A Nugent, Jong G Park, Yan Wei, Alan P Tenney, Nicole M Gilette, Michelle M DeLisle, Wai-Man Chan, Long Cheng, Elizabeth C Engle
Duane retraction syndrome (DRS) is the most common form of congenital paralytic strabismus in humans and can result from α2-chimaerin (CHN1) missense mutations. We report a knockin α2-chimaerin mouse (Chn1KI/KI) that models DRS. Whole embryo imaging of Chn1KI/KI mice revealed stalled abducens nerve growth and selective trochlear and first cervical spinal nerve guidance abnormalities. Stalled abducens nerve bundles did not reach the orbit, resulting in secondary aberrant misinnervation of the lateral rectus muscle by the oculomotor nerve...
March 27, 2017: Journal of Clinical Investigation
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