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https://www.readbyqxmd.com/read/29913131/multisynaptic-cooperation-shapes-single-glutamatergic-synapse-response
#1
Vito Di Maio, Silvia Santillo, Francesco Ventriglia
The activity of thousands of excitatory synapse in the dendritic tree produces variations of membrane potential which, while can produce the spike generation at soma (hillock), can also influence the output of a single glutamatergic synapse. We used a model of synaptic diffusion and EPSP generation to simulate the effect of different number of active synapses on the output of a single one. Our results show that, also in subthreshold conditions, the excitatory dendritic activity can influence several parameters of the single synaptic output such as its amplitude, its time course, the NMDA-component activation and consequently phenomena like STP and LTP...
June 15, 2018: Brain Research
https://www.readbyqxmd.com/read/29910735/switching-off-adora2b-in-vascular-smooth-muscle-cells-halts-the-development-of-pulmonary-hypertension
#2
Tinne C J Mertens, Ankit Hanmandlu, Ly Tu, Carole Phan, Scott D Collum, Ning-Yuan Chen, Tingting Weng, Jonathan Davies, Chen Liu, Holger K Eltzschig, Soma S K Jyothula, Keshava Rajagopal, Yang Xia, Ashrith Guha, Brian A Bruckner, Michael R Blackburn, Christophe Guignabert, Harry Karmouty-Quintana
Background: Pulmonary hypertension (PH) is a devastating and progressive disease characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and remodeling of the lung vasculature. Adenosine signaling through the ADORA2B receptor has previously been implicated in disease progression and tissue remodeling in chronic lung disease. In experimental models of PH associated with chronic lung injury, pharmacological or genetic inhibition of ADORA2B improved markers of chronic lung injury and hallmarks of PH...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29910731/alpha6-containing-nicotinic-acetylcholine-receptors-mediate-nicotine-induced-structural-plasticity-in-mouse-and-human-ipsc-derived-dopaminergic-neurons
#3
Ginetta Collo, Laura Cavalleri, Michele Zoli, Uwe Maskos, Emiliangelo Ratti, Emilio Merlo Pich
Midbrain dopamine (DA) neurons are considered a critical substrate for the reinforcing and sensitizing effects of nicotine and tobacco dependence. While the role of the α4 and β2 subunit containing nicotinic acetylcholine receptors (α4β2∗ nAChRs) in mediating nicotine effects on DA release and DA neuron activity has been widely explored, less information is available on their role in the morphological adaptation of the DA system to nicotine, eventually leading to dysfunctional behaviors observed in nicotine dependence...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29907798/congenital-hyperinsulinism-as-the-presenting-feature-of-kabuki-syndrome-clinical-and-molecular-characterization-of-10-affected-individuals
#4
Kai Lee Yap, Amy E Knight Johnson, David Fischer, Priscilla Kandikatla, Jacea Deml, Viswateja Nelakuditi, Sara Halbach, George S Jeha, Lindsay C Burrage, Olaf Bodamer, Valeria C Benavides, Andrea M Lewis, Sian Ellard, Pratik Shah, Declan Cody, Alejandro Diaz, Aishwarya Devarajan, Lisa Truong, Siri Atma W Greeley, Diva D De Leó-Crutchlow, Andrew C Edmondson, Soma Das, Paul Thornton, Darrel Waggoner, Daniela Del Gaudio
PURPOSE: Describe the clinical and molecular findings of patients with Kabuki syndrome (KS) who present with hypoglycemia due to congenital hyperinsulinism (HI), and assess the incidence of KS in patients with HI. METHODS: We documented the clinical features and molecular diagnoses of 10 infants with persistent HI and KS via a combination of sequencing and copy-number profiling methodologies. Subsequently, we retrospectively evaluated 100 infants with HI lacking a genetic diagnosis, for causative variants in KS genes...
June 15, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29907658/degradation-of-dendritic-cargos-requires-rab7-dependent-transport-to-somatic-lysosomes
#5
Chan Choo Yap, Laura Digilio, Lloyd P McMahon, A Denise R Garcia, Bettina Winckler
Neurons are large and long lived, creating high needs for regulating protein turnover. Disturbances in proteostasis lead to aggregates and cellular stress. We characterized the behavior of the short-lived dendritic membrane proteins Nsg1 and Nsg2 to determine whether these proteins are degraded locally in dendrites or centrally in the soma. We discovered a spatial heterogeneity of endolysosomal compartments in dendrites. Early EEA1-positive and late Rab7-positive endosomes are found throughout dendrites, whereas the density of degradative LAMP1- and cathepsin (Cat) B/D-positive lysosomes decreases steeply past the proximal segment...
June 15, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29906340/sympatho-excitatory-response-to-pulmonary-chemosensitive-spinal-afferent-activation-in-anesthetized-vagotomized-rats
#6
Julia Shanks, Zhiqiu Xia, Steven J Lisco, George J Rozanski, Harold D Schultz, Irving H Zucker, Han-Jun Wang
The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague-Dawley rats...
June 2018: Physiological Reports
https://www.readbyqxmd.com/read/29905123/the-somal-patterning-of-the-aii-amacrine-cell-mosaic-in-the-mouse-retina-is-indistinguishable-from-random-simulations-matched-for-density-and-constrained-by-soma-size
#7
Patrick W Keeley, Benjamin E Reese
The orderly spacing of retinal neurons is commonly regarded as a characteristic feature of retinal nerve cell populations. Exemplars of this property include the horizontal cells and the cholinergic amacrine cells, where individual cells minimize the proximity to like-type neighbors, yielding regularity in the patterning of their somata. Recently, two types of retinal bipolar cells in the mouse retina were shown to exhibit an order in their somal patterning no different from density-matched simulations constrained by soma size but being otherwise randomly distributed...
January 2018: Visual Neuroscience
https://www.readbyqxmd.com/read/29905119/short-periods-of-darkness-fail-to-restore-visual-or-neural-plasticity-in-adult-cats
#8
Kaitlyn D Holman, Kevin R Duffy, Donald E Mitchell
It has been shown that the visual acuity loss experienced by the deprived eye of kittens following an early period of monocular deprivation (MD) can be alleviated rapidly following 10 days of complete darkness when imposed even as late as 14 weeks of age. To examine whether 10 days of darkness conferred benefits at any age, we measured the extent of recovery of the visual acuity of the deprived eye following the darkness imposed on adult cats that had received the same early period of MD as used in prior experiments conducted on kittens...
January 2018: Visual Neuroscience
https://www.readbyqxmd.com/read/29903841/splitting-of-circulating-red-blood-cells-as-in-vivo-mechanism-of-erythrocyte-maturation-in-developing-zebrafish-chick-and-mouse-embryos
#9
Daniel Brönnimann, Tiziana Annese, Thomas A Gorr, Valentin Djonov
Nucleated circulating red blood cells (RBCs) of developing zebrafish, chick and mouse embryos can actively proliferate. While marrow- or organ-mediated erythropoiesis has been widely studied, transforming in vivo processes of circulating RBCs are under little scrutiny. We employed confocal, stereo- and electron microscopy to document the maturation of intravascular RBCs. In zebrafish embryos (32-72 hours post fertilization), RBC splitting in the caudal vein plexus follows a four-step program: (i) Nuclear division with continued cytoplasmic connection between somata...
June 14, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29901539/prevalence-and-natural-course-of-transverse-ligament-of-the-atlas-calcification-in-asymptomatic-healthy-individuals
#10
Masato Anno, Yasushi Oshima, Yuki Taniguchi, Yoshitaka Matsubayashi, So Kato, Kazuhito Soma, Hiroyuki Oka, Naoto Hayashi, Sakae Tanaka
STUDY DESIGN: A retrospective cross-sectional study. OBJECTIVE: To assess the prevalence and natural course of calcification of the transverse ligament of the atlas (TLA) in healthy subjects and to investigate the relationship between the calcified lesion and clinical factors. SUMMARY OF BACKGROUND DATA: The prevalence and etiology of TLA calcification in healthy individuals remain uncertain. METHODS: We enrolled 1136 participants undergoing computed tomography (CT) scans in their routine medical checkups...
June 12, 2018: Spine
https://www.readbyqxmd.com/read/29900785/the-lysosomal-storage-disease-gm2-gangliosidosis-in-captive-banded-mongoose-siblings-mungos-mungo
#11
Julia Wimmershoff, Kathrin Kuehni-Boghenbor, Adrian C Sewell, Anna Oevermann, Hany Farwanah, Nadia Robert, Stefan Hoby, Christian Wenker, Michael H Stoffel
  This study reports the occurrence of the lysosomal storage disease GM2 gangliosidosis (Sandhoff disease) in two 11-mo-old captive-bred, male and female mongoose siblings ( Mungos mungo). The clinical signs and the pathological findings reported here were similar to those reported in other mammalian species. Light microscopy revealed an accumulation of stored material in neurons and macrophages accompanied by a significant neuronal degeneration (swelling of neuronal soma, loss of Nissl substance, and neuronal loss) and gliosis...
June 2018: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/29899326/jnk2-deficiency-increases-the-rate-of-glaucomatous-neurodegeneration-in-ocular-hypertensive-dba-2j-mice
#12
Jeffrey M Harder, Pete A Williams, Ileana Soto, Nicole E Foxworth, Kimberly A Fernandes, Nelson F Freeburg, Richard T Libby, Simon W M John
The cJun N-terminal kinases (JNKs; JNK1, JNK2, and JNK3) promote degenerative processes after neuronal injury and in disease. JNK2 and JNK3 have been shown to promote retinal ganglion cell (RGC) death after optic nerve injury. In their absence, long-term survival of RGC somas is significantly increased after mechanical optic nerve injury. In glaucoma, because optic nerve damage is thought to be a major cause of RGC death, JNKs are an important potential target for therapeutic intervention. To assess the role of JNK2 and JNK3 in an ocular hypertensive model of glaucoma, null alleles of Jnk2 and Jnk3 were backcrossed into the DBA/2J (D2) mouse...
June 13, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29893711/frequency-dependent-antidromic-activation-in-thalamocortical-relay-neurons-effects-of-synaptic-inputs
#13
Guosheng Yi, Warren M Grill
OBJECTIVE: Deep brain stimulation (DBS) generates action potentials (APs) in presynaptic axons and fibers of passage. The APs may be antidromically propagated to invade the cell body and / or orthodromically transmitted to downstream structures, thereby affecting widespread targets distant from the electrode. Activation of presynaptic terminals also causes trans-synaptic effects, which in turn alter the excitability of the post-synaptic neurons. Our aim was to determine how synaptic inputs affect the antidromic invasion of the cell body...
June 12, 2018: Journal of Neural Engineering
https://www.readbyqxmd.com/read/29892979/germline-expression-of-the-hunchback-orthologues-in-the-asexual-viviparous-aphids-a-conserved-feature-within-the-aphididae
#14
Chen-Yo Chung, Yi-Min Hsiao, Ting-Yu Huang, Tien-Hsien Chang, Chun-Che Chang
In animals, differentiation of germline from soma usually takes place during embryogenesis. Genes and their products that are preferentially expressed in the embryonic germ cells are regarded as candidates for maintaining germline fate or promoting germline identity. In Drosophila, for example, the protein encoded by the germline gene vasa is specifically restricted to the germ cells while products of the gap gene hunchback (hb), a somatic gene, are preferentially expressed in the neuroblasts. In this study, we report the expression of both mRNA and protein encoded by Aphb, an hb orthologue in the asexual viviparous pea aphid Acyrthosiphon pisum, in germ cells as well as in neuroblasts...
June 11, 2018: Insect Molecular Biology
https://www.readbyqxmd.com/read/29892955/whole-genome-variant-analysis-in-three-ethnically-diverse-indians
#15
Seema Malhotra, Sayar Singh, Soma Sarkar
India represents an amazing confluence of geographically, linguistically and socially disparate ethnic populations (Indian Genome Variation Consortium, J Genet 87:3-20, 2008). Understanding the genetic diversity of Indian population remains a daunting task. In this paper we present detailed analysis of genomic variations (high-depth coverage (~ 30×) using Illumina Hiseq 2000 platform) from three healthy Indian male individuals each belonging to three geographically delineated regions and linguistic phylum viz...
May 2018: Genes & Genomics
https://www.readbyqxmd.com/read/29891731/local-bdnf-delivery-to-the-injured-cervical-spinal-cord-using-an-engineered-hydrogel-enhances-diaphragmatic-respiratory-function
#16
Biswarup Ghosh, Zhicheng Wang, Jia Nong, Mark W Urban, Zhiling Zhang, Victoria A Trovillion, Megan C Wright, Yinghui Zhong, Angelo C Lepore
We developed an innovative biomaterial-based approach to repair the critical neural circuitry that controls diaphragm activation by locally delivering brain-derived neurotrophic factor (BDNF) to injured cervical spinal cord. BDNF can be used to restore respiratory function via a number of potential repair mechanisms; however, widespread BDNF biodistribution resulting from delivery methods such as systemic injection or lumbar puncture can lead to inefficient drug delivery and adverse side effects. As a viable alternative, we developed a novel hydrogel-based system loaded with polysaccharide-BDNF particles self-assembled by electrostatic interactions that can be safely implanted in the intrathecal space for achieving local BDNF delivery with controlled dosing and duration...
June 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29887308/small-rna-mediated-trans-nuclear-and-trans-element-communications-in-tetrahymena-dna-elimination
#17
Tomoko Noto, Kazufumi Mochizuki
Epigenetic inheritance of acquired traits is widespread among eukaryotes, but how and to what extent such information is transgenerationally inherited is still unclear. The patterns of programmed DNA elimination in ciliates are epigenetically and transgenerationally inherited, and it has been proposed that small RNAs, which shuttle between the germline and the soma, regulate this epigenetic inheritance. In this study, we test the existence and role of such small-RNA-mediated communication by epigenetically disturbing the pattern of DNA elimination in Tetrahymena...
May 25, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29885287/cellular-fate-decisions-in-the-developing-female-anteroventral-periventricular-nucleus-are-regulated-by-canonical-notch-signaling
#18
Matthew J Biehl, Kerim B Kaylan, Robert J Thompson, Rachel V Gonzalez, Karen E Weis, Gregory H Underhill, Lori T Raetzman
The hypothalamic anteroventral periventricular nucleus (AVPV) is the major regulator of reproductive function within the hypothalamic-pituitary-gonadal (HPG) axis. Despite an understanding of the function of neuronal subtypes within the AVPV, little is known about the molecular mechanisms regulating their development. Previous work from our laboratory has demonstrated that Notch signaling is required in progenitor cell maintenance and formation of kisspeptin neurons of the arcuate nucleus (ARC) while simultaneously restraining POMC neuron number...
June 6, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29884189/potentially-clinically-relevant-concentrations-of-cefazolin-midazolam-propofol-and-sufentanil-in-auto-transfused-blood-in-congenital-cardiac-surgery
#19
Gerda A Zeilmaker-Roest, Annewil van Saet, Joost van Rosmalen, Soma Bahmany, Antony van Dijk, Enno D Wildschut, Dick Tibboel, Ad J J C Bogers
BACKGROUND: Use of donor blood in congenital cardiac surgery increases the risk for post-operative morbidity and mortality. To reduce the need for allogenic blood transfusion a technique for peri-operative mechanical red cell salvage is applied. Blood from the operation site is collected in a reservoir, processed, passed through a lipophilic filter and returned to the patient. Influence of this cellsaver system on coagulation, fibrinolysis and inflammatory markers is known. To our knowledge no studies have been performed on the effects of autotransfusion on drug concentrations...
June 8, 2018: Journal of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/29883765/activation-of-axon-initial-segmental-gaba-a-receptors-inhibits-action-potential-generation-in-neocortical-gabaergic-interneurons
#20
Yanbo Jiang, Yujie Xiao, Xiaoxue Zhang, Yousheng Shu
Ionotropic GABAA receptors expressing at the axon initial segment (AIS) of glutamatergic pyramidal cell (PC) in the cortex plays critical roles in regulating action potential generation. However, it remains unclear whether these receptors also express at the AIS of cortical GABAergic interneurons. In mouse prefrontal cortical slices, we performed experiments at the soma and AIS of the two most abundant GABAergic interneurons: parvalbumin (PV) and somatostatin (SST) positive neurons. Local application of GABA at the perisomatic axonal regions could evoke picrotoxin-sensitive currents with a reversal potential near the Cl- equilibrium potential...
May 23, 2018: Neuropharmacology
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