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https://www.readbyqxmd.com/read/29331501/incorporating-upper-motor-neuron-health-in-als-drug-discovery
#1
REVIEW
Ina Dervishi, P Hande Ozdinler
Amyotrophic lateral sclerosis (ALS) is a complex disease, affecting the motor neuron circuitry. After consecutive failures in clinical trials for the past 20 years, edaravone was recently approved as the second drug for ALS. This generated excitement in the field and revealed the need to improve preclinical assays for continued success. Here, we focus on the importance and relevance of upper motor neuron (UMN) pathology in ALS, and discuss how incorporation of UMN survival in preclinical assays will improve inclusion criteria for clinical trials and expedite the drug discovery effort in ALS and related motor neuron diseases...
January 10, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29331449/quantifying-axonal-responses-in-patient-specific-models-of-subthalamic-deep-brain-stimulation
#2
Kabilar Gunalan, Bryan Howell, Cameron C McIntyre
Medical imaging has played a major role in defining the general anatomical targets for deep brain stimulation (DBS) therapies. However, specifics on the underlying brain circuitry that is directly modulated by DBS electric fields remain relatively undefined. Detailed biophysical modeling of DBS provides an approach to quantify the theoretical responses to stimulation at the cellular level, and has established a key role for axonal activation in the therapeutic mechanisms of DBS. Estimates of DBS-induced axonal activation can then be coupled with advances in defining the structural connectome of the human brain to provide insight into the modulated brain circuitry and possible correlations with clinical outcomes...
January 10, 2018: NeuroImage
https://www.readbyqxmd.com/read/29331264/altered-levels-of-the-splicing-factor-muscleblind-modifies-cerebral-cortical-function-in-mouse-models-of-myotonic-dystrophy
#3
Gang Chen, Russell E Carter, John D Cleary, Tammy S Reid, Laura P Ranum, Maurice S Swanson, Timothy J Ebner
Myotonic dystrophy (DM) is a progressive, multisystem disorder affecting skeletal muscle, heart, and central nervous system. In both DM1 and DM2, microsatellite expansions of CUG and CCUG RNA repeats, respectively, accumulate and disrupt functions of alternative splicing factors, including muscleblind (MBNL) proteins. Grey matter loss and white matter changes, including the corpus callosum, likely underlie cognitive and executive function deficits in DM patients. However, little is known how cerebral cortical circuitry changes in DM...
January 10, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29330264/ependymoma-superenhancer-profiling-reveals-potential-therapeutic-targets
#4
(no author information available yet)
Ependymoma superenhancer landscapes delineate molecular subgroups and define transcriptional circuitries.
January 12, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29330149/voluntary-exercise-and-depression-like-behavior-in-rodents-are-we-running-in-the-right-direction
#5
Joram D Mul
Acute or chronic exposure to stress can increase the risk to develop major depressive disorder, a severe, recurrent and common psychiatric condition. Depression places an enormous social and financial burden on modern society. Although many depressed patients are treated with antidepressants, their efficacy is only modest, underscoring the necessity to develop clinically-effective pharmaceutical or behavioral treatments. Exercise training produces beneficial effects on stress-related mental disorders, indicative of clinical potential...
January 12, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29330137/the-intersection-of-stress-and-reward-bnst-modulation-of-aversive-and-appetitive-states
#6
REVIEW
Sarah Ch'ng, Jingjing Fu, Robyn M Brown, Stuart J McDougall, Andrew J Lawrence
The bed nucleus of the stria terminalis (BNST) is widely acknowledged as a brain structure that regulates stress and anxiety states, as well as aversive and appetitive behaviours. The diverse roles of the BNST are afforded by its highly modular organisation, neurochemical heterogeneity, and complex intrinsic and extrinsic circuitry. There has been growing interest in the BNST in relation to psychopathologies such as anxiety and addiction. Although research on the human BNST is still in its infancy, there have been extensive preclinical studies examining the molecular signature and hodology of the BNST and their involvement in stress and reward seeking behaviour...
January 9, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29326173/transcriptional-regulator-zeb2-is-essential-for-bergmann-glia-development
#7
Li He, Kun Yu, Fanghui Lu, Jiajia Wang, Laiman N Wu, Chuntao Zhao, Qianmei Li, Xianyao Zhou, Hanmin Liu, Dezhi Mu, Mei Xin, Mengsheng Qiu, Q Richard Lu
Bergmann glia facilitate granule neuron migration during development and maintain the cerebellar organization and functional integrity. At present, molecular control of Bergmann glia specification from cerebellar radial glia is not fully understood. In this report, we show that Zeb2 (a.k.a. Sip1 or Zfhx1b), a Mowat-Wilson-syndrome-associated transcriptional regulator, is highly expressed in Bergmann glia, but hardly detectable in astrocytes in the cerebellum. The mice lacking Zeb2 in cerebellar radial glia exhibit severe deficits in Bergmann glia specification, and develop cerebellar cortical lamination dysgenesis and locomotion defects...
January 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29325615/inherited-dystonias-clinical-features-and-molecular-pathways
#8
Corinne E Weisheit, Samuel S Pappas, William T Dauer
Recent decades have witnessed dramatic increases in understanding of the genetics of dystonia - a movement disorder characterized by involuntary twisting and abnormal posture. Hampered by a lack of overt neuropathology, researchers are investigating isolated monogenic causes to pinpoint common molecular mechanisms in this heterogeneous disease. Evidence from imaging, cellular, and murine work implicates deficiencies in dopamine neurotransmission, transcriptional dysregulation, and selective vulnerability of distinct neuronal populations to disease mutations...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29324675/a-time-domain-analog-spatial-compressed-sensing-encoder-for-multi-channel-neural-recording
#9
Takayuki Okazawa, Ippei Akita
A time-domain analog spatial compressed sensing encoder for neural recording applications is proposed. Owing to the advantage of MEMS technologies, the number of channels on a silicon neural probe array has doubled in 7.4 years, and therefore, a greater number of recording channels and higher density of front-end circuitry is required. Since neural signals such as action potential (AP) have wider signal bandwidth than that of an image sensor, a data compression technique is essentially required for arrayed neural recording systems...
January 11, 2018: Sensors
https://www.readbyqxmd.com/read/29324357/a-pilot-study-of-the-role-of-the-claustrum-in-attention-and-seizures-in-rats
#10
Arezou Bayat, Sweta Joshi, Sahar Jahan, Phillip Connell, Komei Tsuchiya, David Chau, Tanvir Syed, Patrick Forcelli, Mohamad Z Koubeissi
OBJECTIVE: The claustrum has been implicated in consciousness, and MRIs of patients with status epilepticus have shown increased claustral signal intensity. In an attempt to investigate the role of claustrum in cognition and seizures, we (1) assessed the effect of high-frequency stimulation (HFS) of the claustrum on performance in the operant chamber; (2) studied interclaustral and claustrohippocampal connectivity through cerebro-cerebral evoked potentials (CCEPs); and (3) investigated the role of claustrum in kainate-induced (KA) seizures...
January 5, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29323720/tfcp2l1-safeguards-the-maintenance-of-human-embryonic-stem-cell-self-renewal
#11
Hongwei Sun, Yu You, Mengmeng Guo, Xiaohu Wang, Yan Zhang, Shoudong Ye
Tfcp2l1 is a transcription factor critical for mouse embryonic stem cell (mESC) maintenance. However, its role in human ESCs (hESCs) remains unclear. Here, we investigated the functions of Tfcp2l1 in controlling hESC activity and showed that Tfcp2l1 is functionally important in the maintenance of hESC identity. Tfcp2l1 expression is highly enriched in hESCs and dramatically decreases upon differentiation. Forced expression of Tfcp2l1 promoted hESC self-renewal. Functional analysis of the mutant forms of Tfcp2l1 revealed that both the CP2- and SAM-like domains are indispensable for Tfcp2l1 to maintain the undifferentiated state of hESCs...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29323553/revealing-the-structural-neural-circuitry-of-attention-deficit-hyperactivity-disorder-with-diffusion-mri-implications-for-future-diagnosis-and-treatment
#12
Vitria Adisetiyo
OBJECTIVE: Rates of attention deficit hyperactivity disorder (ADHD) diagnosis and psychostimulant prescriptions continue to rise, yet there are no clear diagnostic tests or biomarkers for the disorder. The purpose of this article is to highlight the role of diffusion MRI in bolstering a neurobiologic conceptualization of ADHD and how this holds promise for optimizing future diagnosis. CONCLUSION: Diffusion MRI is a powerful neuroimaging tool for noninvasive assessment of the structural neural circuitry underlying brain function and behavior...
January 11, 2018: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/29323409/in-vitro-comparison-of-two-neonatal-ecmo-circuits-using-a-roller-or-centrifugal-pump-with-three-different-in-line-hemoconcentrators-for-maintaining-hemodynamic-energy-delivery-to-the-patient
#13
Madison Force, Morgan Moroi, Shigang Wang, David A Palanzo, Allen R Kunselman, Akif Ündar
The objective of this study was to compare three different hemoconcentrators (Hemocor HPH 400, Mini, and Junior) with two different neonatal ECMO circuits using a roller or a centrifugal pump at different pseudo-patient pressures and flow rates in terms of hemodynamic properties. This evidence-based research is necessary to optimize the ECMO circuitry for neonates. The circuits used a 300-mL soft-shell reservoir as a pseudo-patient approximating the blood volume of a 3 kg neonate, two blood pumps, and a Quadrox-iD Pediatric oxygenator with three different in-line hemoconcentrators (Hemocor HPH 400, Mini, and Junior)...
January 11, 2018: Artificial Organs
https://www.readbyqxmd.com/read/29321592/amyloid-%C3%AE-causes-excitation-inhibition-imbalance-through-dopamine-receptor-1-dependent-disruption-of-fast-spiking-gabaergic-input-in-anterior-cingulate-cortex
#14
Si-Qiang Ren, Wen Yao, Jing-Zhi Yan, Chunhui Jin, Jia-Jun Yin, Jianmin Yuan, Shui Yu, Zaohuo Cheng
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. At the early stages of AD development, the soluble β-amyloid (Aβ) induces synaptic dysfunction, perturbs the excitation/inhibition balance of neural circuitries, and in turn alters the normal neural network activity leading to cognitive decline, but the underlying mechanisms are not well established. Here by using whole-cell recordings in acute mouse brain slices, we found that 50 nM Aβ induces hyperexcitability of excitatory pyramidal cells in the cingulate cortex, one of the most vulnerable areas in AD, via depressing inhibitory synaptic transmission...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320737/genomic-circuitry-underlying-immunological-response-to-pediatric-acute-respiratory-infection
#15
Sarah E Henrickson, Sasikanth Manne, Douglas V Dolfi, Kathleen D Mansfield, Kaela Parkhouse, Rakesh D Mistry, Elizabeth R Alpern, Scott E Hensley, Kathleen E Sullivan, Susan E Coffin, E John Wherry
Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29319406/completed-suicide-in-an-autopsy-confirmed-case-of-early-onset-alzheimer-s-disease
#16
Jennifer Wiener Hartzell, Richard Geary, Kymberly Gyure, Venkata Ravi Chivukula, Marc W Haut
We report a case of a 57-year-old male with clinically diagnosed and autopsy-confirmed early onset Alzheimer's disease who completed suicide by gunshot wound to the chest. This case has several unique aspects that have not been discussed in previous case reports of completed suicide in Alzheimer's disease. In particular, our patient's death was highly planned with successful compensation for his cognitive deficits. After all firearms had been removed from the home as a safety precaution, he obtained a new weapon, hid it and left himself cues to find and use it...
January 10, 2018: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/29319211/design-and-assembly-of-covalently-functionalized-polyoxofluorovanadate-molecular-hybrids
#17
Maria Nicolaou, Michael Papanikolaou, Athanassios Tsipis, Themistoklis Kabanos, Anastasios Keramidas, Stephen Sproules, Haralampos N Miras
Mixed-valent polyoxometalate (POM) clusters are one of the most interesting host species showing a wide range of structural features and properties. We report the facile preparation and functionalization of a mixed-valent polyoxofluorovanadates where two electrons are trapped to antipodal sites of the clusters. The first members of this family of clusters with the general formula, [VV12VIV2O16(μ-O)10(μ3-O)10(μ3-F)2(L)2]6-, where L: py = pyridine (1); pyr = pyrazine (2); im = imidazole (3), are unique organic-inorganic hybrids with the addition of a N-donor ligand at either end of the polyoxofluorovanadate...
January 10, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29317484/chemogenetic-excitation-of-accumbens-projecting-infralimbic-cortical-neurons-blocks-toluene-induced-conditioned-place-preference
#18
Wesley N Wayman, John J Woodward
Abuse rates for inhalants among adolescents continue to be high, yet preclinical models for studying mechanisms underlying inhalant abuse remain limited. Our lab has previously shown that, in male rats, an acute binge-like exposure to toluene vapor that mimics human solvent abuse modifies the intrinsic excitability of medial prefrontal cortex (mPFC) pyramidal neurons projecting to the nucleus accumbens (NAc). These changes showed region (infralimbic; IL vs. prelimbic; PRL), layer (shallow; 2/3 vs. deep; 5/6), target (core vs...
January 9, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29315268/mirna-influences-in-neuroblast-modulation-an-introspective-analysis
#19
REVIEW
Vanessa Zammit, Byron Baron, Duncan Ayers
Neuroblastoma (NB) is the most common occurring solid paediatric cancer in children under the age of five years. Whether of familial or sporadic origin, chromosome abnormalities contribute to the development of NB and cause dysregulation of microRNAs (miRNAs). MiRNAs are small non-coding, single stranded RNAs that target messenger RNAs at the post-transcriptional levels by repressing translation within all facets of human physiology. Such gene 'silencing' activities by miRNAs allows the development of regulatory feedback loops affecting multiple functions within the cell, including the possible differentiation of neural stem cell (NSC) lineage selection...
January 9, 2018: Genes
https://www.readbyqxmd.com/read/29311559/injured-adult-motor-and-sensory-axons-regenerate-into-appropriate-organotypic-domains-of-neural-progenitor-grafts
#20
Jennifer N Dulin, Andrew F Adler, Hiromi Kumamaru, Gunnar H D Poplawski, Corinne Lee-Kubli, Hans Strobl, Daniel Gibbs, Ken Kadoya, James W Fawcett, Paul Lu, Mark H Tuszynski
Neural progenitor cell (NPC) transplantation has high therapeutic potential in neurological disorders. Functional restoration may depend on the formation of reciprocal connections between host and graft. While it has been reported that axons extending out of neural grafts in the brain form contacts onto phenotypically appropriate host target regions, it is not known whether adult, injured host axons regenerating into NPC grafts also form appropriate connections. We report that spinal cord NPCs grafted into the injured adult rat spinal cord self-assemble organotypic, dorsal horn-like domains...
January 8, 2018: Nature Communications
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