206 research outputs found
Posttraumatic Stress Disorder or Combat Experience? A Functional Near-infrared Spectroscopy Study of Trauma-related Auditory and Olfactory Cues
While the clinical communities are aware of the prevalence of posttraumatic stress disorder (PTSD) among OEF/OIF/OND veterans, further efforts are necessary to bolster comprehensive strategies for assessment and treatment. The purpose of this study was to investigate whether a combat-related PTSD symptom provocation paradigm would elicit unique neurological responses via functional near-infrared spectroscopy across three groups – combat veterans with PTSD, combat veterans without PTSD, and nonmilitary participants without PTSD. Results indicated that combat veterans with PTSD demonstrated significant activation during exposure to a trauma-related sound compared to nonmilitary personnel at channels 14 (d = 1.03) and 15 (d = 1.30) and combat veterans without PTSD at channel 14 (d = 0.87). Specifically, this increased neural activation was approximately located in the right superior/medial prefrontal cortex (BA 9/10), associated with evaluating cue-familiarity and emotional detachment. Results were less clear with respect to a combat-related odor. These results suggest a specific neurophysiological response to trauma-related cues and if replicated, may offer a biomarker for combat-related PTSD. Such a response could provide incremental validity over diagnostic assessments alone and assist in planning and monitoring of treatment outcome
Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses
Activity-dependence of synaptic vesicle dynamics
The proper function of synapses relies on efficient recycling of synaptic vesicles. The small size of synaptic boutons has hampered efforts to define the dynamical states of vesicles during recycling. Moreover, whether vesicle motion during recycling is regulated by neural activity remains largely unknown. We combined nanoscale-resolution tracking of individual synaptic vesicles in cultured hippocampal neurons from rats of both sexes with advanced motion analyses to demonstrate that the majority of recently endocytosed vesicles undergo sequences of transient dynamical states including epochs of directed, diffusional, and stalled motion. We observed that vesicle motion is modulated in an activity-dependent manner, with dynamical changes apparent in ∼20% of observed boutons. Within this subpopulation of boutons, 35% of observed vesicles exhibited acceleration and 65% exhibited deceleration, accompanied by corresponding changes in directed motion. Individual vesicles observed in the remaining ∼80% of boutons did not exhibit apparent dynamical changes in response to stimulation. More quantitative transient motion analyses revealed that the overall reduction of vesicle mobility, and specifically of the directed motion component, is the predominant activity-evoked change across the entire bouton population. Activity-dependent modulation of vesicle mobility may represent an important mechanism controlling vesicle availability and neurotransmitter release.SIGNIFICANCE STATEMENTMechanisms governing synaptic vesicle dynamics during recycling remain poorly understood. Using nanoscale resolution tracking of individual synaptic vesicles in hippocampal synapses and advanced motion analysis tools we demonstrate that synaptic vesicles undergo complex sets of dynamical states that include epochs of directed, diffusive, and stalled motion. Most importantly, our analyses revealed that vesicle motion is modulated in an activity-dependent manner apparent as the reduction in overall vesicle mobility in response to stimulation. These results define the vesicle dynamical states during recycling and reveal their activity-dependent modulation. Our study thus provides fundamental new insights into the principles governing synaptic function
X-ray diffraction studies on the Pb/Si(111) system
Title from PDF of title page (University of Missouri--Columbia, viewed on May 25, 2012).The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Dissertation advisor: Dr. Paul F. MiceliVita.Ph. D. University of Missouri--Columbia 2011."December 2011"This dissertation investigates the structure of the Pb wetting layer on the Si(111)7x7 using X-ray diffraction techniques. It was found that the wetting layer shows a surprising kinetic behavior within the structure over a 200C temperature range. When grown at low temperature (150C), the wetting layer and the Si(111)7x7 transition to a Pb lattice gas on the Si(111)1x1 surface, removing the 7x7 reconstruction. Moreover, the rate of transition also increases with temperature. These kinetic observations resulted in a surface preparation procedure for a stable Pb/Si(111)7x7 wetting layer. The structure of the stable Pb/Si(111)7x7 wetting layer was solved with X-ray scattering. The samples were prepared and studied in ultrahigh vacuum (in-situ) using synchrotron radiation at the Advanced Photon Source, on the 6IDC beamline. The scattering measurements were a combination of reflectivity, in-plane diffraction, and truncation rod geometries. The structure has two Pb layers along with a modified Si adatom layer. The wetting layer is densely packed, with atoms distributed between bulk Si sites and a lattice of commensurate 8x8 sites. Directly below the wetting layer is a low density, ~6 Pb atom, Pb layer occupying sits directly above Si 7x7 atoms. The 12 atoms in the initial Si 7x7 adatom layer are displaced toward the edges of the unit cell, in the presence of Pb. Moreover, they maintain a 6x6 distance commensurate with the 7x7 unit cell. The structural model proposed here addresses conflicting models that appear in the literature and it solves a long-standing problem that is important to quantum size effect systems.Includes bibliographical reference
Neurological Reactivity to Personalized Odors and Sounds in Combat-related Posttraumatic Stress Disorder
Functional near-infrared spectroscopy (fNIRS) is a neurophysiological procedure that offers immense clinical utility due to its cost effectiveness, ease of use, and mobile application. Using fNIRS to measure neurological reactions to personalized trauma-related cues might strengthen diagnostic screening, tailor treatment planning, and improve detection of remission among individuals with posttraumatic stress disorder (PTSD). Odors elicit strong emotional responses but remain underutilized in clinical research. This fNIRS study examined whether personalizing combat-related odors and sounds to have a higher or lower match to distressing combat experiences increased the observed neurological effect among combat veterans with and without combat-related PTSD. This study gathered data from 58 male, right-handed combat veterans of Iraq or Afghanistan, ages 26 to 68, recruited from the community. The results indicated a significant increase in activation at the left ventral lateral prefrontal cortex (VLPFC) following an interaction between higher PTSD severity and higher match ratings for the combat-related odors (R2 = .20, p = .003; f2 = .25). Furthermore, the left VLPFC showed a significant increase in activation following an interaction between having a PTSD diagnosis and higher match ratings for the combat-related odors (R2 = .25, p = .005; f2 = .33). The findings for the combat-related sounds were less clear. The left VLPFC is associated with facilitating regulation of memory and emotional processes. Overall, the presentation of odors with higher similarity to distressing combat experiences altered the neurological response of the prefrontal cortex and may contribute to better understanding of the neurophysiological mechanisms of combat-related PTSD
Myosin V regulates spatial localization of different forms of neurotransmitter release in central synapses
Synaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicular (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites in an activity-dependent manner. Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center toward periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition of myosin V also reduces preferential utilization of central release sites during MVR, leading to more spatially distributed and temporally uniform MVR that occurs farther away from the AZ center. Using a modeling approach, we provide a conceptual framework that unites spatial and temporal functions of myosin V in vesicle release by controlling the gradient of release site release probability across the AZ, which in turn determines the spatiotemporal organization of both UVR and MVR. Thus myosin V regulates both temporal and spatial utilization of release sites during two main forms of synchronous release
Recently recycled synaptic vesicles use multi-cytoskeletal transport and differential presynaptic capture probability to establish a retrograde net flux during ISVE in central neurons
Presynapses locally recycle synaptic vesicles to efficiently communicate information. During use and recycling, proteins on the surface of synaptic vesicles break down and become less efficient. In order to maintain efficient presynaptic function and accommodate protein breakdown, new proteins are regularly produced in the soma and trafficked to presynaptic locations where they replace older protein-carrying vesicles. Maintaining a balance of new proteins and older proteins is thus essential for presynaptic maintenance and plasticity. While protein production and turnover have been extensively studied, it is still unclear how older synaptic vesicles are trafficked back to the soma for recycling in order to maintain balance. In the present study, we use a combination of fluorescence microscopy, hippocampal cell cultures, and computational analyses to determine the mechanisms that mediate older synaptic vesicle trafficking back to the soma. We show that synaptic vesicles, which have recently undergone exocytosis, can differentially utilize either the microtubule or the actin cytoskeleton networks. We show that axonally trafficked vesicles traveling with higher speeds utilize the microtubule network and are less likely to be captured by presynapses, while slower vesicles utilize the actin network and are more likely to be captured by presynapses. We also show that retrograde-driven vesicles are less likely to be captured by a neighboring presynapse than anterograde-driven vesicles. We show that the loss of synaptic vesicle with bound molecular motor myosin V is the mechanism that differentiates whether vesicles will utilize the microtubule or actin networks. Finally, we present a theoretical framework of how our experimentally observed retrograde vesicle trafficking bias maintains the balance with previously observed rates of new vesicle trafficking from the soma
Peri-interventional combined anticoagulation and antithrombotic therapy in atrial fibrillation ablation: A retrospective safety analysis
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 Background: Catheter ablation (CA) of atrial fibrillation (AF) requires an intensified peri-interÂventional anticoagulation scheme to avoid thromboembolic complications. In patients with cardiac or extracardiac artery disease, an additional antiplatelet treatment (AAT) is at least temporally necessary especially after a percutaneous intervention with stent implantation. This raises the question whether these patients have a higher peri-interventional bleeding risk during CA of AF.
Methods: The data of 1235 patients with CA of AF were retrospectively analyzed in terms of bleeding events, ablation type, antithrombotic medication and comorbidities such as coronary artery disease and components of the HAS- BLED score. Peri-interventional bleeding events were classified in accordance with the BARC classification. Differentiations were made between slight femoral bleeding (based on type 1), severe femoral bleeding and pericardial effusion without pericardiocentesis (based on type 2) with the need of further hospitalization, the need of transfusion (based on type 3a) and pericardial tamponades requiring pericardiocentesis (based on type 3b).
Results: 1131/1235 (91.6%) patients were exclusively under anticoagulation and 187 (15.3%) patients were also on AAT. There were no statistically significant differences in type 1 and 3b bleeding complicaÂtions or the occurrence of femoral pseudoaneurysms between both groups. However, type 2/3a bleeding complications, mostly femoral bleedings, were significantly more frequent in the patient group with AAT (3.2% vs. 7.5%, p = 0.006).
Conclusions: An additional antiplatelet therapy increases the risk of severe femoral bleeding events during CA of AF. It appears reasonable to perform the elective procedure of AF ablation after the disÂcontinuation of AAT.
Antisense-mediated exon skipping: a therapeutic strategy for titin-based dilated cardiomyopathy
Frameshift mutations in the TTN gene encoding titin are a major cause for inherited forms of dilated cardiomyopathy (DCM), a heart disease characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure. To date, there are no specific treatment options for DCM patients but heart transplantation. Here, we show the beneficial potential of reframing titin transcripts by antisense oligonucleotide (AON)-mediated exon skipping in human and murine models of DCM carrying a previously identified autosomal-dominant frameshift mutation in titin exon 326. Correction of TTN reading frame in patient-specific cardiomyocytes derived from induced pluripotent stem cells rescued defective myofibril assembly and stability and normalized the sarcomeric protein expression. AON treatment in Ttn knock-in mice improved sarcomere formation and contractile performance in homozygous embryos and prevented the development of the DCM phenotype in heterozygous animals. These results demonstrate that disruption of the titin reading frame due to a truncating DCM mutation canbe restored by exon skipping in both patient cardiomyocytes invitro and mouse heart invivo, indicating RNA-based strategies as a potential treatment option for DCM
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