scholarly journals Bayesian mapping of the striatal microcircuit reveals robust asymmetries in the probabilities and distances of connections

2021 ◽  
Author(s):  
Francois Cinotti ◽  
Mark D Humphries
Keyword(s):  
Bayesian Approach ◽  
D2 Receptor ◽  
Cognitive Disorders ◽  
Projection Neuron ◽  
Current Data ◽  
Projection Neurons ◽  
Range Of Movement ◽  
Precise Knowledge ◽  
Wide Range ◽  
Using Data

The striatum's complex microcircuit is made by connections within and between its D1- and D2-receptor expressing projection neurons and at least five species of interneuron. Precise knowledge of this circuit is likely essential to understanding striatum's functional roles and its dysfunction in a wide range of movement and cognitive disorders. We introduce here a Bayesian approach to mapping neuron connectivity using intracellular recording data, which lets us simultaneously evaluate the probability of connection between neuron types, the strength of evidence for it, and its dependence on distance. Using it to synthesise a complete map of the rodent striatum, we find strong evidence for two asymmetries: a selective asymmetry of projection neuron connections, with D2 neurons connecting twice as densely to other projection neurons than do D1 neurons, but neither subtype preferentially connecting to another; and a length-scale asymmetry, with interneuron connection probabilities remaining non-negligible at more than twice the distance of projection neuron connections. We further show our Bayesian approach can evaluate evidence for wiring changes, using data from the developing striatum and a mouse model of Huntington's disease. By quantifying the uncertainty in our knowledge of the microcircuit, our approach reveals a wide range of potential striatal wiring diagrams consistent with current data.

A Bayesian Approach on Investigating Helicopter Emergency Medical Fatal Accidents

2021 ◽  
Vol 92 (7) ◽  
pp. 563-569
Author(s):  
Richard J. Simonson ◽  
Joseph R. Keebler ◽  
Alex Chaparro
Keyword(s):  
Bayesian Approach ◽  
Prior Information ◽  
Helicopter Emergency Medical Service ◽  
Current Data ◽  
Influential Factors ◽  
Fatal Accidents ◽  
Factors Associated ◽  
Emergency Medical ◽  
Accident Data ◽  
Using Data

INTRODUCTION: Helicopter Emergency Medical Service (HEMS) is a mode of transportation designed to expedite the transport of a patient. Compared to other modes of emergency transport and other areas of aviation, historically HEMS has had the highest accident-related fatality rates. Analysis of these accident data has revealed factors associated with an increased likelihood of accident-based fatalities. Here we report the results of an analysis on the likelihood of a fatality based on various factors as a result of a HEMS accident, employing a Bayesian framework.METHODS: A retrospective study was conducted using data extracted from the NTSB aviation accident database from April 31, 2005, to April 26, 2018. Evidence from Baker et al. (2006) was also used as prior information spanning from January 1, 1983, to April 30, 2005.RESULTS: A Bayesian logistic regression was implemented using the prior information and current data to calculate a posterior distribution confidence interval of possible values in predicting accident fatality. The results of the model indicate that flying at night (OR 3.06; 95 C.I 2.14, 4.48; PoD 100), flying under Instrument Flight Rules (OR 7.54; 95 C.I 3.94, 14.44; PoD 100), and post-crash fires (OR 18.73; 95 C.I 10.07, 34.12; PoD 100) significantly contributed to the higher likelihood of a fatality.CONCLUSION: Our results provide a comprehensive analysis of the most influential factors associated with an increased likelihood of a fatal accident occurring. We found that over the past 35 yr these factors were consistently associated with a higher likelihood of a fatality occurring.Simonson RJ, Keebler JR, Chaparro A. A Bayesian approach on investigating helicopter emergency medical fatal accidents. Aerosp Med Hum Perform. 2021; 92(7):563569.

Nanoparticles Functionalized with Venom-Derived Peptides and Toxins for Pharmaceutical Applications

2020 ◽  
Vol 21 (2) ◽  
pp. 97-109 ◽  
Author(s):  
Ana P. dos Santos ◽  
Tamara G. de Araújo ◽  
Gandhi Rádis-Baptista
Keyword(s):  
Oral Absorption ◽  
Current Data ◽  
Pharmacological Activities ◽  
Venom Peptides ◽  
Essential Components ◽  
Wide Range ◽  
Different Types ◽  
Direct Use ◽  
Animal Venoms ◽  
Pharmaceutical Biotechnology

Venom-derived peptides display diverse biological and pharmacological activities, making them useful in drug discovery platforms and for a wide range of applications in medicine and pharmaceutical biotechnology. Due to their target specificities, venom peptides have the potential to be developed into biopharmaceuticals to treat various health conditions such as diabetes mellitus, hypertension, and chronic pain. Despite the high potential for drug development, several limitations preclude the direct use of peptides as therapeutics and hamper the process of converting venom peptides into pharmaceuticals. These limitations include, for instance, chemical instability, poor oral absorption, short halflife, and off-target cytotoxicity. One strategy to overcome these disadvantages relies on the formulation of bioactive peptides with nanocarriers. A range of biocompatible materials are now available that can serve as nanocarriers and can improve the bioavailability of therapeutic and venom-derived peptides for clinical and diagnostic application. Examples of isolated venom peptides and crude animal venoms that have been encapsulated and formulated with different types of nanomaterials with promising results are increasingly reported. Based on the current data, a wealth of information can be collected regarding the utilization of nanocarriers to encapsulate venom peptides and render them bioavailable for pharmaceutical use. Overall, nanomaterials arise as essential components in the preparation of biopharmaceuticals that are based on biological and pharmacological active venom-derived peptides.

scholarly journals Risk factors for severity on admission and the disease progression during hospitalisation in a large cohort of patients with COVID-19 in Japan

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e047007
Author(s):  
Mari Terada ◽  
Hiroshi Ohtsu ◽  
Sho Saito ◽  
Kayoko Hayakawa ◽  
Shinya Tsuzuki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Chronic Respiratory Disease ◽  
Major Effect ◽  
Secondary Outcome ◽  
Healthcare Facilities ◽  
Wide Range ◽  
Registration Number ◽  
Using Data ◽  
Obesity Hypertension

ObjectivesTo investigate the risk factors contributing to severity on admission. Additionally, risk factors of worst severity and fatality were studied. Moreover, factors were compared based on three points: early severity, worst severity and fatality.DesignAn observational cohort study using data entered in a Japan nationwide COVID-19 inpatient registry, COVIREGI-JP.SettingAs of 28 September 2020, 10480 cases from 802 facilities have been registered. Participating facilities cover a wide range of hospitals where patients with COVID-19 are admitted in Japan.ParticipantsParticipants who had a positive test result on any applicable SARS-CoV-2 diagnostic tests were admitted to participating healthcare facilities. A total of 3829 cases were identified from 16 January to 31 May 2020, of which 3376 cases were included in this study.Primary and secondary outcome measuresPrimary outcome was severe or nonsevere on admission, determined by the requirement of mechanical ventilation or oxygen therapy, SpO2 or respiratory rate. Secondary outcome was the worst severity during hospitalisation, judged by the requirement of oxygen and/orinvasive mechanical ventilation/extracorporeal membrane oxygenation.ResultsRisk factors for severity on admission were older age, men, cardiovascular disease, chronic respiratory disease, diabetes, obesity and hypertension. Cerebrovascular disease, liver disease, renal disease or dialysis, solid tumour and hyperlipidaemia did not influence severity on admission; however, it influenced worst severity. Fatality rates for obesity, hypertension and hyperlipidaemia were relatively lower.ConclusionsThis study segregated the comorbidities influencing severity and death. It is possible that risk factors for severity on admission, worst severity and fatality are not consistent and may be propelled by different factors. Specifically, while hypertension, hyperlipidaemia and obesity had major effect on worst severity, their impact was mild on fatality in the Japanese population. Some studies contradict our results; therefore, detailed analyses, considering in-hospital treatments, are needed for validation.Trial registration numberUMIN000039873. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045453

Differential Involvement of Projection Neurons During Emergence of Spontaneous Activity in the Developing Avian Hindbrain

2009 ◽  
Vol 101 (2) ◽  
pp. 591-602 ◽  
Author(s):  
Hiraku Mochida ◽  
Gilles Fortin ◽  
Jean Champagnat ◽  
Joel C. Glover
Keyword(s):  
Spontaneous Activity ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Charge Coupled Device ◽  
Neuron Populations ◽  
Motor Nerves ◽  
Differential Involvement ◽  
A Charge ◽  
The Brain ◽  
Calcium Green

To better characterize the emergence of spontaneous neuronal activity in the developing hindbrain, spontaneous activity was recorded optically from defined projection neuron populations in isolated preparations of the brain stem of the chicken embryo. Ipsilaterally projecting reticulospinal (RS) neurons and several groups of vestibuloocular (VO) neurons were labeled retrogradely with Calcium Green-1 dextran amine and spontaneous calcium transients were recorded using a charge-coupled-device camera mounted on a fluorescence microscope. Simultaneous extracellular recordings were made from one of the trigeminal motor nerves (nV) to register the occurrence of spontaneous synchronous bursts of activity. Two types of spontaneous activity were observed: synchronous events (SEs), which occurred in register with spontaneous bursts in nV once every few minutes and were tetrodotoxin (TTX) dependent, and asynchronous events (AEs), which occurred in the intervals between SEs and were TTX resistant. AEs occurred developmentally before SEs and were in general smaller and more variable in amplitude than SEs. SEs appeared at the same stage as nV bursts early on embryonic day 4, first in RS neurons and then in VO neurons. All RS neurons participated equally in SEs from the outset, whereas different subpopulations of VO neurons participated differentially, both in terms of the proportion of neurons that exhibited SEs, the fidelity with which the SEs in individual neurons followed the nV bursts, and the developmental stage at which SEs appeared and matured. The results show that spontaneous activity is expressed heterogeneously among hindbrain projection neuron populations, suggesting its differential involvement in the formation of different functional neuronal circuits.

Postnatal Development of Electrophysiological Properties of Nucleus Accumbens Neurons

2000 ◽  
Vol 84 (5) ◽  
pp. 2204-2216 ◽  
Author(s):  
Marc L. Belleau ◽  
Richard A. Warren
Keyword(s):  
Nucleus Accumbens ◽  
Postnatal Development ◽  
Action Potentials ◽  
Membrane Resistance ◽  
Inward Rectification ◽  
Resting Membrane Potential ◽  
Projection Neurons ◽  
Patch Clamp Technique ◽  
Whole Cell ◽  
Wide Range

We have studied the postnatal development of the physiological characteristics of nucleus accumbens (nAcb) neurons in slices from postnatal day 1 ( P1) to P49 rats using the whole cell patch-clamp technique. The majority of neurons (102/108) were physiologically identified as medium spiny (MS) projection neurons, and only these were subjected to detailed analysis. The remaining neurons displayed characteristics suggesting that they were not MS neurons. Around the time of birth and during the first postnatal weeks, the membrane and firing characteristics of MS neurons were quite different from those observed later. These characteristics changed rapidly during the first 3 postnatal weeks, at which point they began to resemble those found in adults. Both whole cell membrane resistance and membrane time constant decreased more than fourfold during the period studied. The resting membrane potential (RMP) also changed significantly from an average of −50 mV around birth to less than −80 mV by the end of the third postnatal week. During the first postnatal week, the current-voltage relationship of all encountered MS neurons was linear over a wide range of membrane potentials above and below RMP. Through the second postnatal week, the proportion of neurons displaying inward rectification in the hyperpolarized range increased steadily and after P15, all recorded MS neurons displayed significant inward rectification. At all ages, inward rectification was blocked by extracellular cesium and tetra-ethyl ammonium and was not changed by 4-aminopyridine; this shows that inward rectification was mediated by the same currents in young and mature MS neurons. MS neurons fired single and repetitive Na+/K+ action potentials as early as P1. Spike threshold and amplitude remained constant throughout development in contrast to spike duration, which decreased significantly over the same period. Depolarizing current pulses from rest showed that immature MS neurons fired action potentials more easily than their older counterparts. Taken together, the results from the present study suggest that young and adult nAcb MS neurons integrate excitatory synaptic inputs differently because of differences in their membrane and firing properties. These findings provide important insights into signal processing within nAcb during this critical period of development.

scholarly journals Tonic engagement of nicotinic receptors bidirectionally controls striatal spiny projection neuron spike timing

2021 ◽  
Author(s):  
Lior Matityahu ◽  
Jeffrey Malgady ◽  
Meital Schirelman ◽  
Yvonne Johansson ◽  
Jennifer Wilking ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Gaba Release ◽  
Projection Neuron ◽  
Spike Timing ◽  
Projection Neurons ◽  
Striatal Slices ◽  
Cholinergic Interneurons ◽  
Α7 Nachr ◽  
Α7 Nachrs

Striatal spiny projection neurons (SPNs) transform convergent excitatory corticostriatal inputs into an inhibitory signal that shapes basal ganglia output. This process is fine-tuned by striatal GABAergic interneurons (GINs), which receive overlapping cortical inputs and mediate rapid corticostriatal feedforward inhibition of SPNs. Adding another level of control, cholinergic interneurons (CINs), which are also vigorously activated by corticostriatal excitation, can 1) disynaptically inhibit SPNs by activating α4β2 nicotinic acetylcholine receptors (nAChRs) on various GINs and 2) directly modulate corticostriatal synaptic strength via pre-synaptic α7 nAChR receptors. Measurements of the disynaptic inhibitory pathway, however, indicate that it is too slow to compete with direct GIN-mediated feed-forward inhibition. Moreover, functional nAChRs are also present on populations of GINs that do not respond to phasic activation of CINs, such as parvalbumin-positive fast-spiking interneurons (PV-FSIs), making the overall role of nAChRs in shaping striatal synaptic integration unclear. Using acute striatal slices we show that upon synchronous optogenetic activation of corticostriatal projections, blockade of α7 nAChRs delayed SPN spikes, whereas blockade of α4β2 nAChRs advanced SPN spikes and increased postsynaptic depolarizations. The nAChR-dependent inhibition was mediated by downstream GABA release, and data suggest that the GABA source was not limited to GINs that respond to phasic CIN activation. In particular, the observed spike-advancement caused by nAChR blockade was associated with a diminished frequency of spontaneous inhibitory postsynaptic currents in SPNs, and a parallel hyperpolarization of PV-FSIs. Taken together, we describe opposing roles for tonic (as opposed to phasic) engagement of nAChRs in striatal function. We conclude that tonic activation of nAChRs by CINs both sharpens the temporal fidelity of corticostriatal signaling via pre-synaptic α7 nAChRs and maintains a GABAergic brake on cortically-driven striatal output, processes that may shape SPN spike timing, striatal processing and synaptic plasticity.

scholarly journals Nesting of Great Cormorants (Phalacrocorax carbo) on man-made structures in Ukraine

2016 ◽  
Vol 24 (2) ◽  
Author(s):  
A. I. Sidorenko ◽  
V. D. Siokhin
Keyword(s):  
National Level ◽  
Field Work ◽  
Current Data ◽  
Great Cormorant ◽  
Phalacrocorax Carbo ◽  
Breeding Sites ◽  
Breeding Territory ◽  
Wide Range ◽  
Maintenance Work ◽  
Great Cormorants

In Ukraine the Great Cormorant (Phalacrocorax carbo Linnaeus, 1758) uses a rather wide range of habitats for nesting: islands, trees and shrubs, reedbeds and a variety of man-made structures. In general, the strategy of nesting on man-made structures is uncommon both in Ukraine and Europe, and Cormorantsdo this only in the absence of other sites suitable for nesting. Special research onCormorant colonies on technogenic constructions was carried out during the field expeditions by the Research Institute of Biodiversity of Terrestrial and Aquatic Ecosystems of Ukraine in 2002–2003 and 2012–2016. Besides this, we used retrospective and current data from the literature and Internet resources. Most of the field work was carried out by making surveys by boat and on foot. As a result, we found 8 Cormorant colonies on technogenic constructions in Ukraine: gas platforms in the Sea of Azov (near the village Strilkove, Henichesk district of Kherson region); sunken ships – targets for bombing training near the Arabat Spit (these are also known as «ship islands»); electricity pylons of the high-voltage Enerhodar Dnipro Power Line where it crosses the Kakhovka Reservoir; the dock in Yahorlyk Bayk, used in the past as a target for bombing training bombing; artificial island-platforms on Lake Chernine (Kinburn Peninsula); an artificial island on the Sasyk Lagoon (Odessa region); artificial islands, made as navigation markers on the Kremenchuk and Kiev reservoirs. The study found that in most cases the accompanying species was the CaspianGull (Larus cachinnans Pallas, 1811), which actively destroys the Cormorants’ nests and eats their eggs and chicks. The number of nests in the colonies varied greatly (5–30 nests on the navigation marker islands and ca. 2 000–2 300 on the «ship-islands» and gas platforms). This is due, primarily, to the area of the breeding territory. The research found that fierce territorial competition was observed in most of the colonies both with Caspian Gulls and between Cormorants. In addition, we observed anthropogenic interference in the colonies by fishermen and workers conducting routine maintenance work (as happened in the case of electricity pylons and gas platforms). The benefit of this study is that it is the first research in Ukraine conducted at national level onthis type of nesting by Cormorants. Moreover, the study examines the history of emergence of these nesting territories and population dynamics of the Great Cormorant from the time of initial settlement of the breeding sites till the present.

scholarly journals Digital Curation for Science, Digital Libraries, and Individuals

2008 ◽  
Vol 1 ◽  
pp. 3-16 ◽  
Author(s):  
Neil Beagrie
Keyword(s):  
Digital Libraries ◽  
Digital Information ◽  
Digital Curation ◽  
Wide Range ◽  
Intellectual Assets ◽  
Information Professionals ◽  
Using Data ◽  
Traditional Roles ◽  
Significant Effort ◽  
Digital Assets

The creation, management and use of digital materials are of increasing importance for a wide range of activities. Much of the knowledge base and intellectual assets of institutions and individuals are now in digital form. The term digital curation is increasingly being used for the actions needed to add value to and maintain these digital assets over time for current and future generations of users. The paper explores this emerging field of digital curation as an area of inter-disciplinary research and practice, and the trends which are influencing its development. It analyses the genesis of the term and how traditional roles relating to digital assets are in transition. Finally it explores some of the drivers for curation ranging from trends such as exponential growth in digital information, to "life-caching", digital preservation, the Grid and new opportunities for publishing, sharing, and re-using data. It concludes that significant effort needs to be put into developing a persistent information infrastructure for digital materials and into developing the digital curation skills of researchers and information professionals. Without this, current investment in digitisation and digital content will only secure short-term rather than lasting benefits.

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