Population Coding of Capsaicin Concentration by Sensory Neurons Revealed Using Ca2+ Imaging of Dorsal Root Ganglia Explants from Adult pirt-GCaMP3 Mouse

Background/Aims: Nociceptors detect noxious capsaicin (CAPS) via the transient receptor potential vanilloid 1 (TRPV1) ion channel, but coding mechanisms for relaying CAPS concentration [CAPS] remain obscure. Prolonged (up to 1h.) exposure to CAPS is used clinically to desensitise sensory fibres for treatment of neuropathic pain, but its signalling has typically been studied in cultures of dissociated sensory neurons employing low cell numbers and very short exposure times. Thus, it was pertinent to examine responses to longer CAPS exposures in large populations of adult neurons. Methods: Confocal fluorescence microscopy was used to monitor the simultaneous excitation by CAPS of neuronal populations in intact L3/4 dorsal root ganglia (DRG) explants from adult pirt-GCaMP3 mice that express a cytoplasmic, genetically-encoded Ca2+ sensor in almost all primary sensory neurons. Peak analysis was performed using GraphPad Prism 9 to deconstruct the heterogenous and complex fluorescence signals observed into informative, readily-comparable measurements: number of signals, their lag time, maximum intensity relative to baseline (Max.) and duration. Results: Exposure for 5 min. to CAPS activated plasmalemmal TRPV1 and led to increased fluorescence due to Ca2+ entry into DRG neurons (DRGNs), as it was prevented by capsazepine or removal of extracellular Ca2+. Increasing [CAPS] (0.3, 1 and 10 μM, respectively) evoked signals from more neurons (123, 275 and 390 from 5 DRG) with shorter average lag (6.4 ± 0.4, 3.3 ± 0.2 and 1.9 ± 0.1 min.) and longer duration (1.4 ± 0.2, 2.9 ± 0.2 and 4.8 ± 0.3 min.). Whilst raising [CAPS] produced a modest augmentation of Max. for individual neurons, those with large increases were selectively expedited; this contributed to a faster onset and higher peak of cumulative fluorescence for an enlarged responding neuronal population. CAPS caused many cells to fluctuate between high and low levels of fluorescence, with consecutive pulses increasing Max. and duration especially when exposure was extended from 5 to 20 min. Such signal facilitation counteracted tachyphylaxis, observed upon repeated exposure to 1 μM CAPS, preserving the cumulative fluorescence over time (signal density) in the population. Conclusion: Individual neurons within DRG differed extensively in the dynamics of response to CAPS, but systematic changes elicited by elevating [CAPS] increased signal density in a graded manner, unveiling a possible mechanism for population coding of responses to noxious chemicals. Signal density is sustained during prolonged and repeated exposure to CAPS, despite profound tachyphylaxis in some neurons, by signal facilitation in others. This may explain the burning sensation that persists for several hours when CAPS is used clinically.

Novel Features for Binary Time Series Based on Branch Length Similarity Entropy

Branch length similarity (BLS) entropy is defined in a network consisting of a single node and branches. In this study, we mapped the binary time-series signal to the circumference of the time circle so that the BLS entropy can be calculated for the binary time-series. We obtained the BLS entropy values for “1” signals on the time circle. The set of values are the BLS entropy profile. We selected the local maximum (minimum) point, slope, and inflection point of the entropy profile as the characteristic features of the binary time-series and investigated and explored their significance. The local maximum (minimum) point indicates the time at which the rate of change in the signal density becomes zero. The slope and inflection points correspond to the degree of change in the signal density and the time at which the signal density changes occur, respectively. Moreover, we show that the characteristic features can be widely used in binary time-series analysis by characterizing the movement trajectory of Caenorhabditis elegans. We also mention the problems that need to be explored mathematically in relation to the features and propose candidates for additional features based on the BLS entropy profile.

Higher choroidal thickness and lower choriocapillaris blood flow signal density based on optical coherence tomography angiography in diabetics

Diabetes mellitus (DM) is one of the fastest growing chronic diseases in the world and one of the main causes of vision loss. Whether or not diabetic choroidopathy (DC) is involved in the initiation and progression of diabetic ocular complications needs to be explored. We included 54 diabetic eyes from 36 diabetic patients, and 54 healthy eyes from 32 control subjects after propensity scores matching. All of the subjects were given pupil light and dark adaptation examination and optical coherence tomography angiography (OCTA). Scotopic pupil diameter (SPD), pupil contraction amplitude, and velocity of pupil contraction of the diabetic group were significantly lower than that of the healthy control group (P < 0.05).Choroidal thickness at temporal quadrant (at 750 μm) and superior quadrant (at 1500 μm and 2250 μm) increased in diabetic group compared to control group(P < 0.05).In the diabetic group, choriocapillaris blood flow signal density (CCBFSD) in the macular area (diameter = 2000 μm) were significantly decreased compared with the healthy control group (P < 0.05). Apparent changes in pupil and choroidal blood flow were observed in the diabetic patients.

Hypermanganesemia-Induced Cerebral Toxicity Mimicking an Acute Ischemic Stroke: A Case Report and Review of Overlapping Pathologies

Objective: To review and consider risk factors associated with the accumulation of and toxicity from manganese in patients receiving total parenteral nutrition (TPN). Case Summary: A 66-year-old female presented to the emergency department with right facial and arm weakness that initiated 1 hour prior to admission. Past medical history includes oral cancer with chronic aspiration and gastroparesis secondary to chemotherapy, TPN for 9 months, and a previous episode of right facial and arm parasthesias due to hypertensive emergency 4 years prior. The patient was assigned a National Institutes of Health Stroke Scale score of 6, cleared of an intracranial hemorrhage on imaging, and was administered tPA (tissue plasminogen activator) for an acute ischemic stroke after managing her hypertension to <185/110 mm Hg. Resolution of symptoms occurred within 24 hours. A magnetic resonance imaging of the patient’s brain 24-hours post-tPA indicated an increased signal density in the globus pallidus, which in turn is linked with encephalopathy and has been described as a marker for hypermanganesemia. Discussion: Manganese is an essential trace element with a critical role in numerous physiologic functions. Though readily obtained from dietary sources and rarely causing issue, manganese provided to patients via TPN may result in toxicities. Though the presentation of neurotoxicities associated with TPN-delivered manganese has been previously documented, the clinical presentation of toxicity has never mimicked an acute ischemic stroke. Conclusion: Though an evaluation of overlapping pathologies is warranted, this patient’s clinical presentation of manganese toxicity mimicked an acute ischemic stroke and resulted in the administration of a fibrinolytic. A more comprehensive appreciation of the implications of trace elements is demanded of clinicians.

Photoreceptor alteration in intermediate age-related macular degeneration

The aim of this study was to analyze photoreceptor alterations occurring in eyes with intermediate age-related macular degeneration (AMD) and to investigate their associations with choriocapillaris (CC) flow. In this retrospective case–control study, we collected data from 35 eyes with intermediate AMD from 35 patients who had swept source optical coherence tomography structural and angiography imaging obtained. A control group of 35 eyes from 35 healthy subjects was included for comparison. Our main outcome measure for comparison between groups was the normalized reflectivity of en face image segmented at the ellipsoid zone (EZ) level, which was calculated to quantify the photoreceptor damage. OCTA metrics to quantify CC flow signal were also computed. These metrics were measured in a circle centered on the fovea and with a diameter of 5 mm. In intermediate AMD eyes, the macular area occupied by drusen was identified. Therefore, the EZ reflectivity and CC flow signal were separately measured in regions without drusen (“drusen-free” region). Measurements were generated using previously published algorithms. Mean ± SD age was 74.1 ± 6.8 years in the intermediate AMD group and 72.1 ± 6.0 years in the control group (p = 0.206). The normalized EZ reflectivity was 0.76 ± 0.10 in the intermediate AMD group and 0.85 ± 0.08 in the control group (p < .0001). In the “drusen-free” region, the normalized EZ reflectivity was 0.77 ± 0.10 (p < .0001 vs. healthy controls) and was positively correlated with the CC flow signal density (ρ = − 0.340 and p = 0.020). In conclusion, eyes with intermediate AMD exhibit a diffuse reduced EZ normalized reflectivity, and this reduction is correlated with CC flow signal in the regions without drusen. This study supports the concept of the damage of the unit comprised of photoreceptor, CC, and intervening tissues as an early event in AMD.

Life cycle of Bacillus subtilis population: biofilm life cycle generation and response to environmental pH

Microbial populations are ubiquitous and some form a robust, multicellular structure called a biofilm that protects the cells from environmental damage. The biofilm life cycle is critical for controlling the population of important target microbes (both pathogenic and beneficial). Here we show that the hysteresis of Bacillus subtilis cell-type regulation with respect to auto-inducing signal strength leads to the life cycle of the cell population. We investigate life cycle generation and its dependence on environmental conditions by quantitative analysis of cyclically expanding, concentric circular colonies. Next, we construct an input/output model that controls cell types in response to environmental conditions and signal density. On the basis of this model, we propose a life cycle generation model for cell populations. The proposed model will widely predict biofilm-related phenomena and provide the basis for the description of highly self-regulating multicellular systems.

Data-Driven Methodology for Prioritizing Traffic Signal Retiming Operations

Signal retiming is one of the chief responsibilities of municipal transportation agencies, and is an important means of reducing congestion and improving transportation quality and reliability. Many agencies conduct signal retiming and adjustment in a schedule-based manner. However, leveraging a data-driven, need-based approach to signal retiming to prioritize operations could better optimize use of agency resources. Additionally, the growing availability of probe vehicle data has made it an increasingly popular tool for use in roadway performance measurement. This paper presents a methodology for using segment-level probe-based speed data to rank the performance of traffic signal corridors for retiming purposes. This methodology is then demonstrated in an analysis of 79 traffic signal corridors maintained by the City of Austin, Texas. The analysis considers 15-minute speed records for all weekdays in September 2016 and September 2017 to compute metrics and rank corridors based on their relative performance across time periods. The results show that the ranking methodology compares corridors equitably despite differences in road length, functional class, and traffic signal density. Additionally, the results indicate that the corridors prioritized by the ranking methodology represent a much greater potential for improving travel time than the corridors selected under the schedule-based approach.

Safety Evaluation of Freight Intermodal Connectors in Tennessee State

This paper evaluates the traffic safety along freight intermodal connectors (FICs), which are also known as “first mile/last mile roadways,” connecting facilities that link freight-intensive land uses to main freight routes. Using Tennessee’s FICs as a case study, the paper digests the safety with reference to crash frequency, crash rates, and statistical significance of attributing traffic and geometric factors. It was found that connectors leading to pipeline terminals have high crash rates (almost double) compared with other type of terminals, whereas port terminal connectors have the lowest safety problem indices. The study established correlative contributing causes of crash frequencies and rates along FICs that included average annual daily traffic, lanes, shoulders, access, and median types. Traffic signal density was found to strongly and significantly affect the probability of crashes, together with the presence of a two-way left-turn lane (TWLTL), which surprisingly tends to decrease the probability of crashes along these connectors. The presence of shoulders along intermodal connectors was found to help reduce the probability of crashes, whereas the presence of curb and gutter tends to increase crash frequency. Analysis indicated that most of the FICs with high crash rates were also operating at a lower traffic operations level of service (LOS), especially for critical movements toward freight facilities because of high truck volumes.

Real-Time Recursive Fingerprint Radio Map Creation Algorithm Combining Wi-Fi and Geomagnetism

Fingerprint is a typical indoor-positioning algorithm, which measures the strength of wireless signals and creates a radio map. Using this radio map, the position is estimated through comparisons with the received signal strength measured in real-time. The radio map has a direct effect on the positioning performance; therefore, it should be designed accurately and managed efficiently, according to the type of wireless signal, amount of space, and wireless-signal density. This paper proposes a real-time recursive radio map creation algorithm that combines Wi-Fi and geomagnetism. The proposed method automatically recreates the radio map using geomagnetic radio-map dual processing (GRDP), which reduces the time required to create it. It also reduces the size of the radio map by actively optimizing its dimensions using an entropy-based minimum description length principle (MDLP) method. Experimental results in an actual building show that the proposed system exhibits similar map creation time as a system using a Wi-Fi–based radio map. Geomagnetic radio maps exhibiting over 80% positioning accuracy were created, and the dimensions of the radio map that combined the two signals were found to be reduced by 23.81%, compared to the initially prepared radio map. The dimensions vary according to the wireless signal state, and are automatically reduced in different environments.

Modeling Spatio-temporal Dynamics of Chromatin Marks

ABSTRACTTo model spatial changes of chromatin mark peaks over time we developed and applied ChromTime, a computational method that predicts regions for which peaks either expand or contract significantly or hold steady between time points. Predicted expanding and contracting peaks can mark regulatory regions associated with transcription factor binding and gene expression changes. Spatial dynamics of peaks provided information about gene expression changes beyond localized signal density changes. ChromTime detected asymmetric expansions and contractions, which for some marks associated with the direction of transcription. ChromTime facilitates the analysis of time course chromatin data in a range of biological systems.