Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 99
Filter
1.
AIDS Behav ; 28(6): 2034-2053, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38605253

ABSTRACT

Ensuring adequate and equitable access to affordable HIV testing is a crucial step toward ending the HIV epidemic (EHE). Using the high-burden Baton Rouge Metropolitan Statistical Area (MSA) as an example, we measure spatial access to HIV testing facilities for vulnerable populations and assess whether their access would improve if eliminating a considerable barrier-costs. Locations and status (free, low-cost, and full cost) of HIV testing facilities are searched on the Internet and confirmed through a field survey. Vulnerable populations include the uninsured and people living with HIV (PLWH), disaggregated from county-level HIV prevalence data. Spatial access is computed by a normalized urban-rural two-step floating catchment area (NUR2SFCA) method. Our survey confirms that only 11% and 37% of the 103 Internet-searched HIV testing facilities are indeed free and low-cost. Making more facilities cheaper or free increases the average access of PLWH, the uninsured, and the entire population but their geographic patterns vary. Free testing facilities, clustered in Baton Rouge city, are highly accessible to 82.6%, 69.4%, and 70.2% of three population groups living in East and West Baton Rouge Parish. In comparison, making all low-cost facilities free increases access in most outlying parishes but at the cost of reducing access in East Baton Rouge Parish, leaving west Livingston, north Iberville, and east Pointe Coupee Parish with the poorest access. Making all full-cost facilities cheaper or free exhibits a similar pattern. The study has important policy implications for where and how to improve access to HIV testing for vulnerable populations.


RESUMEN: Medimos el acceso espacial a las instalaciones de pruebas de VIH para poblaciones vulnerables y evaluamos si su acceso mejoraría si se eliminaran las barreras de costos, utilizando como ejemplo el área estadística metropolitana de Baton Rouge, que tiene una alta carga. Nuestra encuesta confirma que el 11% y el 37% de los 103 centros de pruebas de VIH buscados en Internet son efectivamente gratuitos y de bajo costo. Hacer que más instalaciones sean más baratas o gratuitas aumenta el acceso promedio de las PLWH, las personas sin seguro y toda la población, pero sus patrones geográficos varían. Las instalaciones de pruebas gratuitas, agrupadas en la ciudad de Baton Rouge, son muy accesibles para el 82,6%, el 69,4% y el 70,2% de los tres grupos de población del este y oeste de Baton Rouge. En comparación, hacer que las instalaciones de bajo costo sean gratuitas aumenta el acceso en las parroquias periféricas, pero a costa de reducir el acceso en East Baton Rouge. Hacer que las instalaciones de costo total sean más baratas o gratuitas muestra un patrón similar. El estudio tiene importantes implicaciones políticas para mejorar el acceso a las pruebas del VIH para las poblaciones vulnerables.


Subject(s)
HIV Infections , HIV Testing , Health Services Accessibility , Vulnerable Populations , Humans , Health Services Accessibility/statistics & numerical data , HIV Infections/epidemiology , HIV Infections/diagnosis , HIV Testing/statistics & numerical data , Louisiana/epidemiology , Female , Male , Urban Population/statistics & numerical data , Medically Uninsured/statistics & numerical data , Prevalence , Adult , Mass Screening/statistics & numerical data , Spatial Analysis
2.
J Pharmacol Toxicol Methods ; 126: 107498, 2024.
Article in English | MEDLINE | ID: mdl-38432528

ABSTRACT

BACKGROUND AND PURPOSE: A recent paradigm shift in proarrhythmic risk assessment suggests that the integration of clinical, non-clinical, and computational evidence can be used to reach a comprehensive understanding of the proarrhythmic potential of drug candidates. While current computational methodologies focus on predicting the incidence of proarrhythmic events after drug administration, the objective of this study is to predict concentration-response relationships of QTc as a clinical endpoint. EXPERIMENTAL APPROACH: Full heart computational models reproducing human cardiac populations were created to predict the concentration-response relationship of changes in the QT interval as recommended for clinical trials. The concentration-response relationship of the QT-interval prolongation obtained from the computational cardiac population was compared against the relationship from clinical trial data for a set of well-characterized compounds: moxifloxacin, dofetilide, verapamil, and ondansetron. KEY RESULTS: Computationally derived concentration-response relationships of QT interval changes for three of the four drugs had slopes within the confidence interval of clinical trials (dofetilide, moxifloxacin and verapamil) when compared to placebo-corrected concentration-ΔQT and concentration-ΔQT regressions. Moxifloxacin showed a higher intercept, outside the confidence interval of the clinical data, demonstrating that in this example, the standard linear regression does not appropriately capture the concentration-response results at very low concentrations. The concentrations corresponding to a mean QTc prolongation of 10 ms were consistently lower in the computational model than in clinical data. The critical concentration varied within an approximate ratio of 0.5 (moxifloxacin and ondansetron) and 1 times (dofetilide, verapamil) the critical concentration observed in human clinical trials. Notably, no other in silico methodology can approximate the human critical concentration values for a QT interval prolongation of 10 ms. CONCLUSION AND IMPLICATIONS: Computational concentration-response modelling of a virtual population of high-resolution, 3-dimensional cardiac models can provide comparable information to clinical data and could be used to complement pre-clinical and clinical safety packages. It provides access to an unlimited exposure range to support trial design and can improve the understanding of pre-clinical-clinical translation.


Subject(s)
Fluoroquinolones , Long QT Syndrome , Phenethylamines , Sulfonamides , Humans , Dose-Response Relationship, Drug , Electrocardiography , Fluoroquinolones/adverse effects , Heart Rate , Long QT Syndrome/chemically induced , Long QT Syndrome/drug therapy , Moxifloxacin/therapeutic use , Ondansetron/therapeutic use , Verapamil
3.
Front Neurol ; 14: 1114718, 2023.
Article in English | MEDLINE | ID: mdl-37456634

ABSTRACT

Introduction: A significant number of Restitution Training (RT) paradigms claim to ameliorate visual field loss after stroke by re-activating neuronal connections in the residual visual cortex due to repeated bright light-stimulation at the border of the blind and intact fields. However, the effectiveness of RT has been considered controversial both in science and clinical practice for years. The main points of the controversy are (1) the reliability of perimetric results which may be affected by compensatory eye movements and (2) heterogeneous samples consisting of patients with visual field defects and/or visuospatial neglect. Methods: By means of our newly developed and validated Virtual Reality goggles Salzburg Visual Field Trainer (SVFT) 16 stroke patients performed RT on a regular basis for 5 months. By means of our newly developed and validated Eye Tracking Based Visual Field Analysis (EFA), we conducted a first-time full eye-movement-controlled perimetric pre-post intervention study. Additionally, patients subjectively rated the size of their intact visual field. Results: Analysis showed that patients' mean self-assessment of their subjective visual field size indicated statistically significant improvement while, in contrast, objective eye tracking controlled perimetric results revealed no statistically significant effect. Discussion: Bright-light detection RT at the blind-field border solely induced a placebo effect and did not lead to training-induced neuroplasticity in the visual cortex of the type needed to ameliorate the visual field size of stroke patients.

4.
J Cell Sci ; 136(15)2023 08 01.
Article in English | MEDLINE | ID: mdl-37401342

ABSTRACT

The phospholipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] acts as a signaling lipid at the plasma membrane (PM) with pleiotropic regulatory actions on multiple cellular processes. Signaling specificity might result from spatiotemporal compartmentalization of the lipid and from combinatorial binding of PI(4,5)P2 effector proteins to additional membrane components. Here, we analyzed the spatial distribution of tubbyCT, a paradigmatic PI(4,5)P2-binding domain, in live mammalian cells by total internal reflection fluorescence (TIRF) microscopy and molecular dynamics simulations. We found that unlike other well-characterized PI(4,5)P2 recognition domains, tubbyCT segregates into distinct domains within the PM. TubbyCT enrichment occurred at contact sites between PM and endoplasmic reticulum (ER) (i.e. at ER-PM junctions) as shown by colocalization with ER-PM markers. Localization to these sites was mediated in a combinatorial manner by binding to PI(4,5)P2 and by interaction with a cytosolic domain of extended synaptotagmin 3 (E-Syt3), but not other E-Syt isoforms. Selective localization to these structures suggests that tubbyCT is a novel selective reporter for a ER-PM junctional pool of PI(4,5)P2. Finally, we found that association with ER-PM junctions is a conserved feature of tubby-like proteins (TULPs), suggesting an as-yet-unknown function of TULPs.


Subject(s)
Biosensing Techniques , Phosphatidylinositol 4,5-Diphosphate , Animals , Phosphatidylinositol 4,5-Diphosphate/metabolism , Cell Membrane/metabolism , Phosphatidylinositols/metabolism , Endoplasmic Reticulum/metabolism , Mammals/metabolism
5.
Humanit Soc Sci Commun ; 10(1): 215, 2023.
Article in English | MEDLINE | ID: mdl-37192951

ABSTRACT

The present multi-study article investigates the subjective experience of professional football (a.k.a. soccer) referees and players during the COVID-19 pandemic and the so-called ghost games (i.e., games without supporters). Referees from the Austrian Football Association completed questionnaires inquiring about self-efficacy, motivation, and general personal observations and perceptions (e.g., arousal or confidence). In addition, two players and one referee in the Austrian Football Bundesliga were interviewed retrospectively regarding their subjective experience during ghost games and the effects of emotions on behavior and performance using semi-structured, video-taped interviews. Results of the referee survey indicate that the most profound differences between regular games and ghost games lie in the domain of intrinsic motivation and multiple aspects of subjective experience. Specifically, the experience in ghost games compared with regular games was reported by referees as being significantly less motivating, less excited/tense, less emotional, less focused, and overall, more negative, despite being easier to referee and the players behaving more positively. Qualitative analyses of the video-taped interview footage indicated (i) substantial inter-individual variability regarding the extent of the effect of the empty stadiums on the subjective experience of emotions, (ii) consequently, different strategies to regulate emotions and arousal from suboptimal to optimal levels, both before and during competition, and (iii) interactions between reported emotions, arousal, motivation, self-confidence, behavior and performance on the pitch. In addition, non-verbal expressions of emotion were captured using fully automated AI-software that coded facial movements during interviews. The results of this exploratory facial expression analysis revealed varying degrees of arousal and valence in relation to the content of the statements during the interviews, demonstrating the convergent validity of our findings. Our findings contribute to the growing literature on the effects of football games without fans during the COVID-19 pandemic and provide insights into the subjective experience of professional football referees. Concerning referees and players alike, emotions are investigated as potential processes related to home-field advantage and performance in professional football by means of a multi-methods approach. Further, the combination of qualitative and quantitative measures-as well as verbal and non-verbal communication channels-can deepen our understanding of the emotional influence of (missing) spectators on the subjective experience and the behavior of sports professionals is discussed.

6.
iScience ; 26(1): 105836, 2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36636344

ABSTRACT

The endosymbiotic bacterium Wolbachia pipientis blocks replication of several arboviruses in transinfected Aedes aegypti mosquitoes. However, the mechanism of virus blocking remains poorly understood. Here, we characterized an RNase HI gene from Wolbachia, which is rapidly induced in response to dengue virus (DENV) infection. Knocking down w RNase HI using antisense RNA in Wolbachia-transinfected mosquito cell lines and A. aegypti mosquitoes led to increased DENV replication. Furthermore, overexpression of wRNase HI, in the absence of Wolbachia, led to reduced replication of a positive sense RNA virus, but had no effect on a negative sense RNA virus, a familiar scenario in Wolbachia-infected cells. Altogether, our results provide compelling evidence for the missing link between early Wolbachia-mediated virus blocking and degradation of viral RNA. These findings and the successful pioneered knockdown of Wolbachia genes using antisense RNA in cell line and mosquitoes enable new ways to manipulate and study the complex endosymbiont-host interactions.

7.
J Gen Virol ; 103(1)2022 01.
Article in English | MEDLINE | ID: mdl-35006065

ABSTRACT

Mosquito-borne flaviviruses are responsible for viral infections and represent a considerable public health burden. Aedes aegypti is the principal vector of dengue virus (DENV), therefore understanding the intrinsic virus-host interactions is vital, particularly in the presence of the endosymbiont Wolbachia, which blocks virus replication in mosquitoes. Here, we examined the transcriptional response of Wolbachia-transinfected Ae. aegypti Aag2 cells to DENV infection. We identified differentially expressed immune genes that play a key role in the activation of anti-viral defence such as the Toll and immune deficiency pathways. Further, genes encoding cytosine and N6-adenosine methyltransferases and SUMOylation, involved in post-transcriptional modifications, an antioxidant enzyme, and heat-shock response were up-regulated at the early stages of DENV infection and are reported here for the first time. Additionally, several long non-coding RNAs were among the differentially regulated genes. Our results provide insight into Wolbachia-transinfected Ae. aegypti's initial virus recognition and transcriptional response to DENV infection.


Subject(s)
Aedes/virology , Dengue Virus/genetics , Dengue/virology , Wolbachia/physiology , Aedes/microbiology , Animals , Dengue Virus/physiology , Host Microbial Interactions , Humans , Mosquito Vectors/microbiology , Mosquito Vectors/virology , RNA, Long Noncoding , Sumoylation , Virus Replication
8.
Methods ; 197: 54-62, 2022 01.
Article in English | MEDLINE | ID: mdl-33677061

ABSTRACT

Biosensing atomic force microscopy (AFM) offers the unique feature to determine the energy landscape of a bimolecular interaction at the real single molecule level. Furthermore, simultaneous and label-free mapping of molecular recognition and the determination of sample topography at the nanoscale gets possible. A prerequisite and one of the major parts in biosensing AFM are the bio-functionalized AFM tips. In the past decades, different approaches for tip functionalization have been developed. Using these functionalization strategies, several biological highly relevant interactions at the single molecule level have been explored. For the most common approach, the use of a heterobifunctional poly(ethylenglycol) crosslinker, a broad range of linkers for different chemical coupling strategies is available. Nonetheless, the time consuming functionalization protocol as well as the broad distribution of rupture length reduces the possibility of automation and may reduce the accuracy of the results. Here we present a stable and fast forward approach based on tetra-functional DNA tetrahedra. A fast functionalization and a sharp defined distribution of rupture length gets possible with low effort and high success rate. We tested the performance on the classical avidin biotin system by using tetrahedra with three disulfide legs for stable and site directed coupling to gold coated tips and a biotinylated end at the fourth vertex. A special advantage appears when working with a DNA aptamer as sensing molecule. In this case, the fourth strand can be extended by a certain DNA sequence complementary to the linkage part of an aptamer. This AFM tip functionalization protocol was applied on thrombin using DNA aptamers directed against the fibrinogen binding side of human thrombin.


Subject(s)
Aptamers, Nucleotide , Avidin , Aptamers, Nucleotide/metabolism , Avidin/chemistry , Avidin/metabolism , Biotin/chemistry , DNA , Humans , Microscopy, Atomic Force/methods
9.
Front Psychol ; 13: 933438, 2022.
Article in English | MEDLINE | ID: mdl-36619058

ABSTRACT

Mouth-to-nose face masks became ubiquitous due to the COVID-19 pandemic. This ignited studies on the perception of emotions in masked faces. Most of these studies presented still images of an emotional face with a face mask digitally superimposed upon the nose-mouth region. A common finding of these studies is that smiles become less perceivable. The present study investigated the recognition of basic emotions in video sequences of faces. We replicated much of the evidence gathered from presenting still images with digitally superimposed masks. We also unearthed fundamental differences in comparison to existing studies with regard to the perception of smile which is less impeded than previous studies implied.

10.
Cells ; 10(12)2021 11 30.
Article in English | MEDLINE | ID: mdl-34943878

ABSTRACT

Subtype-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are promising tools, e.g., to assess the potential of drugs to cause chronotropic effects (nodal hiPSC-CMs), atrial fibrillation (atrial hiPSC-CMs), or ventricular arrhythmias (ventricular hiPSC-CMs). We used single-cell patch-clamp reverse transcriptase-quantitative polymerase chain reaction to clarify the composition of the iCell cardiomyocyte population (Fujifilm Cellular Dynamics, Madison, WI, USA) and to compare it with atrial and ventricular Pluricytes (Ncardia, Charleroi, Belgium) and primary human atrial and ventricular cardiomyocytes. The comparison of beating and non-beating iCell cardiomyocytes did not support the presence of true nodal, atrial, and ventricular cells in this hiPSC-CM population. The comparison of atrial and ventricular Pluricytes with primary human cardiomyocytes showed trends, indicating the potential to derive more subtype-specific hiPSC-CM models using appropriate differentiation protocols. Nevertheless, the single-cell phenotypes of the majority of the hiPSC-CMs showed a combination of attributes which may be interpreted as a mixture of traits of adult cardiomyocyte subtypes: (i) nodal: spontaneous action potentials and high HCN4 expression and (ii) non-nodal: prominent INa-driven fast inward current and high expression of SCN5A. This may hamper the interpretation of the drug effects on parameters depending on a combination of ionic currents, such as beat rate. However, the proven expression of specific ion channels supports the evaluation of the drug effects on ionic currents in a more realistic cardiomyocyte environment than in recombinant non-cardiomyocyte systems.


Subject(s)
Electrophysiological Phenomena , Induced Pluripotent Stem Cells/metabolism , Ion Channels/metabolism , Myocytes, Cardiac/metabolism , Cells, Cultured , Gene Expression Regulation , Humans , Ion Channel Gating , Myocytes, Cardiac/cytology , Single-Cell Analysis
11.
Front Sports Act Living ; 3: 720488, 2021.
Article in English | MEDLINE | ID: mdl-34490426

ABSTRACT

Due to the COVID-19 pandemic, European elite football (a.k.a. soccer) leagues played the remaining season 2019/20 without or strongly limited attendance of supporters (i.e., "ghost games"). From a sport psychological perspective this situation poses a unique opportunity to investigate the crowd's influence on referee decisions and the associated effect of "home advantage." A total of 1286 matches-played in the top leagues of Spain, England, Germany, Italy, Russia, Turkey, Austria and the Czech Republic-were analyzed for results, fouls, bookings and reasons for bookings and contrasted between respective matchdays of season 2018/19 (regular attendance) and season 2019/20 (ghost games). Following recent methodological developments in the research on the home advantage effect, four different statistical analyses-including Pollard's traditional method-were used for the assessment of the home advantage effect. There are two main findings. First, home teams were booked significantly more often with yellow cards for committing fouls in ghost games. Most importantly, this effect was independent of the course of the games. In contrast, bookings for other reasons (criticism and unfair sportsmanship) changed similarly for both home and away teams in ghost games. Second, the overall home performance and home advantage effect in the respective elite leagues-identified in the respective matches of the regular 2018/19 season-vanished in the ghost games of the 2019/20 season. We conclude that the lack of supporters in top European football during the COVID-19 pandemic led to decreased social pressure from the ranks on referees, which also had a potential impact on the home advantage. Referees assessed the play of home teams more objectively, leading to increased yellow cards awarded for fouls committed by the home teams. Since there were no significant changes in referee decisions against the away teams, we argue that our observations reflect a reduction of unconscious favoritism of referees for the home teams.

12.
PLoS One ; 16(9): e0249762, 2021.
Article in English | MEDLINE | ID: mdl-34529704

ABSTRACT

OBJECTIVE: "Visual Restitution Therapies" (VRT) claim to ameliorate visual field defects of neurological patients by repeated visual light stimulation, leading to training-related neuroplasticity and resulting in reconnection of lesioned neurons in early cortical areas. Because existing systems are stationary, uncomfortable, and unreliable, we developed a training instrument based on virtual reality goggles. The goal of the "Salzburg Visual Field Trainer" (SVFT) is twofold: (1) The device facilitates the clinical evaluation of established neuropsychological rehabilitation approaches, such as VRT. (2) The device enables patients to independently perform VRT based (or other) neuropsychological training methodologies flexibly and comfortably. METHODS AND ANALYSIS: The SVFT was developed on the principles of VRT. Individual configuration of the SVFT is based on perimetric data of the respective patient's visual field. To validate the utmost important aspect of neuropsychological rehabilitation methodologies-that is displaying stimuli precisely in desired locations in the user's visual field-two steps were conducted in this proof-of-concept study: First, we assessed the individual "blind spots" location and extent of 40 healthy, normal sighted participants. This was done with the help of our recently developed perimetric methodology "Eye Tracking Based Visual Field Analysis" (EFA). Second, depending on the individual characteristics of every participant's blind spots, we displayed-by means of the SVFT-15 stimuli in the respective locations of every participants' blind spots and 85 stimuli in the surrounding, intact visual area. The ratio between visible and non-visible stimuli, which is reflected in the behavioral responses (clicks on a remote control) of the 40 participants, provides insight into the accuracy of the SVFT to display training stimuli in areas desired by the investigator. As the blind spot is a naturally occurring, absolute scotoma, we utilized this blind area as an objective criterion and a "simulated" visual field defect to evaluate the theoretical applicability of the SVFT. RESULTS: Outcomes indicate that the SVFT is highly accurate in displaying training stimuli in the desired areas of the user's visual field with an accuracy of 99.0%. Data analysis further showed a sensitivity of .98, specificity of .99, a positive predictive value of .96, a negative predictive value of .996, a hit rate of .99, a random hit rate of .74 and a RATZ-Index of .98. This translates to 14.7% correct non-reactions, 0.7% false non-reactions, 0.3% false reactions and 84.3% correct reactions to displayed test stimuli during the evaluation study. Reports from participants further indicate that the SVFT is comfortable to wear and intuitive to use. CONCLUSIONS: The SVFT can help to investigate the true effects of VRT based methodologies (or other neuropsychological approaches) and the underlying mechanisms of training-related neuroplasticity in the visual cortex in neurological patients suffering from visual field defects.


Subject(s)
Virtual Reality , Visual Fields , Biofeedback, Psychology , Equipment Design , Healthy Volunteers , Humans , Photic Stimulation , Proof of Concept Study , Rehabilitation/instrumentation , Rehabilitation/methods , Rehabilitation/psychology
13.
PLoS One ; 16(8): e0253591, 2021.
Article in English | MEDLINE | ID: mdl-34411128

ABSTRACT

This research compares and evaluates different approaches to approximate offense times of crimes. It contributes to and extends all previously proposed naïve and aoristic temporal approximation methods and one recent study [1] that showed that the addition of historical crimes with accurately known time stamps to temporal approximation methods can outperform all traditional approximation methods. It is paramount to work with crime data that possess precise temporal information to conduct reliable (spatiotemporal) analysis and modeling. This study contributes to and extends existing studies on temporal analysis. One novel and one relatively new temporal approximation methods are introduced that rely on weighting aoristic scores with historic offenses with exactly known offense times. It is hypothesized that these methods enhance the accuracy of the temporal approximation. In total, eight different methods are evaluated for apartment burglaries in Vienna, Austria, for yearly and seasonal differences. Results show that the one novel and one relatively new method applied in this research outperform all other existing approximation methods to estimate and predict offense times. These two methods are particularly useful for both researchers and practitioners, who often work with temporally imprecise crime data.


Subject(s)
Crime , Austria , Housing , Humans , Seasons , Theft , Time Factors
14.
Neurocase ; 27(3): 308-318, 2021 06.
Article in English | MEDLINE | ID: mdl-34278959

ABSTRACT

A patient suffering from visuo-spatial neglect was investigated as a special interest case during a study on the effectiveness of "restorative approaches" after visual field loss. This patient trained with our newly developed Virtual Reality (VR) system "Salzburg Visual Field Trainer" for 254 days. Perimetric results show a visual field expansion of 48.8% (left eye) and 36.8% (right eye) translating to an improvement of approximately 5.5° to 10.5° of visual angle. Further, subjective self-report shows improvements of up to 317% in visual field functionality. Our results indicate that patients suffering from visuo-spatial neglect could benefit from a VR-based restorative intervention.


Subject(s)
Stroke Rehabilitation , Stroke , Virtual Reality Exposure Therapy , Virtual Reality , Humans , Visual Fields
15.
mSphere ; : e0043321, 2021 Jun 30.
Article in English | MEDLINE | ID: mdl-34190587

ABSTRACT

Aedes aegypti transmits one of the most significant mosquito-borne viruses, dengue virus (DENV). The absence of effective vaccines and clinical treatments and the emergence of insecticide resistance in A. aegypti necessitate novel vector control strategies. A new approach uses the endosymbiotic bacterium Wolbachia pipientis to reduce the spread of arboviruses. However, the Wolbachia-mediated antiviral mechanism is not well understood. To shed light on this mechanism, we investigated an unexplored aspect of Wolbachia-virus-mosquito interaction. We used RNA sequencing to examine the transcriptional response of Wolbachia to DENV infection in A. aegypti Aag2 cells transinfected with the wAlbB strain of Wolbachia. Our results suggest that genes encoding an endoribonuclease (RNase HI), a regulator of sigma 70-dependent gene transcription (6S RNA), essential cellular, transmembrane, and stress response functions and primary type I and IV secretion systems were upregulated, while a number of transport and binding proteins of Wolbachia, ribosome structure, and elongation factor-associated genes were downregulated due to DENV infection. Furthermore, bacterial retrotransposon, transposable, and phage-related elements were found among the up- and downregulated genes. We show that Wolbachia elicits a transcriptional response to virus infection and identify differentially expressed Wolbachia genes mostly at the early stages of virus infection. These findings highlight Wolbachia's ability to alter its gene expression in response to DENV infection of the host cell. IMPORTANCE Aedes aegypti is a vector of several pathogenic viruses, including dengue, Zika, chikungunya, and yellow fever viruses, which are of importance to human health. Wolbachia is an endosymbiotic bacterium currently used in transinfected mosquitoes to suppress replication and transmission of dengue viruses. However, the mechanism of Wolbachia-mediated virus inhibition is not fully understood. While several studies have shown mosquitoes' transcriptional responses to dengue virus infection, none have investigated these responses in Wolbachia, which may provide clues to the inhibition mechanism. Our results suggest changes in the expression of a number of functionally important Wolbachia genes upon dengue virus infection, including those involved in stress responses, providing insights into the endosymbiont's reaction to virus infection.

16.
R Soc Open Sci ; 8(4): 201574, 2021 Apr 28.
Article in English | MEDLINE | ID: mdl-34007459

ABSTRACT

Humans grossly underestimate exponential growth, but are at the same time overconfident in their (poor) judgement. The so-called 'exponential growth bias' is of new relevance in the context of COVID-19, because it explains why humans have fundamental difficulties to grasp the magnitude of a spreading epidemic. Here, we addressed the question, whether logarithmic scaling and contextual framing of epidemiological data affect the anticipation of exponential growth. Our findings show that underestimations were most pronounced when growth curves were linearly scaled and framed in the context of a more advanced epidemic progression. For logarithmic scaling, estimates were much more accurate, on target for growth rates around 31%, and not affected by contextual framing. We conclude that the logarithmic depiction is conducive for detecting exponential growth during an early phase as well as resurgences of exponential growth.

17.
J Biol Chem ; 296: 100728, 2021.
Article in English | MEDLINE | ID: mdl-33933454

ABSTRACT

Hydrophobins are surface-active proteins produced by filamentous fungi. The amphiphilic structure of hydrophobins is very compact, containing a distinct hydrophobic patch on one side of the molecule, locked by four intramolecular disulfide bridges. Hydrophobins form dimers and multimers in solution to shield these hydrophobic patches from water exposure. Multimer formation in solution is dynamic, and hydrophobin monomers can be exchanged between multimers. Unlike class I hydrophobins, class II hydrophobins assemble into highly ordered films at the air-water interface. In order to increase our understanding of the strength and nature of the interaction between hydrophobins, we used atomic force microscopy for single molecule force spectroscopy to explore the molecular interaction forces between class II hydrophobins from Trichoderma reesei under different environmental conditions. A genetically engineered hydrophobin variant, NCys-HFBI, enabled covalent attachment of proteins to the apex of the atomic force microscopy cantilever tip and sample surfaces in controlled orientation with sufficient freedom of movement to measure molecular forces between hydrophobic patches. The measured rupture force between two assembled hydrophobins was ∼31 pN, at a loading rate of 500 pN/s. The results indicated stronger interaction between hydrophobins and hydrophobic surfaces than between two assembling hydrophobin molecules. Furthermore, this interaction was stable under different environmental conditions, which demonstrates the dominance of hydrophobicity in hydrophobin-hydrophobin interactions. This is the first time that interaction forces between hydrophobin molecules, and also between naturally occurring hydrophobic surfaces, have been measured directly at a single-molecule level.


Subject(s)
Fungal Proteins/chemistry , Hydrophobic and Hydrophilic Interactions , Single Molecule Imaging , Hypocreales , Surface Properties , Water/chemistry
18.
BMJ Open Ophthalmol ; 6(1): e000429, 2021.
Article in English | MEDLINE | ID: mdl-33791433

ABSTRACT

OBJECTIVE: Several studies report evidence for training-related neuroplasticity in the visual cortex, while other studies suggest that improvements simply reflect inadequate eye fixation control during perimetric prediagnostics and postdiagnostics. METHODS AND ANALYSIS: To improve diagnostics, a new eye-tracking-based methodology for visual field analysis (eye-tracking-based visual field analysis (EFA)) was developed. The EFA is based on static automated perimetry and additionally takes individual eye movements in real time into account and compensates for them. In the present study, an evaluation of the EFA with the help of blind spots of 58 healthy participants and the individual visual field defects of 23 clinical patients is provided. With the help of the EFA, optical coherence tomography, Goldmann perimetry and a Humphrey field analyser, these natural and acquired scotomas were diagnosed and the results were compared accordingly. RESULTS: The EFA provides a SE of measurement of 0.38° for the right eye (OD) and 0.50° for the left eye (OS), leading to 0.44° of visual angle for both eyes (OU). Based on participants' individual results, the EFA provides disattenuated correlation (validity) of 1.00 for both OD and OS. Results from patients suffering from cortical lesions and glaucoma further indicate that the EFA is capable of diagnosing acquired scotoma validly and is applicable for clinical use. CONCLUSION: Outcomes indicate that the EFA is highly reliable and precise in diagnosing individual shape and location of scotoma and capable of recording changes of visual field defects (after intervention) with unprecedented precision. Test duration is comparable to established instruments and due to the high customisability of the EFA, assessment duration can be shortened by adapting the diagnostic procedure to the patients' individual visual field characteristics. Therefore, the saccade-compensating methodology enables researchers and healthcare professionals to rule out eye movements as a source of inaccuracies in pre-, post-, and follow-up assessments.

19.
Article in English | MEDLINE | ID: mdl-33572674

ABSTRACT

Spatial crime analysis, together with perceived (crime) safety analysis have tremendously benefitted from Geographic Information Science (GISc) and the application of geospatial technology. This research study discusses a novel methodological approach to document the use of emerging geospatial technologies to explore perceived urban safety from the lenses of fear of crime or crime perception in the city of Baton Rouge, USA. The mixed techniques include a survey, spatial video geonarrative (SVG) in the field with study participants, and the extraction of moments of stress (MOS) from biosensing wristbands. This study enrolled 46 participants who completed geonarratives and MOS detection. A subset of 10 of these geonarratives are presented here. Each participant was driven in a car equipped with audio recording and spatial video along a predefined route while wearing the Empatica E4 wristbands to measure three physiological variables, all of them linked by timestamp. The results show differences in the participants' sentiments (positive or negative) and MOS in the field based on gender. These mixed-methods are encouraging for finding relationships between actual crime occurrences and the community perceived fear of crime in urban areas.


Subject(s)
Crime , Cities , Humans , Louisiana , Surveys and Questionnaires
20.
Accid Anal Prev ; 152: 105985, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33493940

ABSTRACT

The consolidation of Highway-Railroad Grade Crossing (HRGC) is one of the effective approaches to decrease the number of crashes between trains and vehicles. From 2015-2019, there were 57 HRGC crashes at crossings in East Baton Rouge Parish (EBRP), resulting in thirteen injuries with $346,875 cost of vehicle damages. Consolidation programs help to close redundant crossings and thereby decrease the crash risks; however, it is difficult to find the best crossing in a neighborhood for closure. In our previous research working on HRGC consolidation models in 2019, from among four Machine Learning algorithms, eXtreme Gradient Boosting (XGboost) performed better in HRGC prediction models. In continuation of our previous studies on developing a HRGC prediction model, this research employed Text Mining Techniques, and Geospatial Analysis in addition to the XGboost Machine Learning algorithm. The aim was to develop a consolidation model that is customized for local implementation. The results indicated an overall accuracy of 88 % for the proposed model. The relative importance of the variables input to the model was also reported and offers an in-depth understanding of the model's behavior. Considering the different correlation threshold, a sensitivity analysis was also performed on different aggregation gain values. Subsequently, it resulted in the development of a simplified model utilizing 14 variables, with aggregated gain values of 95 % and a correlation threshold of 0.5. Based on this model, 15 % of current highway-rail grade crossings should be closed.


Subject(s)
Accidents, Traffic/prevention & control , Data Mining , Machine Learning , Models, Theoretical , Railroads , Spatial Analysis , Humans , Male
SELECTION OF CITATIONS
SEARCH DETAIL
...