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1.
Nucleic Acids Res ; 52(10): 6017-6035, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38709902

RESUMEN

Archaeal transcription is carried out by a multi-subunit RNA polymerase (RNAP) that is highly homologous in structure and function to eukaryotic RNAP II. Among the set of basal transcription factors, only Spt5 is found in all domains of life, but Spt5 has been shaped during evolution, which is also reflected in the heterodimerization of Spt5 with Spt4 in Archaea and Eukaryotes. To unravel the mechanistic basis of Spt4/5 function in Archaea, we performed structure-function analyses using the archaeal transcriptional machinery of Pyrococcus furiosus (Pfu). We report single-particle cryo-electron microscopy reconstructions of apo RNAP and the archaeal elongation complex (EC) in the absence and presence of Spt4/5. Surprisingly, Pfu Spt4/5 also binds the RNAP in the absence of nucleic acids in a distinct super-contracted conformation. We show that the RNAP clamp/stalk module exhibits conformational flexibility in the apo state of RNAP and that the enzyme contracts upon EC formation or Spt4/5 engagement. We furthermore identified a contact of the Spt5-NGN domain with the DNA duplex that stabilizes the upstream boundary of the transcription bubble and impacts Spt4/5 activity in vitro. This study, therefore, provides the structural basis for Spt4/5 function in archaeal transcription and reveals a potential role beyond the well-described support of elongation.


Asunto(s)
Proteínas Arqueales , ARN Polimerasas Dirigidas por ADN , Modelos Moleculares , Elongación de la Transcripción Genética , Factores de Elongación Transcripcional , Proteínas Arqueales/química , Proteínas Arqueales/metabolismo , Proteínas Arqueales/genética , Proteínas Cromosómicas no Histona/química , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Microscopía por Crioelectrón , ARN Polimerasas Dirigidas por ADN/metabolismo , ARN Polimerasas Dirigidas por ADN/química , ARN Polimerasas Dirigidas por ADN/genética , Unión Proteica , Pyrococcus furiosus/enzimología , Pyrococcus furiosus/genética , Factores de Elongación Transcripcional/metabolismo , Factores de Elongación Transcripcional/química , Factores de Elongación Transcripcional/genética
2.
EMBO Rep ; 25(5): 2391-2417, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38605278

RESUMEN

ELYS is a nucleoporin that localizes to the nuclear side of the nuclear pore complex (NPC) in interphase cells. In mitosis, it serves as an assembly platform that interacts with chromatin and then with nucleoporin subcomplexes to initiate post-mitotic NPC assembly. Here we identify ELYS as a major binding partner of the membrane protein VAPB during mitosis. In mitosis, ELYS becomes phosphorylated at many sites, including a predicted FFAT (two phenylalanines in an acidic tract) motif, which mediates interaction with the MSP (major sperm protein)-domain of VAPB. Binding assays using recombinant proteins or cell lysates and co-immunoprecipitation experiments show that VAPB binds the FFAT motif of ELYS in a phosphorylation-dependent manner. In anaphase, the two proteins co-localize to the non-core region of the newly forming nuclear envelope. Depletion of VAPB results in prolonged mitosis, slow progression from meta- to anaphase and in chromosome segregation defects. Together, our results suggest a role of VAPB in mitosis upon recruitment to or release from ELYS at the non-core region of the chromatin in a phosphorylation-dependent manner.


Asunto(s)
Mitosis , Unión Proteica , Humanos , Fosforilación , Células HeLa , Cromatina/metabolismo , Factores de Transcripción/metabolismo , Segregación Cromosómica , Proteínas de Complejo Poro Nuclear/metabolismo , Membrana Nuclear/metabolismo , Proteínas de la Membrana/metabolismo , Anafase
3.
Transplantation ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38685197

RESUMEN

BACKGROUND: Kidney transplantation (KTx) from small donors is associated with inferior graft survival in registry studies, whereas single-center studies show favorable results. METHODS: We compared 175 pediatric KTx from small donors ≤20 kg (SDKTx) with 170 age-matched recipients from adult donors (ADKTx) from 20 centers within the Cooperative European Paediatric Renal Transplant Initiative registry. Graft survival and estimated glomerular filtration rate (eGFR) were analyzed by Cox regression and mixed models. Detailed data on surgical and medical management were tested for association with graft survival. RESULTS: One-year graft survival was lower after SDKTx compared with ADKTx (90.9% versus 96.5%; odds ratio of graft loss, 2.92; 95% confidence interval [CI], 1.10-7.80; P = 0.032), but 5-y graft survival was comparable (90.9% versus 92.7%; adjusted hazard ratio of graft loss 1.9; 95% CI, 0.85-4.25; P = 0.119). SDKTx recipients had an annual eGFR increase of 8.7 ±â€…6.2 mL/min/1.73 m² compared with a decrease of 6.9 ±â€…5.7 mL/min/1.73 m² in ADKTx recipients resulting in a superior 5-y eGFR (80.5 ±â€…25.5 in SDKTx versus 65.7 ±â€…23.1 mL/min/1.73 m² in ADKTx; P = 0.008). At 3 y posttransplant, eGFR after single SDKTx was lower than after en bloc SDKTx (86.6 ±â€…20.4 versus 104.6 ±â€…35.9; P = 0.043) but superior to ADKTx (68.1 ±â€…23.9 mL/min/1.73 m²). Single-kidney SDKTx recipients had a lower rate of hypertension at 3 y than ADKTx recipients (40.0% versus 64.7%; P = 0.008). CONCLUSIONS: Compared with ADKTx, 5-y graft function is superior in SDKTx and graft survival is similar, even when performed as single KTx. Utilizing small donor organs, preferably as single kidneys in experienced centers, is a viable option to increase the donor pool for pediatric recipients.

4.
Brain Sci ; 13(5)2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37239192

RESUMEN

Sensory augmentation provides novel opportunities to broaden our knowledge of human perception through external sensors that record and transmit information beyond natural perception. To assess whether such augmented senses affect the acquisition of spatial knowledge during navigation, we trained a group of 27 participants for six weeks with an augmented sense for cardinal directions called the feelSpace belt. Then, we recruited a control group that did not receive the augmented sense and the corresponding training. All 53 participants first explored the Westbrook virtual reality environment for two and a half hours spread over five sessions before assessing their spatial knowledge in four immersive virtual reality tasks measuring cardinal, route, and survey knowledge. We found that the belt group acquired significantly more accurate cardinal and survey knowledge, which was measured in pointing accuracy, distance, and rotation estimates. Interestingly, the augmented sense also positively affected route knowledge, although to a lesser degree. Finally, the belt group reported a significant increase in the use of spatial strategies after training, while the groups' ratings were comparable at baseline. The results suggest that six weeks of training with the feelSpace belt led to improved survey and route knowledge acquisition. Moreover, the findings of our study could inform the development of assistive technologies for individuals with visual or navigational impairments, which may lead to enhanced navigation skills and quality of life.

5.
Cells ; 12(9)2023 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-37174733

RESUMEN

The urinary albumin- and protein-to-creatinine ratios (UACR and UPCR, respectively) are key endpoints in most clinical trials assessing risk of progression of chronic kidney disease (CKD). For the first time, the current study compares the UACR versus the UPCR head-to-head at early stages of CKD, taking use of the hereditary podocytopathy Alport syndrome (AS) as a model disease for any CKD. Urine samples originated from the prospective randomized, controlled EARLY PRO-TECT Alport trial (NCT01485978). Urine samples from 47 children with confirmed diagnoses of AS at very early stages of CKD were divided according to the current stage of AS: stage 0 (UACR < 30 mg/g), stage 1 (30-300 mg/g) or stage 2 (>300 mg/g). The range of estimated glomerular filtration rate was 75-187.6 mL/min. The mean age was 10.4 ± 4.5 years. In children at stage 0, proteinuria in spot urine, confirmed in 24 h urine, was almost ten times higher than albuminuria (106.4 ± 42.2 vs. 12.5 ± 9.7; p < 0.05); it was "only" about three times higher in stage 1 (328.5 ± 210.1 vs. 132.3 ± 80.5; p < 0.05) and almost equal in stage 2 (1481.9 ± 983.4 vs. 1109.7 ± 873.6; p = 0.36). In 17 children, UACRs and UPCRs were measured simultaneously in 24 h urine and spot urine in the same study visit. Interestingly, the UACR (and UPCR) in 24 h urine vs. in spot urine varied by less than 10% (266.8 ± 426.4 vs. 291.2 ± 530.2). In conclusion, our study provides the first evidence that in patients with normal glomerular filtration rate (GFR) and low amounts of albuminuria, especially in children with podocytopathies such as AS, measuring the UACR and UPCR in spot urine is a reliable and convenient alternative to 24 h urine collection. Our study advocates both the UACR and the UPCR as relevant diagnostic biomarkers in future clinical trials in children with glomerular diseases because the UPCR seems to be a very significant parameter at very early stages of podocytopathies. The German Federal Ministry of Education and Research funded this trial (01KG1104).


Asunto(s)
Nefritis Hereditaria , Insuficiencia Renal Crónica , Adolescente , Niño , Humanos , Albúminas/metabolismo , Albuminuria , Creatinina , Nefritis Hereditaria/diagnóstico , Estudios Prospectivos
6.
BMC Pediatr ; 22(1): 570, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-36195856

RESUMEN

BACKGROUND: IgA vasculitis (IgAV) is the most common form of systemic vasculitis in childhood and frequently involves the kidney. A minority of patients with IgA vasculitis nephritis (IgAVN), especially those presenting with heavy proteinuria and/or kidney failure at onset, are at risk of chronic end-stage kidney disease. For deciding upon treatment intensity, knowledge of the short-term clinical course of IgAVN is needed to improve treatment algorithms. METHODS: For this retrospective multicenter study, the medical records of 66 children with biopsy-proven IgAVN were reviewed. Age, gender, medical history and therapeutic interventions were recorded. Laboratory data included serum creatinine, albumin, urinary protein excretion (UPE) and glomerular filtration rate (eGFR). Threshold values were determined for each parameter, full remission was defined as no proteinuria and eGFR > 90 ml/min/1.73m2. RESULTS: Median age at onset of IgAVN was 8.9 years. 14.1% of the children presented with nephrotic syndrome, 50% had an eGFR below 90 ml/min/1.73 m2 and 51.5% showed cellular crescents in renal histology. The treatment regimens varied notably. Forty-four patients were treated with immunosuppression; 17 patients with crescents or nephrotic syndrome were treated with corticosteroid (CS) pulse therapy. After 6 months, UPE had decreased from 3.7 to 0.3 g/g creatinine and the proportion of patients with a decreased eGFR had fallen from 50.0% to 35.5%. Thirteen children (26.5%) achieved full remission within 6 months. CONCLUSIONS: In most patients with IgAVN proteinuria decreases slowly and kidney function improves, but full remission is reached only in a minority after 6 months. Persistent heavy proteinuria in the first two months rarely developed into long-term proteinuria. Therefore, decisions for more intense treatment should take into account the course of UPE over time. For a comparison of treatment effects, patient numbers were too small. Prospective, randomized controlled trials are necessary to clarify risk factors and the effect of immunosuppressive therapies.


Asunto(s)
Vasculitis por IgA , Nefritis , Síndrome Nefrótico , Corticoesteroides/uso terapéutico , Albúminas/uso terapéutico , Biopsia , Niño , Creatinina , Femenino , Humanos , Vasculitis por IgA/complicaciones , Vasculitis por IgA/diagnóstico , Vasculitis por IgA/tratamiento farmacológico , Masculino , Nefritis/complicaciones , Nefritis/patología , Síndrome Nefrótico/complicaciones , Proteinuria/tratamiento farmacológico , Proteinuria/etiología , Estudios Retrospectivos
7.
PLoS Comput Biol ; 18(6): e1009485, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35666726

RESUMEN

Vision provides the most important sensory information for spatial navigation. Recent technical advances allow new options to conduct more naturalistic experiments in virtual reality (VR) while additionally gathering data of the viewing behavior with eye tracking investigations. Here, we propose a method that allows one to quantify characteristics of visual behavior by using graph-theoretical measures to abstract eye tracking data recorded in a 3D virtual urban environment. The analysis is based on eye tracking data of 20 participants, who freely explored the virtual city Seahaven for 90 minutes with an immersive VR headset with an inbuild eye tracker. To extract what participants looked at, we defined "gaze" events, from which we created gaze graphs. On these, we applied graph-theoretical measures to reveal the underlying structure of visual attention. Applying graph partitioning, we found that our virtual environment could be treated as one coherent city. To investigate the importance of houses in the city, we applied the node degree centrality measure. Our results revealed that 10 houses had a node degree that exceeded consistently two-sigma distance from the mean node degree of all other houses. The importance of these houses was supported by the hierarchy index, which showed a clear hierarchical structure of the gaze graphs. As these high node degree houses fulfilled several characteristics of landmarks, we named them "gaze-graph-defined landmarks". Applying the rich club coefficient, we found that these gaze-graph-defined landmarks were preferentially connected to each other and that participants spend the majority of their experiment time in areas where at least two of those houses were visible. Our findings do not only provide new experimental evidence for the development of spatial knowledge, but also establish a new methodology to identify and assess the function of landmarks in spatial navigation based on eye tracking data.


Asunto(s)
Navegación Espacial , Realidad Virtual , Humanos , Conocimiento , Visión Ocular
8.
Front Microbiol ; 13: 822304, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35495653

RESUMEN

CRISPR-Cas constitutes an adaptive prokaryotic defence system against invasive nucleic acids like viruses and plasmids. Beyond their role in immunity, CRISPR-Cas systems have been shown to closely interact with components of cellular DNA repair pathways, either by regulating their expression or via direct protein-protein contact and enzymatic activity. The integrase Cas1 is usually involved in the adaptation phase of CRISPR-Cas immunity but an additional role in cellular DNA repair pathways has been proposed previously. Here, we analysed the capacity of an archaeal Cas1 from Haloferax volcanii to act upon DNA damage induced by oxidative stress and found that a deletion of the cas1 gene led to reduced survival rates following stress induction. In addition, our results indicate that Cas1 is directly involved in DNA repair as the enzymatically active site of the protein is crucial for growth under oxidative conditions. Based on biochemical assays, we propose a mechanism by which Cas1 plays a similar function to DNA repair protein Fen1 by cleaving branched intermediate structures. The present study broadens our understanding of the functional link between CRISPR-Cas immunity and DNA repair by demonstrating that Cas1 and Fen1 display equivalent roles during archaeal DNA damage repair.

9.
Pediatr Transplant ; 26(4): e14265, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35263498

RESUMEN

BACKGROUND: Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients. METHODS: This is a retrospective, observational multicenter registry study. All pediatric kidney transplant recipients in the CERTAIN database with at least one documented serum uric acid level and a follow-up of 5 years posttransplant were eligible. We identified 151 patients with 395 measurements of serum uric acid. We calculated the prevalence of hyperuricemia, analyzed potential risk factors and clinical consequences such as elevated blood pressure and reduced estimated glomerular filtration rate (eGFR). Statistical analysis was performed using IBM SPSS Statistics 26. RESULTS: One hundred and ten of 395 (27.8%) serum uric acid levels were above 416 µmol/L (7.0 mg/dL), defined as the upper limit of normal. Univariate analysis showed a significant (p = .026) inverse association of serum uric acid with eGFR overtime. There was no significant association of serum uric acid concentrations with body mass index (z-score), blood pressure (z-score), or sex. No episodes of gout were documented. CONCLUSION: This study shows that hyperuricemia is present in a considerable number of patients sometime after pediatric kidney transplantation and is associated with lower eGFR. Whether hyperuricemia contributes to faster decline of graft function or to the overall cardiovascular risk of these patients remains to be elucidated.


Asunto(s)
Hiperuricemia , Trasplante de Riñón , Niño , Tasa de Filtración Glomerular/fisiología , Humanos , Hiperuricemia/complicaciones , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiología , Trasplante de Riñón/efectos adversos , Prevalencia , Sistema de Registros , Factores de Riesgo , Ácido Úrico
10.
Sensors (Basel) ; 21(21)2021 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-34770689

RESUMEN

Spatial orientation and navigation depend primarily on vision. Blind people lack this critical source of information. To facilitate wayfinding and to increase the feeling of safety for these people, the "feelSpace belt" was developed. The belt signals magnetic north as a fixed reference frame via vibrotactile stimulation. This study investigates the effect of the belt on typical orientation and navigation tasks and evaluates the emotional impact. Eleven blind subjects wore the belt daily for seven weeks. Before, during and after the study period, they filled in questionnaires to document their experiences. A small sub-group of the subjects took part in behavioural experiments before and after four weeks of training, i.e., a straight-line walking task to evaluate the belt's effect on keeping a straight heading, an angular rotation task to examine effects on egocentric orientation, and a triangle completion navigation task to test the ability to take shortcuts. The belt reduced subjective discomfort and increased confidence during navigation. Additionally, the participants felt safer wearing the belt in various outdoor situations. Furthermore, the behavioural tasks point towards an intuitive comprehension of the belt. Altogether, the blind participants benefited from the vibrotactile belt as an assistive technology in challenging everyday situations.


Asunto(s)
Dispositivos de Autoayuda , Personas con Daño Visual , Ceguera , Humanos , Percepción Espacial
11.
Sensors (Basel) ; 21(5)2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33800215

RESUMEN

With the further development of highly automated vehicles, drivers will engage in non-related tasks while being driven. Still, drivers have to take over control when requested by the car. Here, the question arises, how potentially distracted drivers get back into the control-loop quickly and safely when the car requests a takeover. To investigate effective human-machine interactions, a mobile, versatile, and cost-efficient setup is needed. Here, we describe a virtual reality toolkit for the Unity 3D game engine containing all the necessary code and assets to enable fast adaptations to various human-machine interaction experiments, including closely monitoring the subject. The presented project contains all the needed functionalities for realistic traffic behavior, cars, pedestrians, and a large, open-source, scriptable, and modular VR environment. It covers roughly 25 km2, a package of 125 animated pedestrians, and numerous vehicles, including motorbikes, trucks, and cars. It also contains all the needed nature assets to make it both highly dynamic and realistic. The presented repository contains a C++ library made for LoopAR that enables force feedback for gaming steering wheels as a fully supported component. It also includes all necessary scripts for eye-tracking in the used devices. All the main functions are integrated into the graphical user interface of the Unity® editor or are available as prefab variants to ease the use of the embedded functionalities. This project's primary purpose is to serve as an open-access, cost-efficient toolkit that enables interested researchers to conduct realistic virtual reality research studies without costly and immobile simulators. To ensure the accessibility and usability of the mentioned toolkit, we performed a user experience report, also included in this paper.


Asunto(s)
Peatones , Realidad Virtual , Adaptación Fisiológica , Automóviles , Humanos , Vehículos a Motor
12.
Kidney Int ; 97(6): 1275-1286, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32299679

RESUMEN

Children with Alport syndrome develop renal failure early in life. Since the safety and efficacy of preemptive nephroprotective therapy are uncertain we conducted a randomized, placebo-controlled, double-blind trial in 14 German sites of pediatric patients with ramipril for three to six years plus six months follow-up to determine these parameters. Pretreated children and those whose parents refused randomization became an open-arm control, which were compared to prospective real-world data from untreated children. The co-primary endpoints were safety (adverse drug reactions) and efficacy (time to progression). Out of 66 oligosymptomatic children, 22 were randomized and 44 joined the open-arm comparison. Ramipril therapy showed no safety issues (total of 216.4 patient-years on ramipril; adverse event rate-ratio 1.00; 95% confidence interval 0.66-1.53). Although not significant, our results cautiously showed that ramipril therapy was effective: in the randomized arm, Ramipril decreased the risk of disease progression by almost half (hazard ratio 0.51 (0.12-2.20)), diminished the slope of albuminuria progression and the decline in glomerular filtration. In adjusted analysis, indications of efficacy were supported by prospective data from participants treated open label compared with untreated children, in whom ramipril again seemed to reduce progression by almost half (0.53 (0.22-1.29)). Incorporating these results into the randomized data by Bayesian evidence synthesis resulted in a more precise estimate of the hazard-ratio of 0.52 (0.19-1.39). Thus, our study shows the safety of early initiation of therapy and supports the hope to slow renal failure by many years, emphasizing the value of preemptive therapy. Hence, screening programs for glomerular hematuria in children and young adults could benefit from inclusion of genetic testing for Alport-related gene-variants.


Asunto(s)
Nefritis Hereditaria , Ramipril , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Teorema de Bayes , Niño , Método Doble Ciego , Tasa de Filtración Glomerular , Humanos , Nefritis Hereditaria/genética , Estudios Prospectivos , Ramipril/efectos adversos
13.
Pediatr Nephrol ; 35(3): 415-426, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31811541

RESUMEN

BACKGROUND: High prevalence of arterial hypertension is known in pediatric renal transplant patients, but how blood pressure (BP) distribution and control differ between age groups and whether sex and age interact and potentially impact BP after transplantation have not been investigated. METHODS: This retrospective analysis included 336 pediatric renal transplant recipients (62% males) from the Cooperative European Pediatric Renal Transplant Initiative Registry (CERTAIN) with complete BP measurement at discharge and 1, 2 and 3 years post-transplant. RESULTS: At discharge and 3 years post-transplant, arterial hypertension was highly prevalent (84% and 77%); antihypertensive drugs were used in 73% and 68% of the patients. 27% suffered from uncontrolled and 9% from untreated hypertension at 3 years post-transplant. Children transplanted at age < 5 years showed sustained high systolic BP z-score and received consistently less antihypertensive treatment over time. Younger age, shorter time since transplantation, male sex, higher body mass index (BMI), high cyclosporine A (CSA) trough levels, and a primary renal disease other than congenital anomalies of the kidney and urinary tract (CAKUT) were significantly associated with higher systolic BP z-score. Sex-stratified analysis revealed a significant association between high CSA and higher systolic BP in older girls that likely had started puberty already. An association between BP and estimated glomerular filtration rate was not detected. CONCLUSIONS: BP control during the first 3 years was poor in this large European cohort. The description of age- and sex-specific risk profiles identified certain recipient groups that may benefit from more frequent BP monitoring (i.e. young children) or different choices of immunosuppression (i.e. older girls).


Asunto(s)
Hipertensión/epidemiología , Trasplante de Riñón/efectos adversos , Adolescente , Factores de Edad , Determinación de la Presión Sanguínea/estadística & datos numéricos , Niño , Preescolar , Ciclosporina/administración & dosificación , Ciclosporina/efectos adversos , Ciclosporina/farmacocinética , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Inmunosupresores/farmacocinética , Estudios Longitudinales , Masculino , Prevalencia , Sistema de Registros/estadística & datos numéricos , Estudios Retrospectivos , Factores Sexuales , Tacrolimus/administración & dosificación , Tacrolimus/efectos adversos , Tacrolimus/farmacocinética , Factores de Tiempo , Receptores de Trasplantes/estadística & datos numéricos
14.
Front Hum Neurosci ; 13: 240, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31354457

RESUMEN

To become acquainted with large-scale environments such as cities people combine direct experience and indirect sources such as maps. To ascertain which type of spatial knowledge is acquired by which source is difficult to evaluate. Using virtual reality enables the possibility to investigate whether knowledge is learned by direct experience or the use of a map differentially. Therefore, we designed a large virtual city, comprised of over 200 houses, and evaluated spatial knowledge acquisition after city exploration with an interactive map following one and three 30-min exploration sessions. We tested subjects' knowledge of the orientation of houses facing directions toward cardinal north, of orientations of houses facing directions relative to each other and pointing from one house to another. Our results revealed that increased familiarity after extended exploration with the map improved task accuracy. Further, it revealed task differences, caused mainly by a better accuracy in the relative orientation task than the pointing task. Time for cognitive reasoning improved overall task accuracy. Learning with our VR city map revealed an absence of distance effect, an alignment effect of tested house orientation toward map north and an angular difference effect between tested stimuli. Self-reported knowledge of cardinal directions learned in the real environment was positively correlated with task accuracy testing houses orientations toward cardinal north. Overall, our results suggest that participants learned spatial information that is directly available in the interactive map, while a spatial task that needed integration of learned knowledge stayed at lower accuracy levels.

15.
J Eye Mov Res ; 12(1)2019 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33828721

RESUMEN

The intent of this paper is to provide an introduction into the bourgeoning field of eye tracking in Virtual Reality (VR). VR itself is an emerging technology on the consumer market, which will create many new opportunities in research. It offers a lab environment with high immersion and close alignment with reality. An experiment which is using VR takes place in a highly controlled environment and allows for a more in-depth amount of information to be gathered about the actions of a subject. Techniques for eye tracking were introduced more than a century ago and are now an established technique in psychological experiments, yet recent development makes it versatile and affordable. In combination, these two techniques allow unprecedented monitoring and control of human behavior in semi-realistic conditions. This paper will explore the methods and tools which can be applied in the implementation of experiments using eye tracking in VR following the example of one case study. Accompanying the technical descriptions, we present research that displays the effectiveness of the technology and show what kind of results can be obtained when using eye tracking in VR. It is meant to guide the reader through the process of bringing VR in combination with eye tracking into the lab and to inspire ideas for new experiments.

16.
Psychol Res ; 83(3): 498-513, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28770385

RESUMEN

Theories of Enactivism propose an action-oriented approach to understand human cognition. So far, however, empirical evidence supporting these theories has been sparse. Here, we investigate whether spatial navigation based on allocentric reference frames that are independent of the observer's physical body can be understood within an action-oriented approach. Therefore, we performed three experiments testing the knowledge of the absolute orientation of houses and streets towards north, the relative orientation of two houses and two streets, respectively, and the location of houses towards each other in a pointing task. Our results demonstrate that under time pressure, the relative orientation of two houses can be retrieved more accurately than the absolute orientation of single houses. With infinite time for cognitive reasoning, the performance of the task using house stimuli increased greatly for the absolute orientation and surpassed the slightly improved performance in the relative orientation task. In contrast, with streets as stimuli participants performed under time pressure better in the absolute orientation task. Overall, pointing from one house to another house yielded the best performance. This suggests, first, that orientation and location information about houses are primarily coded in house-to-house relations, whereas cardinal information is deduced via cognitive reasoning. Second, orientation information for streets is preferentially coded in absolute orientations. Thus, our results suggest that spatial information about house and street orientation is coded differently and that house orientation and location is primarily learned in an action-oriented way, which is in line with an enactive framework for human cognition.


Asunto(s)
Cognición/fisiología , Aprendizaje/fisiología , Orientación Espacial/fisiología , Solución de Problemas/fisiología , Percepción Espacial/fisiología , Navegación Espacial/fisiología , Adulto , Femenino , Alemania , Humanos , Masculino , Adulto Joven
17.
Pediatr Nephrol ; 33(2): 277-286, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28983704

RESUMEN

BACKGROUND: This study correlates the clinical presentation of Henoch-Schönlein purpura nephritis (HSPN) with findings on initial renal biopsy. METHODS: Data from 202 pediatric patients enrolled in the HSPN registry of the German Society of Pediatric Nephrology reported by 26 centers between 2008 and 2014 were analyzed. All biopsy reports were re-evaluated for the presence of cellular crescents or chronic pathological lesions (fibrous crescents, glomerular sclerosis, tubular atrophy >5%, and interstitial fibrosis >5%). RESULTS: Patients with HSPN with cellular glomerular crescents were biopsied earlier after onset of nephritis (median 24 vs 36 days, p = 0.04) than those without, whereas patients with chronic lesions were biopsied later (57 vs 19 days, p < 0.001) and were older (10.3 vs 8.6 years, p = 0.01) than those without. Patients biopsied more than 30 days after the onset of HSPN had significantly more chronic lesions (52 vs 22%, p < 0.001), lower eGFR (88 vs 102 ml/min/1.73m2, p = 0.01), but lower proteinuria (2.3 vs 4.5 g/g, p < 0.0001) than patients biopsied earlier. Children above 10 years of age had lower proteinuria (1.98 vs 4.58 g/g, p < 0.001), lower eGFR (86 vs 101 ml/min/1.73m2, p = 0.002) and were biopsied significantly later after onset of nephritis (44 vs 22 days, p < 0.001) showing more chronic lesions (45 vs 30%, p = 0.03). Proteinuria and renal function at presentation decreased with age. CONCLUSIONS: In summary, we find an age-dependent presentation of HSPN with a more insidious onset of non-nephrotic proteinuria, impaired renal function, longer delay to biopsy, and more chronic histopathological lesions in children above the age of 10 years. Thus, HSPN presents more like Immunoglobulin A (IgA) nephritis in older than in younger children.


Asunto(s)
Vasculitis por IgA/patología , Riñón/patología , Nefritis/patología , Factores de Edad , Biopsia , Niño , Femenino , Humanos , Masculino
18.
Clin J Am Soc Nephrol ; 12(12): 1974-1983, 2017 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-29146700

RESUMEN

BACKGROUND AND OBJECTIVES: Genetic heterogeneity and phenotypic variability are major challenges in familial nephronophthisis and related ciliopathies. To date, mutations in 20 different genes (NPHP1 to -20) have been identified causing either isolated kidney disease or complex multiorgan disorders. In this study, we provide a comprehensive and detailed characterization of 152 children with a special focus on extrarenal organ involvement and the long-term development of ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We established an online-based registry (www.nephreg.de) to assess the clinical course of patients with nephronophthisis and related ciliopathies on a yearly base. Cross-sectional and longitudinal data were collected. Mean observation time was 7.5±6.1 years. RESULTS: In total, 51% of the children presented with isolated nephronophthisis, whereas the other 49% exhibited related ciliopathies. Monogenetic defects were identified in 97 of 152 patients, 89 affecting NPHP genes. Eight patients carried mutations in other genes related to cystic kidney diseases. A homozygous NPHP1 deletion was, by far, the most frequent genetic defect (n=60). We observed a high prevalence of extrarenal manifestations (23% [14 of 60] for the NPHP1 group and 66% [61 of 92] for children without NPHP1). A homozygous NPHP1 deletion not only led to juvenile nephronophthisis but also was able to present as a predominantly neurologic phenotype. However, irrespective of the initial clinical presentation, the kidney function of all patients carrying NPHP1 mutations declined rapidly between the ages of 8 and 16 years, with ESRD at a mean age of 11.4±2.4 years. In contrast within the non-NPHP1 group, there was no uniform pattern regarding the development of ESRD comprising patients with early onset and others preserving normal kidney function until adulthood. CONCLUSIONS: Mutations in NPHP genes cause a wide range of ciliopathies with multiorgan involvement and different clinical outcomes.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Ciliopatías/genética , Enfermedades Renales Quísticas/congénito , Fallo Renal Crónico/genética , Proteínas de la Membrana/genética , Fenotipo , Adolescente , Anemia/genética , Antígenos de Neoplasias/genética , Proteínas de Unión a Calmodulina/genética , Proteínas Portadoras/genética , Proteínas de Ciclo Celular , Niño , Ciliopatías/complicaciones , Estudios Transversales , Proteínas del Citoesqueleto , Femenino , Tasa de Filtración Glomerular/genética , Homocigoto , Humanos , Riñón/diagnóstico por imagen , Enfermedades Renales Quísticas/complicaciones , Enfermedades Renales Quísticas/diagnóstico por imagen , Enfermedades Renales Quísticas/genética , Fallo Renal Crónico/fisiopatología , Cinesinas/genética , Estudios Longitudinales , Masculino , Proteínas de Neoplasias/genética , Enfermedades del Sistema Nervioso/genética , Poliuria/genética , Proteínas/genética , Ultrasonografía , Adulto Joven
19.
Sci Rep ; 7(1): 2311, 2017 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-28536434

RESUMEN

Many eye-tracking studies investigate visual behavior with a focus on image features and the semantic content of a scene. A wealth of results on these aspects is available, and our understanding of the decision process where to look has reached a mature stage. However, the temporal aspect, whether to stay and further scrutinize a region (exploitation) or to move on and explore image regions that were yet not in the focus of attention (exploration) is less well understood. Here, we investigate the trade-off between these two processes across stimuli with varying properties and sizes. In a free viewing task, we examined gaze parameters in humans, involving the central tendency, entropy, saccadic amplitudes, number of fixations and duration of fixations. The results revealed that the central tendency and entropy scaled with stimulus size. The mean saccadic amplitudes showed a linear increase that originated from an interaction between the distribution of saccades and the spatial bias. Further, larger images led to spatially more extensive sampling as indicated by a higher number of fixations at the expense of reduced fixation durations. These results demonstrate a profound shift from exploitation to exploration as an adaptation of main gaze parameters with increasing image size.


Asunto(s)
Conducta Exploratoria/fisiología , Movimientos Oculares/fisiología , Fijación Ocular/fisiología , Percepción Visual/fisiología , Adolescente , Atención/fisiología , Femenino , Humanos , Masculino , Estimulación Luminosa/métodos , Movimientos Sacádicos/fisiología , Factores de Tiempo , Campos Visuales/fisiología , Adulto Joven
20.
PLoS One ; 11(12): e0166647, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27959914

RESUMEN

Theories of embodied cognition propose that perception is shaped by sensory stimuli and by the actions of the organism. Following sensorimotor contingency theory, the mastery of lawful relations between own behavior and resulting changes in sensory signals, called sensorimotor contingencies, is constitutive of conscious perception. Sensorimotor contingency theory predicts that, after training, knowledge relating to new sensorimotor contingencies develops, leading to changes in the activation of sensorimotor systems, and concomitant changes in perception. In the present study, we spell out this hypothesis in detail and investigate whether it is possible to learn new sensorimotor contingencies by sensory augmentation. Specifically, we designed an fMRI compatible sensory augmentation device, the feelSpace belt, which gives orientation information about the direction of magnetic north via vibrotactile stimulation on the waist of participants. In a longitudinal study, participants trained with this belt for seven weeks in natural environment. Our EEG results indicate that training with the belt leads to changes in sleep architecture early in the training phase, compatible with the consolidation of procedural learning as well as increased sensorimotor processing and motor programming. The fMRI results suggest that training entails activity in sensory as well as higher motor centers and brain areas known to be involved in navigation. These neural changes are accompanied with changes in how space and the belt signal are perceived, as well as with increased trust in navigational ability. Thus, our data on physiological processes and subjective experiences are compatible with the hypothesis that new sensorimotor contingencies can be acquired using sensory augmentation.


Asunto(s)
Estado de Conciencia , Aprendizaje , Corteza Sensoriomotora/fisiología , Percepción Espacial , Adulto , Cognición , Femenino , Humanos , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Masculino , Sueño
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