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Article ; Online: Genetics and therapy for pediatric eye diseases

Holly.Y. Chen / Ordan J. Lehmann / Anand Swaroop

EBioMedicine, Vol 67, Iss , Pp 103360- (2021)

2021

Abstract: Ocular morphogenesis in vertebrates is a highly organized process, orchestrated largely by intrinsic genetic programs that exhibit stringent spatiotemporal control. Alternations in these genetic instructions can lead to hereditary or nonhereditary ... ...

Abstract	Ocular morphogenesis in vertebrates is a highly organized process, orchestrated largely by intrinsic genetic programs that exhibit stringent spatiotemporal control. Alternations in these genetic instructions can lead to hereditary or nonhereditary congenital disorders, a major cause of childhood visual impairment, and contribute to common late-onset blinding diseases. Currently, limited treatment options exist for clinical phenotypes involving eye development. This review summarizes recent advances in our understanding of early-onset ocular disorders and highlights genetic complexities in development and diseases, specifically focusing on coloboma, congenital glaucoma and Leber congenital amaurosis. We also discuss innovative paradigms for potential therapeutic modalities.
Keywords	Eye organogenesis ; Congenital disorders ; Ocular diseases ; Vision impairment ; Retinal development ; Therapy ; Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: General population normative data from seven European countries for the K10 and K6 scales for psychological distress

J. Lehmann / M. J. Pilz / B. Holzner / G. Kemmler / J. M. Giesinger

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 11

Abstract: Abstract The 10-item Kessler Psychological Distress scale (K10) and its 6-item short-form version (K6) measure psychological distress, particularly anxiety or depressive symptoms. While these questionnaire scales are widely used in various settings and ... ...

Abstract	Abstract The 10-item Kessler Psychological Distress scale (K10) and its 6-item short-form version (K6) measure psychological distress, particularly anxiety or depressive symptoms. While these questionnaire scales are widely used in various settings and populations, general population normative data are rarely available. To facilitate the interpretation of K10 and K6 scores, we provide normative general population data from seven European countries. We used an online survey to collect K10 data from general population samples in Austria, Italy, Germany, France, the Netherlands, Poland and Spain. We calculated the age- and sex-specific normative values separately for each country. For more specific estimates of K10 and K6 scores for individuals or groups, we also established a multivariable regression model based on socio-demographic and health data. In total, N = 7,087 adults participated in our study (51.6% women; mean age, 49.6 years). The mean K10 score in the total sample was 8.5 points (standard deviation, 7.3) on 0–40 points metric, with mean scores in individual countries ranging from 6.9 (the Netherlands) to 9.9 (Spain). Women showed higher scores than men and younger participants scored higher than older participants. Our study is the first to present normative K10 and K6 data from several European countries using a consistent sampling approach. These reference values will facilitate the interpretation of K10 and K6 scores in clinical research and practice and also highlight the variation in psychological distress levels across countries and groups according to their socio-demographic and health characteristics.
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Spatial Representations in Local Field Potential Activity of Primate Anterior Intraparietal Cortex (AIP).

Sebastian J Lehmann / Hansjörg Scherberger

PLoS ONE, Vol 10, Iss 11, p e

2015 Volume 0142679

Abstract: The execution of reach-to-grasp movements in order to interact with our environment is an important subset of the human movement repertoire. To coordinate such goal-directed movements, information about the relative spatial position of target and ... ...

Abstract	The execution of reach-to-grasp movements in order to interact with our environment is an important subset of the human movement repertoire. To coordinate such goal-directed movements, information about the relative spatial position of target and effector (in this case the hand) has to be continuously integrated and processed. Recently, we reported the existence of spatial representations in spiking-activity of the cortical fronto-parietal grasp network (Lehmann & Scherberger 2013), and in particular in the anterior intraparietal cortex (AIP). To further investigate the nature of these spatial representations, we explored in two rhesus monkeys (Macaca mulatta) how different frequency bands of the local field potential (LFP) in AIP are modulated by grip type, target position, and gaze position, during the planning and execution of reach-to-grasp movements. We systematically varied grasp type, spatial target, and gaze position and found that both spatial and grasp information were encoded in a variety of frequency bands (1-13Hz, 13-30Hz, 30-60Hz, and 60-100Hz, respectively). Whereas the representation of grasp type strongly increased towards and during movement execution, spatial information was represented throughout the task. Both spatial and grasp type representations could be readily decoded from all frequency bands. The fact that grasp type and spatial (reach) information was found not only in spiking activity, but also in various LFP frequency bands of AIP, might significantly contribute to the development of LFP-based neural interfaces for the control of upper limb prostheses.
Keywords	Medicine ; R ; Science ; Q
Subject code	910
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Exploring the sensitivity of Northern Hemisphere atmospheric circulation to different surface temperature forcing using a statistical–dynamical atmospheric model

S. Totz / S. Petri / J. Lehmann / E. Peukert / D. Coumou

Nonlinear Processes in Geophysics, Vol 26, Pp 1-

2019 Volume 12

Abstract: Climate and weather conditions in the mid-latitudes are strongly driven by the large-scale atmosphere circulation. Observational data indicate that important components of the large-scale circulation have changed in recent decades, including the strength ...

Abstract	Climate and weather conditions in the mid-latitudes are strongly driven by the large-scale atmosphere circulation. Observational data indicate that important components of the large-scale circulation have changed in recent decades, including the strength and the width of the Hadley cell, jets, storm tracks and planetary waves. Here, we use a new statistical–dynamical atmosphere model (SDAM) to test the individual sensitivities of the large-scale atmospheric circulation to changes in the zonal temperature gradient, meridional temperature gradient and global-mean temperature. We analyze the Northern Hemisphere Hadley circulation, jet streams, storm tracks and planetary waves by systematically altering the zonal temperature asymmetry, the meridional temperature gradient and the global-mean temperature. Our results show that the strength of the Hadley cell, storm tracks and jet streams depend, in terms of relative changes, almost linearly on both the global-mean temperature and the meridional temperature gradient, whereas the zonal temperature asymmetry has little or no influence. The magnitude of planetary waves is affected by all three temperature components, as expected from theoretical dynamical considerations. The width of the Hadley cell behaves nonlinearly with respect to all three temperature components in the SDAM. Moreover, some of these observed large-scale atmospheric changes are expected from dynamical equations and are therefore an important part of model validation.
Keywords	Science ; Q ; Physics ; QC1-999 ; Geophysics. Cosmic physics ; QC801-809
Subject code	551
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Copernicus Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: High-resolution analysis of individual Drosophila melanogaster larvae uncovers individual variability in locomotion and its neurogenetic modulation

Michael Thane / Emmanouil Paisios / Torsten Stöter / Anna-Rosa Krüger / Sebastian Gläß / Anne-Kristin Dahse / Nicole Scholz / Bertram Gerber / Dirk J. Lehmann / Michael Schleyer

Open Biology, Vol 13, Iss

2023 Volume 4

Abstract: Neuronally orchestrated muscular movement and locomotion are defining faculties of multicellular animals. Due to its simple brain and genetic accessibility, the larva of the fruit fly Drosophila melanogaster allows one to study these processes at ... ...

Abstract	Neuronally orchestrated muscular movement and locomotion are defining faculties of multicellular animals. Due to its simple brain and genetic accessibility, the larva of the fruit fly Drosophila melanogaster allows one to study these processes at tractable levels of complexity. However, although the faculty of locomotion clearly pertains to the individual, most studies of locomotion in larvae use measurements aggregated across animals, or animals tested one by one, an extravagance for larger-scale analyses. This prevents grasping the inter- and intra-individual variability in locomotion and its neurogenetic determinants. Here, we present the IMBA (individual maggot behaviour analyser) for analysing the behaviour of individual larvae within groups, reliably resolving individual identity across collisions. We use the IMBA to systematically describe the inter- and intra-individual variability in locomotion of wild-type animals, and how the variability is reduced by associative learning. We then report a novel locomotion phenotype of an adhesion GPCR mutant. We further investigated the modulation of locomotion across repeated activations of dopamine neurons in individual animals, and the transient backward locomotion induced by brief optogenetic activation of the brain-descending ‘mooncrawler’ neurons. In summary, the IMBA is an easy-to-use toolbox allowing an unprecedentedly rich view of the behaviour and its variability of individual larvae, with utility in multiple biomedical research contexts.
Keywords	locomotion ; dopamine ; tracking ; variability ; Latrophilin ; learning ; Biology (General) ; QH301-705.5
Subject code	590 ; 612
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	The Royal Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Understanding a sequence of sequences

A. Unger / N. Dräger / M. Sips / Dirk. J. Lehmann

IEEE Transactions on Visualization and Computer Graphics

Visual exploration of categorical states in lake sediment cores

2018

Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Repeatable glucocorticoid expression is associated with behavioural syndromes in males but not females in a wild primate

P. J. Tkaczynski / C. Ross / J. Lehmann / M. Mouna / B. Majolo / A. MacLarnon

Royal Society Open Science, Vol 6, Iss

2019 Volume 9

Abstract: Behavioural syndromes are a well-established phenomenon in human and non-human animal behavioural ecology. However, the mechanisms that lead to correlations among behaviours and individual consistency in their expression at the apparent expense of ... ...

Abstract	Behavioural syndromes are a well-established phenomenon in human and non-human animal behavioural ecology. However, the mechanisms that lead to correlations among behaviours and individual consistency in their expression at the apparent expense of behavioural plasticity remain unclear. The ‘state-dependent' hypothesis posits that inter-individual variation in behaviour arises from inter-individual variation in state and that the relative stability of these states within an individual leads to consistency of behaviour. The endocrine stress response, in part mediated by glucocorticoids (GCs), is a proposed behavioural syndrome-associated state as GC levels are linked to an individual's behavioural responses to stressors. In this study, in wild Barbary macaques (Macaca sylvanus), consistent inter-individual differences were observed in both sexes for GC activity (faecal glucocorticoid, fGC concentrations), but not GC variation (coefficient of variation in fGC concentrations). The expression of the behavioural syndrome ‘Excitability' (characterized by the frequencies of brief affiliation or aggressive interactions) was related to GC activity in males but not in females; more ‘excitable' males had lower GC activity. There was no relationship in females between any of the behavioural syndromes and GC activity, nor in either sex with GC variation. The negative relationship between GC activity and Excitability in males provides some support for GC expression as a behavioural syndrome-generating state under the state-dependent framework. The absence of this relationship in females highlights that state-behavioural syndrome associations may not be generalizable within a species and that broader sex differences in state need to be considered for understanding the emergence and maintenance of behavioural syndromes.
Keywords	coping styles ; repeatability ; glucocorticoids ; middle atlas ; barbary macaques ; state-dependent model ; Science ; Q
Subject code	590
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	The Royal Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Surface guided radiation therapy

V. Batista / M. Gober / F. Moura / A. Webster / M. Oellers / M. Ramtohul / M. Kügele / P. Freislederer / M. Buschmann / G. Anastasi / E. Steiner / H. Al-Hallaq / J. Lehmann

Technical Innovations & Patient Support in Radiation Oncology, Vol 22, Iss , Pp 1-

An international survey on current clinical practice

2022 Volume 8

Abstract: Introduction: Surface Guided Radiation Therapy (SGRT) is being increasingly implemented into clinical practice across a number of techniques and irradiation-sites. This technology, which is provided by different vendors, can be used with most simulation- ...

Abstract	Introduction: Surface Guided Radiation Therapy (SGRT) is being increasingly implemented into clinical practice across a number of techniques and irradiation-sites. This technology, which is provided by different vendors, can be used with most simulation- and delivery-systems. However, limited guidelines and the complexity of clinical settings have led to diverse patterns of operation. With the aim to understand current clinical practice a survey was designed focusing on specifics of the clinical implementation and usage. Materials and methods: A 32-question survey covered: type and number of systems, quality assurance (QA), clinical workflows, and identification of strengths/limitations. Respondents from different professional groups and countries were invited to participate. The survey was distributed internationally via ESTRO-membership, social media and vendors. Results: Of the 278 institutions responding, 172 had at least one SGRT-system and 136 use SGRT clinically. Implementation and QA were primarily based on the vendors’ recommendations and phantoms. SGRT was mainly implemented in breast RT (116/136), with strong but diverse representation of other sites. Many (58/135) reported at least partial elimination of skin-marks and a third (43/126) used open-masks. The most common imaging protocol reported included the combination of radiographic imaging with SGRT. Patient positioning (115/136), motion management (104/136) and DIBH (99/136) were the main applications.Main barriers to broader application were cost, system integration issues and lack of demonstrated clinical value. A lack of guidelines in terms of QA of the system was highlighted. Conclusions: This overview of the SGRT status has the potential to support users, vendors and organisations in the development of practices, products and guidelines.
Keywords	Survey ; SGRT ; Clinical practices ; Surface-guided ; Motion management ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	610
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The effect of intergroup competition on intragroup affiliation in primates

Majolo, B / A. de Bortoli Vizioli / J. Lehmann

The Association for the Study of Animal Behaviour Animal behaviour. 2016 Apr., v. 114

2016

Abstract: Researchers from various disciplines have hypothesized a positive correlation between the level of intergroup contest competition (IGCC) and the evolution of behavioural traits, such as cooperation, altruism and friendship, which promote intragroup ... ...

Abstract	Researchers from various disciplines have hypothesized a positive correlation between the level of intergroup contest competition (IGCC) and the evolution of behavioural traits, such as cooperation, altruism and friendship, which promote intragroup affiliation. Empirical support for this hypothesis is, however, scarce and mainly available from humans. We tested whether the level of IGCC affects intragroup affiliation (i.e. intragroup grooming exchange) among male and female nonhuman primates. To quantify intragroup affiliation, we used social network measures and a grooming index. Our measure of IGCC combined frequency of intergroup encounters and proportion of aggressive encounters and was calculated separately for males and females. We ran our analyses on 27 wild groups of primates belonging to 15 species (13 Cercopithecinae, one Colobinae and one Cebinae). Our analyses reveal a clear pattern of correlated evolution between grooming network density and interindividual variation in the number of grooming partners on the one hand and the intensity of IGCC on the other in females, but not males. Thus, our results suggest that the exact nature of the relationship between IGCC and intragroup affiliation is sex specific. These results may be explained by the differential costs and benefits males and females experience during aggressive intergroup confrontations and by sex-specific differences in intragroup affiliation.
Keywords	Primates ; altruism ; animal behavior ; evolution ; females ; humans ; interpersonal relationships ; males ; researchers ; social networks
Language	English
Dates of publication	2016-04
Size	p. 13-19.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	281-1
ISSN	0003-3472
ISSN	0003-3472
DOI	10.1016/j.anbehav.2016.01.009
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Impaired neural differentiation of MPS IIIA patient induced pluripotent stem cell-derived neural progenitor cells

Rebecca J. Lehmann / Lachlan A. Jolly / Brett V. Johnson / Megan S. Lord / Ha Na Kim / Jennifer T. Saville / Maria Fuller / Sharon Byers / Ainslie L.K. Derrick-Roberts

Molecular Genetics and Metabolism Reports, Vol 29, Iss , Pp 100811- (2021)

2021

Abstract: Mucopolysaccharidosis type IIIA (MPS IIIA) is characterised by a progressive neurological decline leading to early death. It is caused by bi-allelic loss-of-function mutations in SGSH encoding sulphamidase, a lysosomal enzyme required for heparan ... ...

Abstract	Mucopolysaccharidosis type IIIA (MPS IIIA) is characterised by a progressive neurological decline leading to early death. It is caused by bi-allelic loss-of-function mutations in SGSH encoding sulphamidase, a lysosomal enzyme required for heparan sulphate glycosaminoglycan (HS GAG) degradation, that results in the progressive build-up of HS GAGs in multiple tissues most notably the central nervous system (CNS). Skin fibroblasts from two MPS IIIA patients who presented with an intermediate and a severe clinical phenotype, respectively, were reprogrammed into induced pluripotent stem cells (iPSCs). The intermediate MPS IIIA iPSCs were then differentiated into neural progenitor cells (NPCs) and subsequently neurons. The patient derived fibroblasts, iPSCs, NPCs and neurons all displayed hallmark biochemical characteristics of MPS IIIA including reduced sulphamidase activity and increased accumulation of an MPS IIIA HS GAG biomarker. Proliferation of MPS IIIA iPSC-derived NPCs was reduced compared to control, but could be partially rescued by reintroducing functional sulphamidase enzyme, or by doubling the concentration of the mitogen fibroblast growth factor 2 (FGF2). Whilst both control heparin, and MPS IIIA HS GAGs had a similar binding affinity for FGF2, only the latter inhibited FGF signalling, suggesting accumulated MPS IIIA HS GAGs disrupt the FGF2:FGF2 receptor:HS signalling complex. Neuronal differentiation of MPS IIIA iPSC-derived NPCs was associated with a reduction in the expression of neuronal cell marker genes βIII-TUBULIN, NF-H and NSE, revealing reduced neurogenesis compared to control. A similar result was achieved by adding MPS IIIA HS GAGs to the culture medium during neuronal differentiation of control iPSC-derived NPCs. This study demonstrates the generation of MPS IIIA iPSCs, and NPCs, the latter of which display reduced proliferation and neurogenic capacity. Reduced NPC proliferation can be explained by a model in which soluble MPS IIIA HS GAGs compete with cell surface HS for FGF2 binding. The ...
Keywords	Induced pluripotent stem cells ; MPS IIIA ; Neurogenesis ; Heparan sulphate glycosaminoglycan ; Fibroblast growth factor 2 ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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