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Müller, Juliane ; Müller, Steffen ; Stoll, Josefine ; Rector, Michael V. ; Baur, Heiner ; Mayer, Frank
Stability of the trunk is relevant in determining trunk response to different loading in everyday tasks initiated by the limbs. Descriptions of the trunk’s mechanical movement patterns in response to different loads while lifting objects are still under debate. Hence, the aim of this study was to analyze the influence of weight on 3-dimensional segmental motion of the trunk during 1-handed lifting. Ten asymptomatic subjects were included (29 ± 3 y; 1.79 ± 0.09 m; 75 ± 14 kg). Subjects lifted 3× a light and heavy load from the ground up onto a table. Three-dimensional segmental trunk motion was measured (12 markers; 3 segments: upper thoracic area [UTA], lower thoracic area [LTA], lumbar area [LA]). Outcomes were total motion amplitudes (ROM;[°]) for anterior flexion, lateral flexion, and rotation of each segment. The highest ROM was observed in the LTA segment (anterior flexion), and the smallest ROM in the UTA segment (lateral flexion). ROM differed for all planes between the 3 segments for both tasks (P < .001). There were no differences in ROM between light and heavy loads (P > .05). No interaction effects (load × segment) were observed, as ROM did not reveal differences between loading tasks. Regardless of weight, the 3 segments did reflect differences, supporting the relevance of multisegmental analysis.
Eldridge, Tilly ; Langowski, Lukasz ; Stacey, Nicola ; Jantzen, Friederike ; Moubayidin, Laila ; Sicard, Adrien ; Southam, Paul ; Kennaway, Richard ; Lenhard, Michael ; Coen, Enrico S. ; Ostergaard, Lars
Fruits exhibit a vast array of different 3D shapes, from simple spheres and cylinders to more complex curved forms; however, the mechanism by which growth is oriented and coordinated to generate this diversity of forms is unclear. Here, we compare the growth patterns and orientations for two very different fruit shapes in the Brassicaceae: the heart-shaped Capsella rubella silicle and the near-cylindrical Arabidopsis thaliana silique. We show, through a combination of clonal and morphological analyses, that the different shapes involve different patterns of anisotropic growth during three phases. These experimental data can be accounted for by a tissue level model in which specified growth rates vary in space and time and are oriented by a proximodistal polarity field. The resulting tissue conflicts lead to deformation of the tissue as it grows. The model allows us to identify tissue-specific and temporally specific activities required to obtain the individual shapes. One such activity may be provided by the valve-identity gene FRUITFULL, which we show through comparative mutant analysis to modulate fruit shape during post-fertilisation growth of both species. Simple modulations of the model presented here can also broadly account for the variety of shapes in other Brassicaceae species, thus providing a simplified framework for fruit development and shape diversity.
Cuong Nguyen Huu ; Kappel, Christian ; Keller, Barbara ; Sicard, Adrien ; Takebayashi, Yumiko ; Breuninger, Holger ; Nowak, Michael D. ; Bäurle, Isabel ; Himmelbach, Axel ; Burkart, Michael ; Ebbing-Lohaus, Thomas ; Sakakibara, Hitoshi ; Altschmied, Lothar ; Conti, Elena ; Lenhard, Michael
Heterostyly is a wide-spread floral adaptation to promote outbreeding, yet its genetic basis and evolutionary origin remain poorly understood. In Primula (primroses), heterostyly is controlled by the S-locus supergene that determines the reciprocal arrangement of reproductive organs and incompatibility between the two morphs. However, the identities of the component genes remain unknown. Here, we identify the Primula CYP734A50 gene, encoding a putative brassinosteroid-degrading enzyme, as the G locus that determines the style-length dimorphism. CYP734A50 is only present on the short-styled S-morph haplotype, it is specifically expressed in S-morph styles, and its loss or inactivation leads to long styles. The gene arose by a duplication specific to the Primulaceae lineage and shows an accelerated rate of molecular evolution. Thus, our results provide a mechanistic explanation for the Primula style-length dimorphism and begin to shed light on the evolution of the S-locus as a prime model for a complex plant supergene.
Biskaborn, Boris ; Subetto, D. A. ; Savelieva, L. A. ; Vakhrameeva, P. S. ; Hansche, A. ; Herzschuh, Ulrike ; Klemm, J. ; Heinecke, L. ; Pestryakova, Luidmila Agafyevna ; Meyer, H. ; Kuhn, G. ; Diekmann, Bernhard
Although the climate development over the Holocene in the Northern Hemisphere is well known, palaeolimnological climate reconstructions reveal spatiotemporal variability in northern Eurasia. Here we present a multi-proxy study from north-eastern Siberia combining sediment geochemistry, and diatom and pollen data from lake-sediment cores covering the last 38,000 cal. years. Our results show major changes in pyrite content and fragilarioid diatom species distributions, indicating prolonged seasonal lake-ice cover between similar to 13,500 and similar to 8900 cal. years BP and possibly during the 8200 cal. years BP cold event. A pollen-based climate reconstruction generated a mean July temperature of 17.8 degrees C during the Holocene Thermal Maximum (HTM) between similar to 8900 and similar to 4500 cal. years BP. Naviculoid diatoms appear in the late Holocene indicating a shortening of the seasonal ice cover that continues today. Our results reveal a strong correlation between the applied terrestrial and aquatic indicators and natural seasonal climate dynamics in the Holocene. Planktonic diatoms show a strong response to changes in the lake ecosystem due to recent climate warming in the Anthropocene. We assess other palaeolimnological studies to infer the spatiotemporal pattern of the HTM and affirm that the timing of its onset, a difference of up to 3000 years from north to south, can be well explained by climatic teleconnections. The westerlies brought cold air to this part of Siberia until the Laurentide ice sheet vanished 7000 years ago. The apparent delayed ending of the HTM in the central Siberian record can be ascribed to the exceedance of ecological thresholds trailing behind increases in winter temperatures and decreases in contrast in insolation between seasons during the mid to late Holocene as well as lacking differentiation between summer and winter trends in paleolimnological reconstructions. (C) 2015 Elsevier Ltd. All rights reserved.
Intziegianni, Konstantina ; Cassel, Michael ; Rauf, S. ; White, S. ; Rector, Michael V. ; Kaplick, Hannes ; Wahmkow, Gunnar ; Kratzenstein, S. ; Mayer, Frank
Prevalence of Achilles tendinopathy increases with age leading to a weaker tendon with predisposition to rupture. Conclusive evidence of the influence of age and pathology on Achilles tendon (AT) properties remains limited, as previous studies are based on standardized isometric conditions. The study investigates the influence of age and pathology on AT properties during single-leg vertical jump (SLVJ). 10 children (C), 10 asymptomatic adults (A), and 10 tendinopathic patients (T) were included. AT elongation [mm] from rest to maximal displacement during a SLVJ on a force-plate was sonographically assessed. AT compliance [mm/N]) and strain [%] was calculated by dividing elongation by peak ground reaction force [N] and length, respectively. One-way ANOVA followed by Bonferroni post-hoc correction (=0.05) were used to compare C with A and A with T. AT elongation (p=0.004), compliance (p=0.001), and strain were found to be statistically significant higher in C (27 +/- 3mm, 0.026 +/- 0.006[mm/N], 13 +/- 2%) compared to A (21 +/- 4mm, 0.017 +/- 0.005[mm/N], 10 +/- 2%). No statistically significant differences (p0.05) was found between A and T (25 +/- 5mm, 0.019 +/- 0.004[mm/N], 12 +/- 3%). During SLVJ, tendon responded differently in regards to age and pathology with children having the most compliant AT. Higher compliance found in healthy tendons might be considered as a protective factor against load-related injuries.
Balci, K. ; Akkaya, Y. ; Akyuz, S. ; Collier, W. B. ; Stricker, M. C. ; Stover, D. D. ; Ritzhaupt, G. ; Koch, Andreas ; Kleinpeter, Erich
In this study, the stable conformers of neutral anserine were searched by molecular dynamics simulations and energy minimization calculations using the MM2 force field. Thermochemical calculations at B3LYP/6-31G(d) level of theory followed these preliminary calculations. The results confirmed that neutral anserine has quite a flexible structure and many stable gauche and trans conformers at room temperature. Nevertheless, two are considerably more favourable in energy than the others and expected to dominate the gas-phase and matrix IR spectra of the molecule. The corresponding structural and vibrational spectral data for these two conformers of neutral anserine, whose relative stabilities were also examined by high-accuracy energy calculations carried out using G3MP2B3 method, and for the most stable conformer of anserine in zwitterion form were calculated at B3LYP/6-311++G(d,p) level of theory. The calculated harmonic force constants were refined using the Scaled Quantum Mechanical Force Field (SQM-FF) method and then used to produce the refined wavenumbers, potential energy distributions (PEDs) and IR and Raman intensities. These refined data together with the scaled harmonic wavenumbers obtained using another method, Dual Scale factors (DS), enabled us to correctly analyse the observed IR and Raman spectra of anserine and revealed the effects of conformation and zwitterionic tautomerism on its structural and vibrational spectral data. (C) 2016 Elsevier B.V. All rights reserved.
Background
Overweight and obesity are increasing health problems that are not restricted to adults only. Childhood obesity is associated with metabolic, psychological and musculoskeletal comorbidities. However, knowledge about the effect of obesity on the foot function across maturation is lacking. Decreased foot function with disproportional loading characteristics is expected for obese children. The aim of this study was to examine foot loading characteristics during gait of normal-weight, overweight and obese children aged 1-12 years.
Methods
A total of 10382 children aged one to twelve years were enrolled in the study. Finally, 7575 children (m/f: n = 3630/3945; 7.0 +/- 2.9yr; 1.23 +/- 0.19m; 26.6 +/- 10.6kg; BMI: 17.1 +/- 2.4kg/m(2)) were included for (complete case) data analysis. Children were categorized to normalweight (>= 3rd and <90th percentile; n = 6458), overweight (>= 90rd and <97th percentile; n = 746) or obese (>97th percentile; n = 371) according to the German reference system that is based on age and gender-specific body mass indices (BMI). Plantar pressure measurements were assessed during gait on an instrumented walkway. Contact area, arch index (AI), peak pressure (PP) and force time integral (FTI) were calculated for the total, fore-, mid-and hindfoot. Data was analyzed descriptively (mean +/- SD) followed by ANOVA/Welch-test (according to homogeneity of variances: yes/no) for group differences according to BMI categorization (normal-weight, overweight, obesity) and for each age group 1 to 12yrs (post-hoc Tukey Kramer/Dunnett's C; alpha = 0.05).
Results
Mean walking velocity was 0.95 +/- 0.25 m/s with no differences between normal-weight, overweight or obese children (p = 0.0841). Results show higher foot contact area, arch index, peak pressure and force time integral in overweight and obese children (p< 0.001). Obese children showed the 1.48-fold (1 year-old) to 3.49-fold (10 year-old) midfoot loading (FTI) compared to normal-weight.
Conclusion
Additional body mass leads to higher overall load, with disproportional impact on the midfoot area and longitudinal foot arch showing characteristic foot loading patterns. Already the feet of one and two year old children are significantly affected. Childhood overweight and obesity is not compensated by the musculoskeletal system. To avoid excessive foot loading with potential risk of discomfort or pain in childhood, prevention strategies should be developed and validated for children with a high body mass index and functional changes in the midfoot area. The presented plantar pressure values could additionally serve as reference data to identify suspicious foot loading patterns in children.
Neuromuscular response of the trunk to sudden gait disturbances: Forward vs. backward perturbation
(2016)
Mueller, Juliane ; Engel, Tilman ; Mueller, Steffen ; Kopinski, Stephan ; Baur, Heiner ; Mayer, Frank
The study aimed to analyse neuromuscular activity of the trunk comparing four different perturbations during gait. Thirteen subjects (28 +/- 3 yrs) walked (1 m/s) on a split-belt treadmill, while 4 (belt) perturbations (F1, F2, B1, B2) were randomly applied. Perturbations differed, related to treadmill belt translation, in direction (forward (F)/backward (B)) and amplitude (20 m/s(2) (1)/40 m/s(2) (2)). Trunk muscle activity was assessed with a 12-lead-EMG. EMG-RMS [%] (0-200 ms after perturbation; normalized to RMS of normal gait) was analyzed for muscles and four trunk areas (ventral left/right; dorsal left/right). Ratio of ventral: dorsal muscles were calculated. Muscle onset [ms] was determined. Data analysis was conducted descriptively, followed by ANOVA (post hoc Tukey-Kramer (alpha = 0.05)). All perturbations lead to an increase in EMG-RMS (428 +/- 289%). F1 showed the lowest and F2 the highest increase for the flexors. B2 showed the highest increase for the extensors. Significant differences between perturbations could be observed for 6 muscles, as well as the 4 trunk areas. Ratio analysis revealed no significant differences (range 1.25 (B1) to 1.71 (F2) between stimuli. Muscle response time (ventral: 87.0 +/- 21.7 ms; dorsal: 88.4 +/- 17.0 ms) between stimuli was only significant (p = 0.005) for the dorsal muscles. Magnitude significantly influences neuromuscular trunk response patterns in healthy adults. Regardless of direction ventral muscles always revealed higher relative increase of activity while compensating the walking perturbations. (C) 2016 Elsevier Ltd. All rights reserved.
This study aimed to determine the relative and absolute reliability of ultrasound (US) measurements of the thickness and echogenicity of the plantar fascia (PF) at different measurement stations along its length using a standardized protocol. Twelve healthy subjects (24 feet) were enrolled. The PF was imaged in the longitudinal plane. Subjects were assessed twice to evaluate the intra-rater reliability. A quantitative evaluation of the thickness and echogenicity of the plantar fascia was performed using Image J, a digital image analysis and viewer software. A sonography evaluation of the thickness and echogenicity of the PF showed a high relative reliability with an Intra class correlation coefficient of 0.88 at all measurement stations. However, the measurement stations for both the PF thickness and echogenicity which showed the highest intraclass correlation coefficient (ICCs) did not have the highest absolute reliability. Compared to other measurement stations, measuring the PF thickness at 3 cm distal and the echogenicity at a region of interest 1 cm to 2 cm distal from its insertion at the medial calcaneal tubercle showed the highest absolute reliability with the least systematic bias and random error. Also, the reliability was higher using a mean of three measurements compared to one measurement. To reduce discrepancies in the interpretation of the thickness and echogenicity measurements of the PF, the absolute reliability of the different measurement stations should be considered in clinical practice and research rather than the relative reliability with the ICC.
Objective: To assess the intra-and inter-session reliability of estimates of motor unit behavior and muscle fiber properties derived from high-density surface electromyography (HDEMG). Methods: Ten healthy subjects performed submaximal isometric knee extensions during three recording sessions (separate days) at 10%, 30%, 50% and 70% of their maximum voluntary effort. The discharge timings of motor units of the vastus lateralis and medialis muscles were automatically identified from HDEMG by a decomposition algorithm. We characterized the number of detected motor units, their discharge rates, the coefficient of variation of their inter-spike intervals (CoVisi), the action potential conduction velocity and peak-to-peak amplitude. Reliability was assessed for each motor unit characteristics by intra-class correlation coefficient (ICC). Additionally, a pulse-to-noise ratio (PNR) was calculated, to verify the accuracy of the decomposition. Results: Good to excellent reliability within and between sessions was found for all motor unit characteristics at all force levels (ICCs > 0.8), with the exception of CoVisi that presented poor reliability (ICC < 0.6). PNR was high and similar for both muscles with values ranging between 45.1 and 47.6 dB (accuracy > 95%). Conclusion: Motor unit features can be assessed non-invasively and reliably within and across sessions over a wide range of force levels. Significance: These results suggest that it is possible to characterize motor units in longitudinal intervention studies. (C) 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Barta, Petra ; Szatmari, Istvan ; Fueloep, Ferenc ; Heydenreich, Matthias ; Koch, Andreas ; Kleinpeter, Erich
Through the reactions of 1- or 2-naphthol and 4,5-dihydro-3H-benz[c]azepine or 6,7-dihydrothieno[3,2-c]pyridine, new aminonaphthol derivatives were prepared. The syntheses were extended by using N-containing naphthol analogues such as 5-hydroxyisoquinoline and 6-hydroxyquinoline. The ring closures of the novel bifunctional compounds were also achieved, resulting in new naphth[2,1-e][1,3]oxazines, naphth[1,2-e][1,3]oxazines, isoquinolino[5,6-e][1,3]oxazines and quinolino[5,6-e][1,3]oxazines. H-1 NMR spectra of the target heterocycles 16, 20 and 21 were sufficiently resolved to indentify the present stereochemistry; therefore, beside computed structures, spatial experimental (dipolar coupling-NOE) and computed (ring current effect of the naphthyl moiety-TSNMRS) NMR studies were employed. The studied heterocycles exist exclusively as S(14b),R(N), R(14b),S(N), and S(16b)S(N) isomers, respectively. The flexible moieties of the studied compounds prefer. (C) 2016 Elsevier Ltd. All rights reserved.
Rasovic, Aleksandar ; Blagojevic, Vladimir ; Baranac-Stojanovic, Marija ; Kleinpeter, Erich ; Markovic, Rade ; Minic, Dragica M.
Information about the strength of donor-acceptor interactions in push-pull alkenes is valuable, as this so-called "push-pull effect' influences their chemical reactivity and dynamic behaviour. In this paper, we discuss the applicability of NMR spectral data and barriers to rotation around the CQC double bond to quantify the push-pull effect in biologically important 2-alkylidene-4-oxothiazolidines. While olefinic proton chemical shifts and differences in C-13 NMR chemical shifts of the two carbons constituting the CQC double bond fail to give the correct trend in the electron withdrawing ability of the substituents attached to the exocyclic carbon of the double bond, barriers to rotation prove to be a reliable quantity in providing information about the extent of donor-acceptor interactions in the push-pull systems studied. In particular all relevant kinetic data, that is the Arrhenius parameters ( apparent activation energy Ea and frequency factor A) and activation parameters ( Delta S-double dagger, Delta H-double dagger and Delta G(double dagger)), were determined from the data of the experimentally studied configurational isomerization of ( E)-9a. These results were compared to previously published related data for other two compounds, ( Z)-1b and ( 2E, 5Z)-7, showing that experimentally determined Delta G(double dagger) values are a good indicator of the strength of push-pull character. Theoretical calculations of the rotational barriers of eight selected derivatives excellently correlate with the calculated CQC bond lengths and corroborate the applicability of Delta G(double dagger) for estimation of the strength of the push-pull effect in these and related systems.
Background Overweight and obesity are increasing health problems that are not restricted to adults only. Childhood obesity is associated with metabolic, psychological and musculoskeletal comorbidities. However, knowledge about the effect of obesity on the foot function across maturation is lacking. Decreased foot function with disproportional loading characteristics is expected for obese children. The aim of this study was to examine foot loading characteristics during gait of normal-weight, overweight and obese children aged 1-12 years. Methods Results Mean walking velocity was 0.95 +/- 0.25 m/s with no differences between normal-weight, overweight or obese children (p = 0.0841). Results show higher foot contact area, arch index, peak pressure and force time integral in overweight and obese children (p< 0.001). Obese children showed the 1.48-fold (1 year-old) to 3.49-fold (10 year-old) midfoot loading (FTI) compared to normal-weight. Conclusion Additional body mass leads to higher overall load, with disproportional impact on the midfoot area and longitudinal foot arch showing characteristic foot loading patterns. Already the feet of one and two year old children are significantly affected. Childhood overweight and obesity is not compensated by the musculoskeletal system. To avoid excessive foot loading with potential risk of discomfort or pain in childhood, prevention strategies should be developed and validated for children with a high body mass index and functional changes in the midfoot area. The presented plantar pressure values could additionally serve as reference data to identify suspicious foot loading patterns in children.
Stumbling led to an increase in ROM, compared to unperturbed gait, in all segments and planes. These increases ranged between 107 +/- 26% (UTA/rotation) and 262 +/- 132% (UTS/lateral flexion), significant only in lateral flexion. EMG activity of the trunk was increased during stumbling (abdominal: 665 +/- 283%; back: 501 +/- 215%), without significant differences between muscles. Provoked stumbling leads to a measurable effect on the trunk, quantifiable by an increase in ROM and EMG activity, compared to normal walking. Greater abdominal muscle activity and ROM of lateral flexion may indicate a specific compensation pattern occurring during stumbling. (C) 2015 Elsevier Ltd. All rights reserved.
Polyadenylation is a critical 3-end processing step during maturation of pre-mRNAs, and the length of the poly(A) tail affects mRNA stability, nuclear export and translation efficiency. The Arabidopsis thaliana genome encodes three canonical nuclear poly(A) polymerase (PAPS) isoforms fulfilling specialized functions, as reflected by their different mutant phenotypes. While PAPS1 affects several processes, such as the immune response, organ growth and male gametophyte development, the roles of PAPS2 and PAPS4 are largely unknown. Here we demonstrate that PAPS2 and PAPS4 promote flowering in a partially redundant manner. The enzymes act antagonistically to PAPS1, which delays the transition to flowering. The opposite flowering-time phenotypes in paps1 and paps2 paps4 mutants are at least partly due to decreased or increased FLC activity, respectively. In contrast to paps2 paps4 mutants, plants with increased PAPS4 activity flower earlier than the wild-type, concomitant with reduced FLC expression. Double mutant analyses suggest that PAPS2 and PAPS4 act independently of the autonomous pathway components FCA, FY and CstF64. The direct polyadenylation targets of the three PAPS isoforms that mediate their effects on flowering time do not include FLC sense mRNA and remain to be identified. Thus, our results uncover a role for canonical PAPS isoforms in flowering-time control, raising the possibility that modulating the balance of the isoform activities could be used to fine tune the transition to flowering. Significance Statement The length of the poly(A) tail affects mRNA stability, nuclear export and translation efficiency. Arabidopsis has three isoforms of nuclear poly(A) polymerase (PAPS): PAPS1 plays a major role in organ growth and plant defence. Here we show that PAPS2 and PAPS4 redundantly promote flowering and act antagonistically to PAPS1, which delays flowering. We suggest that modulating the activity of these isoforms fine-tunes the transition to flowering.
Jöst, Moritz ; Hensel, Goetz ; Kappel, Christian ; Druka, Arnis ; Sicard, Adrien ; Hohmann, Uwe ; Beier, Sebastian ; Himmelbach, Axel ; Waugh, Robbie ; Kumlehn, Jochen ; Stein, Nils ; Lenhard, Michael
Variation in the size, shape, and positioning of leaves as the major photosynthetic organs strongly impacts crop yield, and optimizing these aspects is a central aim of cereal breeding [1, 2]. Leaf growth in grasses is driven by cell proliferation and cell expansion in a basal growth zone [3]. Although several factors influencing final leaf size and shape have been identified from rice and maize [4-14], what limits grass leaf growth in the longitudinal or transverse directions during leaf development remains poorly understood. To identify factors involved in this process, we characterized the barley mutant broad leaf1 (blf1). Mutants form wider but slightly shorter leaves due to changes in the numbers of longitudinal cell files and of cells along the leaf length. These differences arise during primordia outgrowth because of more cell divisions in the width direction increasing the number of cell files. Positional cloning, analysis of independent alleles, and transgenic complementation confirm that BLF1 encodes a presumed transcriptional regulator of the INDETERMINATE DOMAIN family. In contrast to loss-of-function mutants, moderate overexpression of BLF1 decreases leaf width below wild-type levels. A functional BLF1-vYFP fusion protein expressed from the endogenous promoter shows a dynamic expression pattern in the shoot apical meristem and young leaf primordia. Thus, we propose that the BLF1 gene regulates barley leaf size by restricting cell proliferation in the leaf-width direction. Given the agronomic importance of canopy traits in cereals, identifying functionally different BLF1 alleles promises to allow for the generation of optimized cereal ideotypes.
Sicard, Adrien ; Kappel, Christian ; Lee, Young Wha ; Wozniak, Natalia Joanna ; Marona, Cindy ; Stinchcombe, John R. ; Wright, Stephen I. ; Lenhard, Michael
Mating system shifts recurrently drive specific changes in organ dimensions. The shift in mating system from out-breeding to selfing is one of the most frequent evolutionary transitions in flowering plants and is often associated with an organ-specific reduction in flower size. However, the evolutionary paths along which polygenic traits, such as size, evolve are poorly understood. In particular, it is unclear how natural selection can specifically modulate the size of one organ despite the pleiotropic action of most known growth regulators. Here, we demonstrate that allelic variation in the intron of a general growth regulator contributed to the specific reduction of petal size after the transition to selfing in the genus Capsella. Variation within this intron affects an organ-specific enhancer that regulates the level of STERILE APETALA (SAP) protein in the developing petals. The resulting decrease in SAP activity leads to a shortening of the cell proliferation period and reduced number of petal cells. The absence of private polymorphisms at the causal region in the selfing species suggests that the small-petal allele was captured from standing genetic variation in the ancestral out-crossing population. Petal-size variation in the current out-crossing population indicates that several small-effect mutations have contributed to reduce petal-size. These data demonstrate how tissue-specific regulatory elements in pleiotropic genes contribute to organ-specific evolution. In addition, they provide a plausible evolutionary explanation for the rapid evolution of flower size after the out-breeding-to-selfing transition based on additive effects of segregating alleles.
Ronquillo, Cecinio C. ; Hanke-Gogokhia, Christin ; Revelo, Monica P. ; Frederick, Jeanne M. ; Jiang, Li ; Baehr, Wolfgang
Null mutations in the human IQCB1/NPHP5 (nephrocystin-5) gene that encodes NPHP5 are the most frequent cause of Senior-LOken syndrome, a ciliopathy that is characterized by Leber congenital amaurosis and nephronophthisis. We generated germline Nphp5-knockout mice by placing a -Geo gene trap in intron 4, thereby truncating NPHP5 at Leu87 and removing all known functional domains. At eye opening, Nphp5(-/-) mice exhibited absence of scotopic and photopic electroretinogram responses, a phenotype that resembles Leber congenital amaurosis. Outer segment transmembrane protein accumulation in Nphp5(-/-) endoplasmic reticulum was evident as early as postnatal day (P)6. EGFP-CETN2, a centrosome and transition zone marker, identified basal bodies in Nphp5(-/-) photoreceptors, but without fully developed transition zones. Ultrastructure of P6 and 10 Nphp5(-/-) photoreceptors revealed aberrant transition zones of reduced diameter. Nphp5(-/-) photoreceptor degeneration was complete at 1 mo of age but was delayed significantly in Nphp5(-/-);Nrl(-/-) (cone only) retina. Nphp5(-/-) mouse embryonic fibroblast developed normal cilia, and Nphp5(-/-) kidney histology at 1 yr of age showed no significant pathology. Results establish that nephrocystin-5 is essential for photoreceptor outer segment formation but is dispensable for kidney and mouse embryonic fibroblast ciliary formation.
Sas, Claudia ; Mueller, Frank ; Kappel, Christian ; Kent, Tyler V. ; Wright, Stephen I. ; Hilker, Monika ; Lenhard, Michael
The enormous species richness of flowering plants is at least partly due to floral diversification driven by interactions between plants and their animal pollinators [1, 2]. Specific pollinator attraction relies on visual and olfactory floral cues [3-5]; floral scent can not only attract pollinators but also attract or repel herbivorous insects [6-8]. However, despite its central role for plant-animal interactions, the genetic control of floral scent production and its evolutionary modification remain incompletely understood [9-13]. Benzenoids are an important class of floral scent compounds that are generated from phenylalanine via several enzymatic pathways [14-17]. Here we address the genetic basis of the loss of floral scent associated with the transition from outbreeding to selfing in the genus Capsella. While the outbreeding C. grandiflora emits benzaldehyde as a major constituent of its floral scent, this has been lost in the selfing C. rubella. We identify the Capsella CNL1 gene encoding cinnamate: CoA ligase as responsible for this variation. Population genetic analysis indicates that CNL1 has been inactivated twice independently in C. rubella via different novel mutations to its coding sequence. Together with a recent study in Petunia [18], this identifies cinnamate: CoA ligase as an evolutionary hotspot for mutations causing the loss of benzenoid scent compounds in association with a shift in the reproductive strategy of Capsella from pollination by insects to self-fertilization.
Iurchuk, V. ; Schick, D. ; Bran, J. ; Colson, D. ; Forget, A. ; Halley, D. ; Koc, Azize ; Reinhardt, Mathias ; Kwamen, C. ; Morley, N. A. ; Bargheer, Matias ; Viret, M. ; Gumeniuk, R. ; Schmerber, G. ; Doudin, B. ; Kundys, B.
We present an optically induced remanent photostriction in BiFeO3, resulting from the photovoltaic effect, which is used to modify the ferromagnetism of Ni film in a hybrid BiFeO3/Ni structure. The 75% change in coercivity in the Ni film is achieved via optical and nonvolatile control. This photoferromagnetic effect can be reversed by static or ac electric depolarization of BiFeO3. Hence, the strain dependent changes in magnetic properties are written optically, and erased electrically. Light-mediated straintronics is therefore a possible approach for low-power multistate control of magnetic elements relevant for memory and spintronic applications.
Ultrafast X-ray diffraction experiments require careful adjustment of the spatial overlap between the optical excitation and the X-ray probe pulse. This is especially challenging at high laser repetition rates. Sample distortions caused by the large heat load on the sample and the relatively low optical energy per pulse lead to only tiny signal changes. In consequence, this results in small footprints of the optical excitation on the sample, which turns the adjustment of the overlap difficult. Here a method for reliable overlap adjustment based on reciprocal space mapping of a laser excited thin film is presented.
Garbusow, Maria ; Schad, Daniel ; Sebold, Miriam Hannah ; Friedel, Eva ; Bernhardt, Nadine ; Koch, Stefan P. ; Steinacher, Bruno ; Kathmann, Norbert ; Geurts, Dirk E. M. ; Sommer, Christian ; Mueller, Dirk K. ; Nebe, Stephan ; Paul, Soeren ; Wittchen, Hans-Ulrich ; Zimmermann, Ulrich S. ; Walter, Henrik ; Smolka, Michael N. ; Sterzer, Philipp ; Rapp, Michael Armin ; Huys, Quentin J. M. ; Schlagenhauf, Florian ; Heinz, Andreas
In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.
During visual fixation, the eye generates microsaccades and slower components of fixational eye movements that are part of the visual processing strategy in humans. Here, we show that ongoing heartbeat is coupled to temporal rate variations in the generation of microsaccades. Using coregistration of eye recording and ECG in humans, we tested the hypothesis that microsaccade onsets are coupled to the relative phase of the R-R intervals in heartbeats. We observed significantly more microsaccades during the early phase after the R peak in the ECG. This form of coupling between heartbeat and eye movements was substantiated by the additional finding of a coupling between heart phase and motion activity in slow fixational eye movements; i.e., retinal image slip caused by physiological drift. Our findings therefore demonstrate a coupling of the oculomotor system and ongoing heartbeat, which provides further evidence for bodily influences on visuomotor functioning.
Sebold, Miriam Hannah ; Schad, Daniel ; Nebe, Stephan ; Garbusow, Maria ; Juenger, Elisabeth ; Kroemer, Nils B. ; Kathmann, Norbert ; Zimmermann, Ulrich S. ; Smolka, Michael N. ; Rapp, Michael Armin ; Heinz, Andreas ; Huys, Quentin J. M.
Behavioral choice can be characterized along two axes. One axis distinguishes reflexive, model-free systems that slowly accumulate values through experience and a model-based system that uses knowledge to reason prospectively. The second axis distinguishes Pavlovian valuation of stimuli from instrumental valuation of actions or stimulus–action pairs. This results in four values and many possible interactions between them, with important consequences for accounts of individual variation. We here explored whether individual variation along one axis was related to individual variation along the other. Specifically, we asked whether individuals' balance between model-based and model-free learning was related to their tendency to show Pavlovian interferences with instrumental decisions. In two independent samples with a total of 243 participants, Pavlovian–instrumental transfer effects were negatively correlated with the strength of model-based reasoning in a two-step task. This suggests a potential common underlying substrate predisposing individuals to both have strong Pavlovian interference and be less model-based and provides a framework within which to interpret the observation of both effects in addiction.
Postural control is important to cope with demands of everyday life. It has been shown that both attentional demand (i.e., cognitive processing) and fatigue affect postural control in young adults. However, their combined effect is still unresolved. Therefore, we investigated the effects of fatigue on single- (ST) and dual-task (DT) postural control. Twenty young subjects (age: 23.7 ± 2.7) performed an all-out incremental treadmill protocol. After each completed stage, one-legged-stance performance on a force platform under ST (i.e., one-legged-stance only) and DT conditions (i.e., one-legged-stance while subtracting serial 3s) was registered. On a second test day, subjects conducted the same balance tasks for the control condition (i.e., non-fatigued). Results showed that heart rate, lactate, and ventilation increased following fatigue (all p < 0.001; d = 4.2–21). Postural sway and sway velocity increased during DT compared to ST (all p < 0.001; d = 1.9–2.0) and fatigued compared to non-fatigued condition (all p < 0.001; d = 3.3–4.2). In addition, postural control deteriorated with each completed stage during the treadmill protocol (all p < 0.01; d = 1.9–3.3). The addition of an attention-demanding interference task did not further impede one-legged-stance performance. Although both additional attentional demand and physical fatigue affected postural control in healthy young adults, there was no evidence for an overadditive effect (i.e., fatigue-related performance decrements in postural control were similar under ST and DT conditions). Thus, attentional resources were sufficient to cope with the DT situations in the fatigue condition of this experiment.
Different systems for habitual versus goal-directed control are thought to underlie human decision-making. Working memory is known to shape these decision-making systems and
their interplay, and is known to support goal-directed decision making even under stress. Here, we investigated if and how decision systems are differentially influenced by breaks filled with diverse everyday life activities known to modulate working memory performance. We used a within-subject design where young adults listened to music and played a video game during breaks interleaved with trials of a sequential two-step Markov decision task, designed to assess habitual as well as goal-directed decision making. Based on a neurocomputational model of task performance, we observed that for individuals with a rather limited
working memory capacity video gaming as compared to music reduced reliance on the goal-directed decision-making system, while a rather large working memory capacity prevented such a decline. Our findings suggest differential effects of everyday activities on key decision-making processes.
Postural control is important to cope with demands of everyday life. It has been shown that both attentional demand (i.e., cognitive processing) and fatigue affect postural control in young adults. However, their combined effect is still unresolved. Therefore, we investigated the effects of fatigue on single-(ST) and dual-task (DT) postural control. Twenty young subjects (age: 23.7 +/- 2.7) performed an all-out incremental treadmill protocol. After each completed stage, one-legged-stance performance on a force platform under ST (i.e., one-legged-stance only) and DT conditions (i.e., one-legged-stance while subtracting serial 3s) was registered. On a second test day, subjects conducted the same balance tasks for the control condition (i.e., non-fatigued). Results showed that heart rate, lactate, and ventilation increased following fatigue (all p < 0.001; d = 4.2-21). Postural sway and sway velocity increased during DT compared to ST (all p < 0.001; d = 1.9-2.0) and fatigued compared to non-fatigued condition (all p < 0.001; d = 3.3-4.2). In addition, postural control deteriorated with each completed stage during the treadmill protocol (all p < 0.01; d = 1.9-3.3). The addition of an attention-demanding interference task did not further impede one-legged-stance performance. Although both additional attentional demand and physical fatigue affected postural control in healthy young adults, there was no evidence for an overadditive effect (i.e., fatigue-related performance decrements in postural control were similar under ST and DT conditions). Thus, attentional resources were sufficient to cope with the DT situations in the fatigue condition of this experiment.
Effects of Backpack Carriage on Dual-Task Performance in Children During Standing and Walking
(2016)
Heinzel, Stephan ; Lorenz, Robert C. ; Pelz, Patricia ; Heinz, Andreas ; Walter, Henrik ; Kathmann, Norbert ; Rapp, Michael Armin ; Stelzel, Christine
As indicated by previous research, aging is associated with a decline in working memory (WM) functioning, related to alterations in fronto-parietal neural activations. At the same time, previous studies showed that WM training in older adults may improve the performance in the trained task (training effect), and more importantly, also in untrained WM tasks (transfer effects). However, neural correlates of these transfer effects that would improve understanding of its underlying mechanisms, have not been shown in older participants as yet. In this study, we investigated blood-oxygen-level-dependent (BOLD) signal changes during n-back performance and an untrained delayed recognition (Sternberg) task following 12 sessions (45 min each) of adaptive n-back training in older adults. The Sternberg task used in this study allowed to test for neural training effects independent of specific task affordances of the trained task and to separate maintenance from updating processes. Thirty-two healthy older participants (60-75 years) were assigned either to an n-back training or a no-contact control group. Before (t1) and after (t2) training/waiting period, both the n-back task and the Sternberg task were conducted while BOLD signal was measured using functional Magnetic Resonance Imaging (fMRI) in all participants. In addition, neuropsychological tests were performed outside the scanner. WM performance improved with training and behavioral transfer to tests measuring executive functions, processing speed, and fluid intelligence was found. In the training group, BOLD signal in the right lateral middle frontal gyrus/caudal superior frontal sulcus (Brodmann area, BA 6/8) decreased in both the trained n-back and the updating condition of the untrained Sternberg task at t2, compared to the control group. fMRI findings indicate a training-related increase in processing efficiency of WM networks, potentially related to the process of WM updating. Performance gains in untrained tasks suggest that transfer to other cognitive tasks remains possible in aging. (C) 2016 Elsevier Inc. All rights reserved.
Bakanidze, George ; Brandl, Eva J. ; Hutzler, Christine ; Aurass, Friederike ; Onken, Silke ; Rapp, Michael Armin ; Puls, Imke
Background: Despite extensive research in the past decades, the influence of genetics on cognitive functions in schizophrenia remains unclear. Dystrobrevin-binding protein 1 (DTNBP1) is one of the most promising candidate genes in schizophrenia. An association of DTNBP1 with cognitive dysfunction, particularly memory impairment, has been reported in a number of studies. However, the results remain inconsistent. The aim of this study was to measure the association between DTNBP1 polymorphisms and cognitive domains in a well-characterized sample. Methods: Ninety-one clinically stable schizophrenia outpatients underwent a battery of cognitive tests. Six single nucleotide polymorphisms (SNPs) of DTNBP1 were genotyped in all participants. Statistical and multivariate analyses were performed. Results: Factor analysis revealed 4 factors corresponding to distinct cognitive domains, namely sustained attention, set-shifting, executive functioning, and memory. We found a significant association of the rs909706 polymorphism with attention (p = 0.030) and a nonsignificant trend for set-shifting (p = 0.060). The other SNPs and haplotypes were not associated with cognitive function. Discussion: Replication of this finding in a larger sample is needed in order to confirm the importance of this particular polymorphism in the genetics of schizophrenia, particularly the distinct cognitive domains. In conclusion, the present study supports the involvement of DTNBP1 in the regulation of cognitive processes and demonstrates association in particular with sustained attention and set-shifting in schizophrenia patients. (C) 2016 S. Karger AG, Basel
We tested the independent influences of two content-based factors on dual-task costs, and on the parallel processing ability: The pairing of S-R modalities and the pairing of relevant features between stimuli and responses of two tasks. The two pairing factors were realized across four dual-task groups. Within each group the two tasks comprised two different stimulus modalities (visual and auditory), two different relevant stimulus features (spatial and verbal) and two response modalities (manual and vocal). Pairings of S-R modalities (standard: visual-manual and auditory-vocal, non-standard: visual-vocal and auditory manual) and feature pairings (standard: spatial-manual and verbal-vocal, non-standard: spatial-vocal and verbal-manual) varied across groups. All participants practiced their respective dual-task combination in a paradigm with simultaneous stimulus onset before being transferred to a psychological refractory period paradigm varying stimulus-onset asynchrony. A comparison at the end of practice revealed similar dual-task costs and similar pairing effects in both paradigms. Dual-task costs depended on modality and feature pairings. Groups training with non-standard feature pairings (i.e., verbal stimulus features mapped to spatially separated response keys, or spatial stimulus features mapped to verbal responses) and non-standard modality pairings (i.e., auditory stimulus mapped to manual response, or visual stimulus mapped to vocal responses) had higher dual-task costs than respective standard pairings. In contrast, irrespective of modality pairing dual-task costs virtually disappeared with standard feature pairings after practice in both paradigms. The results can be explained by crosstalk between feature-binding processes for the two tasks. Crosstalk was present for non-standard but absent for standard feature pairings. Therefore, standard feature pairings enabled parallel processing at the end of practice. (C) 2016 Elsevier B.V. All rights reserved.
Objective: To estimate the prevalence and type of antidepressant medication prescribed by German primary care physicians for patients with depression and osteoporosis. Methods: This study was a retrospective database analysis conducted in Germany utilizing the Disease Analyzer (R) Database (IMS Health, Germany). The study population included 3,488 female osteoporosis patients aged between 40 and 90 years recruited from 1,179 general practitioner practices and who were initially diagnosed with depression during the index period (January 2004 to December 2013). Follow-up lasted up to 12 months and was completed in August 2015. Also included in this study were 3,488 nonosteoporosis controls who were matched (1 : 1) to osteoporosis cases on the basis of age, health insurance coverage, severity of depression, and physician carrying out the diagnosis. Results: After 12 months of followup, 30.1% of osteoporosis and 29.9% of nonosteoporosis patients with mild depression (p = 0.783), 52.4% of osteoporosis and 48.0% of non-osteoporosis patients with moderate depression (p = 0.003), and 39.4% of osteoporosis and 35.1% of nonosteoporosis patients with severe depression (p = 0.147) were being treated with antidepressants. Osteoporosis patients with moderate depression had a higher chance of being prescribed antidepressant therapy at the initial diagnosis (hazard ratio (HR): 1.12, p = 0.014). No differences were found between osteoporosis and nonosteoporosis patients regarding the proportion of patients receiving selective serotonin reuptake inhibitors (SSRI)/serotonin-noradrenaline reuptake inhibitors (SNRI), tricyclic antidepressant (TCA), or other antidepressants. Osteoporosis patients were more often referred to hospitals or psychiatrists for consultation. Conclusion: Osteoporosis patients are more often treated initially with antidepressants than non-osteoporosis patients, especially within the groups of patients with moderate or severe depression. TCA was the most frequently used antidepressant therapy class on initial diagnosis in both patient groups. Osteo-porosis patients receive referrals to hospitals or psychiatrists more often than patients without osteoporosis.
Saccades to single targets in peripheral vision are typically characterized by an undershoot bias. Putting this bias to a test, Kapoula [1] used a paradigm in which observers were presented with two different sets of target eccentricities that partially overlapped each other. Her data were suggestive of a saccadic range effect (SRE): There was a tendency for saccades to overshoot close targets and undershoot far targets in a block, suggesting that there was a response bias towards the center of eccentricities in a given block. Our Experiment 1 was a close replication of the original study by Kapoula [1]. In addition, we tested whether the SRE is sensitive to top-down requirements associated with the task, and we also varied the target presentation duration. In Experiments 1 and 2, we expected to replicate the SRE for a visual discrimination task. The simple visual saccade-targeting task in Experiment 3, entailing minimal top-down influence, was expected to elicit a weaker SRE. Voluntary saccades to remembered target locations in Experiment 3 were expected to elicit the strongest SRE. Contrary to these predictions, we did not observe a SRE in any of the tasks. Our findings complement the results reported by Gillen et al. [2] who failed to find the effect in a saccade-targeting task with a very brief target presentation. Together, these results suggest that unlike arm movements, saccadic eye movements are not biased towards making saccades of a constant, optimal amplitude for the task.
Background: The goal of this study was to estimate the prevalence of and risk factors for diagnosed depression in heart failure (HF) patients in German primary care practices. Methods: This study was a retrospective database analysis in Germany utilizing the Disease Analyzer (R) Database (IMS Health, Germany). The study population included 132,994 patients between 40 and 90 years of age from 1,072 primary care practices. The observation period was between 2004 and 2013. Follow-up lasted up to five years and ended in April 2015. A total of 66,497 HF patients were selected after applying exclusion criteria. The same number of 66,497 controls were chosen and were matched (1:1) to HF patients on the basis of age, sex, health insurance, depression diagnosis in the past, and follow-up duration after index date. Results: HF was a strong risk factor for diagnosed depression (p < 0.0001). A total of 10.5% of HF patients and 6.3% of matched controls developed depression after one year of follow-up (p < 0.001). Depression was documented in 28.9% of the HF group and 18.2% of the control group after the five-year follow-up (p < 0.001). Cancer, dementia, osteoporosis, stroke, and osteoarthritis were associated with a higher risk of developing depression. Male gender and private health insurance were associated with lower risk of depression. Conclusions: The risk of diagnosed depression is significantly increased in patients with HF compared to patients without HF in primary care practices in Germany.
Häusler, Andreas ; Sánchez, Alba ; Gellert, Paul ; Deeken, Friederike ; Rapp, Michael Armin ; Nordheim, Johanna
Background: Given the well-established association between perceived stress and quality of life (QoL) in dementia patients and their partners, our goal was to identify whether relationship quality and dyadic coping would operate as mediators between perceived stress and QoL. Results: We found negative correlations between stress and QoL in both partners (QoL-AD: r = -0.62; p < 0.001; WHO-QOL Overall: r = -0.27; p = 0.02). Spousal caregivers had a significantly lower DCI total score than dementia patients (p < 0.001). Dyadic coping was a significant mediator of the relationship between stress and QoL in spousal caregivers (z = 0.28; p = 0.02), but not in dementia patients. Likewise, relationship quality significantly mediated the relationship between stress and QoL in caregivers only (z = -2.41; p = 0.02). Conclusions: This study identified dyadic coping as a mediator on the relationship between stress and QoL in (caregiving) partners of dementia patients. In patients, however, we found a direct negative effect of stress on QoL. The findings suggest the importance of stress reducing and dyadic interventions for dementia patients and their partners, respectively.
Background/Aims: To analyze the duration of treatment with antipsychotics in German dementia patients. Methods: This study included patients aged 60 years and over with dementia who received a first-time antipsychotic prescription by psychiatrists between 2009 and 2013. The main outcome measure was the treatment rate for more than 6 months following the index date. Results: A total of 12,979 patients with dementia (mean age 82 years, 52.1% living in nursing homes) were included. After 2 years of follow-up, 54.8%, 57.2%, 61.1%, and 65.4% of patients aged 60 - 69, 70 - 79, 80 - 89, and 90 - 99 years, respectively, received antipsychotic prescriptions. 63.9% of subjects living in nursing homes and 55.0% of subjects living at home also continued their treatment (p-value < 0.001). Conclusion: The percentage of dementia patients treated with anti psychotics is very high.
As a contribution to a theoretical debate about the degree of high-level influences on saccade targeting during sentence reading, we investigated eye movements during the reading of structurally ambiguous Chinese character strings and examined whether parafoveal word segmentation could influence saccade-target selection. As expected, ambiguous strings took longer to process. More critically there were theoretically relevant interactions between ambiguity and launch site when first-fixation location and saccade amplitude served as dependent variables: Ambiguous strings in the parafovea triggered longer saccades and more rightward fixations for close launch sites than unambiguous ones; the reverse result was obtained for far launch sites. These crossover interactions indicate that parafoveal word segmentation influences saccade generation in Chinese and provide support of the hypothesis that high-level information can be involved in the decision about where to fixate next.
Bauer, M. ; Banaschewski, Tobias ; Heinz, A. ; Kamp-Becker, I. ; Meyer-Lindenberg, A. ; Padberg, F. ; Rapp, Michael Armin ; Rupprecht, R. ; Schneider, F. ; Schulze, T. G. ; Wittchen, Hans-Ulrich
Mental disorders are among the greatest medical and social challenges facing us. They can occur at all stages of life and are among the most important commonly occurring diseases. In Germany 28 % of the population suffer from a mental disorder every year, while the lifetime risk of suffering from a mental disorder is almost 50 %. Mental disorders cause great suffering for those affected and their social network. Quantitatively speaking, they can be considered to be among those diseases creating the greatest burden for society due to reduced productivity, absence from work and premature retirement. The Federal Ministry of Education and Research is funding a new research network from 2015 to 2019 with up to 35 million euros to investigate mental disorders in order to devise and develop better therapeutic measures and strategies for this population by means of basic and translational clinical research. This is the result of a competitive call for research proposals entitled research network for mental diseases. It is a nationwide network of nine consortia with up to ten psychiatric and clinical psychology partner institutions from largely university-based research facilities for adults and/or children and adolescents. Furthermore, three cross-consortia platform projects will seek to identify shared causes of diseases and new diagnostic modalities for anxiety disorders, attention deficit hyperactivity disorders (ADHS), autism, bipolar disorders, depression, schizophrenia and psychotic disorders as well as substance-related and addictive disorders. The spectrum of therapeutic approaches to be examined ranges from innovative pharmacological and psychotherapeutic treatment to novel brain stimulation procedures. In light of the enormous burden such diseases represent for society as a whole, a sustainable improvement in the financial support for those researching mental disorders seems essential. This network aims to become a nucleus for long overdue and sustained support for a German center for mental disorders.
The Summary Thirty-five thousand four hundred eighty-three female osteoporosis patients were compared with 35,483 patients without osteoporosis regarding the incidence of depression. The risk of depression is significantly increased for patients with osteoporosis compared with patients without osteoporosis in primary care practices within Germany. Introduction The objectives of the present study were to analyze the incidence of depression in German female patients with osteoporosis and to evaluate the risk factors for depression diagnosis within this patient population. Methods This study was a retrospective database analysis conducted in Germany utilizing the Disease Analyzer (R) Database (IMS Health, Germany). The study population included 70,966 patients between 40 and 80 years of age from 1072 primary care practices. The observation period was between 2004 and 2013. Follow-up duration was 5 years and was completed in April 2015. A total of 35,483 osteoporosis patients were selected after applying exclusion criteria, and 35,483 controls were chosen and then matched (1:1) to osteoporosis patients based on age, sex, health insurance coverage, depression diagnosis in the past, and follow-up duration after index date. The analyses of depression-free survival were carried out using Kaplan-Meier curves and log-rank tests. Cox proportional hazards models (dependent variable: depression) were used to adjust for confounders. Results Depression diagnoses were presented in 33.0% of the osteoporosis group and 22.7% of the control group after the 5-year follow-up (p < 0.001). Dementia, cancer, heart failure, coronary heart disease, and diabetes were associated with a higher risk of developing depression (p < 0.001). Private health insurance was associated with a lower risk of depression. There was no significant effect of fractures on depression risk. Conclusion The risk of depression is significantly increased for patients with osteoporosis in primary care practices within Germany.
Objective: To estimate the prevalence and the type of antidepressant medication prescribed by German psychiatrists to patients with depression and cardiovascular diseases (CVD). Methods: This study was a retrospective database analysis in Germany using the Disease Analyzer Database (IMS Health, Germany). The study population included 2,288 CVD patients between 40 and 90 years of age from 175 psychiatric practices. The observation period was between 2004 and 2013. Follow-up lasted up to 12 months and ended in April 2015. Also included were 2,288 non-CVD controls matched (1 : 1) to CVD cases on the basis of age, gender, health insurance coverage, depression severity, and diagnosing physician. Results: Mean age was 68.6 years. 46.2% of patients were men, and 5.9% had private health insurance coverage. Mild, moderate, or severe depression was present in 18.7%, 60.7%, and 20.6% of patients, respectively. Most patients had treatment within a year, many of them immediately after depression diagnosis. Patients with moderate and severe depression were more likely to receive treatment than patients with mild depression. There was no difference between CVD and non-CVD in the proportion of patients treated. Nonetheless, CVD patients received selective serotonin reuptake inhibitors / serotonin-noradrenaline reuptake inhibitors (SSRIs/SNRIs) significantly more frequently. Conversely, patients without CVD were more often treated with TCA. Conclusion: There was no association between CVD and the initiation of depression treatment. Furthermore, CVD patients received SSRIs/SNRIs more frequently.
AIM To determine the prevalence of depression and its risk factors among patients with coronary heart disease (CHD) treated in German primary care practices. METHODS Longitudinal data from nationwide general practices in Germany (n = 1072) were analyzed. Individuals initially diagnosed with CHD (2009-2013) were identified, and 59992 patients were included and matched (1: 1) to 59992 controls. The primary outcome measure was an initial diagnosis of depression within five years after the index date among patients with and without CHD. Cox proportional hazards models were used to adjust for confounders. RESULTS Mean age was equal to 68.0 years (SD = 11.3). A total of 55.9% of patients were men. After a five-year follow-up, 21.8% of the CHD group and 14.2% of the control group were diagnosed with depression (P < 0.001). In the multivariate regression model, CHD was a strong risk factor for developing depression (HR = 1.54, 95% CI: 1.49-1.59, P < 0.001). Prior depressive episodes, dementia, and eight other chronic conditions were associated with a higher risk of developing depression. Interestingly, older patients and women were also more likely to be diagnosed with depression compared with younger patients and men, respectively. CONCLUSION The risk of depression is significantly increased among patients with CHD compared with patients without CHD treated in primary care practices in Germany. CHD patients should be routinely screened for depression to ensure improved treatment and management.
Saccadic eye movements are frequently followed by smaller secondary saccades which are generally assumed to correct for the error in primary saccade landing position. However, secondary saccades can also occur after accurate primary saccades and they are often as small as microsaccades, therefore raising the need to further scrutinize the processes involved in secondary saccade generation. Following up a previous study, we analyzed secondary saccades using rate analysis which allows us to quantify experimental effects as shifts in distributions, therefore going beyond comparisons of mean differences. We use Aalen’s additive hazards model to delineate the time course of key influences on the secondary saccade rate. In addition to the established effect of primary saccade error, we observed a time-varying influence of under- vs. overshooting – with a higher risk of generating secondary saccades following undershoots. Moreover, increasing target eccentricity influenced the programming of secondary saccades, therefore demonstrating that error-unrelated variables co-determine secondary saccade programs. Our results provide new insights into the generative mechanisms of small saccades during postsaccadic fixation that need to be accounted for by secondary saccade models.
Persistence with antidepressant drugs in patients with dementia: a retrospective database analysis
(2016)
Background: The aims of the present study are to determine what proportion of patients with dementia receives antidepressants, how long the treatment is administered, and what factors increase the risk of discontinuation. Methods: The study was based on Disease Analyzer database and included 1,203 general practitioners (GP) and 209 neurologists/psychiatrists (NP). 12,281 patients with a diagnosis of dementia and an initial prescription of an antidepressant drug between January 2004 and December 2013 were included. The main outcome measure was antidepressant discontinuation rates within 6 months of the index date. Results: After 6 months of follow-up, 52.7% of dementia patients treated with antidepressants had stopped medication intake. There was a significantly decreased risk for treatment discontinuation for patients using selective serotonin reuptake inhibitors (SSRRIs) or serotonin and norepinephrine reuptake inhibitors (SSNRIs) compared to tricyclic antidepressants. There was a significantly increased risk of treatment discontinuation for older patients and patients treated in NP practice. Comorbidity of diabetes or history of stroke was associated with a decreased risk of treatment discontinuation. Conclusion: The study results show insufficient persistence in antidepressant treatment in dementia patients in a real world setting. The improvement must be achieved to ensure the treatment recommended in the guidelines.
Background: Dementia is a psychiatric condition the development of which is associated with numerous aspects of life. Our aim was to estimate dementia risk factors in German primary care patients.
Methods: The case-control study included primary care patients (70-90 years) with first diagnosis of dementia (all-cause) during the index period (01/2010-12/2014) (Disease Analyzer, Germany), and controls without dementia matched (1:1) to cases on the basis of age, sex, type of health insurance, and physician. Practice visit records were used to verify that there had been 10 years of continuous follow-up prior to the index date. Multivariate logistic regression models were fitted with dementia as a dependent variable and the potential predictors.
Conclusions: Risk factors for dementia found in this study are consistent with the literature. Nevertheless, the associations between statin, PPI and antihypertensive drug use, and decreased risk of dementia need further investigations.
Vences, Miguel ; Lyra, Mariana L. ; Kueneman, Jordan G. ; Bletz, Molly C. ; Archer, Holly M. ; Canitz, Julia ; Handreck, Svenja ; Randrianiaina, Roger-Daniel ; Struck, Ulrich ; Bhuju, Sabin ; Jarek, Michael ; Geffers, Robert ; McKenzie, Valerie J. ; Tebbe, Christoph C. ; Haddad, CLio F. B. ; Glos, Julian
Animal-associated microbial communities can play major roles in the physiology, development, ecology, and evolution of their hosts, but the study of their diversity has yet focused on a limited number of host species. In this study, we used high-throughput sequencing of partial sequences of the bacterial 16S rRNA gene to assess the diversity of the gut-inhabiting bacterial communities of 212 specimens of tropical anuran amphibians from Brazil and Madagascar. The core gut-associated bacterial communities among tadpoles from two different continents strongly overlapped, with eight highly represented operational taxonomic units (OTUs) in common. In contrast, the core communities of adults and tadpoles from Brazil were less similar with only one shared OTU. This suggests a community turnover at metamorphosis. Bacterial diversity was higher in tadpoles compared to adults. Distinct differences in composition and diversity occurred among gut bacterial communities of conspecific tadpoles from different water bodies and after experimental fasting for 8 days, demonstrating the influence of both environmental factors and food on the community structure. Communities from syntopic tadpoles clustered by host species both in Madagascar and Brazil, and the Malagasy tadpoles also had species-specific isotope signatures. We recommend future studies to analyze the turnover of anuran gut bacterial communities at metamorphosis, compare the tadpole core communities with those of other aquatic organisms, and assess the possible function of the gut microbiota as a reservoir for protective bacteria on the amphibian skin.
Schennen, Stephan ; Tronicke, Jens ; Wetterich, Sebastian ; Allroggen, Niklas ; Schwamborn, Georg ; Schirrmeister, Lutz
Ice complex deposits are characteristic, ice-rich formations in northern East Siberia and represent an important part in the arctic carbon pool. Recently, these late Quaternary deposits are the objective of numerous investigations typically relying on outcrop and borehole data. Many of these studies can benefit from a 3D structural model of the subsurface for upscaling their observations or for constraining estimations of inventories, such as the local carbon stock. We have addressed this problem of structural imaging by 3D ground-penetrating radar (GPR), which, in permafrost studies, has been primarily used for 2D profiling. We have used a 3D kinematic GPR surveying strategy at a field site located in the New Siberian Archipelago on top of an ice complex. After applying a 3D GPR processing sequence, we were able to trace two horizons at depths below 20 m. Taking available borehole and outcrop data into account, we have interpreted these two features as interfaces of major lithologic units and derived a 3D cryostratigraphic model of the subsurface. Our data example demonstrated that a 3D surveying and processing strategy was crucial at our field site and showed the potential of 3D GPR to image geologic structures in complex ice-rich permafrost landscapes.
Analysis of time-lapse ground-penetrating radar (GPR) data can provide information regarding subsurface hydrological processes, such as preferential flow. However, the analysis of time-lapse data is often limited by data quality; for example, for noisy input data, the interpretation of difference images is often difficult. Motivated by modern image-processing tools, we have developed two robust GPR attributes, which allow us to distinguish amplitude (contrast similarity) and time-shift (structural similarity) variations related to differences between individual time-lapse GPR data sets. We tested and evaluated our attributes using synthetic data of different complexity. Afterward, we applied them to a field data example, in which subsurface flow was induced by an artificial rainfall event. For all examples, we identified our structural similarity attribute to be a robust measure for highlighting time-lapse changes also in data with low signal-to-noise ratios. We determined that our new attribute-based workflow is a promising tool to analyze time-lapse GPR data, especially for imaging subsurface hydrological processes.
We present an algorithm that performs sequentially one-dimensional inversion of subsurface magnetic permeability and electrical conductivity by using multi-configuration electromagnetic induction sensor data. The presented method is based on the conversion of the in-phase and out-of-phase data into effective magnetic permeability and electrical conductivity of the equivalent homogeneous half-space. In the case of small-offset systems, such as portable electromagnetic induction sensors, for which in-phase and out-of-phase data are moderately coupled, the effective half-space magnetic permeability and electrical conductivity can be inverted sequentially within an iterative scheme. We test and evaluate the proposed inversion strategy using synthetic and field examples. First, we apply it to synthetic data for some highly magnetic environments. Then, the method is tested on real field data acquired in a basaltic environment to image a formation of archaeological interest. These examples demonstrate that a joint interpretation of in-phase and out-of-phase data leads to a better characterisation of the subsurface in magnetic environments such as volcanic areas.