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Biomedical subjects

Jörg Schumacher

Publications and source records attributed to Jörg Schumacher.

At least 19 recordsLinked to original sources

Geometry of intensive scalar dissipation events in turbulence.

The maxima of the scalar dissipation rate in turbulence appear in the form of sheets and correspond to the potentially most intensive scalar mixing events. Their cross section extension determines a locally varying diffusion scale of the mixing process and extends the classical Batchelor picture of one mean diffusion scale. The distribution of the local diffusion scales is analyzed for different Reynolds and Schmidt numbers with a fast multiscale technique applied to very high-resolution simulation data. The scales always take values across the whole Batchelor range and beyond. Furthermore, their distribution is traced back to the distribution of the contractive short-time Lyapunov exponent of the flow.

Journal Article↗

Heterogeneous nucleotide occupancy stimulates functionality of phage shock protein F, an AAA+ transcriptional activator.

The catalytic AAA+ domain (PspF1-275) of an enhancer-binding protein is necessary and sufficient to contact sigma54-RNA polymerase holoenzyme (Esigma54), remodel it, and in so doing catalyze open promoter complex formation. Whether ATP binding and hydrolysis is coordinated between subunits of PspF and the precise nature of the nucleotide(s) bound to the oligomeric forms responsible for substrate remodeling are unknown. We demonstrate that ADP stimulates the intrinsic ATPase activity of PspF1-275 and propose that this heterogeneous nucleotide occupancy in a PspF1-275 hexamer is functionally important for specific activity. Binding of ADP and ATP triggers the formation of functional PspF1-275 hexamers as shown by a gain of specific activity. Furthermore, ATP concentrations congruent with stoichiometric ATP binding to PspF1-275 inhibit ATP hydrolysis and Esigma54-promoter open complex formation. Demonstration of a heterogeneous nucleotide-bound state of a functional PspF1-275.Esigma54 complex provides clear biochemical evidence for heterogeneous nucleotide occupancy in this AAA+ protein. Based on our data, we propose a stochastic nucleotide binding and a coordinated hydrolysis mechanism in PspF1-275 hexamers.

Adenosine Diphosphate↗

Structures and organisation of AAA+ enhancer binding proteins in transcriptional activation.

Initiation of transcription is a major point of transcriptional regulation and invariably involves the transition from a closed to an open RNA polymerase (RNAP) promoter complex. In the case of the sigma(54)-RNAP, this multi step process requires energy, provided by ATP hydrolysis occurring within the AAA+ domain of enhancer binding proteins (EBPs). Typically, EBPs have an N-terminal regulatory domain, a central AAA+ domain that directly contacts sigma(54) and a C-terminal DNA binding domain. The following AAA+ EBP crystal structures have recently become available: heptameric AAA+ domains of NtrC1 and dimeric NtrC1 with its regulatory domain, hexameric AAA+ domains of ZraR with DNA binding domains, apo and nucleotide bound forms of the AAA+ domain of PspF as well as a cryo-EM structure of the AAA+ domain of PspF complexed with sigma(54). These AAA+ domains reveal the structural conservation between EBPs and other AAA+ domains. EBP specific structural features involved in substrate remodelling are located proximal to the pore of the hexameric ring. Parallels with the substrate binding elements near the central pore of other AAA+ members are drawn. We propose a structural model of EBPs in complex with a sigma(54)-RNAP-promoter complex.

Adenosine Triphosphate↗

Structural basis of the nucleotide driven conformational changes in the AAA+ domain of transcription activator PspF.

Bacterial enhancer-binding proteins (EBP) activate transcription by hydrolyzing ATP to restructure the sigma(54)-RNA polymerase-promoter complex. We compare six high resolution structures (<2.1 A) of the AAA(+) domain of EBP phage shock protein F (PspF) including apo, AMPPNP, Mg(2+)-ATP, and ADP forms. These structures permit a description of the atomic details underpinning the origins of the conformational changes occurring during ATP hydrolysis. Conserved regions of PspF's AAA(+) domain respond distinctively to nucleotide binding and hydrolysis, suggesting functional roles during the hydrolysis cycle, which completely agree with those derived from activities of PspF mutated at these positions. We propose a putative atomic switch that is responsible for coupling structural changes in the nucleotide-binding site to the repositioning of the sigma(54)-interacting loops. Striking similarities in nucleotide-specific conformational changes and atomic switch exist between PspF and the large T antigen helicase, suggesting conservation in the origin of those events amongst AAA(+) proteins.

Adenosine Diphosphate↗

[Resilience as a protective personality characteristic in the elderly].

In a sample of elderly from the general population aged 60 years and older (N = 599, 53.6 % female; mean age 69.6 years) resilience was assessed as a protective personality factor for physical well-being by means of the resilience scale (RS; Wagnild and Young, 1993). The elderly reported lower subjective body complaints, when the amount of resilience was higher. The results of a regression analysis showed that resilience was a significant predictive variable for physical well-being besides age and sex. The amount of resilience was lower in women as in men. An age-related effect could not be found.

Aged↗

Lagrangian tracers on a surface flow: the role of time correlations.

Finite time correlations of the velocity in a surface flow are found to be important for the formation of clusters of Lagrangian tracers. The degree of clustering characterized by the Lyapunov spectrum of the flow is numerically shown to be in qualitative agreement with the predictions for the white-in-time compressible Kraichnan flow, but to deviate quantitatively. For intermediate values of compressibility the clustering is surprisingly weakened by time correlations.

Journal Article↗

Sign-symmetry of temperature structure functions.

New scalar structure functions with different sign-symmetry properties are defined. These structure functions possess different scaling exponents even when their order is the same. Their scaling properties are investigated for second and third orders, using data from high-Reynolds-number atmospheric boundary layer. It is only when structure functions with disparate sign-symmetry properties are compared can the extended self-similarity detect two different scaling ranges that may exist, as in the example of convective turbulence.

Journal Article↗

ATP-dependent transcriptional activation by bacterial PspF AAA+protein.

Transcription activation by bacterial sigma(54)-dependent enhancer-binding proteins (EBPs) requires their tri-nucleotide hydrolysis to restructure the sigma(54) RNA polymerase (RNAP). EBPs share sequence similarity with guanine nucleotide binding-proteins and ATPases associated with various cellular activities (AAA) proteins, especially in the mononucleotide binding P-loop fold. Using the phage shock protein F (PspF) EBP, we identify P-loop residues responsible for nucleotide binding and hydrolysis, consistent with their roles in other P-loop NTPases. We show the refined low-resolution structure of an EBP, PspF, revealing a hexameric ring organisation characteristic of AAA proteins. Functioning of EBPs involves ATP binding, higher oligomer formation and ATP hydrolysis coupled to the restructuring of the RNAP. This is thought to be a highly coordinated multi-step process, but the nucleotide-driven mechanism of oligomerisation and ATP hydrolysis is little understood. Our kinetic and structural data strongly suggest that three PspF dimers assemble to form a hexamer upon nucleotide binding. During the ATP hydrolysis cycle, both ATP and ADP are bound to oligomeric PspF, in line with a sequential hydrolysis cycle. We identify a putative R-finger, and show its involvement in ATP hydrolysis. Substitution of this arginine residue results in nucleotide-independent formation of hexameric rings, structurally linking the putative R-finger and, by inference, a specific nucleotide interaction to the control of PspF oligomerisation.

Adenosine Diphosphate↗

Scalar gradient fields by geometric measure theory.

Upper bounds of the Hausdorff volume of scalar gradient field graphs are derived by means of geometric measure theory. The approach reproduces that scalar gradient fields along a mean imposed scalar gradient become space filling for sufficiently high values of Schmidt numbers Sc. The bounds are consistent with findings from recent high-resolution numerical experiments for 1< or =Sc< or =64, but too rough when compared with numerical simulations. A Reynolds number dependence of the bounds is found due to the additional scalar gradient stretching term in the equation of motion.

Journal Article↗

Geometric features of the mixing of passive scalars at high Schmidt numbers.

The mixing of passive scalars of decreasing diffusivity, advected in each case by the same three-dimensional Navier-Stokes turbulence, is studied. The mixing becomes more isotropic with decreasing diffusivity. The local flow in the vicinity of steepest negative and positive scalar gradients is in general different, and its behavior is studied for various values of the scalar diffusivity. Mixing approaches monofractal properties with diminishing diffusivity. We consider these results in the context of possible singularities of scalar dissipation.

Journal Article↗

The ATP hydrolyzing transcription activator phage shock protein F of Escherichia coli: identifying a surface that binds sigma 54.

Members of the protein family called ATPases associated with various cellular activities (AAA(+)) play a crucial role in transforming chemical energy into biological events. AAA(+) proteins are complex molecular machines and typically form ring-shaped oligomeric complexes that are crucial for ATPase activity and mechanism of action. The Escherichia coli transcription activator phage shock protein F (PspF) is an AAA(+) mechanochemical enzyme that functions to sense and relay the energy derived from nucleoside triphosphate hydrolysis to catalyze transcription by the sigma(54)-RNA polymerase. Closed promoter complexes formed by the sigma(54)-RNA polymerase are substrates for the action of PspF. By using a protein fragmentation approach, we identify here at least one sigma(54)-binding surface in the PspF AAA(+) domain. Results suggest that ATP hydrolysis by PspF is coupled to the exposure of at least one sigma(54)-binding surface. This nucleotide hydrolysis-dependent presentation of a substrate binding surface can explain why complexes that form between sigma(54) and PspF are transient and could be part of a mechanism used generally by other AAA(+) proteins to regulate activity.

Adenosine Triphosphatases↗

[The psychometric quality of the Nottingham Health Profile (NHP) in the general population].

The Nottingham Health Profile (NHP) is a questionnaire that assesses health related quality of life. The aim of this paper is to test the psychometric quality of the instrument based on a subject sample which is representative for the German population. The sample consisted of 1996 persons with ages between 18 and 92 years. They were asked to fill in several questionnaires including the NHP. The results show that the NHP does not differentiate between subjects in the range of low and medium levels of complaints. Only one half of the subject sample agreed to at least one of the 38 items. All six subscales showed significant age and sex effects which were proved with nonlinear regression analyses. The validity was assessed through correlations with other health related questionnaires. It can be concluded that the use of the NHP cannot be recommended when studies in the general population are conducted.

Adult↗

Clustering dynamics of Lagrangian tracers in free-surface flows.

We study the formation of clusters of passive Lagrangian tracers in a nonsmooth turbulent flow in a flat free-slip surface as a model for particle dynamics on free surfaces. Single particle and pair dispersion show different behavior for short and large times: on short times particles cluster exponentially rapidly until patches of the size of the divergence correlation length are depleted; on larger times the pair dispersion is dominated by almost ballistic hopping between clusters. We also find that the distribution of particle density is close to algebraic and can trace this back to the exponential distribution of the divergence field of the surface flow.

Journal Article↗

Mechanism of action of the Escherichia coli phage shock protein PspA in repression of the AAA family transcription factor PspF.

The PspA protein, a negative regulator of the Escherichia coli phage shock psp operon, is produced when virulence factors are exported through secretins in many Gram-negative pathogenic bacteria and its homologue in plants, VIPP1, plays a critical role in thylakoid biogenesis, essential for photosynthesis. Activation of transcription by the enhancer-dependent bacterial sigma(54) containing RNA polymerase occurs through ATP hydrolysis-driven protein conformational changes enabled by activator proteins that belong to the large AAA(+) mechanochemical protein family. We show that PspA directly and specifically acts upon and binds to the AAA(+) domain of the PspF transcription activator. Interactions involving PspF and nucleotide are changed by the action of PspA. These changes and the complexes that form between PspF and PspA can explain how PspA exerts its negative effects upon transcription activated by PspF, and are of significance when considering how activities of other AAA(+) proteins might be controlled.

Adenosine Triphosphatases↗

[Recalled parental rearing and the wish to have a child - are there associations?].

The present study concerns the impact of recalled parental rearing behaviour on both the intensity of the wish to have a child and on different motives to have a child. Until now there are no empirical studies as to this objective. Our study is based on a representative sample of 1509 persons aged 18 to 50 years. The statistical analyses were restricted to those subjects who lived in partnership and reported an actual wish to have a child (n = 331). The data were assessed by self-reporting scales: The Questionnaire of Recalled Parental Rearing Behaviour "Fragebogen zum erinnerten elterlichen Erziehungsverhalten, FEE", the Partnership Questionnaire "Partnerschaftsfragebogen, PFB", and the Leipzig Questionnaire of Motives to Have a Child "Leipziger Fragebogen zu Kinderwunschmotiven, LKM". A recalled parental rearing behaviour, which was characterized as having been rejective, overprotective and less emotionally warm was associated with such motives which do not promote the wish to have own children (fear of personal restrictions and a low degree of social support). Simultaneously, a negative parental rearing behaviour was correlated with a stronger desire for social recognition by an own child. The recalled maternal rearing behaviour was altogether stronger associated with motives to have a child than the paternal. On the other hand, no relevant associations could be found between the recalled parental rearing behaviour and the intensity of the wish to have a child.

Adolescent↗

[Somatoform complaints in the German population].

The study presents the subjective responses of a representative sample of the German population (2050 subjects, aged 14 to 92 years) on the prevalence of somatoform complaints, using the SOMS (Screening for somatoform disorders) developed by Rief et al. (1997). The results show that somatoform disorders are widespread in the German population. The symptoms named most frequently were pains in the back, aching limbs, pains in the arms or legs, headaches, facial pains and sensations of fullness in the stomach. Women named more somatoform complaints than men and elderly suffered more than the young. The higher rate found in East Germany could be accounted for by the responses of the East German women. Of particular economic and political relevance is the health care utilization behaviour of this group of patients. High medical consultation frequencies and increasing drug consumption were found for a significant proportion of all patients with somatoform disorders. In apparent contradiction to these findings is the classification according to DSM-IV and ICD-10, which diagnose somatoform disorders in only 0.2%-0.4% of the population. Such low prevalence can be attributed to the restrictive diagnostic criteria applied by these systems which obscure the real frequency of somatoform syndromes requiring specific treatment.

Adolescent↗

[Perceived parental rearing behaviour and adult attachment patterns in intimate relationships].

Based on the assumption that the parental rearing behaviour recalled by adults can be conceptualized as a specific mental representation of attachment, the study examines the associations between these rearing-related memories and adult attachment patterns in intimate relationships. The data for this study were obtained from a large community-based sample of the German population (1509 subjects between the ages of 18 and 50 years). Both, the perceived parental rearing behaviour and the adult attachment patterns have been assessed via questionnaires (Questionnaire of Recalled Parental Rearing Behaviour [Fragebogen zum erinnerten elterlichen Erziehungsverhalten, FEE] and Bielefeld Partnership Expectations Questionnaire [Bielefelder Fragebogen zu Partnerschaftserwartungen, BFPE]). As the result of the study it could be shown that a secure adult attachment pattern in intimate relationships is associated with a parental rearing behaviour that has been perceived as positive, while on the other hand insecure attachment patterns are rather associated with more negative experiences of parental rearing.

Adolescent↗