Binding patterns of homo-peptides on bare magnetic nanoparticles: insights into environmental dependence

Magnetic nanoparticles (MNP) are intensively investigated for applications in nanomedicine, catalysis and biotechnology, where their interaction with peptides and proteins plays an important role. However, the characterisation of the interaction of individual amino acids with MNP remains challenging. Here, we classify the affinity of 20 amino acid homo-hexamers to unmodified iron oxide nanoparticles using peptide arrays in a variety of conditions as a basis to identify and rationally design selectively binding peptides. The choice of buffer system is shown to strongly influence the availability of peptide binding sites on the MNP surface. We find that under certain buffer conditions peptides of different charges can bind the MNP and that the relative strength of the interactions can be modulated by changing the buffer. We further present a model for the competition between the buffer and the MNP’s electrostatically binding to the adsorption sites. Thereby, we demonstrate that the charge distribution on the surface can be used to correlate the binding of positively and negatively charged peptides to the MNP. This analysis enables us to engineer the binding of MNP on peptides and contribute to better understand the bio-nano interactions, a step towards the design of affinity tags for advanced biomaterials

Surface Gap Soliton Ground States for the Nonlinear Schr\"{o}dinger Equation

We consider the nonlinear Schr\"{o}dinger equation $(-\Delta +V(x))u = \Gamma(x) |u|^{p-1}u$, $x\in \R^n$ with $V(x) = V_1(x) \chi_{\{x_1>0\}}(x)+V_2(x) \chi_{\{x_1<0\}}(x)$ and $\Gamma(x) = \Gamma_1(x) \chi_{\{x_1>0\}}(x)+\Gamma_2(x) \chi_{\{x_1<0\}}(x)$ and with $V_1, V_2, \Gamma_1, \Gamma_2$ periodic in each coordinate direction. This problem describes the interface of two periodic media, e.g. photonic crystals. We study the existence of ground state $H^1$ solutions (surface gap soliton ground states) for $0<\min \sigma(-\Delta +V)$. Using a concentration compactness argument, we provide an abstract criterion for the existence based on ground state energies of each periodic problem (with $V\equiv V_1, \Gamma\equiv \Gamma_1$ and $V\equiv V_2, \Gamma\equiv \Gamma_2$) as well as a more practical criterion based on ground states themselves. Examples of interfaces satisfying these criteria are provided. In 1D it is shown that, surprisingly, the criteria can be reduced to conditions on the linear Bloch waves of the operators $-\tfrac{d^2}{dx^2} +V_1(x)$ and $-\tfrac{d^2}{dx^2} +V_2(x)$.Comment: definition of ground and bound states added, assumption (H2) weakened (sign changing nonlinearity is now allowed); 33 pages, 4 figure

Use of Placebos and Nonspecific and Complementary Treatments by German Physicians - Rationale and Development of a Questionnaire for a Nationwide Survey

Background: We are performing a nationwide survey in a random sample ofGerman general practitioners (GPs), orthopedists, and internists on theuse of placebos and nonspecific as well as complementary treatments andtheir association with basic professional attitudes. In this article weexplain the theoretical considerations behind the study approach and thedevelopment of the questionnaire. Methods: Based on a systematic reviewof published surveys, own surveys on the topic, and on theoreticalconsiderations we developed a preliminary version of a 4-pagequestionnaire that was tested for feasibility in a convenience sample of80 participants of a general medical education event. We also performedcognitive interviews with 8 physicians to investigate whether thequestions were understood adequately. Results: The questions on typicalplacebos and complementary treatments were well understood and easy toanswer for participants. Discussions about the phrasing of questions onnonspecific treatments during interview reflected the vagueness of thisconcept; but this did not seem to create major problems when answeringthe related questions. The original questions regarding basicprofessional attitudes partly were not understood in the mannerintended. The relevant questions were modified but the interviewssuggest that these issues are difficult to grasp in a quantitativesurvey. Conclusion: Our testing procedures suggest that ourquestionnaire is well-suited to investigate our questions with somelimitations regarding the issue of basic professional attitudes

Fermionic decays of sfermions: a complete discussion at one-loop order

We present a definition of an on-shell renormalization scheme for the sfermion and chargino-neutralino sector of the Minimal Supersymmetric Standard Model (MSSM). Then, apply this renormalization framework to the interaction between charginos/neutralinos and sfermions. A kind of universal corrections is identified, which allow to define effective chargino/neutralino coupling matrices. In turn, these interactions generate (universal) non-decoupling terms that grow as the logarithm of the heavy mass. Therefore the full MSSM spectrum must be taken into account in the computation of radiative corrections to observables involving these interactions. As an application we analyze the full one-loop electroweak radiative corrections to the partial decay widths \Gamma(\tilde{f} -> f\neut) and \Gamma(\tilde{f} -> f'\cplus) for all sfermion flavours and generations. These are combined with the QCD corrections to compute the corrected branching ratios of sfermions. It turns out that the electroweak corrections can have an important impact on the partial decay widths, as well as the branching ratios, in wide regions of the parameter space. The precise value of the corrections is strongly dependent on the correlation between the different particle masses.Comment: LaTeX 53 pages, 22 figures, 3 tables. Typos correcte

Contribución al conocimiento de Porosagrotis gypaetina (Guen.) (Lep.:Noctuidae)

p.15-22Este trabajo tiene por finalidad brindar una descripcion detallada de los diferentes estados de desarrollo, asi como de los estadios larvales, de Porosagrotis gypaetina (Guen.) y estimar sus principales parametros biologicos. Se trata de una oruga conocida vulgarmente como gusano pardo que frecuenta cultivos de alfalfa, trebol bianco, maiz y girasol y determinadas malezas. Los caracteres considerados para su identificacion fueron, en el huevo: numero y distribucion de costas; en la larva: pigmentacion, distribucion de manchas y cerdas corporales; en la pupa: tamaño, forma y color y caracteristicas del cremaster; y en el adulto: ubicacion y coloracion de maculas y nervaduras alares. La emergencia de imagos alcanzo su maximo en abril y mayo. El periodo embrionario se completo en 22 a 26 dias. Aproximadamente la mitad de las larvas cumplieron su ciclo en 6 estadios y las restantes en 7; la duracion total del periodo larval fue de 134 a 141 dias, sin considerar la forma prepupal e independientemente del numero de estadios. Las orugas permanecieron como prepupas durante la temporada estival (aproximadamente 161 dias). El estado pupal duro 40 a 57 dias. Las observaciones realizadas permiten expresar que, inediante los caracteres descriptos, es factible reconocer la especie a traves no solo de los adultos, sino de sus estados inmaduros. Posee una sola generacion anual; transcurre el inviemo como larva; el daño tipico de corte lo produce a partir del cuarto estadio larval

Serum after Autologous Transplantation Stimulates Proliferation and Expansion of Human Hematopoietic Progenitor Cells

Regeneration after hematopoietic stem cell transplantation (HSCT) depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC) after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34+ cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT) significantly enhanced proliferation, maintained primitive immunophenotype (CD34+, CD133+, CD45−) for more cell divisions and increased colony forming units (CFU) as well as the number of cobblestone area-forming cells (CAFC). The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT). Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1) increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool

The influence of age, gender and socio-economic status on multimorbidity patterns in primary care. first results from the multicare cohort study

Background: Multimorbidity is a phenomenon with high burden and high prevalence in the elderly. Our previous research has shown that multimorbidity can be divided into the multimorbidity patterns of 1) anxiety, depression, somatoform disorders (ADS) and pain, and 2) cardiovascular and metabolic disorders. However, it is not yet known, how these patterns are influenced by patient characteristics. The objective of this paper is to analyze the association of socio-demographic variables, and especially socio-economic status with multimorbidity in general and with each multimorbidity pattern. Methods: The MultiCare Cohort Study is a multicentre, prospective, observational cohort study of 3.189 multimorbid patients aged 65+ randomly selected from 158 GP practices. Data were collected in GP interviews and comprehensive patient interviews. Missing values have been imputed by hot deck imputation based on Gower distance in morbidity and other variables. The association of patient characteristics with the number of chronic conditions is analysed by multilevel mixed-effects linear regression analyses. Results: Multimorbidity in general is associated with age (+0.07 chronic conditions per year), gender (-0.27 conditions for female), education (-0.26 conditions for medium and -0.29 conditions for high level vs. low level) and income (-0.27 conditions per logarithmic unit). The pattern of cardiovascular and metabolic disorders shows comparable associations with a higher coefficient for gender (-1.29 conditions for female), while multimorbidity within the pattern of ADS and pain correlates with gender (+0.79 conditions for female), but not with age or socioeconomic status. Conclusions: Our study confirms that the morbidity load of multimorbid patients is associated with age, gender and the socioeconomic status of the patients, but there were no effects of living arrangements and marital status. We could also show that the influence of patient characteristics is dependent on the multimorbidity pattern concerned, i.e. there seem to be at least two types of elderly multimorbid patients. First, there are patients with mainly cardiovascular and metabolic disorders, who are more often male, have an older age and a lower socio-economic status. Second, there are patients mainly with ADS and pain-related morbidity, who are more often female and equally distributed across age and socio-economic groups

An interdisciplinary intervention to prevent falls in community-dwelling elderly persons: protocol of a cluster-randomized trial [PreFalls]

<p>Abstract</p> <p>Background</p> <p>Prevention of falls in the elderly is a public health target in many countries around the world. While a large number of trials have investigated the effectiveness of fall prevention programs, few focussed on interventions embedded in the general practice setting and its related network. In the Prevent Falls (PreFalls) trial we aim to investigate the effectiveness of a pre-tested multi-modal intervention compared to usual care in this setting.</p> <p>Methods/Design</p> <p>PreFalls is a controlled multicenter prospective study with cluster-randomized allocation of about 40 general practices to an experimental or a control group. We aim to include 382 community dwelling persons aged 65 and older with an increased risk of falling. All participating general practitioners are trained to systematically assess the risk of falls using a set of validated tests. Patients from intervention practices are invited to participate in a 16-weeks exercise program with focus on fall prevention delivered by specifically trained local physiotherapists. Patients from practices allocated to the control group receive usual care. Main outcome measure is the number of falls per individual in the first 12 months (analysis by negative binomial regression). Secondary outcomes include falls in the second year, the proportion of participants falling in the first and the second year, falls associated with injury, risk of falls, fear of falling, physical activity and quality of life.</p> <p>Discussion</p> <p>Reducing falls in the elderly remains a major challenge. We believe that with its strong focus on a both systematic and realistic fall prevention strategy adapted to primary care setting PreFalls will be a valuable addition to the scientific literature in the field.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01032252">NCT01032252</a></p

Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta

Recessive osteogenesis imperfecta (OI) is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. The molecular mechanisms by which TMEM38B mutations cause OI are unknown. We identified 3 probands with recessive defects in TMEM38B. TRIC-B protein is undetectable in proband fibroblasts and osteoblasts, although reduced TMEM38B transcripts are present. TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability. Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery. The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps. Collagen helical lysine hydroxylation is reduced, while telopeptide hydroxylation is increased, despite increased LH1 and decreased Ca2+-dependent FKBP65, respectively. Although PDI levels are maintained, procollagen chain assembly is delayed in proband cells. The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50-70% reduction in secreted collagen. Lower-stability forms of collagen that elude proteasomal degradation are not incorporated into extracellular matrix, which contains only normal stability collagen, resulting in matrix insufficiency. These data support a role for TRIC-B in intracellular Ca2+ homeostasis, and demonstrate that absence of TMEM38B causes OI by dysregulation of calcium flux kinetics in the ER, impacting multiple collagen-specific chaperones and modifying enzymes