Copeptin is associated with kidney length, renal function, and prevalence of simple cysts in a population-based study.

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts.

Protein oligomers studied by solid-state NMR the case of the full-length nucleoid-associated protein histone-like nucleoid structuring protein

Members of the histone-like nucleoid structuring protein (H-NS) family play roles both as architectural proteins and as modulators of gene expression in Gram-negative bacteria. The H-NS protein participates in modulatory processes that respond to environmental changes in osmolarity, pH, or temperature. H-NS oligomerization is essential for its activity. Structural models of different truncated forms are available. However, high-resolution structural details of full-length H-NS and its DNA-bound state have largely remained elusive. We report on progress in characterizing the biologically active H-NS oligomers with solid-state NMR. We compared uniformly ((13)C,(15)N)-labeled ssNMR preparations of the isolated N-terminal region (H-NS 1-47) and full-length H-NS (H-NS 1-137). In both cases, we obtained ssNMR spectra of good quality and characteristic of well-folded proteins. Analysis of the results of 2D and 3D (13)C-(13)C and (15)N-(13)C correlation experiments conducted at high magnetic field led to assignments of residues located in different topological regions of the free full-length H-NS. These findings confirm that the structure of the N-terminal dimerization domain is conserved in the oligomeric full-length protein. Small changes in the dimerization interface suggested by localized chemical shift variations between solution and solid-state spectra may be relevant for DNA recoginition.

Scrfl restriction fragment length polymorphism at the D7S23 locus (probe pKM.19), closely linked to cystic fibrosis

Source/Description: pKM.19 is a 1.0 kb EcoRI genomic fragment in pUC13 (ref. 1,2). pPl was isolated independently but contains the same fragment as pKM.19 (ref. 3)...

Lack of GDAP1 induces neuronal calcium and mitochondrial defects in a knockout mouse model of charcot-marie-tooth neuropathy.

Mutations in GDAP1, which encodes protein located in the mitochondrial outer membrane, cause axonal recessive (AR-CMT2), axonal dominant (CMT2K) and demyelinating recessive (CMT4A) forms of Charcot-Marie-Tooth (CMT) neuropathy. Loss of function recessive mutations in GDAP1 are associated with decreased mitochondrial fission activity, while dominant mutations result in impairment of mitochondrial fusion with increased production of reactive oxygen species and susceptibility to apoptotic stimuli. GDAP1 silencing in vitro reduces Ca2+ inflow through store-operated Ca2+ entry (SOCE) upon mobilization of endoplasmic reticulum (ER) Ca2+, likely in association with an abnormal distribution of the mitochondrial network. To investigate the functional consequences of lack of GDAP1 in vivo, we generated a Gdap1 knockout mouse. The affected animals presented abnormal motor behavior starting at the age of 3 months. Electrophysiological and biochemical studies confirmed the axonal nature of the neuropathy whereas histopathological studies over time showed progressive loss of motor neurons (MNs) in the anterior horn of the spinal cord and defects in neuromuscular junctions. Analyses of cultured embryonic MNs and adult dorsal root ganglia neurons from affected animals demonstrated large and defective mitochondria, changes in the ER cisternae, reduced acetylation of cytoskeletal α-tubulin and increased autophagy vesicles. Importantly, MNs showed reduced cytosolic calcium and SOCE response. The development and characterization of the GDAP1 neuropathy mice model thus revealed that some of the pathophysiological changes present in axonal recessive form of the GDAP1-related CMT might be the consequence of changes in the mitochondrial network biology and mitochondria-endoplasmic reticulum interaction leading to abnormalities in calcium homeostasis.

Cardan Gear Mechanism versus Slider-Crank Mechanism in Pumps and Engines

In machine design we always want to save space, save energy and produce as much power as possible. We can often reduce accelerations, inertial loads and energy consumption by changing construction. In this study the old cardan gear mechanism (hypocycloid mechanism) has been compared with the conventional slider-crank mechanism in air pumps and four-stroke engines. Comprehensive Newtonian dynamics has been derived for the both mechanisms. First the slidercrank and the cardan gear machines have been studied as lossless systems. Then the friction losses have been added to the calculations. The calculation results show that the cardan gear machines can be more efficient than the slider-crank machines. The smooth running, low mass inertia, high pressures and small frictional power losses make the cardan gear machines clearly better than the slider-crank machines. The dynamic tooth loads of the original cardan gear construction do not rise very high when the tooth clearances are kept tight. On the other hand the half-size crank length causes high bearing forces in the cardan gear machines. The friction losses of the cardan gear machines are generally quite small. The mechanical efficiencies are much higher in the cardan gear machines than in the slider-crank machines in normal use. Crankshaft torques and power needs are smaller in the cardan gear air pumps than in the equal slider-crank air pumps. The mean crankshaft torque and the mean output power are higher in the cardan gear four-stroke engines than in the slider-crank four-stroke engines in normal use. The cardan gear mechanism is at its best, when we want to build a pump or an engine with a long connecting rod (≈ 5⋅crank length) and a thin piston (≈ 1.5⋅crank length) rotating at high angular velocity and intermittently high angular acceleration. The cardan gear machines can be designed also as slide constructions without gears. Suitable applications of the cardan gear machines are three-cylinder half-radial engines for motorcycles, sixcylinder radial engines for airplanes and six-cylinder double half-radial engines for sport cars. The applied equations of Newtonian dynamics, comparative calculations, calculation results (tables, curves and surface plots) and recommendations presented in this study hold novelty value and are unpublished before. They have been made and written by the author first time in this study.

Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial.

INTRODUCTION: Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. METHODS AND RESULTS: A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). CONCLUSIONS: Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.

Meta-analysis of the influence of bonding parameters on the clinical outcome of tooth-colored cervical restorations

PURPOSE: To meta-analyze the literature on the clinical performance of Class V restorations to assess the factors that influence retention, marginal integrity, and marginal discoloration of cervical lesions restored with composite resins, glass-ionomer-cement-based materials [glass-ionomer cement (GIC) and resin-modified glass ionomers (RMGICs)], and polyacid-modified resin composites (PMRC). MATERIALS AND METHODS: The English literature was searched (MEDLINE and SCOPUS) for prospective clinical trials on cervical restorations with an observation period of at least 18 months. The studies had to report about retention, marginal discoloration, marginal integrity, and marginal caries and include a description of the operative technique (beveling of enamel, roughening of dentin, type of isolation). Eighty-one studies involving 185 experiments for 47 adhesives matched the inclusion criteria. The statistical analysis was carried out by using the following linear mixed model: log (-log (Y /100)) = β + α log(T ) + error with β = log(λ), where β is a summary measure of the non-linear deterioration occurring in each experiment, including a random study effect. RESULTS: On average, 12.3% of the cervical restorations were lost, 27.9% exhibited marginal discoloration, and 34.6% exhibited deterioration of marginal integrity after 5 years. The calculation of the clinical index was 17.4% of failures after 5 years and 32.3% after 8 years. A higher variability was found for retention loss and marginal discoloration. Hardly any secondary caries lesions were detected, even in the experiments with a follow-up time longer than 8 years. Restorations placed using rubber-dam in teeth whose dentin was roughened showed a statistically significantly higher retention rate than those placed in teeth with unprepared dentin or without rubber-dam (p < 0.05). However, enamel beveling had no influence on any of the examined variables. Significant differences were found between pairs of adhesive systems and also between pairs of classes of adhesive systems. One-step self-etching had a significantly worse clinically index than two-step self-etching and three-step etch-and-rinse (p = 0.026 and p = 0.002, respectively). CONCLUSION: The clinical performance is significantly influenced by the type of adhesive system and/or the adhesive class to which the system belongs. Whether the dentin/enamel is roughened or not and whether rubberdam isolation is used or not also significantly influenced the clinical performance. Composite resin restorations placed with two-step self-etching and three-step etch-and-rinse adhesive systems should be preferred over onestep self-etching adhesive systems, GIC-based materials, and PMRCs.

Reversal of a full-length mutant huntingtin neuronal cell phenotypeby chemical inhibitors of polyglutamine-mediated aggregation

Background: Huntington's disease (HD) is an inherited neurodegenerative disorder triggered by an expanded polyglutamine tract in huntingtin that is thought to confer a new conformational property on this large protein. The propensity of small amino-terminal fragments with mutant, but not wild-type, glutamine tracts to self-aggregate is consistent with an altered conformation but such fragments occur relatively late in the disease process in human patients and mouse models expressing full-length mutant protein. This suggests that the altered conformational property may act within the full-length mutant huntingtin to initially trigger pathogenesis. Indeed, genotypephenotype studies in HD have defined genetic criteria for the disease initiating mechanism, and these are all fulfilled by phenotypes associated with expression of full-length mutant huntingtin, but not amino-terminal fragment, in mouse models. As the in vitro aggregation of amino-terminal mutant huntingtin fragment offers a ready assay to identify small compounds that interfere with the conformation of the polyglutamine tract, we have identified a number of aggregation inhibitors, and tested whether these are also capable of reversing a phenotype caused by endogenous expressionof mutant huntingtin in a striatal cell line from the HdhQ111/Q111 knock-in mouse. Results: We screened the NINDS Custom Collection of 1,040 FDA approved drugs and bioactive compounds for their ability to prevent in vitro aggregation of Q58-htn 1¿171 amino terminal fragment. Ten compounds were identified that inhibited aggregation with IC50 < 15 ¿M, including gossypol, gambogic acid, juglone, celastrol, sanguinarine and anthralin. Of these, both juglone and celastrol were effective in reversing the abnormal cellular localization of full-length mutant huntingtin observed in mutant HdhQ111/Q111 striatal cells. Conclusions: At least some compounds identified as aggregation inhibitors also prevent a neuronal cellular phenotype caused by full-length mutant huntingtin, suggesting that in vitro fragment aggregation can act as a proxy for monitoring the disease-producing conformational property in HD. Thus, identification and testing of compounds that alter in vitro aggregation is a viable approach for defining potential therapeutic compounds that may act on the deleterious conformational property of full-length mutant huntingtin.

Age-Related Tooth Wear Differs between Forest and Savanna Primates

Tooth wear in primates is caused by aging and ecological factors. However, comparative data that would allow us to delineate the contribution of each of these factors are lacking. Here, we contrast age-dependent molar tooth wear by scoring percent of dentine exposure (PDE) in two wild African primate populations from Gabonese forest and Kenyan savanna habitats. We found that forest-dwelling mandrills exhibited significantly higher PDE with age than savanna yellow baboons. Mandrills mainly feed on large tough food items, such as hard-shell fruits, and inhabit an ecosystem with a high presence of mineral quartz. By contrast, baboons consume large amounts of exogenous grit that adheres to underground storage organs but the proportion of quartz in the soils where baboons live is low. Our results support the hypothesis that not only age but also physical food properties and soil composition, particularly quartz richness, are factors that significantly impact tooth wear. We further propose that the accelerated dental wear in mandrills resulting in flatter molars with old age may represent an adaptation to process hard food items present in their environment.

Occlusal and dentofacial characteristics of the deciduous dentition and treatment effects of the eruption guidance appliance in the early mixed dentition

The aim of this investigation was to analyze the dental occlusion in the deciduous dentition, and the effects of orthodontic treatment carried out in the early mixed dentition with the eruption guidance appliance. The deciduous occlusion and craniofacial morphology of 486 children (244 girls and 242 boys) were investigated at the onset of the mixed dentition period (mean age 5.1 years, range 4.0-7.8 years). Treatment in the treatment group and follow-up in the control group were started when the first deciduous incisor was exfoliated (T1) and ended when all permanent incisors and first molars were fully erupted (T2). The mean age of the children was 5.1 years (SD 0.5) at T1 and 8.4 years (SD 0.5) at T2. Treatment was carried out with the eruption guidance appliance. Occlusal changes that took place in 167 children were compared with those of 104 untreated control children. Pre- and post-treatment cephalometric radiographs were taken, and the craniofacial morphology of 115 consecutively treated children was compared with that of 104 control children. The prevalence of malocclusion in the deciduous dentition was 68% or 93% depending on how the cut-off value between the acceptable and non-acceptable occlusal characteristic was defined. The early dentofacial features of children with distal occlusion, large overjet and deepbite differed from those with normal occlusion. However, the skeletal pattern of these three malocclusions showed considerable similarity each being characterized by a retrusive mandible, small maxillo-mandibular difference, convex profile, retrusive lower incisors, and large interincisal angle. In the treatment group, overjet and overbite decreased significantly from T1 to T2. Following treatment, a tooth-to-tooth contact was found in 99% of the treated children but only in 24% of the controls. A Class I molar relationship was observed in 90% of the children in the treatment group, and in 48% in the control group. Good alignment of the incisors was observed in 98% of the treated children, whereas upper crowding was found in 32% and lower crowding in 47% of the controls. A significant difference between the groups was found in the mandibular length, midfacial length and maxillo-mandibular differential. The occlusal correction, brought about by the eruption guidance appliance, was achieved mainly through changes in the dentoalveolar region of the mandible. In addition, the appliance seemed to enhance the growth of the mandible. Treatment in the early mixed dentition using the eruption guidance appliance is an effective method to normalize occlusion and reduce further need of orthodontic treatment. Only few spontaneous corrective changes can be expected without active intervention.

Maxillary dentigerous cyst and supernumerary tooth. Is it a frequent association?

Dentigerous cysts, also known as follicular cysts, are a relatively common pathology in our field. They are associated with unerupted or semi-erupted teeth and are usually not related to supernumerary teeth. OBJECTIVE: To describe a dentigerous cyst case associated to a supernumerary tooth. CASE-REPORT: A large-sized dentigerous cyst is described, associated with a supernumerary tooth, affecting the whole maxillary anterior area. Appropriate treatment consists of performing root canals and a Partsch II procedure with a cystectomy, extracting the unerupted teeth, carrying out an apicoectomy and retro-filling the affected teeth. The defect is filled with a bone xenograft. Possible therapeutic alternatives and the connection between the dentigerous cysts and supernumerary teeth are considered in the discussion.

Effects of interband and intraband impurity scattering on coherence length in the pnictide superconductors

After discovery of cuprates, a search for new high temperature superconducting families began and it led to the discovery of layered pnictide compounds with critical temperatures limited up to ∼56 K. Pnictides consist elements from Group V of Periodic Table (nitrogen, phosphorus, arsenic, antimony and bismuth). In this work coherence length h in mixed state of pnictide superconductors is calculated numerically. In calculation is taken into account interband and intraband impurity scattering in framework of quasiclassical Eilenberger theory for s± pairing symmetry. Differences between Ginzburg-Landau and Eilenberger theories is shown and the comparison with existing models is done.

Effects of interband and intraband impurity scattering on coherence length in the pnictide superconductors

After discovery of cuprates, a search for new high temperature superconducting families began and it led to the discovery of layered pnictide compounds with critical temperatures limited up to ~56 K. Pnictides consist elements from Group V of Periodic Table (nitrogen, phosphorus, arsenic, antimony and bismuth). In this work coherence length ξh in mixed state of pnictide superconductors is calculated numerically. In calculation is taken into account interband and intraband impurity scattering in framework of quasiclassical Eilenberger theory for s± pairing symmetry. Differences between Ginzburg-Landau and Eilenberger theories is shown and the comparison with existing models is done.

Centralized Motion Control of a Linear Tooth Belt Drive: Analysis of the Performance and Limitations

A centralized robust position control for an electrical driven tooth belt drive is designed in this doctoral thesis. Both a cascaded control structure and a PID based position controller are discussed. The performance and the limitations of the system are analyzed and design principles for the mechanical structure and the control design are given. These design principles are also suitable for most of the motion control applications, where mechanical resonance frequencies and control loop delays are present. One of the major challenges in the design of a controller for machinery applications is that the values of the parameters in the system model (parameter uncertainty) or the system model it self (non-parametric uncertainty) are seldom known accurately in advance. In this thesis a systematic analysis of the parameter uncertainty of the linear tooth beltdrive model is presented and the effect of the variation of a single parameter on the performance of the total system is shown. The total variation of the model parameters is taken into account in the control design phase using a Quantitative Feedback Theory (QFT). The thesis also introduces a new method to analyze reference feedforward controllers applying the QFT. The performance of the designed controllers is verified by experimentalmeasurements. The measurements confirm the control design principles that are given in this thesis.