Active fluctuations of axoneme oscillations scale with number of dynein motors.

Fluxes of energy generate active forces in living matter, yet also active fluctuations. As a canonical example, collections of molecular motors exhibit spontaneous oscillations with frequency jitter caused by nonequilibrium phase fluctuations. We investigate phase fluctuations in reactivated axonemes, which are accessible to direct manipulation.

Gliding motility of the diatom Craspedostauros australis coincides with the intracellular movement of raphid-specific myosins.

Raphid diatoms are one of the few eukaryotes capable of gliding motility, which is remarkably fast and allows for quasi-instantaneous directional reversals. Besides other mechanistic models, it has been suggested that an actomyosin system provides the force for diatom gliding. However, in vivo data on the dynamics of actin and myosin in diatoms are lacking.

Horizontal Magnetic Tweezers to Directly Measure the Force-Velocity Relationship for Multiple Kinesin Motors.

Transport of intracellular cargo along cytoskeletal filaments is often achieved by the concerted action of multiple motor molecules. While single-molecule studies have provided profound insight into the mechano-chemical principles and force generation of individual motors, studies on multi-motor systems are less advanced. Here, a horizontal magnetic-tweezers setup is applied, capable of producing up to 150 pN of horizontal force onto 2.

Predicting the locations of force-generating dyneins in beating cilia and flagella.

Cilia and flagella are slender cylindrical organelles whose bending waves propel cells through fluids and drive fluids across epithelia. The bending waves are generated by dynein motor proteins, ATPases whose force-generating activity changes over time and with position along the axoneme, the motile structure within the cilium. A key question is: where, in an actively beating axoneme, are the force-generating dyneins located? Answering this question is crucial for determining which of the conformational states adopted by the dynein motors generate the forces that bend the axoneme.

Multivalent electrostatic microtubule interactions of synthetic peptides are sufficient to mimic advanced MAP-like behavior.

Microtubule-associated proteins (MAPs) are a functionally highly diverse class of proteins that help to adjust the shape and function of the microtubule cytoskeleton in space and time. For this purpose, MAPs structurally support microtubules, modulate their dynamic instability, or regulate the activity of associated molecular motors. The microtubule-binding domains of MAPs are structurally divergent, but often depend on electrostatic interactions with the negatively charged surface of the microtubule.

Curvature regulation of the ciliary beat through axonemal twist.

Cilia and flagella are hairlike organelles that propel cells through fluid. The active motion of the axoneme, the motile structure inside cilia and flagella, is powered by molecular motors of the axonemal dynein family. These motors generate forces and torques that slide and bend the microtubule doublets within the axoneme.

Differences in the Clinical Profile and Outcomes of Typical and Atypical Takotsubo Syndrome: Data From the International Takotsubo Registry.

Importance: Apical ballooning is broadly recognized as the classic form of takotsubo syndrome (TTS). Atypical subtypes of TTS also exist, which constitute about 20% of all cases. To date, clinical profile and course of atypical TTS types have rarely been studied.

Dynamic curvature regulation accounts for the symmetric and asymmetric beats of Chlamydomonas flagella.

Cilia and flagella are model systems for studying how mechanical forces control morphology. The periodic bending motion of cilia and flagella is thought to arise from mechanical feedback: dynein motors generate sliding forces that bend the flagellum, and bending leads to deformations and stresses, which feed back and regulate the motors. Three alternative feedback mechanisms have been proposed: regulation by the sliding forces, regulation by the curvature of the flagellum, and regulation by the normal forces that deform the cross-section of the flagellum.

Broken detailed balance at mesoscopic scales in active biological systems.

Systems in thermodynamic equilibrium are not only characterized by time-independent macroscopic properties, but also satisfy the principle of detailed balance in the transitions between microscopic configurations. Living systems function out of equilibrium and are characterized by directed fluxes through chemical states, which violate detailed balance at the molecular scale. Here we introduce a method to probe for broken detailed balance and demonstrate how such nonequilibrium dynamics are manifest at the mesosopic scale.

Automatic optimal filament segmentation with sub-pixel accuracy using generalized linear models and B-spline level-sets.

Biological filaments, such as actin filaments, microtubules, and cilia, are often imaged using different light-microscopy techniques. Reconstructing the filament curve from the acquired images constitutes the filament segmentation problem. Since filaments have lower dimensionality than the image itself, there is an inherent trade-off between tracing the filament with sub-pixel accuracy and avoiding noise artifacts.

Independent Control of the Static and Dynamic Components of the Chlamydomonas Flagellar Beat.

When the green alga Chlamydomonas reinhardtii swims, it uses the breaststroke beat of its two flagella to pull itself forward [1]. The flagellar waveform can be decomposed into a static component, corresponding to an asymmetric time-averaged shape, and a dynamic component, corresponding to the time-varying wave [2]. Extreme lightening conditions photoshock the cell, converting the breaststroke beat into a symmetric sperm-like beat, which causes a reversal of the direction of swimming [3].

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy.

Background: The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood.

Methods: The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome.

Feasibility of second-generation bioresorbable vascular scaffold implantation in complex anatomical and clinical scenarios.

Background: Bioresorbable vascular scaffolds (BVS) have become an emerging tool to treat coronary artery disease. However, the current use of BVS is still widely restricted to stable patients and non-complex lesions. In real-world practice patients are far more complex than those with simple type A lesions and the extended use of BVS to complex lesions and high-risk patients needs to be evaluated.

Motor regulation results in distal forces that bend partially disintegrated Chlamydomonas axonemes into circular arcs.

The bending of cilia and flagella is driven by forces generated by dynein motor proteins. These forces slide adjacent microtubule doublets within the axoneme, the motile cytoskeletal structure. To create regular, oscillatory beating patterns, the activities of the axonemal dyneins must be coordinated both spatially and temporally.

Cell-body rocking is a dominant mechanism for flagellar synchronization in a swimming alga.

The unicellular green alga Chlamydomonas swims with two flagella that can synchronize their beat. Synchronized beating is required to swim both fast and straight. A long-standing hypothesis proposes that synchronization of flagella results from hydrodynamic coupling, but the details are not understood.

Reconstitution of flagellar sliding.

The motile structure within eukaryotic cilia and flagella is the axoneme. This structure typically consists of nine doublet microtubules arranged around a pair of singlet microtubules. The axoneme contains more than 650 different proteins that have structural, force-generating, and regulatory functions.

[Urinary bladder function disorders in childhood].

Bladder dysfunction in children is a very common and heterogeneous problem. There can be disturbances either in bladder storage or during voiding phases. First of all it is important to distinguish between non-neurogenic and neuropathic bladder dysfuction.

A comparison of international breast cancer guidelines - do the national guidelines differ in treatment recommendations?

Aim Of The Study: Clinical practice guidelines (CPG) are an appropriate method to optimise routine clinical care. Numerous CPGs for the diagnosis and treatment of breast cancer have been developed by national health institutions or medical societies. While a comparison of methodological criteria has been undertaken before, it is unknown whether these CPGs differ in their actual treatment recommendations.

[Vesicoureteral reflux: diagnostics and therapy].

The current management of vesicoureteral reflux (VUR) remains controversial. Recent well thought-out randomized studies on VUR in children have led to a debate on diagnostic and therapeutic algorithms. Individual parameters, such as age, gender, clinical course, renal function and scars, dysfunctional elimination syndrome and last but not least the compliance of the parents have gained in importance.

Does guideline-adherent therapy improve the outcome for early-onset breast cancer patients?

Background And Objective: Guidelines for the treatment of early-onset breast cancer have been proposed in several countries, but to date, their impact on outcomes is unverified. The objective of this study was to evaluate the association between guideline-adherent versus nonadherent treatment and recurrence-free survival (RFS) and overall survival (OAS) in early-onset breast cancer patients.

Methods: A total of 1,778 patients were included in the study, of whom 111 were 35 years or younger and 1,667 were between 36 and 55 years.

Effects of guideline adherence in primary breast cancer--a 5-year multi-center cohort study of 3976 patients.

Background: The aim of that study was to analyze the impact of German-S3-breast cancer guideline adherence on clinical outcomes.

Methods: A retrospective study analyzed 3976 patients first diagnosed with primary breast cancer according to an S3-guideline-based model that classified patients retrospectively into groups receiving "guideline-adherent and "guideline non-adherent" therapy.

Results: There was a significant association between treatment adherence and prolonged recurrence free and overall survival (p = 0.

Comparison of early onset breast cancer patients to older premenopausal breast cancer patients.

Background: The objective of this study was to show differences between breast cancer patients < or =35 and >35 years with regard to tumor characteristics and to present the patient-relevant outcomes overall survival (OAS) and recurrence-free survival (RFS).

Methods: We analyzed data from 119 women aged 35 years or younger with breast cancer and compared multiple parameters against breast cancer patients between 36 and 55 (n = 1,097), all pre-menopausal. Data were adjusted for tumor characteristics and therapy.

Activation of human alveolar macrophages via P2 receptors: coupling to intracellular Ca2+ increases and cytokine secretion.

Alveolar macrophages play a crucial role in the pathogenesis of inflammatory airway diseases. By the generation and release of different inflammatory mediators they contribute to both recruitment of different leukocytes into the lung and to airway remodeling. A potent stimulus for the release of inflammatory cytokines is ATP, which mediates its cellular effects through the interaction with different membrane receptors, belonging to the P2X and P2Y families.

[Cystitis emphysematosa--a case report].

We present a rare case of cystitis emphysematosa in an 85-year-old female patient in whom the typical risk factors were present: diabetes of long standing, neurogenic bladder and urinary infection with E.coli. Thanks to early diagnosis by cystoscopy and abdominal CT, after antibiotic treatment, appropriate insulin therapy and continuous bladder drainage the course was uneventful.