Evolutionary Dynamics and Optimization: Neutral Networks as Model-Landscapes for RNA Secondary-Structure Folding-Landscapes

We view the folding of RNA-sequences as a map that assigns a pattern of base pairings to each sequence, known as secondary structure. These preimages can be constructed as random graphs (i.e. the neutral networks associated to the structure $s$). By interpreting the secondary structure as biological information we can formulate the so called Error Threshold of Shapes as an extension of Eigen's et al. concept of an error threshold in the single peak landscape. Analogue to the approach of Derrida & Peliti for a of the population on the neutral network. On the one hand this model of a single shape landscape allows the derivation of analytical results, on the other hand the concept gives rise to study various scenarios by means of simulations, e.g. the interaction of two different networks. It turns out that the intersection of two sets of compatible sequences (with respect to the pair of secondary structures) plays a key role in the search for ''fitter'' secondary structures.Comment: 20 pages, uuencoded compressed postscript-file, Proc. of ECAL '95 conference, to appear., email: chris @ imb-jena.d

Light Phase Testing of Social Behaviors: Not a Problem

The rich repertoire of mouse social behaviors makes it possible to use mouse models to study neurodevelopmental disorders characterized by social deficits. The fact that mice are naturally nocturnal animals raises a critical question of whether behavioral experiments should be strictly conducted in the dark phase and whether light phase testing is a major methodologically mistake. Although mouse social tasks have been performed in both phases in different laboratories, there seems to be no general consensus on whether testing phase is a critical factor or not. A recent study from our group showed remarkably similar social scores obtained from inbred mice tested in the light and the dark phase, providing evidence that light phase testing could yield reliable results as robust as dark phase testing for the sociability test. Here we offer a comprehensive review on mouse social behaviors measured in light and dark phases and explain why it is reasonable to test laboratory mice in experimental social tasks in the light phase

Chronic lymphocytic leukaemia: clinical-aetiological findings in 66 patients and their families

<p>Abstract</p> <p>Background</p> <p>Little is known about the aetiology of chronic lymphocytic leukaemia (CLL). The family medical history is a "genomic tool" capturing interactions of genetic susceptibility, shared environment and common behaviours.</p> <p>Methods</p> <p>A cohort of 66 consecutives patients with CLL (probands) was studied in a medical oncology practice (W.W.) from 1981 until 2005. A German version of the NCI medical history questionnaire for cancer aetiology was used. Familial clustering analysis was done by comparing the proportion of specific tumours in the first degree relatives of the CLL practice cohort with corresponding proportions of population-based cancer registry data.</p> <p>Results</p> <p>18 (41%) male and 5 (23%) female CLL probands had multiple malignancies, e.g. 2 meningiomas, 7 and 19 years after diagnosis of CLL. 46 (12%) first degree relatives had malignancies with an excess of CLL. Other conspicuous familial associations are CLL with malignancies of the upper GI tract (oesophagus, stomach) and of the nervous system.</p> <p>Conclusion</p> <p>1. Chronic lymphocytic leukaemia clusters in some families like any other disease. Predisposition genes should be searched. 2. Cancer prevention and early detection should be continued in CLL patients because of their longevity and high risk for multiple malignancies. 3. The overrepresentation of upper GI malignancies in first degree relatives of CLL patients calls for targeted oesophago-gastroscopy screening studies.</p

PREDICTING 3D GROUND REACTION FORCE FROM 2D VIDEO VIA NEURAL NETWORKS IN SIDESTEPPING TASKS

Sports science practitioners often measure ground reaction forces (GRFs) to assess performance, rehabilitation and injury risk. However, recording of GRFs during dynamic tasks has historically been limited to lab settings. This work aims to use neural networks (NN) to predict three-dimensional (3D) GRF via pose estimation keypoints as inputs, determined from 2D video data. Two different NN were trained on a dataset containing 1474 samples from 14 participants and their prediction accuracy compared with ground truth force data. Results for both NN showed correlation coefficients ranging from 0.936 to 0.954 and normalised root mean square errors from 11.05% to 13.11% for anterior-posterior and vertical GRFs, with poorer results found in the medio-lateral direction. This study demonstrates the feasibility and utility of predicting GRFs from 2D video footage

Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning.

The intracellular bacterium Chlamydia trachomatis develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both ARF isoforms are required for the repositioning of Golgi complex fragments around the inclusion. We demonstrate that CT813 directly recruits ARF GTPases on the inclusion membrane and plays a pivotal role in their activation. Together, these results reveal that Chlamydia uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion.IMPORTANCEChlamydia trachomatis is an important cause of morbidity and a significant economic burden in the world. However, how Chlamydia develops its intracellular compartment, the so-called inclusion, is poorly understood. Using genetically engineered Chlamydia mutants, we discovered that the effector protein CT813 recruits and activates host ADP-ribosylation factor 1 (ARF1) and ARF4 to regulate microtubules. In this context, CT813 acts as a molecular platform that induces the posttranslational modification of microtubules around the inclusion. These cages are then used to reposition the Golgi complex during infection and promote the development of the inclusion. This study provides the first evidence that ARF1 and ARF4 play critical roles in controlling posttranslationally modified microtubules around the inclusion and that Chlamydia trachomatis hijacks this novel function of ARF to reposition the Golgi complex

Parasitic behavior in competing chemically fueled reaction cycles

Non-equilibrium, fuel-driven reaction cycles serve as model systems of the intricate reaction networks of life. Rich and dynamic behavior is observed when reaction cycles regulate assembly processes, such as phase separation. However, it remains unclear how the interplay between multiple reaction cycles affects the success of emergent assemblies. To tackle this question, we created a library of molecules that compete for a common fuel that transiently activates products. Often, the competition for fuel implies that a competitor decreases the lifetime of these products. However, in cases where the transient competitor product can phase-separate, such a competitor can increase the survival time of one product. Moreover, in the presence of oscillatory fueling, the same mechanism reduces variations in the product concentration while the concentration variations of the competitor product are enhanced. Like a parasite, the product benefits from the protection of the host against deactivation and increases its robustness against fuel variations at the expense of the robustness of the host. Such a parasitic behavior in multiple fuel-driven reaction cycles represents a lifelike trait, paving the way for the bottom-up design of synthetic life

Debates en el campo de la salud mental : Práctica profesional y políticas públicas

El presente libro recupera discusiones fundamentales que se vienen desarrollando en el campo de la salud mental. La intención con la que compilamos los distintos artículos que integran esta publicación, es aportar a la reflexión acerca de una problemática que aunque relegada, ha cobrado vitalidad y fuerza en los últimos años. Esto ha sido producto de múltiples luchas que los colectivos de usuarios y trabajadores del sistema de salud han tenido que dar a lo largo de décadas; en este sentido creemos que se configura un escenario propicio para consolidar una perspectiva de derechos para pensar la salud mental. No es tarea sencilla, la lógica manicomial se erigió con solidez durante más de dos siglos, principalmente porque cumplía con propósitos societales, que aún cumple; desarmar ese andamiaje resultará una tarea colectiva. Las discusiones aquí presentes son producto del intercambio en el marco del Grupo de Estudios Políticas Públicas y Salud Mental del Centro de Estudios Trabajo Social y Sociedad de la Facultad de Trabajo Social de la UNLP; asimismo se suman los aportes de la experiencia docente durante siente años consecutivos en el desarrollo del seminario de grado: Salud Mental y Trabajo Social en la Facultad de Trabajo Social (UNLP) que coordinamos, donde hemos podido enriquecer los debates junto a colegas y estudiantes. Los mismos se han centrado en el análisis de herramientas teórico metodológicas para la intervención en el campo de la salud mental, así como la revisión de las tendencias e indagaciones actuales en el ámbito de las ciencias sociales que aportan a la problematización del mismo en un momento histórico signado por la revisión de los marcos jurídicos y las modalidades de asistencia.Facultad de Trabajo Socia

Measurement of cerebral oxygen pressure in living mice by two-photon phosphorescence lifetime microscopy

The ability to quantify partial pressure of oxygen (pO2) is of primary importance for studies of metabolic processes in health and disease. Here, we present a protocol for imaging of oxygen distributions in tissue and vasculature of the cerebral cortex of anesthetized and awake mice. We describe in vivo two-photon phosphorescence lifetime microscopy (2PLM) of oxygen using the probe Oxyphor 2P. This minimally invasive protocol outperforms existing approaches in terms of accuracy, resolution, and imaging depth