The mechanical control of nervous system development.

The development of the nervous system has so far, to a large extent, been considered in the context of biochemistry, molecular biology and genetics. However, there is growing evidence that many biological systems also integrate mechanical information when making decisions during differentiation, growth, proliferation, migration and general function. Based on recent findings, I hypothesize that several steps during nervous system development, including neural progenitor cell differentiation, neuronal migration, axon extension and the folding of the brain, rely on or are even driven by mechanical cues and forces.This work was supported by the Medical Research CouncilThis is the accepted version of the original publication available at http://dev.biologists.org/content/140/15/3069

Mapping of the Tacaribe Arenavirus Z-Protein Binding Sites on the L Protein Identified both Amino Acids within the Putative Polymerase Domain and a Region at the N Terminus of L That Are Critically Involved in Binding

Tacaribe virus (TacV) is the prototype of the New World group of arenaviruses. The TacV genome encodes four proteins: the nucleoprotein (N), the glycoprotein precursor, the polymerase (L), and a RING finger protein (Z). Using a reverse genetics system, we demonstrated that TacV N and L are sufficient to drive transcription and replication mediated by TacV-like RNAs and that Z is a powerful inhibitor of these processes (Lopez et al., J. Virol. 65:12241-12251, 2001). More recently, we provided the first evidence of an interaction between Z and L and showed that Z's inhibitory activity was dependent on its ability to bind to L (Jácamo et al., J. Virol. 77:10383-10393, 2003). In the present study, we mapped the TacV Z-binding sites on the 2,210-amino-acid L polymerase. To that end, we performed deletion analysis and point mutations of L and studied the Z-L interaction by coimmunoprecipitation with specific sera. We found that the C-terminal region of L was not essential for the interaction and identified two noncontiguous regions that were critical for binding: one at the N-terminus of L between residues 156 and 292 and a second one in the polymerase domain (domain III). The importance of domain III in binding was revealed by substitutions in D1188 and H1189 within motif A and in each residue of the conserved SDD sequence (residues 1328, 1329, and 1330) within motif C. Our results showed that of the substituted residues, only H1189 and D1329 appeared to be critically involved in binding Z.Fil: Wilda, Maximiliano. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lopez, Nora Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Casabona, Juan Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Franze Fernandez, Maria T.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentin

A qualitative inquiry on the impact of family preservation programs

This project focuses on the impact of family preservation programs on family functioning through a qualitative follow up study of the Child Abuse Prevention Intervention and Treatment (CAPIT) program at Pacific Clinics in Yucca Valley, California. The results found that family functioning (particularly in areas of interpersonal skills and communication) had improved since completion of the program. Improvement was correlated with the service content of the program and with counselor characteristics. Due to limitations, including sample size (n=9), results cannot be generalized

Vergleich von zwei Rinderrassen hinsichtlich ihrer Eignung zur Ökologischen Milchproduktion – Teilfrage: Tiergesundheit

According to the rules of organic farming, prophylaxis shall be supported by selection of appropriate breeds. Nevertheless, today high yielding breeds predominate in organic dairy herds. Since 2004 the Institute of Organic Farming in Trenthorst compares two breeds under the same management conditions on its experimental farm. The evaluation of the data gained between March 2006 and March 2008 revealed a higher treatment rate in the milk orientated Holstein-Friesian cows compared to the German Red Pied, a local dual purpose breed. Although treatment of claw disorders were much more frequent in Holstein-Friesian cows, the lameness scoring carried out every fortnight did not show any difference between the two breeds (Chi2 3=3.506, n. s.). In 24 of 134 cases, cows needed support during calving but the frequency did not differ between the groups (Chi2 2=0.125, n. s.). Due to the low cell frequency the reasons for culling could not be evaluated, yet. Even if a comparison of breeds has to take into account the genotype-environment-interactions, these first results show no clear advantage of an assumed robust breed under the conditions of our organic farm

Force Generation by Molecular-Motor-Powered Microtubule Bundles; Implications for Neuronal Polarization and Growth.

The heavily cross-linked microtubule (MT) bundles found in neuronal processes play a central role in the initiation, growth and maturation of axons and dendrites; however, a quantitative understanding of their mechanical function is still lacking. We here developed computer simulations to investigate the dynamics of force generation in 1D bundles of MTs that are cross-linked and powered by molecular motors. The motion of filaments and the forces they exert are investigated as a function of the motor type (unipolar or bipolar), MT density and length, applied load, and motor connectivity. We demonstrate that only unipolar motors (e.g., kinesin-1) can provide the driving force for bundle expansion, while bipolar motors (e.g., kinesin-5) oppose it. The force generation capacity of the bundles is shown to depend sharply on the fraction of unipolar motors due to a percolation transition that must occur in the bundle. Scaling laws between bundle length, force, MT length and motor fraction are presented. In addition, we investigate the dynamics of growth in the presence of a constant influx of MTs. Beyond a short equilibration period, the bundles grow linearly in time. In this growth regime, the bundle extends as one mass forward with most filaments sliding with the growth velocity. The growth velocity is shown to be dictated by the inward flux of MTs, to inversely scale with the load and to be independent of the free velocity of the motors. These findings provide important molecular-level insights into the mechanical function of the MT cytoskeleton in normal axon growth and regeneration after injury.We thank François Nédélec for his help with the Cytosim software and to Sarah Foster and Thomas Martin for proofreading. We are grateful to the UK Medical Research Council (Career Development Award to KF), the Israel Science Foundation (grant no. 1396/09 to AZ) and the Bonn Cologne Graduate School as well as Erasmus+ (MJ) for financial support.This is the final version of the article. It first appeared from Frontiers via http://dx.doi.org/10.3389/fncel.2015.0044

Common temperature-growth dependency and acclimation response in three herbivorous protists

Phytoplankton growth dependence on temperature is recognized and has been quantified comprehensively. However, no similar relationship exists for the major phytoplankton predators, the herbivorous protists, especially at low temperatures representing polar and coastal oceans during most seasons. Their acclimation to changing temperatures is also largely unexplored. Here we report acclimated growth and acclimation rates from 0 to 22°C for 3 cosmopolitan herbivorous dinoflagellates. Due to interactive effects between size and temperature, growth increased 40% more rapidly with increasing temperature for production- compared to division-based growth rates (0.043 and 0.062 d-1 °C-1, respectively). Biomass-based growth rates were 10-fold higher than abundance-based rates at low temperatures, reflecting an average 50% increase in biovolume at ≤2°C. Thus, there was significant biomass accumulation at low temperatures, despite low cell-division rates. Testing different acclimation procedures, we established that acclimated rates emerged after 3 generations. Herbivores required 1.25 d °C-1 when acclimating towards higher temperatures and 2.5 d °C-1 when transitioning towards lower temperatures. Growth rates increased linearly with temperature, implying a weaker temperature effect on growth than the commonly assumed exponential dependency. A possible consequence is that herbivore growth rates are underestimated at cold and overestimated at warm temperatures. Current and future ocean assessments could thus underestimate trophic transfer rates in polar and cold-water regions and overestimate herbivore growth and thus grazing impact in future ocean predictions. Identifying physiological responses that transcend species-specificity supports cross-biome comparisons of ecosystem structure and function that rely on accurate predictions of matter and energy flow in planktonic food webs