66 research outputs found
On paper, immigrant detention centers meet standards to prevent sexual assault. But assault continues. Why?
Since 2014, Immigration and Customs Enforcement detainees have been protected by the federal law known as the Prison Rape Elimination Act, or PREA, designed to make facilities safer, give detainees better access to report sexual harm and increase transparency. Advocates, lawyers and detainees, however, say these standards are limited, and that the ability to report abuse is easily thwarted. A consulting company, The Nakamoto Group, was hired to conduct ICE\u27s PREA audits. But critics, including former ICE employees and the Department of Homeland Security\u27s own watchdog, question the substance of the audits and charge that the company’s auditors have overlooked serious problems for years. A review of 30 available DHS PREA audits showed that substantiated cases of sexual abuse were found at several facilities that aced their audits
DAAM is required for thin filament formation and Sarcomerogenesis during muscle development in Drosophila.
During muscle development, myosin and actin containing filaments assemble into the highly organized sarcomeric structure critical for muscle function. Although sarcomerogenesis clearly involves the de novo formation of actin filaments, this process remained poorly understood. Here we show that mouse and Drosophila members of the DAAM formin family are sarcomere-associated actin assembly factors enriched at the Z-disc and M-band. Analysis of dDAAM mutants revealed a pivotal role in myofibrillogenesis of larval somatic muscles, indirect flight muscles and the heart. We found that loss of dDAAM function results in multiple defects in sarcomere development including thin and thick filament disorganization, Z-disc and M-band formation, and a near complete absence of the myofibrillar lattice. Collectively, our data suggest that dDAAM is required for the initial assembly of thin filaments, and subsequently it promotes filament elongation by assembling short actin polymers that anneal to the pointed end of the growing filaments, and by antagonizing the capping protein Tropomodulin
Formin1 Mediates the Induction of Dendritogenesis and Synaptogenesis by Neurogenin3 in Mouse Hippocampal Neurons
Neurogenin3, a proneural transcription factor controlled by Notch receptor, has been recently shown to regulate dendritogenesis and synaptogenesis in mouse hippocampal neurons. However, little is known about the molecular mechanisms involved in these actions of Ngn3. We have used a microarray analysis to identify Ngn3 regulated genes related with cytoskeleton dynamics. One of such genes is Fmn1, whose protein, Formin1, is associated with actin and microtubule cytoskeleton. Overexpression of the Fmn1 isoform-Ib in cultured mouse hippocampal neurons induced an increase in the number of primary dendrites and in the number of glutamatergic synaptic inputs at 4 days in vitro. The same changes were provoked by overexpression of Ngn3. In addition downregulation of Fmn1 by the use of Fmn1-siRNAs impaired such morphological and synaptic changes induced by Ngn3 overexpression in neurons. These results reveal a previously unknown involvement of Formin1 in dendritogenesis and synaptogenesis and indicate that this protein is a key component of the Ngn3 signaling pathway that controls neuronal differentiation
Periodic actin structures in neuronal axons are required to maintain microtubules
Axons are the cable-like neuronal processes wiring the nervous system. They contain parallel bundles of microtubules as structural backbones, surrounded by regularly-spaced actin rings termed the periodic membrane skeleton (PMS). Despite being an evolutionarily-conserved, ubiquitous, highly-ordered feature of axons, the function of PMS is unknown. Here we studied PMS abundance, organisation and function, combining versatile Drosophila genetics with super-resolution microscopy and various functional readouts. Analyses with 11 different actin regulators and 3 actin-targeting drugs suggest PMS to contain short actin filaments which are depolymerisation resistant and sensitive to spectrin, adducin and nucleator deficiency - consistent with microscopy-derived models proposing PMS as specialised cortical actin. Upon actin removal we observed gaps in microtubule bundles, reduced microtubule polymerisation and reduced axon numbers suggesting a role of PMS in microtubule organisation. These effects become strongly enhanced when carried out in neurons lacking the microtubule-stabilising protein Short stop (Shot). Combining the aforementioned actin manipulations with Shot deficiency revealed a close correlation between PMS abundance and microtubule regulation, consistent with a model in which PMS-dependent microtubule polymerisation contributes to their maintenance in axons. We discuss potential implications of this novel PMS function along axon shafts for axon maintenance and regeneration
Crystal Structure of the Formin mDia1 in Autoinhibited Conformation
Formin proteins utilize a conserved formin homology 2 (FH2) domain to nucleate new actin filaments. In mammalian diaphanous-related formins (DRFs) the FH2 domain is inhibited through an unknown mechanism by intramolecular binding of the diaphanous autoinhibitory domain (DAD) and the diaphanous inhibitory domain (DID).Here we report the crystal structure of a complex between DID and FH2-DAD fragments of the mammalian DRF, mDia1 (mammalian diaphanous 1 also called Drf1 or p140mDia). The structure shows a tetrameric configuration (4 FH2 + 4 DID) in which the actin-binding sites on the FH2 domain are sterically occluded. However biochemical data suggest the full-length mDia1 is a dimer in solution (2 FH2 + 2 DID). Based on the crystal structure, we have generated possible dimer models and found that architectures of all of these models are incompatible with binding to actin filament but not to actin monomer. Furthermore, we show that the minimal functional monomeric unit in the FH2 domain, termed the bridge element, can be inhibited by isolated monomeric DID. NMR data on the bridge-DID system revealed that at least one of the two actin-binding sites on the bridge element is accessible to actin monomer in the inhibited state.Our findings suggest that autoinhibition in the native DRF dimer involves steric hindrance with the actin filament. Although the structure of a full-length DRF would be required for clarification of the presented models, our work here provides the first structural insights into the mechanism of the DRF autoinhibition
Dissonance-Based Interventions for the Prevention of Eating Disorders: Using Persuasion Principles to Promote Health
The limited efficacy of prior eating disorder (ED) prevention programs led to the development of dissonance-based interventions (DBI) that utilize dissonance-based persuasion principles from social psychology. Although DBIs have been used to change other attitudes and behaviors, only recently have they been applied to ED prevention. This article reviews the theoretical rationale and empirical support for this type of prevention program. Relative to assessment-only controls, DBIs have produced greater reductions in ED risk factors, ED symptoms, future risk for onset of threshold or subthreshold EDs, future risk for obesity onset, and mental health utilization, with some effects persisting through 3-year follow-up. DBIs have also produced significantly stronger effects than alternative interventions for many of these outcomes, though these effects typically fade more quickly. A meta-analysis indicated that the average effects for DBIs were significantly stronger than those for non-DBI ED prevention programs that have been evaluated. DBIs have produced effects when delivered to high-risk samples and unselected samples, as well as in efficacy and effectiveness trials conducted by six independent labs, suggesting that the effects are robust and that DBIs should be considered for the prevention of other problems, such as smoking, substance abuse, HIV, and diabetes care
Invasive cells in animals and plants: searching for LECA machineries in later eukaryotic life
IT tools implemented in the information system supporting management in the range of knowledge management in mechanical engineering enterprises
In the paper the authors showed and characterized IT tools implemented in the information system supporting management in the range of knowledge management in mechanical engineering enterprises. The authors gave a detailed description of the implementation of the following IT tools: knowledge objects management, risk management, case based reasoning
The conception of the system supporting management in the area of knowledge management in enterprises of mechanical engineering industry
The paper presents the conception of the system supporting management in the area of knowledge management in mechanical engineering industry enterprises. Specified conditions and assumptions for the construction of the working out IT system were given. The detailed structural range of the information system was discussed. Additionally, the authors presented the universal tool, knowledge network system KNS, which is useful in dealing with qualitative information, which frequently occur in knowledge management
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