TRIM5α requires Ube2W to anchor Lys63-linked ubiquitin chains and restrict reverse transcription

TRIM5α is an antiviral, cytoplasmic, E3 ubiquitin (Ub) ligase that assembles on incoming retroviral capsids and induces their premature dissociation. It inhibits reverse transcription of the viral genome and can also synthesize unanchored polyubiquitin (polyUb) chains to stimulate innate immune responses. Here, we show that TRIM5α employs the E2 Ub-conjugating enzyme Ube2W to anchor the Lys63-linked polyUb chains in a process of TRIM5α auto-ubiquitination. Chain anchoring is initiated, in cells and in vitro, through Ube2W-catalyzed monoubiquitination of TRIM5α. This modification serves as a substrate for the elongation of anchored Lys63-linked polyUb chains, catalyzed by the heterodimeric E2 enzyme Ube2N/Ube2V2. Ube2W targets multiple TRIM5α internal lysines with Ub especially lysines 45 and 50, rather than modifying the N-terminal amino group, which is instead αN-acetylated in cells. E2 depletion or Ub mutation inhibits TRIM5α ubiquitination in cells and restores restricted viral reverse transcription, but not infection. Our data indicate that the stepwise formation of anchored Lys63-linked polyUb is a critical early step in the TRIM5α restriction mechanism and identify the E2 Ub-conjugating cofactors involved

Critical analysis of the influence of transnational capitalism on institutions and organizations

This paper aims to analyze the development of capitalism and its influences on institutions and organizations from its beginnings to reach the highest stage in the processes of neoliberal economic globalization and the New Economy version with support of information and communication technologies. In raising this development from a critical analysis, it examines the impacts and effects on individuals, communities and the nation state. Subsequently it is questioned the scope of the imposed transnational neoliberal capitalism model. Finally, it is concluded that it needs a cultural transformation for not accepting the forms of domination, power and alignment of globalizing capitalism and to reconstruct the identity of communities through individual action and asserting collective self-determination, independence and self-management

Discovering the Phylodynamics of RNA Viruses

The advent of extremely high throughput DNA sequencing ensures that genomic data from microbial organisms can be acquired in unprecedented quantities and with remarkable rapidity. Although this genomic revolution will affect all microbes alike, our focus here is on RNA viruses, as the rapidity of their evolution, which is observable over the time scale of human observation, allows phylodynamic inferences to be made with great precision. In the foreseeable future it is likely that complete genome sequencing will become the standard method of viral characterization, providing the highest possible resolution for phylogenetic studies. The rapidity with which genome sequence data were generated from the ongoing epidemic of swine-origin H1N1 influenza A virus [1] is testament to the power of this technology

How can chiropractic become a respected mainstream profession? The example of podiatry

<p>Abstract</p> <p>Background</p> <p>The chiropractic profession has succeeded to remain in existence for over 110 years despite the fact that many other professions which had their start at around the same time as chiropractic have disappeared. Despite chiropractic's longevity, the profession has not succeeded in establishing cultural authority and respect within mainstream society, and its market share is dwindling. In the meantime, the podiatric medical profession, during approximately the same time period, has been far more successful in developing itself into a respected profession that is well integrated into mainstream health care and society.</p> <p>Objective</p> <p>To present a perspective on the current state of the chiropractic profession and to make recommendations as to how the profession can look to the podiatric medical profession as a model for how a non-allopathic healthcare profession can establish mainstream integration and cultural authority.</p> <p>Discussion</p> <p>There are several key areas in which the podiatric medical profession has succeeded and in which the chiropractic profession has not. The authors contend that it is in these key areas that changes must be made in order for our profession to overcome its shrinking market share and its present low status amongst healthcare professions. These areas include public health, education, identity and professionalism.</p> <p>Conclusion</p> <p>The chiropractic profession has great promise in terms of its potential contribution to society and the potential for its members to realize the benefits that come from being involved in a mainstream, respected and highly utilized professional group. However, there are several changes that must be made within the profession if it is going to fulfill this promise. Several lessons can be learned from the podiatric medical profession in this effort.</p

Structural Brain Alterations in Individuals at Ultra-high Risk for Psychosis: A Review of Magnetic Resonance Imaging Studies and Future Directions

Individuals at ultra-high-risk (UHR) for psychosis have become a major focus for research designed to explore markers for early detection of and clinical intervention in schizophrenia. In particular, structural magnetic resonance imaging studies in UHR individuals have provided important insight into the neurobiological basis of psychosis and have shown the brain changes associated with clinical risk factors. In this review, we describe the structural brain abnormalities in magnetic resonance images in UHR individuals. The current accumulated data demonstrate that abnormalities in the prefrontal and temporal cortex and anterior cingulate cortex occur before illness onset. These regions are compatible with the regions of structural deficits found in schizophrenia and first-episode patients. In addition, the burgeoning evidence suggests that such structural abnormalities are potential markers for the transition to psychosis. However, most findings to date are limited because they are from cross-sectional rather than longitudinal studies. Recently, researchers have emphasized neurodevelopmental considerations with respect to brain structural alterations in UHR individuals. Future studies should be conducted to characterize the differences in the brain developmental trajectory between UHR individuals and healthy controls using a longitudinal design. These new studies should contribute to early detection and management as well as provide more predictive markers of later psychosis

LTC: a novel algorithm to improve the efficiency of contig assembly for physical mapping in complex genomes

<p>Abstract</p> <p>Background</p> <p>Physical maps are the substrate of genome sequencing and map-based cloning and their construction relies on the accurate assembly of BAC clones into large contigs that are then anchored to genetic maps with molecular markers. High Information Content Fingerprinting has become the method of choice for large and repetitive genomes such as those of maize, barley, and wheat. However, the high level of repeated DNA present in these genomes requires the application of very stringent criteria to ensure a reliable assembly with the FingerPrinted Contig (FPC) software, which often results in short contig lengths (of 3-5 clones before merging) as well as an unreliable assembly in some difficult regions. Difficulties can originate from a non-linear topological structure of clone overlaps, low power of clone ordering algorithms, and the absence of tools to identify sources of gaps in Minimal Tiling Paths (MTPs).</p> <p>Results</p> <p>To address these problems, we propose a novel approach that: (i) reduces the rate of false connections and Q-clones by using a new cutoff calculation method; (ii) obtains reliable clusters robust to the exclusion of single clone or clone overlap; (iii) explores the topological contig structure by considering contigs as networks of clones connected by significant overlaps; (iv) performs iterative clone clustering combined with ordering and order verification using re-sampling methods; and (v) uses global optimization methods for clone ordering and Band Map construction. The elements of this new analytical framework called Linear Topological Contig (LTC) were applied on datasets used previously for the construction of the physical map of wheat chromosome 3B with FPC. The performance of LTC vs. FPC was compared also on the simulated BAC libraries based on the known genome sequences for chromosome 1 of rice and chromosome 1 of maize.</p> <p>Conclusions</p> <p>The results show that compared to other methods, LTC enables the construction of highly reliable and longer contigs (5-12 clones before merging), the detection of "weak" connections in contigs and their "repair", and the elongation of contigs obtained by other assembly methods.</p