Characterizing the RNA Binding Properties of the Intrinsically Disordered FUS Protein and RGG/RG Domains

Recent developments in the comprehensive identification of the RNA-binding protein (RBP) repertoire has accelerated discovery of new RBPs. According to these studies, 20% of both known and novel RNA-binding proteins are highly disordered. Moreover, analysis of the human mRNA interactome revealed most disease related mutations are found within intrinsically disordered RNA-binding domains (RBDs). For most of these proteins, their RNA-binding properties are poorly characterized. Thus, deciphering intrinsically disordered RBD-RNA interactions on a molecular scale is essential to understanding their impact upon human physiology and diseases. RGG/RG (arginine/glycine) domains are the second most common RNA binding domain in the human genome, yet their RNA-binding properties have not been well understood. Proteins containing RGG/RG domains regulate all aspects of RNA metabolism including transcription, processing, nucleocytoplasmic shuttling and translation. Proteins such as Fused in Sarcoma (FUS), Fragile X mental retardation (FMRP) and hnRNP U, bind a majority of the cellular transcriptome such that their recognition of RNAs has been considered to be non-specific or “promiscuous”. Here, I report a detailed analysis of the RNA-binding characteristics of the RGG/RG domains from FUS, FMRP and hnRNP U. While previous studies of FUS focused on RNA binding by the RRM and zinc finger (ZnF) domains, my analysis showed RNA binding activity is driven by the RGG/RG domains. Further, I observed a strong synergy between the RRM and adjacent RGG/RG domains to achieve RNA binding affinities of the full-length FUS. To better characterize RNA-binding properties of RGG/RG domains, we have analyzed RGG/RG domains of FUS, FMRP and hnRNP U in vitro against a spectrum of different RNAs with well-defined structural and sequence features. These experiments revealed that RGG/RG domains have different degrees of preference for binding to RNAs but share consistent trends in their selectivity towards RNAs with complex secondary structure. Thus, the binding behavior of RGG domains is best described as “degenerate specificity” reflecting that RGG/RG domains interact with a broad spectrum of RNAs that contain frequently observed sequence/structural elements. This mode of specificity is likely further facilitated by the intrinsically disordered nature of RGG/RG domains that enable them to adopt multiple conformations to adaptively bind RNA

The Introduction of a Marine Species Atherina boyeri into Bayramiç Reservoir, Çanakkale

This study reports the first recorded instance of Atherina boyeri (Risso, 1810) in the Bayramiç Reservoir, located on the Karamenderes Stream. Since 2005, ichthyological researches have been carried out in the Bayramiç Reservoir by various researchers, but none of them have noted the existence of A. boyeri in this reservoir. In the field studies conducted between May 2016 and July 2017, a total of 98 A. boyeri specimens was caught. In these samplings, a 70 m long and 2 m wide beach seine net with 10 mm a mesh size was used. Although a small number of A. boyeri was caught during the first observation in October 2016, more individuals were observed in July 2017. The fork length of the A. boyeri observed was between 2.7-8.8 cm and the weight ranged between 0.06-4.31 g. The bimodal length distribution of the specimens indicates that there have been multiple incidents of adult specimens entering the reservoir and that these individuals have given birth to new offspring. The translocation of A. boyeri into the Bayramiç Reservoir might have been due to unauthorized introduction by fishermen or through illegal release by anglers as fish bait. However, the distribution map of A. boyeri in inland waters in Turkey shows significant overlap with the migration routes of big waterfowl. The waterfowl might partially be responsible for the spread of the adult specimens across short distances

Implications for ID practice of Instructional Designers' Cultural Identities

Are there social and political purposes for design that are culturally based? A growing body of research is concerned with the design of culturally-appropriate learning resources and environments, but the emphasis of this panel is on the instructional designer as the agent of the design. Colloquially put, if we design for ourselves, we should understand the sociocultural influences on us and how they inform our practices. We should also develop respect for, and learn from, how various global cultures address similar design problems differently. This panel includes instructional design scholars and practitioners from a range of geopolitical regions, who will share culturally-based narratives and metaphors of ID, and invite participants to do the same. (Authors' abstract

A Mechanism for Chronic Filarial Hydrocele with Implications for Its Surgical Repair

Chronic hydrocele is the accumulation of fluid around the testis leading to an increase in the volume of the scrotal contents. Depending on the volume of fluid, hydrocele can be disfiguring and even incapacitating. Chronic hydrocele has multiple etiologies, but irrespective of the cause, surgery is the standard form of treatment and this can be done using different surgical techniques. The prevalence of chronic hydrocele in bancroftian filariasis endemic areas—a parasitic disease transmitted by mosquito—is very high and represents the most common clinical manifestation of bancroftosis, following by swollen legs of lower limbs or lymphedema among women. In Greater Recife, northeastern, Brazil, a bancroftian filariasis endemic area, a pioneering, prospective surgical study proposes a new mechanism for filarial-induced hydrocele and presents evidence that the filarial hydrocele fluid may damage the testis. Thus, based on the findings presented, the authors propose that in bancroftian filariasis endemic areas hydrocele patients should be operated on using a specific surgical technique in order to avoid recurrence of the disease, and consequently, additional damage to the testicle

Management of hydrocele in adolescent patients

Hydrocele is defined as an abnormal collection of serous fluid in the potential space between the parietal and visceral layers of the tunica vaginalis. In the majority of affected adolescents, hydrocele is acquired and is idiopathic in origin. The pathogenesis of idiopathic hydrocele is thought to be an imbalance in the normal process of fluid production and reabsorption. The diagnosis is usually clinical. Taking a thorough history is essential to rule out any fluctuation in size, which is an indication of a patent processus vaginalis. Scrotal ultrasonography is mandatory in nonpalpable testicles to rule out a subtending testicular solid mass requiring inguinal exploration. Otherwise, open hydrocelectomy via a scrotal incision is the standard treatment of idiopathic hydroceles. The second most common cause of hydrocele in adolescents is varicocelectomy. The risk of hydrocele formation is higher with non-artery-sparing procedures or those performed without microsurgical aid, and in surgery requiring cord dissection. If hydrocele occurs after varicocelectomy, initial management should include observation with or without hydrocele aspiration. Large persistent hydroceles are best served by open hydrocelectomy

Colloidal liquid crystal reinforced nanocomposites

The main objective of this research is to investigate the use of colloidal Boehmite rods as reinforcement filler for polymer nanocomposites and to introduce them as an alternative to the well-known clay systems. Since Boehmite rods have been studied for many years as a model nematic system, the motivation was to explore some additional properties which could arise from their nematic behaviour in a polymer matrix. The Boehmite system was expected to retain the nematic behavior in the polymer matrix, giving rise to unusual optical properties and a discontinuous mechanical response such that the storage modulus of the matrix polymer would jump to higher values after the isotropic-nematic phase transition. Although such a discontinuity in mechanical properties has not been observed, Boehmite particles have affected dramatically the thermal and mechanical properties as well as the crystal morphology of the polymer system. It has been proven that the Boehmite rods show nematic behavior also in the polymer matrix and increase the storage modulus of the polymer.Applied Science