On RAF Sets and Autocatalytic Cycles in Random Reaction Networks

The emergence of autocatalytic sets of molecules seems to have played an important role in the origin of life context. Although the possibility to reproduce this emergence in laboratory has received considerable attention, this is still far from being achieved. In order to unravel some key properties enabling the emergence of structures potentially able to sustain their own existence and growth, in this work we investigate the probability to observe them in ensembles of random catalytic reaction networks characterized by different structural properties. From the point of view of network topology, an autocatalytic set have been defined either in term of strongly connected components (SCCs) or as reflexively autocatalytic and food-generated sets (RAFs). We observe that the average level of catalysis differently affects the probability to observe a SCC or a RAF, highlighting the existence of a region where the former can be observed, whereas the latter cannot. This parameter also affects the composition of the RAF, which can be further characterized into linear structures, autocatalysis or SCCs. Interestingly, we show that the different network topology (uniform as opposed to power-law catalysis systems) does not have a significantly divergent impact on SCCs and RAFs appearance, whereas the proportion between cleavages and condensations seems instead to play a role. A major factor that limits the probability of RAF appearance and that may explain some of the difficulties encountered in laboratory seems to be the presence of molecules which can accumulate without being substrate or catalyst of any reaction.Comment: pp 113-12

A single sub-km Kuiper Belt object from a stellar Occultation in archival data

The Kuiper belt is a remnant of the primordial Solar System. Measurements of its size distribution constrain its accretion and collisional history, and the importance of material strength of Kuiper belt objects (KBOs). Small, sub-km sized, KBOs elude direct detection, but the signature of their occultations of background stars should be detectable. Observations at both optical and X-ray wavelengths claim to have detected such occultations, but their implied KBO abundances are inconsistent with each other and far exceed theoretical expectations. Here, we report an analysis of archival data that reveals an occultation by a body with a 500 m radius at a distance of 45 AU. The probability of this event to occur due to random statistical fluctuations within our data set is about 2%. Our survey yields a surface density of KBOs with radii larger than 250 m of 2.1^{+4.8}_{-1.7} x 10^7 deg^{-2}, ruling out inferred surface densities from previous claimed detections by more than 5 sigma. The fact that we detected only one event, firmly shows a deficit of sub-km sized KBOs compared to a population extrapolated from objects with r>50 km. This implies that sub-km sized KBOs are undergoing collisional erosion, just like debris disks observed around other stars.Comment: To appear in Nature on December 17, 2009. Under press embargo until 1800 hours London time on 16 December. 19 pages; 7 figure

An effective all-atom potential for proteins

We describe and test an implicit solvent all-atom potential for simulations of protein folding and aggregation. The potential is developed through studies of structural and thermodynamic properties of 17 peptides with diverse secondary structure. Results obtained using the final form of the potential are presented for all these peptides. The same model, with unchanged parameters, is furthermore applied to a heterodimeric coiled-coil system, a mixed alpha/beta protein and a three-helix-bundle protein, with very good results. The computational efficiency of the potential makes it possible to investigate the free-energy landscape of these 49--67-residue systems with high statistical accuracy, using only modest computational resources by today's standards

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

KSHV gB associated RGD interactions promote attachment of cells by inhibiting the potential migratory signals induced by the disintegrin-like domain

Background: Kaposi's sarcoma-associated herpesvirus (KSHV) glycoprotein B (gB) is not only expressed on the envelope of mature virions but also on the surfaces of cells undergoing lytic replication. Among herpesviruses, KSHV gB is the only glycoprotein known to possess the RGD (Arg-Gly-Asp) binding integrin domain critical to mediating cell attachment. Recent studies described gB to also possess a disintegrin-like domain (DLD) said to interact with non-RGD binding integrins. We wanted to decipher the roles of two individually distinct integrin binding domains (RGD versus DLD) within KSHV gB in regulating attachment of cells over cell migration

Physical education undergraduate students’ perceptions of their learning using the jigsaw learning method

Recognising the limited research around the use of cooperative learning in higher education, this case study sought to explore physical education students’ perceptions of learning using the jigsaw learning method. It examined the impact of two different aesthetic activities and two different groupings on students’ perceptions of their learning. A purposive sample of 36 third-year undergraduates was selected for the study. Data were collected using focus group interviews and reflective journals. Inductive analysis illustrated students’ perceptions of their own and others’ abilities, students’ empathy towards their peers, and how their perceptions of gymnastics and dance impacted on their perceptions of learning. Students felt that heterogeneous and friendship groupings have the potential to encourage high-order social and cognitive learning. However, those students with limited psychomotor abilities appear to be better served in friendship groupings to facilitate such learning. Students also favoured the ‘structured’ nature of gymnastics in comparison to dance for their own teaching and learning purposes. Irrespective of aesthetic activity or grouping utilised, students felt their psychomotor learning was limited. It is recommended that university staff consider using a mixture of groupings with a single cohort dependent on the practical ability of students and the use of more ‘structured’ activities. In doing so, students’ perceptions of their social, cognitive and psychomotor learning may improve and thereby encourage greater and more effective use of this innovative method in schools

Magnetic Anisotropic Energy Gap and Strain Effect in Au Nanoparticles

We report on the observation of the size effect of thermal magnetization in Au nanoparticles. The thermal deviation of the saturation magnetization departs substantially from that predicted by the Bloch T3/2-law, indicating the existence of magnetic anisotropic energy. The results may be understood using the uniaxial anisotropy Heisenberg model, in which the surface atoms give rise to polarized moments while the magnetic anisotropic energy decreases as the size of the Au nanoparticles is reduced. There is a significant maximum magnetic anisotropic energy found for the 6 nm Au nanoparticles, which is associated with the deviation of the lattice constant due to magnetocrystalline anisotropy

Liver injury and fibrosis induced by dietary challenge in the ossabaw miniature Swine

BACKGROUND: Ossabaw miniature swine when fed a diet high in fructose, saturated fat and cholesterol (NASH diet) develop metabolic syndrome and nonalcoholic steatohepatitis (NASH) characterized by liver injury and fibrosis. This study was conducted to further characterize the development of NASH in this large animal model. METHODS: Ossabaw swine were fed standard chow (control group; n = 6) or NASH diet (n = 6) for 24 weeks. Blood and liver tissue were collected and liver histology were characterized at 0, 8, 16 and 24 weeks of dietary intervention. Hepatic apoptosis and lipid levels were assessed at week 24. RESULTS: The NASH diet group developed metabolic syndrome and progressive histologic features of NASH including: (a) hepatocyte ballooning at 8 weeks which progressed to extensive ballooning (>90% hepatocytes), (b) hepatic fibrosis at week 16, which progressed to moderate fibrosis, and (c) Kupffer cell accumulation with vacuolization at 8 weeks which progressed through week 24. The NASH diet group showed increased hepatocyte apoptosis that correlated with hepatic total and free cholesterol and free fatty acids, but not esterified cholesterol or triglycerides. CONCLUSIONS: This report further characterizes the progression of diet-induced NASH in the Ossabaw swine model. In Ossabaw swine fed the NASH diet: (a) hepatocyte injury and fibrosis can occur without macrovesicular steatosis or excess triglyceride accumulation; (b) hepatocyte ballooning generally precedes the development of fibrosis; (c) there is increased hepatocyte apoptosis, and it is correlated more significantly with hepatic free cholesterol than hepatic free fatty acids and had no correlation with hepatic triglycerides

MSMEG_2731, an Uncharacterized Nucleic Acid Binding Protein from Mycobacterium smegmatis, Physically Interacts with RPS1

While the M. smegmatis genome has been sequenced, only a small portion of the genes have been characterized experimentally. Here, we purify and characterize MSMEG_2731, a conserved hypothetical alanine and arginine rich M. smegmatis protein. Using ultracentrifugation, we show that MSMEG_2731 is a monomer in vitro. MSMEG_2731 exists at a steady level throughout the M. smegmatis life-cycle. Combining results from pull-down techniques and LS-MS/MS, we show that MSMEG_2731 interacts with ribosomal protein S1. The existence of this interaction was confirmed by co-immunoprecipitation. We also show that MSMEG_2731 can bind ssDNA, dsDNA and RNA in vitro. Based on the interactions of MSMEG_2731 with RPS1 and RNA, we propose that MSMEG_2731 is involved in the transcription-translation process in vivo