Nucleotide Binding Switches the Information Flow in Ras GTPases

The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins) that are essential to intracellular signal transduction. The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (SGDP and SGTP, respectively). For all the considered systems, the intrinsic flexibility of SGDP was higher than that of SGTP, suggesting that Guanine Exchange Factor (GEF) recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. Indeed, SGDP of Gαt, is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. Moreover, mechanically distinct domains implicated in nucleotide switch could be detected in the presence of GDP but not in the presence of GTP. Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. The average solvent exposure of these amino acids correlates in turn with the rate of GDP release, suggesting for them either direct or indirect roles in the process of nucleotide switch. Collectively, nucleotide binding changes the information flow through the conserved Ras-like domain, where GDP enhances the flexibility of mechanically distinct portions involved in nucleotide switch, and favors long distance allosteric communication (in Gα proteins), compared to GTP

Institutions and governance of communal rangelands in South Africa

The creation of local institutions with a mandate over land access and control is seen as a prerequisite for successful decentralisation of land tenure and effective local resource management in sub-Saharan Africa. However, with land tenure reform in South Africa currently at a state of legislative impasse, real uncertainty now exists over land rights and governance of rangeland in many communal areas. This paper draws on case study material from Eastern Cape province to illustrate how this ongoing uncertainty has resulted in the operation of a range of traditional authority and civil society institutions in different communal areas with varying degrees of legitimate authority over land administration and highly variable performance in managing rangeland resources. Collective management of rangeland resources seems most difficult in environments where land rights are contested because of the coexistence of traditional leaders and civil society institutions. On this basis an approach to tenure reform is advocated, which vests all powers over local land administration in democratically elected and accountable civil society institutions. Some successful examples of this already exist and might serve to guide policy formation, which must be flexible enough to accommodate collective management approaches that emphasise cooperation both within and between communities.Keywords: common property, land tenure, natural resource management, traditional leadersAfrican Journal of Range & Forage Science 2013, 30(1&2): 77–8

Self-prioritization and perceptual matching: The effects of temporal construal.

Recent research has revealed that self-referential processing enhances perceptual judgments - the so-called self-prioritization effect. The extent and origin of this effect remains unknown, however. Noting the multifaceted nature of the self, here we hypothesized that temporal influences on self-construal (i.e., past/future-self continuity) may serve as an important determinant of stimulus prioritization. Specifically, as representations of the self increase in abstraction as a function of temporal distance (i.e., distance from now), self-prioritization may only emerge when stimuli are associated with the current self. The results of three experiments supported this prediction. Self-relevance only enhanced performance in a standard perceptual-matching task when stimuli (i.e., geometric shapes) were connected with the current self; representations of the self in the future (Expts. 1 & 2) and past (Expt. 3) failed to facilitate decision making. To identify the processes underlying task performance, data were interrogated using a hierarchical drift diffusion model (HDDM) approach. Results of these analyses revealed that self-prioritization was underpinned by a stimulus bias (i.e., rate of information uptake). Collectively, these findings elucidate when and how self-relevance influences decisional processing

Treatment of forefoot problems in older people: study protocol for a randomised clinical trial comparing podiatric treatment to standardised shoe advice

<p>Abstract</p> <p>Background</p> <p>Foot problems in general and forefoot problems in particular can lead to a decrease in mobility and a higher risk of falling. Forefoot problems increase with age and are more common in women than in men. Around 20% of people over 65 suffer from non-traumatic foot problems and 60% of these problems are localised in the forefoot. Little is known about the best way to treat forefoot problems in older people. The aim of this study is to compare the effects of two common modes of treatment in the Netherlands: shoe advice and podiatric treatment. This paper describes the design of this study.</p> <p>Methods</p> <p>The study is designed as a pragmatic randomised clinical trial (RCT) with 2 parallel intervention groups. People aged 50 years and over who have visited their general practitioner (GP) with non traumatic pain in the forefoot in the preceding year and those who will visit their GP during the recruitment period with a similar complaint will be recruited for this study. Participants must be able to walk unaided for 7 metres and be able to fill in questionnaires. Exclusion criteria are: rheumatoid arthritis, neuropathy of the foot or pain caused by skin problems (e.g. warts, eczema). Inclusion and exclusion criteria will be assessed by a screening questionnaire and baseline assessment. Those consenting to participation will be randomly assigned to either a group receiving a standardised shoe advice leaflet (n = 100) or a group receiving podiatric treatment (n = 100). Primary outcomes will be the severity of forefoot pain (0-10 on a numerical rating scale) and foot function (Foot Function 5-pts Index and Manchester Foot Pain and Disability Index). Treatment adherence, social participation and quality of life will be the secondary outcomes. All outcomes will be obtained through self-administered questionnaires at the start of the study and after 3, 6, 9 and 12 months. Data will be analysed according to the "intention-to-treat" principle using multilevel level analysis.</p> <p>Discussion</p> <p>Strength of this study is the comparison between two common primary care treatments for forefoot problems, ensuring a high external validity of this trial.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2212">NTR2212</a></p

Microbial mediation of benthic biogenic silica dissolution

Pore water profiles from 24 stations in the South Atlantic (located in the Guinea, Angola, Cape, Guyana, and Argentine basins) show good correlations of oxygen and silicon, suggesting microbially mediated dissolution of biogenic silica. We used simple analytical transport and reaction models to show the tight coupling of the reconstructed process kinetics of aerobic respiration and silicon regeneration. A generic transport and reaction model successfully reproduced the majority of Si pore water profiles from aerobic respiration rates, confirming that the dissolution of biogenic silica (BSi) occurs proportionally to O 2 consumption. Possibly limited to well-oxygenated sediments poor in BSi, benthic Si fluxes can be inferred from O 2 uptake with satisfactory accuracy. Compared to aerobic respiration kinetics, the solubility of BSi emerged as a less influential parameter for silicon regeneration. Understanding the role of bacteria for silicon regeneration requires further investigations, some of which are outlined. The proposed aerobic respiration control of benthic silicon cycling is suitable for benthic–pelagic models. The empirical relation of BSi dissolution to aerobic respiration can be used for regionalization assessments and estimates of the silicon budget to increase the understanding of global primary and export production patterns