Great metalloclusters in enzymology

Metallocluster-containing enzymes catalyze some of the most basic redox transformations in the biosphere. The reactions catalyzed by these enzymes typically involve small molecules such as N2, CO, and H2 that are used to generate both chemical building blocks and energy for metabolic purposes. During the past decade, structures have been established for the iron-sulfur-based metalloclusters present in the molybdenum nitrogenase, the iron-only hydrogenase, and the nickel-carbon monoxide dehydrogenase, and for the copper-sulfide-based cluster in nitrous oxide reductase. Although these clusters are built from interactions observed in simpler metalloproteins, they contain novel features that may be relevant for their catalytic function. The mechanisms of metallocluster-containing enzymes are still poorly defined, and represent substantial and continuing challenges to biochemists, biophysicists, and synthetic chemists. These proteins also provide a window into the union of the biological and inorganic worlds that may have been relevant to the early evolution of biochemical catalysis

Neural correlates of consciousness are not pictorial representations

O'Regan & Noe (O&N) are pessimistic about the prospects for discovering the neural correlates of consciousness. They argue that there can be no one-to-one correspondence between awareness and patterns of neural activity in the brain, so a project attempting to identify the neural correlates of consciousness is doomed to failure. We believe that this degree of pessimism may be overstated; recent empirical data show some convergence in describing consistent patterns of neural activity associated with visual consciousness

An exploration of the potential of creating a coaching culture in a primary school

The aim of this research is to explore the potential that coaching, as a leadership style and process of professional growth, could have in a school. As educationalists and policy makers in the United Kingdom (UK) debate the increasing challenges that schools face, organisations such as the Department for Education (DfE) and Office for standards in Education (Ofsted), are also questioning the contribution that stringent accountability measures, experienced in many UK mainstream schools, and often linked to the term ‘school improvement’, have had on schools. This study explores alternative approaches to leading, teaching and learning, that promote an integrated model of continuous professional growth, as part of the solution to the many problems that schools face. The research findings suggest that building a culture of trust and resilience amongst practitioners is about getting the ethos right; something that starts with the style and tone of leadership. The findings show that it was through seemingly insignificant daily rituals between practitioners, identified by one participant as ‘little conversations’, that deep and trusting professionalism began to build a momentum towards what is described as ‘collective teacher efficacy’ (Goddard, et al., 2000). The research explores how deep trust can also lead to high levels of ‘discretionary effort’ (Buck, 2017, p19), the vital component that can take a school from good to great. The term ‘little conversations’ used by one of the participants, was identified as a contributing factor to deeper practitioner reflection, in a culture of openness and professionalism. Throughout this study I explore the connections and parallels between effective teaching and the best approaches to professional growth, moving away from a more traditional command and control leadership style, holding practitioners to account through performance management largely based on data. Ethical considerations were carefully researched before and throughout the project; particularly my role as both insider researcher and head teacher and the issue of power relations. Throughout the data collection and project write-up, due to the on-going nature of ethics, these considerations were returned to day by day, considering each participant individually. The ethical considerations have been of paramount importance to me as a researcher, so that they would not affect the integrity of the research findings. The data collection was a combination of 1-1 semi-structured interviews with senior leaders based on The Skilled Helper model (Egan, 2007) and focus groups of teachers using the Appreciative Inquiry model, (Cooperrider and Whitney, 2005) over a 15 month period. Senior leaders were invited to use reflective journals as a means of identifying key moments between coaching sessions, to explore in greater depth in future sessions. The data from the 1-1 coachees and focus group participants was transcribed and evaluated for emerging themes, culminating in an evaluation or ‘convergence’ of viewpoints from both groups. The findings of this small scale ethnographic study have implications for leadership development, recruitment and retention of staff, and the workload, well-being and professional growth of practitioners. The study concludes with a detailed contribution to national practice. This includes the recommendation to move away from a focus on stringent accountability measures, linked with school improvement, towards a more humanistic, integrated model that invests in career-long professional growth. The research suggests that government investment in promoting a coaching culture of professional growth, across maintained schools in the UK, could transform relationships and outcomes, for the benefit of all

How many metals does it take to fix N2? A mechanistic overview of biological nitrogen fixation

During the process of biological nitrogen fixation, the enzyme nitrogenase catalyzes the ATP-dependent reduction of dinitrogen to ammonia. Nitrogenase consists of two component metalloproteins, the iron (Fe) protein and the molybdenum-iron (MoFe) protein; the Fe protein mediates the coupling of ATP hydrolysis to interprotein electron transfer, whereas the active site of the MoFe protein contains the polynuclear FeMo cofactor, a species composed of seven iron atoms, one molybdenum atom, nine sulfur atoms, an interstitial light atom, and one homocitrate molecule. This Perspective provides an overview of biological nitrogen fixation and introduces three contributions to this special feature that address central aspects of the mechanism and assembly of nitrogenase

Nitrogenase: A nucleotide-dependent molecular switch

In the simplest terms, the biological nitrogen cycle is the reduction of atmospheric dinitrogen (N2) to ammonia with the subsequent reoxidation ammonia to dinitrogen (1). At the reduction level of ammonia, nitrogen incorporated into precursors for biological macromolecules such as proteins and nucleic acids. Reoxidation of ammonia to dinitrogen ("denitrification") by a variety of microbes (by way of nitrite and other oxidation levels of nitrogen) leads to the depletion of the "fixed," biologically usable, nitrogen pool. Besides the relatively small contribution from commercial ammonical fertilizer production, replenishing of the nitrogen pool falls mainly to a limited number of physiologically diverse microbes (e.g. eubacteria and archaebacteria; free-living and symbiotic; aerobic and anaerobic) that contain the nitrogenase enzyme system

Crystallographic Analyses of Ion Channels: Lessons and Challenges

Membrane proteins fascinate at many levels, from their central functional roles in transport, energy transduction, and signal transduction processes to structural questions concerning how they fold and operate in the exotic environments of the membrane bilayer and the water-bilayer interface and to methodological issues associated with studying membrane proteins either in situ or extracted from the membrane. This interplay is beautifully exemplified by ion channels, a collection of integral membrane proteins that mediate the transmembrane passage of ions down their electrochemical potential gradient (for general reviews, see Refs. 1 and 2). Ion channels are key elements of signaling and sensing pathways, including nerve cell conduction, hormone response, and mechanosensation. The characteristic properties of ion channels reflect their conductance, ion selectivity, and gating. Ion channels are often specific for a particular type of ion (such as potassium or chloride) or a class of ions (such as anions) and are typically regulated by conformational switching of the protein structure between "open" and "closed" states. This conformational switching may be gated in response to changes in membrane potential, ligand binding, or application of mechanical forces. Detailed functional characterizations of channels and their gating mechanisms have been achieved, reflecting exquisite methodological advances such as patch clamp methods that can monitor the activities of individual channels (3). Until recently, corresponding information about the three-dimensional structures of channels was not available, reflecting difficulties in obtaining sufficient quantities of membrane proteins for crystallization trials. Happily, this situation has started to change with the structure determinations of the Streptomyces lividans K+ channel (KcsA (4)) and the Mycobacterium tuberculosis mechanosensitive channel (MscL (5)). A variety of reviews (6-12) have appeared recently that discuss functional implications of these channel structures. This review discusses these developments from a complementary perspective, by considering the implications of these structures from within the larger framework of membrane protein structure and function. Because of space restrictions, this review necessarily emphasizes membrane proteins that are composed primarily of alpha-helical bundles, such as KcsA and MscL, rather than beta-barrel proteins, such as porins, typically found in bacterial outer membranes

Formation of Supermassive Black Holes by Direct Collapse in Pregalactic Halos

We describe a mechanism by which supermassive black holes can form directly in the nuclei of protogalaxies, without the need for seed black holes left over from early star formation. Self-gravitating gas in dark matter halos can lose angular momentum rapidly via runaway, global dynamical instabilities, the so-called "bars within bars" mechanism. This leads to the rapid buildup of a dense, self-gravitating core supported by gas pressure - surrounded by a radiation pressure-dominated envelope - which gradually contracts and is compressed further by subsequent infall. These conditions lead to such high temperatures in the central region that the gas cools catastrophically by thermal neutrino emission, leading to the formation and rapid growth of a central black hole. We estimate the initial mass and growth rate of the black hole for typical conditions in metal-free halos with T_vir ~ 10^4 K, which are the most likely to be susceptible to runaway infall. The initial black hole should have a mass of <~20 solar masses, but in principle could grow at a super-Eddington rate until it reaches ~ 10^4-10^6 solar masses. Rapid growth may be limited by feedback from the accretion process and/or disruption of the mass supply by star formation or halo mergers. Even if super-Eddington growth stops at \~10^3-10^4 solar masses, this process would give black holes ample time to attain quasar-size masses by a redshift of 6, and could also provide the seeds for all supermassive black holes seen in the present universe.Comment: 11 pages, 2 figures, Monthly Notices of the Royal Astronomical Society, in press. Minor revision

Limits from rapid TeV variability of Mrk 421

The extreme variability event in the TeV emission of Mrk 421, recently reported by the Whipple team, imposes the tightest limits on the typical size of the TeV emitting regions in Active Galactic Nuclei (AGN). We examine the consequences that this imposes on the bulk Lorentz factor of the emitting plasma and on the radiation fields present in the central region of this Active Nucleus. No strong evidence is found for extreme Lorentz factors. However, energetics arguments suggest that any accretion in Mrk 421 has to take place at small rates, compatible with an advection-dominated regime.Comment: 5 pages (Latex MNRAS style), revised version, submitted to MNRA

Implications of very rapid TeV variability in blazars

We discuss the implications of rapid (few-minute) variability in the TeV flux of blazars, which has been observed recently with the HESS and MAGIC telescopes. The variability timescales seen in PKS 2155-304 and Mrk 501 are much shorter than inferred light-crossing times at the black hole horizon, suggesting that the variability involves enhanced emission in a small region within an outflowing jet. The enhancement could be triggered by dissipation in part of the black hole's magnetosphere at the base of the outflow, or else by instabilities in the jet itself. By considering the energetics of the observed flares, along with the requirement that TeV photons escape without producing pairs, we deduce that the bulk Lorentz factors in the jets must be >50. The distance of the emission region from the central black hole is less well-constrained. We discuss possible consequences for multi-wavelength observations.Comment: 5 pages, no figures, accepted for publication in Monthly Notices of the Royal Astronomical Society Letter