Statistical properties of multistep enzyme-mediated reactions

Enzyme-mediated reactions may proceed through multiple intermediate conformational states before creating a final product molecule, and one often wishes to identify such intermediate structures from observations of the product creation. In this paper, we address this problem by solving the chemical master equations for various enzymatic reactions. We devise a perturbation theory analogous to that used in quantum mechanics that allows us to determine the first () and the second (variance) cumulants of the distribution of created product molecules as a function of the substrate concentration and the kinetic rates of the intermediate processes. The mean product flux V=d/dt (or "dose-response" curve) and the Fano factor F=variance/ are both realistically measurable quantities, and while the mean flux can often appear the same for different reaction types, the Fano factor can be quite different. This suggests both qualitative and quantitative ways to discriminate between different reaction schemes, and we explore this possibility in the context of four sample multistep enzymatic reactions. We argue that measuring both the mean flux and the Fano factor can not only discriminate between reaction types, but can also provide some detailed information about the internal, unobserved kinetic rates, and this can be done without measuring single-molecule transition events.Comment: 8 pages, 3 figure

The Rubetum taxandriae ass. nov. (Lonicero-Rubion silvatici, Lonicero-Rubetea plicati), a new bramble association from the Belgian and Dutch Campine

Bramble scrubs are among the least known and understood vegetation types in Europe. In the Dutch National Vegetation Overview, three associations belonging to the Lonicero-Rubion silvatici were distinguished, viz. the Rubetum grati, Rubetum silvatici, and Rubetum pedemontani. During several vegetation mapping projects and Rubus excursions, a distinct type of bramble scrub was recorded repeatedly in the Campine in the province Noord-Brabant in the southern part of the Netherlands. In this paper, this scrub is described as a new association, the Rubetum taxandriae Haveman, de Ronde & Weeda, with R. taxandriae, R. campaniensis, and R. baronicus as character species, and R. insectifolius as regional character species. Variation, ecology and distribution of this new association are given and discussed, and two subassociations are distinguished. The differences with the Rubetum silvatici, to which this community was believed to belong, are discussed. Based on an earlier analysis of the centres of diversity of the genus Rubus in the Netherlands, it is supposed that the Rubetum silvatici in its circumscription in the Dutch National Vegetation Overview can be divided in more regionally distributed communities, partly as subassociations of the Rubetum silvatici, partly as independent associations

Little-studied arc-backarc system in the spotlight

A research cruise has documented changes in rift tectonics, volcanism, and hydrothermalism along the least studied and most enigmatic sector of a crustal complex in the southwest Pacific Ocean. Results from the longitudinal transect are expected to provide insight into processes involving the Kermadec arc-Havre backarc (KAHB) system, a continuum from oceanic spreading to continental rifting at a convergent plate boundary KAHB forms the central sector of an active, 2000-km arc-backarc complex between Tonga and New Zealand (Figure 1). The expedition also engaged in the first comprehensive survey of submarine vents in the Taupo Volcanic Zone (TVZ) at the south end of the KAHB system. Identified in the off-shore segment of TVZ were three major hydrothermal vent areas associated with late Quaternary fault structures. Data from the expedition and from other recent research in the same area addressed questions concerning the type of hydrothermal venting, magmatic heterogeneity along and across KAHB, the style of backarc rifting, and tectonic and magmatic consequences of anomalous terranes colliding with the subduction margin

Insights in a restricted temporary pacemaker strategy in a lean transcatheter aortic valve implantation program

OBJECTIVES: To study the safety and feasibility of a restrictive temporary‐RV‐pacemaker use and to evaluate the need for temporary pacemaker insertion for failed left ventricular (LV) pacing ability (no ventricular capture) or occurrence of high‐degree AV‐blocks mandating continuous pacing. BACKGROUND: Ventricular pacing remains an essential part of contemporary transcatheter aortic valve implantation (TAVI). A temporary‐right‐ventricle (RV)‐pacemaker lead is the standard approach for transient pacing during TAVI but requires central venous access. METHODS: An observational registry including 672 patients who underwent TAVI between June 2018 and December 2020. Patients received pacing on the wire when necessary, unless there was a high‐anticipated risk for conduction disturbances post‐TAVI, based on the baseline‐ECG. The follow‐up period was 30 days. RESULTS: A temporary‐RV‐pacemaker lead (RVP‐cohort) was inserted in 45 patients, pacing on the wire (LVP‐cohort) in 488 patients, and no pacing (NoP‐cohort) in 139 patients. A bailout temporary pacemaker was implanted in 14 patients (10.1%) in the NoP‐cohort and in 24 patients (4.9%) in the LVP‐cohort. One patient in the LVP‐cohort needed an RV‐pacemaker for incomplete ventricular capture. Procedure time was significantly longer in the RVP‐cohort (68 min [IQR 52–88.] vs. 55 min [IQR 44–72] in NoP‐cohort and 55 min [IQR 43–71] in the LVP‐cohort [p < 0.005]). Procedural high‐degree AV‐block occurred most often in the RVP‐cohort (45% vs. 14% in the LVP and 16% in the NoP‐cohort [p ≤ 0.001]). Need for new PPI occurred in 47% in the RVP‐cohort, versus 20% in the NoP‐cohort and 11% in the LVP‐cohort (p ≤ 0.001). CONCLUSION: A restricted RV‐pacemaker strategy is safe and shortens procedure time. The majority of TAVI‐procedures do not require a temporary‐RV‐pacemaker

Louisville seamount subduction and its implication on mantle flow beneath the central Tonga–Kermadec arc

Subduction of intraplate seamounts beneath a geochemically depleted mantle wedge provides a seldom opportunity to trace element recycling and mantle flow in subduction zones. Here we present trace element and Sr, Nd and Pb isotopic compositions of lavas from the central Tonga–Kermadec arc, west of the contemporary Louisville–Tonga trench intersection, to provide new insights into the effects of Louisville seamount subduction. Elevated 206Pb/204Pb, 208Pb/204Pb, 86Sr/87Sr in lavas from the central Tonga–Kermadec arc front are consistent with localized input of subducted alkaline Louisville material (lavas and volcaniclastics) into sub-arc partial melts. Furthermore, absolute Pacific Plate motion models indicate an anticlockwise rotation in the subducted Louisville seamount chain that, combined with estimates of the timing of fluid release from the subducting slab, suggests primarily trench-normal mantle flow beneath the central Tonga–Kermadec arc system

Stochastic pump effect and geometric phases in dissipative and stochastic systems

The success of Berry phases in quantum mechanics stimulated the study of similar phenomena in other areas of physics, including the theory of living cell locomotion and motion of patterns in nonlinear media. More recently, geometric phases have been applied to systems operating in a strongly stochastic environment, such as molecular motors. We discuss such geometric effects in purely classical dissipative stochastic systems and their role in the theory of the stochastic pump effect (SPE).Comment: Review. 35 pages. J. Phys. A: Math, Theor. (in press

Bead Array Direct rRNA Capture Assay (rCapA) for Amplification Free Speciation of Mycobacterium Cultures

Mycobacterium cultures, from patients suspected of tuberculosis or nontuberculous mycobacteria (NTM) infection, need to be identified. It is most critical to identify cultures belonging to the Mycobacterium tuberculosis complex, but also important to recognize clinically irrelevant or important NTM to allow appropriate patient management. Identification of M. tuberculosis can be achieved by a simple and cheap lateral flow assay, but identification of other Mycobacterium spp. generally requires more complex molecular methods. Here we demonstrate that a paramagnetic liquid bead array method can be used to capture mycobacterial rRNA in crude lysates of positive cultures and use a robust reader to identify the species in a direct and sensitive manner. We developed an array composed of paramagnetic beads coupled to oligonucleotides to capture 16 rRNA from eight specific Mycobacterium species and a single secondary biotinilated reporter probe to allow the captured rRNA to be detected. A ninth less specific bead and its associated reporter probe, designed to capture 23S rRNA from mycobacteria and related genera, is included as an internal control to confirm the presence of bacterial rRNA from a GC rich Gram variable genera. Using this rRNA capture assay (rCapA) with the array developed we were already able to confirm the presence of members of the M. tuberculosis complex and to discriminate a range of NTM species. This approach is not based on DNA amplification and therefore does not require precautions to avoid amplicon contamination. Moreover, the new generation of stable and cost effective liquid bead readers provides the necessary multiplexing potential to develop a robust and highly discriminatory assay