Interdependence of behavioural variability and response to small stimuli in bacteria

The chemotaxis signalling network in Escherichia coli that controls the locomotion of bacteria is a classic model system for signal transduction. This pathway modulates the behaviour of flagellar motors to propel bacteria towards sources of chemical attractants. Although this system relaxes to a steady state in response to environmental changes, the signalling events within the chemotaxis network are noisy and cause large temporal variations of the motor behaviour even in the absence of stimulus. That the same signalling network governs both behavioural variability and cellular response raises the question of whether these two traits are independent. Here, we experimentally establish a fluctuation-response relationship in the chemotaxis system of living bacteria. Using this relationship, we demonstrate the possibility of inferring the cellular response from the behavioural variability measured before stimulus. In monitoring the pre- and post-stimulus switching behaviour of individual bacterial motors, we found that variability scales linearly with the response time for different functioning states of the cell. This study highlights that the fundamental relationship between fluctuation and response is not constrained to physical systems at thermodynamic equilibrium but is extensible to living cells. Such a relationship not only implies that behavioural variability and cellular response can be coupled traits, but it also provides a general framework within which we can examine how the selection of a network design shapes this interdependence.     

Pleats in crystals on curved surfaces

Hexagons can easily tile a flat surface, but not a curved one. Introducing heptagons and pentagons (defects with topological charge) makes it easier to tile curved surfaces; for example, soccer balls based on the geodesic domes of Buckminster Fuller have exactly 12 pentagons (positive charges). Interacting particles that invariably form hexagonal crystals on a plane exhibit fascinating scarred defect patterns on a sphere. Here we show that, for more general curved surfaces, curvature may be relaxed by pleats: uncharged lines of dislocations (topological dipoles) that vanish on the surface and play the same role as fabric pleats. We experimentally investigate crystal order on surfaces with spatially varying positive and negative curvature. On cylindrical capillary bridges, stretched to produce negative curvature, we observe a sequence of transitions-consistent with our energetic calculations-from no defects to isolated dislocations, which subsequently proliferate and organize into pleats; finally, scars and isolated heptagons (previously unseen) appear. This fine control of crystal order with curvature will enable explorations of general theories of defects in curved spaces. From a practical viewpoint, it may be possible to engineer structures with curvature (such as waisted nanotubes and vaulted architecture) and to develop novel methods for soft lithography and directed self-assembly.     

Zircon U-Pb and Hf isotopes of volcanic rocks from the Batamayineishan Formation in the eastern Junggar Basin

An internal structural study was conducted to investigate U-Pb age, trace elements and Hf isotopes of basaltic zircons from the Batamayineishan Formation. The basalt was obtained from drill well San-Can 1 on the eastern Luliang uplift within the Junggar Basin. Trace element data of zircons show that all samples are magmatic, with similar REE patterns, including positive Ce (δCe=5.06–134), but negative Eu (δEu=0.06⦒0.55) anomalies and enrichment in heavy rare earth elements. Among 25 grains, the concordant ages were subdivided into three groups; ages of 300.4±1.3 Ma (n=11), 339.2±2.7 Ma (n=3) and 392.0±1.7 Ma (n=8). Three remaining grains were nearly concordant, with ²⁰⁶Pb/²³⁸U ages of 510±7, 488±6 and 453±6 Ma, respectively. The youngest concordant age (i.e., 300.4±1.3 Ma) could be interpreted as the formation age of the studied basaltic rock; this is consistent with the sampling position at the upper part of the Batamayineishan Formation. On the other hand, ages such as Ordovician and early Devonian are consistent with the ages of island-arc volcanic rocks (enrichment in Pb) or ophiolites around the basin. Moreover, the positive ɛ _Hf(t) values of the early and middle Paleozoic zircons (+3.6–+10.5) may suggest that the basement traversed by the studied volcanic rocks may be Paleozoic in age, formed from the residual oceanic crust and island-arc complex. The ɛ _Hf(t) values (+4.2–+17.1) of the late Paleozoic (∼300.4 Ma) zircons suggest that the basaltic magmas were derived from partial melting of the asthenospheric mantle or depleted lithospheric mantle. These magmas were slightly contaminated by the existence of early-middle Paleozoic materials. The late Carboniferous basalts represent direct eruption of mantle-derived magmas at the upper crustal level during a post-collisional tectonic setting. We therefore consider that extensive vertical growth of the continental crust to have occurred before the late Carboniferous.     

覆盖粗糙集上近似的研究

分析Pawlak粗糙集上下近似具有的性质,结合上下近似的含义和近似精度,讨论覆盖粗糙集上近似的定义方法,提出覆盖粗糙集最小上近似的概念,对其存在性及唯一性进行分析。最后,讨论最小上近似与其他上近似的关系,并对此作了证明。     

Processing technologies for gold-telluride ores

Gold telluride ores are important gold refractory ores due to the presence of sulfides and other gangue materials. The classification and main physical properties of gold telluride ores were described, and possible treatment methods including flotation, leaching, and oxidation were reviewed. The results show that flotation procedures are much easier for gold tellurides compared to other refractory gold-bearing ores. For the conventional cyanide leaching process, pretreatment such as oxidation is required to achieve high gold recovery. Roasting is a relatively simple but not environment-friendly method; bio-oxidation technology seems to be more suitable for the oxidation of flotation concentrate. Other treatment methods involve cyanide leaching, thiourea leaching, ammoniacal thiosulfate leaching, carbon-in-pulp, and resin-in-pulp, all of which are less commonly utilized.     

Structure and dynamics of the M3 muscarinic acetylcholine receptor

Acetylcholine, the first neurotransmitter to be identified, exerts many of its physiological actions via activation of a family of G-protein-coupled receptors (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five mAChR subtypes (M1-M5) share a high degree of sequence homology, they show pronounced differences in G-protein coupling preference and the physiological responses they mediate. Unfortunately, despite decades of effort, no therapeutic agents endowed with clear mAChR subtype selectivity have been developed to exploit these differences. We describe here the structure of the G(q/11)-coupled M3 mAChR ('M3 receptor', from rat) bound to the bronchodilator drug tiotropium and identify the binding mode for this clinically important drug. This structure, together with that of the G(i/o)-coupled M2 receptor, offers possibilities for the design of mAChR subtype-selective ligands. Importantly, the M3 receptor structure allows a structural comparison between two members of a mammalian GPCR subfamily displaying different G-protein coupling selectivities. Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. These simulations offer a structural view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportunities for the design of ligands with different affinities or binding kinetics for different mAChR subtypes. Our findings not only offer insights into the structure and function of one of the most important GPCR families, but may also facilitate the design of improved therapeutics targeting these critical receptors.     

Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing

Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level. To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions.