Collecting airs and ideas: Priestley’s style of experimental reasoning

It has often been claimed that Priestley was a skilful experimenter who lacked the capacities to analyze his own experiments and bring them to a theoretical closure. In attempts to revise this view some scholars have alluded to Priestley’s ‘synoptic’ powers while others stressed the contextual role of British Enlightenment in understanding his chemical research. A careful analysis of his pneumatic reports, privileging the dynamics of his experimental practice, uncovers significant yet neglected aspects of Priestley’s science. By focusing on his early experimental conduct and writing on nitrous air, I demonstrate how his methodological and rhetorical devices, far from being consequences of compulsive writing or theoretical naïveté, were deeply entwined with his chemical research. I employ the notion of ‘style of experimental reasoning’ (SER)—derived from A. C. Crombie and I. Hacking—to shed light on the intersection at which Priestley’s unique method, literary style, and epistemology converged to generate scientific knowledge. Establishing Priestley’s SER advances a finer understanding of the interactive character of his pneumatic experimentalism, peculiar dimensions of which have evaded both traditional as well as revisionist scholarship, thus infusing the longstanding historiographic debate over his scientific merits.     

微波结构分析的奇异积分方程方法

上世纪70年代以来与微波结构有关的某些计算问题通常是借助共形映射解析解决，且限于一维或二维情形（近年来由于计算机的发展被扩充到三维的某些情形）。本书作者积30多年的经验创立了一种新的方法——基于奇异积分方程（SIE）理论，给出边值问题解的积分表示，从而确定某些二维和三维微波结构的电动力学特性。本书系统全面地论述了这种方法，包括理论基础、用于数值分析的一些算法、以及各种典型应用实例。     

Streptococcal M1 protein constructs a pathological host fibrinogen network

M1 protein, a major virulence factor of the leading invasive strain of group A Streptococcus, is sufficient to induce toxic-shock-like vascular leakage and tissue injury. These events are triggered by the formation of a complex between M1 and fibrinogen that, unlike M1 or fibrinogen alone, leads to neutrophil activation. Here we provide a structural explanation for the pathological properties of the complex formed between streptococcal M1 and human fibrinogen. A conformationally dynamic coiled-coil dimer of M1 was found to organize four fibrinogen molecules into a specific cross-like pattern. This pattern supported the construction of a supramolecular network that was required for neutrophil activation but was distinct from a fibrin clot. Disruption of this network into other supramolecular assemblies was not tolerated. These results have bearing on the pathophysiology of streptococcal toxic shock.     

An extant, indigenous tortoise population in Baja California Sur, Mexico, with the description of a new species of Xerobates (Testudines: Testudinidae)

An extant, indigenous desert tortoise population is reported from the cape region of Baja California Sur, Mexico. This population is described and figured as a new species, Xerobates lepidocephalus , distinct from all other North American tortoises including Xerobates agassizii , X. berlandieri , Gopherus flavomarginatus , and G. polyphemus . Xerobates lepidocephalus , or the scaly-headed tortoise, whose range is known only from an extremely small area in the gulf-drainage mountains just south of La Paz, appears to be a peninsular relict whose closest living relative is probably X. agassizii . However, carpal bone affinities connote a close relationship between X. lepidocephalus and the Oligoeene species X. laticunea from Wyoming and Colorado, suggesting that the former species may be one of the more primitive contemporary tortoises of the Xerobates lineage. Such evidence indicates that X. lepidocephalus is not of vicariant origin resulting from the formation of the cape of Baja California. Scaly-headed tortoises likely ranged, and may yet be discovered, in other medium-elevation mountain ranges of the cape.     

Distant metastasis occurs late during the genetic evolution of pancreatic cancer

Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy. Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.     

Anthrax toxins cooperatively inhibit endocytic recycling by the Rab11/Sec15 exocyst

Bacillus anthracis is the causative agent of anthrax in humans and other mammals. In lethal systemic anthrax, proliferating bacilli secrete large quantities of the toxins lethal factor (LF) and oedema factor (EF), leading to widespread vascular leakage and shock. Whereas host targets of LF (mitogen-activated protein-kinase kinases) and EF (cAMP-dependent processes) have been implicated in the initial phase of anthrax, less is understood about toxin action during the final stage of infection. Here we use Drosophila melanogaster to identify the Rab11/Sec15 exocyst, which acts at the last step of endocytic recycling, as a novel target of both EF and LF. EF reduces levels of apically localized Rab11 and indirectly blocks vesicle formation by its binding partner and effector Sec15 (Sec15-GFP), whereas LF acts more directly to reduce Sec15-GFP vesicles. Convergent effects of EF and LF on Rab11/Sec15 inhibit expression of and signalling by the Notch ligand Delta and reduce DE-cadherin levels at adherens junctions. In human endothelial cells, the two toxins act in a conserved fashion to block formation of Sec15 vesicles, inhibit Notch signalling, and reduce cadherin expression at adherens junctions. This coordinated disruption of the Rab11/Sec15 exocyst by anthrax toxins may contribute to toxin-dependent barrier disruption and vascular dysfunction during B. anthracis infection.     

Defining the core Arabidopsis thaliana root microbiome

Land plants associate with a root microbiota distinct from the complex microbial community present in surrounding soil. The microbiota colonizing the rhizosphere (immediately surrounding the root) and the endophytic compartment (within the root) contribute to plant growth, productivity, carbon sequestration and phytoremediation. Colonization of the root occurs despite a sophisticated plant immune system, suggesting finely tuned discrimination of mutualists and commensals from pathogens. Genetic principles governing the derivation of host-specific endophyte communities from soil communities are poorly understood. Here we report the pyrosequencing of the bacterial 16S ribosomal RNA gene of more than 600 Arabidopsis thaliana plants to test the hypotheses that the root rhizosphere and endophytic compartment microbiota of plants grown under controlled conditions in natural soils are sufficiently dependent on the host to remain consistent across different soil types and developmental stages, and sufficiently dependent on host genotype to vary between inbred Arabidopsis accessions. We describe different bacterial communities in two geochemically distinct bulk soils and in rhizosphere and endophytic compartments prepared from roots grown in these soils. The communities in each compartment are strongly influenced by soil type. Endophytic compartments from both soils feature overlapping, low-complexity communities that are markedly enriched in Actinobacteria and specific families from other phyla, notably Proteobacteria. Some bacteria vary quantitatively between plants of different developmental stage and genotype. Our rigorous definition of an endophytic compartment microbiome should facilitate controlled dissection of plant-microbe interactions derived from complex soil communities.     

Rab5 is necessary for the biogenesis of the endolysosomal system in vivo

An outstanding question is how cells control the number and size of membrane organelles. The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis. Here, to test this hypothesis, we developed a mathematical model of endosome dependency on Rab5 and validated it by titrating down all three Rab5 isoforms in adult mouse liver using state-of-the-art RNA interference technology. Unexpectedly, the endocytic system was resilient to depletion of Rab5 and collapsed only when Rab5 decreased to a critical level. Loss of Rab5 below this threshold caused a marked reduction in the number of early endosomes, late endosomes and lysosomes, associated with a block of low-density lipoprotein endocytosis. Loss of endosomes caused failure to deliver apical proteins to the bile canaliculi, suggesting a requirement for polarized cargo sorting. Our results demonstrate for the first time, to our knowledge, the role of Rab5 as an endosome organizer in vivo and reveal the resilience mechanisms of the endocytic system.