Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut

The largest mucosal surface in the body is in the gastrointestinal tract, a location that is heavily colonized by microbes that are normally harmless. A key mechanism required for maintaining a homeostatic balance between this microbial burden and the lymphocytes that densely populate the gastrointestinal tract is the production and transepithelial transport of poly-reactive IgA (ref. 1). Within the mucosal tissues, B cells respond to cytokines, sometimes in the absence of T-cell help, undergo class switch recombination of their immunoglobulin receptor to IgA, and differentiate to become plasma cells. However, IgA-secreting plasma cells probably have additional attributes that are needed for coping with the tremendous bacterial load in the gastrointestinal tract. Here we report that mouse IgA(+) plasma cells also produce the antimicrobial mediators tumour-necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), and express many molecules that are commonly associated with monocyte/granulocytic cell types. The development of iNOS-producing IgA(+) plasma cells can be recapitulated in vitro in the presence of gut stroma, and the acquisition of this multifunctional phenotype in vivo and in vitro relies on microbial co-stimulation. Deletion of TNF-α and iNOS in B-lineage cells resulted in a reduction in IgA production, altered diversification of the gut microbiota and poor clearance of a gut-tropic pathogen. These findings reveal a novel adaptation to maintaining homeostasis in the gut, and extend the repertoire of protective responses exhibited by some B-lineage cells.     

Molecular architecture of native HIV-1 gp120 trimers

The envelope glycoproteins (Env) of human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate virus binding to the cell surface receptor CD4 on target cells to initiate infection. Env is a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120), and forms trimers on the surface of the viral membrane. Using cryo-electron tomography combined with three-dimensional image classification and averaging, we report the three-dimensional structures of trimeric Env displayed on native HIV-1 in the unliganded state, in complex with the broadly neutralizing antibody b12 and in a ternary complex with CD4 and the 17b antibody. By fitting the known crystal structures of the monomeric gp120 core in the b12- and CD4/17b-bound conformations into the density maps derived by electron tomography, we derive molecular models for the native HIV-1 gp120 trimer in unliganded and CD4-bound states. We demonstrate that CD4 binding results in a major reorganization of the Env trimer, causing an outward rotation and displacement of each gp120 monomer. This appears to be coupled with a rearrangement of the gp41 region along the central axis of the trimer, leading to closer contact between the viral and target cell membranes. Our findings elucidate the structure and conformational changes of trimeric HIV-1 gp120 relevant to antibody neutralization and attachment to target cells.     

Cancer-related inflammation

The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.     

Mn_7C_3@C核壳型纳米粒子制备及其超级电容器电极特性

以甲烷作为碳源气体,块体锰作为原料,采用一种简单的直流电弧等离子体法成功制备了Mn_7C_3@C核壳型纳米粒子,用于高性能超级电容器的电极材料.所制备的Mn_7C_3@C核壳型纳米粒子平均直径为30~35nm.拉曼光谱结果显示石墨碳壳具有良好的导电性.通过循环伏安、恒电流充放电及电化学交流阻抗谱对Mn_7C_3@C核壳型纳米粒子电极材料进行电化学性能分析,结果表明其具有高比电容、快速充放电等优异的电化学性能.在扫描速率为1mV/s时,比电容最高可达185.8F/g.同时具有良好的循环稳定性,在100mV/s扫描速率下1 000次循环伏安测试后,比电容仍保持为最初的88%,与单纯Mn_7C_3(79%)相比,有明显提高.Mn_7C_3@C核壳型纳米粒子电极材料优异的电化学性能归因于其良好的核壳结构,富缺陷碳层具有良好的导电性,有助于离子的传输和结构的稳定,而内核Mn_7C_3主要产生赝电容,在C和Mn_7C_3的协同作用下产生双电层和赝电容双模式储能机制.     

Giordano Bruno and the heresy of many worlds

This paper analyses the importance of Giordano Bruno's belief in many worlds, including the Moon, the planets and the stars, in the context of his trial by the Inquisitions in Venice and Rome. Historians have claimed that this belief was not heretical and therefore was not a major factor in Bruno's trial or execution. On the contrary, by examining neglected treatises on theology, heresies and Catholic canon law, I show that the belief in many worlds was formally heretical. Multiple Christian authorities denounced it. A systematic analysis of the extant primary sources shows that Bruno's belief in many worlds was, surprisingly, of primary importance in his trial and execution. The evidence includes recent and newly discovered primary sources.     

The law of refraction and Kepler’s heuristics

Archive for History of Exact Sciences - Johannes Kepler dedicated much of his work to discover a law for the refraction of light. Unfortunately, he formulated an incorrect law. Nevertheless, it was...     

Diplecogaster tonstricula,a new species of cleaning clingfish (Teleostei: Gobiesocidae) from the Canary Islands and Senegal,eastern Atlantic Ocean,with a review of the Diplecogaster-ctenocrypta species-group

The Diplecogaster-ctenocrypta species-group is reviewed; it comprises two species. The clingfish Diplecogaster ctenocrypta from the Canary Islands is redescribed. The new species Diplecogaster tonstricula, a facultative cleaner of other teleosts, is described on the basis of eight specimens and colour photos from Senegal and the Canary Islands, eastern Atlantic Ocean. The species is small, apparently not exceeding 23 mm total length; it is characterised by having nine dorsal-fin rays, eight anal-fin rays, 24–25 pectoral-fin rays, 14–15 principal caudal-fin rays, 13–16 rakers on third gill arch, pelvic disc without lateral papillae in region A, disc region B with two rows of weak papillae, interorbital distance 4.1–4.6 in head length, distance between disc and anus 14–17% of SL, head and body with 10–13 narrow vertical brownish bars, cheek with a white ocellus surrounded by black, and with a small black spot in the middle. The new species is compared with other species of the genus; a key to the six known species of the eastern Atlantic, Mediterranean and Black Sea and South African genus Diplecogaster is presented. A checklist is provided for the species of Diplecogaster and their synonyms.