The multiple roles of monocyte subsets in steady state and inflammation

Monocytes participate importantly in immunity. Produced in the bone marrow and released into the blood, they circulate in blood or reside in a spleen reservoir before entering tissue and giving rise to macrophages or dendritic cells. Monocytes are more than transitional cells that adapt to a particular tissue environment indiscriminately. Accumulating evidence now indicates that monocytes are heterogeneous in several species and are themselves predetermined for particular function in the steady state and inflammation. Future therapeutics may harness this heterogeneity to target harmful functions while sparing those that are beneficial. Here, we review recent advances on the ontogeny and function of monocytes and their subsets in humans and mice.     

计算湍流的不可压缩流动 应用数学，总体和精华，第4卷

本书是“应用数学，总体和精华”数学教学改革计划的系列丛书第4卷，总体（计算数学）和精华（包括应用的分析数学）计划的总目标是：计算数学模拟的自动化（ACMM），它包括离散、优化和模拟三个自动化关键步骤，ACMM的目的是为计算机演算（CC）在科学中的大规模应用打开大门。ACMM将在开放的软件计划（FEniCS）中实现，     

Spintronics (Communication arising): Spin accumulation in mesoscopic systems

Johnson suggests that our results are not due to spin transport but rather are caused by spurious effects, in particular the anisotropic magneto resistance of the ferromagnetic contacts. However, our experiment was designed explicitly to eliminate any magneto-resistance effects that might arise from the ferromagnetic contacts.     

Introduction. Meaningfulness,Volunteers, Citizenship

This introductory article starts by describing the genesis of this special issue and the interconnection of its topics. The editors offer a variety of reading entries into the key-note articles and responses. The article reconstructs the research interests underpinning the idea of integrating meaningfulness, volunteers and citizenship. It highlights the explicit interdisciplinary design of the special issue, and shows how the key-note authors, and their respondents, weave connections between meaningfulness, volunteering and citizenship. And, finally, the editors bring the background understandings of the key-note papers to the foreground, and reconstruct a non-intentional meta-level discussion on two fundamental concepts and their interplay: self and world.     

The influence of intraperitoneal adaptation to histamine on the histamine ulcerations in the guinea-pig

Résumé Les cobyes adaptés à l'histamine par voie intrapéritonéale sont protegés contre l'ulcère de l'estomac posthistaminique.

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The work was supported by grants from the Polish Academy of Sciences.     

tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia

Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.     

Civic Meaningfulness

This paper starts from qualitative research on volunteering and citizenship, with a special focus on volunteering within a setting of restorative justice and mediation. In a first stage, the author reconstructs two models of meaningfulness as hermeneutical lenses to better understand how volunteers see their engagement and experiences as a source of meaningfulness. The paper argues that a biographical model of meaningfulness (Wolf’s theoretical framework) is in need of a complementary approach to meaningfulness (an existential model of meaningfulness), which focuses on transformational experiences with a strong existential depth. In a second stage, the paper dialogues with the experiences and narratives of the volunteers, and shows how their understanding of citizenship informs, and transforms their ideas of meaningfulness. Both the biographical and the existential approach to meaningfulness appear to be deeply influenced by the volunteers’ civic imaginaries.     

The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule

Many physiological events require transient increases in cytosolic Ca(2+) concentrations. Ryanodine receptors (RyRs) are ion channels that govern the release of Ca(2+) from the endoplasmic and sarcoplasmic reticulum. Mutations in RyRs can lead to severe genetic conditions that affect both cardiac and skeletal muscle, but locating the mutated residues in the full-length channel structure has been difficult. Here we show the 2.5?? resolution crystal structure of a region spanning three domains of RyR type 1 (RyR1), encompassing amino acid residues 1-559. The domains interact with each other through a predominantly hydrophilic interface. Docking in RyR1 electron microscopy maps unambiguously places the domains in the cytoplasmic portion of the channel, forming a 240-kDa cytoplasmic vestibule around the four-fold symmetry axis. We pinpoint the exact locations of more than 50 disease-associated mutations in full-length RyR1 and RyR2. The mutations can be classified into three groups: those that destabilize the interfaces between the three amino-terminal domains, disturb the folding of individual domains or affect one of six interfaces with other parts of the receptor. We propose a model whereby the opening of a RyR coincides with allosterically coupled motions within the N-terminal domains. This process can be affected by mutations that target various interfaces within and across subunits. The crystal structure provides a framework to understand the many disease-associated mutations in RyRs that have been studied using functional methods, and will be useful for developing new strategies to modulate RyR function in disease states.     

Myocardial infarction accelerates atherosclerosis

During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.