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Dynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied. The extracellular cues controlling cilia disassembly remain elusive, however. Here, we show that lysophosphatidic acid (LPA), a multifunctional bioactive phospholipid, acts as a physiological extracellular factor to initiate cilia disassembly and promote neurogenesis. Through systematic analysis of serum components, we identify a small molecular—LPA as the major driver of cilia disassembly. Genetic inactivation and pharmacological inhibition of LPA receptor 1 (LPAR1) abrogate cilia disassembly triggered by serum. The LPA-LPAR-G-protein pathway promotes the transcription and phosphorylation of cilia disassembly factors-Aurora A, through activating the transcription coactivators YAP/TAZ and calcium/CaM pathway, respectively. Deletion of Lpar1 in mice causes abnormally elongated cilia and decreased proliferation in neural progenitor cells, thereby resulting in defective neurogenesis. Collectively, our findings establish LPA as a physiological initiator of cilia disassembly and suggest targeting the metabolism of LPA and the LPA pathway as potential therapies for diseases with dysfunctional ciliogenesis., Dynamic assembly and disassembly of primary cilia is critical for tissue development and homeostasis. Here the authors identify lysophosphatidic acid (LPA) as a physiological extracellular factor that initiates cilia disassembly through both YAP/TAZ mediated transcription and calcium/calmodulin mediated activation of Aurora A.

The internal circadian rhythm is controlled by the central pacemaker in the hypothalamic suprachiasmatic nucleus (SCN). SCN drives coherent and synchronized circadian oscillations via intercellular coupling, which are resistant to environmental perturbations. Here we report that primary cilium is a critical device for intercellular coupling among SCN neurons and acts as a gatekeeper to maintain the internal clock in mice. A subset of SCN neurons, namely neuromedin S-producing (NMS) neurons, exhibit cilia dynamics with a pronounced circadian rhythmicity. Genetic ablation of ciliogenesis in NMS neurons enables a rapid phase shift of the internal clock under experimental jet lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lose their coherence following external perturbations. Rhythmic cilia dynamics drive oscillations of Sonic Hedgehog (Shh) signaling and oscillated expressions of multiple circadian genes in SCN neurons. Genetic and chemical inactivation of Shh signaling in NMS neurons phenocopies the effect of cilia ablation. Our findings establish ciliary signaling as a novel interneuronal coupling mechanism in the SCN and may lead to novel therapy of circadian disruption-linked diseases.One-Sentence SummaryRhythmic cilium is a critical device for intercellular coupling among SCN neurons and acts as gatekeeper for the internal clock.

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110–CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110–CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.

The aim of the present study was to investigate the potential of the Immuknow immune cell function assay for the diagnosis of infection after pediatric living-donor liver transplantation (LDLT). Based on clinical data obtained following liver transplantation, 66 patients were divided into infection (n=28) and non-infection (n=38) groups. The following factors were considered in the present analysis: Primary disease, lymphocyte count, tacrolimus plasma concentration/dose (C0/D) ratio, CD4+ T lymphocyte ATP levels, at pre-transplant stage and at weeks 1-4, and 2 and 3 months post-transplant. The CD4+ T lymphocyte ATP values were plotted in a receiver operating characteristic (ROC) curve. The CD4+ T lymphocyte ATP value of the infection group was significantly lower compared with that of the non-infection group (188.6±93.5 vs. 424.4±198.1 ng/ml, respectively; P

Freestanding FeCrAl-Y2O3 amorphous/crystalline composite coating with a thickness of about 200μm has been produced from electron-beam physical vapor deposition of FeCrAl and yttria materials with a substrate temperature of 500 oC around. The microstructure was composed of columnar grains near the substrate side and an amorphous top layer. Local crystallization occurred during room temperature preservation. It is inferred that the crystallization activation energy of the material is very low.

As a rapid deposition method, Electron Beam Physical Vapor Deposition (EBPVD) permits the fast fabrication of self-standing thick coatings with thickness in the range from several micrometers to hundreds of micrometers. In this paper, we present a new way to fabricate ferritic ODS alloy foil. By this method, 1.2 wt.% of yttria was successfully added to the ferritic base material. The base alloys are mainly composed of bcc structured Fe (Cr,Al) solid solution. The steady state creep rate of ferritic ODS is almost two magnitudes lower than that of FeCrAl alloy. Further thermo-mechanical treatment is expected to improve strength and ductility of both ODS and non-ODS material.

Large-size Ni-based alloy sheet was prepared by electron beam physical vapor deposition (EB-PVD). Thickness uniformity of large-size sheet for application is important. Based on the Knudsen’s cosine law and the character of the evaporation during EB-PVD, thickness distribution model of condensate on rotary substrate by EB-PVD was established. The thickness model is not consistent with the traditional cosine law, but cosnθ relationship, n=5.3 in this paper. The predicted data of thickness model agrees well with the measured data. The thickness distribution model is not limited to specific vapor source material, therefore, it provides significant insight on the thickness distribution profile for film, coating and sheet deposited on the rotary substrate by EB-PVD.

Steel bar corrosion monitoring is a very important part of structure health monitoring and full-life design in civil engineering. Many electrochemical methods have been developed in the last decades for corrosion research, but for field corrosion, pulse perturbation is the fast method. The corrosion of Q235 carbon steel in cement mortar has been researched by potentiostatic pulse method. The solution resistance Rs, the polarization resistance Rp, capacity of double layer and time constant have got by cure fitting. The amplitude of voltage perturbation affected the accurate of result little. The polarization resistance decreases with increasing temperature.

Large scale Ni-based alloy sheets are prepared by electron beam physical vapor deposition with and without tungsten added into melting pools respectively. Addition W increased vapor rate and decreased compositional transformation during deposition. Chemical constitution of the sheet prepared through tungsten is more similar to that of the ingot. Microstructure of two alloy sheets is observed by scanning electron microscope (SEM) and atom force microscope (AFM). The results show that both of the sheets consist of columnar grains, whose major axes are almost parallel to the normal direction of the sheet. However, the average diameter of grains of the sheet through tungsten is larger than that of the sheet not through tungsten in minor axis direction. Mechanical properties and failure mechanisms of both sheets are studied. Tensile tests are conducted on a number of specimens. Strength, strain-to-failure are estimated under loading condition. The results show that the sheet prepared by EB-PVD through tungsten has a superior strength and an elongation percentage than that of the one prepared without tungsten.

Large-sized Fe-based ODS (Oxide Dispersive Strengthen) high-temperature alloy sheets were successfully synthesized by EBPVD (Electron Beam Physical Vapor Deposition) technique. The sheets were about 120μm thick, and having a diameter of 1000mm, whose surface roughness was less than 1μm (Ra