Subdistal appendages (sDAPs) are centriolar elements that are observed proximal to the distal appendages (DAPs) in vertebrates. Despite the obvious presence of sDAPs, structural and functional ...understanding of them remains elusive. Here, by combining super-resolved localization analysis and CRISPR-Cas9 genetic perturbation, we find that although DAPs and sDAPs are primarily responsible for distinct functions in ciliogenesis and microtubule anchoring, respectively, the presence of one element actually affects the positioning of the other. Specifically, we find dual layers of both ODF2 and CEP89, where their localizations are differentially regulated by DAP and sDAP integrity. DAP depletion relaxes longitudinal occupancy of sDAP protein ninein to cover the DAP region, implying a role of DAPs in sDAP positioning. Removing sDAPs alter the distal border of centrosomal γ-tubulins, illustrating a new role of sDAPs. Together, our results provide an architectural framework for sDAPs that sheds light on functional understanding, surprisingly revealing coupling between DAPs and sDAPs.
Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand.
We identified circulating, ...cell-free microRNAs as potential biomarkers using in vitro VC models in which both rat and human aortic vascular smooth muscle cells were treated with high levels of phosphate to mimic uremic hyperphosphatemia. Using an Affymetrix microRNA array, we found that miR-125b and miR-382 expression levels declined significantly as biomineralization progressed, but this decline was only observed for miR-125b in the culture medium. A time-dependent decrease in aortic tissue and serum miR-125b levels was also found in both ex vivo and in vivo renal failure models. We examined the levels of circulating, cell-free miR-125b in sera from patients with end-stage renal diseases (n=88) and found an inverse association between the severity of VC and the circulating miR-125b level, irrespective of age or mineral-related hormones (odds ratio, 0.71;
=0.03). Furthermore, serum miR-125b levels on enrollment can predict VC progression years later (for high versus low, odds ratio, 0.14;
<0.01; for the highest versus lowest tertile and middle versus lowest tertile, odds ratio, 0.55 and 0.13;
=0.3 and <0.01, respectively). The uremic VC prediction efficacy using circulating miR-125b levels was also observed in an independent cohort (n=135).
The results suggest that serum miR-125b levels are associated with VC severity and serve as a novel predictive marker for the risk of uremia-associated calcification progression.
The 1H(e,e'pi+)n cross section was measured at four-momentum transfers of Q2=1.60 and 2.45 GeV2 at an invariant mass of the photon nucleon system of W=2.22 GeV. The charged pion form factor (F(pi)) ...was extracted from the data by comparing the separated longitudinal pion electroproduction cross section to a Regge model prediction in which F(pi) is a free parameter. The results indicate that the pion form factor deviates from the charge-radius constrained monopole form at these values of Q2 by one sigma, but is still far from its perturbative quantum chromodynamics prediction.
Background
Biomarkers that can risk‐stratify children with influenza virus lower respiratory infection may identify patients for targeted intervention. Early elevation of alveolar‐related proteins in ...the bloodstream in these patients could indicate more severe lung damage portending worse outcomes.
Methods
We used a mouse model of human influenza infection and evaluated relationships between lung pathophysiology and surfactant protein D (SP‐D), SP‐A, and Club cell protein 16 (CC16). We then measured SP‐A, SP‐D, and CC16 levels in plasma samples from 94 children with influenza‐associated acute respiratory failure (PICFLU cohort), excluding children with underlying conditions explaining disease severity. We tested for associations between levels of circulating proteins and disease severity including the diagnosis of acute respiratory distress syndrome (ARDS), mechanical ventilator, intensive care unit and hospital days, and hospital mortality.
Results
Circulating SP‐D showed a greater increase than SP‐A and CC16 in mice with increased alveolar‐vascular permeability following influenza infection. In the PICFLU cohort, SP‐D was associated with moderate‐severe ARDS diagnosis (p = 0.01) and with mechanical ventilator (r = 0.45, p = 0.002), ICU (r = 0.44, p = 0.002), and hospital days (r = 0.37, p = 0.001) in influenza‐infected children without bacterial coinfection. Levels of SP‐D were lower in children with secondary bacterial pneumonia (p = 0.01) and not associated with outcomes. CC16 and SP‐A levels did not differ with bacterial coinfection and were not consistently associated with severe outcomes.
Conclusions
SP‐D has potential as an early circulating biomarker reflecting a degree of lung damage caused directly by influenza virus infection in children. Secondary bacterial pneumonia alters SP‐D biomarker performance.
碩士
國立中興大學
生物醫學研究所
100
14-3-3zeta protein is well-known in many cellular processes and has been identified as an oncogene. However, 14-3-3zeta has not been reported previously to be a secretable ...protein and its secretion involved in tumor biology is still unclear. Therefore, the objective of this study is to investigate the secretion machenism of 14-3-3zeta and its effect on lung cancer progression. First, secreted 14-3-3zeta of lung cancer cells was detected by purification of the conditioned medium. Next, an immunofluorescent staining showed that the purified GFP-tagged 14-3-3zeta was taken up and transported into the cytosol and nucleus of lung cancer cells. Uptake of secretable protein by the cells is major through endocytosis. Owing to intracellular EGFR plays an important role in lung cancer, we first examined the interaction between 14-3-3zeta and EGFR. A co-immunoprecipitation assay showed that 14-3-3zeta bound to EGFR in a highly invasive lung cancer cell line. An immunofluorescent staining also revea
7‐Aminoquinoline (7AQ) and various amino derivatives thereof (‐NHR) have been strategically designed and synthesized to study their excited‐state proton‐transfer (ESPT) properties. Due to the large ...separation between the proton donor ‐NHR and the acceptor ‐N‐ site, ESPT in 7AQ derivatives, if available, should proceed under protic solvent catalysis. ESPT is found to be influenced by the acidity of ‐NHR and the basicity of the proton‐acceptor ‐N‐ in the quinoline moiety. The latter is varied by the resonance effect at the quinoline ‐N‐ site induced by the ‐NHR substituent. For those 7AQ derivatives undergoing ESPT, increased quinoline basicity results in a faster rate of ESPT, implying that proton donation from methanol to the quinoline moiety may serve as a key step in the process. Our studies also indicate the existence of an equilibrium between cis and trans arrangements of ‐NHR in terms of its hydrogen‐bond (H‐bond) configuration with methanol, whereby only the cis‐H‐bonded form undergoes methanol‐assisted ESPT. With one exception, the interconversion between cis and trans configurations is much faster than the rate of ESPT, yielding amino‐type (normal form) and imine‐type (proton‐transfer tautomer) emissions with distinct relaxation dynamics.
Solvent‐assisted proton transfer: 7‐Aminoquinoline derivatives undergo excited‐state proton transfer (ESPT) catalyzed by methanol. An increase in quinoline basicity results in a faster rate of ESPT, implying that proton donation from methanol to the quinoline moiety may be a key step in the process.
The lack of structural information impeded the access of efficient luminescence for the exciplex type thermally activated delayed fluorescence (TADF). We report here the pump-probe Step-Scan Fourier ...transform infrared spectra of exciplex composed of a carbazole-based electron donor (CN-Cz2) and 1,3,5-triazine-based electron acceptor (PO-T2T) codeposited as the solid film that gives intermolecular charge transfer (CT), TADF, and record-high exciplex type cyan organic light emitting diodes (external quantum efficiency: 16%). The transient infrared spectral assignment to the CT state is unambiguous due to its distinction from the local excited state of either the donor or the acceptor chromophore. Importantly, a broad absorption band centered at ~2060 cm
was observed and assigned to a polaron-pair absorption. Time-resolved kinetics lead us to conclude that CT excited states relax to a ground-state intermediate with a time constant of ~3 µs, followed by a structural relaxation to the original CN-Cz2:PO-T2T configuration within ~14 µs.
A new series of molecules, T1–T4, possessing thermally activated delayed fluorescence (TADF) have been strategically designed and synthesized. Molecules T1–T4 contain the dimethyl acridine as the ...electron donor, which is linked to either symmetrical or unsymmetrical diphenyl pyrimidine as an acceptor. In comparison to the ubiquitous triazine acceptor, the selection of pyrimidine as an acceptor has advantages of facile functionalization and less stabilized unoccupied π orbitals, so that the energy gap toward the blue region can be accessed. Together with acridine donors, the resulting donor–acceptor functional materials reveal remarkable TADF properties. In the solid state, molecules T1–T4 all exhibit intriguing mechanochromism. The crystal structures, together with spectroscopy and dynamics acquired upon application of stressing, lead us to propose two types of structural arrangement that give distinct emission properties, one with and the other without TADF. Upon fabricating organic light‐emitting diodes, the T1–T4 films prepared from sublimation all exhibit dominant TADF behavior; this accounts for their high performance: an electroluminescent emission at λ=490 nm, with an external quantum efficiency of 14.2 %, can be attained when T2 is used as an emitter.
Functional pyrimidine acceptors: A new series of molecules, T1–T4, possessing thermally activated delayed fluorescence (TADF) have been strategically designed and synthesized. Together with acridine donors, the resulting donor– acceptor functional materials reveal remarkable TADF properties. In the solid state, molecules T1–T4 also exhibit intriguing mechanochromism (see figure).
In adult brain, new neurons are generated throughout adulthood in the subventricular zone and the dentate gyrus; this process is commonly known as adult neurogenesis. The regulation or modulation of ...adult neurogenesis includes various intrinsic pathways (signal transduction pathway and epigenetic or genetic modulation pathways) or extrinsic pathways (metabolic growth factor modulation, vascular, and immune system pathways). Altered neurogenesis has been identified in Alzheimer's disease (AD), in both human AD brains and AD rodent models. The exact mechanism of the dysregulation of adult neurogenesis in AD has not been completely elucidated. However, neuroinflammation has been demonstrated to alter adult neurogenesis. The presence of various inflammatory components, such as immune cells, cytokines, or chemokines, plays a role in regulating the survival, proliferation, and maturation of neural stem cells. Neuroinflammation has also been considered as a hallmark neuropathological feature of AD. In this review, we summarize current, state-of-the art perspectives on adult neurogenesis, neuroinflammation, and the relationship between these two phenomena in AD. Furthermore, we discuss the potential therapeutic approaches, focusing on the anti-inflammatory and proneurogenic interventions that have been reported in this field.
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