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1.
Nat Commun ; 11(1): 319, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949159

RESUMO

Optimal functioning of neuronal networks is critical to the complex cognitive processes of memory and executive function that deteriorate in Alzheimer's disease (AD). Here we use cellular and animal models as well as human biospecimens to show that AD-related stressors mediate global disturbances in dynamic intra- and inter-neuronal networks through pathologic rewiring of the chaperome system into epichaperomes. These structures provide the backbone upon which proteome-wide connectivity, and in turn, protein networks become disturbed and ultimately dysfunctional. We introduce the term protein connectivity-based dysfunction (PCBD) to define this mechanism. Among most sensitive to PCBD are pathways with key roles in synaptic plasticity. We show at cellular and target organ levels that network connectivity and functional imbalances revert to normal levels upon epichaperome inhibition. In conclusion, we provide proof-of-principle to propose AD is a PCBDopathy, a disease of proteome-wide connectivity defects mediated by maladaptive epichaperomes.

2.
Anesthesiology ; 132(2): 357-372, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31939851

RESUMO

BACKGROUND: Prolonged endoplasmic reticulum stress has been identified in various diseases. Inflammatory mediators, which have been shown to induce endoplasmic reticulum stress in several studies, have been suggested to serve as the important modulators in pain development. In this study, the authors hypothesized that the endoplasmic reticulum stress triggered by inflammatory mediators contributed to pain development. METHODS: The authors used a male mouse model of bone cancer pain. The control mice were intrathecally injected with tumor necrosis factor-α (TNF-α) and lipopolysaccharide, the bone cancer pain mice were intrathecally injected with the endoplasmic reticulum stress inhibitors 4-PBA and GSK2606414. The nociceptive behaviors, endoplasmic reticulum stress markers, and inflammatory mediators were assessed. RESULTS: Increased expression of the p-RNA-dependent protein kinase-like endoplasmic reticulum kinase and p-eukaryotic initiation factor 2α were found in the spinal neurons during bone cancer pain, along with upregulation of inflammatory mediators (TNF-α, interleukin 1ß, and interleukin 6). Intrathecal administration of TNF-α or lipopolysaccharide increased the expression of endoplasmic reticulum stress markers in control mice. Inhibition of endoplasmic reticulum stress by intrathecal administration of 4-PBA (baseline vs. 3 h: 0.34 ± 0.16 g vs. 1.65 ± 0.40 g in paw withdrawal mechanical threshold, 8.00 ± 1.20 times per 2 min vs. 0.88 ± 0.64 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) or GSK2606414 (baseline vs. 3 h: 0.37 ± 0.08 g vs. 1.38 ± 0.11 g in paw withdrawal mechanical threshold, 8.00 ± 0.93 times per 2 min vs. 3.25 ± 1.04 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) showed time- and dose-dependent antinociception. Meanwhile, decreased expression of inflammatory mediators (TNF-α, interleukin 1ß, and interleukin 6), as well as decreased activation of astrocytes in the spinal cord, were found after 4-PBA or GSK2606414 treatment. CONCLUSIONS: Inhibition of inflammatory mediator-triggered endoplasmic reticulum stress in spinal neurons attenuates bone cancer pain via modulation of neuroinflammation, which suggests new approaches to pain relief.

3.
Thromb Haemost ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31940677

RESUMO

BACKGROUND: Western guidelines recommend an international normalized ratio (INR) range of 2 to 3 when using warfarin for stroke prevention in atrial fibrillation (AF), but lower INR ranges are frequently used in East Asia. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) in AF patients comparing the effect of lower versus standard INR targets on thromboembolism, major bleeding, and mortality. METHODS: We searched Western databases including Cochrane CENTRAL, Medline, and Embase as well as Chinese databases including SinoMed, CNKI, and Wanfang Data. We pooled risk ratios (RRs) using random-effects model. We grouped INR targets in two ways: (1) any study-specific lower versus standard targets and (2) INR ranges of approximately 1.5 to 2 versus 2 to 3. RESULTS: Seventy-nine RCTs (n = 12,928) met eligibility criteria: 74 (n = 11,322) from East Asia and 5 (n = 1,606) from Western countries. Compared with standard targets, lower INR ranges were associated with higher rates of thromboembolism (76 RCTs, n = 12,577: 7.1% vs. 4.4%, RR 1.50, 95% confidence interval [CI] 1.29-1.74, I 2 = 0%), lower rates of major bleeding (61 RCTs, n = 10,815: 2.2% vs. 4.4%, RR 0.54, 95% CI 0.44-0.67, I 2 = 0%), and similar mortality (32 RCTs, n = 7,327: 4.8% vs. 5.2%, RR 1.00, 95% CI 0.85-1.19, I 2 = 0%). Results were similar when comparing target ranges of approximately 1.5 to 2 versus 2 to 3. CONCLUSION: Moderate quality evidence suggests lower INR targets reduce bleeding but increase thromboembolism in AF. The data are dominated by East-Asian studies, limiting generalizability to Western populations. Until higher quality data demonstrate otherwise, an INR range of 2 to 3 should remain standard for thromboembolic prophylaxis in AF.

4.
6.
J Agric Food Chem ; 2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31927923

RESUMO

Fat deposition is one of the most important economic traits of pigs. Decreasing the subcutaneous fat (SC) and increasing the intramuscular fat (IM) are believed to be an effective way to improve pork quality, which is one of the main goals of pig breeding. Identifying key genes that control porcine lipid metabolism is essential for achieving this goal. Apolipoprotein R (apoR) was identified as the crucial molecule in the process of pig adipose reduction by clenbuterol. In this study, transgenic mice with adipose tissue-specific over-expression of pig apoR (apoR mice) were constructed. The apoR mice gained less weight than wild-type (WT) mice after 18 weeks of feeding a high-fat diet. A comparison of organs between the two genotypes revealed that the weight of white adipose tissue, including inguinal (IWAT) and epididymal fat tissue (EWAT), was significantly decreased and the weight of liver tissue was increased in apoR mice compared with WT mice. Glucose and insulin intolerance tests showed that the glucose metabolism of apoR mice was similar to that of WT mice. Histological staining proved that the adipocytes of apoR mice had a reduced average size, and gene expression analysis indicated that lipolysis in the adipose tissue of apoR mice was enhanced. Finally, primary culture of inguinal adipocytes revealed that apoR promotes lipolysis via the Erk1/2 pathway. Taken together, the results indicate that adipose tissue-specific expression of pig apoR protects mice from diet-induced obesity by enhancing lipolysis.

7.
J Environ Sci (China) ; 87: 205-212, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791493

RESUMO

This study aims to investigate the effect of a magnetic field on nitrous oxide (N2O) emission from a sequencing batch reactor treating low-strength domestic wastewater at low temperature (10°C). After running for 124 days in parallel, results indicated that the conversion rate of N2O for a magnetic field-sequencing batch reactor (MF-SBR) decreased by 34.3% compared to that of a conventional SBR (C-SBR). Meanwhile, the removal efficiencies for total nitrogen (TN) and ammonia nitrogen (NH4-N) of the MF-SBR were 22.4% and 39.5% higher than those of the C-SBR. High-throughput sequencing revealed that the abundances of AOB (Nitrosomonas), NOB (Nitrospira) and denitrifiers (Zoogloea), which could reduce N2O to N2, were promoted significantly in the MF-SBR. Enzyme activities (Nir) and gene abundances (nosZ nirS and nirK) for denitrification in the MF-SBR were also notably higher compared to C-SBR. Our study shows that application of a magnetic field is a useful approach for inhibiting the generation of N2O and promoting the nitrogen removal efficiency by affecting the microbial characteristics of sludge in an SBR treating domestic wastewater at low temperature.


Assuntos
Reatores Biológicos , Campos Magnéticos , Óxido Nitroso/análise , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias , Temperatura Baixa , Desnitrificação , Nitrificação , Nitrogênio , Nitrosomonas
8.
Sci Rep ; 9(1): 18321, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797961

RESUMO

The novel methods for efficient plant regeneration via direct somatic embryogenesis (SE) and SE-mediated transformation system under high concentration of NAA in Ranunculus sceleratus were established. On MS media containing a high concentration of NAA (10.0 mg/L) in the dark, all inoculated explants (root, stem and leaf) formed somatic embryos at high frequencies, respectively, 66.03, 126.47 and 213.63 embryoids per explant, and 100% of the embryoids developed into plantlets on 1/2 MS rooting media. Morphological and histological analyses revealed that SE in R. sceleratus followed a classical pattern. All inoculated explants can be used as receptors for genetic transformation in R. sceleratus, through direct SE-mediated method after Agrobacterium infection. RcLEC1-B, as a marker gene, changed the number and morphology of flower organs and the development of cuticle in R. sceleratus, which indicated that the efficient transgenic system of R. sceleratus was established. To our knowledge, this is the first observation that both direct SE and transgenic transformation system, via induction of a single plant growth regulator, have been successfully constructed in R. sceleratus.

9.
Org Lett ; 21(23): 9425-9429, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31810112

RESUMO

A simple and efficient method for the synthesis of isoquinolone and isocoumarin derivatives is reported. The method for the first time provides a one-step divergent synthesis of important isoquinolone and isocoumarin skeletons from benzoic acid by switching the coupling partners. In addition, a reliable mechanism has been proposed on the basis of experimental investigations, including kinetic isotope effect experiments, 13C labeling experiments, time-tracking experiments, and competitive experiments, as well as DFT calculation studies.

10.
Aging Dis ; 10(6): 1233-1245, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788335

RESUMO

Autophagy is a lysosome-dependent cellular catabolic mechanism that mediates the turnover of dysfunctional organelles and aggregated proteins. It has a neuroprotective role on neurodegenerative diseases. Here, we hypothesized that autophagy may also have a neuroprotective role in diabetes-associated cognitive decline (DACD). In current study, we found that db/db mice display cognitive decline with inferior learning and memory function. The accumulation of ß-amyloid1-42 (Aß1-42), which is a characteristic of Alzheimer's disease (AD), was markedly higher in the prefrontal cortex (PFC), cornu ammon1 (CA1), and dentate gyrus (DG) areas of the hippocampus in db/db mice. Moreover, BDNF and microtubule associated protein 2 (MAP2) levels were lower in the hippocampus of db/db mice. However, there was no noticeable differences in the level of apoptosis in the hippocampus between control (CON) mice and db/db mice. Markers of autophagy in the hippocampus were elevated in db/db mice. The expression levels of ATG5, ATG7, and LC3B were higher, and the level of P62 was lower. An autophagy inhibitor, 3-MA, and ATG7 siRNA significantly reversed the activation of autophagy in vitro, which was accompanied with a higher level of apoptosis. Taken together, our current study suggests that diabetes is associated with cognitive decline, and activation of autophagy has a neuroprotective role in DACD.

11.
Nanoscale Res Lett ; 14(1): 360, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792627

RESUMO

Hybrid heterojunctions based on two-dimensional (2D) and conventional three-dimensional (3D) materials provide a promising way toward nanoelectronic devices with engineered features. In this work, we investigated the band alignment of a mixed-dimensional heterojunction composed of transferred MoS2 on ß-Ga2O3([Formula: see text]01) with and without nitridation. The conduction and valence band offsets for unnitrided 2D-MoS2/3D-ß-Ga2O3 heterojunction were determined to be respectively 0.43 ± 0.1 and 2.87 ± 0.1 eV. For the nitrided heterojunction, the conduction and valence band offsets were deduced to 0.68 ± 0.1 and 2.62 ± 0.1 eV, respectively. The modified band alignment could result from the dipole formed by charge transfer across the heterojunction interface. The effect of nitridation on the band alignments between group III oxides and transition metal dichalcogenides will supply feasible technical routes for designing their heterojunction-based electronic and optoelectronic devices.

12.
Exp Neurol ; 324: 113138, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31794745

RESUMO

After spinal cord injury (SCI), the inhibitory molecules derived from scars at the lesion sites and the limited regenerative capacity of neuronal axons pose difficulties for the recovery after SCI. Remodeling of cytoskeleton structures including microtubule assembly and tubulin post-translational modification are widely accepted to play a crucial role in initiation of growth cone and regrowth of injured axon. Although increasing studies have focused on the association between tubulin acetylation and autophagy due to the role of tubulin acetylation in organelles and substances transport, there are no studies exploring the effect of tubulin acetylation on autophagy after spinal cord injury (SCI). Here, we found that histone deacetylase 6 (HDAC6) was significantly up-regulated after SCI, while inhibition of HDAC6 by Tubastatin A induced functional recovery after SCI. In view of enzyme-dependent and -independent mechanisms of HDAC6 to adjust diverse cellular processes, such as autophagy, the ubiquitin proteasome system and post-translational modification of tubulin, we mainly focused on the significance of HDAC6 in axonal regeneration and autophagy after SCI. Western blotting, Co-immunoprecipitation and immunofluorescence staining were conducted to showed that Tubastatin A treatment in nocodazole-treated cells and mice suffering from SCI prompted acetylation and stabilization of microtubules and thus restored transport function, which may contribute to restored autophagic flux and increased axonal length. Whereas inhibition of degradation of autolysosomes by bafilomycin A1 (Baf-A1) reversed functional recovery caused by Tubastatin A, revealing the association between tubulin acetylation and autophagy, which supports HDAC6 inhibition as a potential target for SCI treatment.

13.
Nano Lett ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31804841

RESUMO

The inertness of the graphene basal plane has notably limited its viable chemical modification pathways. We report direct azidation and subsequent click chemistry of the graphene basal plane through the electrochemical oxidation of an aqueous sodium azide solution at the graphene surface. An ∼20% nitrogen-to-carbon ratio is achieved for monolayer graphene under ambient conditions and neutral pH, and the degree of functionalization is tunable through the applied voltage. The functionalized azide groups enable both copper-catalyzed and copper-free alkyne cycloaddition click chemistry, as well as subsequent bioconjugation, and fluorescence microscopy indicates uniform functionalization across the graphene surface. Notably, we find that as the azidation, cycloaddition, and bioconjugation processes substantially shift the graphene doping level, high electrical conductivity and carrier mobility are maintained throughout the different functionalization states. By integrating the electrochemical azidation scheme with electrochemical exfoliation, we further demonstrate one-step bulk production of azidated graphene flakes from graphite. We thus open a new door to the facile preparation of diverse graphene derivatives under ambient conditions.

14.
Cancer Cell Int ; 19: 295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807117

RESUMO

The potent pleiotropic lipid mediator sphingosine-1-phosphate (S1P) participates in numerous cellular processes, including angiogenesis and cell survival, proliferation, and migration. It is formed by one of two sphingosine kinases (SphKs), SphK1 and SphK2. These enzymes largely exert their various biological and pathophysiological actions through one of five G protein-coupled receptors (S1PR1-5), with receptor activation setting in motion various signaling cascades. Considerable evidence has been accumulated on S1P signaling and its pathogenic roles in diseases, as well as on novel modulators of S1P signaling, such as SphK inhibitors and S1P agonists and antagonists. S1P and ceramide, composed of sphingosine and a fatty acid, are reciprocal cell fate regulators, and S1P signaling plays essential roles in several diseases, including inflammation, cancer, and autoimmune disorders. Thus, targeting of S1P signaling may be one way to block the pathogenesis and may be a therapeutic target in these conditions. Increasingly strong evidence indicates a role for the S1P signaling pathway in the progression of cancer and its effects. In the present review, we discuss recent progress in our understanding of S1P and its related proteins in cancer progression. Also described is the therapeutic potential of S1P receptors and their downstream signaling cascades as targets for cancer treatment.

15.
Ann Transl Med ; 7(20): 521, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807503

RESUMO

Background: One of the largest challenges in endoscopic surgical training is adapting to a two-dimensional (2D) view. The glasses-free three-dimensional (GF-3D) display system was designed to integrate the merits of both 2D and conventional 3D (C-3D) displays, allowing surgeons to perform video-assisted endoscopic surgery under a stereoscopic view without heavy and cumbersome 3D glasses. Methods: In this study, 15 junior thoracic surgeons were divided to test one routine and one complex task three times each via traditional high-definition 2D (HD-2D) and GF-3D to determine whether there was any advantage when using the GF-3D system to acquire endoscopic skills. The duration, numbers of stitches, and distance between every two stitches were recorded for every procedure. Results: Seven participants were enrolled in the HD-2D group and eight participants were enrolled in the GF-3D group. All 15 participants successfully completed porcine skin continuous suture and tracheal continuous anastomosis procedures three times each. For skin continuous suture, there was no significant difference between the two groups in terms of the learning curve for speed (P=0.683) and accuracy (P=0.556). For tracheal continuous anastomosis, there was a significant difference between the two groups in terms of the learning curve for speed (P=0.001), but no significant difference was observed between the two groups in terms of the learning curve for accuracy (P=0.211). Conclusions: In summary, both HD-2D and GF-3D display systems are efficient for routine and complex endoscopic surgery. With the help of GF-3D, surgeons can acquire new complex endoscopic skills faster than HD-2D and be free from burdensome polarized glasses. More comparative studies in a clinical setting are needed to further explore the feasibility, necessity, and economic aspects of the GF-3D display system.

16.
Stem Cell Res Ther ; 10(1): 378, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823825

RESUMO

BACKGROUND: Magnesium (Mg2+)-enriched microenvironment promotes odontogenic differentiation in human dental pulp stem cells (DPSCs), but the regulatory mechanisms remain undefined. The aim of this work was to assess magnesium's function in the above process and to explore the associated signaling pathway. METHODS: DPSCs underwent culture in odontogenic medium with the addition of 0, 1, 5, or 10 mM MgCl2. Intracellular Mg2+ levels in DPSCs were evaluated flow cytometrically using Mag-Fluo-4-AM. Mg2+-entry was inhibited by TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB). RNA-Sequencing was carried out for assessing transcriptome alterations in DPSCs during odontogenic differentiation associated with high extracellular Mg2+. KEGG pathway analysis was performed to determine pathways related to the retrieved differentially expressed genes (DEGs). Immunoblot was performed for assessing magnesium's role and exploring ERK/BMP2/Smads signaling. RESULTS: Mg2+-enriched microenvironment promoted odontogenic differentiation in DPSCs via intracellular Mg2+ increase. Consistently, the positive effect of high extracellular Mg2+ on odontogenic differentiation in DPSCs was blocked by 2-APB, which reduced Mg2+ entry. RNA-sequencing identified 734 DEGs related to odontogenic differentiation in DPSCs in the presence of high extracellular Mg2+. These DEGs participated in many cascades such as MAPK and TGF-ß pathways. Consistently, ERK and BMP2/Smads pathways were activated in DPSCs treated with high extracellular Mg2+. In agreement, ERK signaling inhibition by U0126 blunted the effect of high extracellular Mg2+ on mineralization and odontogenic differentiation in DPSCs. Interestingly, BMP2, BMPR1, and phosphorylated Smad1/5/9 were significantly decreased by U0126, indicating that BMP2/Smads acted as downstream of ERK. CONCLUSIONS: Mg2+-enriched microenvironment promotes odontogenic differentiation in DPSCs by activating ERK/BMP2/Smads signaling via intracellular Mg2+ increase. This study revealed that Mg2+-enriched microenvironment could be used as a new strategy for dental pulp regeneration.

17.
Int J Nanomedicine ; 14: 9631-9645, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824156

RESUMO

Background: Photothermal therapy (PTT) has great potential in the clinical treatment of tumors. However, most photothermal materials are difficult to apply due to their insufficient photothermal conversion efficiencies (PCEs), poor photostabilities and short circulation times. Furthermore, tumor recurrence is likely to occur using PTT only. In the present study, we prepared cyclo (Arg-Gly-Asp-d-Phe-Cys) [c(RGD)] conjugated doxorubicin (DOX)-loaded Fe3O4@polydopamine (PDA) nanoparticles to develop a multifunctional-targeted nanocomplex for integrated tumor diagnosis and treatment. Materials and methods: Cytotoxicity of Fe3O4@PDA-PEG-cRGD-DOX against HCT-116 cells was determined by cck-8 assay. Cellular uptake was measured by confocal laser scanning microscope (CLSM). Pharmacokinetic performance of DOX was evaluated to compare the differences between free DOX and DOX in nanocarrier. Performance in magnetic resonance imaging (MRI) and antitumor activity of complex nanoparticles were evaluated in tumor-bearing nude mice. Results: Fe3O4@PDA-PEG-cRGD-DOX has a particle size of 200-300 nm and a zeta potential of 22.7 mV. Further studies in vitro and in vivo demonstrated their excellent capacity to target tumor cells and promote drug internalization, and significantly higher cytotoxicity with respect to that seen in a control group was shown for the nanoparticles. In addition, they have good thermal stability, photothermal conversion efficiencies (PCEs) and pH responsiveness, releasing more DOX in a mildly acidic environment, which is very conducive to their chemotherapeutic effectiveness in the tumor microenvironment. Fe3O4@PDA-PEG-cRGD-DOX NPs were used in a subcutaneous xenograft tumor model of nude mouse HCT-116 cells showed clear signal contrast in T2-weighted images and effective anti-tumor chemo-photothermal therapy under NIR irradiation. Conclusion: According to our results, Fe3O4@PDA-PEG-cRGD-DOX had a satisfactory antitumor effect on colon cancer in nude mice and could be further developed as a potential integrated platform for the diagnosis and treatment of cancer to improve its antitumor activity against colon cancer.

18.
Cell Mol Neurobiol ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31828466

RESUMO

Neurodegenerative diseases all share several common features such as involvement of oxidative damage and mitochondrial dysfunction in pathogenesis. Oxidative stress induced by overproduction of mitochondrial reactive oxygen species (ROS) or impairment of the antioxidant deficiency results in mitochondrial dysfunction and initiation of the cell death cascade. Berberine (BBR), a traditional Chinese medicine, has been reported to exert anti-oxidative stress and anti-apoptosis effect in CNS diseases. However, the mechanism of BBR on regulating mitophagy and protecting mitochondrial function under oxidative stress remains unclear. In present study, we evaluated the beneficial effects of BBR on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity. Furthermore, we explored the protective role of BBR in mitochondrial function and mitophagy under oxidative stress in PC-12 cells. Our results demonstrated that BBR effectively inhibited t-BHP-induced apoptosis which is associated with the decreased leakage of lactate dehydrogenase (LDH) and ROS overproduction. Moreover, BBR significantly suppressed cytochrome c expression, upregulated the ratio of Bcl-2/Bax, and ameliorated mitochondrial dysfunction by optimizing mitochondria membrane potential (ΔΨm) status and ATP production. In addition, BBR reduced the expression of autophagy-specific marker LC3, SQTM1/p62, and maintained lysosome normal function which involved the restoration of upstream signaling pathway AKT and mTOR phosphorylation level. Collectively, these findings suggested that BBR protects PC-12 cells from oxidative injury through inhibiting ROS level, mitochondria dysfunction, and mitophagy via PI3K/AKT/mTOR signaling pathways, which suggest a potential therapeutic strategy for oxidative stress and neurotoxic damages.

19.
Elife ; 82019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829937

RESUMO

Conserved proteins drive clathrin-mediated endocytosis (CME), which from yeast to humans involves a burst of actin assembly. To gain mechanistic insights into this process, we performed a side-by-side quantitative comparison of CME in two distantly related yeast species. Though endocytic protein abundance in S. pombe and S. cerevisiae is more similar than previously thought, membrane invagination speed and depth are two-fold greater in fission yeast. In both yeasts, accumulation of ~70 WASp molecules activates the Arp2/3 complex to drive membrane invagination. In contrast to budding yeast, WASp-mediated actin nucleation plays an essential role in fission yeast endocytosis. Genetics and live-cell imaging revealed core CME spatiodynamic similarities between the two yeasts, although the assembly of two zones of actin filaments is specific for fission yeast and not essential for CME. These studies identified conserved CME mechanisms and species-specific adaptations with broad implications that are expected to extend from yeast to humans.

20.
Epidemiol Infect ; 147: e325, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31858924

RESUMO

Influenza activity is subject to environmental factors. Accurate forecasting of influenza epidemics would permit timely and effective implementation of public health interventions, but it remains challenging. In this study, we aimed to develop random forest (RF) regression models including meterological factors to predict seasonal influenza activity in Jiangsu provine, China. Coefficient of determination (R2) and mean absolute percentage error (MAPE) were employed to evaluate the models' performance. Three RF models with optimum parameters were constructed to predict influenza like illness (ILI) activity, influenza A and B (Flu-A and Flu-B) positive rates in Jiangsu. The models for Flu-B and ILI presented excellent performance with MAPEs <10%. The predicted values of the Flu-A model also matched the real trend very well, although its MAPE reached to 19.49% in the test set. The lagged dependent variables were vital predictors in each model. Seasonality was more pronounced in the models for ILI and Flu-A. The modification effects of the meteorological factors and their lagged terms on the prediction accuracy differed across the three models, while temperature always played an important role. Notably, atmospheric pressure made a major contribution to ILI and Flu-B forecasting. In brief, RF models performed well in influenza activity prediction. Impacts of meteorological factors on the predictive models for influenza activity are type-specific.

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