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1.
Protein Expr Purif ; 178: 105783, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33122138

RESUMO

Natural killer (NK) cells are potent cytotoxic effector cells of the innate immune system and play an important role in tumor immunosurveillance and control. NKG2D is an activating receptor of NK cells. The NKG2D receptor-ligand system has contributed to immune cells recognizing tumor cells and the tumor microenvironment. In order to stretch the application of NK cells on adoptive immunotherapy for B-cell malignancies, we designed and produced a novel bispecific ULBP1×CD19-scFv fusion protein, in which the extracellular domain of NKG2D ligand ULBP1 was fused to a single chain variable fragment (scFv) of anti-CD19. The vector expressing ULBP1×CD19-scFv protein was constructed and expressed in Pichia pastoris. Effects of medium composition, concentration of methanol as the inducer, induction time and broth content in shake flask on the expression of the recombinant protein were investigated. The results showed that the optimized conditions for ULBP1×CD19-scFv expression were 1% methanol induction for 96 h with 15% broth content. The secreted recombinant protein was purified using ammonium sulfate fractionation and Ni-NTA affinity chromatography and the purity is about 93%. The cytotoxicity of NK92-MI cells against CD19+ Raji cells was enhanced in the presence of purified ULBP1×CD19-scFv protein. These results indicated that ULBP1 could be used as an activating element of bispecific killer engagers (BiKEs) and Pichia pastoris yeast might be an alternative expression host for BiKEs production.

2.
Int J Biol Macromol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33157139

RESUMO

Alpha-fetoprotein (AFP) is one of the most important biomarkers associated with primary liver cancer, and the main approaches for diagnosis are based on immunoassay. Affibody is a 58 amino acids peptide derived from the Z domain of staphylococcal protein A and generally applied in imaging diagnosis, clinical therapeutics and biotechnology research. The aim of this study was therefore to develop a novel affibody-based ELISA for detection of AFP. After three rounds of biopanning, six AFP-binding affibody peptides were selected using phage display technology, among them affibody ZAFPD2 showed high and specific binding affinity to AFP. An affibody dimer of ZAFPD2 was created, named (ZAFP D2)2, expressed in E.coli and the purified (ZAFP D2)2 recombinant protein showed higher binding affinity to AFP, as well as high thermal stability. A novel affibody-based two-site ELISA method using ZAFPD2 or (ZAFP D2)2 and polyclonal antibody to detect AFP was developed, the detection limit of the immunoassay using (ZAFP D2)2 was 2 ng mL-1 that was 4 times lower than ZAFPD2, which meets the requirements for practical application. Therefore, this concept of affibody-based ELISA may provide a new method for the detection of various cancer biomarkers.

3.
Am J Surg Pathol ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33177339

RESUMO

Lung cancer screening has improved mortality among high-risk smokers but has coincidentally detected a fraction of nonprogressive adenocarcinoma historically classified as bronchoalveolar carcinoma (BAC). In the National Lung Screening Trial (NLST) the majority of BAC-comprising 29% of computed tomography-detected stage I lung adenocarcinoma-were considered overdiagnosis after extended follow-up comparison with the control arm. In the current classification, adenocarcinoma in situ and minimally invasive adenocarcinoma have replaced BAC but together comprise only ∼5% of stage I lung adenocarcinoma. Lepidic and subsets of papillary and acinar adenocarcinoma also infrequently recur. We, therefore, propose criteria for low malignant potential (LMP) adenocarcinoma among nonmucinous adenocarcinoma measuring ≤3 cm in total, exhibiting ≥15% lepidic growth, and lacking nonpredominant high-grade patterns (≥10% cribriform, ≥5% micropapillary, ≥5% solid), >1 mitosis per 2 mm, angiolymphatic or visceral pleural invasion, spread through air spaces or necrosis. We tested these criteria in a multi-institutional cohort of 328 invasive stage I (eighth edition) and in situ adenocarcinomas and observed 16% LMP and 7% adenocarcinoma in situ/minimally invasive adenocarcinoma which together (23%) approximated the frequency of overdiagnosed stage I BAC in the NLST. The LMP group had 100% disease-specific survival. The proposed LMP criteria, incorporating multiple histologic parameters, may be a clinically useful "low-grade" prognostic group. Validation of these criteria in additional retrospective cohorts and prospective screen-detected cohorts should be considered.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33139019

RESUMO

Hydrogen peroxide (H2O2) is a significant biomarker in physiological processes. Abnormal levels of H2O2 are considered to be closely related to some acute diseases. Therefore, it is important to monitor the H2O2 levels in bio-samples. Herein, we present a novel non-enzymatic electrochemical H2O2 sensor based on the excellent electrocatalytic performance of a composite comprising Zn-Cr-Co ternary spinel metal oxide nanodots (ZnCrCoO4) anchored on the surface of nitrogen-doped carbon nanotubes (NCNTs), denoted as ZnCrCoO4/NCNTs, toward H2O2 reduction. ZnCrCoO4/NCNTs were synthesized using a facile one-pot hydrothermal strategy. The enhanced electrocatalytic performance of ZnCrCoO4 is resulted from the partial substitution of Co in spinel zinc cobaltate (ZnCo2O4) with Cr, which modifies the CoO electronic structure and enhances electroconductivity. The ZnCrCoO4/NCNTs-based H2O2 sensor exhibited a wide quantitative detection range from 1 to 7330 µM with a detection limit of 1 µM. The sensor showed excellent reproducibility and selectivity for H2O2 sensing. In addition, remarkable recoveries were obtained for H2O2-spiked fish serum samples. These results demonstrated that the as-developed sensor has a great potential in monitoring H2O2 levels in practical applications.

5.
J Cell Physiol ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33135190

RESUMO

Lung cancer is the leading cause of cancer death worldwide. Although diagnostic methods and targeted drugs have been rapidly developed in recent years, the underlying molecular mechanisms in the pathogenesis of lung cancer remain enigmatic. The N6-methyladenosine (m6 A) modification is the most common modification of messenger RNA in eukaryotes and plays critical roles in many diseases, especially cancers. Ectopic m6 A modification is associated with human carcinogenesis, including lung cancer. The m6 A modification is mediated by methyltransferases (writers) and demethylases (erasers) and indirectly affects biological processes through the recruitment of specific reader proteins (readers). Many studies have shown that m6 A writers, erasers, and readers serve as specific and sensitive biomarkers for lung cancer diagnosis, prognosis, and therapy. This review summarizes recent studies on the biological functions of the m6 A modification in lung cancer and discusses the potential application of m6 A regulators in lung cancer diagnosis and therapeutics.

6.
J Affect Disord ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33229018

RESUMO

OBJECTIVES: Convergent evidence has demonstrated that trait impulsivity, a key feature in obsessive-compulsive disorder (OCD), involves dysregulated frontal-striatal circuits. The present study aims to explore relationships between frontal-striatal circuits, trait impulsivity, and obsessive-compulsive symptoms. METHODS: Thirty-six unmedicated patients with OCD and 50 healthy controls (HCs) matched for age, sex, and years of education underwent a magnetic resonance imaging (MRI) procedure. Voxel-wise statistical parametric analysis was used to investigate the differences in resting-state functional connectivity between brain regions functionally connected to six pairs of a-priori defined striatal seed regions, between patients with OCD and HCs. Associations between frontal-striatal connectivity and both trait impulsivity and symptom severity of OCD were analyzed. RESULTS: The results showed altered striatal functional connectivity in OCD group compared to HCs, including increased connectivity of dorsal caudate (DC)-orbitofrontal cortex (OFC), ventral striatum (VS)-OFC, VS-medial prefrontal cortex, and putamen-sensorimotor area, and decreased functional connectivity of DC-anterior cingulate cortex (ACC), putamen-ACC, and putamen-dorsolateral prefrontal cortex (DLPFC). Furthermore, the putamen-DLPFC connectivity was negatively correlated with attentional impulsivity in the OCD group, but showed a positive correlation in HCs. CONCLUSIONS: The present findings suggested that dorsal cognitive circuits could reflect the level of inhibitory control, which is balanced with the impulsive drive in healthy controls, but breakdown in OCD. Our findings supported that DLPFC-putamen connectivity underlying trait impulsivity, which were involved in the pathophysiology of OCD. The findings have provided new insights into the neurobiological mechanisms of OCD.

7.
Elife ; 92020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33136002

RESUMO

Legionella pneumophila extensively modulates the host ubiquitin network to create the Legionella-containing vacuole (LCV) for its replication. Many of its virulence factors function as ubiquitin ligases or deubiquitinases (DUBs). Here, we identify Lem27 as a DUB that displays a preference for diubiquitin formed by K6, K11, or K48. Lem27 is associated with the LCV where it regulates Rab10 ubiquitination in concert with SidC and SdcA, two bacterial E3 ubiquitin ligases. Structural analysis of the complex formed by an active fragment of Lem27 and the substrate-based suicide inhibitor ubiquitin-propargylamide (PA) reveals that it harbors a fold resembling those in the OTU1 DUB subfamily with a Cys-His catalytic dyad and that it recognizes ubiquitin via extensive hydrogen bonding at six contact sites. Our results establish Lem27 as a DUB that functions to regulate protein ubiquitination on L. pneumophila phagosomes by counteracting the activity of bacterial ubiquitin E3 ligases.

8.
Clin Cancer Res ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199490

RESUMO

PURPOSE: Vascular endothelial growth factor (VEGF) is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase 2 study of pembrolizumab alone or with bevacizumab in recurrent glioblastoma. EXPERIMENTAL DESIGN: Eighty bevacizumab-naive, recurrent glioblastoma patients randomized to pembrolizumab with bevacizumab (cohort A, n=50) or pembrolizumab monotherapy (cohort B, n=30). The primary endpoint was six-month progression-free survival (PFS-6). Assessed biomarkers included evaluation of tumor PD-L1 expression, TIL density, immune activation gene expression signature and plasma cytokines. The Neurologic Assessment in Neuro-Oncology (NANO) scale was used to prospectively assess neurologic function. RESULTS: Pembrolizumab alone or with bevacizumab was well tolerated but of limited benefit. For cohort A, PFS-6 was 26.0% (95% CI: 16.3, 41.5), median OS was 8.8 months (95% CI: 7.7, 14.2), ORR was 20% and median duration of response was 48 weeks. For cohort B, PFS-6 was 6.7% (95% CI: 1.7, 25.4), median OS was 10.3 months (95% CI: 8.5, 12.5) and ORR was 0%. Tumor immune markers were not associated with OS, but worsened OS correlated with baseline dexamethasone use and increased post-therapy plasma VEGF (cohort A) and mutant IDH1, unmethylated MGMT and increased baseline PlGF and sVEGFR1 levels (cohort B). The NANO scale contributed to overall outcome assessment. CONCLUSIONS: Pembrolizumab was ineffective as monotherapy and with bevacizumab for recurrent glioblastoma. The infrequent radiographic responses to combinatorial therapy were durable. Tumor immune biomarkers did not predict outcome. Baseline dexamethasone use and tumor MGMT warrant further study as potential biomarkers in GBM immunotherapy trials.

9.
Clin Exp Rheumatol ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33200733

RESUMO

OBJECTIVES: Previous studies demonstrated that connective tissue diseases-associated pulmonary arterial hypertension (CTD-PAH) had a worse prognosis than idiopathic pulmonary arterial hypertension (IPAH), although the former one had better haemodynamic profiles and right heart function. To find potential explanations for this contradictory phenomenon, we compared the exercise pathophysiology of CTD-PAH with that of IPAH using cardiopulmonary exercise testing (CPET). METHODS: Ninety-three CTD-PAH patients were retrospectively enrolled and matched 1:1 with 93 IPAH patients according to age, gender, body mass index, and body surface area. Multiple linear regression analysis was performed to adjust confounding factors. RESULTS: CTD-PAH had higher rest heart rate (HR@Rest) and lower rest oxygen uptake/HR (VO2/HR@Rest) than IPAH. During exercise, the peak power (Power@Peak), VO2@Peak, peak metabolic equivalents (METS@Peak), peak minute ventilation (VE@Peak), peak tidal volume (VT@Peak), HR@Peak, peak systolic blood pressure (SBP@Peak) and peak diastolic blood pressure (DBP@Peak) of CTD-PAH were lower than those of IPAH. After adjustment, CTD-PAH still had lower values of Power@Peak, VO2@Peak, METS@Peak, VT@Peak, VO2/HR@Rest, DBP@Peak and had higher HR@Rest than IPAH. CONCLUSIONS: CTD-PAH had more impaired ventilation, cardiac function and muscular strength (reflected by CPET-derived parameters) than IPAH, in despite of better haemodynamic profiles and comparable heart structure (assessed by echocardiography) and functional status (indicated by World Health Organisation functional class, N-terminal pro-brain natriuretic peptide and six-minute walk distance).

10.
Am J Pathol ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33129760

RESUMO

Colorectal cancer (CRC) is a leading nonfamilial cause of cancer mortality among men and women. Although various genetic and epigenetic mechanisms have been identified, the full molecular mechanisms deriving CRC tumorigenesis are incompletely understood. This study demonstrates that cell adhesion molecule transmembrane and immunoglobulin domain containing 1 (TMIGD1) is highly expressed in mouse and human normal intestinal epithelial cells. TMIGD1 knockout mice were developed, and the loss of TMIGD1 in mice was shown to result in the development of adenomas in small intestine and colon. In addition, the loss of TMIGD1 significantly impaired intestinal epithelium brush border membrane, junctional polarity, and maturation. Mechanistically, TMIGD1 inhibits tumor cell proliferation and cell migration, arrests cell cycle at the G2/M phase, and induces expression of p21CIP1 (cyclin-dependent kinase inhibitor 1), and p27KIP1 (cyclin-dependent kinase inhibitor 1B) expression, key cell cycle inhibitor proteins involved in the regulation of the cell cycle. Moreover, TMIGD1 is shown to be progressively down-regulated in sporadic human CRC, and its downregulation correlates with poor overall survival. The findings herein identify TMIGD1 as a novel tumor suppressor gene and provide new insights into the pathogenesis of colorectal cancer and a novel potential therapeutic target.

11.
Chemosphere ; : 128916, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33213877

RESUMO

Recently, interfacial solar evaporation has been developed for water treatment. However, the high cost and low stability of solar evaporators significantly hinder their practical applications. In this study, layered graphene and polymethylmethacrylate were used to fabricate a composited film (GF) by electrospinning, which acted as a solar absorber. Together with a water transporter (polyurethane sponge) and a thermal insulator (polystyrene foam), the GF-based evaporator was constructed for solar distillation. Taking advantage of the porous three-dimensional structure of GF, the light path could be extended, rendering an efficient broadband solar absorption (92%). More importantly, although the content of layered graphene in the GF-based evaporator (1.75 g m-2) was only 5.8-17.5% of that in the current reported graphene-based evaporators (10-30 g m-2), a comparable water evaporation efficiency was acquired, which was induced by the much higher utilization efficiency of photothermal nanomaterials in the GF-based evaporator than that in the reported devices, ensuring its economic feasibility. Meanwhile, more than 99.9% heavy metal ions and 99.8% organic dye could be removed by the GF-based evaporator. Combining the merits of long-term and stable evaporation, salt rejection, and resistance to harsh environment, the GF-based evaporator was promising for freshwater recycling from both seawater and wastewater.

12.
Sci Rep ; 10(1): 18509, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116163

RESUMO

The potential therapeutic effects of molecular hydrogen (H2) have now been confirmed in various human and animal-disease models. However, the effects of H2 on the physiological function in a normal state have been largely neglected. Hydrogen-rich water (HRW) intake and hydrogen inhalation (HI) are the most common used methods for hydrogen administration, the difference in the effects between HRW intake and HI remains elusive. In the present study, the body weight and 13 serum biochemical parameters were monitored during the six-month hydrogen intervention, all these parameters were significantly altered by oral intake of HRW or HI. Among the 13 parameters, the most striking alterations induced by hydrogen treatment were observed in serum myocardial enzymes spectrum. The results also showed that the changes in these parameters occurred at different time points, and the alterations in most of the parameters were much more significant in HI than HRW. The results of this study provides the basic data for the mechanism research and application of molecular hydrogen in the future.

13.
J Adv Nurs ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074555

RESUMO

AIMS: To assess the prevalence and associated factors of psychological distress among patients with chronic hepatitis B receiving oral antiviral therapy and explore the association between psychological distress and self-management behaviours among this population. DESIGN: A cross-sectional study. METHODS: A convenience sample of 188 patients with chronic hepatitis B receiving oral antiviral therapy was recruited from March-October 2018 to complete a self-report questionnaire including the Chinese version of Depression Anxiety Stress Scale-21 and Chronic Hepatitis B Self-Management Scale. Logistic regression analysis and hierarchical multiple regression analysis were used to determine the factors associated with psychological distress and the association between psychological distress and self-management behaviours respectively. RESULTS: The prevalence of depression, anxiety, and stress symptoms were 33.0%, 38.3% and 17.6% respectively. Depression was associated with older age, female gender, lower education level and longer treatment duration; anxiety was associated with female gender and longer treatment duration; and stress was associated with age of 31-40 years, female gender and unmarried status. There were significant associations between depression and anxiety symptoms and self-management behaviours. CONCLUSION: Psychological distress was prevalent among patients with chronic hepatitis B receiving oral antiviral therapy and had a negative impact on self-management. Interventions targeting depression and anxiety symptoms may be beneficial to improve self-management behaviours for this population. IMPACT: This study explored the factors associated with psychological distress in patients with chronic hepatitis B receiving oral antiviral therapy. The findings showed psychological distress was more common in patients who were with older age, female, less educated, unmarried and receiving longer duration of treatment and psychological distress was significantly associated with self-management behaviours. Nurses and other healthcare providers should provide interventions to reduce the risk of psychological distress and improve self-management behaviours for this population.

14.
J Colloid Interface Sci ; 583: 351-361, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33011405

RESUMO

Oxygen reduction reaction (ORR) catalyst is one of the most significant influential factors for the application of proton exchange membrane fuel cells. This work introduces a mass-producible high-performance PtZn alloy integrative structure ORR catalyst, synthesized with the atomically dispersive metal-organic framework precursors. This PtZn catalyst displays excellent catalytic activity with the onset reduction potential of 1.0 VRHE@ 0.16 mA cm-2 (Reversible hydrogen electrode; RHE) and the half-wave potential of 0.934 VRHE for the ORR catalysis. The calculated specific activity and mass activity at 0.9 V are 9.44 A m-2 and 544 A gPt-1, respectively, which are 5.62 times and 5.77 times as high as the commercial Pt/C. The mass activity is remarkably higher than the target put forward by the Department of Energy (DOE; 440 A gPt-1). Furthermore, this PtZn catalyst also exhibits outstanding stability after the 10,000 potential cyclic degeneration test. The ORR current is much higher than Pt/C in the whole potential range not only before but also after the 10,000 potential cycles with identical Pt loading. This catalyst has a multifarious active-site catalytic structure with PtZn alloyed particles and atomically dispersive metal-N active sites on the N-doped graphited carbon matrix, exhibiting appealing ORR catalytic activity and sound stability for the application and scalable production of fuel cell catalysts.

15.
Proc Natl Acad Sci U S A ; 117(42): 26053-26060, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33020296

RESUMO

In the presence of Lewis acid salts, the cyclic ether, dioxolane (DOL), is known to undergo ring-opening polymerization inside electrochemical cells to form solid-state polymer batteries with good interfacial charge-transport properties. Here we report that LiNO3, which is unable to ring-open DOL, possesses a previously unknown ability to coordinate with and strain DOL molecules in bulk liquids, completely arresting their crystallization. The strained DOL electrolytes exhibit physical properties analogous to amorphous polymers, including a prominent glass transition, elevated moduli, and low activation entropy for ion transport, but manifest unusually high, liquidlike ionic conductivities (e.g., 1 mS/cm) at temperatures as low as -50 °C. Systematic electrochemical studies reveal that the electrolytes also promote reversible cycling of Li metal anodes with high Coulombic efficiency (CE) on both conventional planar substrates (1 mAh/cm2 over 1,000 cycles with 99.1% CE; 3 mAh/cm2 over 300 cycles with 99.2% CE) and unconventional, nonplanar/three-dimensional (3D) substrates (10 mAh/cm2 over 100 cycles with 99.3% CE). Our finding that LiNO3 promotes reversibility of Li metal electrodes in liquid DOL electrolytes by a physical mechanism provides a possible solution to a long-standing puzzle in the field about the versatility of LiNO3 salt additives for enhancing reversibility of Li metal electrodes in essentially any aprotic liquid electrolyte solvent. As a first step toward understanding practical benefits of these findings, we create functional Li||lithium iron phosphate (LFP) batteries in which LFP cathodes with high capacity (5 to 10 mAh/cm2) are paired with thin (50 µm) lithium metal anodes, and investigate their galvanostatic electrochemical cycling behaviors.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33079528

RESUMO

Li-rich cathodes have been in considerable attention for their high reversible capacity. However, they have serious problems like poor cycling with intense capacity decay and voltage fading, which restrict their access to practical applications. In this work, a facile and efficient strategy is proposed to alleviate these intrinsic issues with a high-efficiency electrolyte system. This special electrolyte enables Li-rich cathodes to deliver superior integrated performance with a high initial discharge capacity of 301 mAh·g-1, outstanding cycling stability with a capacity retention of 88% at 0.5 C over 500 cycles, and a remarkable rate capability of 136 mAh·g-1 at 5 C, respectively. What is more, the voltage fading is largely suppressed. Physical and electrochemical characterizations demonstrate that the robust CEI film formed on the cathode surface contributes to the improved electrochemical performance. This work provides a new approach to surmount defects of Li-rich materials and will largely promote their practical applications on Li-ion batteries.

18.
J Chem Theory Comput ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079552

RESUMO

Embedded (emb-) correlated wavefunction (CW) theory enables accurate assessments of both ground- and excited-state reaction mechanisms involved in heterogeneous catalysis. Embedded multireference second-order perturbation theory (emb-MRPT2) based on reference wavefunctions generated via embedded complete active space self-consistent field (emb-CASSCF) theory is currently state-of-the-art. However, the factorial scaling of CASSCF limits the size of active space and the complexity of systems that can be studied. Here, we assess the efficacy of an alternative CW method, adaptive sampling configuration interaction (ASCI)-which enables large active spaces to be used-for studying surface reactions. We couple ASCI with density functional embedding theory (DFET) and benchmark its performance for two reactions: H2 desorption from and CH4 dissociation on the Cu(111) surface. Unlike embedded complete active space second-order perturbation theory (emb-CASPT2) that accurately reproduces a measured H2 desorption barrier, embedded ASCI, using a very large active space (though one that still comprises a small portion of the full set of orbitals) fails to do so. Adding an extra correlation term from embedded Møller-Plesset second-order perturbation theory (emb-MP2) improves the desorption barrier and endothermicity predictions. Thus, the inaccuracy of embedded ASCI comes from the missing dynamic correlation from the many other electrons and orbitals not included in the active space. For CH4 dissociation, again embedded ASCI overestimates the dissociation barrier compared to emb-CASPT2 predictions. Adding dynamic correlation from emb-MP2 helps correct the barrier. However, this composite approach suffers from double counting of correlation within embedded ASCI followed by emb-MP2 calculations. We therefore conclude that the state-of-the-art emb-MRPT2 based on reference wavefunctions generated via emb-CASSCF remains the method of choice for studying surface reactions. emb-ASCI is useful when large active spaces beyond the limit of emb-CASSCF are essential, such as to study complex surface reactions with significant multiconfigurational character (static correlation) but weak dynamic correlation.

19.
Nat Commun ; 11(1): 5371, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097715

RESUMO

Autoinducer-2 (AI-2) is a quorum sensing signal that mediates communication within and between many bacterial species. However, its known receptors (LuxP and LsrB families) are not found in all the bacteria capable of responding to this signaling molecule. Here, we identify a third type of AI-2 receptor, consisting of a dCACHE domain. AI-2 binds to the dCACHE domain of chemoreceptors PctA and TlpQ of Pseudomonas aeruginosa, thus inducing chemotaxis and biofilm formation. Boron-free AI-2 is the preferred ligand for PctA and TlpQ. AI-2 also binds to the dCACHE domains of histidine kinase KinD from Bacillus subtilis and diguanylate cyclase rpHK1S-Z16 from Rhodopseudomonas palustris, enhancing their enzymatic activities. dCACHE domains (especially those belonging to a subfamily that includes the AI-2 receptors identified in the present work) are present in a large number of bacterial and archaeal proteins. Our results support the idea that AI-2 serves as a widely used signaling molecule in the coordination of cell behavior among prokaryotic species.


Assuntos
Quimiotaxia/fisiologia , Homosserina/análogos & derivados , Homosserina/metabolismo , Lactonas/metabolismo , Células Procarióticas/metabolismo , Proteínas Arqueais , Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Liases de Carbono-Enxofre/genética , Liases de Carbono-Enxofre/metabolismo , Proteínas de Transporte/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli , Homosserina/química , Homosserina/genética , Lactonas/química , Ligantes , Fósforo-Oxigênio Liases , Pseudomonas aeruginosa/metabolismo , Percepção de Quorum , Rodopseudomonas/metabolismo , Transdução de Sinais/fisiologia
20.
J Vis Exp ; (162)2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32925876

RESUMO

A high platform can fix rats without restriction and completely expose the acupoints on the back during acupuncture manipulation. This article describes methods for the fabrication of the high platform, establishes a rat model of asthma and measures changes in respiratory function using a noninvasive and real-time whole-body plethysmography (WBP) system.

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