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1.
Cell ; 186(2): 287-304.e26, 2023 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-36610399

RESUMEN

Whether and how certain transposable elements with viral origins, such as endogenous retroviruses (ERVs) dormant in our genomes, can become awakened and contribute to the aging process is largely unknown. In human senescent cells, we found that HERVK (HML-2), the most recently integrated human ERVs, are unlocked to transcribe viral genes and produce retrovirus-like particles (RVLPs). These HERVK RVLPs constitute a transmissible message to elicit senescence phenotypes in young cells, which can be blocked by neutralizing antibodies. The activation of ERVs was also observed in organs of aged primates and mice as well as in human tissues and serum from the elderly. Their repression alleviates cellular senescence and tissue degeneration and, to some extent, organismal aging. These findings indicate that the resurrection of ERVs is a hallmark and driving force of cellular senescence and tissue aging.


Asunto(s)
Envejecimiento , Retrovirus Endógenos , Anciano , Animales , Humanos , Ratones , Envejecimiento/genética , Envejecimiento/patología , Senescencia Celular , Retrovirus Endógenos/genética , Primates
2.
Proc Natl Acad Sci U S A ; 120(3): e2218899120, 2023 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-36638211

RESUMEN

Cleavage of the flavivirus premembrane (prM) structural protein during maturation can be inefficient. The contribution of partially mature flavivirus virions that retain uncleaved prM to pathogenesis during primary infection is unknown. To investigate this question, we characterized the functional properties of newly-generated dengue virus (DENV) prM-reactive monoclonal antibodies (mAbs) in vitro and using a mouse model of DENV disease. Anti-prM mAbs neutralized DENV infection in a virion maturation state-dependent manner. Alanine scanning mutagenesis and cryoelectron microscopy of anti-prM mAbs in complex with immature DENV defined two modes of attachment to a single antigenic site. In vivo, passive transfer of intact anti-prM mAbs resulted in an antibody-dependent enhancement of disease. However, protection against DENV-induced lethality was observed when the transferred mAbs were genetically modified to inhibit their ability to interact with Fcγ receptors. These data establish that in addition to mature forms of the virus, partially mature infectious prM+ virions can also contribute to pathogenesis during primary DENV infections.


Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Antivirales , Virus del Dengue , Dengue , Microscopía por Crioelectrón , Proteínas del Envoltorio Viral/metabolismo , Virión/metabolismo , Animales , Ratones
3.
Proc Natl Acad Sci U S A ; 119(12): e2110491119, 2022 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-35294288

RESUMEN

Mosquito-borne flaviviruses (MBFs) adapt to a dual-host transmission circle between mosquitoes and vertebrates. Dual-host affiliated insect-specific flaviviruses (dISFs), discovered from mosquitoes, are phylogenetically similar to MBFs but do not infect vertebrates. Thus, dISF­MBF chimeras could be an ideal model to study the dual-host adaptation of MBFs. Using the pseudoinfectious reporter virus particle and reverse genetics systems, we found dISFs entered vertebrate cells as efficiently as the MBFs but failed to initiate replication. Exchange of the untranslational regions (UTRs) of Donggang virus (DONV), a dISF, with those from Zika virus (ZIKV) rescued DONV replication in vertebrate cells, and critical secondary RNA structures were further mapped. Essential UTR-binding host factors were screened for ZIKV replication in vertebrate cells, displaying different binding patterns. Therefore, our data demonstrate a post-entry cross-species transmission mechanism of MBFs, while UTR-host interaction is critical for dual-host adaptation.


Asunto(s)
Culicidae , Flavivirus , Infección por el Virus Zika , Virus Zika , Animales , Adaptación al Huésped , Mosquitos Vectores , Replicación Viral
4.
J Virol ; 96(23): e0087922, 2022 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-36377874

RESUMEN

The glycan loop of Zika virus (ZIKV) envelope protein (E) contains the glycosylation site and has been well documented to be important for viral pathogenesis and transmission. In the present study, we report that deletions in the E glycan loop, which were recorded in African ZIKV strains previously, have re-emerged in their contemporary Asian lineages. Here, we generated recombinant ZIKV containing specific deletions in the E glycan loop by reverse genetics. Extensive in vitro and in vivo characterization of these deletion mutants demonstrated an attenuated phenotype in an adult A129 mouse model and reduced oral infections in mosquitoes. Surprisingly, these glycan loop deletion mutants exhibited an enhanced neurovirulence phenotype, and resulted in a more severe microcephalic brain in neonatal mouse models. Crystal structures of the ZIKV E protein and a deletion mutant at 2.5 and 2.6 Å, respectively, revealed that deletion of the glycan loop induces encephalitic flavivirus-like conformational alterations, including the appearance of perforations on the surface and a clear change in the topology of the loops. Overall, our results demonstrate that the E glycan loop deletions represent neonatal mouse neurovirulence markers of ZIKV. IMPORTANCE Zika virus (ZIKV) has been identified as a cause of microcephaly and acquired evolutionary mutations since its discovery. Previously deletions in the E glycan loop were recorded in African ZIKV strains, which have re-emerged in the contemporary Asian lineages recently. The glycan loop deletion mutants are not glycosylated, which are attenuated in adult A129 mouse model and reduced oral infections in mosquitoes. More importantly, the glycan loop deletion mutants induce an encephalitic flavivirus-like conformational alteration in the E homodimer, resulting in a significant enhancement of neonatal mouse neurovirulence. This study underscores the critical role of glycan loop deletion mutants in ZIKV pathogenesis, highlighting a need for global virological surveillance for such ZIKV variants.


Asunto(s)
Proteínas del Envoltorio Viral , Infección por el Virus Zika , Virus Zika , Animales , Ratones , Modelos Animales de Enfermedad , Polisacáridos/química , Proteínas del Envoltorio Viral/genética , Virulencia , Replicación Viral/genética , Virus Zika/genética , Virus Zika/patogenicidad , Infección por el Virus Zika/virología
5.
PLoS Pathog ; 17(3): e1009393, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33684175

RESUMEN

Classical swine fever virus (CSFV) is an important pathogen in the swine industry. Virion attachment is mediated by envelope proteins Erns and E2, and E2 is indispensable. Using a pull-down assay with soluble E2 as the bait, we demonstrated that ADAM17, a disintegrin and metalloproteinase 17, is essential for CSFV entry. Loss of ADAM17 in a permissive cell line eliminated E2 binding and viral entry, but compensation with pig ADAM17 cDNA completely rescued these phenotypes. Similarly, ADAM17 silencing in primary porcine fibroblasts significantly impaired virus infection. In addition, human and mouse ADAM17, which is highly homologous to pig ADAM17, also mediated CSFV entry. The metalloproteinase domain of ADAM17 bound directly to E2 protein in a zinc-dependent manner. A surface exposed region within this domain was mapped and shown to be critical for CSFV entry. These findings clearly demonstrate that ADAM17 serves as an essential attachment factor for CSFV.


Asunto(s)
Proteína ADAM17/metabolismo , Virus de la Fiebre Porcina Clásica/metabolismo , Receptores Virales/metabolismo , Proteínas del Envoltorio Viral/metabolismo , Internalización del Virus , Animales , Peste Porcina Clásica , Virus de la Fiebre Porcina Clásica/patogenicidad , Humanos , Porcinos
6.
J Med Virol ; 95(5): e28806, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37219050

RESUMEN

Intranasal (i.n.) vaccines can induce mucosal and systemic immunity against respiratory pathogens. Previously, we demonstrated that the recombinant vesicular stomatitis virus (rVSV)-based COVID-19 vaccine rVSV-SARS-CoV-2, with poor immunogenicity via the intramuscular route (i.m.), is more suitable for i.n. administration in mice and nonhuman primates. Here, we found that the rVSV-SARS-CoV-2 Beta variant was more immunogenic than the wild-type strain and other variants of concern (VOCs) in golden Syrian hamsters. Furthermore, the immune responses elicited by rVSV-based vaccine candidates via the i.n. route were significantly higher than those of two licensed vaccines: the inactivated vaccine KCONVAC delivered via the i.m. route and the adenovirus-based Vaxzevria delivered i.n. or i.m. We next assessed the booster efficacy of rVSV following two i.m. doses of KCONVAC. Twenty-eight days after receiving two i.m. doses of KCONVAC, hamsters were boosted with a third dose of KCONVAC (i.m.), Vaxzevria (i.m. or i.n.), or rVSVs (i.n.). Consistent with other heterologous booster studies, Vaxzevria and rVSV elicited significantly higher humoral immunity than the homogenous KCONVAC. In summary, our results confirmed that two i.n. doses of rVSV-Beta elicited significantly higher humoral immune responses than commercial inactivated and adeno-based COVID vaccines in hamsters. As a heterologous booster dose, rVSV-Beta induced potent, persistent, and broad-spectrum humoral and mucosal neutralizing responses against all VOCs, highlighting its potential to be developed into a nasal-spray vaccine.


Asunto(s)
COVID-19 , Vacunas Virales , Humanos , Animales , Ratones , Vacunas contra la COVID-19 , Roedores , Rociadores Nasales , ChAdOx1 nCoV-19 , COVID-19/prevención & control , SARS-CoV-2/genética , Vesiculovirus , Anticuerpos Antivirales , Anticuerpos Neutralizantes
7.
J Med Virol ; 95(8): e29035, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37605995

RESUMEN

Recombinant LL-37 Lactococcus lactis (Oral LL-37) was designed to prevent progression of COVID-19 by targeting virus envelope, however, effectiveness and safety of Oral LL-37 in clinical application was unclear. A total of 238 adult inpatients, open-labelled, randomized, placebo-controlled, single-center study was conducted to investigate the primary end points, including negative conversion time (NCT) of SARS-CoV-2 RNA and adverse events (AEs). As early as intervened on 6th day of case confirmed, Oral LL-37 could significantly shorten NCT (LL-37 9.80 ± 2.67 vs. placebo 14.04 ± 5.89, p < 0.01). For Oral LL-37, as early as treated in 6 days, the adjusted hazard ratio (HR) for a primary event of nucleic acid negative outcome was 6.27-fold higher than 7-day-later (HR: 6.276, 95% confidence interval [CI]: 3.631-10.848, p < 0.0001), and the adjusted HR of Oral LL-37 within 6 days is higher than placebo (HR: 2.427 95% CI: 1.239-4.751, p = 0.0097). No severe AEs were observed during hospitalization and follow-up investigation. This study shows that early intervention of Oral LL-37 incredibly reduces NCT implying a potential for clearance of Omicron BA.5.1.3 without evident safety concerns.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Humanos , COVID-19/prevención & control , ARN Viral , Hospitalización , Pacientes Internos
8.
Adv Exp Med Biol ; 1407: 329-348, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36920706

RESUMEN

Vesicular stomatitis virus (VSV) is prototype virus in the family of Rhabdoviridae. Reverse genetic platform has enabled the genetic manipulation of VSV as a powerful live viral vector. Replicating-competent VSV is constructed by replacing the original VSV glycoprotein gene with heterologous envelope genes. The resulting recombinant viruses are able to replicate in permissive cells and incorporate the foreign envelope proteins on the surface of the viral particle without changing the bullet-shape morphology. Correspondingly, the cell tropism of replicating-competent VSV is determined by the foreign envelope proteins. Replicating-competent VSVs have been successfully used for selecting critical viral receptors or host factors, screening mutants that escape therapeutic antibodies, and developing VSV-based live viral vaccines.


Asunto(s)
Vesiculovirus , Pseudotipado Viral , Vesiculovirus/genética , Virus de la Estomatitis Vesicular Indiana/genética , Glicoproteínas/genética , Vectores Genéticos/genética , Proteínas del Envoltorio Viral/genética
9.
Emerg Infect Dis ; 28(12): 2491-2499, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36417938

RESUMEN

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne bandavirus mainly transmitted by Haemaphysalis longicornis ticks in East Asia, mostly in rural areas. As of April 2022, the amplifying host involved in the natural transmission of SFTSV remained unidentified. Our epidemiologic field survey conducted in endemic areas in China showed that hedgehogs were widely distributed, had heavy tick infestations, and had high SFTSV seroprevalence and RNA prevalence. After experimental infection of Erinaceus amurensis and Atelerix albiventris hedgehogs with SFTSV, we detected robust but transitory viremias that lasted for 9-11 days. We completed the SFTSV transmission cycle between hedgehogs and nymph and adult H. longicornis ticks under laboratory conditions with 100% efficiency. Furthermore, naive H. longicornis ticks could be infected by SFTSV-positive ticks co-feeding on naive hedgehogs; we confirmed transstadial transmission of SFTSV. Our study suggests that the hedgehogs are a notable wildlife amplifying host of SFTSV in China.


Asunto(s)
Phlebovirus , Síndrome de Trombocitopenia Febril Grave , Garrapatas , Animales , Erizos , Estudios Seroepidemiológicos , Filogenia , Phlebovirus/genética , China/epidemiología
10.
Emerg Infect Dis ; 28(2): 363-372, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35075994

RESUMEN

Severe fever with thrombocytopenia syndrome virus (SFTSV) is spreading rapidly in Asia. This virus is transmitted by the Asian longhorned tick (Haemaphysalis longicornis), which has parthenogenetically and sexually reproducing populations. Parthenogenetic populations were found in ≥15 provinces in China and strongly correlated with the distribution of severe fever with thrombocytopenia syndrome cases. However, distribution of these cases was poorly correlated with the distribution of populations of bisexual ticks. Phylogeographic analysis suggested that the parthenogenetic population spread much faster than bisexual population because colonization is independent of sexual reproduction. A higher proportion of parthenogenetic ticks was collected from migratory birds captured at an SFTSV-endemic area, implicating the contribution to the long-range movement of these ticks in China. The SFTSV susceptibility of parthenogenetic females was similar to that of bisexual females under laboratory conditions. These results suggest that parthenogenetic Asian longhorned ticks, probably transported by migratory birds, play a major role in the rapid spread of SFTSV.


Asunto(s)
Infecciones por Bunyaviridae , Ixodidae , Phlebovirus , Síndrome de Trombocitopenia Febril Grave , Garrapatas , Animales , Infecciones por Bunyaviridae/epidemiología , Femenino , Phlebovirus/genética , Filogenia
11.
PLoS Pathog ; 16(12): e1009019, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33315931

RESUMEN

Testicular invasion and persistence are features of Zika virus (ZIKV), but their mechanisms are still unknown. Here, we showed that S100A4+ macrophages, a myeloid macrophage subpopulation with susceptibility to ZIKV infection, facilitated ZIKV invasion and persistence in the seminiferous tubules. In ZIKV-infected mice, S100A4+ macrophages were specifically recruited into the interstitial space of testes and differentiated into interferon-γ-expressing M1 macrophages. With interferon-γ mediation, S100A4+ macrophages down-regulated Claudin-1 expression and induced its redistribution from the cytosol to nucleus, thus increasing the permeability of the blood-testis barrier which facilitated S100A4+ macrophages invasion into the seminiferous tubules. Intraluminal S100A4+ macrophages were segregated from CD8+ T cells and consequently helped ZIKV evade cellular immunity. As a result, ZIKV continued to replicate in intraluminal S100A4+ macrophages even when the spermatogenic cells disappeared. Deficiencies in S100A4 or interferon-γ signaling both reduced ZIKV infection in the seminiferous tubules. These results demonstrated crucial roles of S100A4+ macrophages in ZIKV infection in testes.


Asunto(s)
Macrófagos/metabolismo , Proteína de Unión al Calcio S100A4/inmunología , Infección por el Virus Zika/inmunología , Animales , Claudina-1/genética , Claudina-1/metabolismo , Interferón gamma/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Viral , Proteína de Unión al Calcio S100A4/metabolismo , Túbulos Seminíferos/virología , Testículo/inmunología , Testículo/virología , Replicación Viral/inmunología , Replicación Viral/fisiología , Virus Zika/inmunología , Infección por el Virus Zika/virología
12.
J Environ Sci (China) ; 121: 187-198, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35654509

RESUMEN

Particulate matter (i.e., PM1.0 and PM2.5), considered as the key atmospheric pollutants, exerts negative effects on visibility, global climate, and human health by associated chemical compositions. However, our understanding of PM and its chemical compositions in Beijing under the current atmospheric environment is still not complete after witnessing marked alleviation during 2013-2017. Continuous measurements can be crucial for further air quality improvement by better characterizing PM pollution and chemical compositions in Beijing. Here, we conducted simultaneous measurements on PM in Beijing during 2018-2019. Results indicate that annual mean PM1.0 and PM2.5 concentrations were 35.49 ± 18.61 µg/m3 and 66.58 ± 60.17 µg/m3, showing a positive response to emission controls. The contribution of sulfate, nitrate, and ammonium (SNA) played an enhanced role with elevated PM loading and acted as the main contributors to pollution episodes. Discrepancies observed among chemical species between PM1.0 and PM2.5 in spring suggest that sand particles trend to accumulate in the range of 1-2.5 µm. Pollution episodes occurred accompanied with southerly clusters and high formation of SNA by heterogeneous reactions in summer and winter, respectively. Results from positive matrix factorization (PMF) combined with potential source contribution function (PSCF) models showed that potential areas were seasonal dependent, secondary and vehicular sources became much more important compared with previous studies in Beijing. Our study presented a continuous investigation on PM and sources origins in Beijing, which provides a better understanding for further emission control as well as a reference for other cities in developing countries.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Beijing , Monitoreo del Ambiente , Humanos , Nitratos , Compuestos Orgánicos/análisis , Material Particulado/análisis , Sulfatos
13.
J Environ Sci (China) ; 122: 83-91, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35717093

RESUMEN

We investigated variations of PM2.5 and water-soluble inorganic ions chemical characteristics at nine urban and rural sites in China using ground-based observations. From 2015 to 2019, mean PM2.5 concentration across all sites decreased by 41.9 µg/m3 with a decline of 46% at urban sites and 28% at rural sites, where secondary inorganic aerosol (SIAs) contributed to 21% (urban sites) and 17% (rural sites) of the decreased PM2.5. SIAs concentrations underwent a decline at urban locations, while sulfate (SO42-), nitrate (NO3-), and ammonium (NH4+) decreased by 49.5%, 31.3% and 31.6%, respectively. However, only SO42- decreased at rural sites, NO3- increased by 21% and NH4+ decreased slightly. Those changes contributed to an overall SIAs increase in 2019. Higher molar ratios of NO3- to SO42- and NH4+ to SO42- were observed at urban sites than rural sites, being highest in the heavily polluted days. Mean molar ratios of NH3/NHx were higher in 2019 than 2015 at both urban and rural sites, implying increasing NHx remained as free NH3. Our observations indicated a slower transition from sulfate-driven to nitrate-driven aerosol pollution and less efficient control of NOx than SO2 related aerosol formation in rural regions than urban regions. Moreover, the common factor at urban and rural sites appears to be a combination of lower SO42- levels and an increasing fraction of NO3- to PM2.5 under NH4+-rich conditions. Our findings imply that synchronous reduction in NOx and NH3 emissions especially rural areas would be effective to mitigate NO3--driven aerosol pollution.


Asunto(s)
Contaminantes Atmosféricos , Material Particulado , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , China , Monitoreo del Ambiente , Nitratos/análisis , Óxidos de Nitrógeno , Material Particulado/análisis , Estaciones del Año , Sulfatos/análisis , Agua
14.
Entropy (Basel) ; 23(7)2021 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-34356460

RESUMEN

Cross-modality person re-identification is the study of images of people matching under different modalities (RGB modality, IR modality). Given one RGB image of a pedestrian collected under visible light in the daytime, cross-modality person re-identification aims to determine whether the same pedestrian appears in infrared images (IR images) collected by infrared cameras at night, and vice versa. Cross-modality person re-identification can solve the task of pedestrian recognition in low light or at night. This paper aims to improve the degree of similarity for the same pedestrian in two modalities by improving the feature expression ability of the network and designing appropriate loss functions. To implement our approach, we introduce a deep neural network structure combining heterogeneous center loss (HC loss) and a non-local mechanism. On the one hand, this can heighten the performance of feature representation of the feature learning module, and, on the other hand, it can improve the similarity of cross-modality within the class. Experimental data show that the network achieves excellent performance on SYSU-MM01 datasets.

15.
Biochim Biophys Acta Biomembr ; 1860(5): 1216-1230, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29447917

RESUMEN

The envelope (E) protein of Dengue virus rearranges to a trimeric hairpin to mediate fusion of the viral and target membranes, which is essential for infectivity. Insertion of E into the target membrane serves to anchor E and possibly also to disrupt local order within the membrane. Both aspects are likely to be affected by the depth of insertion, orientation of the trimer with respect to the membrane normal, and the interactions that form between trimer and membrane. In the present work, we resolved the depth of insertion, the tilt angle, and the fundamental interactions for the soluble portion of Dengue E trimers (sE) associated with planar lipid bilayer membranes of various combinations of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol (POPG), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), and cholesterol (CHOL) by neutron reflectivity (NR) and by molecular dynamics (MD) simulations. The results show that the tip of E containing the fusion loop (FL) is located at the interface of the headgroups and acyl chains of the outer leaflet of the lipid bilayers, in good agreement with prior predictions. The results also indicate that E tilts with respect to the membrane normal upon insertion, promoted by either the anionic lipid POPG or CHOL. The simulations show that tilting of the protein correlates with hydrogen bond formation between lysines and arginines located on the sides of the trimer close to the tip (K246, K247, and R73) and nearby lipid headgroups. These hydrogen bonds provide a major contribution to the membrane anchoring and may help to destabilize the target membrane.


Asunto(s)
Membrana Dobles de Lípidos/metabolismo , Proteínas del Envoltorio Viral/metabolismo , Internalización del Virus , Secuencia de Aminoácidos , Animales , Células Cultivadas , Enlace de Hidrógeno , Membrana Dobles de Lípidos/química , Fusión de Membrana , Modelos Moleculares , Simulación de Dinámica Molecular , Neutrones , Unión Proteica , Spodoptera , Proteínas del Envoltorio Viral/química , Acoplamiento Viral
16.
Biochim Biophys Acta ; 1858(11): 2753-2762, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27425029

RESUMEN

We describe a new method to measure the activation energy for unbinding (enthalpy ΔH*u and free energy ΔG*u) of a strongly-bound membrane-associated protein from a lipid membrane. It is based on measuring the rate of release of a liposome-bound protein during centrifugation on a sucrose gradient as a function of time and temperature. The method is used to determine ΔH*u and ΔG*u for the soluble dengue virus envelope protein (sE) strongly bound to 80:20 POPC:POPG liposomes at pH5.5. ΔH*u is determined from the Arrhenius equation whereas ΔG*u is determined by fitting the data to a model based on mean first passage time for escape from a potential well. The binding free energy ΔGb of sE was also measured at the same pH for the initial, predominantly reversible, phase of binding to a 70:30 PC:PG lipid bilayer. The unbinding free energy (20±3kcal/mol, 20% PG) was found to be roughly three times the binding energy per monomer, (7.8±0.3kcal/mol for 30% PG, or est. 7.0kcal/mol for 20% PG). This is consistent with data showing that free sE is a monomer at pH5.5, but assembles into trimers after associating with membranes. This new method to determine unbinding energies should be useful to understand better the complex interactions of integral monotopic proteins and strongly-bound peripheral membrane proteins with lipid membranes.


Asunto(s)
Membrana Dobles de Lípidos/química , Fosfatidilcolinas/química , Fosfatidilgliceroles/química , Liposomas Unilamelares/química , Proteínas del Envoltorio Viral/química , Animales , Células Cultivadas , Virus del Dengue/química , Drosophila melanogaster , Concentración de Iones de Hidrógeno , Cinética , Unión Proteica , Termodinámica
17.
Heart Lung Circ ; 26(4): 404-412, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27574735

RESUMEN

BACKGROUND: It is reported that glucagon-like peptide-1 (GLP-1) has direct cardioprotective effects. We hypothesise that Exenatide, a long half-life analog of GLP-1, might protect the heart against ischaemia/reperfusion (I/R) injury. In this study, the role and mechanism of Exenatide in I/R was investigated. METHODS: Two p38 mitogen-activated protein kinase (MAPK) isoforms p38α or p38γ, were knocked down by recombinant adeno-associated virus (rAAV) in male Sprague-Dawley rats. Then, rats were randomly treated with Exenatide or phosphate buffered saline (PBS) before I/R. Left ventricular function was measured. The translocation of glucose transporter 4 (GLUT4), GLUT1 and fatty acid transporter (FAT)/CD36 was assessed. RESULTS: Exenatide treatment increased the p38γ expression, but not p38α, in I/R rats. Exenatide significantly improved post-ischaemic cardiac function of I/R rats. The administration of Exenatide stimulated the translocation of GLUT4 and GLUT1, while it also increased the GLUT1 expression in the cytoplasm. Meanwhile, it reduced the translocation of FAT/CD36 (p<0.05). However, cardiac down-regulation of p38γ mediated by rAAV abolished not only the Exenatide-induced cardioprotective effects but also the GLUT4, GLUT1 and FAT/CD36 translocation. CONCLUSIONS: These results demonstrated that Exenatide improved cardiac function, increased translocation of GLUTs, and suppressed translocation of FAT/CD36 after myocardial I/R injury. This protective effect was mediated, at least in part, through modulation of the cardiac p38γ MAPK.


Asunto(s)
Cardiotónicos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteína Quinasa 12 Activada por Mitógenos/metabolismo , Daño por Reperfusión Miocárdica/enzimología , Miocardio/enzimología , Péptidos/farmacología , Ponzoñas/farmacología , Animales , Cadherinas/metabolismo , Exenatida , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Masculino , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/fisiopatología , Ratas , Ratas Sprague-Dawley , Función Ventricular Izquierda/efectos de los fármacos
18.
Microorganisms ; 12(4)2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38674766

RESUMEN

Haemaphysalis longicornis, a three-host tick with a wide host range, is widely distributed in different countries and regions. It stands out among ticks due to its unique feature of having both parthenogenetic and bisexual populations. Despite their morphological resemblance, the characteristics of the parthenogenetic population have been overlooked. In this comprehensive study, we systematically compared the similarities and differences between these two populations. Our investigation revealed that the parthenogenetic H. longicornis, widely distributed in China, was found in ten provinces, surpassing the previously reported distribution. Notably, individuals from the parthenogenetic population exhibited a prolonged blood-feeding duration during the larval and nymph stages compared to their bisexual counterparts. Additionally, the life cycle of the parthenogenetic population was observed to be longer. A flow cytometry analysis indicated a DNA content ratio of approximately 2:3 between the bisexual and parthenogenetic populations. A phylogenetic analysis using whole mitochondrial genome sequences resulted in the separation of the phylogenetic tree into two distinct branches. A molecular analysis unveiled a consistent single T-base deletion at nucleotide 8497 in the parthenogenetic population compared to the bisexual population. Both populations displayed high viral infection capability and significant resistance to ivermectin. Intriguingly, despite these differences, the parthenogenetic population exhibited a similar life cycle to the bisexual population, retaining the ability to transmit pathogens such as Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland Virus (HRTV). These findings contribute to a deeper understanding of the distinct characteristics and similarities between different populations of H. longicornis, laying the foundation for future research in this field.

19.
Front Microbiol ; 15: 1337402, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38384265

RESUMEN

Introduction: Revealing factors and mechanisms in determining species co-existence are crucial to community ecology, but studies using gut microbiota data are still lacking. Methods: Using gut microbiota data of 556 Brandt's voles from 37 treatments in eight experiments, we examined the relationship of species co-occurrence of gut microbiota in Brandt's voles (Lasiopodomys brandtii) with genetic distance (or genetic relatedness), community diversity, and several environmental variables. Results: We found that the species co-occurrence index (a larger index indicates a higher co-occurrence probability) of gut microbiota in Brandt's voles was negatively associated with the genetic distance between paired ASVs and the number of cohabitating voles in the experimental space (a larger number represents more crowding social stress), but positively with Shannon diversity index, grass diets (representing natural foods), and non-physical contact within an experimental space (representing less stress). Discussion: Our study demonstrated that high diversity, close genetic relatedness, and favorable living conditions would benefit species co-occurrence of gut microbiota in hosts. Our results provide novel insights into factors and mechanisms that shape the community structure and function of gut microbiota and highlight the significance of preserving the biodiversity of gut microbiota.

20.
Huan Jing Ke Xue ; 45(7): 3765-3777, 2024 Jul 08.
Artículo en Zh | MEDLINE | ID: mdl-39022925

RESUMEN

Atmospheric precipitation samples were collected in 2018, 2019, and 2021 in Beijing to study the concentrations and changes of the main metal elements and water-soluble ions; the wet deposition fluxes of heavy metals, water-soluble ions, dissolved inorganic nitrogen, and sulfur in the atmospheric precipitation and their impacts on the ecological environment; and the scavenging mechanisms of the typical precipitation to atmospheric pollutants during the study period. The results showed that the precipitation in Beijing during the study period was mostly neutral or alkaline, and the frequency of acid rain occurrence was very low, only accounting for 3.06%. The total concentrations of major metal elements in 2018, 2019, and 2021 were (4 787.46 ±4 704.31), (7 663.07 ±8 395.05), and (2 629.13 ±2 369.51) µg·L-1, respectively. The total equivalent concentrations of ions in 2018, 2019, and 2021 were (851.68 ±649.16), (973.98 ±850.94), and (644.31 ±531.16) µeq·L-1, respectively. The interannual changes in major metal elements and ions followed the order of 2019 > 2018 > 2021. The seasonal average total concentrations of major metal elements in spring, summer, autumn, and winter were (9 624.25 ±7 327.92), (4 088.67 ±5 710.14), (3 357.68 ±3 995.64), and (6 203.19 ±3 857.43) µg·L-1, respectively, and the seasonal average total equivalent concentrations of ions in spring, summer, autumn, and winter were (1 014.71 ±512.21), (729.83 ±589.90), (724.35 ±681.40), and (1 014.03 ±359.67) µeq·L-1, respectively, all presenting the order of spring > winter > summer > autumn. NO3- and SO42- were the main acid-causing ions in precipitation, whereas NH4+ and Ca2+ were the main acid-neutralizing ions. The wet deposition fluxes of the heavy metal Cd were very low [(0.05 ±0.01) mg·ï¼ˆm2·a)-1], only accounting for (0.13 ±0.04)% of the total wet deposition fluxes of main metal elements; however, its soil safety years were 291 years, significantly lower than those of other heavy metals, displaying that its ecological risk was relatively the highest. The total wet precipitation flux of water-soluble ions NH4+, Ca2+, NO3-, and SO42- accounted for (85.72 ±2.18)% of the wet precipitation flux of total ions, suggesting that their comprehensive impact on the ecological environment might have been higher. DIN wet deposition flux was mainly characterized by NH4+-N, which had a positive impact on the ecological environment in summer. SO42--S wet deposition flux was higher in summer, so its positive impact on the ecological environment was also greater. The scavenging effects of atmospheric precipitations to pollutants from the air were impacted by various factors, and the synergism effects of these factors could directly influence the scavenging mechanisms of precipitation to pollutants.

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