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1.
Mol Neurobiol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618332

RESUMO

Macrophage/microglial modulation plays a critical role in the pathogenesis of multiple sclerosis (MS), which is an inflammatory disorder of the central nervous system. Dynamin-related protein 1 is a cytoplasmic molecule that regulates mitochondrial fission. It has been proven that mitochondrial fission inhibitor 1 (Mdivi-1), a small molecule inhibitor of Drp1, can relieve experimental autoimmune encephalomyelitis (EAE), a preclinical animal model of MS. Whether macrophages/microglia are involved in the pathological process of Mdivi-1-treated EAE remains to be determined. Here, we studied the anti-inflammatory effect of Mdivi-1 on mice with oligodendrocyte glycoprotein peptide35-55 (MOG35-55)-induced EAE. We found that Drp1 phosphorylation at serine 616 in macrophages/microglia was decreased with Mdivi-1 treatment, which was accompanied by decreased antigen presentation capacity of the macrophages/microglia in the EAE mouse spinal cord. The Mdivi-1 treatment caused macrophage/microglia to produce low levels of proinflammatory molecules, such as CD16/32, iNOS, and TNF-α, and high levels of anti-inflammatory molecules, such as CD206, IL-10, and Arginase-1, suggesting that Mdivi-1 promoted the macrophage/microglia shift from the inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Moreover, Mdivi-1 was able to downregulate the expression of TRL2, TRL4, GSK-3ß, and phosphorylated NF-κB-p65 and prevent NF-κB-mediated IL-1ß and IL-6 production. In conclusion, these results indicate that Mdivi-1 significantly alleviates inflammation in mice with EAE by promoting M2 polarization by inhibiting TLR2/4- and GSK3ß-mediated NF-κB activation.

2.
Biochem Soc Trans ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34495335

RESUMO

Bacteria direct their movement in respond to gradients of nutrients and other stimuli in the environment through the chemosensory system. The behavior is mediated by chemosensory arrays that are made up of thousands of proteins to form an organized array near the cell pole. In this review, we briefly introduce the architecture and function of the chemosensory array and its core signaling unit. We describe the in vivo and in vitro systems that have been used for structural studies of chemosensory array by cryoEM, including reconstituted lipid nanodiscs, 2D lipid monolayer arrays, lysed bacterial ghosts, bacterial minicells and native bacteria cells. Lastly, we review recent advances in structural analysis of chemosensory arrays using state-of-the-art cryoEM and cryoET methodologies, focusing on the latest developments and insights with a perspective on current challenges and future directions.

3.
Nat Commun ; 12(1): 5393, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518553

RESUMO

Dynamin belongs to the large GTPase superfamily, and mediates the fission of vesicles during endocytosis. Dynamin molecules are recruited to the neck of budding vesicles to assemble into a helical collar and to constrict the underlying membrane. Two helical forms were observed: the one-start helix in the constricted state and the two-start helix in the super-constricted state. Here we report the cryoEM structure of a super-constricted two-start dynamin 1 filament at 3.74 Å resolution. The two strands are joined by the conserved GTPase dimeric interface. In comparison with the one-start structure, a rotation around Hinge 1 is observed, essential for communicating the chemical power of the GTPase domain and the mechanical force of the Stalk and PH domain onto the underlying membrane. The Stalk interfaces are well conserved and serve as fulcrums for adapting to changing curvatures. Relative to one-start, small rotations per interface accumulate to bring a drastic change in the helical pitch. Elasticity theory rationalizes the diversity of dynamin helical symmetries and suggests corresponding functional significance.

4.
Proc Natl Acad Sci U S A ; 118(37)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34503999

RESUMO

The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (NFIA), vascular development (SEMA3E), and heat production by brown adipose tissue (UCP1) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.

5.
Oxid Med Cell Longev ; 2021: 6693921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394830

RESUMO

Fluorine is an important trace element that is widely dispersed, and studies showed that fluorine could cause severe toxicity to fish. The aim of this study was to investigate the effects of fluorine on neutrophil extracellular trap (NET) formation in common carp and clarify the possible mechanism. The neutrophils were isolated and exposed to 0.25, 0.5, or 1 mM sodium fluoride (NaF). The results showed that NaF could induce the formation of NETs which exhibited a DNA-based network structure modified with histones and myeloperoxidase (MPO). Furthermore, NaF led to the production of reactive oxygen species (ROS) in neutrophils. Western blot results showed that NaF significantly increased the phosphorylation of AMPK and p38. In addition, our results showed that NaF-induced NET formation could be inhibited by an AMPK or p38 inhibitor. In conclusion, our results showed that NaF induced NET formation in neutrophils through regulation of the AMPK/p38 signaling pathway.

6.
Nat Commun ; 12(1): 4349, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272394

RESUMO

Bacterial extracellular polysaccharides (EPSs) play critical roles in virulence. Many bacteria assemble EPSs via a multi-protein "Wzx-Wzy" system, involving glycan polymerization at the outer face of the cytoplasmic/inner membrane. Gram-negative species couple polymerization with translocation across the periplasm and outer membrane and the master regulator of the system is the tyrosine autokinase, Wzc. This near atomic cryo-EM structure of dephosphorylated Wzc from E. coli shows an octameric assembly with a large central cavity formed by transmembrane helices. The tyrosine autokinase domain forms the cytoplasm region, while the periplasmic region contains small folded motifs and helical bundles. The helical bundles are essential for function, most likely through interaction with the outer membrane translocon, Wza. Autophosphorylation of the tyrosine-rich C-terminus of Wzc results in disassembly of the octamer into multiply phosphorylated monomers. We propose that the cycling between phosphorylated monomer and dephosphorylated octamer regulates glycan polymerization and translocation.


Assuntos
Cápsulas Bacterianas/química , Cápsulas Bacterianas/metabolismo , Proteínas de Escherichia coli/química , Escherichia coli/metabolismo , Proteínas de Membrana/química , Periplasma/metabolismo , Polissacarídeos Bacterianos/metabolismo , Proteínas Tirosina Quinases/química , Motivos de Aminoácidos , Domínio Catalítico , Microscopia Crioeletrônica , Citoplasma/metabolismo , Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Espectrometria de Massas , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Modelos Moleculares , Periplasma/química , Fosforilação , Conformação Proteica em alfa-Hélice , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Tirosina/química , Tirosina/metabolismo
7.
Appl Radiat Isot ; 176: 109873, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34315033

RESUMO

Plutonium isotopes in the coral were determined with chemical separation method using AG 1-X8 and AG-MP-1M anion exchange resins and sector field inductively coupled plasma mass spectrometry (SF-ICP-MS) in order to elucidate the activity concentration and source of Pu around Weizhou land in Beibu Gulf, China. Furthermore, the activity concentrations of other radionuclides (238U, 226Ra, 232Th, 137Cs, 40K and 210Pb) were measured by a HPGe spectrometer. The activity concentration of 240+239Pu in the coral is determined to be in the range of 8.95-27.84 mBq/kg. The 240Pu/239Pu atom ratios in the samples range from 0.173 to 0.225, indicating that the main source of plutonium in this area is global fallout while the contribution of PPG is about 30%. Further, the activity concentrations of 238U, 232Th, 40K and 226Ra are determined to be in the range of 18.72-64.63, 1.37-20.8, 29.78-72.52 and 3.48-61.97 Bq/kg, respectively.

8.
Nat Commun ; 12(1): 4629, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330917

RESUMO

Since the outbreak of the SARS-CoV-2 pandemic, there have been intense structural studies on purified viral components and inactivated viruses. However, structural and ultrastructural evidence on how the SARS-CoV-2 infection progresses in the native cellular context is scarce, and there is a lack of comprehensive knowledge on the SARS-CoV-2 replicative cycle. To correlate cytopathic events induced by SARS-CoV-2 with virus replication processes in frozen-hydrated cells, we established a unique multi-modal, multi-scale cryo-correlative platform to image SARS-CoV-2 infection in Vero cells. This platform combines serial cryoFIB/SEM volume imaging and soft X-ray cryo-tomography with cell lamellae-based cryo-electron tomography (cryoET) and subtomogram averaging. Here we report critical SARS-CoV-2 structural events - e.g. viral RNA transport portals, virus assembly intermediates, virus egress pathway, and native virus spike structures, in the context of whole-cell volumes revealing drastic cytppathic changes. This integrated approach allows a holistic view of SARS-CoV-2 infection, from the whole cell to individual molecules.


Assuntos
COVID-19/imunologia , SARS-CoV-2/imunologia , Montagem de Vírus/imunologia , Liberação de Vírus/imunologia , Replicação Viral/imunologia , Animais , COVID-19/epidemiologia , COVID-19/virologia , Chlorocebus aethiops , Microscopia Crioeletrônica , Tomografia com Microscopia Eletrônica , Humanos , Pandemias/prevenção & controle , SARS-CoV-2/fisiologia , SARS-CoV-2/ultraestrutura , Células Vero , Montagem de Vírus/fisiologia , Liberação de Vírus/fisiologia , Replicação Viral/fisiologia
9.
Nat Commun ; 12(1): 3475, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108457

RESUMO

How thylakoid membranes are generated to form a metabolically active membrane network and how thylakoid membranes orchestrate the insertion and localization of protein complexes for efficient electron flux remain elusive. Here, we develop a method to modulate thylakoid biogenesis in the rod-shaped cyanobacterium Synechococcus elongatus PCC 7942 by modulating light intensity during cell growth, and probe the spatial-temporal stepwise biogenesis process of thylakoid membranes in cells. Our results reveal that the plasma membrane and regularly arranged concentric thylakoid layers have no physical connections. The newly synthesized thylakoid membrane fragments emerge between the plasma membrane and pre-existing thylakoids. Photosystem I monomers appear in the thylakoid membranes earlier than other mature photosystem assemblies, followed by generation of Photosystem I trimers and Photosystem II complexes. Redistribution of photosynthetic complexes during thylakoid biogenesis ensures establishment of the spatial organization of the functional thylakoid network. This study provides insights into the dynamic biogenesis process and maturation of the functional photosynthetic machinery.


Assuntos
Membranas Intracelulares/metabolismo , Tilacoides/metabolismo , Proteínas de Bactérias/metabolismo , Membranas Intracelulares/ultraestrutura , Luz , Microscopia Eletrônica , Modelos Biológicos , Complexo de Proteínas do Centro de Reação Fotossintética/metabolismo , Multimerização Proteica , Proteômica , Synechococcus/crescimento & desenvolvimento , Synechococcus/metabolismo , Synechococcus/ultraestrutura , Tilacoides/ultraestrutura
10.
Gynecol Obstet Invest ; 86(3): 231-238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34192701

RESUMO

PURPOSE: The study was aimed to systematically assess the effect and safety of remifentanil patient-controlled analgesia (rPCA) versus epidural analgesia (EA) during labor. METHODS: Eligible trials were retrieved from PubMed, EMBASE, ScienceDirect, and Cochrane Library before April 2020. The primary outcomes were patient satisfaction with pain relief and average visual analog scale (VAS) pain scores during labor; the secondary outcomes were rate of spontaneous delivery, oxygen desaturation, maternal hyperthermia, and neonatal Apgar scores <7 at 1 and 5 min. RESULTS: Eleven studies involving 3,039 parturients were included. We found that parturients receiving rPCA were similarly satisfied with pain relief compared to those receiving EA (standardized mean difference: -0.19; 95% confidence interval [CI]: -0.57, 0.18), though had significantly higher VAS pain scores during labor (weighted mean difference: 1.41; 95% CI: 0.32, 2.50). The rate of spontaneous delivery was comparable. rPCA increased the risk of maternal oxygen desaturation (risk ratio [RR]:3.23, 95% CI: 1.98, 5.30). There was no statistical significance regarding hyperthermia (RR: 0.49, 95% CI: 0.24, 1.01). No significant difference was found for neonatal Apgar scores <7 at 1 and 5 min. CONCLUSION: rPCA could be an optional alternative for pain relief to EA without worsening maternal satisfaction with pain relief, delivery modes, or neonatal morbidity. However, rPCA was associated with higher pain intensity during labor and higher incidence of maternal oxygen desaturation. The routine use of rPCA in labor must be armed with close respiratory monitoring. Continued well-designed studies are required to provide more robust evidence.


Assuntos
Analgesia Epidural , Analgesia Obstétrica , Dor do Parto , Analgesia Epidural/efeitos adversos , Analgesia Obstétrica/efeitos adversos , Analgesia Controlada pelo Paciente , Feminino , Humanos , Recém-Nascido , Dor do Parto/tratamento farmacológico , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Remifentanil
11.
Mol Vis ; 27: 206-220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967574

RESUMO

Purpose: To explore synaptic changes and the response of microglia in a light-induced photoreceptor degeneration model. Methods: Sprague-Dawley rats were euthanized 1 h, 1 day, 3 days, 7 days, and 14 days after being exposed to intense blue light for 24 h. Hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to evaluate changes in the outer nuclear layer (ONL). Transmission electron microscopy (TEM) was applied to observe the ultrastructural changes in the synapses between the photoreceptors and second-order neurons. Western blotting was conducted to evaluate specific proteins, including postsynaptic density-95 (PSD-95), metabotropic glutamate receptor 6 (mGluR6), synapsin I, and synaptophysin. Immunofluorescence of CD11b and PKC-α or mGluR6 was used to explore the spatial relationships between microglial processes and synaptic elements. Immunoelectron microscopy of PSD-95 was performed to further confirm its engulfment of synaptic materials. Results: H&E and TUNEL staining showed that the thickness of the ONL decreased markedly, and the number of apoptotic photoreceptors peaked at day 1. TEM revealed darkened photoreceptor terminals and that ribbons of them were floating in the cytoplasm, coinciding with the downregulation of PSD-95 and mGluR6. Downstream synaptic protein synapsin I and synaptophysin exhibited upregulation in the inner plexiform layer. Activated microglia migrated to the outer retina, and their processes were found in close proximity to synapses in the outer plexiform layer under light and electron microscopy levels. Double immunostaining of CD11b and mGluR6 showed colocalization. PSD-95-immunoreactive electron-dense materials were observed inside the microglia suggesting engulfment of synaptic components. Conclusions: The study showed that there are early synaptic impairment and late compensatory changes in downstream synapses in this photic injury model. Activated microglia touched and directly engulfed synaptic materials. Microglia may play a role or a partial role in synaptic changes.

13.
Commun Biol ; 4(1): 481, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863979

RESUMO

Gag is the HIV structural precursor protein which is cleaved by viral protease to produce mature infectious viruses. Gag is a polyprotein composed of MA (matrix), CA (capsid), SP1, NC (nucleocapsid), SP2 and p6 domains. SP1, together with the last eight residues of CA, have been hypothesized to form a six-helix bundle responsible for the higher-order multimerization of Gag necessary for HIV particle assembly. However, the structure of the complete six-helix bundle has been elusive. Here, we determined the structures of both Gag in vitro assemblies and Gag viral-like particles (VLPs) to 4.2 Å and 4.5 Å resolutions using cryo-electron tomography and subtomogram averaging by emClarity. A single amino acid mutation (T8I) in SP1 stabilizes the six-helix bundle, allowing to discern the entire CA-SP1 helix connecting to the NC domain. These structures provide a blueprint for future development of small molecule inhibitors that can lock SP1 in a stable helical conformation, interfere with virus maturation, and thus block HIV-1 infection.


Assuntos
Tomografia com Microscopia Eletrônica , HIV-1/química , Produtos do Gene gag do Vírus da Imunodeficiência Humana/química , Microscopia Crioeletrônica , HIV-1/genética
14.
Integr Zool ; 16(4): 586-593, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33733613

RESUMO

Indo-Pacific humpback dolphins (Sousa chinensis) inhabit shallow coastal waters of the Indo-Pacific region including southeast China, with at least 6 putative populations identified to date in Chinese waters. However, the connectivity among these populations has not yet been fully investigated. In the present study, we compared and cross-matched photographic catalogs of individual dolphins collected to date in the Pearl River Delta region, Leizhou Bay, Sanniang Bay, and waters southwest of Hainan Island, a total of 3158 individuals, and found no re-sighting of individual dolphins among the 4 study areas. Furthermore, there was a notable difference in the pigmentation pattern displayed by individuals from these 4 regions. We suggest that this may be a phenotypical expression of fine-scale regional differentiation among humpback dolphin groups, possibly distinct populations. Given the considerable conservation management implications it may carry (e.g. definition of management units), further research is much needed.


Assuntos
Golfinhos/classificação , Distribuição Animal , Animais , China , Golfinhos/anatomia & histologia , Fotografação , Pigmentação
15.
Commun Biol ; 4(1): 402, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767359

RESUMO

Osteocytes act as mechanosensors in bone; however, the underlying mechanism remains poorly understood. Here we report that deleting Kindlin-2 in osteocytes causes severe osteopenia and mechanical property defects in weight-bearing long bones, but not in non-weight-bearing calvariae. Kindlin-2 loss in osteocytes impairs skeletal responses to mechanical stimulation in long bones. Control and cKO mice display similar bone loss induced by unloading. However, unlike control mice, cKO mice fail to restore lost bone after reloading. Osteocyte Kindlin-2 deletion impairs focal adhesion (FA) formation, cytoskeleton organization and cell orientation in vitro and in bone. Fluid shear stress dose-dependently increases Kindlin-2 expression and decreases that of Sclerostin by downregulating Smad2/3 in osteocytes; this latter response is abolished by Kindlin-2 ablation. Kindlin-2-deficient osteocytes express abundant Sclerostin, contributing to bone loss in cKO mice. Collectively, we demonstrate an indispensable novel role of Kindlin-2 in maintaining skeletal responses to mechanical stimulation by inhibiting Sclerostin expression during osteocyte mechanotransduction.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Osso e Ossos/fisiologia , Proteínas do Citoesqueleto/genética , Mecanotransdução Celular/genética , Proteínas Musculares/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas do Citoesqueleto/metabolismo , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Knockout , Proteínas Musculares/metabolismo
16.
mBio ; 12(2)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758083

RESUMO

Human immunodeficiency virus type 1 (HIV-1) capsid binds host proteins during infection, including cleavage and polyadenylation specificity factor 6 (CPSF6) and cyclophilin A (CypA). We observe that HIV-1 infection induces higher-order CPSF6 formation, and capsid-CPSF6 complexes cotraffic on microtubules. CPSF6-capsid complex trafficking is impacted by capsid alterations that reduce CPSF6 binding or by excess cytoplasmic CPSF6 expression, both of which are associated with decreased HIV-1 infection. Higher-order CPSF6 complexes bind and disrupt HIV-1 capsid assemblies in vitro Disruption of HIV-1 capsid binding to CypA leads to increased CPSF6 binding and altered capsid trafficking, resulting in reduced infectivity. Our data reveal an interplay between CPSF6 and CypA that is important for cytoplasmic capsid trafficking and HIV-1 infection. We propose that CypA prevents HIV-1 capsid from prematurely engaging cytoplasmic CPSF6 and that differences in CypA cellular localization and innate immunity may explain variations in HIV-1 capsid trafficking and uncoating in CD4+ T cells and macrophages.IMPORTANCE HIV is the causative agent of AIDS, which has no cure. The protein shell that encases the viral genome, the capsid, is critical for HIV replication in cells at multiple steps. HIV capsid has been shown to interact with multiple cell proteins during movement to the cell nucleus in a poorly understood process that may differ during infection of different cell types. In this study, we show that premature or too much binding of one human protein, cleavage and polyadenylation specificity factor 6 (CPSF6), disrupts the ability of the capsid to deliver the viral genome to the cell nucleus. Another human protein, cyclophilin A (CypA), can shield HIV capsid from premature binding to CPSF6, which can differ in CD4+ T cells and macrophages. Better understanding of how HIV infects cells will allow better drugs to prevent or inhibit infection and pathogenesis.


Assuntos
Proteínas do Capsídeo/genética , Capsídeo/fisiologia , Ciclofilina A/metabolismo , HIV-1/fisiologia , Interações Hospedeiro-Patógeno , Fatores de Poliadenilação e Clivagem de mRNA/genética , Linfócitos T CD4-Positivos/virologia , Proteínas do Capsídeo/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/virologia , Células HEK293 , Células HeLa , Humanos , Imunidade Inata , Macrófagos/virologia , Replicação Viral
17.
Integr Zool ; 16(4): 612-625, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33560551

RESUMO

The currently recognized Indo-Pacific humpback dolphin occurs in estuaries and surrounding shallow waters from the South China Sea to the Asian coast of the Indian Ocean. However, a recent study suggested that the humpback dolphin from the Bay of Bengal may represent a distinct phylogenetic species. In this study, we sequenced 915-bp mtDNA segments from five geographic populations in both Chinese and Thai waters; together with previously published sequences, these data revealed that the ancestral Indo-Pacific humpback dolphin might have split during the transition from the Oligocene to Miocene (23.45 Mya, 95% HPD: 16.65-26.55 Mya), and then dispersed along the Pacific and Indian Ocean coasts of Asia. Genetic differentiation was detected between most of the examined populations, except for only a few pairwise populations in the northern South China Sea. Genetic differentiation/distance between the humpback dolphins from the northern and southern South China Sea met the sub-species threshold value proposed for marine mammals, whereas that between the humpback dolphins in the Pacific and the Indian Ocean was above the species threshold. Bayesian inference of historic gene flow indicated low but constant northward gene flow along the Indian Ocean coast; however, there was a recent abrupt increase in gene flow in the Pacific region, likely due to the shortening coastline at the low stand of sea level. Our results revealed that the current taxonomic classification of Indo-Pacific humpback dolphins may not reflect their phylogeography.


Assuntos
Golfinhos/classificação , Golfinhos/genética , Filogeografia , Animais , DNA Mitocondrial , Fluxo Gênico , Oceano Índico , Oceano Pacífico , Análise de Sequência de DNA , Especificidade da Espécie
18.
J Environ Radioact ; 229-230: 106548, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33581482

RESUMO

The 239+240Pu and 137Cs activities and 240Pu/239Pu atom ratios in surface soil and soil core collected from Qinghai-Tibet Plateau were investigated. The maximum of 239+240Pu and 137Cs activity concentrations in five soil cores were found in upper layers and have a same trend: the maximum followed by exponential decline. The 240Pu/239Pu atom ratio ranged from 0.160 ± 0.009 to 0.212 ± 0.012, clarified that the plutonium mainly came from the global fallout and the contribution of Lop Nor test sites was negligible. In addition, the vertical profiles of radionuclides (210Pb, 238U, 232Th, 226Ra, 40K) have been studied and a high correlation has been found between them. The correlations of Pu between organic matter (OM) and heavy metals were also studied. Person Correlation Coefficients revealed Pu had significant positive correlations with organic matter and Cd, Cu, Co, Zn, but negative correlation with Tl. The results have important implication for further understanding of the sources, records and environmental impacts of global and regional nuclear activities, which expanded the database of Pu activity level and atom ratio in Chinese soil and established a foundation for future environmental risk assessment.


Assuntos
Plutônio , Monitoramento de Radiação , Poluentes Radioativos do Solo , Florestas , Humanos , Plutônio/análise , Solo , Poluentes Radioativos do Solo/análise , Tibet
19.
Viruses ; 13(2)2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33557422

RESUMO

Understanding of the construction and function of the HIV capsid has advanced considerably in the last decade. This is due in large part to the development of more sophisticated structural techniques, particularly cryo-electron microscopy (cryoEM) and cryo-electron tomography (cryoET). The capsid is known to be a pleomorphic fullerene cone comprised of capsid protein monomers arranged into 200-250 hexamers and 12 pentamers. The latter of these induce high curvature necessary to close the cone at both ends. CryoEM/cryoET, NMR, and X-ray crystallography have collectively described these interactions to atomic or near-atomic resolutions. Further, these techniques have helped to clarify the role the HIV capsid plays in several parts of the viral life cycle, from reverse transcription to nuclear entry and integration into the host chromosome. This includes visualizing the capsid bound to host factors. Multiple proteins have been shown to interact with the capsid. Cyclophilin A, nucleoporins, and CPSF6 promote viral infectivity, while MxB and Trim5α diminish the viral infectivity. Finally, structural insights into the intra- and intermolecular interactions that govern capsid function have enabled development of small molecules, peptides, and truncated proteins to disrupt or stabilize the capsid to inhibit HIV replication. The most promising of these, GS6207, is now in clinical trial.


Assuntos
Antivirais/metabolismo , Capsídeo/metabolismo , Infecções por HIV/metabolismo , HIV-1/metabolismo , Animais , Antivirais/química , Antivirais/farmacologia , Capsídeo/química , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Infecções por HIV/virologia , HIV-1/química , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Interações Hospedeiro-Patógeno , Humanos , Ligação Proteica , Replicação Viral/efeitos dos fármacos
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