RESUMO
Tropical peatlands cycle and store large amounts of carbon in their soil and biomass1-5. Climate and land-use change alters greenhouse gas (GHG) fluxes of tropical peatlands, but the magnitude of these changes remains highly uncertain6-19. Here we measure net ecosystem exchanges of carbon dioxide, methane and soil nitrous oxide fluxes between October 2016 and May 2022 from Acacia crassicarpa plantation, degraded forest and intact forest within the same peat landscape, representing land-cover-change trajectories in Sumatra, Indonesia. This allows us to present a full plantation rotation GHG flux balance in a fibre wood plantation on peatland. We find that the Acacia plantation has lower GHG emissions than the degraded site with a similar average groundwater level (GWL), despite more intensive land use. The GHG emissions from the Acacia plantation over a full plantation rotation (35.2 ± 4.7 tCO2-eq ha-1 year-1, average ± standard deviation) were around two times higher than those from the intact forest (20.3 ± 3.7 tCO2-eq ha-1 year-1), but only half of the current Intergovernmental Panel on Climate Change (IPCC) Tier 1 emission factor (EF)20 for this land use. Our results can help to reduce the uncertainty in GHG emissions estimates, provide an estimate of the impact of land-use change on tropical peat and develop science-based peatland management practices as nature-based climate solutions.
Assuntos
Florestas , Gases de Efeito Estufa , Solo , Madeira , Dióxido de Carbono/análise , Gases de Efeito Estufa/análise , Indonésia , Metano/análise , Óxido Nitroso/análise , Madeira/química , IncertezaRESUMO
Current evidence suggests that plasma cell-free DNA (cfDNA) is fragmented around a mode of 166 bp. Data supporting this view has been mainly acquired through the analysis of double-stranded cfDNA. The characteristics and diagnostic potential of single-stranded and damaged double-stranded cfDNA in healthy individuals and cancer patients remain unclear. Here, through a combination of high-affinity magnetic bead-based DNA extraction and single-stranded DNA sequencing library preparation (MB-ssDNA), we report the discovery of a large proportion of cfDNA fragments centered at â¼50 bp. We show that these "ultrashort" cfDNA fragments have a greater relative abundance in plasma of healthy individuals (median = 19.1% of all sequenced cfDNA fragments, n = 28) than in plasma of patients with cancer (median = 14.2%, n = 21, P < 0.0001). The ultrashort cfDNA fragments map to accessible chromatin regions of blood cells, particularly in promoter regions with the potential to adopt G-quadruplex (G4) DNA secondary structures. G4-positive promoter chromatin accessibility is significantly enriched in ultrashort plasma cfDNA fragments from healthy individuals relative to patients with cancers (P < 0.0001), in whom G4-cfDNA enrichment is inversely associated with copy number aberration-inferred tumor fractions. Our findings redraw the landscape of cfDNA fragmentation by identifying and characterizing a novel population of ultrashort plasma cfDNA fragments. Sequencing of MB-ssDNA libraries could facilitate the characterization of gene regulatory regions and DNA secondary structures via liquid biopsy. Our data underline the diagnostic potential of ultrashort cfDNA through classification for cancer patients.
Assuntos
Ácidos Nucleicos Livres , Neoplasias , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , DNA/genética , DNA de Cadeia Simples , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Análise de Sequência de DNARESUMO
Gamma-ray bursts (GRBs) are brief flashes of γ-rays and are considered to be the most energetic explosive phenomena in the Universe1. The emission from GRBs comprises a short (typically tens of seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed2. GRBs typically emit most of their energy via γ-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments3. However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive4. Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and γ-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.
RESUMO
Stapled peptides are a promising class of molecules with potential as highly specific probes of protein-protein interactions and as therapeutics. Hydrocarbon stapling affects the peptide properties through the interplay of two factors: enhancing the overall hydrophobicity and constraining the conformational flexibility. By constructing a series of virtual peptides, we study the role of each factor in modulating the structural properties of a hydrocarbon-stapled peptide PM2, which has been shown to enter cells, engage its target Mouse Double Minute 2 (MDM2), and activate p53. Hamiltonian replica exchange molecular dynamics (HREMD) simulations suggest that hydrocarbon stapling favors helical populations of PM2 through a combination of the geometric constraints and the enhanced hydrophobicity of the peptide. To further understand the conformational landscape of the stapled peptides along the binding pathway, we performed HREMD simulations by restraining the peptide at different distances from MDM2. When the peptide approaches MDM2, the binding pocket undergoes dehydration which appears to be greater in the presence of the stapled peptide compared with the linear peptide. In the binding pocket, the helicity of the stapled peptide is increased due to the favorable interactions between the peptide residues as well as the staple and the microenvironment of the binding pocket, contributing to enhanced affinity. The dissection of the multifaceted mechanism of hydrocarbon stapling into individual factors not only deepens fundamental understanding of peptide stapling, but also provides guidelines for the design of new stapled peptides.
RESUMO
Macrocyclic peptides show promise in targeting high-value therapeutically relevant binding sites due to their high affinity and specificity. However, their clinical application is often hindered by low membrane permeability, which limits their effectiveness against intracellular targets. Previous studies focused on peptide conformations in various solvents, leaving a gap in understanding their interactions with and translocation through lipid bilayers. Addressing this, our study explores the membrane interactions of stapled peptides, a subclass of macrocyclic peptides, using solid-state nuclear magnetic resonance (ssNMR) spectroscopy and molecular dynamics (MD) simulations. We conducted ssNMR measurements on ATSP-7041M, a prototypical stapled peptide, to understand its interaction with lipid membranes, leading to an MD-informed model for peptide membrane permeation. Our findings reveal that ATSP-7041M adopts a stable α-helical structure upon membrane binding, facilitated by a cation-π interaction between its phenylalanine side chain and the lipid headgroup. This interaction makes the membrane-bound state energetically favorable, facilitating membrane affinity and insertion. The bound peptide displayed asymmetric insertion depths, with the C-terminus penetrating deeper (approximately 9 Å) than the N-terminus (approximately 4.3 Å) relative to the lipid headgroups. Contrary to expectations, peptide dynamics was not hindered by membrane binding and exhibited rapid motions similar to cell-penetrating peptides. These dynamic interactions and peptide-lipid affinity appear to be crucial for membrane permeation. MD simulations indicated a thermodynamically stable transmembrane conformation of ATSP-7041M, reducing the energy barrier for translocation. Our study offers an in silico view of ATSP-7041M's translocation from the extracellular to the intracellular region, highlighting the significance of peptide-lipid interactions and dynamics in enabling peptide transit through membranes.
Assuntos
Bicamadas Lipídicas , Simulação de Dinâmica Molecular , Proteína Supressora de Tumor p53 , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , Ressonância Magnética Nuclear Biomolecular , Espectroscopia de Ressonância MagnéticaRESUMO
Schwarzites are porous (spongy-like) carbon allotropes with negative Gaussian curvatures. They are proposed by Mackay and Terrones inspired by the works of the German mathematician Hermann Schwarz on Triply-Periodic Minimal Surfaces (TPMS). This review presents and discusses the history of schwarzites and their place among curved carbon nanomaterials. The main works on schwarzites are summarized and are available in the literature. Their unique structural, electronic, thermal, and mechanical properties are discussed. Although the synthesis of carbon-based schwarzites remains elusive, recent advances in the synthesis of zeolite-templates nanomaterials have brought them closer to reality. Atomic-based models of schwarzites are translated into macroscale ones that are 3D-printed. These 3D-printed models are exploited in many real-world applications, including water remediation and biomedical ones.
RESUMO
The extant jawless vertebrates, represented by lampreys and hagfish, are the oldest group of vertebrates and provide an interesting genomic evolutionary pivot point between invertebrates and jawed vertebrates. Through genome analysis of one of these jawless vertebrates, the Japanese lamprey (Lethenteron japonicum), we identified all three members of the important p53 transcription factor family--Tp53, Tp63, and Tp73--as well as the Mdm2 and Mdm4 genes. These genes and their products are significant cellular regulators in human cancer, and further examination of their roles in this most distant vertebrate relative sheds light on their origin and coevolution. Their important role in response to DNA damage has been highlighted by the discovery of multiple copies of the Tp53 gene in elephants. Expression of lamprey p53, Mdm2, and Mdm4 proteins in mammalian cells reveals that the p53-Mdm2 interaction and the Mdm2/Mdm4 E3 ligase activity existed in the common ancestor of vertebrates and have been conserved for >500 million years of vertebrate evolution. Lamprey Mdm2 degrades human p53 with great efficiency, but this interaction is not blocked by currently available small molecule inhibitors of the human HDM2 protein, suggesting utility of lamprey Mdm2 in the study of the human p53 signaling pathway.
Assuntos
Lampreias/genética , Lampreias/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Sequência de Aminoácidos , Animais , Células Cultivadas , Sequência Conservada , Genoma , Humanos , Lampreias/classificação , Camundongos , Modelos Moleculares , Filogenia , Ligação Proteica , Proteólise , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de SequênciaRESUMO
Autophagy is an intracellular catabolic self-cannibalism that eliminates dysfunctional cytoplasmic cargos by the fusion of cargo-containing autophagosomes with lysosomes to maintain cyto-homeostasis. Autophagy sustains a dynamic interlink between cytoprotective and cytostatic function during malignant transformation in a context-dependent manner. The antioxidant and immunomodulatory phyto-products govern autophagy and autophagy-associated signaling pathways to combat cellular incompetence during malignant transformation. Moreover, in a close cellular signaling circuit, autophagy regulates aberrant epigenetic modulation and inflammation, which limits tumor metastasis. Thus, manipulating autophagy for induction of cell death and associated regulatory phenomena will embark on a new strategy for tumor suppression with wide therapeutic implications. Despite the prodigious availability of lead pharmacophores in nature, the central autophagy regulating entities, their explicit target, as well as pre-clinical and clinical assessment remains a major question to be answered. In addition to this, the stage-specific regulation of autophagy and mode of action with natural products in regulating the key autophagic molecules, control of tumor-specific pathways in relation to modulation of autophagic network specify therapeutic target in caner. Moreover, the molecular pathway specificity and enhanced efficacy of the pre-existing chemotherapeutic agents in co-treatment with these phytochemicals hold high prevalence for target specific cancer therapeutics. Hence, the multi-specific role of phytochemicals in a cellular and tumor context dependent manner raises immense curiosity for investigating of novel therapeutic avenues. In this perspective, this review discusses about diverse implicit mechanisms deployed by the bioactive compounds in diagnosis and therapeutics approach during cancer progression with special insight into autophagic regulation.
Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Autofagia , Transformação Celular Neoplásica/metabolismo , Humanos , Lisossomos/patologia , Neoplasias/patologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêuticoRESUMO
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder in which patients lose motor functions due to progressive loss of motor neurons in the cortex, brainstem, and spinal cord. Whilst the loss of neurons is central to the disease, it is becoming clear that glia, specifically astrocytes, contribute to the onset and progression of neurodegeneration. Astrocytes play an important role in maintaining ion homeostasis in the extracellular milieu and regulate multiple brain functions by altering their extracellular concentrations. In this study, we have investigated the ability of astrocytes to maintain K+ homeostasis in the brain via direct measurement of the astrocytic K+ clearance rate in the motor and somatosensory cortices of an ALS mouse model (SOD1G93A ). Using electrophysiological recordings from acute brain slices, we show region-specific alterations in the K+ clearance rate, which was significantly reduced in the primary motor cortex but not the somatosensory cortex. This decrease was accompanied by significant changes in astrocytic morphology, impaired conductivity via Kir4.1 channels and low coupling ratio in astrocytic networks in the motor cortex, which affected their ability to form the K+ gradient needed to disperse K+ through the astrocytic syncytium. These findings indicate that the supportive function astrocytes typically provide to motoneurons is diminished during disease progression and provides a potential explanation for the increased vulnerability of motoneurons in ALS.
Assuntos
Esclerose Lateral Amiotrófica , Camundongos , Animais , Astrócitos , Superóxido Dismutase-1 , Neurônios Motores/fisiologia , Medula Espinal , Modelos Animais de Doenças , Progressão da Doença , Camundongos Transgênicos , Superóxido DismutaseRESUMO
Energy transfer and exciplex emission are not only crucial photophysical processes in many living organisms but also important for the development of smart photonic materials. We report, herein, the rationally designed synthesis and characterization of two highly charged bischromophoric homo[2]catenanes and one cyclophane incorporating a combination of polycyclic aromatic hydrocarbons, i.e., anthracene, pyrene, and perylene, which are intrinsically capable of supporting energy transfer and exciplex formation. The possible coconformations of the homo[2]catenanes, on account of their dynamic behavior, have been probed by Density Functional Theory calculations. The unique photophysical properties of these exotic molecules have been explored by steady-state and time-resolved absorption and fluorescence spectroscopies. The tetracationic pyrene-perylene cyclophane system exhibits emission emanating from a highly efficient Förster resonance energy transfer (FRET) mechanism which occurs in 48 ps, while the octacationic homo[2]catenane displays a weak exciplex photoluminescence following extremely fast (<0.3 ps) exciplex formation. The in-depth fundamental understanding of these photophysical processes involved in the fluorescence of bischromophoric cyclophanes and homo[2]catenanes paves the way for their use in future bioapplications and photonic devices.
RESUMO
Near-infrared (NIR) light is known to have outstanding optical penetration in biological tissues and to be non-invasive to cells compared with visible light. These characteristics make NIR-specific light optimal for numerous biological applications, such as the sensing of biomolecules or in theranostics. Over the years, significant progress has been achieved in the synthesis of fluorescent cyclophanes for sensing, bioimaging, and making optoelectronic materials. The preparation of NIR-emissive porphyrin-free cyclophanes is, however, still challenging. In an attempt for fluorescence emissions to reach into the NIR spectral region, employing organic tetracationic cyclophanes, we have inserted two 9,10-divinylanthracene units between two of the pyridinium units in cyclobis(paraquat-p-phenylene). Steady-state absorption, fluorescence, and transient-absorption spectroscopies reveal the deep-red and NIR photoluminescence of this cyclophane. This tetracationic cyclophane is highly soluble in water and has been employed successfully as a probe for live-cell imaging in a breast cancer cell line (MCF-7).
RESUMO
Hepatic fibrosis is a strong predictor of clinical outcomes following liver transplantation (LT).1 Despite the centrality of hepatic fibrosis in clinical outcomes, the published literature with noninvasive fibrosis assessment in LT recipients is limited and liver biopsy, despite its invasive nature, remains the reference standard. Vibration-controlled transient elastography (VCTE) and clinical prediction models (CPM) are point-of-care tests that can provide noninvasive assessment of hepatic fibrosis2-4; however, the data comparing the diagnostic performance of VCTE and CPM in LT recipients are lacking. The current study evaluated the diagnostic performance of VCTE and CPM in LT recipients using best practices in regulatory sciences for biomarker development.
Assuntos
Regras de Decisão Clínica , Técnicas de Imagem por Elasticidade , Transplante de Fígado , Transplantados , Vibração , Fígado/patologia , Modelos Estatísticos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Fabrication of large-area ionic covalent organic framework membranes (iCOMs) remains a grand challenge. Herein, the authors report the liquid water and water vapor-assisted fabrication of large-area superprotonic conductive iCOMs. A mixed monomer solution containing 1,3,5-triformylphloroglucinol (TFP) in 1,4-dioxane and p-diaminobenzenesulfonic acid (DABA) in water is first polymerized to obtain a pristine membrane which subsequently underwent crystallization process in mixed vapors containing water vapor. During the polymerization stage, water played a role of a diluting agent, weakening the Coulombic repulsion between sulfonic acid groups. During the crystallization stage, water vapor played a role of a structure-directing agent to facilitate the formation of highly crystalline, large-area iCOMs. The resulting membranes achieved a proton conductivity value of 0.76 S cm-1 at 90 °C under 100% relative humidity, which is among the highest ever reported. Using liquid water and water vapor as versatile additives open a novel avenue to the fabrication of large-area membranes from covalent organic frameworks and other kinds of crystalline organic framework materials.
RESUMO
Rab proteins represent the largest family of the Rab superfamily guanosine triphosphatase (GTPase). Aberrant human Rab proteins are associated with multiple diseases, including cancers and neurological disorders. Rab subfamily members display subtle conformational variations that render specificity in their physiological functions and can be targeted for subfamily-specific drug design. However, drug discovery efforts have not focused much on targeting Rab allosteric non-nucleotide binding sites which are subjected to less evolutionary pressures to be conserved, hence are likely to offer subfamily specificity and may be less prone to undesirable off-target interactions and side effects. To discover druggable allosteric binding sites, Rab structural dynamics need to be first incorporated using multiple experimentally and computationally obtained structures. The high-dimensional structural data may necessitate feature extraction methods to identify manageable representative structures for subsequent analyses. We have detailed state-of-the-art computational methods to (i) identify binding sites using data on sequence, shape, energy, etc., (ii) determine the allosteric nature of these binding sites based on structural ensembles, residue networks and correlated motions and (iii) identify small molecule binders through structure- and ligand-based virtual screening. To benefit future studies for targeting Rab allosteric sites, we herein detail a refined workflow comprising multiple available computational methods, which have been successfully used alone or in combinations. This workflow is also applicable for drug discovery efforts targeting other medically important proteins. Depending on the structural dynamics of proteins of interest, researchers can select suitable strategies for allosteric drug discovery and design, from the resources of computational methods and tools enlisted in the workflow.
Assuntos
Sítio Alostérico , Biologia Computacional/métodos , Descoberta de Drogas/métodos , Proteínas rab de Ligação ao GTP/química , Animais , Desenho de Fármacos , Humanos , Proteínas rab de Ligação ao GTP/metabolismoRESUMO
Combining bioclinical parameters with liver stiffness measurement (LSM) has improved the diagnostic performance of vibration-controlled transient elastography (VCTE) for detection of advanced fibrosis in patients with chronic liver disease. However, this approach has not yet been tested in liver transplantation (LT) recipients. Thus, the aim of this study was to evaluate the diagnostic performance of combining LSM-based scores with LSM alone for the detection of advanced fibrosis in LT recipients. Adult LT recipients with a liver biopsy, VCTE, and clinical data necessary to construct LSM-based fibrosis models (FibroScan-AST [FAST], AGILE-3+, and AGILE-4) were included ( n = 132). The diagnostic statistics for advanced fibrosis (fibrosis stage 0-2 vs. 3-4) were determined by optimal cut-off using the Youden index. The area under the receiver operating characteristic curve (AUROC) for LSM was 0.94 (95% confidence interval [95% CI], 0.89-0.99), FAST was 0.65 (95% CI, 0.50-0.79), AGILE-3+ was 0.90 (95% CI, 0.83-0.97), and AGILE-4 was 0.90 (95% CI, 0.83-0.97). No statistically significant differences were noted between the AUROC of LSM versus LSM-based scores. The false-positive rates for AGILE-3+ and AGILE-4 were 14.5% and 11.8% compared with 8.3% for LSM alone. The false-positive rates in LSM-based scores were higher among patients with diabetes mellitus, higher AST levels, and lower platelet counts. The LSM-based scores did not improve the diagnostic performance of LSM alone in LT recipients for the detection of advanced fibrosis. This lack of improvement in diagnostic performance results from the impact of immunosuppression on bioclinical profile and underscores the importance of developing LSM-based scores that are specific to LT patients.
Assuntos
Técnicas de Imagem por Elasticidade , Transplante de Fígado , Adulto , Humanos , Transplante de Fígado/efeitos adversos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/cirurgia , Fibrose , Curva ROC , Técnicas de Imagem por Elasticidade/métodos , BiópsiaRESUMO
Zinc finger protein 36 like 1 (ZFP36L1) enhances the turnover of mRNAs containing AU-rich elements (AREs) in their 3'-untranslated regions (3'UTR). The physiological and pathological functions of ZFP36L1 in liver, however, remain largely unknown. Liver-specific ZFP36L1-deficient (Zfp36l1flox/flox/Cre+; L1LKO) mice were generated to investigate the role of ZFP36L1 in liver physiology and pathology. Under normal conditions, the L1LKO mice and their littermate controls (Zfp36l1flox/flox/Cre-; L1FLX) appeared normal. When fed a Lieber-DeCarli liquid diet containing alcohol, L1LKO mice were significantly protected from developing alcohol-induced hepatic steatosis, injury, and inflammation compared with L1FLX mice. Most importantly, fibroblast growth factor 21 (Fgf21) mRNA was significantly increased in the livers of alcohol diet-fed L1LKO mice compared with the alcohol diet-fed L1FLX group. The Fgf21 mRNA contains three AREs in its 3'UTR, and Fgf21 3'UTR was directly regulated by ZFP36L1 in luciferase reporter assays. Steady-state levels of Fgf21 mRNA were significantly decreased by wild-type ZFP36L1, but not by a non-binding zinc finger ZFP36L1 mutant. Finally, wild-type ZFP36L1, but not the ZFP36L1 mutant, bound to the Fgf21 3'UTR ARE RNA probe. These results demonstrate that ZFP36L1 inactivation protects against alcohol-induced hepatic steatosis and liver injury and inflammation, possibly by stabilizing Fgf21 mRNA. These findings suggest that the modulation of ZFP36L1 may be beneficial in the prevention or treatment of human alcoholic liver disease.
Assuntos
Regiões 3' não Traduzidas , Fator 1 de Resposta a Butirato/metabolismo , Fígado Gorduroso Alcoólico/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Fígado/metabolismo , Estabilidade de RNA , Animais , Fator 1 de Resposta a Butirato/genética , Fígado Gorduroso Alcoólico/genética , Fígado Gorduroso Alcoólico/patologia , Fatores de Crescimento de Fibroblastos/genética , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Fígado/patologia , Camundongos , Camundongos Knockout , MutaçãoRESUMO
T'Ho virus is a poorly characterized orthoflavivirus most closely related to Rocio virus and Ilheus virus, two orthoflaviviruses associated with human disease, suggesting that T'Ho virus could also be a human pathogen. The genome of T'Ho virus has been sequenced but an isolate has never been recovered, impeding its phenotypic characterization. In an attempt to generate recombinant T'Ho virus, the entire viral genome was synthesized as three overlapping DNA fragments, joined by Gibson assembly, and transfected into mosquito cells. Several cell culture passages were performed, but virus was not recovered. Subsequent experiments focused on the development of a chimeric orthoflavivirus that contains the premembrane and envelope protein genes of T'Ho virus in the genetic background of Zika virus. The chimeric virus replicated in mosquito (C6/36) and vertebrate (Vero) cells, demonstrating that the major structural glycoproteins of T'Ho virus permit entry into both cell types. The chimeric virus produced plaques in Vero cells that were significantly smaller than those produced by Zika virus. The chimeric virus can potentially be used as a surrogate diagnostic reagent in place of T'Ho virus in plaque reduction neutralization tests, allowing T'Ho virus to be considered in the differential diagnosis.
Assuntos
Culicidae , Flavivirus , Infecção por Zika virus , Zika virus , Chlorocebus aethiops , Humanos , Animais , Zika virus/genética , Flavivirus/genética , Células Vero , Patrimônio GenéticoRESUMO
During in vitro fertilisation (IVF), pharmacological activation of the murine X chromosome-encoded receptor proteins Toll-like receptor (TLR) 7 and TLR8 reportedly results in male-biased litters by selectively disrupting the motility of X-bearing sperm cells. Thus-in the context of agonist treatment during IVF-these receptors act as 'suicidal' segregation distorters that impair their own transmission to the next generation. Such behaviour would, from an evolutionary perspective, be strongly selected against if present during natural fertilisation. Consequently, TLR7/8 biology in vivo must differ significantly from this in vitro situation to allow these genes to persist in the genome. Here, we use our current understanding of male germ cell biology and TLR function as a starting point to explore the mechanistic and evolutionary aspects of this apparent paradox.
Assuntos
Espermatozoides/fisiologia , Receptores Toll-Like/metabolismo , Cromossomo X , Animais , Evolução Biológica , Humanos , Masculino , Transporte de RNA , Razão de Masculinidade , Espermatogênese , Espermatozoides/citologia , Espermatozoides/metabolismo , Receptores Toll-Like/genéticaRESUMO
We report structural and nonlinear optical properties of 20 nm gold (Au) nanoparticles (NPs) that are dispersed in planar degenerate (non-oriented) and planar oriented nematic liquid crystals (LCs) (4'-Pentyl-4-biphenylcarbonitrile-5CB). Taking advantage of elastic forces in the planar oriented nematic LC, we aligned AuNPs parallel to the 5CB director axis. In the case of planar degenerate, 5CB is not aligned and has no preferred orientation, forcing the AuNPs to disperse randomly. Results show that the linear optical absorption coefficient for the planar oriented 5CB/AuNPs mixture is larger than the corresponding planar degenerate sample. The nonlinear absorption coefficients are greatly enhanced in planar oriented samples at relatively high concentrations which can be attributed to plasmon coupling between the aligned AuNPs. This study demonstrates the utility of LCs for developing the assembly of NPs with enhanced optical properties which may offer important insight and technological advancement for novel applications, including photonic nanomaterials and optoelectronic devices.
RESUMO
Interactions among endophytes and plants are widespread and can vary from neutral or positive or negative. Plants are continually in a functionally dynamic state due to interactions with diverse endophytic microorganisms, which produce various metabolic substances. Through quorum sensing, these substances not only help endophytes to outcompete other host-associated pathogens or microbes but also allow them to overcome the plant immune system. Manifold interactions between endophytic microbiota cause a reflective impact on the host plant functioning and the development of 'endobiomes,' by synthesizing chemicals that fill the gap between host and endophytes. Despite the advances in the field, specific mechanisms for the endophytes' precise methods to modulate plant genome and their effects on host plants remain poorly understood. Deeper genomic exploration can provide a locked away understanding of the competencies of endophytes and their conceivable function in host growth and health. Endophytes also can modify host metabolites, which could manipulate plants' growth, adaptation, and proliferation, and can be a more exciting and puzzling topic that must be properly investigated. The consequence of the interaction of endophytes on the host genome was analyzed as it can help unravel the gray areas of endophytes about which very little or no knowledge exists. This review discusses the recent advances in understanding the future challenges in the emerging research investigating how endosymbionts affect the host's metabolism and gene expression as an effective strategy for imparting resistance to biotic and abiotic challenges.