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1.
Nat Commun ; 12(1): 1876, 2021 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-33767183

RESUMEN

Viruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters host cell metabolism may lead to potential treatments for COVID-19. Here we profile metabolic changes conferred by SARS-CoV-2 infection in kidney epithelial cells and lung air-liquid interface (ALI) cultures, and show that SARS-CoV-2 infection increases glucose carbon entry into the TCA cycle via increased pyruvate carboxylase expression. SARS-CoV-2 also reduces oxidative glutamine metabolism while maintaining reductive carboxylation. Consistent with these changes, SARS-CoV-2 infection increases the activity of mTORC1 in cell lines and lung ALI cultures. Lastly, we show evidence of mTORC1 activation in COVID-19 patient lung tissue, and that mTORC1 inhibitors reduce viral replication in kidney epithelial cells and lung ALI cultures. Our results suggest that targeting mTORC1 may be a feasible treatment strategy for COVID-19 patients, although further studies are required to determine the mechanism of inhibition and potential efficacy in patients.


Asunto(s)
/patología , Ciclo del Ácido Cítrico/fisiología , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Animales , Benzamidas/farmacología , Línea Celular , Chlorocebus aethiops , Glucosa/metabolismo , Glutamina/metabolismo , Células HEK293 , Humanos , Pulmón/metabolismo , Pulmón/virología , Morfolinas/farmacología , Naftiridinas/farmacología , Pirimidinas/farmacología , Piruvato Carboxilasa/biosíntesis , Células Vero , Replicación Viral/efectos de los fármacos
2.
Cell Rep ; 35(1): 108940, 2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33784499

RESUMEN

SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified a small-molecule library of 34 of 430 protein kinase inhibitors that were capable of inhibiting the SARS-CoV-2 cytopathic effect in human epithelial cells. These drug inhibitors are in various stages of clinical trials. We detected key proteins involved in cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-damage response that are critical for SARS-CoV-2 infection. A drug-protein interaction-based secondary screen confirmed compounds, such as the ATR kinase inhibitor berzosertib and torin2 with anti-SARS-CoV-2 activity. Berzosertib exhibited potent antiviral activity against SARS-CoV-2 in multiple cell types and blocked replication at the post-entry step. Berzosertib inhibited replication of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV) as well. Our study highlights key promising kinase inhibitors to constrain coronavirus replication as a host-directed therapy in the treatment of COVID-19 and beyond as well as provides an important mechanism of host-pathogen interactions.

3.
J Phys Chem A ; 125(11): 2324-2333, 2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33710888

RESUMEN

Fragmentation of transient negative ions of tryptophan molecules formed through electron transfer in collisions with potassium atoms is presented for the first time in the laboratory collision energy range of 20 up to 100 eV. In the unimolecular decomposition process, the dominating side-chain fragmentation channel is assigned to the dehydrogenated indoline anion, in contrast to dissociative electron attachment of free low-energy electrons to tryptophan. The role of the collision complex formed by the potassium cation and tryptophan negative ion in the electron transfer process is significant for the mechanisms that operate at lower collision energies. At those collision times, on the order of a few tens of fs, the collision complex may not only influence the lifetime of the anion but also stabilize specific transition states and thus alter the fragmentation patterns considerably. DFT calculations, at the BHandHLYP/6-311++G(3df,2pd) level of theory, are used to explore potential reaction pathways and the evolvement of the charge distribution along those.

4.
J Phys Chem A ; 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33783226

RESUMEN

The NH2 radical is a key component in many astrophysical environments, both in its neutral and cationic forms, being involved in the formation of complex N-bearing species. To gain insight into the photochemical processes into which it operates and to model accurately the ensuing chemical networks, the knowledge of its photoionization efficiency is required, but no quantitative determination has been carried out so far. Combining a flow-tube H-abstraction radical source, a double imaging photoelectron-photoion spectrometer, and a vacuum-ultraviolet synchrotron excitation, the absolute photoionization cross section of the amino radical has been measured in the present work for the first time at two photon energies: σionNH2(12.7 eV) = 7.8 ± 2.2 Mb and σionNH2(13.2 eV) = 7.8 ± 2.0 Mb. These values have been employed to scale the total ion yield previously recorded by Gibson et al. ( J. Chem. Phys. 1985, 83, 4319-4328). The resulting cross section curve spanning the 11.1-15.7 eV energy range will help in refining the current astrophysical models.

5.
J Phys Chem Lett ; 12(9): 2385-2393, 2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33660503

RESUMEN

Structural changes at the molecular level, occurring at the onset of condensation, can be probed by angle-resolved valence photoelectron spectroscopy, which is inherently sensitive to the electronic structure. For larger condensed systems like aerosol particles, the observation of intrinsic angular anisotropies in photoemission (ß parameters) is challenging due to the strong reduction of their magnitude by electron transport effects. Here, we use a less common, more sensitive observable in the form of the chiral asymmetry parameter to perform a comparative study of the VUV photoelectron spectroscopy and photoelectron circular dichroism (PECD) between pure gas phase enantiomers of the amino acid serine and their corresponding homochiral nanoparticles. We observe a relatively large (1%) and strongly kinetic energy-dependent asymmetry, discussed in terms of the emergence of local order and conformational changes potentially counterbalancing the loss of angular information due to electron transport scattering. This demonstrates the potential of PECD as a sensitive probe of the condensation effects from the gas phase to bulk-like chiral aerosol particles surpassing the potential of conventional photoemission observables such as ß parameters.

6.
J Phys Chem A ; 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33472370

RESUMEN

We present a dissociative photoionization study of NO2 in the 15.5-20 eV energy range using synchrotron radiation-based double imaging photoelectron photoion coincidence (i2PEPICO) spectroscopy. The high-lying electronic states of the NO2+ cation, c 3B1, C 1B1, d 3A1, e 3B2, and D 1B2, are prepared in well-resolved vibronic states in order to study their individual dissociation mechanisms. Up to eight dissociation limits of NO2+ are reached, and mass-selected threshold photoelectron spectra (TPES) show that the c 3B1, C 1B1, and d 3A1 states predominantly dissociate into the NO+ + O products, while the e 3B2 and D 1B2 states can undergo fragmentation into both the NO+ + O and the O+ + NO channels, as well as the O2+ + N channel with a small yield. Overall, these product yields are found to be quite sensitive to autoionization processes. Mass-selected high-resolution electron and ion kinetic energy correlation diagrams reveal dissociative mechanisms that possess strong state-specific character.

7.
Cell Stem Cell ; 28(2): 331-342.e5, 2021 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-33450186

RESUMEN

ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe COVID-19. However, it is unclear whether ApoE4 alters COVID-19 susceptibility or severity, and the role of direct viral infection in brain cells remains obscure. We tested the neurotropism of SARS-CoV2 in human-induced pluripotent stem cell (hiPSC) models and observed low-grade infection of neurons and astrocytes that is boosted in neuron-astrocyte co-cultures and organoids. We then generated isogenic ApoE3/3 and ApoE4/4 hiPSCs and found an increased rate of SARS-CoV-2 infection in ApoE4/4 neurons and astrocytes. ApoE4 astrocytes exhibited enlarged size and elevated nuclear fragmentation upon SARS-CoV-2 infection. Finally, we show that remdesivir treatment inhibits SARS-CoV2 infection of hiPSC neurons and astrocytes. These findings suggest that ApoE4 may play a causal role in COVID-19 severity. Understanding how risk factors impact COVID-19 susceptibility and severity will help us understand the potential long-term effects in different patient populations.


Asunto(s)
Apolipoproteínas E/metabolismo , Encéfalo/patología , Encéfalo/virología , Células Madre Pluripotentes Inducidas/virología , Tropismo/fisiología , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/farmacología , Alanina/análogos & derivados , Alanina/farmacología , Animales , Antivirales/farmacología , Astrocitos/efectos de los fármacos , Astrocitos/patología , Astrocitos/virología , Diferenciación Celular , Chlorocebus aethiops , Humanos , Degeneración Nerviosa/patología , Neuritas/patología , Neuronas/efectos de los fármacos , Neuronas/patología , Neuronas/virología , Organoides/efectos de los fármacos , Organoides/patología , Organoides/virología , Isoformas de Proteínas/metabolismo , Sinapsis/patología , Células Vero
8.
JCI Insight ; 2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33284134

RESUMEN

Extra-pulmonary manifestations of COVID-19 are associated with a much higher mortality rate. Yet, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2 induced severe systemic toxicity and multi-organ involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity and failure to thrive. We demonstrate there is metabolic suppression of oxidative phosphorylation and the tri-carboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia and splenic atrophy mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We perform metabolomic profiling of peripheral blood and identify a panel of TCA cycle metabolites that serve as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, that affects expression of immune response genes and could in part contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2 induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19.

9.
Cell Stem Cell ; 27(6): 869-875.e4, 2020 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-33259798

RESUMEN

Current smoking is associated with increased risk of severe COVID-19, but it is not clear how cigarette smoke (CS) exposure affects SARS-CoV-2 airway cell infection. We directly exposed air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term CS and then infected them with SARS-CoV-2. We found an increase in the number of infected airway cells after CS exposure with a lack of ABSC proliferation. Single-cell profiling of the cultures showed that the normal interferon response was reduced after CS exposure with infection. Treatment of CS-exposed ALI cultures with interferon ß-1 abrogated the viral infection, suggesting one potential mechanism for more severe viral infection. Our data show that acute CS exposure allows for more severe airway epithelial disease from SARS-CoV-2 by reducing the innate immune response and ABSC proliferation and has implications for disease spread and severity in people exposed to CS.

10.
bioRxiv ; 2020 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-33269352

RESUMEN

We recently discovered a superantigen-like motif, similar to Staphylococcal enterotoxin B (SEB), near the S1/S2 cleavage site of SARS-CoV-2 Spike protein, which might explain the multisystem-inflammatory syndrome (MIS-C) observed in children and cytokine storm in severe COVID-19 patients. We show here that an anti-SEB monoclonal antibody (mAb), 6D3, can bind this viral motif, and in particular its PRRA insert, to inhibit infection by blocking the access of host cell proteases, TMPRSS2 or furin, to the cleavage site. The high affinity of 6D3 for the furin-cleavage site originates from a poly-acidic segment at its heavy chain CDR2, a feature shared with SARS-CoV-2-neutralizing mAb 4A8. The affinity of 6D3 and 4A8 for this site points to their potential utility as therapeutics for treating COVID-19, MIS-C, or common cold caused by human coronaviruses (HCoVs) that possess a furin-like cleavage site.

11.
Front Immunol ; 11: 571489, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33362760

RESUMEN

Superparamagnetic iron oxide nanoparticles (SPION) are employed as diagnostics and therapeutics following intravenous delivery for the treatment of iron deficiency anemia (IDA) in adult patients with chronic kidney failure. Neutrophils are the first defense against blood borne foreign insult and recruit to vascular sites of inflammation via a sequential process that is characterized by adhesive capture, rolling, and shear resistant arrest. A primary chemotactic agonist presented on the glycocalyx of inflamed endothelium is IL-8, which upon binding to its cognate membrane receptor (CXCR1/2) activates a suite of responses in neutrophils. An early response is degranulation with accompanying upregulation of ß2-integrin (CD11/CD18) and shedding of L-selectin (CD62L) receptors, which exert differential effects on the efficiency of endothelial recruitment. Feraheme is an FDA approved SPION treatment for IDA, but its effect on the innate immune response of neutrophils during inflammation has not been reported. Here, we studied the immunomodulatory effects of Feraheme on neutrophils freshly isolated from healthy human subjects and stimulated in suspension or on inflammatory mimetic substrates with IL-8. Cells treated with Feraheme exhibited reduced sensitivity to stimulation with IL-8, indicated by reduced upregulation of membrane CD11b/CD18 receptors, high affinity (HA) CD18, and shedding of CD62L. Feraheme also inhibited N-formyl-Met-Leu-Phe (fMLP) induced reactive oxygen species production. Neutrophil rolling, arrest, and migration was assessed in vascular mimetic microfluidic channels coated with E-selectin and ICAM-1 to simulate inflamed endothelium. Neutrophils exposed to Feraheme rolled faster on E-selectin and arrested less frequently on ICAM-1, in a manner dependent upon SPION concentration. Subsequent neutrophil shape change, and migration were also significantly inhibited in the presence of Feraheme. Lastly, Feraheme accelerated clearance of cytosolic calcium flux following IL-8 stimulation. We conclude that uptake of Feraheme by neutrophils inhibits chemotactic activation and downregulates normal rolling to arrest under shear flow. The mechanism involves increased calcium clearance following chemotactic activation, which may diminish the efficiency of recruitment from the circulation at vascular sites of inflammation.

12.
Phys Fluids (1994) ; 32(11): 111702, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-33244211

RESUMEN

Syndrome coronavirus 2 (SARS-CoV-2) infectious virions are viable on various surfaces (e.g., plastic, metals, and cardboard) for several hours. This presents a transmission cycle for human infection that can be broken by developing new inactivation approaches. We employed an efficient cold atmospheric plasma (CAP) with argon feed gas to inactivate SARS-CoV-2 on various surfaces including plastic, metal, cardboard, basketball composite leather, football leather, and baseball leather. These results demonstrate the great potential of CAP as a safe and effective means to prevent virus transmission and infections for a wide range of surfaces that experience frequent human contact. Since this is the first-ever demonstration of cold plasma inactivation of SARS-CoV-2, it is a significant milestone in the prevention and treatment of coronavirus disease 2019 (COVID-19) and presents a new opportunity for the scientific, engineering, and medical communities.

13.
Chem Commun (Camb) ; 2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-33236739

RESUMEN

The two isomers of the propylperoxy radical 1-C3H7O2 and 2-C3H7O2, together with their individual rotamers, are identified and assigned by threshold photoelectron spectroscopy with the aid of high-level theoretical computations, from which their accurate adiabatic ionization energies are derived. This study paves the way to probing elusive peroxy radicals and their isomers in advanced mass spectrometry analysis of combustion and atmospheric reactions.

14.
J Chem Phys ; 153(12): 124306, 2020 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-33003730

RESUMEN

We report a synchrotron radiation vacuum ultraviolet photoionization study of the hydroperoxyl radical (HO2), a key reaction intermediate in combustion and atmospheric chemistry as well as astrochemistry, using double imaging photoelectron photoion coincidence spectroscopy. The HO2 radical is formed in a microwave discharge flow tube reactor through a set of reactions initiated by F atoms in a CH4/O2/He gas mixture. The high-resolution threshold photoelectron spectrum of HO2 in the 11 eV-12 eV energy range is acquired without interferences from other species and assigned with the aid of theoretically calculated adiabatic ionization energies (AIEs) and Franck-Condon factors. The three vibrational modes of the radical cation HO2 +, the H-O stretch, the H-O-O bend, and the O-O stretch, have been identified, and their individual frequencies are measured. In addition, the AIEs of the X3A″ ground state and the a1A' first excited electronic state of HO2 + are experimentally determined at 11.359 ± 0.003 eV and 11.639 ± 0.005 eV, respectively, in agreement with high-level theoretically computed results. Furthermore, the former AIE value provides validation of thermochemical networks used to extract the enthalpy of formation of the HO2 radical.

15.
Chemphyschem ; 21(21): 2468-2483, 2020 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-32893958

RESUMEN

The VUV absorption spectrum of fenchone is re-examined using synchrotron radiation Fourier transform spectrometry, revealing new vibrational structure. Picosecond laser (2+1) resonance enhanced multiphoton ionization (REMPI) spectroscopy complements this, providing an alternative view of the 3spd Rydberg excitation region. These spectra display broadly similar appearance, with minor differences that are largely explained by referring to calculated one- and two-photon electronic excitation cross-sections. Both show good agreement with Franck-Condon simulations of the relevant vibrational structures. Parent ion REMPI ionization yields with both femtosecond and picosecond excitation laser pulses are studied as a function of laser polarization and intensity, the latter providing insight into the relative two-photon excitation and one-photon ionization rates. The experimental circular-linear dichroism observed in the parent ion yields varies strongly between the 3s and 3p Rydberg states, in good overall agreement with the calculated two-photon excitation circular-linear dichroism, while corroborating other evidence that the 3pz sub-state plays no more than a very minor role in the (2+1) REMPI spectrum. Vibrationally resolved photoelectron spectra are recorded with picosecond pulse duration (2+1) REMPI at selected intermediate vibrational excitations. The 3s intermediate state displays a very strong Δv=0 propensity on ionization, but the 3p intermediate evidences more complex vibronic dynamics, and we infer some 3p→3s internal conversion prior to ionization.

16.
Phys Chem Chem Phys ; 22(37): 21068-21073, 2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-32939522

RESUMEN

We report a comprehensive vacuum ultraviolet (VUV) photoionization study of the nitrogen dioxide dimer (NO2)2 by using a state-of-the-art method of double imaging photoelectron photoion coincidence (i2PEPICO) spectroscopy at synchrotron SOLEIL. We find that the dimer cation N2O4+ from direct ionization of (NO2)2 is not stable and fully dissociates into the NO2+ and NO2 fragments. After identifying and separating the two different sources of NO2+ cations observed in experiments, direct photoionization of the monomer NO2 and dissociative photoionization of the co-existing dimer (NO2)2, the pure mass-selected threshold photoelectron spectrum (TPES) of the dimer (NO2)2 has been recorded without the need of subtraction. An upper limit of the adiabatic ionization energy of the dimer (AIE ≤ 9.59 ± 0.05 eV) and the appearance energy of the NO2+ fragment (AE = 10.15 ± 0.05 eV) are also given. In addition, the state-selected dynamics of the five low-lying electronic states of the cation N2O4+ have been analyzed from the corresponding kinetic energy release distributions.

17.
Int J Mol Sci ; 21(18)2020 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-32971806

RESUMEN

Electron scattering cross sections for pyridine in the energy range 0-100 eV, which we previously measured or calculated, have been critically compiled and complemented here with new measurements of electron energy loss spectra and double differential ionization cross sections. Experimental techniques employed in this study include a linear transmission apparatus and a reaction microscope system. To fulfill the transport model requirements, theoretical data have been recalculated within our independent atom model with screening corrected additivity rule and interference effects (IAM-SCAR) method for energies above 10 eV. In addition, results from the R-matrix and Schwinger multichannel with pseudopotential methods, for energies below 15 eV and 20 eV, respectively, are presented here. The reliability of this complete data set has been evaluated by comparing the simulated energy distribution of electrons transmitted through pyridine, with that observed in an electron-gas transmission experiment under magnetic confinement conditions. In addition, our representation of the angular distribution of the inelastically scattered electrons is discussed on the basis of the present double differential cross section experimental results.

18.
bioRxiv ; 2020 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-32766588

RESUMEN

Most demographic studies are now associating current smoking status with increased risk of severe COVID-19 and mortality from the disease but there remain many questions about how direct cigarette smoke exposure affects SARS-CoV-2 airway cell infection. We directly exposed mucociliary air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term cigarette smoke and infected them with live SARS-CoV-2. We found an increase in the number of infected airway cells after cigarette smoke exposure as well as an increased number of apoptotic cells. Cigarette smoke exposure alone caused airway injury that resulted in an increased number of ABSCs, which proliferate to repair the airway. But we found that acute SARS-CoV-2 infection or the combination of exposure to cigarette smoke and SARS-CoV-2 did not induce ABSC proliferation. We set out to examine the underlying mechanism governing the increased susceptibility of cigarette smoke exposed ALI to SARS-CoV-2 infection. Single cell profiling of the cultures showed that infected airway cells displayed a global reduction in gene expression across all airway cell types. Interestingly, interferon response genes were induced in SARS-CoV-2 infected airway epithelial cells in the ALI cultures but smoking exposure together with SARS-CoV-2 infection reduced the interferon response. Treatment of cigarette smoke-exposed ALI cultures with Interferon ß-1 abrogated the viral infection, suggesting that the lack of interferon response in the cigarette smoke-exposed ALI cultures allows for more severe viral infection and cell death. In summary, our data show that acute smoke exposure allows for more severe proximal airway epithelial disease from SARS-CoV-2 by reducing the mucosal innate immune response and ABSC proliferation and has implications for disease spread and severity in people exposed to cigarette smoke.

19.
Am J Trop Med Hyg ; 103(5): 2108-2112, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32748782

RESUMEN

Vector control methods that mobilize and impact rapidly during dengue, Zika, and chikungunya outbreaks are urgently needed in urban contexts. We investigated whether one person using a handheld aerosolized insecticide could achieve efficacy levels comparable to targeted indoor residual spraying (TIRS), using pyrethroid-resistant Aedes aegypti in a semi-field setting with experimental houses in Mexico. The insecticide product (H24, a carbamate and pyrethroid mixture), available over-the-counter locally, was sprayed only on known Ae. aegypti-resting surfaces, for example, walls less than 1.5 m and dark hidden areas. In six identical houses with paired bedrooms, one bedroom was treated, and the other remained an untreated control. Each week for 8 weeks, 100 female pyrethroid-resistant Ae. aegypti were released in each bedroom and followed up daily. Mortality rates in treated bedrooms exceeded 90% for at least 2 weeks, and more than 80% (89.2; 95% CI: 79.98-98.35) for 3 weeks or more. Mortality rates in control houses were zero. Results demonstrate that the immediate impact of TIRS can be delivered by one person using existing products, at an estimated cost for the average household in Mexico of under US$3 per month. Triggered by early outbreak signs, dissemination via community hubs and mass/social media of instructions to treat the home immediately, with monthly re-treatment thereafter, provides a simple means to engage and empower householders. Compatible with integrated vector management strategies, it enables self-protection even if existing agencies falter, a situation exemplified by the potential impact on vector control of the restrictions imposed during the 2020 COVID-19 pandemic.


Asunto(s)
Aedes , Resistencia a los Insecticidas , Insecticidas/análisis , Control de Mosquitos/métodos , Mosquitos Vectores , Aerosoles , Animales , Femenino , Vivienda , México , Piretrinas
20.
Sci Rep ; 10(1): 12857, 2020 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-32732984

RESUMEN

The cattle tick, Rhipicephalus microplus, is a monoxenous tick that co-evolved with indicine cattle on the Indian subcontinent. It causes massive damage to livestock worldwide. Cattle breeds present heritable, contrasting phenotypes of tick loads, taurine breeds carrying higher loads of the parasite than indicine breeds. Thus, a useful model is available to analyze mechanisms that determine outcomes of parasitism. We sought to gain insights on these mechanisms and used RNA sequencing and Multidimensional Protein Identification Technology (MudPIT) to generate a transcriptome from whole larvae and salivary glands from nymphs, males and females feeding on genetically susceptible and resistant bovine hosts and their corresponding proteomes. 931,698 reads were annotated into 11,676 coding sequences (CDS), which were manually curated into 116 different protein families. Male ticks presented the most diverse armamentarium of mediators of parasitism. In addition, levels of expression of many genes encoding mediators of parasitism were significantly associated with the level and stage of host immunity and/or were temporally restricted to developmental stages of the tick. These insights should assist in developing novel, sustainable technologies for tick control.

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