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1.
Proc Natl Acad Sci U S A ; 120(11): e2212270120, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36877833

RESUMO

Recently, social media platforms are heavily moderated to prevent the spread of online hate speech, which is usually fertile in toxic words and is directed toward an individual or a community. Owing to such heavy moderation, newer and more subtle techniques are being deployed. One of the most striking among these is fear speech. Fear speech, as the name suggests, attempts to incite fear about a target community. Although subtle, it might be highly effective, often pushing communities toward a physical conflict. Therefore, understanding their prevalence in social media is of paramount importance. This article presents a large-scale study to understand the prevalence of 400K fear speech and over 700K hate speech posts collected from Gab.com. Remarkably, users posting a large number of fear speech accrue more followers and occupy more central positions in social networks than users posting a large number of hate speech. They can also reach out to benign users more effectively than hate speech users through replies, reposts, and mentions. This connects to the fact that, unlike hate speech, fear speech has almost zero toxic content, making it look plausible. Moreover, while fear speech topics mostly portray a community as a perpetrator using a (fake) chain of argumentation, hate speech topics hurl direct multitarget insults, thus pointing to why general users could be more gullible to fear speech. Our findings transcend even to other platforms (Twitter and Facebook) and thus necessitate using sophisticated moderation policies and mass awareness to combat fear speech.


Assuntos
Mídias Sociais , Humanos , Fala , Medo , Fertilidade , Ódio
2.
Nature ; 570(7760): 205-209, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31168098

RESUMO

Some of the most sensitive and precise measurements-for example, of inertia1, gravity2 and rotation3-are based on matter-wave interferometry with free-falling atomic clouds. To achieve very high sensitivities, the interrogation time has to be very long, and consequently the experimental apparatus needs to be very tall (in some cases reaching ten or even one hundred metres) or the experiments must be performed in microgravity in space4-7. Cancelling gravitational acceleration (for example, in atomtronic circuits8,9 and matter-wave guides10) is expected to result in compact devices with extended interrogation times and therefore increased sensitivity. Here we demonstrate smooth and controllable matter-wave guides by transporting Bose-Einstein condensates (BECs) over macroscopic distances. We use a neutral-atom accelerator ring to bring BECs to very high speeds (16 times their sound velocity) and transport them in a magnetic matter-wave guide for 15 centimetres while fully preserving their internal coherence. The resulting high angular momentum of more than 40,000h per atom (where h is the reduced Planck constant) gives access to the higher Landau levels of quantum Hall states, and the hypersonic velocities achieved, combined with our ability to control potentials with picokelvin precision, will facilitate the study of superfluidity and give rise to tunnelling and a large range of transport regimes of ultracold atoms11-13. Coherent matter-wave guides are expected to enable interaction times of several seconds in highly compact devices and lead to portable guided-atom interferometers for applications such as inertial navigation and gravity mapping.

3.
J Neurosci ; 43(44): 7264-7275, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37699715

RESUMO

Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that are involved in synapse assembly and function. The NLGN gene family consists of 5 genes (NLGN1-3, 4X, and 4Y). NLGN3 forms heterodimers with other NLGNs and is expressed at both excitatory and inhibitory synapses, although the distinct role at different synapses is not fully understood. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase that targets various neuronal substrates to impact neuronal migration, neurite outgrowth, synaptic transmission, and plasticity. Both NLGNs and their presynaptic binding partners neurexins are highly associated with neurodevelopmental disorders. The NLGN3 gene is on the X chromosome and variants in NLGN3 have been linked to the pathophysiology in neurodevelopmental disorders. To better understand the endogenous modulation of NLGN3, we generated an HA-tagged knock-in mouse. We found that Cdk5 associates with NLGN3 in vivo and phosphorylates NLGN3 on serine 725 (S725) in the knock-in mouse of either sex. The phosphorylation affects the NLGN3 association with Kalirin-7, a postsynaptic guanine nucleotide exchange factors for Rho GTPase family proteins. We further observed that the phosphorylation modulates NLGN3 surface expression and NLGN3-mediated synaptic currents in cultured rat neurons. Thus, we characterized NLGN3 as a novel Cdk5 substrate and revealed the functional consequences of NLGN3 S725 phosphorylation in neurons. Our study provides a novel molecular mechanism underlying Cdk5-mediated regulation of postsynaptic cell adhesion molecules.SIGNIFICANCE STATEMENT NLGN3 is involved in synapse assembly and function at both excitatory and inhibitory synapses and has been associated with the pathophysiology of neurodevelopmental disorders. Cdk5 has brain-specific activity and is involved in neuronal transmission, synapse function, and plasticity. Here, we characterize NLGN3 as a Cdk5 substrate for the first time and show that Cdk5-mediated phosphorylation regulates NLGN3 function. We demonstrate that NLGN3 S725 is a Cdk5 phosphorylation site, and reveal that the site is important for NLGN3 association with Kalirin-7, NLGN3 surface expression, and NLGN3-mediated synaptic transmission.


Assuntos
Quinase 5 Dependente de Ciclina , Sinapses , Animais , Camundongos , Ratos , Moléculas de Adesão Celular/metabolismo , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/metabolismo , Fosforilação/fisiologia , Fatores de Troca de Nucleotídeo Guanina Rho/metabolismo , Serina/metabolismo , Sinapses/metabolismo , Transmissão Sináptica
4.
Funct Integr Genomics ; 24(2): 41, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38386088

RESUMO

Plant diseases pose a severe threat to the food security of the global human population. One such disease is Fusarium wilt, which affects many plant species and causes up to 100% yield losses. Fusarium pathogen has high variability in its genetic constitution; therefore, it has evolved into different physiological races to infect different plant species spread across the different geographical regions of the world. The pathogen mainly affects plant roots, leading to colonizing and blocking vascular bundle cells, specifically xylem vessels. This blocking results in chlorosis, vascular discoloration, leaf wilting, shortening of plant, and, in severe cases, premature plant death. Due to the soil-borne nature of the wilt pathogen, neither agronomic nor plant protection measures effectively reduce the incidence of the disease. Therefore, the most cost-effective management strategy for Fusarium wilt is developing varieties resistant to a particular race of the fungus wilt prevalent in a given region. This strategy requires understanding the pathogen, its disease cycle, and epidemiology with climate-changing scenarios. Hence, in the review, we will discuss the pathogenic aspect and genetics of the Fusarium wilt, including molecular interventions for developing climate-smart wilt tolerant/resistant varieties of crops. Overall, this review will add to our knowledge for advancing the breeding of resistance against the wilt pandemic.


Assuntos
Fusarium , Pandemias , Humanos , Melhoramento Vegetal , Agricultura , Mudança Climática
5.
Nanotechnology ; 35(27)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38502954

RESUMO

Developing sustainable and innovative approaches for the efficient reduction of nitrophenols is crucial for environmental remediation, for managing health concerns posed by their widespread presence as hazardous pollutants in industrial effluents and contaminated water. We report the use of 12.9 ± 1 nm (TEM data) sized gold carbon dot nanoconjugates (Au@CDs) for catalytic conversion of o, m, p-nitrophenols to aminophenols by sodium borohydride. A simple approach was followed to synthesize ultra-small and highly stable Au@CDs, using citric acid and PEG as reducing and stabilizing agents. X-ray diffraction analysis verified the formation of nano-crystalline nanoconjugates. These nanoconjugates showed a remarkable catalytic activity in the range of 0.22-0.33 s-1(varying with nanoconjugate concentration) which was much higher compared to conventional chemical methods of reduction. All the catalytic reaction experiments were performed at room temperature (27 ± 2 °C). Furthermore, an increase in rate constant was observed with increasing concentration of nanoconjugates. The catalytic activity of Au@CDs nanoconjugates was observed to be in order of m-nitrophenol > o-nitrophenol > p-nitrophenol with apparent rate constant (kaap) values of 0.068, 0.043 and 0.031, respectively. Comparative analysis with GNPs, CDs and Au@CDs nanoconjugates stated that the nanoconjugates had superior catalytic activity. The research can have significant implications in the development of new strategies for environmental remediation and biomedical applications.

6.
Funct Integr Genomics ; 23(4): 296, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37697159

RESUMO

Given the future demand for food crops, increasing crop productivity in drought-prone rainfed areas has become essential. Drought-tolerant varieties are warranted to solve this problem in major crops, with drought tolerance as a high-priority trait for future research. Maize is one such crop affected by drought stress, which limits production, resulting in substantial economic losses. It became a more serious issue due to global climate change. The most drought sensitive among all stages of maize is the reproductive stages and the most important for overall maize production. The exact molecular basis of reproductive drought sensitivity remains unclear due to genes' complex regulation of drought stress. Understanding the molecular biology and signaling of the unexplored area of reproductive drought tolerance will provide an opportunity to develop climate-smart drought-tolerant next-generation maize cultivars. In recent decades, significant progress has been made in maize to understand the drought tolerance mechanism. However, improving maize drought tolerance through breeding is ineffective due to the complex nature and multigenic control of drought traits. With the help of advanced breeding techniques, molecular genetics, and a precision genome editing approach like CRISPR-Cas, candidate genes for drought-tolerant maize can be identified and targeted. This review summarizes the effects of drought stress on each growth stage of maize, potential genes, and transcription factors that determine drought tolerance. In addition, we discussed drought stress sensing, its molecular mechanisms, different approaches to developing drought-resistant maize varieties, and how molecular breeding and genome editing will help with the current unpredictable climate change.


Assuntos
Secas , Zea mays , Zea mays/genética , Melhoramento Vegetal , Resistência à Seca , Produtos Agrícolas/genética , Percepção
7.
Funct Integr Genomics ; 23(3): 210, 2023 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-37355501

RESUMO

Millets are nutrient-rich (nutri-rich) cereals with climate resilience attributes. However, its full productive potential is not realized due to the lack of a focused yield improvement approach, as evidenced by the available literature. Also, the lack of well-characterized genomic resources significantly limits millet improvement. But the recent availability of genomic data and advancement in omics tools has shown its enormous potential to enhance the efficiency and precision faced by conventional breeding in millet improvement. The development of high throughput genotyping platforms based on next-generation sequencing (NGS) has provided a low-cost method for genomic information, specifically for neglected nutri-rich cereals with the availability of a limited number of reference genome sequences. NGS has created new avenues for millet biotechnological interventions such as mutation-based study, GWAS, GS, and other omics technologies. The simultaneous discovery of high-throughput markers and multiplexed genotyping platform has aggressively aided marker-assisted breeding for millet improvement. Therefore, omics technology offers excellent opportunities to explore and combine useful variations for targeted traits that could impart high nutritional value to high-yielding cultivars under changing climatic conditions. In millet improvement, an in-depth account of NGS, integrating genomics data with different biotechnology tools, is reviewed in this context.


Assuntos
Milhetes , Melhoramento Vegetal , Milhetes/genética , Genômica , Grão Comestível/genética , Fenótipo
8.
Biochem Biophys Res Commun ; 655: 97-103, 2023 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-36934590

RESUMO

Serum cholesterol dysregulation is associated with prognosis and diagnosis of many diseases and effective biosensor will improvise their management. A novel electrochemical biosensor was fabricated based on gelatin-Au@CD nanoconjugate films for cholesterol detection. Initially, the surface of indium titanium oxide (ITO) coated glass was modified by drop casting of gelatin-Au@CD nanoconjugates to prepare the electrodes. Electrochemical studies for detection of bioanalytes(such as urea (U), ascorbic acid (AA), oxalic acid (OA), gallic acid (GA), cholesterol (Chox), dextrose (D), l-cysteine (Cys) and citric acid (CA)) were performed using cyclic voltammetry. The presence of nanoconjugates provided an appropriate environment for enhanced electrochemical response for cholesterol. These electrodes exhibited a linear response towards the presence of cholesterol in the linear concentration range of 2-20 mM with a correlation coefficient of 0.95, and the superior sensitivity of 1.36 µA/mM/cm2. Additionally, enhanced sensitivity (2.99 µA/mM/cm2) of nitrogen ion irradiated films up to a fluence of 1016 ions/cm2 was noticed because of morphological changes in the electrode surface brought about by irradiation. Approximately 54% enhancement was found when the ion fluence was 1016 ions/cm2. The designed nanoconjugate electrode showed excellent response towards cholesterol sensing and eliminates the requirement of any enzymes making the overall process simpler, cost-effective and allows for room temperature storage.


Assuntos
Técnicas Biossensoriais , Carbono , Nanoconjugados , Gelatina , Ouro , Colesterol , Eletrodos , Técnicas Eletroquímicas
9.
Biochem Biophys Res Commun ; 675: 99-105, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37463525

RESUMO

In this study, we have fabricated a novel platform for sensing of urea using gelatin/carbon dots nanocomposite system. The sensor electrode was created by depositing the nanocomposite gel onto thin glass plates coated with indium tin oxide (ITO) using the drop casting technique. The behavior of these electrodes was investigated against a number of bioanalytes in the concentration range of 2-20 mM by cyclic voltammetry. The system was observed to be highly selective for urea with a sensitivity of 1.65 µA/mM/cm in the experimental linear range of 2-20 mM. Furthermore, the gelatin/CD-ITO electrode were also subjected to 50 KeV N2+ ion beam irradiation with varying fluence in the range of 1012 to 1016 ions/cm2. Sensing profile of the irradiated samples for urea suggested enhancement in sensitivity to 2 µA/mM cm2, when the ion fluence was 5 × 1015 ions/cm2. This enhancement after irradiation suggests a clear dependence of detection on the fluence of the ion beam. The observed excellent sensitivity of radiation processed nanocomposite material can be used as an enzyme-free platform for urea detection. Additionally, the CDs showed fluorescence quenching on treatment with mere 50 µM urea suggesting the high sensitivity of the platform.


Assuntos
Carbono , Nanocompostos , Ureia , Gelatina , Eletrodos , Íons , Técnicas Eletroquímicas
10.
J Biol Chem ; 296: 100224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33361160

RESUMO

The initial activation step in the gating of ubiquitously expressed Orai1 calcium (Ca2+) ion channels represents the activation of the Ca2+-sensor protein STIM1 upon Ca2+ store depletion of the endoplasmic reticulum. Previous studies using constitutively active Orai1 mutants gave rise to, but did not directly test, the hypothesis that STIM1-mediated Orai1 pore opening is accompanied by a global conformational change of all Orai transmembrane domain (TM) helices within the channel complex. We prove that a local conformational change spreads omnidirectionally within the Orai1 complex. Our results demonstrate that these locally induced global, opening-permissive TM motions are indispensable for pore opening and require clearance of a series of Orai1 gating checkpoints. We discovered these gating checkpoints in the middle and cytosolic extended TM domain regions. Our findings are based on a library of double point mutants that contain each one loss-of-function with one gain-of-function point mutation in a series of possible combinations. We demonstrated that an array of loss-of-function mutations are dominant over most gain-of-function mutations within the same as well as of an adjacent Orai subunit. We further identified inter- and intramolecular salt-bridge interactions of Orai subunits as a core element of an opening-permissive Orai channel architecture. Collectively, clearance and synergistic action of all these gating checkpoints are required to allow STIM1 coupling and Orai1 pore opening. Our results unravel novel insights in the preconditions of the unique fingerprint of CRAC channel activation, provide a valuable source for future structural resolutions, and help to understand the molecular basis of disease-causing mutations.


Assuntos
Sinalização do Cálcio , Cálcio/metabolismo , Ativação do Canal Iônico/genética , Proteínas de Neoplasias/química , Proteína ORAI1/química , Molécula 1 de Interação Estromal/química , Substituição de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Regulação da Expressão Gênica , Genes Reporter , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Lipossomos/química , Lipossomos/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Simulação de Dinâmica Molecular , Mutação , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteína ORAI1/genética , Proteína ORAI1/metabolismo , Técnicas de Patch-Clamp , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo
11.
Infect Immun ; 90(5): e0029121, 2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34780281

RESUMO

Macrophages are key arsenals of the immune system against invaders. After compartmental isolation of a pathogen in phagosomes, the host immune response attempts to neutralize the pathogen. However, pathogens possess the ability to subvert these assaults and can also convert macrophages into their replicative niche. The multiple host defense evasion mechanisms employed by these pathogens include phagosome maturation arrest, molecular mimicry through secretory antigens, interference with host signaling, active radical neutralization, inhibition of phagosome acidification, alteration of programmed cell death, and other mechanisms. Macrophage biology as a part of the host-pathogen interaction has expanded rapidly in the past decade. The present review aims to shed some light upon the macrophage defense evasion strategies employed by pathogens. We have also incorporated recent knowledge in the field of macrophage dynamics during infection and evolutionary perspectives of macrophage dynamics.


Assuntos
Evasão da Resposta Imune , Fagossomos , Apoptose , Interações Hospedeiro-Patógeno , Macrófagos
12.
Proc Natl Acad Sci U S A ; 116(24): 12035-12044, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31138690

RESUMO

PSD-95 is a scaffolding protein that regulates the synaptic localization of many receptors, channels, and signaling proteins. The NLGN gene family encodes single-pass transmembrane postsynaptic cell adhesion molecules that are important for synapse assembly and function. At excitatory synapses, NLGN1 mediates transsynaptic binding with neurexin, a presynaptic cell adhesion molecule, and also binds to PSD-95, although the relevance of the PSD-95 interaction is not clear. We now show that disruption of the NLGN1 and PSD-95 interaction decreases surface expression of NLGN1 in cultured neurons. Furthermore, PKA phosphorylates NLGN1 on S839, near the PDZ ligand, and dynamically regulates PSD-95 binding. A phosphomimetic mutation of NLGN1 S839 significantly reduced PSD-95 binding. Impaired NLGN1/PSD-95 binding diminished synaptic NLGN1 expression and NLGN1-mediated synaptic enhancement. Our results establish a phosphorylation-dependent molecular mechanism that regulates NLGN1 and PSD-95 binding and provides insights into excitatory synaptic development and function.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Animais , Células Cultivadas , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Fosforilação/fisiologia , Ligação Proteica/fisiologia , Sinapses/metabolismo
13.
Physiol Mol Biol Plants ; 28(4): 719-735, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35592484

RESUMO

Insect wounding activates a large number of signals that function coordinately to modulate gene expression and elicit defense responses. How each signal influences gene expression in absence of wounding is also important since it can shed light on changes occurring during the shift to wound response. Using simulated Helicoverpa armigera herbivory on chickpea, we had identified at least 14 WRKY genes that showed 5-50 fold increase in expression within 5-20 min of wounding. Our studies show that contrary to their collective effects upon wounding, individual chemical cues show distinct and often opposite effects in absence of wounding. In particular, jasmonic acid, a key early defense hormone, reduced transcripts of most WRKY genes by > 50% upon treatment of unwounded chickpea leaves as did salicylic acid. Neomycin (a JA biosynthesis inhibitor) delayed and also reduced early wound expression. H2O2 transiently activated several genes within 5-20 min by 5-8 fold while ethylene activated only a few WRKY genes by 2-5 fold. The summation of the individual effects of these chemical cues does not explain the strong increase in transcript levels upon wounding. Detailed studies of a 931 nt region of the CaWRKY41 promoter, show strong wound-responsive GUS expression in Arabidopsis even in presence of neomycin. Surprisingly its expression was lost in the coi1, ein2 and myc2myc3myc4 mutant backgrounds suggesting the requirement of intact ethylene and JA signaling pathways (dependent on MYCs) for wound-responsive expression. The studies highlight the complexity of gene regulation by different chemical cues in the presence and absence of wounding. Supplementary Information: The online version contains Supplementary material available at 10.1007/s12298-022-01170-y.

14.
J Biol Chem ; 295(25): 8575-8588, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32376687

RESUMO

Group I metabotropic glutamate receptors (mGluRs) play important roles in various neuronal functions and have also been implicated in multiple neuropsychiatric disorders like fragile X syndrome, autism, and others. mGluR trafficking not only plays important roles in controlling the spatiotemporal localization of these receptors in the cell but also regulates the activity of these receptors. Despite this obvious significance, the cellular machineries that control the trafficking of group I metabotropic glutamate receptors in the central nervous system have not been studied in detail. The post-synaptic scaffolding protein tamalin has been shown to interact with group I mGluRs and also with many other proteins involved in protein trafficking in neurons. Using a molecular replacement approach in mouse hippocampal neurons, we show here that tamalin plays a critical role in the ligand-dependent internalization of mGluR1 and mGluR5, members of the group I mGluR family. Specifically, knockdown of endogenous tamalin inhibited the ligand-dependent internalization of these two receptors. Both N-terminal and C-terminal regions of tamalin played critical roles in mGluR1 endocytosis. Furthermore, we found that tamalin regulates mGluR1 internalization by interacting with S-SCAM, a protein that has been implicated in vesicular trafficking. Finally, we demonstrate that tamalin plays a critical role in mGluR-mediated internalization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, a process believed to be the cellular correlate for mGluR-dependent synaptic plasticity. Taken together, these findings reveal a mechanistic role of tamalin in the trafficking of group I mGluRs and suggest its physiological implications in the brain.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Receptor de Glutamato Metabotrópico 5/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Endocitose , Guanilato Quinases/antagonistas & inibidores , Guanilato Quinases/genética , Guanilato Quinases/metabolismo , Células HEK293 , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Ligantes , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Domínios Proteicos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptor de Glutamato Metabotrópico 5/genética , Receptores de Glutamato Metabotrópico/genética
15.
J Med Virol ; 93(10): 6045-6049, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34170552

RESUMO

Coronavirus disease 2019 (COVID-19) has been shown to be associated with a lot of neurological complications, of whom Guillain-Barre syndrome (GBS) is an important post-infectious consequentiality. More than 220 patients with GBS have been reported thus far. We intend to share our experience with five patients of GBS where one of them had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the cerebrospinal fluid (CSF). This is the first-ever report demonstrating the presence of SARS-CoV-2 in the CSF of an adult patient; a similar occurrence has recently been described in a pediatric patient. We wish to emphasize the fact that commonly GBS occurs as a result of a post-infectious process but in a few cases where the symptoms of COVID-19 and GBS occur concurrently, corresponding to the viremic phase, separate pathogenesis needs to be thought of. This para-infectious nature is exemplified by the presence of virus in the cerebrospinal fluid of one of our patients. We review the neuroinvasive potential of SARS-Cov-2 in this regard and draw parallels with Cytomegalovirus, Zika virus, and Human Immunodeficiency virus-associated occurrences of GBS.


Assuntos
COVID-19/complicações , Síndrome de Guillain-Barré/etiologia , Adulto , COVID-19/líquido cefalorraquidiano , COVID-19/terapia , Líquido Cefalorraquidiano/virologia , Feminino , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Resultado do Tratamento
16.
J Exp Bot ; 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051078

RESUMO

In contrast to animals, plants cannot avoid unfavorable temperature conditions. Instead, plants have evolved intricate signaling pathways that enable them to perceive and respond to temperature. General acclimation processes that prepare the plant to respond to stressful heat and cold, usually occur throughout the whole plant. More specific temperature responses, however, are limited to certain tissues or cell types. While global responses are amenable to epigenomic analyses, responses which are highly localized are more problematic as the chromatin in question is not easily accessible. Here we review the current knowledge of the epigenetic regulation of FLOWERING LOCUS C and FLOWERING LOCUS T as examples of temperature-responsive flowering time regulators that are expressed broadly throughout the plants and in specific cell types, respectively. While undoubtably extremely successful, we reason that future analyses would benefit from higher spatiotemporal resolution. We conclude by reviewing methods and successful applications of tissue- and cell type-specific epigenomic analyses and provide a brief outlook into the future, single-cell epigenomics.

17.
Phys Rev Lett ; 126(17): 170402, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33988404

RESUMO

In this Letter, we demonstrate magnetogravitational matter-wave lensing as a novel tool in atom-optics in atomtronic waveguides. We collimate and focus matter waves originating from Bose-Einstein condensates and ultracold thermal atoms in ring-shaped time-averaged adiabatic potentials. We demonstrate "delta-kick cooling" of Bose-Einstein condensates, reducing their expansion energies by a factor of 46 down to 800 pK. The atomtronic waveguide ring has a diameter of less than one millimeter, compared to other state-of-the-art experiments requiring zero gravity or free-flight distances of ten meters and more. This level of control with extremely reduced spatial requirements is an important step toward atomtronic quantum sensors.

18.
Clin Chem Lab Med ; 59(5): 921-933, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33554515

RESUMO

OBJECTIVES: Novel treatment options for some carbapenem-resistant Gram-negative pathogens have been identified by the World Health Organization as being of the highest priority. Ceftolozane-tazobactam is a novel cephalosporin-beta-lactamase inhibitor combination antibiotic with potent bactericidal activity against the most difficult-to-treat multi-drug resistant and extensively drug resistant Gram-negative pathogens. This study aimed to develop and validate a liquid chromatography - tandem mass spectrometry method for the simultaneous quantification of ceftolozane and tazobactam in plasma (total and unbound), renal replacement therapy effluent (RRTE), cerebrospinal fluid (CSF) and urine. METHODS: Analytes were separated using mixed-mode chromatography with an intrinsically base-deactivated C18 column and a gradient mobile phase consisting of 0.1% formic acid, 10 mM ammonium formate and acetonitrile. The analytes and internal standards were detected using rapid ionisation switching between positive and negative modes with simultaneous selected reaction monitoring. RESULTS: A quadratic calibration was obtained for plasma (total and unbound), RRTE and CSF over the concentration range of 1-200 mg/L for ceftolozane and 0.5-100 mg/L for tazobactam, and for urine the concentration range of 10-2,000 mg/L for ceftolozane and 5-1,000 mg/L for tazobactam. For both ceftolozane and tazobactam, validation testing for matrix effects, precision and accuracy, specificity and stability were all within the acceptance criteria of ±15%. CONCLUSIONS: This methodology was successfully applied to one pilot pharmacokinetic study in infected critically ill patients, including patients receiving renal replacement therapy, and one case study of a patient with ventriculitis, where all patients received ceftolozane-tazobactam.


Assuntos
Antibacterianos , Cefalosporinas , Tazobactam , Antibacterianos/uso terapêutico , Cromatografia Líquida , Humanos , Preparações Farmacêuticas , Terapia de Substituição Renal , Espectrometria de Massas em Tandem
19.
Molecules ; 27(1)2021 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-35011351

RESUMO

The effect of aqueous solutions of selected ionic liquids solutions on Ideonella sakaiensis PETase with bis(2-hydroxyethyl) terephthalate (BHET) substrate were studied by means of molecular dynamics simulations in order to identify the possible effect of ionic liquids on the structure and dynamics of enzymatic Polyethylene terephthalate (PET) hydrolysis. The use of specific ionic liquids can potentially enhance the enzymatic hydrolyses of PET where these ionic liquids are known to partially dissolve PET. The aqueous solution of cholinium phosphate were found to have the smallest effect of the structure of PETase, and its interaction with (BHET) as substrate was comparable to that with the pure water. Thus, the cholinium phosphate was identified as possible candidate as ionic liquid co-solvent to study the enzymatic hydrolyses of PET.


Assuntos
Burkholderiales/enzimologia , Hidrolases/metabolismo , Líquidos Iônicos/química , Polietilenotereftalatos/química , Ligação de Hidrogênio , Hidrólise , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Ácidos Ftálicos/química , Conformação Proteica , Solventes/química
20.
Physiol Mol Biol Plants ; 27(4): 873-888, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33967469

RESUMO

Elicitor-induced defense response against potential plant pathogens has been widely reported in several crop plants; however, transcriptome dynamics underlying such defense response remains elusive. Our previous study identified and characterized a novel elicitor, κ-carrageenan, from Kappaphycus alvarezii, a marine red seaweed. Our preliminary studies have shown that the elicitor-treatment enhances the tolerance of a susceptible tomato cultivar to Septoria lycopersici (causative agent of leaf spot disease). To gain further insights into the genes regulated during elicitor treatment followed by pathogen infection, we have performed RNA-Seq experiments under different treatments, namely, control (untreated and uninfected), elicitor treatment, pathogen infection alone, and elicitor treatment followed by pathogen infection. To validate the results, forty-three genes belonging to five different classes, namely, ROS activating and detoxifying enzyme encoding genes, DEAD-box RNA helicase genes, autophagy-related genes, cysteine proteases, and pathogenesis-related genes, were chosen. Expression profiling of each gene was performed using qRT-PCR, and the data was correlated with the RNA-seq data. Altogether, the study has pinpointed a repertoire of genes that could be potential candidates for further functional characterization to provide insights into novel elicitor-induced fungal defense and develop transgenic lines resistant to foliar diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-00970-y.

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