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1.
Plant Cell Environ ; 47(4): 1397-1415, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38229005

RESUMO

Jasmonic acid-isoleucine (JA-Ile) is a plant defence hormone whose cellular levels are elevated upon herbivory and regulate defence signalling. Despite their pivotal role, our understanding of the rapid cellular perception of bioactive JA-Ile is limited. This study identifies cell type-specific JA-Ile-induced Ca2+ signal and its role in self-amplification and plant elicitor peptide receptor (PEPR)-mediated signalling. Using the Ca2+ reporter, R-GECO1 in Arabidopsis, we have characterized a monophasic and sustained JA-Ile-dependent Ca2+ signature in leaf epidermal cells. The rapid Ca2+ signal is independent of positive feedback by the JA-Ile receptor, COI1 and the transporter, JAT1. Microarray analysis identified up-regulation of receptors, PEPR1 and PEPR2 upon JA-Ile treatment. The pepr1 pepr2 double mutant in R-GECO1 background exhibits impaired external JA-Ile induced Ca2+ cyt elevation and impacts the canonical JA-Ile responsive genes. JA responsive transcription factor, MYC2 binds to the G-Box motif of PEPR1 and PEPR2 promoter and activates their expression upon JA-Ile treatment and in myc2 mutant, this is reduced. External JA-Ile amplifies AtPep-PEPR pathway by increasing the AtPep precursor, PROPEP expression. Our work shows a previously unknown non-canonical PEPR-JA-Ile-Ca2+ -MYC2 signalling module through which plants sense JA-Ile rapidly to amplify both AtPep-PEPR and jasmonate signalling in undamaged cells.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Isoleucina/análogos & derivados , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Isoleucina/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
2.
Crit Rev Biochem Mol Biol ; 56(5): 482-499, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34162300

RESUMO

The role of guanine quadruplexes (G4) in fundamental biological processes like DNA replication, transcription, translation and telomere maintenance is recognized. G4 structure dynamics is regulated by G4 structure binding proteins and is thought to be crucial for the maintenance of genome integrity in both prokaryotic and eukaryotic cells. Growing research over the last decade has expanded the existing knowledge of the functional diversity of G4 (DNA and RNA) structures across the working models. The control of G4 structure dynamics using G4 binding drugs has been suggested as the putative targets in the control of cancer and bacterial pathogenesis. This review has brought forth the collections of recent information that indicate G4 (mostly G4 DNA) roles in microbial pathogenesis, DNA damaging stress response in bacteria and mammalian cells. Studies in mitochondrial gene function regulation by G4s have also been underscored. Finally, the interdependence of G4s and epigenetic modifications and their speculated medical implications through G4 interacting proteins has been discussed.


Assuntos
Quadruplex G , Animais , DNA , Epigênese Genética , Regulação da Expressão Gênica , RNA
3.
Plant Physiol ; 188(4): 2289-2307, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-34791442

RESUMO

Growth promotion induced by the endosymbiont Piriformospora indica has been observed in various plants; however, except growth phytohormones, specific functional metabolites involved in P. indica-mediated growth promotion are unknown. Here, we used a gas chromatography-mass spectrometry-based untargeted metabolite analysis to identify tomato (Solanum lycopersicum) metabolites whose levels were altered during P. indica-mediated growth promotion. Metabolomic multivariate analysis revealed several primary metabolites with altered levels, with putrescine (Put) induced most significantly in roots during the interaction. Further, our results indicated that P. indica modulates the arginine decarboxylase (ADC)-mediated Put biosynthesis pathway via induction of SlADC1 in tomato. Piriformospora indica did not promote growth in Sladc1-(virus-induced gene silencing of SlADC1) lines of tomato and showed less colonization. Furthermore, using LC-MS/MS we showed that Put promoted growth by elevation of auxin (indole-3-acetic acid) and gibberellin (GA4 and GA7) levels in tomato. In Arabidopsis (Arabidopsis thaliana) adc knockout mutants, P. indica colonization also decreased and showed no plant growth promotion, and this response was rescued upon exogenous application of Put. Put is also important for hyphal growth of P. indica, indicating that it is co-adapted by both host and microbe. Taken together, we conclude that Put is an essential metabolite and its biosynthesis in plants is crucial for P. indica-mediated plant growth promotion and fungal growth.


Assuntos
Basidiomycota , Putrescina , Cromatografia Líquida , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/metabolismo , Putrescina/metabolismo , Putrescina/farmacologia , Espectrometria de Massas em Tandem
4.
NMR Biomed ; : e5017, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37654047

RESUMO

The purpose of this study was to assess the quality of clinical brain imaging in healthy subjects and patients on an FDA-approved commercial 0.55 T MRI scanner, and to provide information about the feasibility of using this scanner in a clinical workflow. In this IRB-approved study, brain examinations on the scanner were prospectively performed in 10 healthy subjects (February-April 2022) and retrospectively derived from 44 patients (February-July 2022). Images collected using the following pulse sequences were available for assessment: axial DWI (diffusion-weighted imaging), apparent diffusion coefficient maps, 2D axial fluid-attenuated inversion recovery images, axial susceptibility-weighted images (both magnitude and phase), sagittal T1 -weighted (T1w) Sampling Perfection with Application Optimized Contrast images, sagittal T1w MPRAGE (magnetization prepared rapid gradient echo) with contrast enhancement, axial T1w turbo spin echo (TSE) with and without contrast enhancement, and axial T2 -weighted TSE. Two readers retrospectively and independently evaluated image quality and specific anatomical features in a blinded fashion on a four-point Likert scale, with a score of 1 being unacceptable and 4 being excellent, and determined the ability to answer the clinical question in patients. For each category of image sequences, the mean, standard deviation, and percentage of unacceptable quality images (<2) were calculated. Acceptable (rating ≥ 2) image quality was achieved at 0.55 T in all sequences for patients and 85% of the sequences for healthy subjects. Radiologists were able to answer the clinical question in all patients scanned. In total, 50% of the sequences used in patients and about 60% of the sequences used in healthy subjects exhibited good (rating ≥ 3) image quality. Based on these findings, we conclude that diagnostic quality clinical brain images can be successfully collected on this commercial 0.55 T scanner, indicating that the routine brain imaging protocol may be deployed on this system in the clinical workflow.

5.
Extremophiles ; 28(1): 7, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062175

RESUMO

Topoisomerases are crucial enzymes in genome maintenance that modulate the topological changes during DNA metabolism. Deinococcus radiodurans, a Gram-positive bacterium is characterized by its resistance to many abiotic stresses including gamma radiation. Its multipartite genome encodes both type I and type II topoisomerases. Time-lapse studies using fluorescently tagged topoisomerase IB (drTopoIB-RFP) and DNA gyrase (GyrA-RFP) were performed to check the dynamics and localization with respect to DNA repair and cell division under normal and post-irradiation growth conditions. Results suggested that TopoIB and DNA gyrase are mostly found on nucleoid, highly dynamic, and show growth phase-dependent subcellular localization. The drTopoIB-RFP was also present at peripheral and septum regions but does not co-localize with the cell division protein, drFtsZ. On the other hand, DNA gyrase co-localizes with PprA a pleiotropic protein involved in radioresistance, on the nucleoid during the post-irradiation recovery (PIR). The topoIB mutant was found to be sensitive to hydroxyurea treatment, and showed more accumulation of single-stranded DNA during the PIR, compared to the wild type suggesting its role in DNA replication stress. Together, these results suggest differential localization of drTopoIB-RFP and GyrA-RFP in D. radiodurans and their interaction with PprA protein, emphasizing the functional significance and role in radioresistance.


Assuntos
DNA Girase , Deinococcus , DNA Girase/genética , DNA Girase/metabolismo , Deinococcus/genética , Deinococcus/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Dano ao DNA , Reparo do DNA
6.
Risk Anal ; 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37772629

RESUMO

Risk and resilience assessments for critical infrastructure focus on myriad objectives, from natural hazard evaluations to optimizing investments. Although research has started to characterize externalities associated with current or possible future states, incorporation of equity priorities at project inception is increasingly being recognized as critical for planning related activities. However, there is no standard methodology that guides development of equity-informed quantitative approaches for infrastructure planning activities. To address this gap, we introduce a logic model that can be tailored to capture nuances about specific geographies and community priorities, effectively incorporating them into different mathematical approaches for quantitative risk assessments. Specifically, the logic model uses a graded, iterative approach to clarify specific equity objectives as well as inform the development of equations being used to support analysis. We demonstrate the utility of this framework using case studies spanning aviation fuel, produced water, and microgrid electricity infrastructures. For each case study, the use of the logic model helps clarify the ways that local priorities and infrastructure needs are used to drive the types of data and quantitative methodologies used in the respective analyses. The explicit consideration of methodological limitations (e.g., data mismatches) and stakeholder engagements serves to increase the transparency of the associated findings as well as effectively integrate community nuances (e.g., ownership of assets) into infrastructure assessments. Such integration will become increasingly important to ensure that planning activities (which occur throughout the lifecycle of the infrastructure projects) lead to long-lasting solutions to meet both energy and sustainable development goals for communities.

7.
Apoptosis ; 27(3-4): 261-282, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35122181

RESUMO

Piperlongumine (PL, piplartine) is an alkaloid derived from the Piper longum L. (long pepper) roots. Originally discovered in 1961, the biological activities of this molecule against some cancer types was reported during the last decade. Whether PL can synergize with doxorubicin and the underlying mechanism in breast cancer remains elusive. Herein, we report the activities of PL in numerous breast cancer cell lines. PL reduced the migration and colony formation by cancer cells. An enhancement in the sub-G1 population, reduction in the mitochondrial membrane potential, chromatin condensation, DNA laddering and suppression in the cell survival proteins was observed by the alkaloid. Further, PL induced ROS generation in breast cancer cells. While TNF-α induced p65 nuclear translocation, PL suppressed the translocation in cancer cells. The expression of lncRNAs such as MEG3, GAS5 and H19 were also modulated by the alkaloid. The molecular docking studies revealed that PL can interact with both p65 and p50 subunits. PL reduced the glucose import and altered the pH of the medium towards the alkaline side. PL also suppressed the expression of glucose and lactate transporter in breast cancer cells. In tumor bearing mouse model, PL was found to synergize with doxorubicin and reduced the size, volume and weight of the tumor. Overall, the effects of doxorubicin in cancer cells are enhanced by PL. The modulation of glucose import, NF-κB activation and lncRNAs expression may have contributory role for the activities of PL in breast cancer.


Assuntos
Alcaloides , Antineoplásicos , Neoplasias da Mama , Dioxolanos , Piper , RNA Longo não Codificante , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Animais , Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Dioxolanos/farmacologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Glucose/farmacologia , Humanos , Camundongos , Simulação de Acoplamento Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Piper/química , RNA Longo não Codificante/genética , Espécies Reativas de Oxigênio/metabolismo
8.
Crit Rev Microbiol ; 47(2): 141-161, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33423591

RESUMO

Bacterial cell cycle is divided into well-coordinated phases; chromosome duplication and segregation, cell elongation, septum formation, and cytokinesis. The temporal separation of these phases depends upon the growth rates and doubling time in different bacteria. The entire process of cell division starts with the assembly of divisome complex at mid-cell position followed by constriction of the cell wall and septum formation. In the mapping of mid-cell position for septum formation, the gradient of oscillating Min proteins across the poles plays a pivotal role in several bacteria genus. The cues in the cell that defines the poles and plane of cell division are not fully characterized in cocci. Recent studies have shed some lights on molecular interactions at the poles and the underlying mechanisms involved in pole determination in non-cocci. In this review, we have brought forth recent findings on these aspects together, which would suggest a model to explain the mechanisms of pole determination in rod shaped bacteria and could be extrapolated as a working model in cocci.


Assuntos
Bactérias/citologia , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Divisão Celular , Parede Celular/genética , Parede Celular/metabolismo
9.
Bioconjug Chem ; 32(11): 2397-2406, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34748323

RESUMO

Site-specific protein labeling is important in biomedical research and biotechnology. While many methods allow site-specific protein modification, a straightforward approach for efficient N-terminal protein labeling is not available. We introduce a novel sortase-mediated swapping approach for a one-step site-specific N-terminal labeling with a near-quantitative yield. We show that this method allows rapid and efficient cleavage and simultaneous labeling of the N or C termini of fusion proteins. The method does not require any prior modification beyond the genetic incorporation of the sortase recognition motif. This new approach provides flexibility for protein engineering and site-specific protein modifications.


Assuntos
Aminoaciltransferases
10.
Environ Sci Technol ; 55(8): 5180-5188, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33724824

RESUMO

Incentivizing bioenergy crop production in locations with marginal soils, where low-input perennial crops can provide net carbon sequestration and economic benefits, will be crucial to building a successful bioeconomy. We developed an integrated assessment framework to compare switchgrass cultivation with corn-soybean rotations on the basis of production costs, revenues, and soil organic carbon (SOC) sequestration at a 100 m spatial resolution. We calculated profits (or losses) when marginal lands are converted from a corn-soy rotation to switchgrass across a range of farm gate biomass prices and payments for SOC sequestration in the State of Illinois, United States. The annual net SOC sequestration and switchgrass yields are estimated to range from 0.1 to 0.4 Mg ha-1 and 7.3 to 15.5 Mg dry matter ha-1, respectively, across the state. Without payments for SOC sequestration, only a small fraction of marginal corn-soybean land would achieve a 20% profit margin if converted to switchgrass, but $40-80 Mg-1 CO2e compensation could increase the economically viable area by 140-414%. With the compensation, switchgrass cultivation for 10 years on 1.6 million ha of marginal land in Illinois will produce biomass worth $1.6-2.9 billion (0.95-1.8 million Mg dry biomass) and mitigate 5-22 million Mg CO2e.


Assuntos
Sequestro de Carbono , Solo , Agricultura , Carbono/análise , Illinois
11.
Cell Mol Life Sci ; 76(10): 1947-1966, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30879091

RESUMO

The long non-coding RNAs (lncRNAs) are the crucial regulators of human chronic diseases. Therefore, approaches such as antisense oligonucleotides, RNAi technology, and small molecule inhibitors have been used for the therapeutic targeting of lncRNAs. During the last decade, phytochemicals and nutraceuticals have been explored for their potential against lncRNAs. The common lncRNAs known to be modulated by phytochemicals include ROR, PVT1, HOTAIR, MALAT1, H19, MEG3, PCAT29, PANDAR, NEAT1, and GAS5. The phytochemicals such as curcumin, resveratrol, sulforaphane, berberine, EGCG, and gambogic acid have been examined against lncRNAs. In some cases, formulation of phytochemicals has also been used. The disease models where phytochemicals have been demonstrated to modulate lncRNAs expression include cancer, rheumatoid arthritis, osteoarthritis, and nonalcoholic fatty liver disease. The regulation of lncRNAs by phytochemicals can affect multi-steps of tumor development. When administered in combination with the conventional drugs, phytochemicals can also produce synergistic effects on lncRNAs leading to the sensitization of cancer cells. Phytochemicals target lncRNAs either directly or indirectly by affecting a wide variety of upstream molecules. However, the potential of phytochemicals against lncRNAs has been demonstrated mostly by preclinical studies in cancer models. How the modulation of lncRNAs by phytochemicals produce therapeutic effects on cancer and other chronic diseases is discussed in this review.


Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , RNA Longo não Codificante/genética , Antineoplásicos Fitogênicos/uso terapêutico , Doença Crônica/tratamento farmacológico , Humanos , Neoplasias/genética , Resveratrol/uso terapêutico
12.
Environ Monit Assess ; 191(Suppl 3): 796, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989356

RESUMO

Environmental factors along with soil physico-chemical properties play a significant role on the diurnal trend of soil CO2 efflux. Soil CO2 efflux in Indian tropical forests is poorly studied. We studied the soil CO2 efflux in a representative tropical deciduous forest at Katerniaghat Wildlife Sanctuary (KWLS), Uttar Pradesh. The three forest communities namely dry mixed (DMF), Sal mixed (SMF), and Teak plantation (TPF) were selected for measuring soil CO2 efflux in the summer season during April to May 2017 using automated LI-COR 8100 soil CO2 flux system. Soil physico-chemical parameters were also studied in the three abovementioned forest communities. We also measured the different microclimatic variables at forest understorey in all three communities during the summer season. Total day time soil CO2 efflux of 826.70, 1089.24, and 828.94 (µmolCO2 m-2d-1) was observed in TPF, SMF, and DMF respectively. Soil CO2 efflux observed significant differences (P < 0.01) among the three forest communities studied for the summer season in tropical deciduous forest of Terai Himalaya. Average soil CO2 efflux rate (µmol CO2 m-2 s-1) of 4.06 ± 0.36, 5.03 ± 0.45, and 4.37 ± 0.79 was observed in TPF, SMF, and DMF, respectively, which is positively correlated with total organic carbon (TOC) and water holding capacity (WHC) among soil physico-chemical variables. Among microclimatic variables, soil temperature (ST, °C) and air temperature (AT, °C) observed strong positive correlation with day time soil CO2 efflux in all three communities. Significant increase in soil CO2 flux was observed with increasing air and soil temperature (AT and ST) in DMF and SMF. Maximum TOC of 19.23 g Kg-1 was observed in SMF among all communities in the summer season. The result showed that soil CO2 efflux is closely associated with TOC, WHC, AT, and ST for Indian deciduous forest ecosystems.


Assuntos
Dióxido de Carbono , Florestas , Solo , Ecossistema , Monitoramento Ambiental , Índia , Árvores
13.
Environ Monit Assess ; 191(Suppl 3): 797, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989261

RESUMO

In this study, we investigated the relationship between soil properties and litter chemistry in three forest communities, i.e., Sal mixed forest (SMF), dry mixed forest (DMF), and teak plantation forest (TPF), in tropical deciduous forest ecosystem in North India. Fresh leaf litter and soil samples were collected at two soil depths (0-15 and 15-30 cm) from all these three forest communities. Litter bag experiment was also conducted to know differences in litter nutrients after its decomposition. The concentrations (mg kg-1) of different nutrients such as sodium (Na) 2.6, potassium (K) 38.5, calcium (Ca) 425, and carbon (C) 45.54% were highest in fresh litter collected from DMF. Total organic carbon (g kg-1) was significantly higher in SMF (19.23) in comparison to DMF (18.41) and TPF (13.61) at 0-15-cm soil depth. Na, K, Ca, available P, total P, available N, and total N were highest in DMF soil. We observed significantly positive correlation between all nutrients of litter and soil. Although soil bulk density (BD) and particle density (PD) showed their significant negative correlation with litter C, total porosity was positively correlated. Similarly, litter Na has its significant negative correlation with BD and positive correlation with PD. The litter chemistry played a significant role in changing soil pH and TOC. All litter nutrients, except total P, have their significant positive correlation with soil pH. Total P, C, and N of litter have their significant positive correlation with total soil organic carbon. This indicates that litter chemistry and soil properties have specific relation among them despite unique species composition in each forest community.


Assuntos
Ecossistema , Florestas , Solo , Carbono , Monitoramento Ambiental , Índia , Folhas de Planta , Árvores
14.
Semin Cancer Biol ; 52(Pt 2): 53-65, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29196189

RESUMO

Neuroblastoma is the most common pediatric solid tumor of neural crest origin. The current treatment options for neuroblastoma produce severe side effects. Programmed death-ligand 1 (PD-L1), chronic inflammation, and non-coding RNAs are known to play a significant role in the pathogenesis of neuroblastoma. Cancer cells and the surrounding cells in the tumor microenvironment express PD-L1. Programmed death-1 (PD-1) is a co-receptor expressed predominantly by T cells. The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system. Chronic inflammation is involved in the recruitment of leukocytes, production of cytokines and chemokines that in turn, lead to survival, metastasis, and angiogenesis in neuroblastoma tumors. The miRNAs and long non-coding (lnc) RNAs have emerged as a novel class of non-coding RNAs that can regulate neuroblastoma associated cell-signaling pathways. The dysregulation of PD-1/PD-L1, inflammatory pathways, lncRNAs, and miRNAs have been reported in clinical and experimental samples of neuroblastoma. These signaling molecules are currently being evaluated for their potential as the biomarker and therapeutic targets in the management of neuroblastoma. A monoclonal antibody called dinutuximab (Unituxin) that attaches to a carbohydrate molecule GD2, on the surface of many neuroblastoma cells, is being used as an immunotherapy drug for neuroblastoma treatment. Atezolizumab (Tecentriq), an engineered monoclonal antibody against PD-L1, are currently in clinical trial for neuroblastoma patients. The lncRNA/miRNA-based therapeutics is being developed to deliver tumor suppressor lncRNAs/miRNAs or silencing of oncogenic lncRNAs/miRNAs. The focus of this review is to discuss the current knowledge on the immune checkpoint molecules, PD-1/PD-L1 signaling, inflammation, and non-coding RNAs in neuroblastoma.


Assuntos
Antígeno B7-H1/genética , Inflamação/genética , Inflamação/imunologia , Neuroblastoma/genética , Neuroblastoma/imunologia , RNA não Traduzido/genética , Animais , Humanos , Oncologia/métodos
15.
J Bacteriol ; 201(17)2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31235513

RESUMO

Guanine quadruplex (G4) DNA/RNA are secondary structures that regulate the various cellular processes in both eukaryotes and bacteria. Deinococcus radiodurans, a Gram-positive bacterium known for its extraordinary radioresistance, shows a genomewide occurrence of putative G4 DNA-forming motifs in its GC-rich genome. N-Methyl mesoporphyrin (NMM), a G4 DNA structure-stabilizing drug, did not affect bacterial growth under normal conditions but inhibited the postirradiation recovery of gamma-irradiated cells. Transcriptome sequencing analysis of cells treated with both radiation and NMM showed repression of gamma radiation-responsive gene expression, which was observed in the absence of NMM. Notably, this effect of NMM on the expression of housekeeping genes involved in other cellular processes was not observed. Stabilization of G4 DNA structures mapped at the upstream of recA and in the encoding region of DR_2199 had negatively affected promoter activity in vivo, DNA synthesis in vitro and protein translation in Escherichia coli host. These results suggested that G4 DNA plays an important role in DNA damage response and in the regulation of expression of the DNA repair proteins required for radioresistance in D. radioduransIMPORTANCEDeinococcus radiodurans can recover from extensive DNA damage caused by many genotoxic agents. It lacks LexA/RecA-mediated canonical SOS response. Therefore, the molecular mechanisms underlying the regulation of DNA damage response would be worth investigating in this bacterium. D. radiodurans genome is GC-rich and contains numerous islands of putative guanine quadruplex (G4) DNA structure-forming motifs. Here, we showed that in vivo stabilization of G4 DNA structures can impair DNA damage response processes in D. radiodurans Essential cellular processes such as transcription, DNA synthesis, and protein translation, which are also an integral part of the double-strand DNA break repair pathway, are affected by the arrest of G4 DNA structure dynamics. Thus, the role of DNA secondary structures in DNA damage response and radioresistance is demonstrated.


Assuntos
DNA/genética , Deinococcus/efeitos da radiação , Quadruplex G , Raios gama , Regulação Bacteriana da Expressão Gênica/efeitos da radiação , Genoma Bacteriano/efeitos da radiação , Deinococcus/genética
16.
J Immunol ; 198(2): 749-756, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27903738

RESUMO

Tissue-resident memory T (TRM) cells, a population of noncirculating memory T cells, are one of the essential components of immunological memory in both mouse and human. Although CD69+CD103+ TRM cells represent a major TRM cell population in barrier tissues including the mucosal surface and the skin, CD69+CD103- TRM cells dominate most nonbarrier tissues, such as the kidney. TGF-ß is required for the differentiation of CD69+CD103+ TRM cells in barrier tissues. However, the developmental control of CD69+CD103- TRM cells in nonbarrier tissues remains largely unknown and the involvement of TGF-ß signaling is less clear. In this study we demonstrated that TGF-ß promoted the formation of kidney-resident T cells via enhancing the tissue entry of effector T cells. Mechanistically, TGF-ß enhanced E- and P-selectin and inflammatory chemokine-mediated extravasation of effector T cells. Thus TGF-ß controls the first developmental checkpoint of TRM cell differentiation in nonbarrier tissues.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Memória Imunológica/imunologia , Rim/imunologia , Subpopulações de Linfócitos T/imunologia , Fator de Crescimento Transformador beta/imunologia , Transferência Adotiva , Animais , Diferenciação Celular/imunologia , Citometria de Fluxo , Camundongos , Camundongos Transgênicos
17.
Brain ; 141(6): 1828-1839, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29672664

RESUMO

While prior work reliably demonstrates that the APOE ɛ4 allele has deleterious group level effects on Alzheimer disease pathology, the homogeneity of its influence across the lifespan and spatially in the brain remains unknown. Further it is unclear what combinations of factors at an individual level lead to observed group level effects of APOE genotype. To evaluate the impact of the APOE genotype on disease trajectories, we examined longitudinal MRI and PET imaging in a cohort of 497 cognitively normal middle and older aged participants. A whole-brain regional approach was used to evaluate the spatial effects of genotype on longitudinal change of amyloid-ß pathology and cortical atrophy. Carriers of the ɛ4 allele had increased longitudinal accumulation of amyloid-ß pathology diffusely through the cortex, but the emergence of this effect across the lifespan differed greatly by region (e.g. age 49 in precuneus, but 65 in the visual cortex) with the detrimental influence already being evident in some regions in middle age. This increased group level effect on accumulation was due to a greater proportion of ɛ4 carriers developing amyloid-ß pathology, on average doing so at an earlier age, and having faster amyloid-ß accumulation even after accounting for baseline amyloid-ß levels. APOE ɛ4 carriers displayed faster rates of structural loss in primarily constrained to the medial temporal lobe structures at around 50 years, although this increase was modest and proportional to the elevated disease severity in APOE ɛ4 carriers. This work indicates that influence of the APOE gene on pathology can be detected starting in middle age.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Encéfalo/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina/metabolismo , Estudos Transversais , Feminino , Genótipo , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Tiazóis/metabolismo
18.
Planta ; 248(4): 981-997, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29987372

RESUMO

MAIN CONCLUSION: Metabolite profiling, biochemical assays, and transcript analysis revealed differential modulation of specific induced defense responses in local, older, and younger systemic leaves in Solanum lycopersicum upon Spodoptera litura herbivory. Plants reconfigure their metabolome upon herbivory to induce production of defense metabolites involved in both direct and indirect defenses against insect herbivores. Herbivory mediated leaf-to-leaf systemic induction pattern of primary and non-volatile secondary metabolites is not well studied in tomato. Here, we show that, in cultivated tomato Solanum lycopersicum herbivory by generalist insect, Spodoptera litura results in differential alteration of primary metabolites, majorly sugars and amino acids and specific secondary metabolites in local, younger, and older systemic leaves. Cluster analysis of 55 metabolites identified by GC-MS showed correlation between local and younger systemic leaves. Re-allocation of primary metabolites like glucose and amino acids from the local to systemic leaf was observed. Secondary metabolites chlorogenic acid, caffeic acid, and catechin were significantly induced during herbivory in systemic leaves. Among specific secondary metabolites, chlorogenic acid and catechin significantly inhibits S. litura larval growth in all stages. Local leaf exhibited increased lignin accumulation upon herbivory. Differential alteration of induced defense responses like reactive oxygen species, polyphenol oxidase activity, proteinase inhibitor, cell wall metabolites, and lignin accumulation was observed in systemic leaves. The metabolite alteration also resulted in increased defense in systemic leaves. Thus, comparative analysis of metabolites in local and systemic leaves of tomato revealed a constant re-allocation of primary metabolites to systemic leaves and differential induction of secondary metabolites and induced defenses upon herbivory.


Assuntos
Herbivoria , Folhas de Planta/química , Folhas de Planta/metabolismo , Solanum lycopersicum/fisiologia , Spodoptera/fisiologia , Animais , Catequina/metabolismo , Catecol Oxidase , Parede Celular/metabolismo , Ácido Clorogênico/análise , Ácido Clorogênico/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/metabolismo , Larva/crescimento & desenvolvimento , Lignina/metabolismo , Solanum lycopersicum/química , Metaboloma , Pupa/fisiologia , Metabolismo Secundário , Transdução de Sinais
19.
Environ Sci Technol ; 52(13): 7566-7576, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29806456

RESUMO

Of the many roles insects serve for ecosystem function, pollination is possibly the most important service directly linked to human well-being. However, land use changes have contributed to the decline of pollinators and their habitats. In agricultural landscapes that also support renewable energy developments such as utility-scale solar energy [USSE] facilities, opportunities may exist to conserve insect pollinators and locally restore their ecosystem services through the implementation of vegetation management approaches that aim to provide and maintain pollinator habitat at USSE facilities. As a first step toward understanding the potential agricultural benefits of solar-pollinator habitat, we identified areas of overlap between USSE facilities and surrounding pollinator-dependent crop types in the United States (U.S.). Using spatial data on solar energy developments and crop types across the U.S., and assuming a pollinator foraging distance of 1.5 km, we identified over 3,500 km2 of agricultural land near existing and planned USSE facilities that may benefit from increased pollination services through the creation of pollinator habitat at the USSE facilities. The following five pollinator-dependent crop types accounted for over 90% of the agriculture near USSE facilities, and these could benefit most from the creation of pollinator habitat at existing and planned USSE facilities: soybeans, alfalfa, cotton, almonds, and citrus. We discuss how our results may be used to understand potential agro-economic implications of solar-pollinator habitat. Our results show that ecosystem service restoration through the creation of pollinator habitat could improve the sustainability of large-scale renewable energy developments in agricultural landscapes.


Assuntos
Ecossistema , Energia Solar , Agricultura , Animais , Abelhas , Humanos , Insetos , Polinização , Estados Unidos
20.
Neuroimage ; 161: 171-178, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28756238

RESUMO

Utilizing [18F]-AV-1451 tau positron emission tomography (PET) as an Alzheimer disease (AD) biomarker will require identification of brain regions that are most important in detecting elevated tau pathology in preclinical AD. Here, we utilized an unsupervised learning, data-driven approach to identify brain regions whose tau PET is most informative in discriminating low and high levels of [18F]-AV-1451 binding. 84 cognitively normal participants who had undergone AV-1451 PET imaging were used in a sparse k-means clustering with resampling analysis to identify the regions most informative in dividing a cognitively normal population into high tau and low tau groups. The highest-weighted FreeSurfer regions of interest (ROIs) separating these groups were the entorhinal cortex, amygdala, lateral occipital cortex, and inferior temporal cortex, and an average SUVR in these four ROIs was used as a summary metric for AV-1451 uptake. We propose an AV-1451 SUVR cut-off of 1.25 to define high tau as described by imaging. This spatial distribution of tau PET is a more widespread pattern than that predicted by pathological staging schemes. Our data-derived metric was validated first in this cognitively normal cohort by correlating with early measures of cognitive dysfunction, and with disease progression as measured by ß-amyloid PET imaging. We additionally validated this summary metric in a cohort of 13 Alzheimer disease patients, and showed that this measure correlates with cognitive dysfunction and ß-amyloid PET imaging in a diseased population.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides/metabolismo , Disfunção Cognitiva , Progressão da Doença , Tomografia por Emissão de Pósitrons/métodos , Aprendizado de Máquina não Supervisionado , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Biomarcadores/metabolismo , Carbolinas/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sintomas Prodrômicos
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