Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 76
Filtrar
1.
Nature ; 583(7818): 768-770, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32728241

RESUMO

Globular clusters are some of the oldest bound stellar structures observed in the Universe1. They are ubiquitous in large galaxies and are believed to trace intense star-formation events and the hierarchical build-up of structure2,3. Observations of globular clusters in the Milky Way, and a wide variety of other galaxies, have found evidence for a 'metallicity floor', whereby no globular clusters are found with chemical (metal) abundances below approximately 0.3 to 0.4 per cent of that of the Sun4-6. The existence of this metallicity floor may reflect a minimum mass and a maximum redshift for surviving globular clusters to form-both critical components for understanding the build-up of mass in the Universe7. Here we report measurements from the Southern Stellar Streams Spectroscopic Survey of the spatially thin, dynamically cold Phoenix stellar stream in the halo of the Milky Way. The properties of the Phoenix stream are consistent with it being the tidally disrupted remains of a globular cluster. However, its metal abundance ([Fe/H] = -2.7) is substantially below the empirical metallicity floor. The Phoenix stream thus represents the debris of the most metal-poor globular clusters discovered so far, and its progenitor is distinct from the present-day globular cluster population in the local Universe. Its existence implies that globular clusters below the metallicity floor have probably existed, but were destroyed during Galactic evolution.

2.
Plant J ; 118(6): 2169-2187, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38558472

RESUMO

Genome-wide association studies (GWAS) are an effective approach to identify new specialized metabolites and the genes involved in their biosynthesis and regulation. In this study, GWAS of Arabidopsis thaliana soluble leaf and stem metabolites identified alleles of an uncharacterized BAHD-family acyltransferase (AT5G57840) associated with natural variation in three structurally related metabolites. These metabolites were esters of glucuronosylglycerol, with one metabolite containing phenylacetic acid as the acyl component of the ester. Knockout and overexpression of AT5G57840 in Arabidopsis and heterologous overexpression in Nicotiana benthamiana and Escherichia coli demonstrated that it is capable of utilizing phenylacetyl-CoA as an acyl donor and glucuronosylglycerol as an acyl acceptor. We, thus, named the protein Glucuronosylglycerol Ester Synthase (GGES). Additionally, phenylacetyl glucuronosylglycerol increased in Arabidopsis CYP79A2 mutants that overproduce phenylacetic acid and was lost in knockout mutants of UDP-sulfoquinovosyl: diacylglycerol sulfoquinovosyl transferase, an enzyme required for glucuronosylglycerol biosynthesis and associated with glycerolipid metabolism under phosphate-starvation stress. GGES is a member of a well-supported clade of BAHD family acyltransferases that arose by duplication and neofunctionalized during the evolution of the Brassicales within a larger clade that includes HCT as well as enzymes that synthesize other plant-specialized metabolites. Together, this work extends our understanding of the catalytic diversity of BAHD acyltransferases and uncovers a pathway that involves contributions from both phenylalanine and lipid metabolism.


Assuntos
Aciltransferases , Arabidopsis , Fenilacetatos , Aciltransferases/genética , Aciltransferases/metabolismo , Arabidopsis/genética , Arabidopsis/enzimologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Estudo de Associação Genômica Ampla , Fenilacetatos/metabolismo
3.
Plant Cell ; 33(3): 492-510, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33955498

RESUMO

The optimal extraction of information from untargeted metabolomics analyses is a continuing challenge. Here, we describe an approach that combines stable isotope labeling, liquid chromatography- mass spectrometry (LC-MS), and a computational pipeline to automatically identify metabolites produced from a selected metabolic precursor. We identified the subset of the soluble metabolome generated from phenylalanine (Phe) in Arabidopsis thaliana, which we refer to as the Phe-derived metabolome (FDM) In addition to identifying Phe-derived metabolites present in a single wild-type reference accession, the FDM was established in nine enzymatic and regulatory mutants in the phenylpropanoid pathway. To identify genes associated with variation in Phe-derived metabolites in Arabidopsis, MS features collected by untargeted metabolite profiling of an Arabidopsis diversity panel were retrospectively annotated to the FDM and natural genetic variants responsible for differences in accumulation of FDM features were identified by genome-wide association. Large differences in Phe-derived metabolite accumulation and presence/absence variation of abundant metabolites were observed in the nine mutants as well as between accessions from the diversity panel. Many Phe-derived metabolites that accumulated in mutants also accumulated in non-Col-0 accessions and was associated to genes with known or suspected functions in the phenylpropanoid pathway as well as genes with no known functions. Overall, we show that cataloguing a biochemical pathway's products through isotopic labeling across genetic variants can substantially contribute to the identification of metabolites and genes associated with their biosynthesis.


Assuntos
Arabidopsis/metabolismo , Estudo de Associação Genômica Ampla/métodos , Metaboloma/fisiologia , Arabidopsis/genética , Marcação por Isótopo , Espectrometria de Massas , Metaboloma/genética , Metabolômica/métodos , Estudos Retrospectivos
4.
J Sport Rehabil ; 33(3): 215-219, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38198793

RESUMO

CONTEXT: Latency is a reliable temporal metric used to evaluate sensorimotor integration of the fibularis longus (FL) and fibularis brevis (FB) during lateral ankle sprain perturbations. Currently, no clinical recommendations exist to select appropriate thresholds to evaluate the closed-loop reflex response of the lateral ankle musculature. The purpose of this study was to assess threshold value on latency of the FL and FB during an unanticipated inversion perturbation that simulates the mechanism of a lateral ankle sprain. DESIGN: Descriptive laboratory study. METHODS: Twenty healthy adults with no history of lateral ankle sprain injury completed an unanticipated single-leg drop landing onto a 25° laterally inclined force platform from a height of 30 cm. Surface electromyography recorded muscle activity data from the FL and FB during the inversion perturbation. Latency was identified at points where muscle activity exceeded 2, 5, and 10 SD above the average muscle activity 200 milliseconds prior to foot contact, and compared across threshold value using a 1-way analysis of variance (P < .05). RESULTS: The 2 SD threshold was significantly shorter than both 5 SD and 10 SD thresholds for the FL (P < .01) and FB (P < .01). Likewise, the 5 SD threshold was significantly shorter than the 10 SD thresholds for FL (P = .004) and FB (P = .003). CONCLUSIONS: More sensitive thresholds results in a shorter closed-loop reflexive response compared to the more rigorous thresholds. We recommend that selection of the appropriate threshold to identify latency of the lateral ankle musculature should be based on the device used to simulate a lateral ankle sprain and the ankle inversion velocity produced during the ankle inversion perturbation.


Assuntos
Traumatismos do Tornozelo , Tornozelo , Adulto , Humanos , Extremidade Inferior , Articulação do Tornozelo , Reflexo
5.
Langmuir ; 38(15): 4747-4762, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35385292

RESUMO

The use of functionalized nanoparticles (NPs) and their aggregation in the presence of a targeted analyte is a well-established molecular detection strategy predicated on harnessing specific molecular interactions to the NP periphery. Molecules able to specifically interact with the functionalized NPs alter the unique optical and electrochemical properties of the NPs as a function of interparticle spacing. While many intermolecular interactions have been successfully exploited in this manner in conjunction with aqueous NP systems, the use of non-aqueous NPs in the same capacity is significantly less explored. A fundamental interaction that has not been previously investigated in NP schemes is halogen bonding (XB). XB is an orthogonal, electrostatic interaction between a region of positive electrostatic potential (δ+) on a halogen atom (i.e., XB donor) and a negative (δ-) Lewis base (XB acceptor) molecule. To couple XB with NP systems, ligands featuring a molecular structure that promotes XB interactions need to be identified, optimized, and synthesized for subsequent attachment to NPs. Herein, density functional theory (DFT) and NMR techniques are used to identify a strong XB-donor moiety (-C6F4I) and a synthetic scheme for a thiolate ligand featuring that functionality is devised and executed with high purity/yield (78%). Ligand-exchange reactions allow functionalization of non-aqueous alkanethiolate-protected gold NPs or monolayer-protected clusters (MPCs) with the XB-donor ligands. Functionalized MPCs (f-MPCs), within both assembled films and in solution, are shown to engage in XB interactions with target XB-acceptor molecules. Molecular recognition events, including induced aggregation of the f-MPCs, are characterized with UV-vis spectroscopy, cyclic voltammetry, TEM imaging, and diffusion-ordered spectroscopy NMR with limits of detection of 50-100 nM for strong XB acceptors. While fundamental exploration of XB interactions is ongoing, this study represents a step toward utilizing XB within molecular detection schemes, an application with implications for supramolecular chemistry, forensic, and environmental chemical sensing.

6.
Ann Hepatol ; 27(4): 100709, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35489641

RESUMO

INTRODUCTION AND AIM: Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases in the United States. Metabolic distress (obese diabetes) is the main causative element of NAFLD. While there is no cure for NAFLD, endurance exercise (EEx) has emerged as a therapeutic strategy against NAFLD. However, mechanisms of EXE-induced hepatic protection especially in female subjects remain unidentified. Thus, the aim of the study is to examine molecular mechanisms of EXE-induced hepatic protection against diet-induced NAFLD in female mice. MATERIAL AND METHODS: Nine-week-old female C57BL/6J mice were randomly divided into three groups: normal-diet control group (CON, n=11); high-fat diet/high-fructose group (HFD/HF, n=11); and HFD/HF+EEx group (HFD/HF+EEx, n=11). The mice assigned to HFD/HF and HFD/HF+EEx groups were fed with HFD/HF for 12 weeks, after which the mice assigned to the EEx group began treadmill exercise for 12 weeks, with HFD/HF continued. RESULTS: EEx attenuated hepatic steatosis, reduced de novo lipogenesis (reduction in ATP-Citrate- Lyase and diacylglycerol-O-acyltransferase 1), and enhanced mitochondrial biogenesis and fatty-acid activation (oxidative phosphorylation enzymes and Acyl-CoA synthetase1). Also, EEx prevented upregulation of gluconeogenic proteins (glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphatase, and phosphoenolpyruvate-carboxykinase1), premature senescence (suppression of p53, p22, and p16, tumor-necrosis-factor-α, and interleukin-1ß, and oxidative stress), and autophagy deficiency. Furthermore, EXE reversed apoptosis arrest (cleaved cysteine-dependent-aspartate-directed protease3 and Poly-(ADP-ribose)-polymerase1). CONCLUSION: EEx-mediated reparations of metabolic and redox imbalance (utilization of pentose phosphate pathway), and autophagy deficiency caused by metabolic distress critically contribute to preventing/delaying severe progression of NAFLD. Also, EEx-induced anti-senescence and cell turnover are crucial protective mechanisms against NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Humanos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle
7.
J Sport Rehabil ; 31(6): 819-825, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35405633

RESUMO

CLINICAL SCENARIO: Chronic ankle instability (CAI) is a condition that involves feelings of the ankle "giving way," pain, and decreased self-reported function. Individuals with CAI often demonstrate persistent biomechanical impairments during gait that are associated with repetitive lateral ankle sprains (LAS) and the development of early onset ankle posttraumatic osteoarthritis (OA). Traditional rehabilitation strategies have not successfully improved these reported aberrant gait biomechanics; thus, traditional rehabilitation may not effectively reduce the risk of recurrent LAS and ankle OA among individuals with CAI. Conversely, targeted gait training with biofeedback may be effective at decreasing the risk of recurring LAS and ankle OA if these rehabilitation strategies can promote individuals with CAI to develop a gait strategy that protects against subsequent LAS and ankle OA. CLINICAL QUESTION: Can targeted gait biofeedback interventions cause individuals with CAI to implement a walking gait pattern that is not associated with recurrent LAS and ankle OA? SUMMARY OF FINDINGS: Five studies assessed gait biofeedback interventions targeting plantar pressure and/or ankle kinematics involving visual biofeedback (n = 3), auditory biofeedback (n = 1), and haptic biofeedback (n = 1). Plantar pressure was medially shifted during a single session while receiving biofeedback (n = 2), immediately after biofeedback (n = 1), and 5 minutes after receiving biofeedback (n = 1) in 3 studies. One study demonstrated reduced ankle inversion after 8 sessions of biofeedback training. One study did not substantially improve plantar pressure while receiving visual feedback. CLINICAL BOTTOM LINE: Targeted gait training strategies appear effective in acutely altering gait biomechanics in individuals with CAI while receiving, and immediately after, biofeedback has been removed. Long-term outcomes are not currently established for gait training strategies in those with CAI. STRENGTH OF RECOMMENDATION: Limited evidence (grade B) suggests that targeted gait biofeedback strategies can alter specific CAI gait biomechanics to a strategy not associated with recurrent LAS, and ankle OA immediately, and after, multiple sessions of gait training.


Assuntos
Traumatismos do Tornozelo , Instabilidade Articular , Tornozelo , Articulação do Tornozelo , Fenômenos Biomecânicos , Doença Crônica , Retroalimentação Sensorial , Marcha , Humanos , Caminhada
8.
J Phys Chem A ; 125(42): 9377-9393, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34661411

RESUMO

Halogen bonding (XB) is a highly directional, non-covalent intermolecular interaction between a molecule (XB donor) presenting a halogen with an electron-deficient region or sigma hole (σ-hole) and an electron-rich or Lewis-base molecule (XB acceptor). A systematic, experimental, and theoretical study of solution-phase XB strength as a function of the molecular structure for both XB donor and acceptor molecules is presented. The impact of specific structural features is assessed using 19F and 1H nuclear magnetic resonance (NMR) titrations to determine association constants, density functional theory calculations for interaction energies and bond lengths, as well as 19F-1H HOESY NMR measurements of intermolecular cross-relaxation between the interacting XB donor-acceptor adducts. For XB donor molecules (perfluoro-halogenated benzenes), results indicate the critical importance of iodine coupled with electron-withdrawing entities. Prominent structural components of XB acceptor molecules include a central atom working in conjunction with a Lewis-base atom to present high electron density directed at the σ-hole (e.g., tributylphosphine oxide). Additionally, larger surrounding aliphatic R groups (e.g., butyl and octyl) were found to significantly stabilize strong XB, particularly in solvents that promote the interaction. With a more thorough understanding of structure-optimized XB, one can envision harnessing XB interactions more strategically for specific design of optimal materials and chemical applications.

10.
Plant Cell ; 28(1): 248-64, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26744217

RESUMO

Bayberry (Myrica pensylvanica) fruits synthesize an extremely thick and unusual layer of crystalline surface wax that accumulates to 32% of fruit dry weight, the highest reported surface lipid accumulation in plants. The composition is also striking, consisting of completely saturated triacylglycerol, diacylglycerol, and monoacylglycerol with palmitate and myristate acyl chains. To gain insight into the unique properties of Bayberry wax synthesis, we examined the chemical and morphological development of the wax layer, monitored wax biosynthesis through [(14)C]-radiolabeling, and sequenced the transcriptome. Radiolabeling identified sn-2 monoacylglycerol as an initial glycerolipid intermediate. The kinetics of [(14)C]-DAG and [(14)C]-TAG accumulation and the regiospecificity of their [(14)C]-acyl chains indicated distinct pools of acyl donors and that final TAG assembly occurs outside of cells. The most highly expressed lipid-related genes were associated with production of cutin, whereas transcripts for conventional TAG synthesis were >50-fold less abundant. The biochemical and expression data together indicate that Bayberry surface glycerolipids are synthesized by a pathway for TAG synthesis that is related to cutin biosynthesis. The combination of a unique surface wax and massive accumulation may aid understanding of how plants produce and secrete non-membrane glycerolipids and also how to engineer alternative pathways for lipid production in non-seeds.


Assuntos
Vias Biossintéticas , Frutas/metabolismo , Glicolipídeos/metabolismo , Myrica/metabolismo , Triglicerídeos/biossíntese , Ceras/metabolismo , Acetatos/metabolismo , Acil Coenzima A/metabolismo , Aciltransferases/metabolismo , Vias Biossintéticas/genética , Radioisótopos de Carbono , Espaço Extracelular/metabolismo , Frutas/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Modelos Biológicos , Myrica/genética , Myrica/crescimento & desenvolvimento , Óleos de Plantas/metabolismo , Sementes/metabolismo
11.
J Sport Rehabil ; 28(6): 593-600, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30040015

RESUMO

CONTEXT: Lateral ankle sprains are a common injury in which the mechanics of injury have been extensively studied. However, the anticipatory mechanisms to ankle inversion perturbations are not well understood. OBJECTIVE: To examine lower-extremity kinematics, including spatial and temporal variables of maximum inversion displacement and maximum inversion velocity, during landings on a tilted surface using a new experimental protocol to replicate a lateral ankle sprain. SETTING: Three-dimensional motion analysis laboratory. PARTICIPANTS: A total of 23 healthy adults. INTERVENTIONS: Participants completed unexpected (UE) and expected (EXP) unilateral landings onto a tilted surface rotated 25° in the frontal plane from a height of 30 cm. MAIN OUTCOME MEASURES: Ankle, knee, and hip kinematics at each discrete time point from 150 ms pre-initial contact (IC) to 150 ms post-IC, in addition to maximum ankle inversion and maximum inversion velocity, were compared between UE and EXP landings. RESULTS: The UE landing produced significantly greater maximum inversion displacement (P < .01) and maximum inversion velocity (P = .02) than the EXP landing. Significantly less ankle inversion and internal rotation were found during pre-IC, whereas during post-IC, significantly greater ankle inversion, ankle internal rotation, knee flexion, and knee abduction were observed for the UE landing (P < .05). In addition, significantly less hip flexion and hip adduction were observed for the UE landing during pre-IC and post-IC (P < .05). CONCLUSIONS: Differences in the UE and EXP landings indicate the experimental protocol presented a UE inversion perturbation that approximates the mechanism of a lateral ankle sprain. Furthermore, knowledge of the inversion perturbation elicited a hip-dominant strategy, which may be utilized to assist with ankle joint stabilization during landing to further protect the lateral ankle from injury.


Assuntos
Traumatismos do Tornozelo/fisiopatologia , Fenômenos Biomecânicos , Amplitude de Movimento Articular , Entorses e Distensões/fisiopatologia , Tornozelo , Feminino , Quadril , Humanos , Joelho , Extremidade Inferior , Masculino , Movimento , Rotação , Adulto Jovem
12.
Nano Lett ; 17(10): 5897-5907, 2017 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-28820602

RESUMO

The strong in-plane anisotropy of rhenium disulfide (ReS2) offers an additional physical parameter that can be tuned for advanced applications such as logic circuits, thin-film polarizers, and polarization-sensitive photodetectors. ReS2 also presents advantages for optoelectronics, as it is both a direct-gap semiconductor for few-layer thicknesses (unlike MoS2 or WS2) and stable in air (unlike black phosphorus). Raman spectroscopy is one of the most powerful characterization techniques to nondestructively and sensitively probe the fundamental photophysics of a 2D material. Here, we perform a thorough study of the resonant Raman response of the 18 first-order phonons in ReS2 at various layer thicknesses and crystal orientations. Remarkably, we discover that, as opposed to a general increase in intensity of all of the Raman modes at excitonic transitions, each of the 18 modes behave differently relative to each other as a function of laser excitation, layer thickness, and orientation in a manner that highlights the importance of electron-phonon coupling in ReS2. In addition, we correct an unrecognized error in the calculation of the optical interference enhancement of the Raman signal of transition metal dichalcogenides on SiO2/Si substrates that has propagated through various reports. For ReS2, this correction is critical to properly assessing the resonant Raman behavior. We also implemented a perturbation approach to calculate frequency-dependent Raman intensities based on first-principles and demonstrate that, despite the neglect of excitonic effects, useful trends in the Raman intensities of monolayer and bulk ReS2 at different laser energies can be accurately captured. Finally, the phonon dispersion calculated from first-principles is used to address the possible origins of unexplained peaks observed in the Raman spectra, such as infrared-active modes, defects, and second-order processes.

13.
J Strength Cond Res ; 32(7): 2066-2071, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29239983

RESUMO

Green, JM, Miller, B, Simpson, J, Dubroc, D, Keyes, A, Neal, K, Gann, J, and Andre, T. Effects of 2% dehydration on lactate concentration during constant-load cycling. J Strength Cond Res 32(7): 2066-2071, 2018-The lactate [La] threshold (LT) can predict endurance performance potential. Dehydration may alter LT. This study examined effects of dehydration on [La] response during constant-load cycling. Recreationally fit (V[Combining Dot Above]O2peak = 48.7 ± 5.2 ml·kg·min) male participants (n = 9) completed 2 × 40-minute constant-load cycling trials; euhydrated (HYD) and after previous evening passive (water bath) dehydration (2% body weight, DEH) (HYD and DEH counterbalanced). Lactate, heart rate (HR), 10-point Omni ratings of perceived exertion (RPE), and rectal temperature (Trec) were measured after warm-up (WU) and at 10, 20, 30, and 40 minutes. Before cycling, urine specific gravity (USG) was measured and participants estimated perceived recovery status (PRS). Urine specific gravity DEH (1.027 ± 0.004) was significantly greater than HYD (1.013 ± 0.007). After WU, [La] was significantly greater (all time points) for DEH (∼4.1 mmol·L) vs. HYD (∼3.5 mmol·L) with similar results for HR (DEH: ∼167, HYD: ∼158 b·min). For DEH, RPE was significantly greater (∼1 unit) at 20, 30, and 40 minutes, and Trec was significantly greater at 30 and 40 minutes (∼0.4° C). DEH (vs. HYD) also resulted in significantly different resting HR (93 ± 6, vs. 85 ± 7 b·min), significantly greater session RPE (7.7 ± 1.1 vs. 5.3 ± 1.1), and significantly lower subjective feelings of recovery (PRS = 6.4 ± 2.9, vs. 9.0 ± 1.5). Current results indicate systematic changes in [La] and associated physiological responses result from previous day dehydration. Hydration status should be a concern in paradigms where [La] assessment is used.


Assuntos
Ciclismo/fisiologia , Desidratação/sangue , Ácido Láctico/sangue , Adulto , Temperatura Corporal/fisiologia , Desidratação/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Esforço Físico/fisiologia , Adulto Jovem
14.
Biochim Biophys Acta ; 1861(9 Pt B): 1243-1252, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26869450

RESUMO

Bayberry (Myrica pensylvanica) fruits are covered with a remarkably thick layer of crystalline wax consisting of triacylglycerol (TAG) and diacylglycerol (DAG) esterified exclusively with saturated fatty acids. As the only plant known to accumulate soluble glycerolipids as a major component of surface waxes, Bayberry represents a novel system to investigate neutral lipid biosynthesis and lipid secretion by vegetative plant cells. The assembly of Bayberry wax is distinct from conventional TAG and other surface waxes, and instead proceeds through a pathway related to cutin synthesis (Simpson and Ohlrogge, 2016). In this study, microscopic examination revealed that the fruit tissue that produces and secretes wax (Bayberry knobs) is fully developed before wax accumulates and that wax is secreted to the surface without cell disruption. Comparison of transcript expression to genetically related tissues (Bayberry leaves, M. rubra fruits), cutin-rich tomato and cherry fruit epidermis, and to oil-rich mesocarp and seeds, revealed exceptionally high expression of 13 transcripts for acyl-lipid metabolism together with down-regulation of fatty acid oxidases and desaturases. The predicted protein sequences of the most highly expressed lipid-related enzyme-encoding transcripts in Bayberry knobs are 100% identical to the sequences from Bayberry leaves, which do not produce surface DAG or TAG. Together, these results indicate that TAG biosynthesis and secretion in Bayberry is achieved by both up and down-regulation of a small subset of genes related to the biosynthesis of cutin and saturated fatty acids, and also implies that modifications in gene expression, rather than evolution of new gene functions, was the major mechanism by which Bayberry evolved its specialized lipid metabolism. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner.


Assuntos
Aldeído Oxirredutases/biossíntese , Ácidos Graxos Dessaturases/biossíntese , Metabolismo dos Lipídeos/genética , Triglicerídeos/genética , Aldeído Oxirredutases/genética , Evolução Molecular , Ácidos Graxos Dessaturases/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Myrica/enzimologia , Myrica/genética , Myrica/metabolismo , Folhas de Planta/metabolismo , Sementes/metabolismo , Triglicerídeos/biossíntese
15.
Proc Natl Acad Sci U S A ; 111(32): E3252-9, 2014 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-25071207

RESUMO

Viral lethal mutagenesis is a strategy whereby the innate immune system or mutagenic pool nucleotides increase the error rate of viral replication above the error catastrophe limit. Lethal mutagenesis has been proposed as a mechanism for several antiviral compounds, including the drug candidate 5-aza-5,6-dihydro-2'-deoxycytidine (KP1212), which causes A-to-G and G-to-A mutations in the HIV genome, both in tissue culture and in HIV positive patients undergoing KP1212 monotherapy. This work explored the molecular mechanism(s) underlying the mutagenicity of KP1212, and specifically whether tautomerism, a previously proposed hypothesis, could explain the biological consequences of this nucleoside analog. Establishing tautomerism of nucleic acid bases under physiological conditions has been challenging because of the lack of sensitive methods. This study investigated tautomerism using an array of spectroscopic, theoretical, and chemical biology approaches. Variable temperature NMR and 2D infrared spectroscopic methods demonstrated that KP1212 existed as a broad ensemble of interconverting tautomers, among which enolic forms dominated. The mutagenic properties of KP1212 were determined empirically by in vitro and in vivo replication of a single-stranded vector containing a single KP1212. It was found that KP1212 paired with both A (10%) and G (90%), which is in accord with clinical observations. Moreover, this mutation frequency is sufficient for pushing a viral population over its error catastrophe limit, as observed before in cell culture studies. Finally, a model is proposed that correlates the mutagenicity of KP1212 with its tautomeric distribution in solution.


Assuntos
Fármacos Anti-HIV/farmacologia , Azacitidina/análogos & derivados , Desoxicitidina/análogos & derivados , HIV/efeitos dos fármacos , HIV/genética , Mutagênicos/farmacologia , Fármacos Anti-HIV/química , Azacitidina/química , Azacitidina/farmacologia , Bacteriófago M13/efeitos dos fármacos , Bacteriófago M13/genética , Bacteriófago M13/fisiologia , Pareamento de Bases , Desoxicitidina/química , Desoxicitidina/farmacologia , Genoma Viral/efeitos dos fármacos , HIV/fisiologia , Humanos , Isomerismo , Espectroscopia de Ressonância Magnética , Modelos Químicos , Mutagênicos/química , Espectrofotometria Infravermelho , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética
16.
Biochemistry ; 54(21): 3231-4, 2015 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-25966286

RESUMO

The newly discovered light-dependent transcription factor CarH uses adenosylcobalamin as a light sensor to regulate expression of protective genes in bacteria upon exposure to sunlight. This use of adenosylcobalamin is a clever adaptation of a classic enzyme cofactor, taking advantage of its photolabile Co-C bond. However, it is also puzzling in that photolysis of adenosylcobalamin generates the 5'-deoxyadenosyl radical that could damage DNA. Here, using liquid chromatography and spectroscopic techniques, we demonstrate that CarH suppresses release of the 5'-deoxyadenosyl radical and instead effects conversion to a nonreactive 4',5'-anhydroadenosine. In this manner, CarH safeguards use of adenosylcobalamin in light-dependent gene regulation.


Assuntos
Adenosina/análogos & derivados , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Cobamidas/metabolismo , Fotólise , Fatores de Transcrição/metabolismo , Adenosina/metabolismo , Luz
17.
J Chem Phys ; 143(24): 244301, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26723665

RESUMO

The diterpene steviol glycoside, rebaudioside A, is a natural high potency non-caloric sweetener extracted from the leaves of Stevia rebaudiana. This compound shows a parabolic change in sweet taste intensity with temperature which contrasts with the general finding for other synthetic or natural sweeteners whose sweet taste increases with temperature. The nonmonotonic taste behavior was determined by sensory analysis using large taste panels. The conformational landscape of rebaudioside A was established at a range of temperatures by means of nuclear magnetic resonance and molecular dynamics simulation. The relationship between various conformations and the observed sweetness of rebaudioside A is described.


Assuntos
Diterpenos do Tipo Caurano/química , Diterpenos do Tipo Caurano/farmacologia , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular , Edulcorantes/química , Paladar/efeitos dos fármacos , Temperatura , Diterpenos do Tipo Caurano/isolamento & purificação , Humanos , Conformação Molecular , Folhas de Planta/química , Soluções , Stevia/química , Edulcorantes/isolamento & purificação , Edulcorantes/farmacologia
18.
PLoS Genet ; 8(11): e1003064, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23166516

RESUMO

Unicellular marine algae have promise for providing sustainable and scalable biofuel feedstocks, although no single species has emerged as a preferred organism. Moreover, adequate molecular and genetic resources prerequisite for the rational engineering of marine algal feedstocks are lacking for most candidate species. Heterokonts of the genus Nannochloropsis naturally have high cellular oil content and are already in use for industrial production of high-value lipid products. First success in applying reverse genetics by targeted gene replacement makes Nannochloropsis oceanica an attractive model to investigate the cell and molecular biology and biochemistry of this fascinating organism group. Here we present the assembly of the 28.7 Mb genome of N. oceanica CCMP1779. RNA sequencing data from nitrogen-replete and nitrogen-depleted growth conditions support a total of 11,973 genes, of which in addition to automatic annotation some were manually inspected to predict the biochemical repertoire for this organism. Among others, more than 100 genes putatively related to lipid metabolism, 114 predicted transcription factors, and 109 transcriptional regulators were annotated. Comparison of the N. oceanica CCMP1779 gene repertoire with the recently published N. gaditana genome identified 2,649 genes likely specific to N. oceanica CCMP1779. Many of these N. oceanica-specific genes have putative orthologs in other species or are supported by transcriptional evidence. However, because similarity-based annotations are limited, functions of most of these species-specific genes remain unknown. Aside from the genome sequence and its analysis, protocols for the transformation of N. oceanica CCMP1779 are provided. The availability of genomic and transcriptomic data for Nannochloropsis oceanica CCMP1779, along with efficient transformation protocols, provides a blueprint for future detailed gene functional analysis and genetic engineering of Nannochloropsis species by a growing academic community focused on this genus.


Assuntos
Genoma , Anotação de Sequência Molecular , Estramenópilas/genética , Sequência de Bases , Genômica , Nitrogênio/administração & dosagem , Nitrogênio/metabolismo , Análise de Sequência de DNA , Análise de Sequência de RNA/métodos , Especificidade da Espécie , Estramenópilas/crescimento & desenvolvimento , Transformação Genética
19.
J Am Chem Soc ; 136(31): 10910-3, 2014 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-25036528

RESUMO

We report here the polymerization of several 7-isopropylidene-2,3-disubstituted norbornadienes, 7-oxa-2,3-dicarboalkoxynorbornadienes, and 11-oxa-benzonorbornadienes with a single tungsten oxo alkylidene catalyst, W(O)(CH-t-Bu)(OHMT)(Me2Pyr) (OHMT = 2,6-dimesitylphenoxide; Me2Pyr = 2,5-dimethylpyrrolide) to give cis, stereoregular polymers. The tacticities of the menthyl ester derivatives of two polymers were determined for two types. For poly(7-isopropylidene-2,3-dicarbomenthoxynorbornadiene) the structure was shown to be cis,isotactic, while for poly(7-oxa-2,3-dicarbomenthoxynorbornadiene) the structure was shown to be cis,syndiotactic. A bis-trifluoromethyl-7-isopropylidene norbornadiene was not polymerized stereoregularly with W(O)(CHCMe2Ph)(Me2Pyr)(OHMT) alone, but a cis, stereoregular polymer was formed in the presence of 1 equiv of B(C6F5)3.

20.
Phys Sportsmed ; : 1-6, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38275138

RESUMO

CONTEXT: The 2019-2020 NBA season was altered significantly by the COVID-19 pandemic with a midseason suspension of games, the NBA 'bubble' tournament, and a shortened offseason. Concerns were raised regarding player conditioning and the potential increased risk of injury due to the schedule changes. The purpose of this study was to determine the impact of the COVID-19 pandemic and associated schedule changes on NBA injuries. It was hypothesized that injury rates would be higher in the year following the pandemic and teams who participated in the bubble would have higher injury rates in the following season than non-bubble teams. Furthermore, the types of injuries would shift toward more severe injuries in the condensed 2019-20 season and the following 2020-21 season. DESIGN: Retrospective Cohort Study. METHODS: The NBA's public injury reports were queried to identify players listed on an injury report. Standardized injury events were calculated for four pre-COVID-19 seasons (2015-2019), the COVID-19 season (2019-2020), and the post-COVID-19 season (2020-2021). Injury characteristics including type and location were extracted for each year and differences within each period were calculated. RESULTS: When excluding injury events related to COVID-19 health and safety protocols, the overall injury events per 1000 exposures were not significantly different between time periods of pre-COVID-19, COVID-19, and post-COVID-19 seasons; (p = 0.199), and no difference was found in the rates of teams who participated in the bubble. Injuries, including soreness and strains, significantly decreased while fracture injuries significantly increased in the COVID-19 year. CONCLUSIONS: The COVID-19 pandemic led to an increased number of games missed, but no increase in injury rates when accounting for health and safety protocols. Additionally, bubble participation had no impact on injury rates. However, despite no changes in injury rates, the types of injuries changed with an increased proportion of severe injuries and decreased proportion of minor injuries.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA