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1.
Environ Res ; 258: 119423, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38889839

RESUMO

High concentration of chromium in aquatic environments is the trigger for researchers to remediate it from wastewater environments. However, conventional water treatment methods have not been satisfactory in removing chromium from water and wastewater over the last decade. Similarly, many adsorption studies have been focused on one aspect of the treatment, but this study dealt with all aspects of adsorption packages to come up with a concrete conclusion. Therefore, this study aimed to prepare pinecone biochar (PBC) via pyrolysis and apply it for Cr(VI) removal from wastewater. The PBC was characterized using FTIR, SEM-EDX, BET surface area, pHpzc, Raman analyses, TGA, and XRD techniques. Chromium adsorption was studied under the influence of PBC dose, solution pH, initial Cr(VI) concentration, and contact time. The characteristics of PBC are illustrated by FTIR spectroscopic functional groups, XRD non-crystallite structure, SEM rough surface morphology, and high BET surface area125 m2/g, pore volume, 0.07 cm3/g, and pore size 1.4 nm. On the other hand, the maximum Cr (VI) adsorption of 69% was found at the experimental condition of pH 2, adsorbent dosage 0.25 mg/50 mL, initial Cr concentration 100 mg/L, and contact time of 120 min. Similarly, the experimental data were well-fitted with the Langmuir adsorption isotherm at R2 0.96 and the pseudo-second-order kinetics model at R2 0.99. This implies the adsorption process is mainly attributed to monolayer orientation between the adsorbent and adsorbate. In the thermodynamics study of adsorption, ΔG was found to be negative implying the adsorption process was feasible and spontaneous whereas the positive values of ΔH and ΔS indicated the adsorption process was endothermic and increasing the degree of randomness, respectively. Finally, adsorbent regeneration and reusability were successful up to three cycles. In conclusion, biochar surface modification and reusability improvements are urgently required before being applied at the pilot scale.

2.
J Prosthet Dent ; 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37914607

RESUMO

STATEMENT OF PROBLEM: The weight of larger obturators places increased stress on the supportive teeth and bearing tissue and allows gravity to act as a dislodging factor affecting the stability and retention of the prosthesis. However, whether conventionally processed and 3-dimensionally (3D) printed hollow obturators have similar reduced weights compared with solid obturators is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the weight difference between conventionally heat-processed complete denture obturators with and without hollowing and 3D printed obturators with a hollow bulb. MATERIAL AND METHODS: Obturators were fabricated as conventionally heat-processed solid obturators, conventionally heat-processed with a hollow obturator bulb, and 3D printed with a hollow obturator bulb. Nine obturator prostheses were fabricated for each type of Aramany Class I, Class II, and Class III defect. The weights of each of the 27 obturator prostheses were measured, and a statistical analysis was performed with exact versions of the Kruskal-Wallis test or Wilcoxon Rank Sum test (α=.05). RESULTS: Conventionally heat-processed solid obturators were significantly heavier than the conventionally heat-processed hollow (P<.001) or the 3D printed hollow obturators (P<.001). No significant difference (P=.222) was found between the conventionally heat-processed hollow and 3D printed hollow obturators. The decrease in weight was proportional to the size of the defect with the Aramany Class I defect having the largest differences in weight between the different fabrication methods, followed by Class II, and then Class III with a much smaller defect. CONCLUSIONS: Additive manufacturing could be a suitable alternative to conventional techniques for the fabrication of a closed hollow obturator because of the comparable weights.

3.
Phys Rev Lett ; 126(13): 131103, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33861094

RESUMO

We report on the first subpicometer interferometer flown in space. It was part of ESA's Laser Interferometer Space Antenna (LISA) Pathfinder mission and performed the fundamental measurement of the positional and angular motion of two free-falling test masses. The interferometer worked immediately, stably, and reliably from switch on until the end of the mission with exceptionally low residual noise of 32.0_{-1.7}^{+2.4} fm/sqrt[Hz], significantly better than required. We present an upper limit for the sensor performance at millihertz frequencies and a model for the measured sensitivity above 200 mHz.

4.
HIV Med ; 20(9): 628-633, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31274241

RESUMO

OBJECTIVES: Since 2013, the London HIV Mortality Review Group has conducted annual reviews of deaths among people with HIV to reduce avoidable mortality. METHODS: All London HIV care Trusts reported data on 2016 patient deaths in 2017. Deaths were submitted using a modified Causes of Death in HIV reporting form and categorized by a specialist HIV pathologist and two HIV clinicians. RESULTS: There were 206 deaths reported; 77% were among men. Median age at death was 56 years. Cause was established for 82% of deaths, with non-AIDS-related malignancies and AIDS-defining illnesses being the most common causes reported. Risk factors in the year before death included: tobacco smoking (37%), excessive alcohol consumption (19%), non-injecting drug use (10%), injecting drug use (7%) and opioid substitution therapy (6%). Thirty-nine per cent of patients had a history of depression, 33% chronic hypertension, 27% dyslipidaemia, 17% coinfection with hepatitis B virus and/or hepatitis C virus and 14% diabetes mellitus. At the time of death, 81% of patients were on antiretroviral therapy (ART), 61% had a CD4 count < 350 cells/µL, and 24% had a viral load ≥ 200 HIV-1 RNA copies/mL. Thirty-six per cent of deaths were unexpected; 61% of expected deaths were in hospital. Two-thirds of expected deaths had a prior end-of-life care discussion documented. CONCLUSIONS: In 2016, most deaths were attributable to non-AIDS-related conditions and the majority of patients were on ART and virally suppressed. However, several potentially preventable deaths were identified and underlying risk factors were common. As London HIV patients are not representative of people with HIV in the UK, a national mortality review is warranted.


Assuntos
Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Causas de Morte , Coinfecção/mortalidade , Infecções por HIV/mortalidade , Síndrome da Imunodeficiência Adquirida , Adulto , Contagem de Linfócito CD4 , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus/mortalidade , Feminino , Inquéritos Epidemiológicos , Hepatite Viral Humana/mortalidade , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Carga Viral
5.
Phys Rev Lett ; 123(11): 111101, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31573236

RESUMO

We report on the results of the LISA Pathfinder (LPF) free-fall mode experiment, in which the control force needed to compensate the quasistatic differential force acting on two test masses is applied intermittently as a series of "impulse" forces lasting a few seconds and separated by roughly 350 s periods of true free fall. This represents an alternative to the normal LPF mode of operation in which this balancing force is applied continuously, with the advantage that the acceleration noise during free fall is measured in the absence of the actuation force, thus eliminating associated noise and force calibration errors. The differential acceleration noise measurement presented here with the free-fall mode agrees with noise measured with the continuous actuation scheme, representing an important and independent confirmation of the LPF result. An additional measurement with larger actuation forces also shows that the technique can be used to eliminate actuation noise when this is a dominant factor.

6.
Int J Phytoremediation ; 21(7): 672-682, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30942084

RESUMO

This study involved the isolation of bacteria endophytes with PAH-degrading ability from plants growing around a sludge dam. A total of 19 distinct isolates that were morphologically identified were isolated from 4 species of plant with a follow-up confirmatory identification using the molecular technique. Polymerase chain reaction (PCR) of the 16S rRNA gene with specific primers (16S-27F PCR and 16S-1491R PCR) was carried out. The sequence of the PCR products was carried out, compared with similar nucleotides available in GenBank. Results of the phylogenetic analysis of the isolates indicated their belonging to 4 different clades including Proteobacteria, Actinobacteria, Cyanobacteria, and Firmicutes. These were related to the genera Bacillus, Pseudomonas, Terribacillus, Virgibacillus, Stenotrophomonas, Paenibacillus, Brevibacterium, Geobacillus, Acinetobacter. From the result, Pseudomonas demonstrated a high incidence in the plants sampled. The in-vitro degradation study and the presence of dioxygenase genes indicated that these lists of endophytes are able to use the list of PAHs tested as their source of food and energy leading to their breakdown. This means that the bacterial endophytes contributed to the remediation of petroleum hydrocarbons in planta, a situation that may have been phytotoxic to plant alone. Therefore, these bacteria endophytes could be potential organisms for enhanced phytoremediation of PAHs.


Assuntos
Endófitos , Esgotos , Biodegradação Ambiental , Filogenia , RNA Ribossômico 16S/genética
7.
Phys Rev Lett ; 120(6): 061101, 2018 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-29481269

RESUMO

In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20 µHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05) fm s^{-2}/sqrt[Hz] above 2 mHz and (6±1)×10 fm s^{-2}/sqrt[Hz] at 20 µHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency.

8.
Neuroimage ; 159: 334-345, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28797738

RESUMO

Alzheimer's disease is connected to a number of other neurodegenerative conditions, known collectively as 'tauopathies', by the presence of aggregated tau protein in the brain. Neuroinflammation and oxidative stress in AD are associated with tau pathology and both the breakdown of axonal sheaths in white matter tracts and excess iron accumulation grey matter brain regions. Despite the identification of myelin and iron concentration as major sources of contrast in quantitative susceptibility maps of the brain, the sensitivity of this technique to tau pathology has yet to be explored. In this study, we perform Quantitative Susceptibility Mapping (QSM) and T2* mapping in the rTg4510, a mouse model of tauopathy, both in vivo and ex vivo. Significant correlations were observed between histological measures of myelin content and both mean regional magnetic susceptibility and T2* values. These results suggest that magnetic susceptibility is sensitive to tissue myelin concentrations across different regions of the brain. Differences in magnetic susceptibility were detected in the corpus callosum, striatum, hippocampus and thalamus of the rTg4510 mice relative to wild type controls. The concentration of neurofibrillary tangles was found to be low to intermediate in these brain regions indicating that QSM may be a useful biomarker for early stage detection of tau pathology in neurodegenerative diseases.


Assuntos
Doença de Alzheimer/patologia , Mapeamento Encefálico/métodos , Encéfalo/patologia , Tauopatias/patologia , Animais , Feminino , Processamento de Imagem Assistida por Computador , Camundongos , Camundongos Transgênicos , Emaranhados Neurofibrilares/patologia
9.
Phys Rev Lett ; 118(17): 171101, 2017 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-28498710

RESUMO

We report on electrostatic measurements made on board the European Space Agency mission LISA Pathfinder. Detailed measurements of the charge-induced electrostatic forces exerted on free-falling test masses (TMs) inside the capacitive gravitational reference sensor are the first made in a relevant environment for a space-based gravitational wave detector. Employing a combination of charge control and electric-field compensation, we show that the level of charge-induced acceleration noise on a single TM can be maintained at a level close to 1.0 fm s^{-2} Hz^{-1/2} across the 0.1-100 mHz frequency band that is crucial to an observatory such as the Laser Interferometer Space Antenna (LISA). Using dedicated measurements that detect these effects in the differential acceleration between the two test masses, we resolve the stochastic nature of the TM charge buildup due to interplanetary cosmic rays and the TM charge-to-force coupling through stray electric fields in the sensor. All our measurements are in good agreement with predictions based on a relatively simple electrostatic model of the LISA Pathfinder instrument.

11.
Neuroimage ; 125: 739-744, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26505297

RESUMO

Increased hyperphosphorylated tau and the formation of intracellular neurofibrillary tangles are associated with the loss of neurons and cognitive decline in Alzheimer's disease, and related neurodegenerative conditions. We applied two diffusion models, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to in vivo diffusion magnetic resonance images (dMRI) of a mouse model of human tauopathy (rTg4510) at 8.5months of age. In grey matter regions with the highest degree of tau burden, microstructural indices provided by both NODDI and DTI discriminated the rTg4510 (TG) animals from wild type (WT) controls; however only the neurite density index (NDI) (the volume fraction that comprises axons or dendrites) from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein. Reductions in diffusion directionality were observed when implementing both models in the white matter region of the corpus callosum, with lower fractional anisotropy (DTI) and higher orientation dispersion (NODDI) observed in the TG animals. In comparison to DTI, histological measures of tau pathology were more closely correlated with NODDI parameters in this region. This in vivo dMRI study demonstrates that NODDI identifies potential tissue sources contributing to DTI indices and NODDI may provide greater specificity to pathology in Alzheimer's disease.


Assuntos
Doença de Alzheimer/patologia , Mapeamento Encefálico/métodos , Encéfalo/patologia , Neuritos/patologia , Emaranhados Neurofibrilares/patologia , Animais , Anisotropia , Imagem de Tensor de Difusão/métodos , Modelos Animais de Doenças , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Proteínas tau/metabolismo
12.
Phys Rev Lett ; 116(23): 231101, 2016 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-27341221

RESUMO

We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2±0.1 fm s^{-2}/sqrt[Hz], or (0.54±0.01)×10^{-15} g/sqrt[Hz], with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8±0.3) fm/sqrt[Hz], about 2 orders of magnitude better than requirements. At f≤0.5 mHz we observe a low-frequency tail that stays below 12 fm s^{-2}/sqrt[Hz] down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA.

13.
mSphere ; 9(3): e0069523, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38349166

RESUMO

Aspergillus fumigatus is a major invasive mold pathogen and the most frequent etiologic agent of invasive aspergillosis. The currently available treatments for invasive aspergillosis are limited in both number and efficacy. Our recent work has uncovered that the ß-glucan synthase inhibitors, the echinocandins, are fungicidal against strains of A. fumigatus with defects in septation initiation network (SIN) kinase activity. These drugs are known to be fungistatic against strains with normal septation. Surprisingly, SIN kinase mutant strains also failed to invade lung tissue and were significantly less virulent in immunosuppressed mouse models. Inhibiting septation in filamentous fungi is therefore an exciting therapeutic prospect to both reduce virulence and improve current antifungal therapy. However, the SIN remains understudied in pathogenic fungi. To address this knowledge gap, we characterized the putative regulatory components of the A. fumigatus SIN. These included the GTPase, SpgA, it's two-component GTPase-activating protein, ByrA/BubA, and the kinase activators, SepM and MobA. Deletion of spgA, byrA, or bubA resulted in no overt septation or echinocandin susceptibility phenotypes. In contrast, our data show that deletion of sepM or mobA largely phenocopies disruption of their SIN kinase binding partners, sepL and sidB, respectively. Reduced septum formation, echinocandin hypersusceptibility, and reduced virulence were generated by loss of either gene. These findings provide strong supporting evidence that septa are essential not only for withstanding the cell wall disrupting effects of echinocandins but are also critical for the establishment of invasive disease. Therefore, pharmacological SIN inhibition may be an exciting strategy for future antifungal drug development.IMPORTANCESepta are important structural determinants of echinocandin susceptibility and tissue invasive growth for the ubiquitous fungal pathogen Aspergillus fumigatus. Components of the septation machinery therefore represent promising novel antifungal targets to improve echinocandin activity and reduce virulence. However, little is known about septation regulation in A. fumigatus. Here, we characterize the predicted regulatory components of the A. fumigatus septation initiation network. We show that the kinase activators SepM and MobA are vital for proper septation and echinocandin resistance, with MobA playing an essential role. Null mutants of mobA displayed significantly reduced virulence in a mouse model, underscoring the importance of this pathway for A. fumigatus pathogenesis.


Assuntos
Aspergilose , Aspergillus fumigatus , Animais , Camundongos , Equinocandinas/farmacologia , Antifúngicos/metabolismo , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Fungos
14.
Front Cell Infect Microbiol ; 14: 1327299, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343890

RESUMO

In this study, two distinct in vitro infection models of Aspergillus fumigatus, using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses of co-incubated A. fumigatus uncovered 140 fungal genes up-regulated in common between both models that, when compared with a previously published in vivo transcriptomic study, allowed the identification of 13 genes consistently up-regulated in all three infection conditions. Among them, the maiA gene, responsible for a critical step in the L-phenylalanine degradation pathway, was identified. Disruption of maiA resulted in a mutant strain unable to complete the Phe degradation pathway, leading to an excessive production of pyomelanin when this amino acid served as the sole carbon source. Moreover, the disruption mutant exhibited noticeable cell wall abnormalities, with reduced levels of ß-glucans within the cell wall but did not show lack of chitin or mannans. The maiA-1 mutant strain induced reduced inflammation in primary macrophages and displayed significantly lower virulence in a neutropenic mouse model of infection. This is the first study linking the A. fumigatus maiA gene to fungal cell wall homeostasis and virulence.


Assuntos
Aspergillus fumigatus , Proteínas Fúngicas , Animais , Humanos , Camundongos , Aspergillus fumigatus/metabolismo , Parede Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Homeostase , Virulência/genética
15.
Nat Commun ; 15(1): 4261, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769341

RESUMO

Triazoles, the most widely used class of antifungal drugs, inhibit the biosynthesis of ergosterol, a crucial component of the fungal plasma membrane. Inhibition of a separate ergosterol biosynthetic step, catalyzed by the sterol C-24 methyltransferase Erg6, reduces the virulence of pathogenic yeasts, but its effects on filamentous fungal pathogens like Aspergillus fumigatus remain unexplored. Here, we show that the lipid droplet-associated enzyme Erg6 is essential for the viability of A. fumigatus and other Aspergillus species, including A. lentulus, A. terreus, and A. nidulans. Downregulation of erg6 causes loss of sterol-rich membrane domains required for apical extension of hyphae, as well as altered sterol profiles consistent with the Erg6 enzyme functioning upstream of the triazole drug target, Cyp51A/Cyp51B. Unexpectedly, erg6-repressed strains display wild-type susceptibility against the ergosterol-active triazole and polyene antifungals. Finally, we show that erg6 repression results in significant reduction in mortality in a murine model of invasive aspergillosis. Taken together with recent studies, our work supports Erg6 as a potentially pan-fungal drug target.


Assuntos
Antifúngicos , Aspergilose , Aspergillus , Ergosterol , Proteínas Fúngicas , Metiltransferases , Triazóis , Animais , Metiltransferases/metabolismo , Metiltransferases/genética , Antifúngicos/farmacologia , Aspergillus/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Camundongos , Aspergilose/microbiologia , Aspergilose/tratamento farmacológico , Ergosterol/metabolismo , Ergosterol/biossíntese , Triazóis/farmacologia , Regulação Fúngica da Expressão Gênica , Aspergillus fumigatus/genética , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/enzimologia , Aspergillus fumigatus/metabolismo , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Hifas/genética , Hifas/metabolismo , Feminino , Testes de Sensibilidade Microbiana , Virulência/genética
16.
Nat Commun ; 15(1): 3642, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684680

RESUMO

Triazole antifungals function as ergosterol biosynthesis inhibitors and are frontline therapy for invasive fungal infections, such as invasive aspergillosis. The primary mechanism of action of triazoles is through the specific inhibition of a cytochrome P450 14-α-sterol demethylase enzyme, Cyp51A/B, resulting in depletion of cellular ergosterol. Here, we uncover a clinically relevant secondary mechanism of action for triazoles within the ergosterol biosynthesis pathway. We provide evidence that triazole-mediated inhibition of Cyp51A/B activity generates sterol intermediate perturbations that are likely decoded by the sterol sensing functions of HMG-CoA reductase and Insulin-Induced Gene orthologs as increased pathway activity. This, in turn, results in negative feedback regulation of HMG-CoA reductase, the rate-limiting step of sterol biosynthesis. We also provide evidence that HMG-CoA reductase sterol sensing domain mutations previously identified as generating resistance in clinical isolates of Aspergillus fumigatus partially disrupt this triazole-induced feedback. Therefore, our data point to a secondary mechanism of action for the triazoles: induction of HMG-CoA reductase negative feedback for downregulation of ergosterol biosynthesis pathway activity. Abrogation of this feedback through acquired mutations in the HMG-CoA reductase sterol sensing domain diminishes triazole antifungal activity against fungal pathogens and underpins HMG-CoA reductase-mediated resistance.


Assuntos
Antifúngicos , Aspergillus fumigatus , Ergosterol , Proteínas Fúngicas , Hidroximetilglutaril-CoA Redutases , Triazóis , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/metabolismo , Aspergillus fumigatus/genética , Antifúngicos/farmacologia , Triazóis/farmacologia , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Ergosterol/metabolismo , Ergosterol/biossíntese , Hidroximetilglutaril-CoA Redutases/metabolismo , Hidroximetilglutaril-CoA Redutases/genética , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Farmacorresistência Fúngica/genética , Farmacorresistência Fúngica/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Testes de Sensibilidade Microbiana , Esterol 14-Desmetilase/metabolismo , Esterol 14-Desmetilase/genética , Humanos , Mutação
17.
Psychol Med ; 43(10): 2097-107, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23339857

RESUMO

BACKGROUND: People with psychosis demonstrate impaired response inhibition on the Stop Signal Task (SST). It is less clear if this impairment extends to reflection impulsivity, a form of impulsivity that has been linked to substance use in non-psychotic samples. METHOD: We compared 49 patients with first-episode psychosis (FEP) and 30 healthy control participants on two forms of impulsivity measured using the Information Sampling Test (IST) and the SST, along with clinical and IQ assessments. We also compared those patients who used cannabis with those who had either given up or never used. RESULTS: Patients with FEP had significantly greater impairment in response inhibition but not in reflection impulsivity compared with healthy controls. By contrast, patients who reported current cannabis use demonstrated greater reflection impulsivity than those that had either given up or never used, whereas there were no differences in response inhibition. CONCLUSIONS: These data suggest that abnormal reflection impulsivity is associated with substance use in psychosis but not psychosis itself ; the opposite relationship may hold for response inhibition.


Assuntos
Cannabis/efeitos adversos , Comportamento Impulsivo/fisiopatologia , Inibição Psicológica , Abuso de Maconha/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Adolescente , Adulto , Comorbidade , Feminino , Humanos , Comportamento Impulsivo/epidemiologia , Londres , Masculino , Abuso de Maconha/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Transtornos Psicóticos/epidemiologia , Adulto Jovem
18.
J Chem Phys ; 139(21): 214707, 2013 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-24320394

RESUMO

A dynamically biased (d-) precursor mediated microcanonical trapping (PMMT) model of the activated dissociative chemisorption of methane on Pt(111) is applied to a wide range of dissociative sticking experiments, and, by detailed balance, to the methane product state distributions from the thermal associative desorption of adsorbed hydrogen with coadsorbed methyl radicals. Tunneling pathways were incorporated into the d-PMMT model to better replicate the translational energy distribution of the desorbing methane product from the laser induced thermal reaction of coadsorbed hydrogen and methyl radicals occurring near T(s) = 395 K. Although tunneling is predicted to be inconsequential to the thermal dissociative chemisorption of CH4 on Pt(111) at the high temperatures of catalytic interest, once the temperature drops to 395 K the tunneling fraction of the reactive thermal flux reaches 15%, and as temperatures drop below 275 K the tunneling fraction exceeds 50%. The d-PMMT model parameters of {E0 = 58.9 kJ/mol, s = 2, η(v) = 0.40} describe the apparent threshold energy for CH4/Pt(111) dissociative chemisorption, the number of surface oscillators involved in the precursor complex, and the efficacy of molecular vibrational energy to promote reaction, relative to translational energy directed along the surface normal. Molecular translations parallel to the surface and rotations are treated as spectator degrees of freedom. Transition state vibrational frequencies are derived from generalized gradient approximation-density functional theory electronic structure calculations. The d-PMMT model replicates the diverse range of experimental data available with good fidelity, including some new effusive molecular beam and ambient gas dissociative sticking measurements. Nevertheless, there are some indications that closer agreement between theory and experiments could be achieved if a surface efficacy less than one was introduced into the modeling as an additional dynamical constraint.

19.
Environ Monit Assess ; 185(12): 10201-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23856811

RESUMO

Constructing various green wetland examples for mangrove wetland systems is a useful way to use natural power to remediate the polluted wetlands at intertidal zones. Metallothioneins (MT) are involved in heavy metal tolerance, homeostasis, and detoxification of intracellular metal ions in plants. In order to understand the mechanism of heavy metal uptake in Aegiceras corniculatum, we isolated its metallothionein gene and studied the MT gene expression in response to heavy metals contamination. Here, we report the isolation and characterization of MT2 genes from young stem tissues of A. corniculatum growing in the cadmium (Cd) and lead (Pb) polluted wetlands of Quanzhou Bay, southeast of China. The obtained cDNA sequence of MT is 512 bp in length, and it has an open reading frame encoding 79 amino acid residues with a molecular weight of 7.92 kDa and the theoretical isoelectric point of 4.55. The amino acids include 14 cysteine residues and 14 glycine residues. It is a non-transmembrane hydrophilic protein. Sequence and homology analysis showed the MT protein sequence shared more than 60% homology with other plant type 2 MT-like protein genes. The results suggested that the expression level of MT gene of A. corniculatum young stems induced by a certain range concentration of Cd(2+) and Pb(2+) stresses (0.2 mmol L(-1) Pb(2+), 1 mmol L(-1) Pb(2+), 0.2 mmol L(-1) Pb(2+), and 40 µmmol L(-1) Cd(2+); 1 mmol L(-1) Pb(2+) and 40 µmol L(-1) Cd(2+)) compared with control might show an adaptive protection. The expression levels of MT gene at 20 h stress treatment were higher than those at 480 h stress treatment. The expression levels of MT gene with 0.2 mmol L(-1) Pb(2+) stress treatment were higher than those with 0.2 mmol L(-1) Pb(2+) and 40 µmol L(-1) Cd(2+) stress treatment, and the MT gene expression levels with 1 mmol L(-1) Pb(2+) treatment were higher than those with 1 mmol L(-1) Pb(2+) and 40 µmol L(-1) Cd(2+) treatment. There exists an antagonistic action between Pb(2+) and Cd(2+) in the MT metabolization of A. corniculatum.


Assuntos
Metalotioneína/genética , Metais Pesados/toxicidade , Primulaceae/genética , Sequência de Aminoácidos , Sequência de Bases , Cádmio/análise , Cádmio/toxicidade , China , DNA Complementar/metabolismo , Monitoramento Ambiental , Expressão Gênica , Chumbo/análise , Chumbo/toxicidade , Metalotioneína/metabolismo , Metais Pesados/análise , Dados de Sequência Molecular , Primulaceae/metabolismo , Áreas Alagadas
20.
bioRxiv ; 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37609350

RESUMO

Ergosterol is a critical component of fungal plasma membranes. Although many currently available antifungal compounds target the ergosterol biosynthesis pathway for antifungal effect, current knowledge regarding ergosterol synthesis remains incomplete for filamentous fungal pathogens like Aspergillus fumigatus. Here, we show for the first time that the lipid droplet-associated sterol C-24 methyltransferase, Erg6, is essential for A. fumigatus viability. We further show that this essentiality extends to additional Aspergillus species, including A. lentulus, A. terreus, and A. nidulans. Neither the overexpression of a putative erg6 paralog, smt1, nor the exogenous addition of ergosterol could rescue erg6 deficiency. Importantly, Erg6 downregulation results in a dramatic decrease in ergosterol and accumulation in lanosterol and is further characterized by diminished sterol-rich plasma membrane domains (SRDs) at hyphal tips. Unexpectedly, erg6 repressed strains demonstrate wild-type susceptibility against the ergosterol-active triazole and polyene antifungals. Finally, repressing erg6 expression reduced fungal burden accumulation in a murine model of invasive aspergillosis. Taken together, our studies suggest that Erg6, which shows little homology to mammalian proteins, is potentially an attractive antifungal drug target for therapy of Aspergillus infections.

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