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1.
J R Soc Interface ; 19(193): 20220391, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35919982

RESUMO

Phosphate and sulfate groups are integral to energy metabolism and introduce negative charges into biological macromolecules. One purpose of such modifications is to elicit precise binding/activation of protein partners. The physico-chemical properties of the two groups, while superficially similar, differ in one important respect-the valency of the central (phosphorus or sulfur) atom. This dictates the distinct properties of their respective esters, di-esters and hence their charges, interactions with metal ions and their solubility. These, in turn, determine the contrasting roles for which each group has evolved in biological systems. Biosynthetic links exist between the two modifications; the sulfate donor 3'-phosphoadenosine-5'-phosphosulfate being formed from adenosine triphosphate (ATP) and adenosine phosphosulfate, while the latter is generated from sulfate anions and ATP. Furthermore, phosphorylation, by a xylosyl kinase (Fam20B, glycosaminoglycan xylosylkinase) of the xylose residue of the tetrasaccharide linker region that connects nascent glycosaminoglycan (GAG) chains to their parent proteoglycans, substantially accelerates their biosynthesis. Following observations that GAG chains can enter the cell nucleus, it is hypothesized that sulfated GAGs could influence events in the nucleus, which would complete a feedback loop uniting the complementary anionic modifications of phosphorylation and sulfation through complex, inter-connected signalling networks and warrants further exploration.


Assuntos
Vias Biossintéticas , Glicosaminoglicanos , Trifosfato de Adenosina/metabolismo , Ésteres , Glicosaminoglicanos/química , Fosforilação , Sulfatos/metabolismo
2.
Mater Sci Eng C Mater Biol Appl ; 121: 111815, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33579459

RESUMO

This work deals with two new molecule-based materials, namely NiII-complexes of general formulae [Ni(L1)2] (Ni1) and [Ni(L2)2] (Ni2), where L1 = trans-cinnamaldehyde-N(4)-methyl thiosemicarbazone and L2 = trans-cinnamaldehyde-N(4)-ethyl thiosemicarbazone, as potential antitumor agents. Both compounds were characterized by elemental analysis, molar conductivity and spectroscopic techniques (FTIR and NMR). Their molecular structures were obtained by single-crystal X-ray diffraction analysis. Each one crystallizes in a monoclinic space group P 21/c, also the asymmetric unit comprises of one NiII ion located on an inversion centre and one anionic ligand, which acts as a κ2N,S-donor affording a five-membered metallaring. The compounds were screened against two selected tumour cell lines (MCF-7 and A549) and non-tumour fibroblasts cell line (MRC-5) via MTT assays. In both tumour cells, all compounds exhibited higher cytotoxicity than the control drug (cisplatin). The IC50 values ranges of 3.70 - 41.37 µM and 1.06 - 14.91 µM were found for MCF-7 and A549, respectively. Importantly, all of them were less toxicity than cisplatin in MRC-5 with SI values ranged at 11.80 - 86.60. The red blood cell (RBC) assay revealed Ni2 as non-toxic due to its reduced haemolytic effect (0--9% at 1--10 µM). The DNA binding was investigated through a combination of spectrophotometric absorption and emission titrations, electrophoresis, and circular dichroism experiments. As a result, these metal complexes were not able to strongly binding to DNA (Kb values ~104 mol L--1) but suggesting groove-binding interactions. The scavenging ability of them towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical was also evaluated in this work, but no important antioxidant behaviour was detected. Further, the interaction of Ni1 and Ni2 to human serum albumin (HSA) was explored by quenching of tryptophan emission, warfarin competitive assay, and molecular docking protocols. The HSA binding analyses indicated good affinity of both complexes to Sudlow site I (Kb values ⁓103 mol L-1).


Assuntos
Antineoplásicos , Complexos de Coordenação , Tiossemicarbazonas , Antineoplásicos/farmacologia , Humanos , Ligantes , Simulação de Acoplamento Molecular , Estrutura Molecular
3.
Diabetol Metab Syndr ; 12: 85, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042229

RESUMO

BACKGROUND: HbA1c variability has been linked to retinopathy, renal disease and autonomic neuropathy in patients with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D). Although the same relationship has been demonstrated for diabetic peripheral neuropathy (DPN) in patients with T2D, data for T1D are still lacking. METHODS: Patients older than 17 years of age with ≥ 10 years of T1D duration and follow-up were included. All patients underwent nerve conduction studies and neurological examination. Laboratorial data was retrospectively extracted from chart review. Mean HbA1c (mHbA1c) over 10 years was calculated, as well as HbA1c variability estimated by standard deviation (HbA1c-SD) and coefficient of variation (HbA1c-CV). RESULTS: Fifty patients with T1D were included (30 females and 21 non-caucasians), with mean age and T1D duration of 25.6 ± 5.0 and 17.9 ± 6.1 years, respectively. The frequency of DPN was 24%. Higher mHbA1c (10.4 ± % vs 8.1 ± %; p < 0.001), HbA1c-SD (1.8 ± 0.8 vs 0.9 ± 0.4; p < 0.001), and HbA1c-CV (1.7 ± 0.8 vs 1.2 ± 1.1; p = 0.006) were observed in patients with DPN compared to others. SD-HbA1c and HbA1c-CV were associated with DPN, diagnosed by either clinical or NCS criteria, independent of mHbA1c, age and gender. CONCLUSIONS: Not only long-term glycemic control, but also its variability is associated with DPN in patients with T1D. Larger studies are required to confirm this finding.

4.
Neotrop Entomol ; 49(4): 578-585, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32347525

RESUMO

The decline in bee populations worldwide has been associated with the use of pesticides in crop systems where these insects forage. The use of biopesticides, like spinosad, is preferred as an alternative method to control pests, because it is considered safer to non-target insects. In this study, we evaluated the lethal and sublethal effects of the spinosad-based formulation Tracer® on foragers of the stingless bee Plebeia lucii Moure (Apidae: Meliponini). Groups of bees were fed a pure diet (negative control) or a diet at different concentrations of spinosad. Positive control groups consisted of bees orally exposed to a diet with the neonicotinoid imidacloprid. Next, flight behavior, body mass, and respiration rate were evaluated in surviving bees. The results showed that bees´ survival was reduced by all concentrations of spinosad, when compared with the negative control. Bee locomotion-walking and flight-was reduced in accordance with the increase in spinosad concentrations; however, body mass and respiration rate were not altered. Our results show that the use of Tracer® in ecosystems visited by P. lucii can reduce forager bee survival and reduce their locomotion, generating a negative impact on pollination services provided by these bees.


Assuntos
Abelhas/efeitos dos fármacos , Agentes de Controle Biológico/toxicidade , Macrolídeos/toxicidade , Animais , Brasil , Combinação de Medicamentos , Voo Animal , Inseticidas/toxicidade , Locomoção , Testes de Toxicidade
5.
J Chem Phys ; 149(17): 174308, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30408986

RESUMO

We report the results of ab initio calculations for elastic scattering and also for excitation of individual electronic states of para-benzoquinone (pBQ) by the impact of low-energy electrons. The calculations for elastic scattering were performed with the Schwinger multichannel method implemented with pseudopotentials (SMCPP) in the static-exchange (SE) plus polarization (SEP) approximation for energies up to 50 eV. The assignments for the resonance spectrum obtained in this study are, in general, in good agreement with previous results available in the literature. For electronic excitation by electron impact, the SMCPP method with N energetically open electronic states (N open ), at either the static-exchange (N open ch-SE) or the static-exchange-plus-polarisation (N open ch-SEP) approximation, was employed to calculate the scattering amplitudes using a channel coupling scheme that ranges from the 1ch-SEP up to the 89ch-SE level of approximation, depending on the energy of interest. Integral cross sections (ICSs) and differential cross sections (DCSs) were obtained for incident electron energies lying between 15 eV and 50 eV. The study focuses on the influence of multichannel coupling effects for electronically inelastic processes, more specifically, on how the number of excited states included in the open-channel space impacts upon the convergence of the cross sections at intermediate and higher energies. In particular, we found that the magnitude of DCS and ICS results for electronic excitation decreases as more channels are included in the calculations. To the best of our knowledge, there are no other experimental or theoretical ICS or DCS results for excitation into individual electronic states of pBQ available in the literature between 15 and 50 eV against which we might compare the present calculations.

6.
J. nurs. health ; 8(2): e188206, Set. 2018.
Artigo em Português | BDENF - Enfermagem | ID: biblio-1029188

RESUMO

Objetivo: analisar o perfil epidemiológico dos novos registros de hanseníase na cidade de Itabuna,Bahia no período de 2010 a 2014. Métodos: estudo exploratório, descritivo e quantitativo, através dacoleta de dados secundários registrados no Sistema de Informação de Agravos de Notificação.Resultados: houve tendência de decréscimo no número de casos entre 2010 e 2014, predominou osexo masculino (56,1%), a faixa etária entre 50 a 64 anos (23,5%), cor da pele parda (58,7%), ensinofundamental incompleto (40,2%) Conclusão: a Hanseníase em Itabuna-BA ocorre mais comumente emadultos e idosos, prevalecendo indivíduos com mais de 50 anos, de cor de pele parda e com baixaescolaridade, indicando pessoas que geralmente são economicamente ativas e com pouco acesso àinformação.


Objective: to analyze the epidemiological profile of the new records of leprosy in the city of Itabuna,Bahia from 2010 to 2014. Methods: exploratory, descriptive and quantitative study was conductedby collecting secondary data recorded in the Information System Notifiable Diseases. Results: therewas a decrease in the number of cases between 2010 and 2014, the predominance of males (56,1%),age between 50 to 64 years (23,5%), brown skin color (58,7%), incomplete elementary school (40,2%).Conclusions: leprosy in Itabuna-BA occurs most commonly in adults and the elderly, with individualsover 50 years of age, from the brown skin color and with low low schooling, indicating people whoare generally economically active and with little access to information.


Assuntos
Humanos , Epidemiologia , Hanseníase , Incidência
7.
Phys Chem Chem Phys ; 20(34): 22368-22378, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30129642

RESUMO

Total electron scattering cross sections, from para-benzoquinone, for impact energies ranging between 1 to 200 eV, have been obtained by measuring the attenuation of a linear electron beam under magnetic confinement conditions. Random uncertainty limits on these values have been found to be within 5%. Systematic errors, due to the axial magnetic beam conditions in combination with the acceptance angle of the detector, have been evaluated by integrating our calculated independent atom model with the screening corrected additivity rule and interference term elastic differential cross sections over that detection acceptance angle. Our previous calculations and measurements on this molecule (Jones et al., J. Chem. Phys., 2018, 148, 124312 and J. Chem. Phys., 2018, 148, 204305), have been compiled and complemented with new elastic and inelastic scattering cross section calculations in order to obtain a comprehensive cross section data base, within the considered energy range, for modelling purposes. The self-consistency of the present data set has been evaluated by simulating the electron transport of 15 eV electrons in para-benzoquinone, and comparing those results with the observed transmitted intensity distribution.

8.
Cancer Treat Rev ; 69: 132-142, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30014951

RESUMO

IMPORTANCE: Clinical equipoise exists around the optimal time to start adjuvant endocrine therapy in patients who will receive post-operative radiotherapy for breast cancer. Concerns continue to exist regarding potential reduced efficacy, or increased toxicity, when radiation, and endocrine therapy are administered concurrently. OBJECTIVE: To perform a systematic review of studies comparing outcomes between sequential and concurrent adjuvant radiation and endocrine therapy in early-stage breast cancer. All modalities of radiation therapy were considered, and endocrine therapy could be either tamoxifen or an aromatase inhibitor. Outcomes of interest included; local, regional or distant recurrence, overall survival and treatment-related toxicities. EVIDENCE REVIEWED: PubMed, Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from 1946 to December 2017. Two reviewers independently assessed each citation using the criteria outlined above. Study quality was assessed using the Cochrane Collaboration's tool for prospective studies, and the Newcastle-Ottawa scale for retrospective studies. FINDINGS: Of 2137 unique citations identified, 13 met eligibility criteria. Eleven were unique studies (7569 patients), while 2 of the studies were updated analyses of previous studies. Studies evaluated the timing of adjuvant radiation, and tamoxifen (5 studies, 1550 patients), or aromatase inhibitors (6 studies, 6019 patients). We identified 1 complete randomized clinical trial (150 patients), and 5 retrospective studies (1580 patients), in addition to conference abstracts (5 studies, 5839 patients). Overall, none of the studies showed a significant difference in efficacy, or toxicity, with concurrent versus sequential treatment. However, given the significant heterogeneity of the study populations, it was not possible to conduct a meta-analysis. CONCLUSIONS AND RELEVANCE: In the absence of high quality data, adequately powered randomized trials are required to answer this important clinical question.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Humanos , Prognóstico , Radioterapia Adjuvante
9.
J Chem Phys ; 148(20): 204305, 2018 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-29865824

RESUMO

We report absolute experimental integral cross sections (ICSs) for the electron impact excitation of 6 bands (Bands 0-V) of unresolved electronic-states in para-benzoquinone, for incident electron energies between 20 and 40 eV. Absolute vibrational-excitation ICSs, for 3 composite vibrational bands (Bands I-III), are also reported in that same energy range. In addition, ICSs calculated within our independent atom model (IAM) with screening corrected additivity rule (SCAR) formalism, extended to account for interference (I) terms that arise due to the multi-centre nature of the scattering problem, are also reported. The sum of those ICSs gives the IAM-SCAR+I total cross section (TCS) for electron-para-benzoquinone scattering. Where possible, those calculated IAM-SCAR+I ICSs are compared against corresponding results from the present measurements with an acceptable level of accord being obtained. Similarly, we also present results from our Schwinger multichannel method with pseudopotential (SMCPP) calculations. Here elastic ICSs and ICSs corresponding to the Bands 0-III of unresolved electronic-states are presented, with agreement between the SMCPP electronic-state ICSs and those from our measurements being in good qualitative accord. The energy range of our SMCPP computations is 16-50 eV. Using the binary-encounter-Bethe (BEB) approach, total ionization cross sections for this collision system were computed. Those total ionization cross sections were then added to our SMCPP ICS results, to derive SMCPP/BEB TCSs that are typically in very good accord with those from our IAM-SCAR+I approach.

10.
Sci Rep ; 8(1): 7932, 2018 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-29785039

RESUMO

Extremely low frequency electromagnetic field (ELF EMF) pollution from overhead powerlines is known to cause biological effects across many phyla, but these effects are poorly understood. Honey bees are important pollinators across the globe and due to their foraging flights are exposed to relatively high levels of ELF EMF in proximity to powerlines. Here we ask how acute exposure to 50 Hz ELF EMFs at levels ranging from 20-100 µT, found at ground level below powerline conductors, to 1000-7000 µT, found within 1 m of the conductors, affects honey bee olfactory learning, flight, foraging activity and feeding. ELF EMF exposure was found to reduce learning, alter flight dynamics, reduce the success of foraging flights towards food sources, and feeding. The results suggest that 50 Hz ELF EMFs emitted from powerlines may represent a prominent environmental stressor for honey bees, with the potential to impact on their cognitive and motor abilities, which could in turn reduce their ability to pollinate crops.


Assuntos
Transtornos Cognitivos/etiologia , Campos Eletromagnéticos/efeitos adversos , Aprendizagem/efeitos da radiação , Transtornos da Memória/etiologia , Transtornos Motores/etiologia , Exposição à Radiação/efeitos adversos , Animais , Abelhas , Transtornos Cognitivos/patologia , Transtornos da Memória/patologia , Transtornos Motores/patologia
11.
J Chem Phys ; 148(12): 124312, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29604872

RESUMO

Angle resolved electron energy loss spectra (EELS) for para-benzoquinone (C6H4O2) have been recorded for incident electron energies of 20, 30, and 40 eV. Measured differential cross sections (DCSs) for electronic band features, composed of a combination of energetically unresolved electronic states, are subsequently derived from those EELS. Where possible, the obtained DCSs are compared with those calculated using the Schwinger multichannel method with pseudopotentials. These calculations were performed using a minimum orbital basis single configuration interaction framework at the static exchange plus polarisation level. Here, quite reasonable agreement between the experimental cross sections and the theoretical cross sections for the summation of unresolved states was observed.

12.
Matrix Biol ; 63: 23-37, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28062282

RESUMO

Syndecans are heparan sulfate proteoglycans characterized as transmembrane receptors that act cooperatively with the cell surface and extracellular matrix proteins. Syn4 knockdown was performed in order to address its role in endothelial cells (EC) behavior. Normal EC and shRNA-Syn4-EC cells were studied comparatively using complementary confocal, super-resolution and non-linear microscopic techniques. Confocal and super-resolution microscopy revealed that Syn4 knockdown alters the level and arrangement of essential proteins for focal adhesion, evidenced by the decoupling of vinculin from F-actin filaments. Furthermore, Syn4 knockdown alters the actin network leading to filopodial protrusions connected by VE-cadherin-rich junction. shRNA-Syn4-EC showed reduced adhesion and increased migration. Also, Syn4 silencing alters cell cycle as well as cell proliferation. Moreover, the ability of EC to form tube-like structures in matrigel is reduced when Syn4 is silenced. Together, the results suggest a mechanism in which Syndecan-4 acts as a central mediator that bridges fibronectin, integrin and intracellular components (actin and vinculin) and once silenced, the cytoskeleton protein network is disrupted. Ultimately, the results highlight Syn4 relevance for balanced cell behavior.


Assuntos
Actinas/metabolismo , Sindecana-4/metabolismo , Vinculina/metabolismo , Animais , Carcinogênese/metabolismo , Células Cultivadas , Células Endoteliais/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos SCID , Transplante de Neoplasias , Coelhos , Transdução de Sinais
13.
Int Nurs Rev ; 64(3): 379-387, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27753089

RESUMO

AIM: To translate, adapt and evaluate psychometric properties of the complete (15 items) and reduced (three items) versions of the Care Transitions Measure into Brazilian Portuguese. INTRODUCTION: The Care Transitions Measure assesses the quality of care transitions, from the perspective of patients. As accomplishing effective transitions is a challenge to healthcare systems, the instrument provides an opportunity to assess care transitions and improve quality initiatives. METHODS: A three-phased design was used for cross-cultural adaptation, pre-testing and evaluation of psychometric properties of the measurement in a Brazilian hospital. After forward translation, back translation and expert committee review, patients evaluated the instrument in a pre-test. Psychometric testing included face and content validity, reliability, stability and factorial analysis. RESULTS: Cross-cultural adaptation was completed successfully with a high clarity rate. Internal consistency was good in the 15-item version and was moderate in the three-item version. Test-retest reliability showed good stability of the two versions over time. The three-item version had satisfactory criterion validity. Four factors were extracted for the 15-item measure. LIMITATIONS: Samples were restricted to a group of patients from one hospital in southern Brazil. Future studies should test the measurement's construct and predictive validity. CONCLUSIONS: The translated version of the Care Transitions Measure has good face and content validity, reliability and stability. It has shown to be a valid measurement for evaluating the quality of care transitions in Brazil. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Results are beneficial for nurses, managers and policy makers for evaluating care transitions and support the need for changes in policies and practices.


Assuntos
Transferência de Pacientes/normas , Qualidade da Assistência à Saúde/normas , Inquéritos e Questionários/normas , Brasil , Humanos , Psicometria , Reprodutibilidade dos Testes , Traduções
14.
J Chem Phys ; 147(24): 244304, 2017 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-29289127

RESUMO

We report on theoretical elastic and experimental vibrational-excitation differential cross sections (DCSs) for electron scattering from para-benzoquinone (C6H4O2), in the intermediate energy range 15-50 eV. The calculations were conducted with two different theoretical methodologies, the Schwinger multichannel method with pseudopotentials (SMCPP) and the independent atom method with screening corrected additivity rule (IAM-SCAR) that also now incorporates a further interference (I) term. The SMCPP with N energetically open electronic states (Nopen) at the static-exchange-plus-polarisation (Nopench-SEP) level was used to calculate the scattering amplitudes using a channel coupling scheme that ranges from 1ch-SE up to the 89ch-SEP level of approximation. We found that in going from the 38ch-SEP to the 89ch-SEP, at all energies considered here, the elastic DCSs did not change significantly in terms of both their shapes and magnitudes. This is a good indication that our SMCPP 89ch-SEP elastic DCSs are converged with respect to the multichannel coupling effect for the investigated intermediate energies. While agreement between our IAM-SCAR+I and SMCPP 89ch-SEP computations improves as the incident electron energy increases from 15 eV, overall the level of accord is only marginal. This is particularly true at middle scattering angles, suggesting that our SCAR and interference corrections are failing somewhat for this molecule below 50 eV. We also report experimental DCS results, using a crossed-beam apparatus, for excitation of some of the unresolved ("hybrid") vibrational quanta (bands I-III) of para-benzoquinone. Those data were derived from electron energy loss spectra that were measured over a scattered electron angular range of 10°-90° and put on an absolute scale using our elastic SMCPP 89ch-SEP DCS results. The energy resolution of our measurements was ∼80 meV, which is why, at least in part, the observed vibrational features were only partially resolved. To the best of our knowledge, there are no other experimental or theoretical vibrational excitation results against which we might compare the present measurements.

15.
Artigo em Inglês | MEDLINE | ID: mdl-27401560

RESUMO

The toxicological stress induced by pesticides, particularly neonicotinoid insecticides, and its consequences in bees has been the focus of much recent attention, particularly for honey bees. However, the emphasis on honey bees and neonicotinoids has led to neglect of the relevance of stingless bees, the prevailing pollinators of natural and agricultural tropical ecosystems, and of other agrochemicals, including other pesticides and even leaf fertilizers. Consequently, studies focusing on agrochemical effects on stingless bees are sparse, usually limited to histopathological studies, and lack a holistic assessment of the effects of these compounds on physiology and behavior. Such effects have consequences for individual and colony fitness and are likely to affect both the stingless bee populations and the associated community, thereby producing a hierarchy of consequences thus far overlooked. Herein, we review the current literature on stingless bee-agrochemical interactions and discuss the underlying mechanisms involved in reported stress symptoms, as well as the potential consequences based on the peculiarities of these pollinators.


Assuntos
Agroquímicos/toxicidade , Abelhas/efeitos dos fármacos , Ecossistema , Estresse Fisiológico/efeitos dos fármacos , Animais , Abelhas/fisiologia , Estresse Fisiológico/fisiologia
16.
Biochim Biophys Acta ; 1861(9 Pt A): 970-979, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27233517

RESUMO

Brown spider phospholipases D from Loxosceles venoms are among the most widely studied toxins since they induce dermonecrosis, triggering inflammatory responses, increase vascular permeability, cause hemolysis, and renal failure. The catalytic (H12 and H47) and metal-ion binding (E32 and D34) residues in Loxosceles intermedia phospholipase D (LiRecDT1) were mutated to understand their roles in the observed activities. All mutants were identified using whole venom serum antibodies and a specific antibody to wild-type LiRecDT1, they were also analyzed by circular dichroism (CD) and differential scanning calorimetry (DSC). The phospholipase D activities of H12A, H47A, H12A-H47A, E32, D34 and E32A-D34A, such as vascular permeability, dermonecrosis, and hemolytic effects were inhibited. The mutant Y228A was equally detrimental to biochemical and biological effects of phospholipase D, suggesting an essential role of this residue in substrate recognition and binding. On the other hand, the mutant C53A-C201A reduced the enzyme's ability to hydrolyze phospholipids and promote dermonecrosis, hemolytic, and vascular effects. These results provide the basis understanding the importance of specific residues in the observed activities and contribute to the design of synthetic and specific inhibitors for Brown spider venom phospholipases D.


Assuntos
Domínio Catalítico/genética , Fosfolipase D/química , Fosfolipídeos/química , Venenos de Aranha/enzimologia , Animais , Aranha Marrom Reclusa/química , Aranha Marrom Reclusa/enzimologia , Permeabilidade Capilar , Dicroísmo Circular , Hemólise , Mutação , Fosfolipase D/metabolismo , Fosfolipídeos/metabolismo , Diester Fosfórico Hidrolases/química , Venenos de Aranha/química
17.
J Chem Phys ; 144(12): 124309, 2016 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-27036450

RESUMO

We report results from a joint experimental and theoretical investigation into electron scattering from the important industrial species furfural (C5H4O2). Specifically, differential cross sections (DCSs) have been measured and calculated for the electron-impact excitation of the electronic states of C5H4O2. The measurements were carried out at energies in the range 20-40 eV, and for scattered-electron angles between 10° and 90°. The energy resolution of those experiments was typically ∼80 meV. Corresponding Schwinger multichannel method with pseudo-potential calculations, for energies between 6-50 eV and with and without Born-closure, were also performed for a sub-set of the excited electronic-states that were accessed in the measurements. Those calculations were undertaken at the static exchange plus polarisation-level using a minimum orbital basis for single configuration interaction (MOB-SCI) approach. Agreement between the measured and calculated DCSs was qualitatively quite good, although to obtain quantitative accord, the theory would need to incorporate even more channels into the MOB-SCI. The role of multichannel coupling on the computed electronic-state DCSs is also explored in some detail.

18.
J Chem Phys ; 144(14): 144303, 2016 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-27083717

RESUMO

We report absolute experimental integral cross sections (ICSs) for electron impact excitation of bands of electronic-states in furfural, for incident electron energies in the range 20-250 eV. Wherever possible, those results are compared to corresponding excitation cross sections in the structurally similar species furan, as previously reported by da Costa et al. [Phys. Rev. A 85, 062706 (2012)] and Regeta and Allan [Phys. Rev. A 91, 012707 (2015)]. Generally, very good agreement is found. In addition, ICSs calculated with our independent atom model (IAM) with screening corrected additivity rule (SCAR) formalism, extended to account for interference (I) terms that arise due to the multi-centre nature of the scattering problem, are also reported. The sum of those ICSs gives the IAM-SCAR+I total cross section for electron-furfural scattering. Where possible, those calculated IAM-SCAR+I ICS results are compared against corresponding results from the present measurements with an acceptable level of accord being obtained. Similarly, but only for the band I and band II excited electronic states, we also present results from our Schwinger multichannel method with pseudopotentials calculations. Those results are found to be in good qualitative accord with the present experimental ICSs. Finally, with a view to assembling a complete cross section data base for furfural, some binary-encounter-Bethe-level total ionization cross sections for this collision system are presented.

19.
Pathobiology ; 83(6): 316-326, 2016.
Artigo em Inglês | LILACS, Sec. Est. Saúde SP | ID: biblio-1024773

RESUMO

Background: ADAMTS are metalloproteases with disintegrin and thrombospondin motifs. They are secreted proteases playing a role in biological processes such as inflammation, angiogenesis, and urogenital development. ADAMTS have specific substrates, such as the proteoglycans (PG) versican, aggrecan, and brevican. Despite data indicating a role of ADAMTS in tumor invasion and metastases, effects played by these molecules in cancer progression are still controversial. In ovarian cancer, the importance of ADAMTS gene mutations was recently described and related to chemotherapy outcome. Objective: To analyze protein levels of ADAMTS-1, -4, and -5, and TIMP-3 in human ovarian cancer classified as benign, borderline, or malignant. We also assessed the expression of the ADAMTS substrates aggrecan, brevican, and versican in these neoplasms. Correlations between overall survival and protein expression were performed. Methods: Tumors were classified according to the WHO Classification of Tumors of Female Reproductive Organs. Protein and PG expression was studied by immunohistochemistry. Differences in labeling were analyzed by percent measurements of stained areas. Results: ADAMTS-1, ADAMTS-5, and its tissue inhibitor TIMP-3 are increased in borderline and malignant tumors compared to benign neoplasms. Aggrecan and versican levels were increased in malignant subtypes compared to benign ovarian cancer. Higher ADAMTS-1, TIMP-3, and versican expression was associated with a shorter overall survival. Conclusions: Comparison of protease, TIMP-3, and substrate expression showed that in malignant tumors all ADAMTS and TIMP-3 expression levels were significantly raised compared to the substrates studied.


Assuntos
Neoplasias Ovarianas , Humanos , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Epiteliais e Glandulares/diagnóstico , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Proteína ADAMTS1/metabolismo , Proteína ADAMTS4/metabolismo , Carcinoma Epitelial do Ovário
20.
J Chem Phys ; 143(22): 224304, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26671372

RESUMO

We report cross sections for electron-impact excitation of vibrational quanta in furfural, at intermediate incident electron energies (20, 30, and 40 eV). The present differential cross sections are measured over the scattered electron angular range 10°-90°, with corresponding integral cross sections subsequently being determined. Furfural is a viable plant-derived alternative to petrochemicals, being produced via low-temperature plasma treatment of biomass. Current yields, however, need to be significantly improved, possibly through modelling, with the present cross sections being an important component of such simulations. To the best of our knowledge, there are no other cross sections for vibrational excitation of furfural available in the literature, so the present data are valuable for this important molecule.

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