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1.
Int J Mol Sci ; 21(6)2020 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-32235717

RESUMO

Previous results evidenced acute exposure to high altitude (HA) weakening the relation between daily melatonin cycle and the respiratory quotient. This review deals with the threat extreme environments pose on body time order, particularly concerning energy metabolism. Working at HA, at poles, or in space challenge our ancestral inborn body timing system. This conflict may also mark many aspects of our current lifestyle, involving shift work, rapid time zone crossing, and even prolonged office work in closed buildings. Misalignments between external and internal rhythms, in the short term, traduce into risk of mental and physical performance shortfalls, mood changes, quarrels, drug and alcohol abuse, failure to accomplish with the mission and, finally, high rates of fatal accidents. Relations of melatonin with energy metabolism being altered under a condition of hypoxia focused our attention on interactions of the indoleamine with redox state, as well as, with autonomic regulations. Individual tolerance/susceptibility to such interactions may hint at adequately dealing with body timing disorders under extreme conditions.

2.
Faraday Discuss ; 221(0): 379-405, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31591627

RESUMO

We present two methods that address the computational complexities arising in hydrogen transfer reactions in enzyme active sites. To address the challenge of reactive rare events, we begin with an ab initio molecular dynamics adaptation of the Caldeira-Leggett system-bath Hamiltonian and apply this approach to the study of the hydrogen transfer rate-determining step in soybean lipoxygenase-1. Through direct application of this method to compute an ensemble of classical trajectories, we discuss the critical role of isoleucine-839 in modulating the primary hydrogen transfer event in SLO-1. Notably, the formation of the hydrogen bond between isoleucine-839 and the acceptor-OH group regulates the electronegativity of the donor and acceptor groups to affect the hydrogen transfer process. Curtailing the formation of this hydrogen bond adversely affects the probability of hydrogen transfer. The second part of this paper deals with complementing the rare event sampled reaction pathways obtained from the aforementioned development through quantum nuclear wavepacket dynamics. Essentially the idea is to construct quantum nuclear dynamics on the potential surfaces obtained along the biased trajectories created as noted above. Here, while we are able to obtain critical insights on the quantum nuclear effects from wavepacket dynamics, we primarily engage in providing an improved computational approach for efficient representation of quantum dynamics data such as potential surfaces and transmission probabilities using tensor networks. We find that utilizing tensor networks yields an accurate and efficient description of time-dependent wavepackets, reduced dimensional nuclear eigenstates and associated potential energy surfaces at much reduced cost.

3.
J Chem Theory Comput ; 15(5): 2780-2796, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31002502

RESUMO

We present an approach to reduce the computational complexity and storage pertaining to quantum nuclear wave functions and potential energy surfaces. The method utilizes tensor networks implemented through sequential singular value decompositions. Two specific forms of tensor networks are considered to adaptively compress the data in multidimensional quantum nuclear wave functions and potential energy surfaces. In one case the well-known matrix product state approximation is used whereas in another case the wave function and potential energy surface space is initially partitioned into "system" and "bath" degrees of freedom through singular value decomposition, following which the individual system and bath tensors (wave functions and potentials) are in turn decomposed as matrix product states. We postulate that this leads to a mean-field version of the well-known projectionally entangled pair state known in the tensor networks community. Both formulations appear as special cases of more general higher order singular value decompositions known in the mathematics literature as Tucker decomposition. The networks are then used to study the hydrogen transfer step in the oxidation of isoprene by peroxy and hydroxy radicals. We find that both networks are extremely efficient in accurately representing quantum nuclear eigenstates and potential energy surfaces and in computing inner products between quantum nuclear eigenstates and a final-state basis to yield product side probabilities. We also present formal protocols that will be useful to perform explicit quantum nuclear dynamics.

4.
Front Physiol ; 9: 798, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30008674

RESUMO

High altitude (HA) exposure may affect human health and performance by involving the body timing system. Daily variations of melatonin may disrupt by HA exposure, thereby possibly affecting its relations with a metabolic parameter like the respiratory quotient (RQ). Sea level (SL) volunteers (7 women and 7 men, 21.0 ± 2.04 y) were examined for daily changes in salivary melatonin concentration (SMC). Sampling was successively done at SL (Antofagasta, Chile) and, on acute HA exposure, at nearby Caspana (3,270 m asl). Saliva was collected in special vials (Salimetrics Oral Swab, United Kingdom) at sunny noon (SMCD) and in the absence of blue light at midnight (SMCN). The samples were obtained after rinsing the mouth with tap water and were analyzed for SMC by immunoassay (ELISA kit; IBL International, Germany). RQ measurements (n = 12) were realized with a portable breath to breath metabolic system (OxiconTM Mobile, Germany), between 8:00 PM and 10:00 PM, once at either location. At SL, SMCD, and SMCN values (mean ± SD) were, respectively, 2.14 ± 1.30 and 11.6 ± 13.9 pg/ml (p < 0.05). Corresponding values at HA were 8.83 ± 12.6 and 13.7 ± 16.7 pg/ml (n.s.). RQ was 0.78 ± 0.07 and 0.89 ± 0.08, respectively, at SL and HA (p < 0.05). Differences between SMCN and SMCD (SMCN-SMCD) strongly correlate with the corresponding RQ values at SL (r = -0.74) and less tight at HA (r = -0.37). Similarly, mean daily SMC values (SMC) tightly correlate with RQ at SL (r = -0.79) and weaker at HA (r = -0.31). SMCN-SMCD, as well as, SMC values at SL, on the other hand, respectively, correlate with the corresponding values at HA (r = 0.71 and r = 0.85). Acute exposure to HA appears to loosen relations of SMC with RQ. A personal profile in daily SMC variation, on the other hand, tends to be conserved at HA.

5.
J Chem Theory Comput ; 14(1): 30-47, 2018 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-29182347

RESUMO

We present two sampling measures to gauge critical regions of potential energy surfaces. These sampling measures employ (a) the instantaneous quantum wavepacket density, an approximation to the (b) potential surface, its (c) gradients, and (d) a Shannon information theory based expression that estimates the local entropy associated with the quantum wavepacket. These four criteria together enable a directed sampling of potential surfaces that appears to correctly describe the local oscillation frequencies, or the local Nyquist frequency, of a potential surface. The sampling functions are then utilized to derive a tessellation scheme that discretizes the multidimensional space to enable efficient sampling of potential surfaces. The sampled potential surface is then combined with four different interpolation procedures, namely, (a) local Hermite curve interpolation, (b) low-pass filtered Lagrange interpolation, (c) the monomial symmetrization approximation (MSA) developed by Bowman and co-workers, and (d) a modified Shepard algorithm. The sampling procedure and the fitting schemes are used to compute (a) potential surfaces in highly anharmonic hydrogen-bonded systems and (b) study hydrogen-transfer reactions in biogenic volatile organic compounds (isoprene) where the transferring hydrogen atom is found to demonstrate critical quantum nuclear effects. In the case of isoprene, the algorithm discussed here is used to derive multidimensional potential surfaces along a hydrogen-transfer reaction path to gauge the effect of quantum-nuclear degrees of freedom on the hydrogen-transfer process. Based on the decreased computational effort, facilitated by the optimal sampling of the potential surfaces through the use of sampling functions discussed here, and the accuracy of the associated potential surfaces, we believe the method will find great utility in the study of quantum nuclear dynamics problems, of which application to hydrogen-transfer reactions and hydrogen-bonded systems is demonstrated here.

6.
Hypertens Pregnancy ; 34(1): 65-79, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25356531

RESUMO

OBJECTIVE: The aim of this study is to evaluate the effect of preeclampsia on the level of lipid peroxidation, activity and expression of both plasma membrane Ca(2+)- and Na(+), K(+)-ATPases in syncytiotrophoblast. METHODS: The level of lipid peroxidation was estimated by measuring TBARS. ATPase activities were quantified by a colorimetric method measuring the amount of inorganic phosphate during the assay. Expression of Ca(2+)- and Na(+), K(+)-ATPases in syncytiotrophoblast plasma membranes and term placenta tissue sections was investigated using Western blot and immunohistochemistry, respectively. RESULTS: Our results show a higher level of lipid peroxidation of syncytiotrophoblast plasma membranes from preeclamptic, as compared to uncomplicated pregnant women. Preeclampsia also significantly reduced the activity of Ca(2+)- and Na(+), K(+)-ATPases; however, expression of both ATPases was unaffected. CONCLUSION: Our findings suggest that the reduction of Ca(2+)- and Na(+), K(+)-ATPase activities during preeclampsia could be at least partially due to an increased level of lipid peroxidation of the syncytiotrophoblast plasma membranes.


Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Peroxidação de Lipídeos , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Adulto , Western Blotting , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Gravidez , Adulto Jovem
7.
High Alt Med Biol ; 15(3): 356-63, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25162792

RESUMO

PURPOSE: To discern whether arrhythmogenesis at high-altitude (HA) may differ depending on ascent or descent, as well as on age. METHODS: Male subjects (37.9±12.0 SD y, n=33) were separated into a young (Y) group (29.6±5.73 SD y, n=18) and an older (O) one (47.9±9.83 SD y, n=15). All subjects were monitored by Holter electrocardiography while successively ascending (41.2±7.51 SD min) and descending (38.7±6.68 SD min) between 2950 and 5050 m as car passengers on a 25 km road in Northern Chile. Arrhythmic events (AE) ensued when the difference between two consecutive RR intervals exceeded 0.16 sec. RESULTS: From 311 AE registered, 29% occurred on ascent and 71% on descent, the sinusal type predominating in both age groups. AE incidence, RR interval duration, and heart rate variability (HRV) in the time domain (RMSSD) increased during descent, as compared to ascent, in the Y group (p<0.05), but not in the O one. Independently of age, AE incidence along descent associates with the time previously spent at 5050 m (p<0.001). CONCLUSIONS: Rapid transitions at HA favor arrhythmogenesis, the latter becoming evident particularly in the Y group on descent. Age-dependent changes of autonomic activity appear to be involved in arrhythmogenesis on transitions at HA.


Assuntos
Altitude , Arritmias Cardíacas/etiologia , Sistema Nervoso Autônomo/fisiologia , Hipóxia/fisiopatologia , Adulto , Fatores Etários , Arritmias Cardíacas/fisiopatologia , Condução de Veículo , Chile , Humanos , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade
8.
J Membr Biol ; 245(3): 141-50, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22391579

RESUMO

Potassium channels play important physiological roles in human syncytiotrophoblasts (hSTBs) from placenta, an epithelium responsible for maternal-fetal exchange. Basal and apical plasma membranes differ in their lipid and protein composition, and the latter contains cholesterol-enriched microdomains. In placental tissue, the specific localization of potassium channels is unknown. Previously, we described two isolated subdomains from the apical membrane (MVM and LMVM) and their respective microdomains (lipid rafts). Here, we report on the distribution of K(ir)2.1, K(v)2.1, TASK-1, and TREK-1 in hSTB membranes and the lipid rafts that segregate them. Immunoblotting experiments showed that these channels are present mainly in the apical membrane from healthy hSTBs. Apical expression versus basal membrane was 84 and 16% for K(ir)2.1 and K(v)2.1, 60 and 30% for TREK-1, and 74 and 26% for TASK-1. Interestingly, K(v)2.1 showed differences between apical membrane subdomains: 26 ± 8% was located in the LMVM and 59 ± 9% in MVM. In pathological placentas, the expression distribution changed in the basal membrane: preeclampsia shifted to 50% and intrauterine growth restriction to 42% for TASK-1 and both pathologies increased to 25% for K(ir)2.1 and K(v)2.1, K(ir)2.1 appeared to be associated with rafts that were sensitive to cholesterol depletion in healthy, but not in pathological, placentas. K(v)2.1 and TREK-1 emerged in the nonraft fractions. The precise membrane localization of ion channels in hSTB membranes is necessary to understand the physiological events.


Assuntos
Microdomínios da Membrana/metabolismo , Placenta/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Complicações na Gravidez/metabolismo , Membrana Celular/metabolismo , Colesterol/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Canais de Potássio de Domínios Poros em Tandem/genética , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Gravidez
9.
J Membr Biol ; 241(3): 127-40, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21573936

RESUMO

Intrauterine growth restriction (IUGR) and preeclampsia (PE) are leading causes of perinatal and maternal morbidity and mortality. Previously we reported the expression of lipid rafts in classical microvillous membrane (MVM) and light microvillous membrane (LMVM), two subdomains in apical membrane from the human placental syncytiotrophoblast (hSTB), which constitute the epithelium responsible for maternal-fetal transport. Here the aim was to study the raft and cytoskeletal proteins from PE and IUGR. Microdomains from MVM and LMVM were tested with raft markers (placental alkaline phosphatase, lipid ganglioside, and annexin 2) and a nonraft marker (hTf-R). No changes were detected with those markers in whole purified apical membranes in normal, PE, and IUGR pregnancies; however, their patterns of distribution in lipid rafts were different in PE and IUGR. Cholesterol depletion modified their segregation, confirming their presence in lipid rafts, although unlike normal placenta, in these pathologies there is only one type of microdomain. Additionally, the cytoskeleton proteins actin, ezrin, and cytokeratin-7 showed clear differences between normal and pathological membranes. Cytokeratin-7 expression decreased to 50% in PE, and the distribution between LMVM and MVM (~43 and 57%, respectively) changed in both PE and IUGR, in contrast with the asymmetrical enrichment obtained in normal LMVM (~62%). In conclusion, lipid rafts from IUGR and PE have different features compared to rafts from normal placentae, and this is associated with alterations in the expression and distribution of cytoskeletal proteins.


Assuntos
Retardo do Crescimento Fetal/metabolismo , Microdomínios da Membrana , Microvilosidades/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Trofoblastos/metabolismo , Actinas/genética , Actinas/metabolismo , Biomarcadores/análise , Western Blotting , Estudos de Casos e Controles , Fracionamento Celular , Colesterol/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Eletroforese em Gel de Poliacrilamida , Feminino , Retardo do Crescimento Fetal/patologia , Expressão Gênica , Humanos , Queratina-7/genética , Queratina-7/metabolismo , Microdomínios da Membrana/química , Microdomínios da Membrana/genética , Microdomínios da Membrana/metabolismo , Microdomínios da Membrana/ultraestrutura , Microscopia Confocal , Microvilosidades/patologia , Especificidade de Órgãos , Placenta/patologia , Pré-Eclâmpsia/patologia , Gravidez , Trofoblastos/patologia
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