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1.
Plant Direct ; 8(6): e593, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38887667

RESUMO

Rice genetic diversity is regulated by multiple genes and is largely dependent on various environmental factors. Uncovering the genetic variations associated with the diversity in rice populations is the key to breed stable and high yielding rice varieties. We performed genome wide association studies (GWASs) on seven rice yielding traits (grain length, grain width, grain weight, panicle length, leaf length, leaf width, and leaf angle) based on a population of 183 rice landraces of Bangladesh. Our GWASs reveal various chromosomal regions and candidate genes that are associated with different traits in Bangladeshi rice varieties. Noteworthy was the recurrent implication of chromosome 10 in all three grain-shape-related traits (grain length, grain width, and grain weight), indicating its pivotal role in shaping rice grain morphology. Our study also underscores the involvement of transposon gene families across these three traits. For leaf related traits, chromosome 10 was found to harbor regions that are significantly associated with leaf length and leaf width. The results of these association studies support previous findings as well as provide additional insights into the genetic diversity of rice. This is the first known GWAS study on various yield-related traits in the varieties of Oryza sativa available in Bangladesh-the fourth largest rice-producing country. We believe this study will accelerate rice genetics research and breeding stable high-yielding rice in Bangladesh.

2.
Inorg Chem ; 63(13): 5972-5981, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38502785

RESUMO

Laves phases AB2 form the most abundant group of intermetallic compounds, consisting of combinations of larger electropositive metals A with smaller metals B. Many practical applications of Laves phases depend on the ability to tune their physical properties through appropriate substitution of either the A or B component. Although simple geometrical and electronic factors have long been thought to control the formation of Laves phases, no single factor alone can make predictions accurately. Several machine learning models have been developed to discover new Laves phases, including variations caused by solid solubility, using elemental properties solely on the basis of chemical composition. These models were trained on a data set comprising about 3700 entries of experimentally known phases AB2 with Laves and non-Laves structures. Among these models, a decision tree algorithm gave very good performance (average recall of 95%, precision of 94%, and accuracy of 96% on the test set) by using only a small set of descriptors, the most important of which relates to the electron density at the boundary of the Wigner-Seitz cell for the B component. This model provides guidance for new experiments by making predictions on >400000 candidates very quickly. A chemically unintuitive candidate Cd(Cu1-xSbx)2 with a limited solid solubility of Sb for Cu was targeted; it was successfully synthesized and confirmed to adopt a cubic MgCu2-type Laves structure.

3.
Molecules ; 29(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38398637

RESUMO

Several types of pollutants have acute adverse effects on living bodies, and the effective removal of these pollutants remains a challenge. Safranin O (a biological dye) and merbromin (a topical mercury-containing antiseptic) are considered organic pollutants, and there are only a few reports on their removal. Synthesized and well-characterized (through PXRD, FTIR, FESEM, and EDS analysis) MOF-5 was used for the first time in the removal of safranin O and merbromin from simulated wastewater and real wastewater. In both cases, MOF-5 effectively removed contaminants. We found that in simulated wastewater, the highest efficiency of removal of safranin O was 53.27% (for 15 mg/L) at pH 10, and for merbromin, it was 41.49% (for 25 mg/L) at pH 6. In the case of real wastewater containing natural ions (Na+, K+, F-, Cl-, SO42-, PO43-, Mg2+, and Ca2+) and other molecules, the removal efficiencies of these two dyes decreased (34.00% and 26.28% for safranin O and merbromin, respectively) because of the presence of other ions and molecules. A plausible mechanism for the removal of these pollutants using MOF-5 was proposed.

4.
Surg Endosc ; 37(12): 9414-9419, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37672111

RESUMO

BACKGROUND: Incisional hernia is a common complication following abdominal surgery. It causes change in function of core abdominal muscles leading to change in abdominal wall dynamics. This study aims to objectively measure and compare preoperative abdominal wall dynamics with surface electromyography (sEMG) in incisional hernia patients with healthy individuals. MATERIALS AND METHODS: In this prospective comparative study, two groups of participants as cases and controls were evaluated for their abdominal wall dynamics by using sEMG. Both cases and controls were evenly matched in terms of age and gender. Statistical analysis was done with STATA 14.1 and p value of < 0.05 was considered significant. RESULTS: Demographic profile was comparable between the two groups. Mean BMI of cases was higher than controls. The most common index procedure was lower segment cesarean section. The strength and power of all three abdominal wall muscles (rectus abdominis, external oblique, internal oblique) were significantly diminished among cases compared to controls. CONCLUSIONS: Abdominal wall dynamics can be objectively and correctly interpreted from sEMG of abdominal wall core muscles in patients with incisional hernia. This study shows that there is a decrease in abdominal wall strength and power in patients suffering from incisional hernia in comparison with healthy controls.


Assuntos
Parede Abdominal , Hérnia Ventral , Hérnia Incisional , Gravidez , Humanos , Feminino , Parede Abdominal/cirurgia , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Estudos Prospectivos , Cesárea , Músculos Abdominais/cirurgia , Hérnia Ventral/cirurgia
5.
Sci Rep ; 13(1): 12121, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495655

RESUMO

We investigate the nature of quantum criticality and topological phase transitions near the critical lines obtained for the extended Kitaev chain with next nearest neighbor hopping parameters and non-Hermitian chemical potential. We surprisingly find multiple gap-less points, the locations of which in the momentum space can change along the critical line unlike the Hermitian counterpart. The interesting simultaneous occurrences of vanishing and sign flipping behavior by real and imaginary components, respectively of the lowest excitation is observed near the topological phase transition. Introduction of non-Hermitian factor leads to an isolated critical point instead of a critical line and hence, reduced number of multi-critical points as compared to the Hermitian case. The critical exponents obtained for the multi-critical and critical points show a very distinct behavior from the Hermitian case.

6.
Inorg Chem ; 62(19): 7304-7314, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37125995

RESUMO

The ternary phase with the composition Ni3InSb has been synthesized by high-temperature synthesis and structurally characterized by a combination of X-ray analysis, neutron diffraction analysis, and theoretical calculations. The structure of Ni3InSb crystallizes in the orthorhombic space group Pnma with lattice constants a = 7.111(3) Å, b = 5.193(3) Å, and c = 8.2113(2) Å. The crystal structure contains ∼20 atoms in its unit cell, which are distributed over four crystallographically independent positions (two Ni, one In, and one Sb). The crystal structure can be considered as a ternary substitutional variant of Ni3Sn2 (Pnma, no. 62), where a trivalent In and a pentavalent Sb orderly occupy two tetravalent Sn sites of Ni3Sn2. This site decoration pattern of two neighboring elements, In and Sb, is unique and confirmed by first principles total energy calculations. The crystal structure can be described by two building units: Ni2Sb (building unit of Ni2In) and NiIn (NiAs-type). They alternate in the crystal structure and form infinite ac-slabs (puckered), and the slabs are stacked along [010]. A triangular lattice formed by Ni atoms indicates the existence of a geometrically frustrated structure. The calculated density of states and crystal orbital Hamilton population enlighten the stability and bonding characteristics of the structure. The temperature-dependent neutron diffraction study down to 5 K reveals that the crystal structure remains in the same orthorhombic symmetry with a weak anomaly in the lattice parameters at ∼100 K. Detailed temperature- and magnetic field-dependent magnetic properties of the title phase Ni3InSb show spin-glass- or spin-disorder-like behaviors below ∼300 K with an unusual magnetic behavior below 100 K, where an enhancement of magnetization with a decrease of the coercive field has been found.

7.
Osong Public Health Res Perspect ; 14(2): 119-128, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37183332

RESUMO

OBJECTIVES: Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) has emerged as a formidable infection in patients with COVID-19. The aggressive management of CAM affects quality of life (QOL); thus, this study was designed to assess the QOL in patients with CAM at a tertiary healthcare institution. METHODS: This cross-sectional study of 57 patients with CAM was conducted over 6 months using a semi-structured standard questionnaire (the abbreviated World Health Organization Quality of Life questionnaire [WHO-BREF]) and a self-rated improvement (SRI) scale ranging from 0 to 9. Cut-off values of ≤52 and <7 were considered to indicate poor QOL and poor improvement, respectively. The correlations of QOL and SRI scores were evaluated using Spearman rho values. RESULTS: In total, 27 patients (47.4%; 95% confidence interval [CI], 34.9%-60.1%) and 26 patients (45.6%; 95% CI, 33.4%-58.4%) had poor QOL and poor SRI scores, respectively. The overall median (interquartile range) QOL score was 52 (41-63). Headache (adjusted B, -12.3), localized facial puffiness (adjusted B , -16.4), facial discoloration (adjusted B, -23.4), loosening of teeth (adjusted B, -18.7), and facial palsy (adjusted B, -38.5) wer e significantly associated with the QOL score in patients with CAM. CONCLUSION: Approximately 1 in 2 patients with CAM had poor QOL and poor improvement. Various CAM symptoms were associated with QOL in these patients. Early recognition is the key to optimal treatment, improved outcomes, and improved QOL in patients with CAM.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34518133

RESUMO

OBJECTIVE: To develop Automatic Oral Cancer Detection algorithm for identification and differentiation of premalignant lesions from buccal cavity images for early detection of oral cancer, which may reduce related fatalities in developing countries. STUDY DESIGN: The oral cavity images of normal, erythroplakia, and leukoplakia (20 images of each) were collected and processed using MATLAB image processing tools. First, maximum red value was used to differentiate between normal and abnormal. Second, mean red value was used for the selection of a processing path through YCbCr. Third, gray-level co-occurrence matrix (GLCM) based features were used to make final decisions. Images have been randomly divided and shuffled between training and test set to rigorously train the algorithm. RESULTS: With 100% efficiency, normal images were separated from abnormal images in the first step by applying R value distribution with a cutoff R value, 11,900. Further, images with a mean R value >200 and <200 were processed by segmentation of Y plane and Cr plane, respectively. For the final decision, abnormal images were analyzed through the GLCM using the entropy feature as one of the key indicators, which can apply to the differentiation decision with 89% efficiency. CONCLUSIONS: The developed algorithm can successfully differentiate premalignant lesions from normal. A graphic user interface was developed, which displays outcomes with reasonable accuracy.


Assuntos
Detecção Precoce de Câncer , Neoplasias Bucais , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Bucais/diagnóstico por imagem
9.
Indian J Crit Care Med ; 25(10): 1167-1172, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34916750

RESUMO

BACKGROUND: Focused assessment with sonography in trauma (FAST) is an important adjunct and an extension of the clinical examination in an emergency setting for the last three decades. e-FAST visualizes the lung bases and injuries related to the lungs in addition to the intra-abdominal and pericardial bleed. In trauma patients, time is precious. Noncontrast computed tomography (NCCT) chest is the gold standard for the evaluation of blunt trauma chest. However, it is cumbersome and time-consuming and leads to increased morbidity and mortality. Therefore, evaluation of trauma patients at the trauma bay with e-FAST which is available at all times will not only save time but also the lives of trauma patients. Our endeavor is to find whether e-FAST can be substituted for NCCT for assessing injuries accurately in a stable blunt trauma patient. PATIENT AND METHODS: Prospective observational study was conducted in a tertiary care trauma center during the period of November 2017 to 2019. Of the 197 patients presenting to the trauma surgeon in the trauma center, 110 were included in the study after satisfying the inclusion criteria. Eighty-seven patients being hemodynamically unstable were excluded from the study. RESULTS: There was no statistical significance in the comparative data between the groups and all with "p" values more than 0.05. This accepts the null hypothesis and establishes the fact that there is no difference between NCCT chest which is the gold standard for chest blunt trauma and e-FAST. CONCLUSION: We conclude that e-FAST is a better adjunct to the diagnosis and management of blunt trauma chest patients. HOW TO CITE THIS ARTICLE: Devadoss H, Sharma P, Nair VV, Rehsi SS, Roy N, Rao PP. Diagnostic Accuracy of e-FAST in Stable Blunt Trauma Chest: A Prospective Analysis of 110 Cases at a Tertiary Care Center. Indian J Crit Care Med 2021;25(10):1167-1172.

10.
J Phys Condens Matter ; 33(33)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34062514

RESUMO

We investigate the nonequilibrium dynamics of entanglement entropy and out-of-time-order correlator (OTOC) of noninteracting fermions at half-filling starting from a product state to distinguish the delocalized, multifractal (in the limit of nearest neighbor hopping), localized and mixed phases hosted by the quasiperiodic Aubry-André-Harper (AAH) model in the presence of long-range hopping. For sufficiently long-range hopping strength a secondary logarithmic behavior in the entanglement entropy is found in the mixed phases whereas the primary behavior is a power-law the exponent of which is different in different phases. The saturation value of entanglement entropy in the delocalized, multifractal and mixed phases depends linearly on system size whereas in the localized phase (in the short-range regime) it is independent of system size. The early-time growth of OTOC shows very different power-law behaviors in the presence of nearest neighbor hopping and long-range hopping. The late time decay of OTOC leads to noticeably different power-law exponents in different phases. The spatial profile of OTOC and its system-size dependence also provide distinct features to distinguish phases. In the mixed phases the spatial profile of OTOC shows two different dependences on space for small and large distances respectively. Interestingly the spatial profile contains large fluctuations at the special locations related to the quasiperiodicity parameter in the presence of multifractal states.

11.
Inorg Chem ; 60(8): 5488-5496, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33779152

RESUMO

A nonstoichiometric line phase, Rh3Cd5-δ (δ ∼ 0.56), is found in close vicinity to RhCd and structurally characterized by single-crystal X-ray diffraction and energy-dispersive X-ray spectroscopy. The compound crystallizes in the cubic space group Im3m (No. 229) with lattice constant a = 6.3859(9) Å and represents a 2 × 2 × 2 superstructure of RhCd, which accommodates a vacancy concentration of nearly 6% in its crystal structure. The first-principles electronic structure calculation on a hypothetical ordered configuration of Rh3Cd5-δ reveals that Rh-Cd heteroatomic interaction plays a major role in the stability of the compound. A combination of the total energy, formation energy, and crystal orbital Hamilton population calculations on hypothetical model configurations establishes that the compound upholds an optimum vacancy concentration in the Cd2a (Cd1) site for the stability of the phase.

12.
Asian Spine J ; 15(6): 874-880, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33355853

RESUMO

Respiratory failure and chronic ventilator dependence in tetraplegics following cervical injuries located high on the spine (C1-C3) constitute significant challenges in the rehabilitation of patients given the occurrence of repeated hospitalizations and an ever-increasing financial burden. A 30-year-old man presented with posttraumatic tetraplegia following an unstable injury at the C1-C2 level with cord compression; he was managed by posterior stabilization and decompression followed by ventilator dependence and no rehabilitation until 6 months postinjury. We implanted phrenic nerve stimulator electrodes bilaterally for indirect diaphragm pacing by an implantable pulse generator that allowed for weaning from mechanical ventilation and spontaneous ventilator-free breathing at 20 weeks post-implantation and which facilitated post-tetraplegia rehabilitation. At 36 months after implantation, the patient is ventilator-free without any procedure-related complications or respiratory infections. Diaphragm pacing with phrenic nerve stimulation may be a way forward for ventilator-dependent tetraplegics in developing countries to pursue effective rehabilitation and improved quality of life.

13.
Autops. Case Rep ; 11: e2020188, 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1142403

RESUMO

Venous aneurysm of the head and neck is a rare clinical entity due to its asymptomatic nature and tendency of clinicians to report only surgical results. Whereas the primary aneurysm of internal jugular vein (IJV) in children is being increasingly recognized, secondary aneurysms of veins of the head and neck in adults, notably the external jugular vein (EJV) aneurysm remains only in anecdotal case reports. We present the case of a 63-year-old previously healthy woman who presented with a gradually progressive right lateral neck swelling over the last 18 months. Following the evaluation, she was diagnosed as a case of isolated spontaneous right-sided EJV aneurysm and was managed by surgical excision of the aneurysm.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Trombose Venosa/patologia , Veias Jugulares/patologia , Aneurisma/patologia
14.
Acta Crystallogr B Struct Sci Cryst Eng Mater ; 76(Pt 1): 47-55, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32831240

RESUMO

A binary phase Ir8Cd41 in the Ir-Cd binary system and novel ternary phases in the Ir-Cd-Cu system have been synthesized from the constituent elements using high-temperature solid-state synthesis. The structure of previously reported Ir8Cd41 and newly found ternary phases in the Ir-Cd-Cu system have been characterized by single crystal X-ray diffraction and EDS analysis. The structural analysis reveals that Ir8Cd41 adopts V8Ga41-type structure and ternary Ir-Cd-Cu phases adopt two 2 × 2 × 2-superstructures of the γ-brass-related phase. The structures of ternary Ir-Cd-Cu phases are associated with structural disorder (vacancies as well as mixed site occupancies). The crystal structures of the ternary phases are viewed using layer description and cluster concept. The 2 × 2 × 2-superstructure of γ-brass-related phases in the Cu-poor region are not isostructural with the phases in the Cu-rich region, and they are consistent with the absence of a continuous phase region between two 2 × 2 × 2-superstructures of γ-brass-related phases. In the Cu-poor region, the structures contain ∼404 atoms per unit cell, whereas in the Cu-rich phases the structures contain ∼411 atoms in their respective unit cells. The crystal structures in the Cu-poor region represent a new type in the 2 × 2 × 2-superstructure of γ-brass-related phases in view of the combination of constituent cluster types, whereas the structures in the Cu-rich region adopt the Rh7Mg44 structure type.

15.
Autops Case Rep ; 11: e2020188, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33968813

RESUMO

Venous aneurysm of the head and neck is a rare clinical entity due to its asymptomatic nature and tendency of clinicians to report only surgical results. Whereas the primary aneurysm of internal jugular vein (IJV) in children is being increasingly recognized, secondary aneurysms of veins of the head and neck in adults, notably the external jugular vein (EJV) aneurysm remains only in anecdotal case reports. We present the case of a 63-year-old previously healthy woman who presented with a gradually progressive right lateral neck swelling over the last 18 months. Following the evaluation, she was diagnosed as a case of isolated spontaneous right-sided EJV aneurysm and was managed by surgical excision of the aneurysm.

16.
Sci Rep ; 9(1): 10857, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350455

RESUMO

The maintenance of cooperative behavior is fundamental for the prosperity of human societies. Empirical studies show that high cooperation is frequently associated with the presence of strong social ties, but they are silent on whether a causal mechanism exists, how it operates, and what features of the social environment are conducive to its emergence. Here we show experimentally that strong ties increase cooperation and welfare by enabling the emergence of a close-knit and strongly bound cooperative elite. Crucially, this cooperative elite is more prevalent in social environments characterized by a large payoff difference between weak and strong ties, and no gradation in the process of strengthening a tie. These features allow cooperative individuals to adopt an all or nothing strategy to tie strengthening based on the well-known mechanism of direct reciprocity: participants become very selective by forming strong ties only with other cooperative individuals and severing ties with everyone else. Once formed, these strong ties are persistent and enhance cooperation. A dichotomous society emerges with cooperators prospering in a close-knit, strongly bound elite, and defectors earning low payoffs in a weakly connected periphery. Methodologically, our set-up provides a framework to investigate the role of the strength of ties in an experimental setting.

17.
Mol Divers ; 19(4): 991-1002, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26303382

RESUMO

The Apicomplexa parasite Plasmodium is a major cause of death in developing countries which are less equipped to bring new medicines to the market. Currently available drugs used for treatment of malaria are limited either by inadequate efficacy, toxicity and/or increased resistance. Availability of the genome sequence, microarray data and metabolic profile of Plasmodium parasite offers an opportunity for the identification of stage-specific genes important to the organism's lifecycle. In this study, microarray data were analysed for differential expression and overlapped onto metabolic pathways to identify differentially regulated pathways essential for transition to successive erythrocytic stages. The results obtained indicate that S-adenosylmethionine decarboxylase/ornithine decarboxylase, a bifunctional enzyme required for polyamine synthesis, is important for the Plasmodium cell growth in the absence of exogenous polyamines. S-adenosylmethionine decarboxylase/ornithine decarboxylase is a valuable target for designing therapeutically useful inhibitors. One such inhibitor, [Formula: see text]-difluoromethyl ornithine, is currently in use for the treatment of African sleeping sickness caused by Trypanosoma brucei. Structural studies of ornithine decarboxylase along with known inhibitors and their analogues were carried out to screen drug databases for more effective and less toxic compounds.


Assuntos
Antimaláricos/química , Plasmodium falciparum/enzimologia , Plasmodium falciparum/crescimento & desenvolvimento , Proteínas de Protozoários/química , Adenosilmetionina Descarboxilase/antagonistas & inibidores , Adenosilmetionina Descarboxilase/química , Antimaláricos/farmacologia , Desenho de Fármacos , Regulação da Expressão Gênica , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , Ornitina Descarboxilase/química , Filogenia , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/antagonistas & inibidores , Relação Estrutura-Atividade
18.
PLoS Negl Trop Dis ; 9(1): e3430, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25568941

RESUMO

Ribose 5-phosphate isomerase is an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, and catalyzes the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Trypanosomatids, including the agent of African sleeping sickness namely Trypanosoma brucei, have a type B ribose-5-phosphate isomerase. This enzyme is absent from humans, which have a structurally unrelated ribose 5-phosphate isomerase type A, and therefore has been proposed as an attractive drug target waiting further characterization. In this study, Trypanosoma brucei ribose 5-phosphate isomerase B showed in vitro isomerase activity. RNAi against this enzyme reduced parasites' in vitro growth, and more importantly, bloodstream forms infectivity. Mice infected with induced RNAi clones exhibited lower parasitaemia and a prolonged survival compared to control mice. Phenotypic reversion was achieved by complementing induced RNAi clones with an ectopic copy of Trypanosoma cruzi gene. Our results present the first functional characterization of Trypanosoma brucei ribose 5-phosphate isomerase B, and show the relevance of an enzyme belonging to the non-oxidative branch of the pentose phosphate pathway in the context of Trypanosoma brucei infection.


Assuntos
Aldose-Cetose Isomerases/metabolismo , Trypanosoma brucei brucei/enzimologia , Tripanossomíase Africana/parasitologia , Aldose-Cetose Isomerases/genética , Animais , Anticorpos Antiprotozoários , Clonagem Molecular , Regulação Enzimológica da Expressão Gênica , Técnicas de Silenciamento de Genes , Camundongos , Interferência de RNA , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo , Tripanossomíase Africana/sangue
19.
PLoS Negl Trop Dis ; 7(12): e2578, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24340117

RESUMO

Asparagine synthetase (AS) catalyzes the ATP-dependent conversion of aspartate into asparagine using ammonia or glutamine as nitrogen source. There are two distinct types of AS, asparagine synthetase A (AS-A), known as strictly ammonia-dependent, and asparagine synthetase B (AS-B), which can use either ammonia or glutamine. The absence of AS-A in humans, and its presence in trypanosomes, suggested AS-A as a potential drug target that deserved further investigation. We report the presence of functional AS-A in Trypanosoma cruzi (TcAS-A) and Trypanosoma brucei (TbAS-A): the purified enzymes convert L-aspartate into L-asparagine in the presence of ATP, ammonia and Mg(2+). TcAS-A and TbAS-A use preferentially ammonia as a nitrogen donor, but surprisingly, can also use glutamine, a characteristic so far never described for any AS-A. TbAS-A knockdown by RNAi didn't affect in vitro growth of bloodstream forms of the parasite. However, growth was significantly impaired when TbAS-A knockdown parasites were cultured in medium with reduced levels of asparagine. As expected, mice infections with induced and non-induced T. brucei RNAi clones were similar to those from wild-type parasites. However, when induced T. brucei RNAi clones were injected in mice undergoing asparaginase treatment, which depletes blood asparagine, the mice exhibited lower parasitemia and a prolonged survival in comparison to similarly-treated mice infected with control parasites. Our results show that TbAS-A can be important under in vivo conditions when asparagine is limiting, but is unlikely to be suitable as a drug target.


Assuntos
Asparagina/metabolismo , Aspartato-Amônia Ligase/antagonistas & inibidores , Trypanosoma brucei brucei/enzimologia , Trypanosoma brucei brucei/genética , Trifosfato de Adenosina/metabolismo , Amônia/metabolismo , Animais , Asparaginase/administração & dosagem , Asparaginase/metabolismo , Aspartato-Amônia Ligase/genética , Ácido Aspártico/metabolismo , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Magnésio/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Parasitemia/parasitologia , Análise de Sobrevida , Trypanosoma brucei brucei/metabolismo , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/genética , Trypanosoma cruzi/metabolismo , Tripanossomíase Africana/parasitologia
20.
Curr Comput Aided Drug Des ; 9(1): 141-50, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23286784

RESUMO

A QSAR study was performed on curcumine derivatives as HIV-1 integrase inhibitors using multiple linear regression. The statistically significant model was developed with squared correlation coefficients (r(2)) 0.891 and cross validated r(2) (r(2) cv) 0.825. The developed model revealed that electronic, shape, size, geometry, substitution's information and hydrophilicity were important atomic properties for determining the inhibitory activity of these molecules. The model was also tested successfully for external validation (r(2) pred = 0.849) as well as Tropsha's test for model predictability. Furthermore, the domain analysis was carried out to evaluate the prediction reliability of external set molecules. The model was statistically robust and had good predictive power which can be successfully utilized for screening of new molecules.


Assuntos
Curcumina/análogos & derivados , Curcumina/farmacologia , Inibidores de Integrase de HIV/química , Inibidores de Integrase de HIV/farmacologia , HIV-1/enzimologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Integrase de HIV/metabolismo , HIV-1/efeitos dos fármacos , Humanos , Modelos Estatísticos , Relação Quantitativa Estrutura-Atividade
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