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1.
Cell Signal ; 65: 109429, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654717

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a fast-growing chronic liver disease worldwide which can lead to liver cirrhosis. Peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor, plays an important role in lipogenesis. Increased Nogo-B expression can be determined in the liver of cirrhosis patients. However, the effect of PPARγ activation on hepatic Nogo-B expression remains unknown. In this study, we found PPARγ activation by rosiglitazone or dephosphorylation increased Nogo-B expression at mRNA and protein levels in HepG2 cells and mouse primary hepatocytes. Furthermore, we identified a PPARγ response element (PPRE) in Nogo-B promoter and found PPARγ enhanced Nogo-B transcription in a PPRE-dependent manner. ChIP assay further confirms rosiglitazone enhanced the binding of PPARγ to Nogo-B promoter. Using a liver specific PPARγ deficient mice, we determined the critical role of PPARγ expression in regulating hepatic Nogo-B expression. Increased glucose and palmitate in culture medium activated Nogo-B and PPARγ expression in mouse primary hepatocytes, and corresponding, high-fat diet (HFD) induced fatty liver associated with increased hepatic Nogo-B and PPARγ expression in mice. Similarly, serum Nogo-B levels in patients with NAFLD were increased. However, rosiglitazone treatment reduced HFD-induced fatty liver and Nogo-B expression. In summary, our study identifies Nogo-B as a new molecular target of PPARγ, and suggests increased Nogo-B might be a potential indicator for NAFLD.

2.
J Sci Food Agric ; 100(1): 235-244, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31512251

RESUMO

BACKGROUND: This study evaluated the effects of early antibiotic exposure (EAE) on subsequent amino acid (AA) profiles and small intestinal AA transporter and receptor expression level in pigs with different dietary crude protein (CP) levels. Eighteen litters of piglets were fed creep feed diets, either with or without antibiotics while with sow on day 7. The pigs were weaned at day 23 and fed the same diets until day 42, when random pigs within each group were offered a normal- or low-CP diet, thereby creating four groups. On day 120, the pigs were euthanized, and jejunal and ileal mucosa and digesta were collected for gene-expression and AA-concentration analysis. RESULTS: With the normal-CP diet, EAE increased (P < 0.05) the concentrations of six essential amino acids (EAA) and three non-essential amino acids (NEAA) in serum, four EAAs and four NEAAs in jejunal mucosa, one EAA and two NEAAs in ileal mucosa, five EAAs and three NEAAs in jejunal digesta, and three EAAs and two NEAAs in ileal digesta. Early antibiotic exposure upregulated (P < 0.05) CAT1, ASCT2, ATB0,+ , CaSR, T1R1, and T1R3 expression in the jejunum, downregulated PepT1 expression with a normal-CP diet. It upregulated (P < 0.05) the expressions of CAT1, ATB0,+ , ATP1A1, and T1R3 in the ileum with a normal-CP diet. CONCLUSION: These results suggest that EAE has long-term effects on AA profiles, mainly in the jejunum and serum, by increasing AA transporter expression in the intestine, and that these effects may be influenced by dietary CP levels. © 2019 Society of Chemical Industry.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117389, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31377683

RESUMO

Rational design chelating fluorescent sensors probing metal ions in biological system are continuously hot essays nowadays, especially for zinc detection. Herein, a naphthylideneimine based zinc fluorescence probe (3) was prepared and characterized in this work. Structural features and optical properties of 3 and its metallic complexes were characterized. Fluorescent experiment indicates 3 is extremely sensitive and selective for Zn2+ with a strong fluorescence enhancement (∼34 folds) in aqueous buffer solution with a limit of detection (LOD) of 3.78 × 10-7 mol L-1. Formation constant (logKa) of the chelating complex of 3 and Zn2+ ion was determined to be 4.45. Theoretical studies were carried out to get deep insight into the response mechanism in the sensing process. Density functional theory (DFT) methods calculated formation Gibbs free energy (ΔrGmÓ©) of the deprotonated complexes model (32- ⊃ Zn) is -2.9 kcal/mol, which is in good agreement with the experimental result. The calculation results show that the low excitation states can be ascribe to S0 → T2 and S0 → S1 at 390-430 nm and 310-330 nm, respectively, due to the π → π∗ transition. Finally, yeast cell imaging experiments indicate that 3 can monitor intracellular Zn2+ as well. These findings would enable this fluorescent probe to be used as a Zinc sensor.

4.
Shanghai Kou Qiang Yi Xue ; 28(4): 435-438, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31792489

RESUMO

PURPOSE: The purpose of this study was to investigate the efficacy of microvascular coupler for arterial anastomosis in head and neck reconstruction during a 2-year period at the Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital. METHODS: Twenty-one cases of microvascular free flaps from October 2013 through December 2014 were retrospectively reviewed. Flap survival and thrombosis of the arterial anastomoses were determined in these cases. RESULTS: A total of 21 consecutive patients underwent microsurgical head and neck reconstruction, including 7(33.33%) radial forearm, nine(42.86%) fibular and 5(23.81%) anterior lateral thigh free flaps. There was 1 complication related to arterial thrombosis in this series, requiring surgical reexploration and a sutured anastomosis was performed. There were no complications related to technical performance of the coupling device. CONCLUSIONS: Use of a coupler device shows reliability for arterial anastomosis in head and neck reconstruction. With proper vessel selection and sufficient experience using the microvascular coupler, arterial coupling may be performed in an expeditious, safe, and reliable fashion with minimal morbidity. Though not commonly practiced, use of coupling device for arterial anastomosis can significantly save time, which is a viable alternative to sutured anastomosis.

5.
Bioresour Technol ; : 122450, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31796377

RESUMO

To investigate the methanogenic pathway and microbial community in a mesophilic anaerobic digestion (AD) system with food waste (FW) ethanol pre-fermentation (EP), two semi-continuous AD systems were operated by feeding FW with (PSR) and without EP (control). In this study, δ13C-ethanol was supplemented as solo substrate for AD sludge when the reactors operation stabilized to analyze the methanogenic pathways. The results suggested that approximately 59.3% of methane was produced from acetotrophic methanogens, while 40.7% was formed by hydrogenotrophic methanogens in the PSR group. On the other hand, compared with control, methane produced via CO2 reduction pathway was increased by 4.70%. Meanwhile, the composition variations of the microbial community in AD supported the above conclusion, since the relative abundances of Clostridium and Methanobacterium were enhanced by 7.6% and 10.2%, respectively in PSR reactor. These results provided a theoretical basis for AD applications and biogas yield improvements with EP process.

6.
Stem Cell Res ; 42: 101651, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31794942

RESUMO

Familial partial lipodystrophy type 2 (FPLD2) is a rare autosomal dominant metabolic disorder caused by heterozygous mutations in the LMNA gene, which encodes for the lamin A/C. A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) of a 30 year-old male patient with FPLD2 who had a heterozygous p.R349W (c.1045C > T) mutation in the LMNA gene using non-integrating episomal vector technique. This iPSC line offers a useful resource to investigate pathogenic mechanisms in FPLD2, as well as a cell-based model for drug development to treat FPLD2.

8.
Nat Commun ; 10(1): 5084, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704940

RESUMO

Thin films of several microns in thickness are ubiquitously used in packaging, electronics, and acoustic sensors. Here we demonstrate that natural wood can be directly converted into an ultrathin film with a record-small thickness of less than 10 µm through partial delignification followed by densification. Benefiting from this aligned and laminated structure, the ultrathin wood film exhibits excellent mechanical properties with a high tensile strength of 342 MPa and a Young's modulus of 43.6 GPa, respectively. The material's ultrathin thickness and exceptional mechanical strength enable excellent acoustic properties with a 1.83-times higher resonance frequency and a 1.25-times greater displacement amplitude than a commercial polypropylene diaphragm found in an audio speaker. As a proof-of-concept, we directly use the ultrathin wood film as a diaphragm in a real speaker that can output music. The ultrathin wood film with excellent mechanical property and acoustic performance is a promising candidate for next-generation acoustic speakers.

9.
Nat Struct Mol Biol ; 26(11): 1063-1070, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31695190

RESUMO

Simultaneous profiling of transcriptome and chromatin accessibility within single cells is a powerful approach to dissect gene regulatory programs in complex tissues. However, current tools are limited by modest throughput. We now describe an ultra high-throughput method, Paired-seq, for parallel analysis of transcriptome and accessible chromatin in millions of single cells. We demonstrate the utility of Paired-seq for analyzing the dynamic and cell-type-specific gene regulatory programs in complex tissues by applying it to mouse adult cerebral cortex and fetal forebrain. The joint profiles of a large number of single cells allowed us to deconvolute the transcriptome and open chromatin landscapes in the major cell types within these brain tissues, infer putative target genes of candidate enhancers, and reconstruct the trajectory of cellular lineages within the developing forebrain.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31745798

RESUMO

When food waste (FW) undergoes anaerobic digestion, the hydrolysis rate is rapid, and thus causes system instability. Sophora flavescens residues (SFRs) are rich in complex hydrolysed substances, such as lignocellulosic material. When combined FW and SFRs can effectively improve the stability of digestion systems and increase biogas yields. In this work, batch anaerobic experiments were conducted at different co-substrate ratios to investigate the performance of co-digestion and the synergistic effect of FW and SFRs. The co-digestion of the two substrates exerted synergistic effects on biogas production and the highest synergy was 120.8%. After digestion, the ratio of hydrolysed chemical oxygen demand (COD) to the entire COD (RCODH) of the co-digestion group was 1.08 times that of the single FW group, which indicated the co-digestion promoted the hydrolysis of substrates. Moreover, the hydrolysis rate constant (kh) of co-digestion group increased by 4.10 times in comparison with that of the single FW group, which indicated the co-digestion increased the hydrolysis rate. In other words, the synergistic effect mainly occurred in the hydrolysis acidification process.

11.
Med Res Rev ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746489

RESUMO

Bacterial infections lead to high morbidity and mortality globally. While current therapies against bacteria often employ antibiotics, most bacterial pathogens can form biofilms and prevent effective treatment of infections. Biofilm cells can aggregate and encased themselves in a self-secreted protective exopolymeric matrix, to reduce the penetration by antibiotics. Biofilm formation is mediated by c-di-GMP signaling, the ubiquitous secondary messenger in bacteria. Synthesis of c-di-GMP by diguanylate cyclases leads to biofilm formation via the loss of motility, increased surface attachment, and production of biofilm matrix, whereas c-di-GMP degradation by phosphodiesterases causes biofilm dispersal to new sites via increased bacterial motility and matrix breakdown. The highly variable nature of biofilm development and antimicrobial tolerance imposes tremendous challenges in conventional antimicrobial therapies, indicating an imperative need to develop anti-biofilm drugs against biofilm infections. In this review, we focus on two main emergent approaches-active dispersal and disruption. While both approaches aim to demolish biofilms, we will discuss their fundamental differences and associated methods. Active dispersal of biofilms involves signaling the bacterial cells to leave the biofilm, where resident cells ditch their sessile lifestyle, gain motility and self-degrade their matrix. Biofilm disruption leads to direct matrix degradation that forcibly releases embedded biofilm cells. Without the protection of biofilm matrix, released bacterial cells are highly exposed to antimicrobials, leading to their eradication in biofilm infections. Understanding the advantages and disadvantages of both approaches will allow optimized utility with antimicrobials in clinical settings.

12.
Molecules ; 24(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671631

RESUMO

Tagetespatula L. is a widely cultivated herbal medicinal plant in China and other countries. In this study, two new 2, 3-dihydrobenzofuran glucosides (1, 2) and fourteen known metabolites (3-16) were isolated from the stems and leaves of T. patula (SLT). The chemical structures of the isolated compounds were characterized comprehensively based on one- and two-dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configurations of compounds 1 and 2 were determined by ECD calculations. Compounds 1 and 2 exhibited moderate in vitro inhibitory activities against human gastric cancer cell lines (AGS) with IC50 values of 41.20 µmol/L and 30.43 µmol/L, respectively. The fingerprint profiles of stems and leaves of T. patula with three color types of flowers (Janie Yellow Bright, Jinmen Orange, Shouyao Red and Yellow color) were established by high-performance liquid chromatography (HPLC). Ten different batches of stems and leaves were examined as follow: Shouyao Red and Yellow color (1, 2, 3), Janie Yellow Bright (4, 5, 6, 7) and Jinmen Orange (8, 9, 10). Twenty-two common peaks were identified with similarity values ranging from 0.910 to 0.977. Meanwhile, the average peak area of SLT in the three types of flowers was different and it was the highest in Janie Yellow Bright.

13.
Appl Opt ; 58(30): 8339-8343, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674510

RESUMO

We demonstrate 10 kW spectral beam combination of six narrow-linewidth fiber amplifiers by two transmission gratings with a combining efficiency about 90%. The wavelengths of incident beams range from 1056 to 1088 nm. Each fiber amplifier delivers 2 kW output power laser with 0.25 nm root-mean-square (RMS) linewidth. A dual-grating beam-combining system is constructed to combine the six beams into a 10 kW level high-power beam and control the beam quality factor ${{\rm M}^2} \lt {2}$M2<2 by dispersion compensation. To the best of our knowledge, this is the highest output power combined by transmission gratings, which verifies the feasibility of transmission grating under high-power density laser radiation and provides an alternative approach for high-power beam combining.

14.
J Orthop Sci ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31668912

RESUMO

BACKGROUND: To investigate the alterations in body movement and their compensatory characteristics under different spinal diseases through an objective and quantitative analysis of the spinal-pelvic-lower limb motor function. METHODS: A total of 120 subjects were recruited from October 2016 to April 2017. The patients were classified into 2 groups in which 65 patients with cervical spondylotic myelopathy (CSM) and 25 patients with idiopathic scoliosis (IS). The former group was evaluated with JOA score while those in the IS group underwent Lenke classification. A control group was set up with 30 healthy subjects. All the subjects were instructed to walk at a constant speed for one minute on a treadmill, and their spinal-pelvic-lower limb motions were monitored simultaneously with a DIERS Formetric 4D® grating system and a QUINTIC gait analysis system. RESULTS: The rotation angle of thoracic and lumbar vertebrae in IS group were larger than those in the control group (P < 0.05), and the knee joint angle A in the CSM group and IS group were larger than the control group (P < 0.05). In the CSM group, the knee joint angular velocity and angular acceleration were both greater than the control group (P < 0.05). And there was a negative linear correlation between the JOA score for the lower extremity of CSM patients and their knee joint angular acceleration. CONCLUSION: IS patients tend to demonstrate increased swing amplitude of the trunk. Those with CSM will also have larger knee joint angular velocity and angular acceleration.

15.
Eur Spine J ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31696337

RESUMO

PURPOSE: To validate the reliability of Berjano and Lamartina classification system of surgical planning in cases of de novo degenerative lumbar scoliosis (DNDLS) combined with degenerative segment disease and identify factors contributing to curve progression. METHODS: Fifty-four cases of type I or II DNDLS were retrospectively reviewed. Health-related quality of life (HRQOL) was assessed using visual analogue scale (VAS) scores for the back and leg, Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) scores. Radiographic parameters were obtained from X-rays. Improvements in HRQOL were confirmed by a paired t test. Changes in radiographic parameters were confirmed by paired t test and Wilcoxon signed-rank test. Clinical relevance between spinopelvic parameters and Cobb angle progression was analyzed by Spearman correlation coefficient. RESULTS: The mean follow-up period was 36.8 ± 14.8 months. The scores taken preoperatively versus at the last follow-up were as follows: mean VAS back score, 4.5 ± 2.4 versus 1.8 ± 1.5 (p < 0.01); and mean VAS leg score, 5.2 ± 2.5 versus 1.7 ± 2.1 (p < 0.01). The ODI score improved from 25.3 ± 8.9% to 10.1 ± 5.4% (p < 0.01), whereas the mean JOA score improved from 14.3 ± 4.9 to 21.0 ± 3.7 (p < 0.01). The mean Cobb angle decreased from 17.1° ± 7.4° to 9.4° ± 4.5° postoperatively but worsened to 14.1° ± 6.4° at the last follow-up with a mean progression of 2.1° per year. Cobb angle correction was lost at a mean 2.1° ± 3.3° per year with correlation to T1 pelvic angle and sagittal vertical axis preoperatively. CONCLUSIONS: Selective decompression and short-segment fusion were effective for treating type I and II cases DNDLS. The Cobb angle increased relative to preoperative sagittal spine alignment. These slides can be retrieved under Electronic Supplementary Material.

16.
Science ; 366(6469): 1134-1139, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31727856

RESUMO

Noncoding genetic variation is a major driver of phenotypic diversity, but functional interpretation is challenging. To better understand common genetic variation associated with brain diseases, we defined noncoding regulatory regions for major cell types of the human brain. Whereas psychiatric disorders were primarily associated with variants in transcriptional enhancers and promoters in neurons, sporadic Alzheimer's disease (AD) variants were largely confined to microglia enhancers. Interactome maps connecting disease-risk variants in cell-type-specific enhancers to promoters revealed an extended microglia gene network in AD. Deletion of a microglia-specific enhancer harboring AD-risk variants ablated BIN1 expression in microglia, but not in neurons or astrocytes. These findings revise and expand the list of genes likely to be influenced by noncoding variants in AD and suggest the probable cell types in which they function.

17.
Nature ; 575(7784): 699-703, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31748743

RESUMO

Oncogenes are commonly amplified on particles of extrachromosomal DNA (ecDNA) in cancer1,2, but our understanding of the structure of ecDNA and its effect on gene regulation is limited. Here, by integrating ultrastructural imaging, long-range optical mapping and computational analysis of whole-genome sequencing, we demonstrate the structure of circular ecDNA. Pan-cancer analyses reveal that oncogenes encoded on ecDNA are among the most highly expressed genes in the transcriptome of the tumours, linking increased copy number with high transcription levels. Quantitative assessment of the chromatin state reveals that although ecDNA is packaged into chromatin with intact domain structure, it lacks higher-order compaction that is typical of chromosomes and displays significantly enhanced chromatin accessibility. Furthermore, ecDNA is shown to have a significantly greater number of ultra-long-range interactions with active chromatin, which provides insight into how the structure of circular ecDNA affects oncogene function, and connects ecDNA biology with modern cancer genomics and epigenetics.

18.
Cell Rep ; 29(9): 2646-2658.e5, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31775035

RESUMO

To systematically explore the genes mediating functional crosstalk between metazoan biological processes, we apply comparative genetic interaction (GI) mapping in Saccharomyces cerevisiae and Caenorhabditis elegans to generate an inter-bioprocess network consisting of 178 C. elegans GIs. The GI network spans six annotated biological processes including aging, intracellular transport, microtubule-based processes, cytokinesis, lipid metabolic processes, and anatomical structure development. By proposing a strategy called "reciprocal functional test" for interacting gene pairs, we discover a group of genes that mediate crosstalk between distinct biological processes. In particular, we identify the ribosomal S6 Kinase/RSKS-1, previously characterized as an mTOR (mechanistic target of rapamycin) effector, as a regulator of DAF-2 endosomal recycling transport, which traces a functional correlation between endocytic recycling and aging processes. Together, our results provide an alternative and effective strategy for identifying genes and pathways that mediate crosstalk between bioprocesses with little prior knowledge.

19.
Proc Natl Acad Sci U S A ; 116(48): 23909-23914, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31699816

RESUMO

Three-dimensional hierarchical morphologies widely exist in natural and biomimetic materials, which impart preferential functions including liquid and mass transport, energy conversion, and signal transmission for various applications. While notable progress has been made in the design and manufacturing of various hierarchical materials, the state-of-the-art approaches suffer from limited materials selection, high costs, as well as low processing throughput. Herein, by harnessing the configurable elastic crack engineering-controlled formation and configuration of cracks in elastic materials-an effect normally avoided in various industrial processes, we report the development of a facile and powerful technique that enables the faithful transfer of arbitrary hierarchical structures with broad material compatibility and structural and functional integrity. Our work paves the way for the cost-effective, large-scale production of a variety of flexible, inexpensive, and transparent 3D hierarchical and biomimetic materials.

20.
Orthop Surg ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750626

RESUMO

OBJECTIVES: Treatment for osteoporotic vertebral fracture (OVF) with cord compression is challenging and it usually requires surgical interventions to decompress nerves and restore spinal sequences. To describe a novel surgical strategy for treating OVFs with cord compression. METHODS: This is a single-center retrospective analysis. The inclusion criteria were Frankel grade C-E, single level T10 -L2 . Between January 2008 and December 2016, a total of 56 OVF patients (47 females and nine males, with an average age of 72 years (66-88 years), comprising of eight grade C, 23 grade D, and 25 grade E patients) were enrolled. The treatment algorithm included preoperative evaluation by MRI, extension CT, and radiography to classify the OVFs as type 1.1 (reducible, stable; n = 13), type1.2 (reducible, unstable; n = 16), type 2 (irreducible; n = 19) or type 2M (modifier; n = 8). Vertebroplasty (VP)/kyphoplasty (KP) was applied in type 1.1. VP/KP with posterior fixation and posterolateral fusion was applied in type 1.2. And additional laminectomy/osteotomy was used in type 2, except in a modifier group (2M) where same procedure as applied for type 1.2 was used. VAS, ODI, Cobb angle, Frankel functional grade, and complications were recorded. RESULTS: Thirteen cases were classified as type 1.1, 16 cases as type 1.2, 19 cases as type 2, and eight cases as type 2M. The follow-up period was 38.9 months (range, 24-108 months). All patients were followed-up in at least 24 months, in which time four patients died, two patients were lost at the last follow-up, and 50 patients completed the full study. The total VAS and ODI improved from 8 (7, 9) and 75.5% (67.2%, 80.0%) preoperatively to 2 (1, 3) and 31% (24.0%, 37.0%) on conclusion, respectively (P < 0.01). The local kyphotic angle was corrected from 22.3° (17.1°, 33. 8°) preoperatively to 10.4° (6.4°, 15.3°) on conclusion (P < 0.01). Twenty-three patients had achieved neurological recovery on conclusion (42E, 8D, P < 0.01). Asymptotic cement leakage was observed in 17/56 cases (30.4%), 6/56 in the affected vertebra (10.7%), and 24/330 in the screw trajectory (7.3%). At 2 years postoperatively, 11 new VFs had occurred in nine patients (16.1%), including VFs in nine adjacent segments that all occurred within 1 year after surgery. No cement migration or implant failure was noted. CONCLUSION: The novel surgical strategy for treating OVFs with cord compression consists of the most tailored and least invasive treatment for each patient. The positive mid- and long-term clinical and radiological outcomes observed could represent a step forward in devising the proposed algorithm.

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