Egfr Activating Mutations And Their Association With Response To Platinum-doublet Chemotherapy In Brazilian Non-small Cell Lung Cancer Patients.

The aim of the study was to analyze the frequency of epidermal growth factor receptor (EGFR) mutations in Brazilian non-small cell lung cancer patients and to correlate these mutations with response to benefit of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Our cohort consisted of prospective patients with NSCLCs who received chemotherapy (platinum derivates plus paclitaxel) at the [UNICAMP], Brazil. EGFR exons 18-21 were analyzed in tumor-derived DNA. Fifty patients were included in the study (25 with adenocarcinoma). EGFR mutations were identified in 6/50 (12 %) NSCLCs and in 6/25 (24 %) adenocarcinomas; representing the frequency of EGFR mutations in a mostly self-reported White (82.0 %) southeastern Brazilian population of NSCLCs. Patients with NSCLCs harboring EGFR exon 19 deletions or the exon 21 L858R mutation were found to have a higher chance of response to platinum-paclitaxel (OR 9.67 [95 % CI 1.03-90.41], p = 0.047). We report the frequency of EGFR activating mutations in a typical southeastern Brazilian population with NSCLC, which are similar to that of other countries with Western European ethnicity. EGFR mutations seem to be predictive of a response to platinum-paclitaxel, and additional studies are needed to confirm or refute this relationship.

Neurodevelopment Of Small-for-gestational Age Infants: Behavioral Aspects In First Year.

The purpose of this study was to compare the behavior of full-term small-for-gestational age (SGA) with full-term appropriate-for gestational age (AGA) infants in the first year of life. We prospectively evaluated 68 infants in the 2nd month, 67 in the 6th month and 69 in the 12th month. The Bayley Scales of Infant Development-II were used, with emphasis on the Behavior Rating Scale (BRS). The groups were similar concerning the item interest in test materials and stimuli; there was a trend toward differences in the items negative affect, hypersensitivity to test materials and adaptation to change in test materials. The mean of Raw Score was significantly lower for the SGA group in the items predominant state, liability of state of arousal, positive affect, soothability when upset, energy, exploration of objects and surroundings, orientation toward examiner. A lower BRS score was associated with the SGA group in the 2nd month.

Assessment Of Robustness On Analysis Using Headspace Solid-phase Microextraction And Comprehensive Two-dimensional Gas Chromatography Through Experimental Designs.

Plackett-Burman experimental design was applied for the robustness assessment of GC×GC-qMS (Comprehensive Two-Dimensional Gas Chromatography with Fast Quadrupolar Mass Spectrometric Detection) in quantitative and qualitative analysis of volatiles compounds from chocolate samples isolated by headspace solid-phase microextraction (HS-SPME). The influence of small changes around the nominal level of six factors deemed as important on peak areas (carrier gas flow rate, modulation period, temperature of ionic source, MS photomultiplier power, injector temperature and interface temperature) and of four factors considered as potentially influential on spectral quality (minimum and maximum limits of the scanned mass ranges, ions source temperature and photomultiplier power). The analytes selected for the study were 2,3,5-trimethylpyrazine, 2-octanone, octanal, 2-pentyl-furan, 2,3,5,6-tetramethylpyrazine, and 2-nonanone e nonanal. The factors pointed out as important on the robustness of the system were photomultiplier power for quantitative analysis and lower limit of mass scanning range for qualitative analysis.

Metal Ions Bound To The Human Milk Immunoglobulin A: Metalloproteomic Approach.

The presence of calcium, iron, and zinc bound to human milk secretory IgA (sIgA) was investigated. The sIgA components were first separated by two-dimensional polyacrylamide gel electrophoresis and then identified by electrospray ionization-tandem mass spectrometry (ESI MS MS). The metal ions were detected by flame atomic absorption spectrometry after acid mineralization of the spots. The results showed eight protein spots corresponding to the IgA heavy chain constant region. Another spot was identified as the transmembrane secretory component. Calcium was bound to both the transmembrane component and the heavy chain constant region, while zinc was bound to the heavy chain constant region and iron was not bound with the identified proteins. The association of a metal ion with a protein is important for a number of reasons, and therefore, the findings of the present study may lead to a better understanding of the mechanisms of action and of additional roles that sIgA and its components play in human milk.

Human Mitochondrial Hsp70 (mortalin): Shedding Light On Atpase Activity, Interaction With Adenosine Nucleotides, Solution Structure And Domain Organization.

The human mitochondrial Hsp70, also called mortalin, is of considerable importance for mitochondria biogenesis and the correct functioning of the cell machinery. In the mitochondrial matrix, mortalin acts in the importing and folding process of nucleus-encoded proteins. The in vivo deregulation of mortalin expression and/or function has been correlated with age-related diseases and certain cancers due to its interaction with the p53 protein. In spite of its critical biological roles, structural and functional studies on mortalin are limited by its insoluble recombinant production. This study provides the first report of the production of folded and soluble recombinant mortalin when co-expressed with the human Hsp70-escort protein 1, but it is still likely prone to self-association. The monomeric fraction of mortalin presented a slightly elongated shape and basal ATPase activity that is higher than that of its cytoplasmic counterpart Hsp70-1A, suggesting that it was obtained in the functional state. Through small angle X-ray scattering, we assessed the low-resolution structural model of monomeric mortalin that is characterized by an elongated shape. This model adequately accommodated high resolution structures of Hsp70 domains indicating its quality. We also observed that mortalin interacts with adenosine nucleotides with high affinity. Thermally induced unfolding experiments indicated that mortalin is formed by at least two domains and that the transition is sensitive to the presence of adenosine nucleotides and that this process is dependent on the presence of Mg2+ ions. Interestingly, the thermal-induced unfolding assays of mortalin suggested the presence of an aggregation/association event, which was not observed for human Hsp70-1A, and this finding may explain its natural tendency for in vivo aggregation. Our study may contribute to the structural understanding of mortalin as well as to contribute for its recombinant production for antitumor compound screenings.

Hyperhoneycomb Iridate β-li_{2}iro_{3} As A Platform For Kitaev Magnetism.

A complex iridium oxide β-Li_{2}IrO_{3} crystallizes in a hyperhoneycomb structure, a three-dimensional analogue of honeycomb lattice, and is found to be a spin-orbital Mott insulator with J_{eff}=1/2 moment. Ir ions are connected to the three neighboring Ir ions via Ir-O_{2}-Ir bonding planes, which very likely gives rise to bond-dependent ferromagnetic interactions between the J_{eff}=1/2 moments, an essential ingredient of Kitaev model with a spin liquid ground state. Dominant ferromagnetic interaction between J_{eff}=1/2 moments is indeed confirmed by the temperature dependence of magnetic susceptibility χ(T) which shows a positive Curie-Weiss temperature θ_{CW}∼+40  K. A magnetic ordering with a very small entropy change, likely associated with a noncollinear arrangement of J_{eff}=1/2 moments, is observed at T_{c}=38  K. With the application of magnetic field to the ordered state, a large moment of more than 0.35  μ_{B}/Ir is induced above 3 T, a substantially polarized J_{eff}=1/2 state. We argue that the close proximity to ferromagnetism and the presence of large fluctuations evidence that the ground state of hyperhoneycomb β-Li_{2}IrO_{3} is located in close proximity of a Kitaev spin liquid.