Pediatric Brain Tumors: Signatures from the Intact Proteome

The present investigation aimed to explore the intact proteome of tissues of pediatric brain tumors of different WHO grades and localizations, including medulloblastoma, pilocytic astrocytoma, and glioblastoma, in comparison with the available data on ependymoma, to contribute to the understanding of the molecular mechanisms underlying the onset and progression of these pathologies. Tissues have been homogenized in acidic water–acetonitrile solutions containing proteases inhibitors and analyzed by LC–high resolution MS for proteomic characterization and label-free relative quantitation. Tandem MS spectra have been analyzed by either manual inspection or software elaboration, followed by experimental/theoretical MS fragmentation data comparison by bioinformatic tools. Statistically significant differences in protein/peptide levels between the different tumor histotypes have been evaluated by ANOVA test and Tukey’s post-hoc test, considering a p-value > 0.05 as significant. Together with intact protein and peptide chains, in the range of molecular mass of 1.3–22.8 kDa, several naturally occurring fragments from major proteins, peptides, and proteoforms have been also identified, some exhibiting proper biological activities. Protein and peptide sequencing allowed for the identification of different post-translational modifications, with acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations being the most frequently characterized. C-terminal truncations, lacking from two to four amino acid residues, particularly characterizing the β-thymosin peptides and ubiquitin, showed a different modulation in the diverse tumors studied. With respect to the other tumors, medulloblastoma, the most frequent malignant brain tumor of the pediatric age, was characterized by higher levels of thymosin β4 and β10 peptides, the latter and its des-IS form particularly marking this histotype. The distribution pattern of the C-terminal truncated forms was also different in glioblastoma, particularly underlying gender differences, according to the definition of male and female glioblastoma as biologically distinct diseases. Glioblastoma was also distinguished for the peculiar identification of the truncated form of the α-hemoglobin chain, lacking the C-terminal arginine, and exhibiting oxygen-binding and vasoconstrictive properties different from the intact form. The proteomic characterization of the undigested proteome, following the top-down approach, was challenging to originally investigate the post-translational events that differently characterize pediatric brain tumors. This study provides a contribution to elucidate the molecular profiles of the solid tumors most frequently affecting the pediatric age, and which are characterized by different grades of aggressiveness and localization.     

Host Restriction Factors Modulating HIV Latency and Replication in Macrophages

In addition to CD4⁺ T lymphocytes, myeloid cells and, particularly, differentiated macrophages are targets of human immunodeficiency virus type-1 (HIV-1) infection via the interaction of gp120Env with CD4 and CCR5 or CXCR4. Both T cells and macrophages support virus replication, although with substantial differences. In contrast to activated CD4⁺ T lymphocytes, HIV-1 replication in macrophages occurs in nondividing cells and it is characterized by the virtual absence of cytopathicity both in vitro and in vivo. These general features should be considered in evaluating the role of cell-associated restriction factors aiming at preventing or curtailing virus replication in macrophages and T cells, particularly in the context of designing strategies to tackle the viral reservoir in infected individuals receiving combination antiretroviral therapy. In this regard, we will here also discuss a model of reversible HIV-1 latency in primary human macrophages and the role of host factors determining the restriction or reactivation of virus replication in these cells.     

Buoyant heat transport in fluids across tilted square cavities discretely heated at one side

Laminar natural convection heat transfer inside fluid-filled, tilted square cavities cooled at one side and partially heated at the opposite side, is studied numerically. A computational code based on the SIMPLE-C algorithm is used for the solution of the system of mass, momentum, and energy transfer equations. Simulations are performed for a complete range of heater sizes and locations, Rayleigh numbers based on the side of the cavity from 10³ to 10⁷, Prandtl numbers from 0.7 to 700, and tilting angles of the enclosure from ?75° to +75°, where negative angles correspond to configurations with the heater facing downwards. It is found that the heat transfer rate increases with increasing the Rayleigh and Prandtl numbers, and the size of the heater. In addition, for negative inclinations of the enclosure the amount of heat exchanged decreases with increasing the tilting angle, while for positive inclinations the heat transfer rate either increases or decreases according as the heater is located toward the top or the bottom of the cavity. Finally, as far as the heater location is specifically concerned, the heat transfer performance has a peak for intermediate positions, the higher are the Rayleigh and Prandtl numbers, as well as the tilting angle for positive inclinations, the closer to the bottom of the cavity is the optimum heater location for maximum heat removal.     

Property specification patterns at work: verification and inconsistency explanation

Innovations in Systems and Software Engineering - Property specification patterns (PSPs) have been proposed to ease the formalization of requirements, yet enable automated verification thereof. In...     

Comments on the article ‘Comparison of calculations for interplanar distances in a crystal lattice’, by Ying Liu,Yue Liu & Michael G. B. Drew

Some statements in the review by Liu et al. [Liu Y, Liu Y, Drew GB. Comparison of calculations for interplanar distances in a crystal lattice. Cryst Rev. 2017] are corrected. The role of metric tensor to simplify calculations of interplanar spacings in crystal lattices is emphasized.     

Preliminary Investigation on the Involvement of Cytoskeleton-Related Proteins,DAAM1 and PREP,in Human Testicular Disorders

Herein, for the first time, the potential relationships between the cytoskeleton-associated proteins DAAM1 and PREP with different testicular disorders, such as classic seminoma (CS), Leydig cell tumor (LCT), and Sertoli cell-only syndrome (SOS), were evaluated. Six CS, two LCT, and two SOS tissue samples were obtained during inguinal exploration in patients with a suspect testis tumor based on clinical examination and ultrasonography. DAAM1 and PREP protein levels and immunofluorescent localization were analyzed. An increased DAAM1 protein level in CS and SOS as compared to non-pathological (NP) tissue was observed, while LCT showed no significant differences. Conversely, PREP protein level increased in LCT, while it decreased in CS and SOS compared to NP tissue. These results were strongly supported by the immunofluorescence staining, revealing an altered localization and signal intensity of DAAM1 and PREP in the analyzed samples, highlighting a perturbed cytoarchitecture. Interestingly, in LCT spermatogonia, a specific DAAM1 nuclear localization was found, probably due to an enhanced testosterone production, as confirmed by the increased protein levels of steroidogenic enzymes. Finally, although further studies are needed to verify the involvement of other formins and microtubule-associated proteins, this report raised the opportunity to indicate DAAM1 and PREP as new potential markers, supporting the cytoskeleton dynamics changes occurring during normal and/or pathological cell differentiation.     

Recent advances in plant early signaling in response to herbivory

Plants are frequently attacked by herbivores and pathogens and therefore have acquired constitutive and induced defenses during the course of their evolution. Here we review recent progress in the study of the early signal transduction pathways in host plants in response to herbivory. The sophisticated signaling network for plant defense responses is elicited and driven by both herbivore-induced factors (e.g., elicitors, effectors, and wounding) and plant signaling (e.g., phytohormone and plant volatiles) in response to arthropod factors. We describe significant findings, illuminating the scenario by providing broad insights into plant signaling involved in several arthropod-host interactions.     

Ytterbium Triflate Promoted One-Pot Three Component Synthesis of 3,4,5-Trisubstituted-3,6-dihydro-2<Emphasis Type="Italic">H</Emphasis>-1,3-oxazines

Abstract  

An efficient one-pot synthesis of 3,4,5-trisubstituted-3,6-dihydro-2H-1,3-oxazines from acetylene dicarboxylates, aromatic and aliphatic amines, and formaldehyde is described. The six member N,O-heterocyclic nucleus was constructed via Yb(OTf)₃ promoted domino hydroamination/Prins reaction/cyclization/dehydration reactions.     

Isoprene rubber filled with silica generated in situ

We modified synthetic isoprene rubber by means of the in situ generation of silica particles through the sol–gel process starting from tetraethoxysilane (TEOS) as an inorganic oxide precursor. Different reaction conditions were investigated with variations in the initial TEOS content, the reaction time of the sol–gel process, and the presence of a coupling/surfactant agent (octyltriethoxysilane). Organic–inorganic hybrid materials with a silica content up to 70 phr were obtained with the complete conversion of TEOS to silica for a long enough sol–gel reaction time. A very homogeneous dispersion of silica particles was observed in all cases together with a very good adhesion between the filler and matrix. The size of the in situ generated silica was controlled by the appropriate addition of octyltriethoxysilane. Swelling and extraction tests and dynamic mechanical analysis indicated that the vulcanization process of isoprene rubber was perturbed by the sol–gel process; this led to a slight decrease in the crosslinking degree. However, a significant reinforcing effect due to the presence of silica particles was observed for all of the investigated samples. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011