Differential geometric analysis of alterations in MH α‐helices

Antigen presenting cells present processed peptides via their major histocompatibility (MH) complex to the T cell receptors (TRs) of T cells. If a peptide is immunogenic, a signaling cascade can be triggered within the T cell. However, the binding of different peptides and/or different TRs to MH is also known to influence the spatial arrangement of the MH α‐helices which could itself be an additional level of T cell regulation. In this study, we introduce a new methodology based on differential geometric parameters to describe MH deformations in a detailed and comparable way. For this purpose, we represent MH α‐helices by curves. On the basis of these curves, we calculate in a first step the curvature and torsion to describe each α‐helix independently. In a second step, we calculate the distribution parameter and the conical curvature of the ruled surface to describe the relative orientation of the two α‐helices. On the basis of four different test sets, we show how these differential geometric parameters can be used to describe changes in the spatial arrangement of the MH α‐helices for different biological challenges. In the first test set, we illustrate on the basis of all available crystal structures for (TR)/pMH complexes how the binding of TRs influences the MH helices. In the second test set, we show a cross evaluation of different MH alleles with the same peptide and the same MH allele with different peptides. In the third test set, we present the spatial effects of different TRs on the same peptide/MH complex. In the fourth test set, we illustrate how a severe conformational change in an α‐helix can be described quantitatively. Taken together, we provide a novel structural methodology to numerically describe subtle and severe alterations in MH α‐helices for a broad range of applications. © 2013 Wiley Periodicals, Inc.     

PALB2 as a potential prognostic biomarker for colorectal cancer

Partner and localizer of BRCA2 (PALB2) is regarded as a colorectal cancer (CRC) risk gene, but the prognostic implication of PALB2 in CRC remains unclear. In this study, we evaluate the prognostic value of the gene copy number alteration (CNA) and mRNA expression of PALB2 in The Cancer Genome Atlas (TCGA) database, and then validated with our database. We downloaded the copy number and mRNA data of PALB2 from TCGA database and examined the relationship among the genetic alterations, expression levels and survival outcomes. Gene ontology (GO) analysis was performed to study the function of PALB2. cBioPortal database was used to explore the potential co-expression genes of PALB2. There were 6.3% (37 of 582) CRC patients diagnosed as PALB2 gene deletion. The PALB2 deletion group expressed significantly lower of PALB2 mRNA than the non-deletion group (P < 0.001). Survival analysis showed that PALB2 deletion was significantly associated with shorter disease-free survival (DFS) (P = 0.026) and overall survival (OS) (P = 0.028). Low mRNA expression of PALB2 correlated with shorter OS (P < 0.001). Multivariate analysis also confirmed that PALB2 deletion and low mRNA expression of PALB2 were independent prognostic factors of poor OS in CRC (P = 0.019, 0.034, respectively). In validation cohort, negative expression of PALB2 was associated with shorter OS (P = 0.006) in stage I patients. Multivariate analysis confirmed that negative expression of PALB2 was a poor-prognostic factor (P = 0.002). GO analysis and co-expression analysis investigated that PALB2 is primarily involved in the DNA repair process. These results suggest that PALB2 gene copy number deletion and low mRNA expression could be novel prognostic biomarkers for CRC.     

Raman spectroscopy of laser‐induced oxidation of titanomagnetites

Titanomagnetites are important carriers of magnetic remanence in nature and can track redox conditions in magma. The titanium concentration in magnetite bears heavily on its magnetic properties, such as saturation moment and Curie temperature. On land and in the deep ocean, however, these minerals are prone to alteration which can mask the primary magnetic signals they once recorded. Thus, it is essential to characterize the cation composition and oxidation state of titanomagnetites that record the paleomagnetic field. Raman spectroscopy provides a unique tool for both purposes. Nonetheless, the heat generated by the excitation laser can itself induce oxidation. We show that the laser power threshold to produce oxidation decreases with increasing titanium content. With confocal Raman spectroscopy and magnetic force microscopy (MFM) on natural and synthetic titanomagnetites, a non‐destructive Raman imaging protocol was established. We applied this protocol to map out the composition and magnetization state within a single ex‐solved titanomagnetite grain in a deep‐sea basalt. Copyright © 2011 John Wiley & Sons, Ltd.     

A study in high-temperature silylation of silica

High-temperature silylation (HTS) used for the deactivation of capillary columns was studied on the silica commonly used in HPLC to gain a better insight into this process. LiChrosorb Si 100 was silylated with disilazanes at different temperatures and the materials obtained were compared in terms of organic and silanol group surface concentration, IR reflection spectra, HPLC behavior, and pore distribution parameters. Applying diphenyltetramethyldisilazane, the volatile reaction products were monitored during the HTS process. With increasing silylation temperature up to 400°C the silanol surface concentration is reduced to a very small level independent of the organic group concentration which exhibits a broad maximum depending upon substituents and temperature. Up to 350°C triorganosiloxy groups prevail as bonded organic groups. It could be proved that HTS is accompanied by pore alterations of the silica matrix. Arguments proposed by different authors in explaining HTS effects are discussed.     

次生作用对原油和油包裹体荧光颜色及光谱参数的影响

在采集多个含油气盆地油样和岩样基础上,利用显微荧光光谱和有机地化参数研究了次生作用对原油和油包裹体荧光颜色及光谱参数的影响。结果表明,原油次生蚀变主要通过改变原油中饱/芳比来影响荧光参数,其中生物降解和水洗作用使原油荧光颜色、谱形发生改变,并使荧光参数发生红移,气侵分馏和裂解作用使得原油荧光参数发生蓝移,混源作用则使两端元油分别发生红移和蓝移。通过原油和油包裹体的QF-535频率直方图可以定性识别研究区的次生作用或主成藏期。建立研究区衡量次生变化的参数与QF-535的关系式,可半定量判别原油遭受次生蚀变的程度。在显微荧光测试中应该剔除遭受过拉伸或渗漏、热裂解和光氧化作用的油包裹体。     

Putative water effects on the cryogenic FSOT capillary chromatography of sulfur-containing gases

Data are presented to illustrate putative water effects on the retention times and peak shapes for seven sulfur-containing compounds when determined by sub-ambient FSOT capillary GC/FPD. The observations are consistent with explanations based upon reported “phase soaking” and “reverse solvent effect” phenomena.     

Hereditary DNA alterations

Mutations and recombinations are hereditary alterations of DNA, which is found mainly in the chromosomes of cells. They can occur spontaneously and they can be induced by high energy radiation or by chemicals. This article considers the developments following the discovery of the DNA structure that have led to a molecular explanation of point mutations, of large chromosome alterations, and of recombination. In conclusion, consequences for human society are drawn from the knowledge gained.     

An ESR Framework for the Study of Consciousness

I will argue that, in an interdisciplinary study of consciousness, epistemic structural realism (ESR) can offer a feasible philosophical background for the study of consciousness and its associated neurophysiological phenomena in neuroscience and cognitive science while also taking into account the mathematical structures involved in this type of research. Applying the ESR principles also to the study of the neurophysiological phenomena associated with free will (or rather conscious free choice) and with various alterations of consciousness (AOCs) generated by various pathologies such as epilepsy would add explanatory value to the matter. This interdisciplinary approach would be in tune with Quine’s well known idea that philosophy is not simple conceptual analysis but is continuous with science and actually represents an abstract branch of the empirical research. The ESR could thus resonate with scientific models of consciousness such as the global neuronal workspace model (inspired by the global workspace theory—GWT) and the integrated information theory (IIT) model. While structural realism has already been employed in physics or biology, its application as a meta-theory contextualising and relating various scientific findings on consciousness is new indeed. Out of the two variants: ontic structural realism (OSR) and epistemic structural realism (ESR), the latter can be considered more suitable for the study of consciousness and its associated neurophysiological phenomena because it removes the pressure of the still unanswered ‘What is consciousness?’ ontological question and allows us to concentrate instead on the ‘What can we know about consciousness?’ epistemological question.     

Kinetic and Molecular Docking Studies to Determine the Effect of Inhibitors on the Activity and Structure of Fused G6PD::6PGL Protein from Trichomonas vaginalis

Trichomoniasis is a sexually transmitted disease with a high incidence worldwide, affecting 270 million people. Despite the existence of a catalog of available drugs to combat this infection, their extensive use promotes the appearance of resistant Trichomonas vaginalis (T. vaginalis), and some side effects in treated people, which are reasons why it is necessary to find new alternatives to combat this infection. In this study, we investigated the impact of an in-house library comprising 55 compounds on the activity of the fused T. vaginalis G6PD::6PGL (TvG6PD::6PGL) protein, a protein mediating the first reaction step of the pentose phosphate pathway (PPP), a crucial pathway involved in the parasite’s energy production. We found four compounds: JMM-3, CNZ-3, CNZ-17, and MCC-7, which inhibited the TvG6PD::6PGL protein by more than 50%. Furthermore, we determined the IC₅₀, the inactivation constants, and the type of inhibition. Our results showed that these inhibitors induced catalytic function loss of the TvG6PD::6PGL enzyme by altering its secondary and tertiary structures. Finally, molecular docking was performed for the best inhibitors, JMM-3 and MCC-7. All our findings demonstrate the potential role of these selected hit compounds as TvG6PD::6PGL enzyme selective inhibitors.