Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring

Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.     

Visualization and quantification of the mechanical deformation induced by an electrical field in poly(ethylene naphthalene 2,6‐dicarboxylate) (PEN) films

An optical nondestructive strain measurement technique was performed to analyze the mechanical deformation induced by an electrical field within the insulating materials. Poly(ethylene naphthalene 2,6‐dicarboxylate) (PEN) films were then subjected to constant electrical fields right up to their electrical breakdown. The experimental technique made it possible to follow the various stages of the mechanical behavior of PEN in real time. The final breakdown occurred in the observation zone and the related mechanical deformation was captured. A “margarita” structure was observed with a hole at the center. The experimental results indicated that the level of the induced‐mechanical deformations depended on the local environment. We defined two different zones representing the inside and the outside of the damaged area. The induced‐deformations were larger in the damaged zone. It was also observed that deformations increased when the sample had a lower degree of crystallinity. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Recognizing, assessing, and intervening with problems of professional competence.

Working collaboratively, psychologist educators and trainers at the doctoral, internship, and postdoctoral levels; credentialers; practitioners; and students offer 8 proposals for psychologists to consider in recognizing, assessing, and intervening with problems of professional competence in students and practicing professionals. In the proposals, the authors address the following topics: definitions and categories; preparing the system; self-assessment; remediation; diversity; communication across various levels of the system; confidentiality; and ethical, regulatory, and legal underpinnings. They also propose future directions for the assessment of problems in professional competence in both students and practicing psychologists. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The impact of CHP generation on CO2 emissions

The combined generation of heat and power (cogeneration) is praised by many as a technique for reducing the emissions of CO₂ in industrialized nations. This is generally true but not always. In this article we discuss the impact of some major variables on the CO₂ emission reduction capacity of cogeneration. Two sets of variables are predominant: the characteristics of the CHP process and the composition of the electricity generation sector. We highlight the interaction between the two sets of variables with the help of diagrams.     

Lack of effects of lesions of the dorsal noradrenergic bundle on behavioral vigilance

The effects of 6-hydroxydopamine (6-OHDA)-induced lesions of the dorsal noradrenergic bundle (DNB) were assessed in animals trained in a task designed to measure sustained attention, or vigilance. Infusions of 6-OHDA reduced frontal cortical noradrenaline contents but did not significantly affect striatal and hypothalamic noradrenaline contents. The performance of lesioned animals did not differ significantly from sham-lesioned controls. The performance of both the lesioned and sham-lesioned animals was impaired by the presentation of a visual distractor and by a decrease in the probability for a signal. The results from this study largely coincide with the results from previous studies on the effects of noradrenergic lesions on various aspects of attention. In contrast to the attentional functions assessed in this experiment, the ability to detect and select stimuli that are associated with activation of sympathetic functions is hypothesized to be sensitive to the effects of DNB lesions.     

Long-term stability of an Au/Al2O3 catalyst prepared by incipient wetness in continuous-flow glucose oxidation

A 0.3% Au/Al₂O₃ catalyst prepared by the incipient wetness (IW) method was investigated in the continuous-flow liquid-phase glucose oxidation. Therefore, a continuous stirred tank reactor (CSTR) system equipped with an ultrasonic separator was used. The continuous-flow glucose oxidation was carried out at 40 °C, pH 9 and 1 bar oxygen partial pressure. Residence time and glucose concentration were varied. The IW gold catalyst showed very high activity and selectivity to gluconic acid within its 110 days of operation and, thus, an excellent long-term stability. Even after severe microbial contaminations of the catalyst, its activity could be completely restored by in situ regeneration with 2-propanol.     

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.     

Prediction of Functional Consequences of Missense Mutations in ANO4 Gene

The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca²⁺-dependent ion channels and/or Ca²⁺-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.     

Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.