Metal Ion‐Terpyridine‐Functionalized L‐Tyrosinamide Aptamers: Nucleoapzymes for Oxygen Insertion into C?H Bonds and the Transformation of L‐Tyrosinamide into Amidodopachrome

A series of metal ion‐terpyridine‐modified L‐tyrosinamide aptamers (M^{n +} = Cu²⁺ or Fe³⁺) act as enzyme‐mimicking catalysts (nucleoapzymes) for oxygen‐insertion into C? H bonds and the transformation of L‐tyrosinamide into amidodopachrome. The reaction proceeds in the presence of H₂O₂ and coadded L‐ascorbic acid. In one series of experiments, the catalyzed oxidation of L‐tyrosinamide to amidodopachrome by a set of nucleoapzymes consisting of Fe³⁺‐ or Cu²⁺‐terpyridine complexes tethered directly or through a 4 × thymidine (4 × T) bridge, to the 5′‐ or 3′‐end of the 49‐mer L‐tyrosinamide aptamer or to a shorter 23‐mer L‐tyrosinamide aptamer is examined. All nucleoapzymes reveal catalytic Michaelis–Menten enzyme‐like activities and the separated Fe³⁺‐ or Cu²⁺‐terpyridine and L‐tyrosinamide aptamer units show only minute catalytic properties. The catalytic activities of the nucleoapzymes are attributed to the concentration of the L‐tyrosinamide substrate by the aptamer units in proximity to the catalytic sites (K_d = (14 ± 0.1) × 10^?6 m for all 49‐mer catalysts and K_d = (2.5 ± 0.1) × 10^?6 m and K_d = (0.8 ± 0.04) × 10^?6 m for the 23‐mer catalysts). Electron spin resonance experiments reveal that ?OH radicals and ascorbate radicals participate in the transformation of tyrosine derivatives to catechol products. An autocatalytic feedback mechanism for the amplified generation of the two radicals is suggested.     

Roles for Selenoprotein I and Ethanolamine Phospholipid Synthesis in T Cell Activation

The selenoprotein family includes 25 members, many of which are antioxidant or redox regulating enzymes. A unique member of this family is Selenoprotein I (SELENOI), which does not catalyze redox reactions, but instead is an ethanolamine phosphotransferase (Ept). In fact, the characteristic selenocysteine residue that defines selenoproteins lies far outside of the catalytic domain of SELENOI. Furthermore, data using recombinant SELENOI lacking the selenocysteine residue have suggested that the selenocysteine amino acid is not directly involved in the Ept reaction. SELENOI is involved in two different pathways for the synthesis of phosphatidylethanolamine (PE) and plasmenyl PE, which are constituents of cellular membranes. Ethanolamine phospholipid synthesis has emerged as an important process for metabolic reprogramming that occurs in pluripotent stem cells and proliferating tumor cells, and this review discusses roles for upregulation of SELENOI during T cell activation, proliferation, and differentiation. SELENOI deficiency lowers but does not completely diminish de novo synthesis of PE and plasmenyl PE during T cell activation. Interestingly, metabolic reprogramming in activated SELENOI deficient T cells is impaired and this reduces proliferative capacity while favoring tolerogenic to pathogenic phenotypes that arise from differentiation. The implications of these findings are discussed related to vaccine responses, autoimmunity, and cell-based therapeutic approaches.     

Simultaneous parametric material and topology optimization with constrained material grading

We consider the problem of parametric material and simultaneous topology optimization of an elastic continuum. To ensure existence of solutions to the proposed optimization problem and to enable the imposition of a deliberate maximal material grading, two approaches are adopted and combined. The first imposes pointwise bounds on design variable gradients, whilst the second applies a filtering technique based on a convolution product. For the topology optimization, the parametrized material is multiplied with a penalized continuous density variable. We suggest a finite element discretization of the problem and provide a proof of convergence for the finite element solutions to solutions of the continuous problem. The convergence proof also implies the absence of checkerboards. The concepts are demonstrated by means of numerical examples using a number of different material parametrizations and comparing the results to global lower bounds.     

The role of tea and tea flavonoids in cardiovascular health

Consumption of green or black tea has been inversely associated with the development and progression of cardiovascular diseases. In this review, the current knowledge about protective effects of tea and tea constituents, particularly flavonoids, on the cardiovascular system is summarized. Underlying mechanisms for the beneficial effects of tea include vasculoprotective, antioxidative, antithrombogenic, anti-inflammatory, and lipid-lowering properties of tea flavonoids. Although promising experimental data on beneficial effects of tea in various cardiovascular diseases are available, results of clinical studies in humans are not uniform. A number of factors are discussed which may contribute to inconsistent data in humans. Overall, tea represents a promising tool for the prevention and treatment of cardiovascular disorders.     

Effects of the inhomogenous co doping on the magnetoresistance of Zn1-xCo(x)O epitaxial films

A series of Zn1-xCo(x)O epitaxial films around 100 nm with nominal Co concentration from 5% to 15% was prepared by ultra high vacuum (UHV) magnetron reactive sputtering. The optical, magnetic and magneto-transport properties of this series of Zn1-xCo(x)O epitaxial films were investigated, respectively. Resonant Raman spectra indicate the high structural and crystalline quality of these Zn1-xCo(x)O (5 < or = x < or = 15%) films, and confirm a consistent correlation between the substituting Co ions content with the Co doping concentration as well. Paramagnetism, superparamagnetism and ferromagnetism with altered Curie temperature from low temperatures to above room temperatures have been observed in these films by SQUID magnetometry. The broad blocking temperature range indicates the presence of inhomogenous distribution of the magnetic nano-clusters in the superparamagnetic films. However, the magneto-transport behaviors do not strongly respond to the change of the magnetic properties from paramagnetism to ferromagnetism of these Zn1-xCo(x)O films. The lack of efficient coupling between the inhomogenous magnetic nanoclusters and the carrier system in ferromagnetic Zn1-xCo(x)O films highlights the absence of the intrinsic magnetic origins in high structural quality Zn1-xCo(x)O (5 < or = x < or = 15%) epitaxial films. On the other hand, the competition between the spin alignments and the inhomogenous local disorder effect by magnetic ions is suggested to be responsible for the carrier properties and the oberseved magnetoresistance in these Co doping Zn1-xCo(x)O (5 < or = x < or = 15%) epitaxial films.     

Does face inversion change spatial frequency tuning?

The authors examined spatial frequency (SF) tuning of upright and inverted face identification using an SF variant of the Bubbles technique (F. Gosselin & P. G. Schyns, 2001). In Experiment 1, they validated the SF Bubbles technique in a plaid detection task. In Experiments 2a–c, the SFs used for identifying upright and inverted inner facial features were investigated. Although a clear inversion effect was present (mean accuracy was 24% higher and response times 455 ms shorter for upright faces), SF tunings were remarkably similar in both orientation conditions (mean r = .98; an SF band of 1.9 octaves centered at 9.8 cycles per face width for faces of about 6°). In Experiments 3a and b, the authors demonstrated that their technique is sensitive to both subtle bottom-up and top-down induced changes in SF tuning, suggesting that the null results of Experiments 2a–c are real. The most parsimonious explanation of the findings is provided by the quantitative account of the face inversion effect: The same information is used for identifying upright and inverted inner facial features, but processing has greater sensitivity with the former. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Validation of a mental health assessment in an African conflict population.

We studied the validity of the assessment of posttraumatic stress disorder (PTSD) and depression within the context of an epidemiological mental health survey among war-affected adolescents and young adults in northern Uganda. Local language versions of the Posttraumatic Diagnostic Scale (PDS) and the Depression section of the Hopkins Symptom Checklist (DHSCL) were administered by trained local interviewers. Correlations with probable predictor variables (i.e., trauma exposure), outcomes (e.g., impaired functioning), and local idioms of distress (i.e., spirit possession) were determined to estimate criterion-related construct validity. To assess convergent validity, expert clinicians reinterviewed a subsample using structured interviews (the Clinician Administered PTSD Scale [CAPS] and the Mini International Neuropsychiatric Interview [MINI]). Depression and PTSD symptoms as assessed by the local interviewers correlated with the context variables as predicted. After optimizing the scoring algorithm, we found good agreement between the PDS-based diagnoses and expert diagnoses. However, the concordance for depression diagnoses was not satisfactory. Results show that mental health assessments in African languages can produce reliable and valid data but that caution is warranted in the unevaluated transfer of cutoff scores and scoring algorithms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)