Design Principles for Cationic,Astrocyte-Targeted Probes

The brain's astrocytes play key roles in normal and pathological brain processes. Targeting small molecules to astrocytes in the presence of the many other cell types in the brain will provide useful tools for their visualization and manipulation. Herein, we explore the functional consequences of synthetic modifications to a recently described astrocyte marker composed of a bright rhodamine-based fluorophore and an astrocyte-targeting moiety. We altered the nature of the targeting moiety to probe the dependence of astrocyte targeting on hydrophobicity, charge, and pK_a when exposed to astrocytes and neurons isolated from the mouse cortex. We found that an overall molecular charge of +2 and a targeting moiety with a heterocyclic aromatic amine are important requirements for specific and robust astrocyte labeling. These results provide a basis for engineering astrocyte-targeted molecular tools with unique properties, including metabolite sensing or optogenetic control.     

Oxidative Stability of Chia (Salvia hispanica L.) and Sesame (Sesamum indicum L.) Oil Blends

Chia and sesame oils are important sources of essential fatty acids; however, their ω-3:ω-6 proportions do not comply with nutritional recommendation. A feasible approach to improve the ratio is to blend different oils, but only after understanding physical and chemical changes of the new matrix. Objective of the investigation was to determine the physico-chemical characteristics and the oxidative stability index (OSI), using the Rancimat method, of chia-sesame oil blends. The four ω-3:ω-6 blends tested (1:4, 1:6, 1:8, and 1:10) were exposed to temperatures of 110, 120, and 130 °C. The OSI values of the mixtures varied between 6.24–8.08, 3.07–4.00, and 1.62–2.01 hours for each temperature, respectively. In addition, their mean activation energy, enthalpy, entropy, and Q₁₀ were 88.4 kJ/mol, 85.2 kJ/mol, −41.1 J/mol K, and 2.0. Finally, a shelf life prediction performed at 25 °C indicated stability times between 80 and 123 days. Therefore, combining chia and sesame oils produced blends with a good balance of essential fatty acids.     

In Silico/In Vitro Hit-to-Lead Methodology Yields SMYD3 Inhibitor That Eliminates Unrestrained Proliferation of Breast Carcinoma Cells

SMYD3 is a lysine methyltransferase that regulates the expression of over 80 genes and is required for the uncontrolled proliferation of most breast, colorectal, and hepatocellular carcinomas. The elimination of SMYD3 restores normal expression patterns of these genes and halts aberrant cell proliferation, making it a promising target for small molecule inhibition. In this study, we sought to establish a proof of concept for our in silico/in vitro hit-to-lead enzyme inhibitor development platform and to identify a lead small molecule candidate for SMYD3 inhibition. We used Schrodinger^® software to screen libraries of small molecules in silico and the five compounds with the greatest predicted binding affinity within the SMYD3 binding pocket were purchased and assessed in vitro in direct binding assays and in breast cancer cell lines. We have confirmed the ability of one of these inhibitors, Inhibitor-4, to restore normal rates of cell proliferation, arrest the cell cycle, and induce apoptosis in breast cancer cells without affecting wildtype cell behavior. Our results provide a proof of concept for this fast and affordable small molecule hit-to-lead methodology as well as a promising candidate small molecule SMYD3 inhibitor for the treatment of human cancer.     

Contact conductivity detection in poly(methyl methacrylate)-based microfluidic devices for analysis of mono- and polyanionic molecules

An on-column contact conductivity detector was developed for the analysis of various mono- and polyanionic compounds separated by electrophoresis chips fabricated in poly(methyl methacrylate) (PMMA) using hot embossing techniques from Ni electroforms. The detector consisted of a pair of Pt wires (127 microm diameter) with an end-to-end spacing of approximately 20 microm and situated within the fluidic channel. The waveform applied to the electrode pair was a bipolar pulse with a frequency of 5.0 kHz and was used to reduce the charging current from measurement so that the current recorded at the end of one pulse is more representative of the solution conductivity. Using the detector, separations of amino acids, peptides, proteins, and oligonucleotides were demonstrated. For the amino acids and peptides, free-solution zone electrophoresis was performed. A calibration plot for the amino acid alanine was found to be linear from approximately 10 to 100 nM in a carrier electrolyte consisting of 10 mM triethylamonium acetate. The concentration detection limit was found to be 8.0 nM, with the corresponding mass detection limit equal to 3.4 amol (injection volume = 425 pL). The protein separations with conductivity detection were performed using MEKC, in which the carrier electrolyte contained the anionic surfactant sodium dodecyl sulfate (SDS) above its cmc. Near baseline resolution was achieved in the PMMA microchip for a solution containing 8 different proteins. In the case of the DNA fragments, capillary electrochromatography was used with a C18-modified PMMA chip and a carrier electrolyte containing an ion-pairing agent.     

The use of background and ability profiles to predict college student outcomes.

To determine whether profiles of predictor variables provide incremental prediction of college student outcomes, the authors 1st applied an empirical clustering method to profiles based on the scores of 2,771 entering college students on a battery of biographical data and situational judgment measures, along with SAT and American College Test scores and high school grade point average, which resulted in 5 student groups. Performance of the students in these clusters was meaningfully different on a set of external variables, including college grade point average, self-rated performance, class absenteeism, organizational citizenship behavior, intent to quit their university, and satisfaction with college. The 14 variables in the profile were all significantly correlated with 1 or more of the outcome measures; however, nonlinear prediction of these outcomes on the basis of cluster membership did not add incrementally to a linear-regression-based combination of these 14 variables as predictors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Protein,ash, lutein and tocols distribution in einkorn (Triticum monococcum L. subsp. monococcum) seed fractions

The distribution of protein, ash, lutein, tocopherols and tocotrienols in the germ, bran and endosperm portions was studied in seeds of two einkorn accessions and one bread wheat. The two einkorns showed a higher content of most compounds, but the distribution within the kernel was similar in both species. The germ fraction showed the highest concentration of protein, lutein, α-tocopherol, β-tocopherol and total tocols. Ash, α-tocotrienol and β-tocotrienol levels were highest in the bran fraction, although significant quantities were detected also in the germ and, for tocotrienols, in the flour.     

A tool for power and phase noise optimization in frequency synthesizers

In this paper, we present a CAD technique to design low-power and low phase noise integrated frequency synthesizers. This technique introduces a key parameter, Phase Noise per Unit Power, which correlates phase noise and power among all the sub-circuits in the frequency synthesizer. By correlating the performance of all the independent circuits together, sophisticated synthesizer design and optimization can be significantly simplified. We demonstrate a 1.8 GHz frequency synthesizer design in a 0.18 μm CMOS process achieving −132 dBc/Hz phase noise at 100 kHz offset with less than 4.3 mW power consumption.     

Stimulant medication improves recognition memory in children diagnosed with attention-deficit/hyperactivity disorder.

The effect of stimulant medication on recognition memory was examined in 18 children with attention-deficit/hyperactivity disorder (ADHD). Recognition memory was assessed using a delayed matching-to-sample task at 6 delays ranging from 1 to 32 s. Each child was tested on 2 separate occasions, once 60 to 90 min after taking stimulant medication and the other at least 18 hr after taking medication. Children performed significantly better on medication than off. Stimulant administration significantly increased accuracy and the number of nickel reinforcers earned. Decreases in observing response latency and correct choice response latency occurred after taking stimulant medication. The results indicate that stimulant medication improved recognition memory for children with ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Biphasic α2β1 Integrin Expression in Breast Cancer Metastasis to Bone

Integrins participate in the pathogenesis and progression of tumors at many stages during the metastatic cascade. However, current evidence for the role of integrins in breast cancer progression is contradictory and seems to be dependent on tumor stage, differentiation status, and microenvironmental influences. While some studies suggest that loss of α2β1 enhances cancer metastasis, other studies suggest that this integrin is pro-tumorigenic. However, few studies have looked at α2β1 in the context of bone metastasis. In this study, we aimed to understand the role of α2β1 integrin in breast cancer metastasis to bone. To address this, we utilized in vivo models of breast cancer metastasis to bone using MDA-MB-231 cells transfected with an α2 expression plasmid (MDA-OEα2). MDA cells overexpressing the α2 integrin subunit had increased primary tumor growth and dissemination to bone but had no change in tumor establishment and bone destruction. Further in vitro analysis revealed that tumors in the bone have decreased α2β1 expression and increased osteolytic signaling compared to primary tumors. Taken together, these data suggest an inverse correlation between α2β1 expression and bone-metastatic potential. Inhibiting α2β1 expression may be beneficial to limit the expansion of primary tumors but could be harmful once tumors have established in bone.