Dynamic Assessment of Functional Lipidomic Analysis in Human Urine

The development of enabling mass spectrometry platforms for the quantification of diverse lipid species in human urine is of paramount importance for understanding metabolic homeostasis in normal and pathophysiological conditions. Urine represents a non‐invasive biofluid that can capture distinct differences in an individual's physiological status. However, currently there is a lack of quantitative workflows to engage in high throughput lipidomic analysis. This study describes the development of a MS/MS^ALL shotgun lipidomic workflow and a micro liquid chromatography–high resolution tandem mass spectrometry (LC–MS/MS) workflow for urine structural and mediator lipid analysis, respectively. This workflow was deployed to understand biofluid sample handling and collection, extraction efficiency, and natural human variation over time. Utilization of 0.5 mL of urine for structural lipidomic analysis resulted in reproducible quantification of more than 600 lipid molecular species from over 20 lipid classes. Analysis of 1 mL of urine routinely quantified in excess of 55 mediator lipid metabolites comprised of octadecanoids, eicosanoids, and docosanoids generated by lipoxygenase, cyclooxygenase, and cytochrome P450 activities. In summary, the high‐throughput functional lipidomics workflow described in this study demonstrates an impressive robustness and reproducibility that can be utilized for population health and precision medicine applications.     

Transcranial Magnetic Stimulation of the Supplementary Motor Area in the Treatment of Obsessive-Compulsive Disorder: A Multi-Site Study

Recently, strategies beyond pharmacological and psychological treatments have been developed for the management of obsessive-compulsive disorder (OCD). Specifically, repetitive transcranial magnetic stimulation (rTMS) has been employed as an adjunctive treatment in cases of treatment-refractory OCD. Here, we investigate six weeks of low frequency rTMS, applied bilaterally and simultaneously over the sensory motor area, in OCD patients in a randomized, double-blind placebo-controlled clinical trial. Twenty-two participants were randomly enrolled into the treatment (ACTIVE = 10) or placebo (SHAM = 12) groups. At each of seven visits (baseline; day 1 and weeks 2, 4, and 6 of treatment; and two and six weeks after treatment) the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was administered. At the end of the six weeks of rTMS, patients in the ACTIVE group showed a clinically significant decrease in Y-BOCS scores compared to both the baseline and the SHAM group. This effect was maintained six weeks following the end of rTMS treatment. Therefore, in this sample, rTMS appeared to significantly improve the OCD symptoms of the treated patients beyond the treatment window. More studies need to be conducted to determine the generalizability of these findings and to define the duration of rTMS’ clinical effect on the Y-BOCS. Clinical Trial Registration Number (NCT) at www.clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00616486","term_id":"NCT00616486"}}NCT00616486.     

Glass with hydration-induced compressive stress profiles

A novel potassium phospho-aluminosilicate composition is described that can be strengthened by water vapor to achieve deep compressive stress (CS) profiles. Water vapor treatment at (A) 85°C and 85% relative humidity for 40 days results in a CS of 389 ± 20 MPa and a compressive depth of layer (DOL) of 18 ± 2 μm. When treated at (B) 160°C and 0.1 MPa for 7 days, a CS of 245 ± 20 MPa and a DOL of 40 ± 2 μm is achieved. Glasses with hydration-induced stress profiles can provide high retained strength following flaw introduction compared with ion-exchanged soda-lime silicate glass. Sample treatment B also has an exemplary Vickers indentation cracking threshold value greater than 20 kgf. The hydration profile determined by secondary ion mass spectrometry (SIMS) is shown to closely match the stress profile for these samples. SIMS analysis also shows that the depth of water enrichment correlates well with the depletion depth of phosphorus. The high tendency towards water-induced strengthening for this new type of glass even enables self-strengthening by the generation of a near-surface CS profile following exposure to ambient conditions.     

Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 Cells

Zinc has been suggested to play a role in carcinogenesis and tumor progression. Serum zinc levels of lung cancer patients are for example lower than in healthy individuals. The activation and expression of the epidermal growth factor receptor (EGFR), which plays a role in tumor biology, are presumably influenced by zinc. EGFR activation influences cell adhesion and immune escape. This study provides insights into the impacts of zinc on the EGFR activation and expression of downstream proteins such as E-cadherin and PD-L1 in the alveolar carcinoma cell line A549. To model chronic changes in zinc homeostasis, A549 cells were cultured in media with different zinc contents. EGFR surface expression of unstimulated and stimulated A549 cells was determined by flow cytometry. EGFR phosphorylation as well as the protein expression of E-cadherin and PD-L1 were analyzed by Western blot. In our hands, chronic zinc deficiency led to increased EGFR surface expression, decreased E-cadherin protein expression and increased PD-L1 protein expression. Zinc supplementation decreased EGFR surface expression and PD-L1 protein expression. In summary, zinc-deficient A549 cells may display a more malignant phenotype. Thus, future clinical research should further focus on the possible benefits of restoring disturbed zinc homeostasis, especially in lung cancer patients.     

Utilizing Genomically Targeted Molecular Data to Improve Patient-Specific Outcomes in Autism Spectrum Disorder

Molecular biology combined with genomics can be a powerful tool for developing potential intervention strategies for improving outcomes in children with autism spectrum disorders (ASD). Monogenic etiologies rarely cause autism. Instead, ASD is more frequently due to many polygenic contributing factors interacting with each other, combined with the epigenetic effects of diet, lifestyle, and environment. One limitation of genomics has been identifying ways of responding to each identified gene variant to translate the information to something clinically useful. This paper will illustrate how understanding the function of a gene and the effects of a reported variant on a molecular level can be used to develop actionable and targeted potential interventions for a gene variant or combinations of variants. For illustrative purposes, this communication highlights a specific genomic variant, SHANK3. The steps involved in developing molecularly genomically targeted actionable interventions will be demonstrated. Cases will be shared to support the efficacy of this strategy and to show how clinicians utilized these targeted interventions to improve ASD-related symptoms significantly. The presented approach demonstrates the utility of genomics as a part of clinical decision-making.     

No pain and gain!—experiences with Mentat on a biological application

Throughout much of the parallel processing community there is the sense that writing software for distributed-memory parallel processors Is subject to a ‘no pain—no gain’ rule: that In order to reap the benefits of parallel computation one must first suffer the pain of converting the application to run on a parallel machine. We believe this Is the result of Inadequate programming tools and not a problem Inherent to parallel processing. We will show that one can parallelize real scientific applications and obtain good performance with little effort If the right tools are used. Our vehicle for this demonstration is a 6000-line DNA and protein sequence comparison application that we have implemented in Mental, an object-oriented parallel processing system for both parallel and distributed architectures. We briefly describe the application and present performance information for both the Mentat version and a hand-coded parallel version of the application.     

Ionothermal synthesis of zeolites, metal-organic frameworks, and inorganic-organic hybrids

Ionothermal synthesis, the use of ionic liquids as both solvent and template (structure-directing agent), has been used to prepare zeolites and inorganic-organic hybrids such as metal-organic frameworks. The underlying properties of the ionothermal method are discussed, and it is compared with traditional hydrothermal preparative methods. The materials resulting from ionothermal synthesis are described, and any structural features that can be related to the ionic liquid used as the solvent are discussed. Future areas of potential interest are also considered.     

EFFECTS OF FLOW DYNAMICS ON THE AQUATIC‐TERRESTRIAL TRANSITION ZONE (ATTZ) OF LOWER MISSOURI RIVER SANDBARS WITH IMPLICATIONS FOR SELECTED BIOTA

Sandbars are an important aquatic terrestrial transition zone (ATTZ) in the active channel of rivers that provide a variety of habitat conditions for riverine biota. Channelization and flow regulation in many large rivers have diminished sandbar habitats and their rehabilitation is a priority. We developed sandbar‐specific models of discharge‐area relationships to determine how changes in flow regime affect the area of different habitat types within the submerged sandbar ATTZ (depth) and exposed sandbar ATTZ (elevation) for a representative sample of Lower Missouri River sandbars. We defined six different structural habitat types within the sandbar ATTZ based on depth or exposed elevation ranges that are important to different biota during at least part of their annual cycle for either survival or reproduction. Scenarios included the modelled natural flow regime, current managed flow regime and two environmental flow options, all modelled within the contemporary river active channel. Thirteen point and wing‐dike sandbars were evaluated under four different flow scenarios to explore the effects of flow regime on seasonal habitat availability for foraging of migratory shorebirds and wading birds, nesting of softshell turtles and nursery of riverine fishes. Managed flows provided more foraging habitat for shorebirds and wading birds and more nursery habitat for riverine fishes within the channelized reach sandbar ATTZ than the natural flow regime or modelled environmental flows. Reduced summer flows occurring under natural and environmental flow alternatives increased exposed sandbar nesting habitat for softshell turtle hatchling emergence. Results reveal how management of channelized and flow regulated large rivers could benefit from a modelling framework that couples hydrologic and geomorphic characteristics to predict habitat conditions for a variety of biota. Published in 2011 by John Wiley & Sons, Ltd.