Long-Lost Relative Claims Orphan Gene: oskar in a Wasp

Organismic and Evolutionary Biolog

Enhancing Next-Generation Sequencing-Guided Cancer Care Through Cognitive Computing

Background: Using next-generation sequencing (NGS) to guide cancer therapy has created challenges in analyzing and reporting large volumes of genomic data to patients and caregivers. Specifically, providing current, accurate information on newly approved therapies and open clinical trials requires considerable manual curation performed mainly by human “molecular tumor boards” (MTBs). The purpose of this study was to determine the utility of cognitive computing as performed by Watson for Genomics (WfG) compared with a human MTB. Materials and Methods: One thousand eighteen patient cases that previously underwent targeted exon sequencing at the University of North Carolina (UNC) and subsequent analysis by the UNCseq informatics pipeline and the UNC MTB between November 7, 2011, and May 12, 2015, were analyzed with WfG, a cognitive computing technology for genomic analysis. Results: Using a WfG-curated actionable gene list, we identified additional genomic events of potential significance (not discovered by traditional MTB curation) in 323 (32%) patients. The majority of these additional genomic events were considered actionable based upon their ability to qualify patients for biomarker-selected clinical trials. Indeed, the opening of a relevant clinical trial within 1 month prior to WfG analysis provided the rationale for identification of a new actionable event in nearly a quarter of the 323 patients. This automated analysis took <3 minutes per case. Conclusion: These results demonstrate that the interpretation and actionability of somatic NGS results are evolving too rapidly to rely solely on human curation. Molecular tumor boards empowered by cognitive computing could potentially improve patient care by providing a rapid, comprehensive approach for data analysis and consideration of up-to-date availability of clinical trials. Implications for Practice: The results of this study demonstrate that the interpretation and actionability of somatic next-generation sequencing results are evolving too rapidly to rely solely on human curation. Molecular tumor boards empowered by cognitive computing can significantly improve patient care by providing a fast, cost-effective, and comprehensive approach for data analysis in the delivery of precision medicine. Patients and physicians who are considering enrollment in clinical trials may benefit from the support of such tools applied to genomic data

Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort

Objective: Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts. Design and methods: Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time. Results: In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3–4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes. Conclusion: This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways

“The Good into the Pot, the Bad into the Crop!”—A New Technology to Free Stem Cells from Feeder Cells

A variety of embryonic and adult stem cell lines require an intial co-culturing with feeder cells for non-differentiated growth, self renewal and maintenance of pluripotency. However for many downstream ES cell applications the feeder cells have to be considered contaminations that might interfere not just with the analysis of experimental data but also with clinical application and tissue engineering approaches. Here we introduce a novel technique that allows for the selection of pure feeder-freed stem cells, following stem cell proliferation on feeder cell layers. Complete and reproducible separation of feeder and embryonic stem cells was accomplished by adaptation of an automated cell selection system that resulted in the aspiration of distinct cell colonies or fraction of colonies according to predefined physical parameters. Analyzing neuronal differentiation we demonstrated feeder-freed stem cells to exhibit differentiation potentials comparable to embryonic stem cells differentiated under standard conditions. However, embryoid body growth as well as differentiation of stem cells into cardiomyocytes was significantly enhanced in feeder-freed cells, indicating a feeder cell dependent modulation of lineage differentiation during early embryoid body development. These findings underline the necessity to separate stem and feeder cells before the initiation of in vitro differentiation. The complete separation of stem and feeder cells by this new technology results in pure stem cell populations for translational approaches. Furthermore, a more detailed analysis of the effect of feeder cells on stem cell differentiation is now possible, that might facilitate the identification and development of new optimized human or genetically modified feeder cell lines

An assessment of monitoring requirements and costs of 'Reduced Emissions from Deforestation and Degradation'

<p>Abstract</p> <p>Background</p> <p>Negotiations on a future climate policy framework addressing Reduced Emissions from Deforestation and Degradation (REDD) are ongoing. Regardless of how such a framework will be designed, many technical solutions of estimating forest cover and forest carbon stock change exist to support policy in monitoring and accounting. These technologies typically combine remotely sensed data with ground-based inventories. In this article we assess the costs of monitoring REDD based on available technologies and requirements associated with key elements of REDD policy.</p> <p>Results</p> <p>We find that the design of a REDD policy framework (and specifically its rules) can have a significant impact on monitoring costs. Costs may vary from 0.5 to 550 US$ per square kilometre depending on the required precision of carbon stock and area change detection. Moreover, they follow economies of scale, i.e. single country or project solutions will face relatively higher monitoring costs.</p> <p>Conclusion</p> <p>Although monitoring costs are relatively small compared to other cost items within a REDD system, they should be shared not only among countries but also among sectors, because an integrated monitoring system would have multiple benefits for non-REDD management. Overcoming initialization costs and unequal access to monitoring technologies is crucial for implementation of an integrated monitoring system, and demands for international cooperation.</p

Systems Biology Modeling Reveals a Possible Mechanism of the Tumor Cell Death upon Oncogene Inactivation in EGFR Addicted Cancers

Despite many evidences supporting the concept of “oncogene addiction” and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR) associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK) and phosphoinositol-3 kinase (PI3K)/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1)/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential) due to the elevated level of reactive oxygen species (ROS) is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers

Adhesion and proliferation of living cell on surface functionalized with glycine nanostructures

This research presents the application of glycine amino acid for establishing firm cell-substrate interaction instead of expensive adhesion proteins, peptides and peptide derivatives. The glycine amino acid is chemically functionalized on the coverslip to achieve self-assembled nanostructure. Glycine self-assembly on NaCl treated coverslips is initiated with SiONa+:COO− linkage while their nanostructure is achieved with formation of glycine chain through NH3+:COO− covalent linkage between the adjacent molecules. The functionalization steps are confirmed by Fourier-transform infrared spectroscopy (FTIR) investigation. The atomic force microscopy (AFM) and scanning electron microscopy (SEM) investigations reveal that glycine growth initiates at 4 Hours (H) post-treatment while maximum growth appears after 8H-10H. Both the vertical and horizontal growth of nanostructures show dependence on functionalization periods. Various levels of glycine functionalized surface show different levels of baby hamster kidney (BHK-21) cell adhesion and proliferation efficiency with maximum performance for 10H functionalized surface. The adhesion and proliferation performance of 10H glycine functionalized surface shows negligible difference when compared with glycine-aspartic acid (RGD) functionalized surface. Finally, growth curves obtained from both glycine and RGD functionalized surface reveal exponential growth phage up to 48H followed by stationary phage between 48H and 72H while death of many cells appears from 72H to 96H. Thus, this research concluded that glycine functionalized surface is equally effective for cell adhesion and proliferation