Building Resilience: An Exercise to Create Network Structures and Assess Resilience with Marshmallows and Spaghetti Noodles or LEGO® Pieces

Scholars, practitioners, and society at large are becoming increasingly interested in how resilience works (Coutu, 2002). This activity gives students the opportunity to build a network structure and assess its resilience, while learning the concepts and calculation steps of basic network metrics including density, reachability, and centralization. The article provides guidelines for preparing necessary materials (e.g., marshmallows and spaghetti noodles or LEGO® pieces), detailed procedures and worksheet for the activity, and debriefing questions for connecting the experiences from the activity with real world examples of communication networks and resilience

RHOA in Gastric Cancer: Functional Roles and Therapeutic Potential

The well-known signal mediator and small GTPase family member, RHOA, has now been associated with the progression of specific malignancies. In this review, we appraise the biomedical literature regarding the role of this enzyme in gastric cancer (GC) signaling, suggesting potential clinical significance. To that end, we examined RHOA activity, with regard to second-generation hallmarks of cancer, finding particular association with the hallmark “activation of invasion and metastasis.” Moreover, an abundance of studies show RHOA association with Lauren classification diffuse subtype, in addition to poorly differentiated GC. With regard to therapeutic value, we found RHOA signaling to influence the activity of specific widely used chemotherapeutics, and its possible antagonism by various dietary constituents. We also review currently available targeted therapies for GC. The latter, however, showed a paucity of such agents, underscoring the urgent need for further investigation into treatments for this highly lethal malignancy

ChimerDB—a knowledgebase for fusion sequences

Chromosome translocation and gene fusion are frequent events in the human genome and are often the cause of many types of tumor. ChimerDB is the database of fusion sequences encompassing bioinformatics analysis of mRNA and expressed sequence tag (EST) sequences in the GenBank, manual collection of literature data and integration with other known database such as OMIM. Our bioinformatics analysis identifies the fusion transcripts that have non-overlapping alignments at multiple genomic loci. Fusion events at exon–exon borders are selected to filter out the cloning artifacts in cDNA library preparation. The result is classified into two groups—genuine chromosome translocation and fusion between neighboring genes owing to intergenic splicing. We also integrated manually collected literature and OMIM data for chromosome translocation as an aid to assess the validity of each fusion event. The database is available at for human, mouse and rat genomes

A simple and efficient numerical method for the Allen–Cahn equation on effective symmetric triangular meshes

In this paper, we propose a novel, simple, efficient, and explicit numerical method for the Allen–Cahn (AC) equation on effective symmetric triangular meshes. First, we compute the net vector of all vectors starting from each node point to its one-ring neighbor vertices and virtually adjust the neighbor vertices so that the net vector is zero. Then, we define the values at the virtually adjusted nodes using linear and quadratic interpolations. Finally, we define a discrete Laplace operator on triangular meshes. We perform several computational experiments to demonstrate the performance of the proposed numerical method for the Laplace operator, the diffusion equation, and the AC equation on triangular meshes

ECgene: an alternative splicing database update

ECgene () was developed to provide functional annotation for alternatively spliced genes. The applications encompass the genome-based transcript modeling for alternative splicing (AS), domain analysis with Gene Ontology (GO) annotation and expression analysis based on the EST and SAGE data. We have expanded the ECgene's AS modeling and EST clustering to nine organisms for which sufficient EST data are available in the GenBank. As for the human genome, we have also introduced several new applications to analyze differential expression. ECprofiler is an ontology-based candidate gene search system that allows users to select an arbitrary combination of gene expression pattern and GO functional categories. DEGEST is a database of differentially expressed genes and isoforms based on the EST information. Importantly, gene expression is analyzed at three distinctive levels—gene, isoform and exon levels. The user interfaces for functional and expression analyses have been substantially improved. ASviewer is a dedicated java application that visualizes the transcript structure and functional features of alternatively spliced variants. The SAGE part of the expression module provides many additional features including SNP, differential expression and alternative tag positions

Mg2+ Effect on Argonaute and RNA Duplex by Molecular Dynamics and Bioinformatics Implications

RNA interference (RNAi), mediated by small non-coding RNAs (e.g., miRNAs, siRNAs), influences diverse cellular functions. Highly complementary miRNA-target RNA (or siRNA-target RNA) duplexes are recognized by an Argonaute family protein (Ago2), and recent observations indicate that the concentration of Mg2+ ions influences miRNA targeting of specific mRNAs, thereby modulating miRNA-mRNA networks. In the present report, we studied the thermodynamic effects of differential [Mg2+] on slicing (RNA silencing cycle) through molecular dynamics simulation analysis, and its subsequent statistical analysis. Those analyses revealed different structural conformations of the RNA duplex in Ago2, depending on Mg2+ concentration. We also demonstrate that cation effects on Ago2 structural flexibility are critical to its catalytic/functional activity, with low [Mg2+] favoring greater Ago2 flexibility (e.g., greater entropy) and less miRNA/mRNA duplex stability, thus favoring slicing. The latter finding was supported by a negative correlation between expression of an Mg2+ influx channel, TRPM7, and one miRNA’s (miR-378) ability to downregulate its mRNA target, TMEM245. These results imply that thermodynamics could be applied to siRNA-based therapeutic strategies, using highly complementary binding targets, because Ago2 is also involved in RNAi slicing by exogenous siRNAs. However, the efficacy of a siRNA-based approach will differ, to some extent, based on the Mg2+ concentration even within the same disease type; therefore, different siRNA-based approaches might be considered for patient-to-patient needs

Resilient Communities: Understanding Networks for Post-Disaster Recovery

Community response and recovery from a disaster can vary widely based on community characteristics. Many disasters leave little time for preparation prior to arrival and can cause widespread death and destruction. Regardless of the impact of the disaster, response and recovery rates vary based upon several factors including resource availability, social and physical infrastructure, and policies in each community

Detection of PIWI and piRNAs in the mitochondria of mammalian cancer cells

AbstractPiwi-interacting RNAs (piRNAs) are 26–31 nt small noncoding RNAs that are processed from their longer precursor transcripts by Piwi proteins. Localization of Piwi and piRNA has been reported mostly in nucleus and cytoplasm of higher eukaryotes germ-line cells, where it is believed that known piRNA sequences are located in repeat regions of nuclear genome in germ-line cells. However, localization of PIWI and piRNA in mammalian somatic cell mitochondria yet remains largely unknown. We identified 29 piRNA sequence alignments from various regions of the human mitochondrial genome. Twelve out 29 piRNA sequences matched stem-loop fragment sequences of seven distinct tRNAs. We observed their actual expression in mitochondria subcellular fractions by inspecting mitochondrial-specific small RNA-Seq datasets. Of interest, the majority of the 29 piRNAs overlapped with multiple longer transcripts (expressed sequence tags) that are unique to the human mitochondrial genome. The presence of mature piRNAs in mitochondria was detected by qRT-PCR of mitochondrial subcellular RNAs. Further validation showed detection of Piwi by colocalization using anti-Piwil1 and mitochondria organelle-specific protein antibodies

Enantioselective Alkynylation of Trifluoromethyl Ketones Catalyzed by Cation-Binding Salen Nickel Complexes

Cation‐binding salen nickel catalysts were developed for the enantioselective alkynylation of trifluoromethyl ketones in high yield (up to 99 %) and high enantioselectivity (up to 97 % ee). The reaction proceeds with substoichiometric quantities of base (10–20 mol % KOt‐Bu) and open to air. In the case of trifluoromethyl vinyl ketones, excellent chemo‐selectivity was observed, generating 1,2‐addition products exclusively over 1,4‐addition products. UV‐vis analysis revealed the pendant oligo‐ether group of the catalyst strongly binds to the potassium cation (K⁺) with 1:1 binding stoichiometry (K_a=6.6×10⁵ M⁻¹)