Structures in Other Domains The methodology of structural analysis discussed in this article has been applied beyond the narrow realm of natural language syntax that we have discussed in this article. Within the study of language, similar methods of analysis have been pervasively applied to the study of sounds (phonology), words (morphology), and meanings (semantics), yielding a range of of abstract structural representations whose properties bear considerable explanatory burden. There are a wealth of cases in each of these domains analogous to those discussed here, though space prevents us from going in these (see Akmajian, Demers, Farmer and Harnish 1995 for a traditional overview, and Jackendo 1994 for one more focused on connections with cognitive science). Additionally, these representations have shed substantial light on the processes of language acquisition and language change. It has been found that variation in the types of sentences that are used, whether during the course of children's acquisition of their native languages or in the centuries-long periods of linguistic change, are best characterized not as super cial and haphazard alterations, but rather in terms of parametric modi cations to the fundamental underlying grammatical rules and constraints. Moving outside the domain of language, one application of these same methods has been in the study of music cognition. Just as the representations of linguistic theory arise out of an attempt to model speakers' intuitions about well-formedness and possible meanings of the sentences of their

Structural analysis

MicroRNA-34 (miR-34) has been reported to be dysregulated in various human cancers and regarded as a tumor suppressive microRNA because of its synergistic effect with the well-known tumor suppressor p53. Along with the application of MRX34, the first tumor-targeted microRNA drug which based on miR-34a mimics, on phase I clinical trial (NCT01829971), the significance of miR-34 is increasingly recognized. miR-34 plays a crucial role on repressing tumor progression by involving in epithelial-mesenchymal transition (EMT) via EMT- transcription factors, p53 and some important signal pathways. Not only that, numerous preclinical researches revealed the giant potential of miR-34a on cancer therapy through diversiform nano-scaled delivery systems. Here, we provide an overview about the function of miR-34 in various cancers and the mechanism of miR-34 in tumor-associated EMT. Furthermore, its potential role as a microRNA therapeutic candidate is also discussed. Notwithstanding some obstacles existed, the extensive application prospect of miR-34 on oncotherapy cannot be neglected.

/pdf/microrna-34-family-a-potential-tumor-suppressor-and-2dgmvyx3su.pdf

MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer.

Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy.

Applications of Spherical Nucleic Acid Nanoparticles as Delivery Systems

Colon cancer is an adenocarcinoma, which subsequently develops into malignant tumors, if not treated properly. The current colon cancer therapy mainly revolves around chemotherapy, radiotherapy and surgery, but the search continues for more effective interventions. With the advancement of nanoparticles (NPs), it is now possible to diagnose and treat colon cancers with different types, shapes, and sizes of NPs. Nanoformulations such as quantum dots, iron oxide, polymeric NPs, dendrimers, polypeptides, gold NPs, silver NPs, platinum NPs, and cerium oxide have been either extensively used alone or in combination with other nanomaterials or drugs in colon cancer diagnosis, and treatments. These nanoformulations possess high biocompatibility and bioavailability, which makes them the most suitable candidates for cancer treatment. The size and shape of NPs are critical to achieving an effective drug delivery in cancer treatment and diagnosis. Most NPs currently are under different testing phases (in vitro, preclinical, and clinical), whereas some of them have been approved for therapeutic applications. We have comprehensively reviewed the recent advances in the applications of NPs-based formulations in colon cancer diagnosis and treatment.

Trends in targeted delivery of nanomaterials in colon cancer diagnosis and treatment

Cell-derived influenza vaccines provide better protection and a host of other advantages compared to the egg-derived vaccines that currently dominate the market, but their widespread use is hampered by a lack of high yield, low cost production platforms. Identification and knockout of innate immune and metabolic restriction factors within relevant host cell lines used to grow the virus could offer a means to substantially increase vaccine yield. In this paper, we describe and validate a novel genome-wide pooled CRISPR/Cas9 screening strategy that incorporates a reporter virus and a FACS selection step to identify and rank restriction factors in a given vaccine production cell line. Using the HEK-293SF cell line and A/PuertoRico/8/1934 H1N1 influenza as a model, we identify 64 putative influenza restriction factors to direct the creation of high yield knockout cell lines. In addition, gene ontology and protein complex enrichment analysis of this list of putative restriction factors offers broader insights into the primary host cell determinants of viral yield in cell-based vaccine production systems. Overall, this work will advance efforts to address the public health burden posed by influenza.

/pdf/a-pooled-genome-wide-screening-strategy-to-identify-and-rank-21goy9crq9.pdf

A pooled genome-wide screening strategy to identify and rank influenza host restriction factors in cell-based vaccine production platforms.

UNLABELLED Chicken anemia virus (CAV) is a single-stranded circular DNA virus that carries 3 genes, the most studied of which is the gene encoding VP3, also known as apoptin. This protein has been demonstrated to specifically kill transformed cells while leaving normal cells unharmed in a manner that is independent of p53 status. Although the mechanistic basis for this differential activity is unclear, it is evident that the subcellular localization of the protein is important for the difference. In normal cells, apoptin exists in filamentous networks in the cytoplasm, whereas in transformed cells, apoptin is present in the nucleus and appears as distinct foci. We have previously demonstrated that DNA damage signaling through the ataxia telangiectasia mutated (ATM) pathway induces the translocation of apoptin from the cytoplasm to the nucleus, where it induces apoptosis. We found that apoptin contains four checkpoint kinase consensus sites and that mutation of either threonine 56 or 61 to alanine restricts apoptin to the cytoplasm. Furthermore, treatment of tumor cells expressing apoptin with inhibitors of checkpoint kinase 1 (Chk1) and Chk2 causes apoptin to localize to the cytoplasm. Importantly, silencing of Chk2 rescues cancer cells from the cytotoxic effects of apoptin. Finally, treatment of virus-producing cells with Chk inhibitor protects them from virus-mediated toxicity and reduces the titer of progeny virus. Taken together, our results indicate that apoptin is a sensor of DNA damage signaling through the ATM-Chk2 pathway, which induces it to migrate to the nucleus during viral replication. IMPORTANCE The chicken anemia virus (CAV) protein apoptin is known to induce tumor cell-specific death when expressed. Therefore, understanding its regulation and mechanism of action could provide new insights into tumor cell biology. We have determined that checkpoint kinase 1 and 2 signaling is important for apoptin regulation and is a likely feature of both tumor cells and host cells producing virus progeny. Inhibition of checkpoint signaling prevents apoptin toxicity in tumor cells and attenuates CAV replication, suggesting it may be a future target for antiviral therapy.

Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation Is Required for Apoptotic Activity and Efficient Viral Replication.

All influenza vaccines currently sold in Canada require one fertilized chicken egg to produce roughly one dose of vaccine. During pandemic influenza outbreaks, the limited availability of eggs stresses the ability of this method to deliver vaccine in a timely manner (1). Unlike eggs, cell lines grow exponentially, resulting in virtually limitless substrate for cultivating influenza vaccines. This ability to rapidly scale production during periods of increased demand is ideal for effectively responding to pandemic influenza outbreaks. While promising, cell-based influenza vaccine production suffers from low volumetric yield (~10-fold lower) compared to egg-based methods (2).

A genome-wide CRISPR screen to generate high-yield cell lines for pandemic influenza vaccine production

The last 10 years have seen a rapid expansion in the use of viral gene transfer vectors, with approved therapies and late stage clinical trials underway for the treatment of genetic disorders, and multiple forms of cancer, as well as prevention of infectious diseases through vaccination With this increased interest and widespread adoption of viral vectors by clinicians and biopharmaceutical industries, there is an imperative to engineer safer and more efficacious vectors, and develop robust, scalable and cost-effective production platforms for industrialization This review will focus on major innovations in viral vector design and production systems for three of the most widely used viral vectors: Adenovirus, Adeno-Associated Virus, and Lentivirus

Advancements in the design and scalable production of viral gene transfer vectors

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A pooled genome-wide screening strategy to identify and rank influenza host restriction factors in cell-based vaccine production platforms.

Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation Is Required for Apoptotic Activity and Efficient Viral Replication.

A genome-wide CRISPR screen to generate high-yield cell lines for pandemic influenza vaccine production

Advancements in the design and scalable production of viral gene transfer vectors