Analysis of Germline Gene Copy Number Variants of Patients with Sporadic Pancreatic Adenocarcinoma Reveals Specific Variations

Objectives: The rapid fatality of pancreatic cancer is, in large part, the result of diagnosis at an advanced stage in the majority of patients. Identification of individuals at risk of developing pancreatic adenocarcinoma would be useful to improve the prognosis of this disease. There is presently no biological or genetic indicator allowing the detection of patients at risk. Our main goal was to identify copy number variants (CNVs) common to all patients with sporadic pancreatic cancer. Methods: We analyzed gene CNVs in leukocyte DNA from 31 patients with sporadic pancreatic adenocarcinoma and from 93 matched controls. Genotyping was performed with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). Results: We identified 431 single nucleotide polymorphism (SNP) probes with abnormal hy-bridization signal present in the DNA of all 31 patients. Of these SNP probes, 284 corresponded to 3 or more copies and 147 corresponded to 1 or 0 copies. Several cancer-associated genes were amplified in all patients. Conversely, several genes supposed to oppose cancer development were present as single copy. Conclusions: These data suggest that a set of 431 CNVs could be associated with the disease. This set could be useful for early diagnosis

The reg4 Gene, Amplified in the Early Stages of Pancreatic Cancer Development, Is a Promising Therapeutic Target

BACKGROUND: The aim of our work was to identify the genes specifically altered in pancreatic adenocarcinoma and especially those that are altered early in cancer development. METHODOLOGY/PRINCIPAL FINDINGS: Gene copy number was systematically assessed with an ultra-high resolution CGH oligonucleotide microarray in DNA from samples of pancreatic cancer. Several new cancer-associated variations were observed. In this work we focused on one of them, involving the reg4 gene. Gene copy number gain of the reg4 gene was confirmed by qPCR in 14 cancer samples. It was also found with increased copy number in most PanIN3 samples. The relationship betweena gain in reg4 gene copy number and cancer development was investigated on the human pancreatic cancer cell line Mia-PaCa2 xenografted under the skin of nude mice. When cells were transfected with a vector allowing reg4 expression, they generated tumors almost twice larger in size. In addition, these tumors were more resistant to gemcitabine treatment than control tumors. Interestingly, weekly intraperitoneal administration of a monoclonal antibody to reg4 halved the size of tumors generated by Mia-PaCa2 cells, suggesting that the antibody interfered with a paracrine/autocrine mechanism involving reg4 and stimulating cancer progression. The addition of gemcitabine resulted in further reduction, tumors becoming 5 times smaller than control. Exposure to reg4 antibody resulted in a significant decrease in intra-tumor levels of pAkt, Bcl-xL, Bcl-2, survivin and cyclin D1. CONCLUSIONS/SIGNIFICANCE: It was concluded that adjuvant therapies targeting reg4 could improve the standard treatment of pancreatic cancer with gemcitabine

Diving into the vertical dimension of elasmobranch movement ecology

This is the final version. Available on open access from the American Association for the Advancement of Science via the DOI in this recordData and materials availability: Processed data and code used in the analysis are accessible from the Zenodo Repository: 10.5281/zenodo.6885455Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements.Bertarelli FoundationResearch EnglandMoore FoundationPackard FoundationInstituto Politecnico NacionalDarwin InitiativeGeorgia AquariumRolex Awards for EnterpriseWhitley Fund for Natur

Biodegradable DFADs: Current Status and Prospects

Until recently, dFAD structure, materials and designs have remained quite rudimentary and virtually the same since their discovery, characterized by the increase of the dimensions and prevailing heavy use of plastic components. Biodegradable materials are called to be an important part of the solution, as they can faster degrade in the environment, free of toxins and heavy metals, reducing their lifespan, and preventing them from accumulating in sensitive areas once they are abandoned, lost or discarded. During last decades, regulatory measures at tRFMOs have advanced in the gradual implementation of biodegradable materials in dFAD constructions together with other measures limiting the number of active dFADs and the use of netting materials. However, more clarity is needed starting with a standardised definition of biodegradable dFADs among tRFMOs, to provide operational guidance. Research with those natural and synthetic materials is required, along with updated data collection for monitoring standards, as well as alternative and complementary actions need to be explored to contribute to minimising dFAD adverse effects on environment. Acknowledging the current difficulties for the implementation of fully biodegradable dFADs a stepwise process towards the implementation of fully biodegradable dFADs should be considered