Amsterdam Declaration on Funding Research Software Sustainability

The Research Software Alliance (ReSA) and the Netherlands eScience Center hosted a two-day international workshop in Amsterdam (the Netherlands) on 8-9 November 2023 to set the future agenda for national and international funders to support sustainable research software. As the importance of software in research has become increasingly apparent, so has the urgent need to sustain it. Funders can play a crucial role in this respect by ensuring structural support. Over the past few years, a variety of methods for sustaining research software have been explored, including improving and extending funding policies and instruments. During the workshop, funding organizations joined forces to explore how they can effectively contribute to making research software sustainable. In preparation of the workshop, a draft of a future international declaration, titled "Amsterdam Declaration on Funding Research Software Sustainability" was created by the Research Software Alliance, the Netherlands eScience Center and with input from stakeholders in the field

Deleted in Liver Cancer 1 (DLC1) Negatively Regulates Rho/ROCK/MLC Pathway in Hepatocellular Carcinoma

Aims: Deleted in liver cancer 1 (DLC1), a member of RhoGTPase activating protein (GAP) family, is known to have suppressive activities in tumorigenicity and cancer metastasis. However, the underlying molecular mechanisms of how DLC1 suppresses cell motility have not been fully elucidated. Rho-kinase (ROCK) is an immediate down-stream effector of RhoA in mediating cellular cytoskeletal events and cell motility. In the present study, we aimed to investigate the effects of DLC1 on Rho/ROCK signaling pathway in hepatocellular carcinoma (HCC). Methodology/Principal Findings: We demonstrated that DLC1 negatively regulated ROCK-dependent actomyosin contractility. From immumofluorescence study, we found that ectopic expression of DLC1 abrogated Rho/ROCK-mediated cytoskeletal reorganization including formation of stress fibers and focal adhesions. It also downregulated cortical phosphorylation of myosin light chain 2 (MLC2). These inhibitory events by DLC1 were RhoGAP-dependent, as RhoGAP-deficient mutant of DLC1 (DLC1 K714E) abolished these inhibitory events. In addition, from western study, DLC1 inhibited ROCK-related myosin light chain phosphatase targeting unit 1 (MYPT1) phosphorylation at Threonine 853. By examining cell morphology under microscope, we found that ectopic expression of dominant-active ROCK released cells from DLC1-induced cytoskeletal collapse and cell shrinkage. Conclusion: Our data suggest that DLC1 negatively regulates Rho/ROCK/ MLC2. This implicates a ROCK-mediated pathway of DLC1 in suppressing metastasis of HCC cells and enriches our understanding in the molecular mechanisms involved in the progression of hepatocellular carcinoma. © 2008 Wong et al.published_or_final_versio

Hypermethylation of the DLC1 CpG island does not alter gene expression in canine lymphoma

<p>Abstract</p> <p>Background</p> <p>This study is a comparative epigenetic evaluation of the methylation status of the <it>DLC1 </it>tumor suppressor gene in naturally-occurring canine lymphoma. Canine non-Hodgkin's lymphoma (NHL) has been proposed to be a relevant preclinical model that occurs spontaneously and may share causative factors with human NHL due to a shared home environment. The canine <it>DLC1 </it>mRNA sequence was derived from normal tissue. Using lymphoid samples from 21 dogs with NHL and 7 normal dogs, the methylation status of the promoter CpG island of the gene was defined for each sample using combined bisulfite restriction analysis (COBRA), methylation-specific PCR (MSP), and bisulfite sequencing methods. Relative gene expression was determined using real-time PCR.</p> <p>Results</p> <p>The mRNA sequence of canine <it>DLC1 </it>is highly similar to the human orthologue and contains all protein functional groups, with 97% or greater similarity in functional regions. Hypermethylation of the 5' and 3' flanking regions of the promoter was statistically significantly associated with the NHL phenotype, but was not associated with silencing of expression or differences in survival.</p> <p>Conclusion</p> <p>The canine <it>DLC1 </it>is constructed highly similarly to the human gene, which has been shown to be an important tumor suppressor in many forms of cancer. As in human NHL, the promoter CpG island of <it>DLC1 </it>in canine NHL samples is abnormally hypermethylated, relative to normal lymphoid tissue. This study confirms that hypermethylation occurs in canine cancers, further supporting the use of companion dogs as comparative models of disease for evaluation of carcinogenesis, biomarker diagnosis, and therapy.</p

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)

Amsterdam Declaration on Funding Research Software Sustainability

The Research Software Alliance (ReSA) and the Netherlands eScience Center hosted a two-day international workshop in Amsterdam (the Netherlands) on 8-9 November 2023 to set the future agenda for national and international funders to support sustainable research software. As the importance of software in research has become increasingly apparent, so has the urgent need to sustain it. Funders can play a crucial role in this respect by ensuring structural support. Over the past few years, a variety of methods for sustaining research software have been explored, including improving and extending funding policies and instruments. During the workshop, funding organizations joined forces to explore how they can effectively contribute to making research software sustainable. In preparation of the workshop, a draft of a future international declaration, titled "Amsterdam Declaration on Funding Research Software Sustainability" was created by the Research Software Alliance, the Netherlands eScience Center and with input from stakeholders in the field