Transcriptome dynamics in the asexual cycle of the chordate Botryllus schlosseri

Background: We performed an analysis of the transcriptome during the blastogenesis of the chordate Botryllus schlosseri, focusing in particular on genes involved in cell death by apoptosis. The tunicate B. schlosseri is an ascidian forming colonies characterized by the coexistence of three blastogenetic generations: filter-feeding adults, buds on adults, and budlets on buds. Cyclically, adult tissues undergo apoptosis and are progressively resorbed and replaced by their buds originated by asexual reproduction. This is a feature of colonial tunicates, the only known chordates that can reproduce asexually. Results: Thanks to a newly developed web-based platform (http://botryllus.cribi.unipd.it), we compared the transcriptomes of the mid-cycle, the pre-take-over, and the take-over phases of the colonial blastogenetic cycle. The platform is equipped with programs for comparative analysis and allows to select the statistical stringency. We enriched the genome annotation with 11,337 new genes; 581 transcripts were resolved as complete open reading frames, translated in silico into amino acid sequences and then aligned onto the non-redundant sequence database. Significant differentially expressed genes were classified within the gene ontology categories. Among them, we recognized genes involved in apoptosis activation, de-activation, and regulation. Conclusions: With the current work, we contributed to the improvement of the first released B. schlosseri genome assembly and offer an overview of the transcriptome changes during the blastogenetic cycle, showing up- and down-regulated genes. These results are important for the comprehension of the events underlying colony growth and regression, cell proliferation, colony homeostasis, and competition among different generations

Suppression of cell-spreading and phagocytic activity on nano-pillared surface: in vitro experiment using hemocytes of the colonial ascidian Botryllus schlosseri.

Nano-scale nipple array on the body surface has been described from various invertebrates including endoparasitic and mesoparasitic copepods, but the functions of the nipple array is not well understood. Using the hydrophilized nanopillar sheets made of polystyrene as a mimetic material of the nipple arrays on the parasites\u2019 body surface, we assayed the cell spreading and phagocytosis of the hemocytes of the colonial ascidian Botryllus schlosseri. On the pillared surface, the number of spreading amebocytes and the number of phagocytizing hemocytes per unit area were always smaller than those on the flat surface (Mann-Whitney test, p < 0.05 - 0.001), probably because the effective area for the cell attachment on the pillared surface is much smaller than the area on the flat sheet. The present results supports the idea that the nipple array on the parasites' body surface reduces the innate immune reaction from the host hemocytes

Life history and ecological genetics of the colonial ascidian Botryllus schlosseri

The colonial ascidian Botryllus schlosseri is a cosmopolitan, marine filter feeder, introduced as a laboratory research organism in the 1950s. Currently, it is widely used in many laboratories to investigate a variety of biological questions. Recently, it has become a species of concern, as it is an invasive species in many coastal environments. Here, we review studies on the geographical distribution of the species, sexual and asexual reproduction in the field, tolerance to temperature, salinity and anthropogenic activity, polychromatism, enzymatic polymorphism, and the genetic basis of pigmentation. Studying the relationship between genetic polymorphism and the adaptation of B. schlosseri to environmental stress is a challenge of future research and will improve our understanding of its evolutionary success and invasive potential

Supporting social innovation through visualisations of community interactions

Online communities that form through the introduction of sociotechnical platforms require significant effort to cultivate and sustain. Providing open, transparent information on community behaviour can motivate participation from community members themselves, while also providing platform administrators with detailed interaction dynamics. However, challenges arise in both understanding what information is conducive to engagement and sustainability, and then how best to represent this information to platform stakeholders. Towards a better understanding of these challenges, we present the design, implementation, and evaluation of a set of simple visualisations integrated into a Collective Awareness Platform for Social Innovation platform titled commonfare.net. We discuss the promise and challenge of bringing social innovation into the digital age, in terms of supporting sustained platform use and collective action, and how the introduction of community visualisations has been directed towards achieving this goal

The evaluation of capacity in dementia: ethical constraints and best practice. A systematic review

The progressive ageing of a population leads to an increase in the number of people suffering from cognitive deterioration. This requires particular attention in terms of the necessity to assess these people's cognitive functions and their capacity to make decisions. The present systematic review analyses the clinical and ethical aspects of any assessment of capacity, with a specific focus on the capacity of the individual to give informed consent for medical treatment and also with regard to their testamentary capacity. The results indicate that the concepts of capacity, competence and decision-making need to be better clarified, ad-hoc devised tools are required and a multidisciplinary, clinical and legal approach to assessments of capacity needs to be adopted. This is crucial to guarantee that the two ethical principles of capacity assessment are adhered to: respect for an individual's autonomy and the protection of fragile individuals

Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part I: influenza life-cycle and currently available drugs

Influenza is a contagious respiratory acute viral disease charac- terized by a short incubation period, high fever and respiratory and systemic symptoms. The burden of influenza is very heavy. Indeed, the World Health Organization (WHO) estimates that annual epidemics affect 5-15% of the world?s population, causing up to 4-5 million severe cases and from 250,000 to 500,000 deaths. In order to design anti-influenza molecules and compounds, it is important to understand the complex replication cycle of the influenza virus. Replication is achieved through various stages. First, the virus must engage the sialic acid receptors present on the free surface of the cells of the respiratory tract. The virus can then enter the cells by different routes (clathrin-mediated endocytosis or CME, caveolae-dependent endocytosis or CDE, clathrin-caveolae-independent endocytosis, or macropinocyto- sis). CME is the most usual pathway; the virus is internalized into an endosomal compartment, from which it must emerge in order to release its nucleic acid into the cytosol. The ribonucleo- protein must then reach the nucleus in order to begin the pro- cess of translation of its genes and to transcribe and replicate its nucleic acid. Subsequently, the RNA segments, surrounded by the nucleoproteins, must migrate to the cell membrane in order to enable viral assembly. Finally, the virus must be freed to invade other cells of the respiratory tract. All this is achieved through a synchronized action of molecules that perform multi- ple enzymatic and catalytic reactions, currently known only in part, and for which many inhibitory or competitive molecules have been studied. Some of these studies have led to the devel- opment of drugs that have been approved, such as Amantadine, Rimantadine, Oseltamivir, Zanamivir, Peramivir, Laninamivir, Ribavirin and Arbidol. This review focuses on the influenza life- cycle and on the currently available drugs, while potential anti- viral compounds for the prevention and treatment of influenza are considered in the subsequent review

Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part II: Future compounds against influenza virus

In the first part of this overview, we described the life cycle of the influenza virus and the pharmacological action of the currently available drugs. This second part provides an overview of the molecular mechanisms and targets of still-experimental drugs for the treatment and management of influenza.Briefly, we can distinguish between compounds with anti-influenza activity that target influenza virus proteins or genes, and molecules that target host components that are essential for viral replication and propagation. These latter compounds have been developed quite recently. Among the first group, we will focus especially on hemagglutinin, M2 channel and neuraminidase inhibitors. The second group of compounds may pave the way for personalized treatment and influenza management. Combination therapies are also discussed.In recent decades, few antiviral molecules against influenza virus infections have been available; this has conditioned their use during human and animal outbreaks. Indeed, during seasonal and pandemic outbreaks, antiviral drugs have usually been administered in monotherapy and, sometimes, in an uncontrolled manner to farm animals. This has led to the emergence of viral strains displaying resistance, especially to compounds of the amantadane family. For this reason, it is particularly important to develop new antiviral drugs against influenza viruses. Indeed, although vaccination is the most powerful means of mitigating the effects of influenza epidemics, antiviral drugs can be very useful, particularly in delaying the spread of new pandemic viruses, thereby enabling manufacturers to prepare large quantities of pandemic vaccine. In addition, antiviral drugs are particularly valuable in complicated cases of influenza, especially in hospitalized patients.To write this overview, we mined various databases, including Embase, PubChem, DrugBank and Chemical Abstracts Service, and patent repositories

Angiogenesis in pancreatic ductal adenocarcinoma: A controversial issue

Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early loco-regional spread and distant metastases at diagnosis, leading to dismal prognosis with a 5-year overall survival rate moderately over than 5%. This malignancy is largely resistant to chemotherapy and radiation, but the reasons of the refractoriness to the therapies is still unknown. Evidence is accumulating to indicate that the PDAC microenvironment and vascularity strongly contribute to the clinical features of this disease. In particular, PDAC is characterized by excessive dense extracellular matrix deposition associated to vasculature collapse and hypoxia with low drug delivery, explaining at least partly the low efficacy of antiangiogenic drugs in this cancer. Strategies aimed to modulate tumor stroma favoring vasculature perfusion and chemotherapeutics delivery are under investigation

A comparison of para, meta, and ortho-carborane centred non-fullerene acceptors for organic solar cells

[Abstract]: We report the first examples of carborane-containing non-fullerene acceptors (NFAs), and their use in organic photovoltaic (OPV) devices. NFAs employing an A–D–A′–D–A type design centred around a central electron withdrawing carborane unit (A′), using either para, meta, or ortho-carborane isomers are reported. We demonstrate that the nature of the isomer has a major impact on device performance, despite minor differences in optoelectronic and morphological properties, with the use of ortho-carborane resulting in the highest device efficiencies. We further show that end-group fluorination is an efficient strategy to modulate energy levels and improve device performance of such NFAs.Reino Unido. Physics Science Research Council; EP/V048686/1Reino Unido. Physics Science Research Council; EP/T028513/1Arabia Saudí. King Abdullah University of Science and Technology; OSR-2019-CRG8-409

RelB activation in anti-inflammatory decidual endothelial cells: a master plan to avoid pregnancy failure?

It is known that excessive inflammation at fetal-maternal interface is a key contributor in a compromised pregnancy. Female genital tract is constantly in contact with microorganisms and several strategies must be adopted to avoid pregnancy failure. Decidual endothelial cells (DECs) lining decidual microvascular vessels are the first cells that interact with pro-inflammatory stimuli released into the environment by microorganisms derived from gestational tissues or systemic circulation. Here, we show that DECs are hypo-responsive to LPS stimulation in terms of IL-6, CXCL8 and CCL2 production. Our results demonstrate that DECs express low levels of TLR4 and are characterized by a strong constitutive activation of the non-canonical NF-\u3baB pathway and a low responsiveness of the canonical pathway to LPS. In conclusion, DECs show a unique hypo-responsive phenotype to the pro-inflammatory stimulus LPS in order to control the inflammatory response at feto-maternal interface