Big Data and Analysis of Data Transfers for International Research Networks Using NetSage

Modern science is increasingly data-driven and collaborative in nature. Many scientific disciplines, including genomics, high-energy physics, astronomy, and atmospheric science, produce petabytes of data that must be shared with collaborators all over the world. The National Science Foundation-supported International Research Network Connection (IRNC) links have been essential to enabling this collaboration, but as data sharing has increased, so has the amount of information being collected to understand network performance. New capabilities to measure and analyze the performance of international wide-area networks are essential to ensure end-users are able to take full advantage of such infrastructure for their big data applications. NetSage is a project to develop a unified, open, privacy-aware network measurement, and visualization service to address the needs of monitoring today's high-speed international research networks. NetSage collects data on both backbone links and exchange points, which can be as much as 1Tb per month. This puts a significant strain on hardware, not only in terms storage needs to hold multi-year historical data, but also in terms of processor and memory needs to analyze the data to understand network behaviors. This paper addresses the basic NetSage architecture, its current data collection and archiving approach, and details the constraints of dealing with this big data problem of handling vast amounts of monitoring data, while providing useful, extensible visualization to end users

Adamantinomatous craniopharyngioma as a model to understand paracrine and senescence-induced tumourigenesis

Cellular senescence is a process that can prevent tumour development in a cell autonomous manner by imposing a stable cell cycle arrest after oncogene activation. Paradoxically, senescence can also promote tumour growth cell non-autonomously by creating a permissive tumour microenvironment that fuels tumour initiation, progression to malignancy and metastasis. In a pituitary tumour known as adamantinomatous craniopharyngioma (ACP), cells that carry oncogenic β-catenin mutations and overactivate the WNT signalling pathway form cell clusters that become senescent and activate a senescence-associated secretory phenotype (SASP). Research in mouse models of ACP has provided insights into the function of the senescent cell clusters and revealed a critical role for SASP-mediated activities in paracrine tumour initiation. In this review, we first discuss this research on ACP and subsequently explore the theme of paracrine tumourigenesis in other tumour models available in the literature. Evidence is accumulating supporting the notion that paracrine signalling brought about by senescent cells may underlie tumourigenesis across different tumours and cancer models

First report of Melittobia australica Girault in Europe and new record of M. acasta (Walker) for Italy

Melittobia acasta and M. australica are newly recorded from Sicily, Italy, and the second species is reported in Europe for the first time. A short historical background about Melittobia parasitoid wasps, their hosts, and distribution, with emphasis in those two species is presented together with illustrations to facilitate their identification. Brief discussion about the presence and possible distribution of the species in Sicily is also included

Stem cells and their role in pituitary tumorigenesis

The presence of adult pituitary stem cells (PSCs) has been described in murine systems by comprehensive cellular profiling and genetic lineage tracing experiments. PSCs are thought to maintain multipotent capacity throughout life and give rise to all hormone-producing cell lineages, playing a role in pituitary gland homeostasis. Additionally, PSCs have been proposed to play a role in pituitary tumorigenesis, in both adenomas and adamantinomatous craniopharyngiomas. In this manuscript, we discuss the different approaches used to demonstrate the presence of PSCs in the murine adult pituitary, from marker analyses to genetic tracing. In addition, we review the published literature suggesting the existence of tumor stem cells in mouse and human pituitary tumors. Finally, we discuss the potential role of PSCs in pituitary tumorigenesis in the context of current models of carcinogenesis and present evidence showing that in contrast to pituitary adenoma, which follows a classical cancer stem cell paradigm, a novel mechanism has been revealed for paracrine, non-cell autonomous tumor initiation in adamantinomatous craniopharyngioma, a benign but clinically aggressive pediatric tumor

The role of cytokine signalling, cellular senescence and its secretory phenotype in normal pituitary development and tumourigenesis

Oncogene-induced senescence (OIS) is classically described as a potent antitumourigenic barrier that restrains the proliferation of pre-malignant cells. Senescent cells can also promote immune clearance by secreting a plethora of chemokines and inflammatory factors, collectively known as the Senescence-Associated Secretory Phenotype (SASP). However, the SASP can also promote tumourigenesis paracrinally. In this study, OIS and the SASP were studied in mouse models for adamantinomatous craniopharyngioma (ACP), which express oncogenic β-catenin in pituitary progenitors/stem cells. Surprisingly, oncogenic β-catenin-targeted cells did not give rise to the tumour mass in the majority of cases and stopped dividing after a short burst of proliferation to form β-catenin-accumulating cell clusters. Here it is demonstrated that β-catenin clusters undergo OIS as determined by a lack of proliferation markers, activation of the p53/p21 and p16/Rb pathways, induction of the DNA damage response (DDR) and activation of the NF-κB pathway. Additionally, unbiased mRNA expression analysis shows enrichment of OIS and SASP genes in β-catenin clusters, while SASP gene expression is corroborated by qRT-PCR and ELISA assays. Of translational significance, these results are recapitulated in the β- catenin clusters of human ACP. Furthermore, evidence is presented indicating that the paracrine signals secreted by the β-catenin clusters are involved in non-cell autonomous tumourigenesis through modification of their microenvironment and the recruitment of endothelial progenitors displaying aberrant SOX9 expression. A genetic strategy demonstrated that induction of OIS and the SASP in the clusters is p53-independent, but that p53 is required to prevent a full bias for cell-autonomous tumourigenesis. Finally, a mouse line that also develops β-catenin clusters, albeit with a dampened SASP is described. These clusters do not appear to modify their microenvironment and tumours do not develop. Together, the mouse and human data suggest that senescence and SASP are likely to modify the tumour microenvironment resulting in cell transformation, tumour growth and survival

Library of Apicomplexan Metabolic Pathways: a manually curated database for metabolic pathways of apicomplexan parasites.

The Library of Apicomplexan Metabolic Pathways (LAMP, http://www.llamp.net) is a web database that provides near complete mapping from genes to the central metabolic functions for some of the prominent intracellular parasites of the phylum Apicomplexa. This phylum includes the causative agents of malaria, toxoplasmosis and theileriosis-diseases with a huge economic and social impact. A number of apicomplexan genomes have been sequenced, but the accurate annotation of gene function remains challenging. We have adopted an approach called metabolic reconstruction, in which genes are systematically assigned to functions within pathways/networks for Toxoplasma gondii, Neospora caninum, Cryptosporidium and Theileria species, and Babesia bovis. Several functions missing from pathways have been identified, where the corresponding gene for an essential process appears to be absent from the current genome annotation. For each species, LAMP contains interactive diagrams of each pathway, hyperlinked to external resources and annotated with detailed information, including the sources of evidence used. We have also developed a section to highlight the overall metabolic capabilities of each species, such as the ability to synthesize or the dependence on the host for a particular metabolite. We expect this new database will become a valuable resource for fundamental and applied research on the Apicomplexa

The Role of Astrocytes in Remyelination.

Remyelination is the regeneration of myelin sheaths following demyelination. This regenerative process is critical for the re-establishment of axonal conduction velocity and metabolic support to the axons. Successful remyelination in the CNS generally depends on the activation, proliferation, and differentiation of oligodendrocyte progenitor cells (OPCs). However, other cell types play critical roles in establishing where a lesion is conducive for regeneration. In the last few years, several studies have described beneficial and detrimental roles played by astrocytes in remyelination. This review will discuss recent developments in the concept of astrocyte reactivity, what is known about the astrocytic contribution to remyelination, and highlight future avenues of investigation.The authors’ laboratory is supported by funding from the UK Multiple Sclerosis Society (MS50), The Adelson Medical Research Foundation, and a core support grant from the Wellcome and MRC to the Wellcome-Medical Research Council Cambridge Stem Cell Institute (203151/Z/16/Z). KSR is supported by a postdoctoral fellowship from the Multiple Sclerosis Society of Canad

Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: a systematic guideline review and expert consensus

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease-oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow-up: strategies in care planning, self-management and medication-related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self-management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.Journal of Internal MedicineKarolinska Institutet Strategic Research Area in Epidemiology (SfoEpi