ImageJ is an image analysis program extensively used in the biological sciences and beyond. Due to its ease of use, recordable macro language, and extensible plug-in architecture, ImageJ enjoys contributions from non-programmers, amateur programmers, and professional developers alike. Enabling such a diversity of contributors has resulted in a large community that spans the biological and physical sciences. However, a rapidly growing user base, diverging plugin suites, and technical limitations have revealed a clear need for a concerted software engineering effort to support emerging imaging paradigms, to ensure the software’s ability to handle the requirements of modern science. We rewrote the entire ImageJ codebase, engineering a redesigned plugin mechanism intended to facilitate extensibility at every level, with the goal of creating a more powerful tool that continues to serve the existing community while addressing a wider range of scientific requirements. This next-generation ImageJ, called “ImageJ2” in places where the distinction matters, provides a host of new functionality. It separates concerns, fully decoupling the data model from the user interface. It emphasizes integration with external applications to maximize interoperability. Its robust new plugin framework allows everything from image formats, to scripting languages, to visualization to be extended by the community. The redesigned data model supports arbitrarily large, N-dimensional datasets, which are increasingly common in modern image acquisition. Despite the scope of these changes, backwards compatibility is maintained such that this new functionality can be seamlessly integrated with the classic ImageJ interface, allowing users and developers to migrate to these new methods at their own pace. Scientific imaging benefits from open-source programs that advance new method development and deployment to a diverse audience. ImageJ has continuously evolved with this idea in mind; however, new and emerging scientific requirements have posed corresponding challenges for ImageJ’s development. The described improvements provide a framework engineered for flexibility, intended to support these requirements as well as accommodate future needs. Future efforts will focus on implementing new algorithms in this framework and expanding collaborations with other popular scientific software suites.

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ImageJ2: ImageJ for the next generation of scientific image data

Macrophages, the most plastic cells of the haematopoietic system, are found in all tissues and show great functional diversity. They have roles in development, homeostasis, tissue repair and immunity. Although tissue macrophages are anatomically distinct from one another, and have different transcriptional profiles and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this Review, we discuss how macrophages regulate normal physiology and development, and provide several examples of their pathophysiological roles in disease. We define the 'hallmarks' of macrophages according to the states that they adopt during the performance of their various roles, taking into account new insights into the diversity of their lineages, identities and regulation. It is essential to understand this diversity because macrophages have emerged as important therapeutic targets in many human diseases.

/pdf/macrophage-biology-in-development-homeostasis-and-disease-2nq2u94n8n.pdf

Macrophage biology in development, homeostasis and disease

Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

Physiology of Microglia

Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner.

The neuropathological hallmarks of Alzheimer disease (AD) include “positive” lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and “negative” lesions such as neuronal and synaptic loss. Despite their inherently cross-sectional nature, postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and, consequently, the development of diagnostic criteria that are now used worldwide. In addition, clinicopathological correlation studies have been crucial to generate hypotheses about the pathophysiology of the disease, by establishing that there is a continuum between “normal” aging and AD dementia, and that the amyloid plaque build-up occurs primarily before the onset of cognitive deficits, while neurofibrillary tangles, neuron loss, and particularly synaptic loss, parallel the progression of cognitive decline. Importantly, these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloid PET and volumetric MRI.

/pdf/neuropathological-alterations-in-alzheimer-disease-2zexumi6x1.pdf

Neuropathological Alterations in Alzheimer Disease

Blood feeding is a feature that is shared by alarge variety of organisms from Protozoa tomammals, and regardless of their diverse phyloge-netic origins most of them digest haemoglobin.This process results in the release of peptides,amino acids and the prosthetic group haem. Freehaem is very toxic and several mechanisms havebeen developed in order to protect organismsagainst its deleterious effects [1]. In

Short communication Haemozoin in Schistosoma mansoni

There is heightened interest to devise therapies that target the oncometabolome. We show that kinase inhibitors (KIs) and biguanides synergistically target melanoma, leukemia, and breast, colon and renal cancer cells, but not non-transformed cells. Metabolic profiling confirmed opposing effects of KIs and biguanides on glycolysis, but this was insufficient to explain the observed synergy between the drugs. Rather, we define a critical role for the synthesis of non-essential amino acids (NEAA) aspartate, asparagine and serine as well as reductive glutamine metabolism, in determining the sensitivity of cancer cells to KI - biguanide combinations. The mTORC1/4E-BP axis regulates aspartate, asparagine and serine synthesis by modulating translation of mRNAs encoding PC, ASNS, PHGDH and PSAT1. Ablation of 4E-BP1 and 2 results in a dramatic increase in serine, aspartate and asparagine levels and a substantial decrease in sensitivity of breast cancer and melanoma cells to KI - biguanide combinations. In turn, efficacy of KI - biguanide combinations is impeded by HIF1α and sustained reductive glutamine metabolism. These findings identify hitherto unappreciated translational reprograming of NEAA synthesis and HIF1α-dependent stimulation of reductive glutamine metabolism as critical metabolic vulnerabilities of cancer that underpin synergy between KIs and biguanides.

https://www.biorxiv.org/content/biorxiv/early/2017/07/07/160879.full.pdf

Translational and HIF1α-dependent metabolic reprograming underpin oncometabolome plasticity and synergy between oncogenic kinase inhibitors and biguanides.

Dendrites form arbors whose size, shape and complexity define how neurons cover their receptive territories. Actin dynamics contribute to growth and remodelling of dendrite arbors. Here we examined how Spire, a conserved actin nucleation factor, promotes formation of new branches in vivo. In live imaging of Drosophila class IV dendritic arborisation (c4da) neurons, Spire was observed at new sites of branch initiation, where it assembled new actin polymer prior to filopodial outgrowth. For dendrite arborization, Spire required intact structural domains to nucleate actin and target the secretory network, and Spire interacted with Rab11 GTPase, a key regulator of recycling endosomes. Together, these findings support a model that Spire cooperates with Rab11 to promote new dendrite branches by linking localized actin assembly with intracellular trafficking of endosomes that deliver lipids and cargoes to fuel protrusive outgrowth of nascent dendrites.

Tiago Ferreira

Papers

Short communication Haemozoin in Schistosoma mansoni

Translational and HIF1α-dependent metabolic reprograming underpin oncometabolome plasticity and synergy between oncogenic kinase inhibitors and biguanides.

The actin nucleator Spire cooperates with Rab11 to initiate nascent dendrite branches