scholarly journals Building a functional connectome of the Drosophila central complex

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Romain Franconville ◽  
Celia Beron ◽  
Vivek Jayaraman

The central complex is a highly conserved insect brain region composed of morphologically stereotyped neurons that arborize in distinctively shaped substructures. The region is implicated in a wide range of behaviors and several modeling studies have explored its circuit computations. Most studies have relied on assumptions about connectivity between neurons based on their overlap in light microscopy images. Here, we present an extensive functional connectome of Drosophila melanogaster’s central complex at cell-type resolution. Using simultaneous optogenetic stimulation, calcium imaging and pharmacology, we tested the connectivity between 70 presynaptic-to-postsynaptic cell-type pairs. We identified numerous inputs to the central complex, but only a small number of output channels. Additionally, the connectivity of this highly recurrent circuit appears to be sparser than anticipated from light microscopy images. Finally, the connectivity matrix highlights the potentially critical role of a class of bottleneck interneurons. All data are provided for interactive exploration on a website.

2019 ◽  
Vol 122 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Adrian L. Harris

AbstractCancer metabolism has undergone a resurgence in the last decade, 70 years after Warburg described aerobic glycolysis as a feature of cancer cells. A wide range of techniques have elucidated the complexity and heterogeneity in preclinical models and clinical studies. What emerges are the large differences between tissues, tumour types and intratumour heterogeneity. However, synergies with inhibition of metabolic pathways have been found for many drugs and therapeutic approaches, and a critical role of window studies and translational trial design is key to success.


2012 ◽  
Vol 18 (2) ◽  
pp. 81 ◽  
Author(s):  
Daniel Lunney

How people coexist and interact with animals has become an intensely debated issue in recent times, particularly with the rise of the animal protection movement following the publication of Peter Singer’s book Animal Liberation in 1975. This paper discusses some shortcomings of the philosophical positions taken in this complex debate. Singer has helped put animals on a new footing as a group that cannot morally be ignored, but his focus is mainly on individual, familiar animals that are used or abused by humans. The argument of this paper is that the ethics of managing wildlife hinges on a broader view of animals, and their contexts, than is apparent from Singer’s text. Wildlife managers aim to conserve populations of a wide range of species, and their habitats, but some mechanisms for achieving these aims, such as research and the control of invasive animals, are frequently opposed by elements of the animal protection movement. We need to adapt our attitude to animals, particularly wildlife, away from the traditional legacy of a few familiar species to embrace an ethic that is more ecological and relevant to Australian contexts. The case argued here has been to see the critical role of context — geographical, ecological, historical, relational — as a basis for a degree of reconciliation between conservation-oriented wildlife managers and the rising interest in the ethics of animal use. There is much to be gained for zoologists, wildlife managers and conservation biologists by framing key elements of their case in ethical arguments. Conversely, the challenge for those in the animal protection movement is to expand their philosophical ideas to include the ethical imperative of the conservation of populations of wildlife.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2016 ◽  
Author(s):  
Meghan M Kozub ◽  
Ryan M Carr ◽  
Gwen L Lomberk ◽  
Martin E Fernandez-Zapico

Histone-modifying enzymes play a critical role in chromatin remodeling and are essential for influencing several genome processes such as gene expression and DNA repair, replication, and recombination. The discovery of lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, dramatically revolutionized research in the field of epigenetics. LSD1 plays a pivotal role in a wide range of biological operations, including development, cellular differentiation, embryonic pluripotency, and disease (for example, cancer). This mini-review focuses on the role of LSD1 in chromatin regulatory complexes, its involvement in epigenetic changes throughout development, and its importance in physiological and pathological processes.


Vision ◽  
2019 ◽  
Vol 3 (4) ◽  
pp. 58 ◽  
Author(s):  
Jason Satel ◽  
Nicholas R. Wilson ◽  
Raymond M. Klein

An inhibitory aftermath of orienting, inhibition of return (IOR), has intrigued scholars since its discovery about 40 years ago. Since then, the phenomenon has been subjected to a wide range of neuroscientific methods and the results of these are reviewed in this paper. These include direct manipulations of brain structures (which occur naturally in brain damage and disease or experimentally as in TMS and lesion studies) and measurements of brain activity (in humans using EEG and fMRI and in animals using single unit recording). A variety of less direct methods (e.g., computational modeling, developmental studies, etc.) have also been used. The findings from this wide range of methods support the critical role of subcortical and cortical oculomotor pathways in the generation and nature of IOR.


Author(s):  
Stanley Heinze

Navigation is the ability of animals to move through their environment in a planned manner. Different from directed but reflex-driven movements, it involves the comparison of the animal’s current heading with its intended heading (i.e., the goal direction). When the two angles don’t match, a compensatory steering movement must be initiated. This basic scenario can be described as an elementary navigational decision. Many elementary decisions chained together in specific ways form a coherent navigational strategy. With respect to navigational goals, there are four main forms of navigation: explorative navigation (exploring the environment for food, mates, shelter, etc.); homing (returning to a nest); straight-line orientation (getting away from a central place in a straight line); and long-distance migration (seasonal long-range movements to a location such as an overwintering place). The homing behavior of ants and bees has been examined in the most detail. These insects use several strategies to return to their nest after foraging, including path integration, route following, and, potentially, even exploit internal maps. Independent of the strategy used, insects can use global sensory information (e.g., skylight cues), local cues (e.g., visual panorama), and idiothetic (i.e., internal, self-generated) cues to obtain information about their current and intended headings. How are these processes controlled by the insect brain? While many unanswered questions remain, much progress has been made in recent years in understanding the neural basis of insect navigation. Neural pathways encoding polarized light information (a global navigational cue) target a brain region called the central complex, which is also involved in movement control and steering. Being thus placed at the interface of sensory information processing and motor control, this region has received much attention recently and emerged as the navigational “heart” of the insect brain. It houses an ordered array of head-direction cells that use a wide range of sensory information to encode the current heading of the animal. At the same time, it receives information about the movement speed of the animal and thus is suited to compute the home vector for path integration. With the help of neurons following highly stereotypical projection patterns, the central complex theoretically can perform the comparison of current and intended heading that underlies most navigation processes. Examining the detailed neural circuits responsible for head-direction coding, intended heading representation, and steering initiation in this brain area will likely lead to a solid understanding of the neural basis of insect navigation in the years to come.


2020 ◽  
Vol 11 ◽  
Author(s):  
Rossana Franzin ◽  
Alessandra Stasi ◽  
Marco Fiorentino ◽  
Giovanni Stallone ◽  
Vincenzo Cantaluppi ◽  
...  

The aberrant activation of complement system in several kidney diseases suggests that this pillar of innate immunity has a critical role in the pathophysiology of renal damage of different etiologies. A growing body of experimental evidence indicates that complement activation contributes to the pathogenesis of acute kidney injury (AKI) such as delayed graft function (DGF) in transplant patients. AKI is characterized by the rapid loss of the kidney’s excretory function and is a complex syndrome currently lacking a specific medical treatment to arrest or attenuate progression in chronic kidney disease (CKD). Recent evidence suggests that independently from the initial trigger (i.e., sepsis or ischemia/reperfusions injury), an episode of AKI is strongly associated with an increased risk of subsequent CKD. The AKI-to-CKD transition may involve a wide range of mechanisms including scar-forming myofibroblasts generated from different sources, microvascular rarefaction, mitochondrial dysfunction, or cell cycle arrest by the involvement of epigenetic, gene, and protein alterations leading to common final signaling pathways [i.e., transforming growth factor beta (TGF-β), p16ink4a, Wnt/β-catenin pathway] involved in renal aging. Research in recent years has revealed that several stressors or complications such as rejection after renal transplantation can lead to accelerated renal aging with detrimental effects with the establishment of chronic proinflammatory cellular phenotypes within the kidney. Despite a greater understanding of these mechanisms, the role of complement system in the context of the AKI-to-CKD transition and renal inflammaging is still poorly explored. The purpose of this review is to summarize recent findings describing the role of complement in AKI-to-CKD transition. We will also address how and when complement inhibitors might be used to prevent AKI and CKD progression, therefore improving graft function.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Mandy O. J. Grootaert ◽  
Lynn Roth ◽  
Dorien M. Schrijvers ◽  
Guido R. Y. De Meyer ◽  
Wim Martinet

Autophagy is a subcellular process that plays an important role in the degradation of proteins and damaged organelles such as mitochondria (a process termed “mitophagy”) via lysosomes. It is crucial for regulating protein and mitochondrial quality control and maintaining cellular homeostasis, whereas dysregulation of autophagy has been implicated in a wide range of diseases including atherosclerosis. Recent evidence has shown that the autophagic process becomes dysfunctional during the progression of atherosclerosis, regardless of whether there are many autophagy-stimulating factors (e.g., reactive oxygen species, oxidized lipids, and cytokines) present within the atherosclerotic plaque. This review highlights the recent insights into the causes and consequences of defective autophagy in atherosclerosis, with a special focus on the role of autophagy and mitophagy in plaque macrophages, vascular smooth muscle cells (VSMCs), and endothelial cells (ECs). It has been shown that defective autophagy can promote apoptosis in macrophages but that it accelerates premature senescence in VSMCs. In the ECs, defective autophagy promotes both apoptosis and senescence. We will discuss the discrepancy between these three cell types in their response to autophagy deficiency and underline the cell type-dependent role of autophagy, which may have important implications for the efficacy of autophagy-targeted treatments for atherosclerosis.


2017 ◽  
Vol 26 (01) ◽  
pp. 53-58
Author(s):  
C. Paton ◽  
T. Karopka

Summary Objective: To give an overview of the role of Free/Libre and Open Source Software (FLOSS) in the context of secondary use of patient data to enable Learning Health Systems (LHSs). Methods: We conducted an environmental scan of the academic and grey literature utilising the MedFLOSS database of open source systems in healthcare to inform a discussion of the role of open source in developing LHSs that reuse patient data for research and quality improvement. Results: A wide range of FLOSS is identified that contributes to the information technology (IT) infrastructure of LHSs including operating systems, databases, frameworks, interoperability software, and mobile and web apps. The recent literature around the development and use of key clinical data management tools is also reviewed. Conclusions: FLOSS already plays a critical role in modern health IT infrastructure for the collection, storage, and analysis of patient data. The nature of FLOSS systems to be collaborative, modular, and modifiable may make open source approaches appropriate for building the digital infrastructure for a LHS.


2021 ◽  
Vol 3 ◽  
pp. 47-64
Author(s):  
Kerk Kee ◽  
Prasad Calyam ◽  
Hariharan Regunath

The COVID-19 pandemic is an unprecedented global emergency. Clinicians and medical researchers are suddenly thrown into a situation where they need to keep up with the latest and best evidence for decision-making at work in order to save lives and develop solutions for COVID-19 treatments and preventions. However, a challenge is the overwhelming numbers of online publications with a wide range of quality. We explain a science gateway platform designed to help users to filter the overwhelming amount of literature efficiently (with speed) and effectively (with quality), to find answers to their scientific questions. It is equipped with a chatbot to assist users to overcome infodemic, low usability, and high learning curve. We argue that human-machine communication via a chatbot play a critical role in enabling the diffusion of innovations.


2022 ◽  

Classic organizational theory was built on ethnographic studies. These studies, which rely on immersion in everyday organizational life, adopting the native’s perspective, and an openness to emergent phenomena, have helped illuminate the complexities and nuances of organizations that were otherwise invisible to outsiders. Today, organizational scholarship boasts of drawing on a wide range of theoretical traditions and diverse methodologies, particularly in quantitative methods that lend generalizability and scientific precision to organizational theory. As such, the role of ethnography has also evolved over the years; its validity has been criticized and defended, its ontological and epistemological foundations reflected on, and its place among other traditions clarified. Besides its critical role in establishing organizational study as a discipline in its own right, ethnographic work is now generally recognized and appreciated in the scholarly community, in what has been termed its Golden Age, for its contributions to new intellectual territories across multiple subfields of organizational theory.


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