The striatum integrates information from multiple brain regions to shape motor learning. The two major projection cell types in striatum target different downstream basal ganglia targets and have ...opposing effects on motivated behavior, yet differential innervation of these neuronal subtypes is not well understood. To examine whether input specificity provides a substrate for information segregation in these circuits, we used a monosynaptic rabies virus system to generate brain-wide maps of neurons that form synapses with direct- or indirect-pathway striatal projection neurons. We discovered that sensory cortical and limbic structures preferentially innervated the direct pathway, whereas motor cortex preferentially targeted the indirect pathway. Thalamostriatal input, dopaminergic input, as well as input from specific cortical layers, was similar onto both pathways. We also confirm synaptic innervation of striatal projection neurons by the raphe and pedunculopontine nuclei. Together, these findings provide a framework for guiding future studies of basal ganglia circuit function.
•Sensory cortical and limbic structures preferentially target direct-pathway neurons•Motor cortex preferentially innervates indirect-pathway neurons•Inputs from thalamus, substantia nigra, and specific cortical layers was similar•Only a small proportion of dopaminergic input was transsynaptically labeled
Striatal direct- and indirect-pathway projection neurons serve distinct motor functions, but the specificity of their synaptic inputs is not known. Wall et al. use genetically targeted rabies virus to generate brain-wide input maps to these pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The tumor microenvironment is replete with factors secreted and internalized by surrounding cells. Exosomes are nano-sized, protein-embedded, membrane-bound vesicles that are released in greater ...quantities from cancer than normal cells and taken up by a variety of cell types. These vesicles contain proteins and genetic material from the cell of origin and in the case of tumor-derived exosomes, oncoproteins and oncogenes. With increasing understanding of the role exosomes play in basic biology, a more clear view of the potential exosomes are seen to have in cancer therapeutics emerges. However, certain essential aspects of exosome function, such as the uptake mechanisms, are still unknown. Various methods of cell-exosome interaction have been proposed, but this review focuses on the protein-protein interactions that facilitate receptor-mediated endocytosis, a broadly used mechanism by a variety of cells.
Biofilm formation is a process in which microbial cells aggregate to form collectives that are embedded in a self-produced extracellular matrix. Bacillus subtilis is a Gram-positive bacterium that is ...used to dissect the mechanisms controlling matrix production and the subsequent transition from a motile planktonic cell state to a sessile biofilm state. The collective nature of life in a biofilm allows emergent properties to manifest, and B. subtilis biofilms are linked with novel industrial uses as well as probiotic and biocontrol processes. In this Review, we outline the molecular details of the biofilm matrix and the regulatory pathways and external factors that control its production. We explore the beneficial outcomes associated with biofilms. Finally, we highlight major advances in our understanding of concepts of microbial evolution and community behaviour that have resulted from studies of the innate heterogeneity of biofilms.
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GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Ovine cutaneous myiasis (‘fly strike’) remains a major sheep health problem in many areas of the world. Myiasis risk is the result of a complex interaction of factors, such as fly and host abundance, ...host susceptibility, climate and, critically, husbandry and management strategies, all of which change seasonally in space and time. Given the complexity of the interacting factors, changes in myiasis incidence are hard to predict, as accordingly are the optimal husbandry responses required to manage the problem. Here the important risk factors are briefly reviewed and the future changes in myiasis incidence under conditions of anticipated climate change are considered. It is concluded that future work should focus in particular on evaluating the optimum use of integrated management, such as the combination of insecticide and trap use, in different environments under a range of farming regimes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary
Here, we review the multiple mechanisms that the Gram‐positive bacterium Bacillus subtilis uses to allow it to communicate between cells and establish community structures. The modes of ...action that are used are highly varied and include routes that sense pheromone levels during quorum sensing and control gene regulation, the intimate coupling of cells via nanotubes to share cytoplasmic contents, and long‐range electrical signalling to couple metabolic processes both within and between biofilms. We explore the ability of B. subtilis to detect ‘kin’ (and ‘cheater cells’) by looking at the mechanisms used to potentially ensure beneficial sharing (or limit exploitation) of extracellular ‘public goods’. Finally, reflecting on the array of methods that a single bacterium has at its disposal to ensure maximal benefit for its progeny, we highlight that a large future challenge will be integrating how these systems interact in mixed‐species communities.
‘Bacillus subtilis is a Gram‐positive bacterium that has evolved multiple mechanisms for communication and cooperation. Here we review processes which include division of labour, nanotube formation, metabolic signalling, and quorum sensing’.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Biofilm formation is a social behaviour that generates favourable conditions for sustained survival in the natural environment. For the Gram‐positive bacterium Bacillus subtilis the process ...involves the differentiation of cell fate within an isogenic population and the production of communal goods that form the biofilm matrix. Here we review recent progress in understanding the regulatory pathways that control biofilm formation and highlight developments in understanding the composition, function and structure of the biofilm matrix.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Ventral tegmental area (VTA) dopamine (DA) neurons have been implicated in reward, aversion, salience, cognition, and several neuropsychiatric disorders. Optogenetic approaches involving transgenic ...Cre-driver mouse lines provide powerful tools for dissecting DA-specific functions. However, the emerging complexity of VTA circuits requires Cre-driver mouse lines that restrict transgene expression to a precisely defined cell population. Because of recent work reporting that VTA DA neurons projecting to the lateral habenula release GABA, but not DA, we performed an extensive anatomical, molecular, and functional characterization of prominent DA transgenic mouse driver lines. We find that transgenes under control of the tyrosine hydroxylase, but not the dopamine transporter, promoter exhibit dramatic non-DA cell-specific expression patterns within and around VTA nuclei. Our results demonstrate how Cre expression in unintentionally targeted cells in transgenic mouse lines can confound the interpretation of supposedly cell-type-specific experiments. This Matters Arising paper is in response to Stamatakis et al. (2013), published in Neuron. See also the Matters Arising Response paper by Stuber et al. (2015), published concurrently with this Matters Arising in Neuron.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Biofilms are communities of microbial cells that underpin diverse processes including sewage bioremediation, plant growth promotion, chronic infections and industrial biofouling. The cells resident ...in the biofilm are encased within a self-produced exopolymeric matrix that commonly comprises lipids, proteins that frequently exhibit amyloid-like properties, eDNA and exopolysaccharides. This matrix fulfils a variety of functions for the community, from providing structural rigidity and protection from the external environment to controlling gene regulation and nutrient adsorption. Critical to the development of novel strategies to control biofilm infections, or the capability to capitalize on the power of biofilm formation for industrial and biotechnological uses, is an in-depth knowledge of the biofilm matrix. This is with respect to the structure of the individual components, the nature of the interactions between the molecules and the three-dimensional spatial organization. We highlight recent advances in the understanding of the structural and functional role that carbohydrates and proteins play within the biofilm matrix to provide three-dimensional architectural integrity and functionality to the biofilm community. We highlight, where relevant, experimental techniques that are allowing the boundaries of our understanding of the biofilm matrix to be extended using Escherichia coli, Staphylococcus aureus, Vibrio cholerae, and Bacillus subtilis as exemplars.
Examining the structure and function of the biofilm extracellular matrix.
Omega-6 (n-6) polyunsaturated fatty acids (PUFA) (e.g., arachidonic acid (AA)) and omega-3 (n-3) PUFA (e.g., eicosapentaenoic acid (EPA)) are precursors to potent lipid mediator signalling molecules, ...termed “eicosanoids,” which have important roles in the regulation of inflammation. In general, eicosanoids derived from n-6 PUFA are proinflammatory while eicosanoids derived from n-3 PUFA are anti-inflammatory. Dietary changes over the past few decades in the intake of n-6 and n-3 PUFA show striking increases in the (n-6) to (n-3) ratio (~15 : 1), which are associated with greater metabolism of the n-6 PUFA compared with n-3 PUFA. Coinciding with this increase in the ratio of (n-6) : (n-3) PUFA are increases in chronic inflammatory diseases such as nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, obesity, inflammatory bowel disease (IBD), rheumatoid arthritis, and Alzheimer's disease (AD). By increasing the ratio of (n-3) : (n-6) PUFA in the Western diet, reductions may be achieved in the incidence of these chronic inflammatory diseases.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
There is a growing body of evidence indicating the potential value of essential oils as control agents against a range of arthropod ectoparasites, particularly lice, mites and ticks. Toxicity has ...been demonstrated following immersion and physical contact with treated surfaces, as well as after exposure to the vapour of these oils; the last of these factors implies that there is a neurotoxic, rather than simply a mechanical, pathway in their mode of action. However, the volatile nature of essential oils suggests that their residual activity is likely to be short‐lived. A possible advantage of essential oils over conventional ectoparasite treatments may refer to their reported ovicidal efficacy, although it is unclear whether this results from neurotoxicity or mechanical suffocation. There are many difficulties in comparing the findings of existing studies of essential oil toxicity. One major issue is the wide variation among batches in the relative concentrations of oil constituents. A second issue concerns the fact that many experimental designs make it difficult to confirm that the effect seen is attributable to the oil; in many cases inappropriate controls mean that the effects of the excipient on mortality cannot be distinguished. Hence, it is important that an excipient‐only control is always included in these bioassays. Furthermore, in direct contact assays, when attempting to identify the toxicity pathway of the essential oil tested, it is important to include a hydrophobic control. Without this, it is impossible to distinguish simple mechanical effects from neurological or other cellular toxicity. The use of essential oils in the control of veterinary ectoparasites is an area which holds considerable potential for the future and research into their use is still at an early stage. More extensive field trials, the standardization of components, the standardization of extraction, the standardization of good experimental design, mammalian toxicology profiling and excipient development, as well as further investigation into the residual activities and shelf‐lives of these oils are all required to allow the full realization of their potential.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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