Most attempts to identify the processes that structure natural communities have focused on conspicuous macroorganisms whereas the processes responsible for structuring microbial communities remain ...relatively unknown. Two main theories explaining these processes have emerged; niche theory, which highlights the importance of deterministic processes, and neutral theory, which focuses on stochastic processes. We examined whether neutral or niche-based mechanisms best explain the composition and structure of communities of a functionally important soil microbe, the arbuscular mycorrhizal (AM) fungi. Using molecular techniques, we surveyed AM fungi from 425 individual plants of 28 plant species along a soil pH gradient. There was evidence that both niche and neutral processes structured this community. Species abundances fitted the zero-sum multinomial distribution and there was evidence of dispersal limitation, both indicators of neutral processes. However, we found stronger support that niche differentiation based on abiotic soil factors, primarily pH, was structuring the AM fungal community. Host plant species affected AM fungal community composition negligibly compared to soil pH. We conclude that although niche partitioning was the primary mechanism regulating the composition and diversity of natural AM fungal communities, these communities are also influenced by stochastic-neutral processes. This study represents one of the most comprehensive investigations of community-level processes acting on soil microbes; revealing a community that although influenced by stochastic processes, still responded in a predictable manner to a major abiotic niche axis, soil pH. The strong response to environmental factors of this community highlights the susceptibility of soil microbes to environmental change.
Understanding the dynamics of rhizosphere microbial communities is essential for predicting future ecosystem function, yet most research focuses on either spatial or temporal processes, ignoring ...combined spatio-temporal effects. Using pyrosequencing, we examined the spatio-temporal dynamics of a functionally important community of rhizosphere microbes, the arbuscular mycorrhizal (AM) fungi. We sampled AM fungi from plant roots growing in a temperate grassland in a spatially explicit manner throughout a year. Ordination analysis of the AM fungal assemblages revealed significant temporal changes in composition and structure. Alpha and beta diversity tended to be negatively correlated with the climate variables temperature and sunshine hours. Higher alpha diversity during colder periods probably reflects more even competitive interactions among AM fungal species under limited carbon availability, a conclusion supported by analysis of beta diversity which highlights how resource limitation may change localized spatial dynamics. Results reveal distinct AM fungal assemblages in winter and summer at this grassland site. A seasonally changing supply of host-plant carbon, reflecting changes in temperature and sunshine hours, may be the driving force in regulating the temporal dynamics of AM fungal communities. Climate change effects on seasonal temperatures may therefore substantially alter future AM fungal community dynamics and ecosystem functioning.
The social amoebas (Dictyostelia) display conditional multicellularity in a wide variety of forms. Despite widespread interest in Dictyostelium discoideum as a model system, almost no molecular data ...exist from the rest of the group. We constructed the first molecular phylogeny of the Dictyostelia with parallel small subunit ribosomal RNA and a-tubulin data sets, and we found that dictyostelid taxonomy requires complete revision. A mapping of characters onto the phylogeny shows that the dominant trend in dictyostelid evolution is increased size and cell type specialization of fruiting structures, with some complex morphologies evolving several times independently. Thus, the latter may be controlled by only a few genes, making their underlying mechanisms relatively easy to unravel.
Wheat yields have plateaued in the UK over the last 25 years, during which time most arable land has been annually cropped continuously with short rotations dominated by cereals. Arable ...intensification has depleted soil organic matter and biology, including mycorrhizas, which are affected by tillage, herbicides, and crop genotype. Here, we test whether winter wheat yields, mycorrhization, and shoot health can be improved simply by adopting less intensive tillage and adding commercial mycorrhizal inoculum to long-term arable fields, or if 3-year grass-clover leys followed direct drilling is more effective for biological regeneration of soil with reduced N fertiliser. We report a trial of mycorrhization, ear pathology, and yield performance of the parents and four double haploid lines from the Avalon x Cadenza winter wheat population in a long-term arable field that is divided into replicated treatment plots. These plots comprised wheat lines grown using ploughing or disc cultivation for 3 years, half of which received annual additions of commercial arbuscular mycorrhizal (AM) inoculum, compared to 3-year mown grass-clover ley plots treated with glyphosate and direct-drilled. All plots annually received 35 kg of N ha
−1
fertiliser without fungicides. The wheat lines did not differ in mycorrhization, which averaged only 34% and 40% of root length colonised (RLC) in the ploughed and disc-cultivated plots, respectively, and decreased with inoculation. In the ley, RLC increased to 52%. Two wheat lines were very susceptible to a sooty ear mould, which was lowest in the ley, and highest with disc cultivation. AM inoculation reduced ear infections by >50% in the susceptible lines. In the ley, yields ranged from 7.2 to 8.3 t ha
−1
, achieving 92 to 106% of UK average wheat yield in 2018 (7.8 t ha
−1
) but using only 25% of average N fertiliser. Yields with ploughing and disc cultivation averaged only 3.9 and 3.4 t ha
−1
, respectively, with AM inoculum reducing yields from 4.3 to 3.5 t ha
−1
in ploughed plots, with no effect of disc cultivation. The findings reveal multiple benefits of reintegrating legume-rich leys into arable rotations as part of a strategy to regenerate soil quality and wheat crop health, reduce dependence on nitrogen fertilisers, enhance mycorrhization, and achieve good yields.
Voltage-gated Na+ channels (VGSCs) mediate action potential firing and regulate adhesion and migration in excitable cells. VGSCs are also expressed in cancer cells. In metastatic breast cancer (BCa) ...cells, the Nav1.5 α subunit potentiates migration and invasion. In addition, the VGSC-inhibiting antiepileptic drug phenytoin inhibits tumor growth and metastasis. However, the functional activity of Nav1.5 and its specific contribution to tumor progression in vivo has not been delineated. Here, we found that Nav1.5 is up-regulated at the protein level in BCa compared with matched normal breast tissue. Na+ current, reversibly blocked by tetrodotoxin, was retained in cancer cells in tumor tissue slices, thus directly confirming functional VGSC activity in vivo. Stable down-regulation of Nav1.5 expression significantly reduced tumor growth, local invasion into surrounding tissue, and metastasis to liver, lungs and spleen in an orthotopic BCa model. Nav1.5 down-regulation had no effect on cell proliferation or angiogenesis within the in tumors, but increased apoptosis. In vitro, Nav1.5 down-regulation altered cell morphology and reduced CD44 expression, suggesting that VGSC activity may regulate cellular invasion via the CD44-src-cortactin signaling axis. We conclude that Nav1.5 is functionally active in cancer cells in breast tumors, enhancing growth and metastatic dissemination. These findings support the notion that compounds targeting Nav1.5 may be useful for reducing metastasis.
Ion channels can regulate the plasma membrane potential (Vm) and cell migration as a result of altered ion flux. However, the mechanism by which Vm regulates motility remains unclear. Here, we show ...that the Nav1.5 sodium channel carries persistent inward Na+ current which depolarizes the resting Vm at the timescale of minutes. This Nav1.5‐dependent Vm depolarization increases Rac1 colocalization with phosphatidylserine, to which it is anchored at the leading edge of migrating cells, promoting Rac1 activation. A genetically encoded FRET biosensor of Rac1 activation shows that depolarization‐induced Rac1 activation results in acquisition of a motile phenotype. By identifying Nav1.5‐mediated Vm depolarization as a regulator of Rac1 activation, we link ionic and electrical signaling at the plasma membrane to small GTPase‐dependent cytoskeletal reorganization and cellular migration. We uncover a novel and unexpected mechanism for Rac1 activation, which fine tunes cell migration in response to ionic and/or electric field changes in the local microenvironment.
Ion channels can regulate the plasma membrane potential (Vm) and cell migration as a result of altered ion flux. We show that the Nav1.5 sodium channel depolarizes the resting Vm, promoting Rac1 activation at the leading edge of migrating cells. By identifying Nav1.5‐mediated Vm depolarization as a regulator of Rac1 activation, we link ionic and electrical signaling at the plasma membrane to small GTPase‐dependent cytoskeletal reorganization and cellular migration.
Voltage-gated Na(+) channels (VGSCs) are heteromeric protein complexes containing pore-forming α subunits and smaller, non-pore-forming β subunits. VGSCs are classically expressed in electrically ...excitable cells, e.g. neurons. VGSCs are also expressed in tumour cells, including breast cancer (BCa) cells, where they enhance cellular migration and invasion. However, despite extensive work defining in detail the molecular mechanisms underlying the expression of VGSCs and their pro-invasive role in cancer cells, there has been a notable lack of clinically relevant in vivo data exploring their value as potential therapeutic targets.
We have previously reported that the VGSC-blocking antiepileptic drug phenytoin inhibits the migration and invasion of metastatic MDA-MB-231 cells in vitro. The purpose of the present study was to establish whether VGSCs might be viable therapeutic targets by testing the effect of phenytoin on tumour growth and metastasis in vivo. We found that expression of Nav1.5, previously detected in MDA-MB-231 cells in vitro, was retained on cells in orthotopic xenografts. Treatment with phenytoin, at a dose equivalent to that used to treat epilepsy (60 mg/kg; daily), significantly reduced tumour growth, without affecting animal weight. Phenytoin also reduced cancer cell proliferation in vivo and invasion into surrounding mammary tissue. Finally, phenytoin significantly reduced metastasis to the liver, lungs and spleen.
This is the first study showing that phenytoin reduces breast tumour growth and metastasis in vivo. We propose that pharmacologically targeting VGSCs, by repurposing antiepileptic or antiarrhythmic drugs, should be further studied as a potentially novel anti-cancer therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hybrids between species are often sterile or inviable. Hybrid unfitness usually evolves first in the heterogametic sex—a pattern known as Haldane's rule. The genetics of Haldane's rule have been ...extensively studied in species where the male is the heterogametic (XX/XY) sex, but its basis in taxa where the female is heterogametic (ZW/ZZ), such as Lepidoptera and birds, is largely unknown. Here, we analyse a new case of female hybrid sterility between geographic subspecies of Heliconius pardalinus. The two subspecies mate freely in captivity, but female F1 hybrids in both directions of cross are sterile. Sterility is due to arrested development of oocytes after they become differentiated from nurse cells, but before yolk deposition. We backcrossed fertile male F1 hybrids to parental females and mapped quantitative trait loci (QTLs) for female sterility. We also identified genes differentially expressed in the ovary as a function of oocyte development. The Z chromosome has a major effect, similar to the ‘large X effect’ in Drosophila, with strong epistatic interactions between loci at either end of the Z chromosome, and between the Z chromosome and autosomal loci on chromosomes 8 and 20. By intersecting the list of genes within these QTLs with those differentially expressed in sterile and fertile hybrids, we identified three candidate genes with relevant phenotypes. This study is the first to characterize hybrid sterility using genome mapping in the Lepidoptera and shows that it is produced by multiple complex epistatic interactions often involving the sex chromosome, as predicted by the dominance theory of Haldane's rule.
Voltage‐gated Na+ channels (VGSCs) are heteromeric proteins composed of pore‐forming α subunits and smaller β subunits. The β subunits are multifunctional channel modulators and are members of the ...immunoglobulin superfamily of cell adhesion molecules (CAMs). β1, encoded by SCN1B, is best characterized in the central nervous system (CNS), where it plays a critical role in regulating electrical excitability, neurite outgrowth and migration during development. β1 is also expressed in breast cancer (BCa) cell lines, where it regulates adhesion and migration in vitro. In the present study, we found that SCN1B mRNA/β1 protein were up‐regulated in BCa specimens, compared with normal breast tissue. β1 upregulation substantially increased tumour growth and metastasis in a xenograft model of BCa. β1 over‐expression also increased vascularization and reduced apoptosis in the primary tumours, and β1 over‐expressing tumour cells had an elongate morphology. In vitro, β1 potentiated outgrowth of processes from BCa cells co‐cultured with fibroblasts, via trans‐homophilic adhesion. β1‐mediated process outgrowth in BCa cells required the presence and activity of fyn kinase, and Na+ current, thus replicating the mechanism by which β1 regulates neurite outgrowth in CNS neurons. We conclude that when present in breast tumours, β1 enhances pathological growth and cellular dissemination. This study is the first demonstration of a functional role for β1 in tumour growth and metastasis in vivo. We propose that β1 warrants further study as a potential biomarker and targeting β1‐mediated adhesion interactions may have value as a novel anti‐cancer therapy.
What's New?
Voltage‐gated sodium channels are best known to regulate electrical excitability and neuronal migration, but recently their β1 subunits were found expressed in breast cancer cell lines where they regulate cellular adhesion and migration. Here, the authors demonstrate that β1 subunits are expressed in clinical breast cancer specimens. In coculture experiments, β1 enhanced outgrowth of neurite‐like processes on cancer cells and in in vivo models, accelerated tumor growth and metastasis. These data underscore the new role of voltage‐gated sodium channel β1 subunits as potential biomarkers and therapeutic targets in breast cancer.
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