Context. Double-double radio galaxies (DDRGs) represent a short but unique phase in the life-cycle of some of the most powerful radio-loud active galactic nuclei (RLAGN). These galaxies display ...large-scale remnant radio plasma in the intergalactic medium left behind by a past episode of active galactic nuclei (AGN) activity, and meanwhile, the radio jets have restarted in a new episode. The knowledge of what causes the jets to switch off and restart is crucial to our understanding of galaxy evolution, while it is important to know if DDRGs form a host galaxy dichotomy relative to RLAGN. Aims. The sensitivity and field of view of LOFAR enables the observation of DDRGs on a population basis rather than single-source observations. Using statistical comparisons with a control sample of RLAGN, we may obtain insights into the nature of DDRGs in the context of their host galaxies, where physical differences in their hosts compared to RLAGN as a population may allow us to infer the conditions that drive restarting jets. Methods. We utilised the LOFAR Two-Metre Sky Survey (LoTSS) DR1, using a visual identification method to compile a sample of morphologically selected candidate DDRGs, showing two pairs of radio lobes. To confirm the restarted nature in each of the candidate sources, we obtained follow-up observations with the Karl. G. Jansky Very Large Array (VLA) at higher resolution to observe the inner lobes or restarted jets, the confirmation of which created a robust sample of 33 DDRGs. We created a comparison sample of 777 RLAGN, matching the luminosity distribution of the DDRG sample, and compared the optical and infrared magnitudes and colours of their host galaxies. Results. We find that there is no statistically significant difference in the brightness of the host galaxies between double-doubles and single-cycle RLAGN. The DDRG and RLAGN samples also have similar distributions in WISE mid-infrared colours, indicating similar ages of stellar populations and dust levels in the hosts of DDRGs. We conclude that DDRGs and “normal” RLAGN are hosted by galaxies of the same type, and that DDRG activity is simply a normal part of the life cycle of RLAGN. Restarted jets, particularly for the class of low-excitation radio galaxies, rather than being a product of a particular event in the life of a host galaxy, must instead be caused by smaller scale changes, such as in the accretion system surrounding the black hole.
Fecal coliforms and enterococci are indicator organisms used worldwide to monitor water quality. These bacteria are used in microbial source tracking (MST) studies, which attempt to assess the ...contribution of various host species to fecal pollution in water. Ideally, all strains of a given indicator organism (IO) would experience equal persistence (maintenance of culturable populations) in water; however, some strains may have comparatively extended persistence outside the host, while others may persist very poorly in environmental waters. Assessment of the relative contribution of host species to fecal pollution would be confounded by differential persistence of strains. Here, freshwater and saltwater mesocosms, including sediments, were inoculated with dog feces, sewage, or contaminated soil and were incubated under conditions that included natural stressors such as microbial predators, radiation, and temperature fluctuations. Persistence of IOs was measured by decay rates (change in culturable counts over time). Decay rates were influenced by IO, inoculum, water type, sediment versus water column location, and Escherichia coli strain. Fecal coliform decay rates were significantly lower than those of enterococci in freshwater but were not significantly different in saltwater. IO persistence according to mesocosm treatment followed the trend: contaminated soil > wastewater > dog feces. E. coli ribotyping demonstrated that certain strains were more persistent than others in freshwater mesocosms, and the distribution of ribotypes sampled from mesocosm waters was dissimilar from the distribution in fecal material. These results have implications for the accuracy of MST methods, modeling of microbial populations in water, and efficacy of regulatory standards for protection of water quality.
Pathogenic human viruses cause over half of gastroenteritis cases associated with recreational water use worldwide. They are relatively difficult to concentrate from environmental waters due to ...typically low concentrations and their small size. Although rapid enumeration of viruses by quantitative PCR (qPCR) has the potential to greatly improve water quality analysis and risk assessment, the upstream steps of capturing and recovering viruses from environmental water sources along with removing PCR inhibitors from extracted nucleic acids remain formidable barriers to routine use. Here, we compared the efficiency of virus recovery for three rapid methods of concentrating two microbial source tracking (MST) viral markers human adenoviruses (HAdVs) and polyomaviruses (HPyVs) from one liter tap water and river water samples on HA membranes (90 mm in diameter). Samples were spiked with raw sewage, and viral adsorption to membranes was promoted by acidification (method A) or addition of MgCl2 (methods B and C). Viral nucleic acid was extracted directly from membranes (method A), or viruses were eluted with NaOH and concentrated by centrifugal ultrafiltration (methods B and C). No inhibition of qPCR was observed for samples processed by method A, but inhibition occurred in river samples processed by B and C. Recovery efficiencies of HAdVs and HPyVs were ∼10-fold greater for method A (31 to 78%) than for methods B and C (2.4 to 12%). Further analysis of membranes from method B revealed that the majority of viruses were not eluted from the membrane, resulting in poor recovery. The modification of the originally published method A to include a larger diameter membrane and a nucleic acid extraction kit that could accommodate the membrane resulted in a rapid virus concentration method with good recovery and lack of inhibitory compounds. The frequently used strategy of viral absorption with added cations (Mg(2+)) and elution with acid were inefficient and more prone to inhibition, and will result in underestimation of the prevalence and concentrations of HAdVs and HPyVs markers in environmental waters.
Context. The phase of radio galaxy evolution after the jets have switched off, often referred to as the remnant phase, is poorly understood and very few sources in this phase are known. Aims. In this ...work we present an extensive search for remnant radio galaxies in the Lockman Hole, a well-studied extragalactic field. We create mock catalogues of low-power radio galaxies based on Monte Carlo simulations to derive first-order predictions of the fraction of remnants in radio flux limited samples for comparison with our Lockman-Hole sample. Methods. Our search for remnant radio galaxies is based on LOFAR observations at 150 MHz combined with public survey data at higher frequencies. To enhance the selection process, and obtain a more complete picture of the remnant population, we use spectral criteria such as ultra-steep spectral index and high spectral curvature, and morphologre biased toward tinuum: galaxie ical criteria such as low radio core prominence and relaxed shapes to identify candidate remnant radio galaxies. Mock catalogues of radio galaxies are created based on existing spectral and dynamical evolution models combined with observed source properties. Results. We have identified 23 candidate remnant radio galaxies which cover a variety of morphologies and spectral characteristics. We suggest that these different properties are related to different stages of the remnant evolution. We find that ultra-steep spectrum remnants represent only a fraction of our remnant sample suggesting a very rapid luminosity evolution of the radio plasma. Results from mock catalogues demonstrate the importance of dynamical evolution in the remnant phase of low-power radio galaxies to obtain fractions of remnant sources consistent with our observations. Moreover, these results confirm that ultra-steep spectrum remnants represent only a small subset of the entire population (~50%) when frequencies higher than 1400 MHz are not included in the selection process, and that they are biased towards old ages.
We report the first chemical syntheses of both (−)-majucin and (−)-jiadifenoxolane A via 10 net oxidations from the ubiquitous terpene (+)-cedrol. Additionally, this approach allows for access to ...other majucin-type sesquiterpenes, like (−)-jiadifenolide, (−)-jiadifenin, and (−)-(1R,10S)-2-oxo-3,4-dehydroxyneomajucin (ODNM) along the synthetic pathway. Site-selective aliphatic C(sp3)-H bond oxidation reactions serve as the cornerstone of this work which offers access to highly oxidized natural products from an abundant and renewable terpene feedstock.
Key points
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The excitatory afferents to the striatum from the cortex and thalamus are critical in the expression of basal ganglia function.
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Thalamostriatal afferents are markedly heterogeneous ...and arise in different subnuclei of the intralaminar thalamus.
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We used an optogenetic approach, to isolate and selectively activate thalamostriatal afferents arising in the central lateral or parafascicular thalamic nuclei, and to study the properties of their synapses with principal striatal neurons, the medium‐spiny neurons.
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Thalamostriatal synapses differ in many aspects and our data suggest that inputs from the central lateral nucleus are efficient drivers of medium‐spiny neuron action potential firing, whereas inputs from the parafascicular nucleus are likely to be modulatory.
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These results suggest distinct roles for thalamostriatal inputs from different subnuclei of the thalamus and will help us understand how the striatal circuit operates in health and disease.
To understand the principles of operation of the striatum it is critical to elucidate the properties of the main excitatory inputs from cortex and thalamus, as well as their ability to activate the main neurons of the striatum, the medium spiny neurons (MSNs). As the thalamostriatal projection is heterogeneous, we set out to isolate and study the thalamic afferent inputs to MSNs using small localized injections of adeno‐associated virus carrying fusion genes for channelrhodopsin‐2 and YFP, in either the rostral or caudal regions of the intralaminar thalamic nuclei (i.e. the central lateral or parafascicular nucleus). This enabled optical activation of specific thalamic afferents combined with whole‐cell, patch‐clamp recordings of MSNs and electrical stimulation of cortical afferents, in adult mice. We found that thalamostriatal synapses differ significantly in their peak amplitude responses, short‐term dynamics and expression of ionotropic glutamate receptor subtypes. Our results suggest that central lateral synapses are most efficient in driving MSNs to depolarization, particularly those of the direct pathway, as they exhibit large amplitude responses, short‐term facilitation and predominantly express postsynaptic AMPA receptors. In contrast, parafascicular synapses exhibit small amplitude responses, short‐term depression and predominantly express postsynaptic NMDA receptors, suggesting a modulatory role, e.g. facilitating Ca2+‐dependent processes. Indeed, pairing parafascicular, but not central lateral, presynaptic stimulation with action potentials in MSNs, leads to NMDA receptor‐ and Ca2+‐dependent long‐term depression at these synapses. We conclude that the main excitatory thalamostriatal afferents differ in many of their characteristics and suggest that they each contribute differentially to striatal information processing.
Nucleosome positioning is important for neurodevelopment, and genes mediating chromatin remodelling are strongly associated with human neurodevelopmental disorders. To investigate changes in ...nucleosome positioning during neural differentiation, we generate genome‐wide nucleosome maps from an undifferentiated human‐induced pluripotent stem cell (hiPSC) line and after its differentiation to the neural progenitor cell (NPC) stage. We find that nearly 3% of nucleosomes are highly positioned in NPC, but significantly, there are eightfold fewer positioned nucleosomes in pluripotent cells, indicating increased positioning during cell differentiation. Positioned nucleosomes do not strongly correlate with active chromatin marks or gene transcription. Unexpectedly, we find a small population of nucleosomes that occupy similar positions in pluripotent and neural progenitor cells and are found at binding sites of the key gene regulators NRSF/REST and CTCF. Remarkably, the presence of these nucleosomes appears to be independent of the associated regulatory complexes. Together, these results present a scenario in human cells, where positioned nucleosomes are sparse and dynamic, but may act to alter gene expression at a distance via the structural conformation at sites of chromatin regulation.
Synopsis
Repositioning of nucleosomes occurs as human iPSC develop into neural progenitor cells, but a small number of nucleosome arrays remain in place at regulatory sites that control long‐range chromatin organisation.
An 8‐fold increase and re‐distribution of positioned nucleosomes occurs during human iPSC neural differentiation.
No correlation is observed between positioned nucleosomes and gene activity at the genome‐wide level.
Positioned nucleosomes are retained at NRSF/REST and CTCF binding sites during cell differentiation, and in the absence of bound regulatory complexes.
Repositioning of nucleosomes occurs as human iPSC develop into neural progenitor cells, but a small number of nucleosome arrays remain in place at regulatory sites that control long‐range chromatin organisation.
Major programs in psychiatric genetics have identified >150 risk loci for psychiatric disorders. These loci converge on a small number of functional pathways, which span conventional diagnostic ...criteria, suggesting a partly common biology underlying schizophrenia, autism and other psychiatric disorders. Nevertheless, the cellular phenotypes that capture the fundamental features of psychiatric disorders have not yet been determined. Recent advances in genetics and stem cell biology offer new prospects for cell-based modeling of psychiatric disorders. The advent of cell reprogramming and induced pluripotent stem cells (iPSC) provides an opportunity to translate genetic findings into patient-specific in vitro models. iPSC technology is less than a decade old but holds great promise for bridging the gaps between patients, genetics and biology. Despite many obvious advantages, iPSC studies still present multiple challenges. In this expert review, we critically review the challenges for modeling of psychiatric disorders, potential solutions and how iPSC technology can be used to develop an analytical framework for the evaluation and therapeutic manipulation of fundamental disease processes.