The development of early pioneer neurons in the annelid Malacoceros fuliginosus

Background Nervous system development is an interplay of many processes: the formation of individual neurons, which depends on whole-body and local patterning processes, and the coordinated growth of neurites and synapse formation. While knowledge of neural patterning in several animal groups is increasing, data on pioneer neurons that create the early axonal scaffold are scarce. Here we studied the first steps of nervous system development in the annelid Malacoceros fuliginosus. Results We performed a dense expression profiling of a broad set of neural genes. We found that SoxB expression begins at 4 h postfertilization, and shortly later, the neuronal progenitors can be identified at the anterior and the posterior pole by the transient and dynamic expression of proneural genes. At 9 hpf, the first neuronal cells start differentiating, and we provide a detailed description of axonal outgrowth of the pioneer neurons that create the primary neuronal scaffold. Tracing back the clonal origin of the ventral nerve cord pioneer neuron revealed that it is a descendant of the blastomere 2d (2d221), which after 7 cleavages starts expressing Neurogenin, Acheate-Scute and NeuroD. Conclusions We propose that an anterior and posterior origin of the nervous system is ancestral in annelids. We suggest that closer examination of the first pioneer neurons will be valuable in better understanding of nervous system development in spirally cleaving animals, to determine the potential role of cell-intrinsic properties in neuronal specification and to resolve the evolution of nervous systems.publishedVersio

原著

摘出ラット上頸交感神経節を用いて,刺激頻度と薬物作用との関係を検討し,次の結果を得た。1.Hexamethonium,d-Tubocurarine,PhysostigmineおよびParaoxon作用下では,神経節伝達抑制作用が低頻度刺激よりも高頻度刺激により増強された。このような薬物効果をType Aとした。2.Adrenaline(Adr.),Nor-Adrenaline(Nor-Adr),MgCl_2,MnCl_2ならびにCa^-deficit Ringer(0.1〜0.4mM CaCl_2)では,低頻度刺激時にみられた抑制効果が高頻度刺激下で著しく回復され,この効果をType Bとした。3.ProcaineおよびPropranolol作用下の抑制効果は,刺激頻度の多少にほとんど影響されなかった。この効果をType Cとした。4.Adr.,Nor-Adr.のType B効果はPhentolamineにより拮抗されたが,ほとんどPropranololの影響をうけなかった。MgCl_2,MnCl_2およびCa^#-deficit効果は,α-,およびβ-効果遮断薬により影響されなかった。5.Type B作用群薬物の効果は,high Ca^-Ringer(9mM CaCl_2)で消失され,low Ca^-Ringer液中で増強された。6.Ringer液中のNa^+およびK^+イオンの増減ならびにOuabain(10μM)はType B効果に影響を与えなかった。7.Sucrose-gap法による実験で,Type B作用群薬物は単発刺激による神経節のspike potentialを消失し,比較的大きなsynaptic potentialを生じた。このsynaptic potentialは,300msec以下の刺激間隔で与えた2発刺激により容易にspike potentialに発展した。また高頻度刺激によっても漸次増大するspike potentialが容易に発生した。8.Type B作用群薬物の作用機構についてとくに神経終末からの伝達物質遊離抑制面から考察した。The relationship between the rate of stimulation and effects of drugs on the superior cervical ganglion was investigated. Under the effect of hexamethonium, d-tubocu-rarine, physostigmine or paraoxon, ganglionic transmission was blocked more effectively with higher rate of stimulation than lower rate of stimulation (Type A drugs). Under the effect of adrenaline, noradrenaline, MgCl_2, MnCl_2 or Ca^-deficit Ringer (0.1-0.4mM CaCl_2,) solution, ganglionic transmission was depressed with lower rate of stimulation, but it was restored with higher rate of stimulation (Type B drugs). The inhibitory effect of procaine and propranolol on the ganglionic transmission was not affected by frequency change in transmission (Type C drugs). The effect of adrenaline or noradrenaline, those belong to the type B group, was blocked by phentolamine but not by propranolol. Phentolamine and propranolol had no effect on the action of MgCl_2, MnCl_2 and Ca^-deficit Ringer solution. The effect of the type B group drugs was decreased in Ringer solution containing higher concentration of Ca^ and augmented in Ringer solution containing lower concentration of Ca^. The effect of the type B group drugs was not affected by increasing or decreasing of the concentration of Na^+ or K^+ in Ringer solution. Ouabain (10μM) had no effect on the action of the type B drugs. By means of the sucrose-gap method, the spike potentials evoked by applying single stimulation were transferred to the synaptic potentials under the influence of the type B drugs. When the synaptic potential was evoked by the doubleshock stimuli of an interval shorter than 300 msec, the synaptic potential easily devoloped to the spike potential. In this work, the mechanism of action of the type B drugs was discussed on the standpoint of the depressed transmitter release

Early divergence, broad distribution, and high diversity of animal chitin synthases

Even though chitin is one of themost abundant biopolymers in nature, current knowledge on chitin formation is largely based only on data from fungi and insects. This study reveals unanticipated broad taxonomic distribution and extensive diversification of chitin synthases (CSs) in Metazoa, shedding newlight on the relevance of chitin in animals and suggesting unforeseen complexity of chitin synthesis in many groups. We uncovered robust orthologs to insect type CSs in several representatives of deuterostomes, which generally are not thought to possess chitin. This suggests a broader distribution and function of chitin in this branch of the animal kingdom. We characterize a new CS type present not only in basal metazoans such as sponges and cnidarians but also in several bilaterian representatives. Themost extensive diversification of CSs took place during emergence of lophotrochozoans, the third large group of protostomes next to arthropods and nematodes, resulting in coexistence of up to ten CS paralogs inmolluscs. Independent fusion to different kinds of myosinmotor domains in fungi and lophotrochozoans points toward high relevance of CS interaction with the cytoskeleton for fine-tuned chitin secretion. Given the fundamental role that chitin plays in themorphology of many animals, the here presented CS diversification revealsmany evolutionary complexities. Our findings strongly suggest a very broad andmultifarious occurrence of chitin and question an ancestral role as cuticular component. The molecular mechanisms underlying regulation of animal chitin synthesis are most likely far more complex and diverse than existing data from insects suggest

Pathfinder first light: alignment, calibration, and commissioning of the LINC-NIRVANA ground-layer adaptive optics subsystem

We present descriptions of the alignment and calibration tests of the Pathfinder, which achieved first light during our 2013 commissioning campaign at the LBT. The full LINC-NIRVANA instrument is a Fizeau interferometric imager with fringe tracking and 2-layer natural guide star multi-conjugate adaptive optics (MCAO) systems on each eye of the LBT. The MCAO correction for each side is achieved using a ground layer wavefront sensor that drives the LBT adaptive secondary mirror and a mid-high layer wavefront sensor that drives a Xinetics 349 actuator DM conjugated to an altitude of 7.1 km. When the LINC-NIRVANA MCAO system is commissioned, it will be one of only two such systems on an 8-meter telescope and the only such system in the northern hemisphere. In order to mitigate risk, we take a modular approach to commissioning by decoupling and testing the LINC-NIRVANA subsystems individually. The Pathfinder is the ground-layer wavefront sensor for the DX eye of the LBT. It uses 12 pyramid wavefront sensors to optically co-add light from natural guide stars in order to make four pupil images that sense ground layer turbulence. Pathfinder is now the first LINC-NIRVANA subsystem to be fully integrated with the telescope and commissioned on sky. Our 2013 commissioning campaign consisted of 7 runs at the LBT with the tasks of assembly, integration and communication with the LBT telescope control system, alignment to the telescope optical axis, off-sky closed loop AO calibration, and finally closed loop on-sky AO. We present the programmatics of this campaign, along with the novel designs of our alignment scheme and our off-sky calibration test, which lead to the Pathfinder's first on-sky closed loop images

Effects of stigmatizing media coverage on stigma measures, self-esteem, and affectivity in persons with depression – an experimental controlled trial

Background: Stigmatization of people with mental illness is still a significant problem even in Western society. Media is an important vector for public messaging that may lead to stigma (and potentially counteract it). There is an ongoing debate about the impact of news with potentially stigmatizing content on people with depression. This experimental study aimed at investigating the direct effects media reporting could have on people with depression, namely, higher levels of stigma attitudes and negative affect, as well as lower levels of self-esteem and positive affect. Methods: Experimental study; target sample size n = 180 patients; eligibility criteria: clinical diagnosis of depressive episode or dysthymia, aged 18–70 years, sufficient cognitive abilities and German language skills; exclusion criteria: acute psychotic, manic or hypomanic episode, addiction symptoms, or suicidal ideation; parallel assignment to one of three arms (each n = 60): watching a short film about a negative event relating to depression (experimental group), about a negative event without relation to depression (control group 1), or about a neutral event relating to depression (control group 2); primary outcomes: degrees of stigma attitudes (stereotype awareness, stereotype agreement, self-concurrence, and self-stigmatization); secondary outcomes: degrees of self-esteem, positive and negative affect; statistical analyses: general linear models with repeated-measures; one-way ANOVAs of the change in scores, followed by Bonferroni-adjusted pairwise comparisons; IBM SPSS Statistics 24.0. Results: Significant group × time interactions in stereotype agreement (medium effect: η = 0.10) and negative affect (large effect: η = 0.26); the level of stereotype agreement increased significantly more in the experimental group than in control groups 1 and 2. The level of negative affect increased significantly more in the experimental group and in control group 1 than in control group 2. All other interaction effects were non-significant. Conclusion: The present study allows statements about the direct effects of potentially stigmatizing media reporting on carriers of the stigmatized attribute, i.e., depression: Even single film presentations of familiar events that contain potentially stigmatizing content have an impact on stereotype agreement and negative affect. The impact of long-term exposure and change in other stigma-measures require a deeper understanding of stigma-processes. Potential explanations and implications for practice and future research are discussed. Trial registration: Deutsche Register Klinischer Studien, Trial registration: DRKS00011855. Registered 23 June 2017, retrospectively registered; for details see Additional file 1

Economic System and Welfare Regime Dynamics in Japan since the Early 2000s-The Case of Occupational Pensions

This article discusses significant changes of Japanese occupational pensions since the early 2000s. Our analysis shows that these schemes have been key components of policies to promote private welfare provision and have been highly compatible with human capital investment strategies that are based on long-term employment relationships of regular workers. However, since the 1990s, occupational pensions have come under increased pressure due to underfunding problems caused by depressed stock markets and changes in accounting standards that made these underfunding problems apparent. In response to these challenges, Japanese companies have restructured their occupational pension arrangements. The nature of these efforts can be explained with reference to existing institutional complementarities with the economic system on the one hand and changes in the cost–benefit calculations of employers, employees and the civil service on the other hand. Whereas complementarities, especially with human resource management factors, have ultimately defined the limits of these changes, an actor-centered analysis helps to explain the particular nature of changes within these boundaries

Mutations in the J domain of DNAJB6 cause dominant distal myopathy

Eight patients from five families with undiagnosed dominant distal myopathy underwent clinical, neurophysiological and muscle biopsy examinations. Molecular genetic studies were performed using targeted sequencing of all known myopathy genes followed by segregation of the identified mutations in the affected families using Sanger sequencing. Two novel mutations in DNAJB6 J domain, c.149C>T (p.A50V) and c.161A>C (p.E54A), were identified as the cause of disease. The muscle involvement with p.A50V was distal calf-predominant, and the p.E54A was more proximo-distal. Histological findings were similar to those previously reported in DNAJB6 myopathy. In line with reported pathogenic mutations in the glycine/phenylalanine (G/F) domain of DNAJB6, both the novel mutations showed reduced anti-aggregation capacity by filter trap assay and TDP-43 disaggregation assays. Modeling of the protein showed close proximity of the mutated residues with the G/F domain. Myopathy-causing mutations in DNAJB6 are not only located in the G/F domain, but also in the J domain. The identified mutations in the J domain cause dominant distal and proximo-distal myopathy, confirming that mutations in DNAJB6 should be considered in distal myopathy cases.Peer reviewe

Interspecies conservation of organisation and function between nonhomologous regional centromeres

International audienceDespite the conserved essential function of centromeres, centromeric DNA itself is not conserved. The histone-H3 variant, CENP-A, is the epigenetic mark that specifies centromere identity. Paradoxically, CENP-A normally assembles on particular sequences at specific genomic locations. To gain insight into the specification of complex centromeres, here we take an evolutionary approach, fully assembling genomes and centromeres of related fission yeasts. Centromere domain organization, but not sequence, is conserved between Schizosaccharomyces pombe, S. octosporus and S. cryophilus with a central CENP-ACnp1 domain flanked by heterochromatic outer-repeat regions. Conserved syntenic clusters of tRNA genes and 5S rRNA genes occur across the centromeres of S. octosporus and S. cryophilus, suggesting conserved function. Interestingly, nonhomologous centromere central-core sequences from S. octosporus and S. cryophilus are recognized in S. pombe, resulting in cross-species establishment of CENP-ACnp1 chromatin and functional kinetochores. Therefore, despite the lack of sequence conservation, Schizosaccharomyces centromere DNA possesses intrinsic conserved properties that promote assembly of CENP-A chromatin

Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78

The pre- and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll-like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up-regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9−/− knockout mice. The asthma-preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78–treated TLR2/3/4/7/9−/− homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78–exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny