The two major lineages of classical dendritic cells (cDCs) express and require either IRF8 or IRF4 transcription factors for their development and function. IRF8-dependent cDCs promote anti-viral and ...T-helper 1 (Th1) cell responses, whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4 (Klf4) is required in IRF4-expressing cDCs to promote Th2, but not Th17, cell responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA) immunization, and house dust mite (HDM) challenge without affecting cytotoxic T lymphocyte (CTL), Th1 cell, or Th17 cell responses to herpes simplex virus, Toxoplasma gondii, and Citrobacter rodentium infections. Further, Klf4 deletion reduced IRF4 expression in pre-cDCs and resulted in selective loss of IRF4-expressing cDCs subsets in several tissues. These results indicate that Klf4 guides a transcriptional program promoting IRF4-expressing cDCs heterogeneity.
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•Klf4 is required for the development of a subset of IRF4-expressing cDCs•Klf4 deletion results in reduced pre-cDCs•A specific Klf4-dependent subset can be identified in several tissues•Klf4fl/flItgax-cre mice have selectively impaired Th2 cell immunity
The IRF4-expressing cDCs subset is highly heterogeneous and has been implicated in priming Th17, as well as Th2 cell immunity. Murphy and colleagues dissect this heterogeneity showing a developmental requirement for Klf4 on specific subsets across several tissues. Moreover, Klf4 guides a transcriptional program necessary for Th2 cell immunity.
MALDI imaging requires careful sample preparation to obtain reliable, high-quality images of small molecules, peptides, lipids, and proteins across tissue sections. Poor crystal formation, ...delocalization of analytes, and inadequate tissue adherence can affect the quality, reliability, and spatial resolution of MALDI images. We report a comparison of tissue mounting and washing methods that resulted in an optimized method using conductive carbon substrates that avoids thaw mounting or washing steps, minimizes protein delocalization, and prevents tissue detachment from the target surface. Application of this method to image ocular lens proteins of small vertebrate eyes demonstrates the improved methodology for imaging abundant crystallin protein products. This method was demonstrated for tissue sections from rat, mouse, and zebrafish lenses resulting in good-quality MALDI images with little to no delocalization. The images indicate, for the first time in mouse and zebrafish, discrete localization of crystallin protein degradation products resulting in concentric rings of distinct protein contents that may be responsible for the refractive index gradient of vertebrate lenses.
Males of most species are more aggressive than females, but the neural mechanisms underlying this dimorphism are not clear. Here, we identify a neuron and a gene that control the higher level of ...aggression characteristic of Drosophila melanogaster males. Males, but not females, contain a small cluster of FruM+ neurons that express the neuropeptide tachykinin (Tk). Activation and silencing of these neurons increased and decreased, respectively, intermale aggression without affecting male-female courtship behavior. Mutations in both Tk and a candidate receptor, Takr86C, suppressed the effect of neuronal activation, whereas overexpression of Tk potentiated it. Tk neuron activation overcame reduced aggressiveness caused by eliminating a variety of sensory or contextual cues, suggesting that it promotes aggressive arousal or motivation. Tachykinin/Substance P has been implicated in aggression in mammals, including humans. Thus, the higher aggressiveness of Drosophila males reflects the sexually dimorphic expression of a neuropeptide that controls agonistic behaviors across phylogeny.
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•A single class of neurons is identified that promotes aggression in male flies•These neurons are FruM+ and sexually dimorphic but do not control courtship•These neurons promote aggressive arousal via release of a neuropeptide, DTK•Tk is a neuropeptide gene that controls aggression in both flies and mammals
A small group of Drosophila neurons that are detectable in male, but not female, brains promote high levels of aggression via the release of a neuropeptide, Tachykinin. Homologs of this neuropeptide are implicated in mammalian aggression.
In 2010 eastern Australia received its highest springtime (September–November) rainfall since 1900. Based on historical relationships with sea surface temperatures (SST) and other climate indices, ...this record rainfall in 2010 was shown to be largely commensurate with the occurrence of a very strong La Niña event and an extreme positive excursion of the SAM. The pattern and magnitude of the tropical SST anomalies in austral spring 2010 were diagnosed to be nearly perfect to produce high rainfall across eastern Australia. Key aspects of this SST pattern were the strong cold anomaly in the central equatorial Pacific, and the strong warm anomalies in the eastern Indian Ocean and the far western Pacific to the north of Australia. Although the recent upward trend in SSTs in the western Pacific/eastern Indian Ocean warm pool accounted for about 50 % of the SST anomaly surrounding northern Australia in 2010, the contribution by the warming trend in these SSTs to the Australian rainfall anomaly in 2010 was assessed to be relatively modest. The strong positive swing in SAM was estimated to have accounted for upwards of 40 % of the regional anomaly along the central east coastal region and about 10 % of the area mean anomaly across eastern Australia. This contribution by the SAM suggests that a significant portion of the rainfall in 2010 may not have been seasonally predictable. However, predictability arising from the promotion of high SAM by the extreme La Nina event can not be ruled out.
With their highly reactive respective C−Na and N−Na bonds, organosodium and sodium amide reagents could be viewed as obvious replacements or even superior reagents to the popular, widely utilised ...organolithiums. However, they have seen very limited applications in synthesis due mainly to poor solubility in common solvents and their limited stability. That notwithstanding in recent years there has been a surge of interest in bringing these sustainable metal reagents into the forefront of organometallics in synthesis. Showcasing the growth in utilisation of organosodium complexes within several areas of synthetic chemistry, this Minireview discusses promising new methods that have been recently reported with the goal of taming these powerful reagents. Special emphasis is placed on coordination and aggregation effects in these reagents which can impart profound changes in their solubility and reactivity. Differences in observed reactivity between more nucleophilic aryl and alkyl sodium reagents and the less nucleophilic but highly basic sodium amides are discussed along with current mechanistic understanding of their reactivities. Overall, this review aims to inspire growth in this exciting field of research to allow for the integration of organosodium complexes within common important synthetic transformations.
With demand for lithium soaring due to its escalating use in energy applications, the heavier organosodium compounds have started to be considered as alternatives in synthesis. Recent reports have tackled their solubility problems, tamed their high reactivity and studied their intermediates constitution, accessing now transformations that were not possible with organolithiums, and opening new vistas for the use of these organosodium reagents.
Aggression is regulated by pheromones in many animal species. However, in no system have aggression pheromones, their cognate receptors and corresponding sensory neurons been identified. Here we show ...that 11-cis-vaccenyl acetate (cVA), a male-specific volatile pheromone, robustly promotes male-male aggression in the vinegar fly Drosophila melanogaster. The aggression-promoting effect of synthetic cVA requires olfactory sensory neurons (OSNs) expressing the receptor Or67d, as well as the receptor itself. Activation of Or67d-expressing OSNs, either by genetic manipulation of their excitability or by exposure to male pheromones in the absence of other classes of OSNs, is sufficient to promote aggression. High densities of male flies can promote aggression by the release of volatile cVA. In turn, cVA-promoted aggression can promote male fly dispersal from a food resource, in a manner dependent on Or67d-expressing OSNs. These data indicate that cVA may mediate negative-feedback control of male population density, through its effect on aggression. Identification of a pheromone-OSN pair controlling aggression in a genetic organism opens the way to unravelling the neurobiology of this evolutionarily conserved behaviour.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Female mice exhibit opposing social behaviors toward males depending on their reproductive state: virgins display sexual receptivity (lordosis behavior), while lactating mothers attack. How a change ...in reproductive state produces a qualitative switch in behavioral response to the same conspecific stimulus is unknown. Using single-cell RNA-seq, we identify two distinct subtypes of estrogen receptor-1-positive neurons in the ventrolateral subdivision of the female ventromedial hypothalamus (VMHvl) and demonstrate that they causally control sexual receptivity and aggressiveness in virgins and lactating mothers, respectively. Between- and within-subject bulk-calcium recordings from each subtype reveal that aggression-specific cells acquire an increased responsiveness to social cues during the transition from virginity to maternity, while the responsiveness of the mating-specific population appears unchanged. These results demonstrate that reproductive-state-dependent changes in the relative activity of transcriptomically distinct neural subtypes can underlie categorical switches in behavior associated with physiological state changes.
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•scRNA-seq reveals distinct cell types in female VMHvl active in mating versus aggressive behaviors•Activation of VMHvlEsr1+,Npy2r− (α) cells promotes mating behaviors in virgins•Activation of VMHvlNpy2r+ (β) cells promotes aggression in both virgins and dams•Response of β, but not α, cells to male social cues increases in lactating dams
Internal states can profoundly alter innate behavioral responses to releasing stimuli. Liu et al. identify distinct neural subpopulations within a single hypothalamic nucleus (VMHvl) that causally control female mating versus aggressive behaviors. Changes in the subpopulations’ relative cue sensitivity underlies a state-dependent switch in social behaviors.
All animals can perform certain survival behaviors without prior experience, suggesting a “hard wiring” of underlying neural circuits. Experience, however, can alter the expression of innate ...behaviors. Where in the brain and how such plasticity occurs remains largely unknown. Previous studies have established the phenomenon of “aggression training,” in which the repeated experience of winning successive aggressive encounters across multiple days leads to increased aggressiveness. Here, we show that this procedure also leads to long-term potentiation (LTP) at an excitatory synapse, derived from the posteromedial part of the amygdalohippocampal area (AHiPM), onto estrogen receptor 1-expressing (Esr1⁺) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl). We demonstrate further that the optogenetic induction of such LTP in vivo facilitates, while optogenetic long-term depression (LTD) diminishes, the behavioral effect of aggression training, implying a causal role for potentiation at AHiPM→VMHvlEsr1 synapses in mediating the effect of this training. Interestingly, ∼25% of inbred C57BL/6 mice fail to respond to aggression training. We show that these individual differences are correlated both with lower levels of testosterone, relative to mice that respond to such training, and with a failure to exhibit LTP after aggression training. Administration of exogenous testosterone to such nonaggressive mice restores both behavioral and physiological plasticity. Together, these findings reveal that LTP at a hypothalamic circuit node mediates a form of experience-dependent plasticity in an innate social behavior, and a potential hormone-dependent basis for individual differences in such plasticity among genetically identical mice.
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