Sex- and Stress-Dependent Effects on Dendritic Morphology and Spine Densities in Putative Orexin Neurons

We recently found that non-stressed female rats have higher basal prepro-orexin expression and activation of orexinergic neurons compared to non-stressed males, which lead to impaired habituation to repeated restraint stress at the behavioral, neural, and endocrine level. Here, we extended our study of sex differences in the orexin system by examining spine densities and dendritic morphology in putative orexin neurons in adult male and female rats that were exposed to 5 consecutive days of 30-min restraint. Analysis of spine distribution and density indicated that putative orexinergic neurons in control non-stressed females had significantly more dendritic spines than those in control males, and the majority of these were mushroom spines. This morphological finding may suggest more excitatory input onto orexin neurons in female rats. As orexin neurons are known to promote the hypothalamic–pituitary–adrenal response, this morphological change in orexin neurons could underlie the impaired habituation to repeated stress in female rats. Dendritic complexity did not differ between non-stressed males and females, however repeated restraint stress decreased total dendritic length, nodes, and branching primarily in males. Thus, reduced dendritic complexity of putative orexinergic neurons is observed in males but not in females after 5 days of repeated restraint stress. This morphological change might be reflective of decreased orexin system function, which may allow males to habituate more fully to repeated restraint than females. These results extend our understanding of the role of orexin neurons in regulating habituation and demonstrate changes in putative orexin cell morphology and spines that may underlie sex differences in habituation

Sex- and Stress-Dependent Effects on Dendritic Morphology and Spine Densities in Putative Orexin Neurons

We recently found that non-stressed female rats have higher basal prepro-orexin expression and activation of orexinergic neurons compared to non-stressed males, which lead to impaired habituation to repeated restraint stress at the behavioral, neural, and endocrine level. Here, we extended our study of sex differences in the orexin system by examining spine densities and dendritic morphology in putative orexin neurons in adult male and female rats that were exposed to 5 consecutive days of 30-min restraint. Analysis of spine distribution and density indicated that putative orexinergic neurons in control non-stressed females had significantly more dendritic spines than those in control males, and the majority of these were mushroom spines. This morphological finding may suggest more excitatory input onto orexin neurons in female rats. As orexin neurons are known to promote the hypothalamic–pituitary–adrenal response, this morphological change in orexin neurons could underlie the impaired habituation to repeated stress in female rats. Dendritic complexity did not differ between non-stressed males and females, however repeated restraint stress decreased total dendritic length, nodes, and branching primarily in males. Thus, reduced dendritic complexity of putative orexinergic neurons is observed in males but not in females after 5 days of repeated restraint stress. This morphological change might be reflective of decreased orexin system function, which may allow males to habituate more fully to repeated restraint than females. These results extend our understanding of the role of orexin neurons in regulating habituation and demonstrate changes in putative orexin cell morphology and spines that may underlie sex differences in habituation

‘Removing Barriers’ and ‘Creating Distance’: Exploring the Logics of Efficiency and Trust in Civic Technology

Oriented around efficiency, civic technology primarily aims to remove barriers by automating and streamlining processes of government. While removing barriers is vital in many matters of governance, should it always be the aim of civic technology? In our ongoing ethnographic research to understand the work of community engagement performed by public officials in local government, we have observed how this orientation around efficiency in civic technology can inadvertently create distance in the relationships between citizens and governments. In this article, we discuss how an orientation around trust could open a space for civic technology that primarily aims to close distance in the relationships between citizens and public officials. We do so by first providing an account of how trust functions in the work of public officials performing community engagement, calling attention to where and when efficiency is at odds with the importance of relationship building between public officials and citizens. We build on ethnographic findings and a series of co-design activities with public officials to develop three strategies that operate under the logic of trust: historicizing engagement, focusing on experience, and mediating expectations. In all, by focusing on trust and the relational work of closing distance, civic technology can move towards addressing the growing crisis in confidence being faced in democracies

TalkFutures: Supporting Qualitative Practices in Distributed Community Engagements

Community engagements are qualitative processes that make use of participants local knowledge for democratic decision-making, but often exclude participants from data analysis and dissemination. This can mean that they are left feeling that their voice is not properly represented in the final output. This paper presents a digital community engagement process, TalkFutures, that actively involves participants in the production, distributed analysis and summarization of qualitative data. The design of TalkFutures was explored through a five-week deployment with the International Federation of Red Cross and Red Crescent Societies (IFRC) as part of a consultation designed to inform future strategy. Our analysis of deployment metrics and post-deployment interviews outline how TalkFutures: (i) increased modes of participation across the qualitative workflow; (ii) reduced barriers to participation; and (iii) improved representation in the engagement processes

Cosmogenic nuclides indicate that boulder fields are dynamic, ancient, multigenerational features

Boulder fields are found throughout the world; yet, the history of these features, as well as the processes that form them, remain poorly understood. In high and mid-latitudes, boulder fields are thought to form and be active during glacial periods; however, few quantitative data support this assertion. Here, we use in situ cosmogenic 10Be and 26Al to quantify the near-surface history of 52 samples in and around the largest boulder field in North America, Hickory Run, in central Pennsylvania, USA. Boulder surface 10Be concentrations (n = 43) increase downslope, indicate minimum near-surface histories of 70-600 k.y., and are not correlated with lithology or boulder size. Measurements of samples from the top and bottom of one boulder and three underlying clasts as well as 26Al/10Be ratios (n = 25) suggest that at least some boulders have complex exposure histories caused by flipping and/or cover by other rocks, soil, or ice. Cosmogenic nuclide data demonstrate that Hickory Run, and likely other boulder fields, are dynamic features that persist through multiple glacial-interglacial cycles because of boulder resistance to weathering and erosion. Long and complex boulder histories suggest that climatic interpretations based on the presence of these rocky landforms are likely over simplifications

ASCA and contemporaneous ground-based observations of the BL Lacertae objects 1749+096 and 2200+420 (BL Lac)

We present ASCA observations of the radio-selected BL Lacertae objects 1749+096 (z=0.32) and 2200+420 (BL Lac, z=0.069) performed in 1995 Sept and Nov, respectively. The ASCA spectra of both sources can be described as a first approximation by a power law with photon index Gamma ~ 2. This is flatter than for most X-ray-selected BL Lacs observed with ASCA, in agreement with the predictions of current blazar unification models. While 1749+096 exhibits tentative evidence for spectral flattening at low energies, a concave continuum is detected for 2200+420: the steep low-energy component is consistent the high-energy tail of the synchrotron emission responsible for the longer wavelengths, while the harder tail at higher energies is the onset of the Compton component. The spectral energy distributions from radio to gamma-rays are consistent with synchrotron-self Compton emission from a single homogeneous region shortward of the IR/optical wavelengths, with a second component in the radio domain related to a more extended emission region. For 2200+420, comparing the 1995 Nov state with the optical/GeV flare of 1997 July, we find that models requiring inverse Compton scattering of external photons provide a viable mechanism for the production of the highest (GeV) energies during the flare. An increase of the external radiation density and of the power injected in the jet can reproduce the flat gamma-ray continuum observed in 1997 July. A directly testable prediction of this model is that the line luminosity in 2200+420 should vary shortly after (~1 month) a non-thermal synchrotron flare.Comment: 28 pages,6 figures, 5 tables; LaTeX document. accepted for publication in the Astrophysical Journa

ΔFosB Regulates Gene Expression and Cognitive Dysfunction in a Mouse Model of Alzheimer\u27s Disease.

Alzheimer\u27s disease (AD) is characterized by cognitive decline and 5- to 10-fold increased seizure incidence. How seizures contribute to cognitive decline in AD or other disorders is unclear. We show that spontaneous seizures increase expression of ΔFosB, a highly stable Fos-family transcription factor, in the hippocampus of an AD mouse model. ΔFosB suppressed expression of the immediate early gene c-Fos, which is critical for plasticity and cognition, by binding its promoter and triggering histone deacetylation. Acute histone deacetylase (HDAC) inhibition or inhibition of ΔFosB activity restored c-Fos induction and improved cognition in AD mice. Administration of seizure-inducing agents to nontransgenic mice also resulted in ΔFosB-mediated suppression of c-Fos, suggesting that this mechanism is not confined to AD mice. These results explain observations that c-Fos expression increases after acute neuronal activity but decreases with chronic activity. Moreover, these results indicate a general mechanism by which seizures contribute to persistent cognitive deficits, even during seizure-free periods

Epigenetic suppression of hippocampal calbindin-D28k by ΔFosB drives seizure-related cognitive deficits.

The calcium-binding protein calbindin-D28k is critical for hippocampal function and cognition, but its expression is markedly decreased in various neurological disorders associated with epileptiform activity and seizures. In Alzheimer\u27s disease (AD) and epilepsy, both of which are accompanied by recurrent seizures, the severity of cognitive deficits reflects the degree of calbindin reduction in the hippocampal dentate gyrus (DG). However, despite the importance of calbindin in both neuronal physiology and pathology, the regulatory mechanisms that control its expression in the hippocampus are poorly understood. Here we report an epigenetic mechanism through which seizures chronically suppress hippocampal calbindin expression and impair cognition. We demonstrate that ΔFosB, a highly stable transcription factor, is induced in the hippocampus in mouse models of AD and seizures, in which it binds and triggers histone deacetylation at the promoter of the calbindin gene (Calb1) and downregulates Calb1 transcription. Notably, increasing DG calbindin levels, either by direct virus-mediated expression or inhibition of ΔFosB signaling, improves spatial memory in a mouse model of AD. Moreover, levels of ΔFosB and calbindin expression are inversely related in the DG of individuals with temporal lobe epilepsy (TLE) or AD and correlate with performance on the Mini-Mental State Examination (MMSE). We propose that chronic suppression of calbindin by ΔFosB is one mechanism through which intermittent seizures drive persistent cognitive deficits in conditions accompanied by recurrent seizures

From Creating Spaces for Civic Discourse to Creating Resources for Action

In this paper, we investigate the role of technology to address the concerns of a civil society group carrying out community-level consultation on the allocation of £1 million of community funds. We explore issues of devolved decision-making through the evaluation of a sociodigital system designed to foster deliberative virtues. We describe the ways in which this group used our system in their consultation practices. Our findings highlight how they adopted our technology to privilege specific forms of expression, ascertain issues in their community, make use of and make sense of community data, and create resources for action within their existing practices. Based on related fieldwork we discuss the impacts of structuring and configuring tools for ‘talk-based’ consultation in order to turn attention to the potential pitfalls and prospects for designing civic technologies that create resources for action for civil society

High-sensitivity in situ capture of endogenous RNA-protein interactions in fixed cells and primary tissues

RNA-binding proteins (RBPs) have pivotal functions in RNA metabolism, but current methods are limited in retrieving RBP-RNA interactions within endogenous biological contexts. Here, we develop INSCRIBE (IN situ Sensitive Capture of RNA-protein Interactions in Biological Environments), circumventing the challenges through in situ RNA labeling by precisely directing a purified APOBEC1-nanobody fusion to the RBP of interest. This method enables highly specific RNA-binding site identification across a diverse range of fixed biological samples such as HEK293T cells and mouse brain tissue and accurately identifies the canonical binding motifs of RBFOX2 (UGCAUG) and TDP-43 (UGUGUG) in native cellular environments. Applicable to any RBP with available primary antibodies, INSCRIBE enables sensitive capture of RBP-RNA interactions from ultra-low input equivalent to ~5 cells. The robust, versatile, and sensitive INSCRIBE workflow is particularly beneficial for precious tissues such as clinical samples, empowering the exploration of genuine RBP-RNA interactions in RNA-related disease contexts