Crucial Physical Dependencies of the Core-Collapse Supernova Mechanism

We explore with self-consistent 2D F{\sc{ornax}} simulations the dependence of the outcome of collapse on many-body corrections to neutrino-nucleon cross sections, the nucleon-nucleon bremsstrahlung rate, electron capture on heavy nuclei, pre-collapse seed perturbations, and inelastic neutrino-electron and neutrino-nucleon scattering. Importantly, proximity to criticality amplifies the role of even small changes in the neutrino-matter couplings, and such changes can together add to produce outsized effects. When close to the critical condition the cumulative result of a few small effects (including seeds) that individually have only modest consequence can convert an anemic into a robust explosion, or even a dud into a blast. Such sensitivity is not seen in one dimension and may explain the apparent heterogeneity in the outcomes of detailed simulations performed internationally. A natural conclusion is that the different groups collectively are closer to a realistic understanding of the mechanism of core-collapse supernovae than might have seemed apparent.Comment: 25 pages; 10 figure

Gamma-Ray Bursts: The Underlying Model

A pedagogical derivation is presented of the ``fireball'' model of gamma-ray bursts, according to which the observable effects are due to the dissipation of the kinetic energy of a relativistically expanding wind, a ``fireball.'' The main open questions are emphasized, and key afterglow observations, that provide support for this model, are briefly discussed. The relativistic outflow is, most likely, driven by the accretion of a fraction of a solar mass onto a newly born (few) solar mass black hole. The observed radiation is produced once the plasma has expanded to a scale much larger than that of the underlying ``engine,'' and is therefore largely independent of the details of the progenitor, whose gravitational collapse leads to fireball formation. Several progenitor scenarios, and the prospects for discrimination among them using future observations, are discussed. The production in gamma- ray burst fireballs of high energy protons and neutrinos, and the implications of burst neutrino detection by kilometer-scale telescopes under construction, are briefly discussed.Comment: In "Supernovae and Gamma Ray Bursters", ed. K. W. Weiler, Lecture Notes in Physics, Springer-Verlag (in press); 26 pages, 2 figure

Deficits in auditory predictive coding in individuals with the psychosis risk syndrome: Prediction of conversion to psychosis

The mismatch negativity (MMN) event-related potential (ERP) component is increasingly viewed as a prediction error signal elicited when a deviant sound violates the prediction that a frequent "standard" sound will repeat. Support for this predictive coding framework emerged with the identification of the repetition positivity (RP), a standard stimulus ERP component that increases with standard repetition and is thought to reflect strengthening of the standard's memory trace and associated predictive code. Using electroencephalographic recordings, we examined the RP elicited by repeating standard tones presented during a traditional "constant standard" MMN paradigm in individuals with the psychosis risk syndrome (PRS; n = 579) and healthy controls (HC; n = 241). Clinical follow-up assessments identified PRS participants who converted to a psychotic disorder (n = 77) and PRS nonconverters who were followed for the entire 24-month clinical follow-up period and either remained symptomatic (n = 144) or remitted from the PRS (n = 94). In HC, RP linearly increased from early-to late-appearing standards within local trains of repeating standards (p <.0001), consistent with auditory predictive code/memory trace strengthening. Relative to HC, PRS participants showed a reduced RP across standards (p =.0056). PRS converters showed a relatively small RP deficit for early appearing standards relative to HC (p =.0.0107) and a more prominent deficit for late-appearing standards (p =.0006) relative to both HC and PRS-remitted groups. Moreover, greater RP deficits predicted shorter time to conversion in a subsample of unmedicated PRS individuals (p=.02). Thus, auditory predictive coding/memory trace deficits precede psychosis onset and predict future psychosis risk in PRS individuals

Declarative memory impairments in Alzheimer's disease and semantic dementia

Semantic dementia (SD) and Alzheimer's disease (AD) are both disorders in which early pathology affects the temporal lobe Net they produce distinct syndromes of declarative memory impairment-loss of established semantic knowledge with relatively preserved episodic memory in the former and the converse in the latter. Groups with mild SD and mild AD who showed a double dissociation in these two aspects of declarative memory were studied-the SD group's episodic memory and the AD group's semantic knowledge each being comparable to controls. Positron emission tomography and volumetric magnetic resonance imaging were used to map deficits in regional cerebral metabolic rate and mesial temporal lobe MTL atrophy, respectively. Episodic memory impairment in AD was associated with dysfunction of an integrated network (mesial temporal lobe, mamillary bodies, dorsomesial thalamus and posterior cingulate). Semantic memory impairment in SD was associated with bilateral rostra] temporal lobe hypometabolism. The SD group had comparable MTL atrophy and hypometabolism to that found in AD but the remainder of their limbic-diencephalic network was preserved suggesting that the latter explains their ability to acquire new episodic memories. The results challenge the view that amnesia in early AD can be explained by the degree of MTL damage alone while showing that semantic impairment can occur with damage restricted to the rostral temporal lobes. (c) 2005 Elsevier Inc. All rights reserved

Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment

The neural basis of the amnesia characterizing early Alzheimer's disease (AD) remains uncertain. Postmortem pathological studies have suggested early involvement of the mesial temporal lobe, whereas in vivo metabolic studies have shown hypometabolism of the posterior cingulate cortex. Using a technique that combined the anatomic precision of magnetic resonance imaging with positron emission tomography, we found severe reductions of metabolism throughout a network of limbic structures (the hippocampal complex, medial thalamus, mamillary bodies, and posterior cingulate) in patients with mild AD. We then studied a cohort with mild cognitive impairment in whom amnesia was the only cognitive abnormality and found comparable hypometabolism through the same network. The AD and mild cognitive impairment groups were differentiated, however, by changes outside this network, the former showing significant hypometabolism in amygdala and temporoparietal and frontal association cortex, whereas the latter did not. The amnesia of very early AD reflects severe but localized limbic dysfunction

Behavioural variant frontotemporal dementia: not all it seems?

Background: the diagnosis of the behavioural variant of frontotemporal dementia (bvFTD) can be challenging. At present there is a paucity of prospective work addressing the specificity of current diagnostic criteria for bvFTD with respect to long-term outcome (i.e., false positives versus true positives).Methods: here we report two individuals who met current clinical criteria for bvFTD and who underwent detailed long-term clinical and neuropsychological follow-up. In addition, both had serial volumetric MRI and functional metabolic (FDG-PET) imaging separated by 5 years.Results: one case had a slow clinical decline as well as both progressive atrophy and hypometabolism in a frontotemporal distribution, consistent with a neurodegenerative FTD syndrome. However, the second developed neither atrophy nor hypometabolism and remained clinically stable, a decade from symptom onset.Conclusion: we propose that these cases illustrate that while there may be a slow evolution in bvFTD, it is possible that some cases who meet current criteria may not have a neurodegenerative syndrome. If correct, this hypothesis has important implications for the current diagnostic criteria. A potential hierarchy for diagnostic certainty in bvFTD is suggested

Dopamine release in dissociable striatal subregions predicts the different effects of oral methylphenidate on reversal learning and spatial working memory.

Contains fulltext : 80907.pdf (publisher's version ) (Open Access

Culture shock: microglial heterogeneity, activation, and disrupted single-cell microglial networks in vitro

Background: Microglia, the resident immune cells of the brain, play a critical role in numerous diseases, but are a minority cell type and difficult to genetically manipulate in vivo with viral vectors and other approaches. Primary cultures allow a more controlled setting to investigate these cells, but morphological and transcriptional changes upon removal from their normal brain environment raise many caveats from in vitro studies. Methods: To investigate whether cultured microglia recapitulate in vivo microglial signatures, we used single-cell RNA sequencing (scRNAseq) to compare microglia freshly isolated from the brain to primary microglial cultures. We performed cell population discovery, differential expression analysis, and gene co-expression module analysis to compare signatures between in vitro and in vivo microglia. We constructed causal predictive network models of transcriptional regulators from the scRNAseq data and identified a set of potential key drivers of the cultured phenotype. To validate this network analysis, we knocked down two of these key drivers, C1qc and Prdx1, in primary cultured microglia and quantified changes in microglial activation markers. Results: We found that, although often assumed to be a relatively homogenous population of cells in culture, in vitro microglia are a highly heterogeneous population consisting of distinct subpopulations of cells with transcriptional profiles reminiscent of macrophages and monocytes, and are marked by transcriptional programs active in neurodegeneration and other disease states. We found that microglia in vitro presented transcriptional activation of a set of “culture shock genes” not found in freshly isolated microglia, characterized by strong upregulation of disease-associated genes including Apoe, Lyz2, and Spp1, and downregulation of homeostatic microglial markers, including Cx3cr1, P2ry12, and Tmem119. Finally, we found that cultured microglia prominently alter their transcriptional machinery modulated by key drivers from the homeostatic to activated phenotype. Knockdown of one of these drivers, C1qc, resulted in downregulation of microglial activation genes Lpl, Lyz2, and Ccl4. Conclusions: Overall, our data suggest that when removed from their in vivo home environment, microglia suffer a severe case of “culture shock”, drastically modulating their transcriptional regulatory network state from homeostatic to activated through upregulation of modules of culture-specific genes. Consequently, cultured microglia behave as a disparate cell type that does not recapitulate the homeostatic signatures of microglia in vivo. Finally, our predictive network model discovered potential key drivers that may convert activated microglia back to their homeostatic state, allowing for more accurate representation of in vivo states in culture. Knockdown of key driver C1qc partially attenuated microglial activation in vitro, despite C1qc being only weakly upregulated in culture. This suggests that even genes that are not strongly differentially expressed across treatments or preparations may drive downstream transcriptional changes in culture. © 2022, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Male–male competition and speciation: aggression bias towards differently coloured rivals varies between stages of speciation in a Lake Victoria cichlid species complex

Sympatric speciation driven by sexual selection by female mate choice on a male trait is a much debated topic. The process is problematic because of the lack of negative frequency-dependent selection that can facilitate the invasion of a novel colour phenotype and stabilize trait polymorphism. It has recently been proposed that male–male competition for mating territories can generate frequency-dependent selection on male colouration. Rare male cichlid fish would enjoy a fitness advantage if territorial defenders bias aggression towards male cichlid fish of their own colour. We used blue (ancestral type) and red phenotypes of the Lake Victoria cichlid species complex Pundamilia. We tested the aggression bias of wild-caught territorial blue male cichlid fish from five separate populations for blue vs. red rival male cichlid fish using simulated intruder choice tests. The different populations vary in the frequency of red male cichlid fish, and in the degree of reproductive isolation between red and blue, reflecting different stages of speciation. Blue male cichlid fish from a population that lack red phenotypes biased aggression towards blue stimulus male cichlid fish. The same was found in two populations where blue and red are reproductively isolated sister species. This aggression bias may facilitate the invasion of a novel colour phenotype and species coexistence. Blue male cichlid fish from two populations where red and blue are hybridizing incipient species biased aggression towards red stimulus male cichlid fish. Thus, after a successful invasion of red, aggression bias alone is not likely to generate frequency dependence required to stabilize the coexistence of phenotypes. The findings show that aggression bias varies between stages of speciation, but is not enough to stabilize the process of speciation.