TREM2-dependent effects on microglia in Alzheimer\u27s Disease

Alzheimer’s disease (AD) is a late-onset dementia characterized by the deposition of amyloid plaques and formation of neurofibrillary tangles (NFTs) which lead to neuronal loss and cognitive deficits. Abnormal protein aggregates in the AD brain are also associated with reactive microglia and astrocytes. Whether this glial response is beneficial or detrimental in AD pathology is under debate. Microglia are the resident innate immune cells in the central nervous system (CNS) that survey the surrounding environment. Genome-wide association studies (GWAS) have identified the R47H variant of triggering receptor expressed on myeloid cell 2 (TREM2) as a risk factor for late-onset AD (LOAD) with an odds ratio of 4.5. TREM2 is an immunoreceptor primarily present on microglia in the CNS that binds to polyanionic molecules. The transmembrane domain of TREM2 signals through DAP12, an adaptor protein that contains an immunoreceptor tyrosine-based activation motif (ITAM), which mediates TREM2 signaling and promotes microglial activation and survival. In mouse models of AD, Trem2 haplodeficiency and deficiency lead to reduced microglial clustering around amyloid β (Aβ) plaques, suggesting TREM2 is required for plaque-associated microglial responses. Recently, TREM2 has been shown to enhance microglial metabolism through the mammalian target of rapamycin (mTOR) pathway. Although aberrant metabolism has long been associated with AD, not much was known regarding how metabolism in microglia might affect disease progression. In this review, we discuss the role of TREM2 and metabolism in AD pathology, highlighting how TREM2-mediated microglial metabolism modulates AD pathogenesis

Path integral Monte Carlo simulation of global and local superfluidity in liquid 4^{4}He reservoirs separated by nanoscale apertures

We present a path integral Monte Carlo study of the global superfluid fraction and local superfluid density in cylindrically-symmetric reservoirs of liquid $^{4}$He separated by nanoaperture arrays. The superfluid response to both translations along the axis of symmetry (longitudinal response) and rotations about the cylinder axis (transverse response) are computed, together with radial and axial density distributions that reveal the microscopic inhomogeneity arising from the combined effects of the confining external potential and the $^4$He-$^4$He interatomic potentials. We make a microscopic determination of the length-scale of decay of superfluidity at the radial boundaries of the system by analyzing the local superfluid density distribution to extract a displacement length that quantifies the superfluid mass displacement away from the boundary. We find that the longitudinal superfluid response is reduced in reservoirs separated by a septum containing sufficiently small apertures compared to a cylinder with no intervening aperture array, for all temperatures below $T_{\lambda}$. For a single aperture in the septum, a significant drop in the longitudinal superfluid response is seen when the aperture diameter is made smaller than twice the empirical temperature-dependent $^4$He healing length, consistent with the formation of a weak link between the reservoirs. Increasing the diameter of a single aperture or the number of apertures in the array results in an increase of the superfluid density toward the expected bulk value.Comment: 12 pages, 6 figure

Responsible Brains: Neuroscience, Law, and Human Culpability

[This download includes the table of contents and chapter 1.] When we praise, blame, punish, or reward people for their actions, we are holding them responsible for what they have done. Common sense tells us that what makes human beings responsible has to do with their minds and, in particular, the relationship between their minds and their actions. Yet the empirical connection is not necessarily obvious. The “guilty mind” is a core concept of criminal law, but if a defendant on trial for murder were found to have serious brain damage, which brain parts or processes would have to be damaged for him to be considered not responsible, or less responsible, for the crime? The authors argue that evidence from neuroscience and the other cognitive sciences can illuminate the nature of responsibility and agency. They go on to offer a novel and comprehensive neuroscientific theory of human responsibility

Torque control system

System stabilizes aximuth of gondolas which are carried by high-altitude balloons as platforms for tracking telescopes. When telescopes must be constantly aimed at specific targets, control system stabilizes gondola to within 5 arc-seconds

Lesbian brides: post-queer popular culture

The last decade has witnessed a proliferation of lesbian representations in European and North American popular culture, particularly within television drama and broader celebrity culture. The abundance of “positive” and “ordinary” representations of lesbians is widely celebrated as signifying progress in queer struggles for social equality. Yet, as this article details, the terms of the visibility extended to lesbians within popular culture often a rm ideals of hetero-patriarchal, white femininity. Focusing on the visual and narrative registers within which lesbian romances are mediated within television drama, this article examines the emergence of what we describe as “the lesbian normal.” Tracking the ways in which the lesbian normal is anchored in a longer history of “the normal gay,” it argues that the lesbian normal is indicative of the emergence of a broader post-feminist and post-queer popular culture, in which feminist and queer struggles are imagined as completed and belonging to the past. Post-queer popular culture is depoliticising in its e ects, diminishing the critical potential of feminist and queer politics, and silencing the actually existing conditions of inequality, prejudice, and stigma that continue to shape lesbian lives

Speaker recognition across languages

This is a draft of a chapter/article that has been accepted for publication by Oxford University Press in the forthcoming book The Oxford Handbook of Voice Perception, edited by S. Frühholz & P. Belin due for publication (in press).Listeners identify voices more accurately in their native language than an unknown, foreign language, in a phenomenon known as the language-familiarity effect in talker identification. This effect has been reliably observed for a wide range of different language pairings and using a variety of different methodologies, including voice line-ups, talker identification training, and talker discrimination. What do listeners know about their native language that helps them recognize voices more accurately? Do listeners gain access to this knowledge when they learn a second language? Is linguistic competence necessary, or can mere exposure to a foreign language help listeners identify voices more accurately? In this chapter, I review the more than three decades of research on the language-familiarity effect in talker identification with an emphasis on how attention to this phenomenon can inform not only better psychological and neural models of memory for voices, but also better models of speech processing.This work was supported in part by NIH R03 DC014045