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When Katharine is found dead at the foot of her stairs, it is the mystery of her life which consumes daughter, Laura. The medical examiner's report, in which precious parts of Katharine's body are weighed and categorized, motivates Laura to write her own version of events. To bear witness to the unbearable blank space between each itemized entry. What emerges is a picture of life lived in the shadows, as well as an attempt to discover how and why her mother died. To make sense of her own grief Laura must piece her mother's body back together and in doing so, she is forced to confront a woman silenced by her own mother and wronged by her husband. A woman who felt shackled by motherhood and unable to love freely. With the heart of a memoir and the pace of a thriller, An Unremarkable Body reveals the overwhelming desire of those who mourn to protest that an unremarkable body does not mean an unremarkable life.

A bstract We consider two possible flat space limits of three dimensional N = 1 , 1 AdS supergravity. They differ by how the supercharges are scaled with the AdS radius ℓ : the first limit (democratic) leads to the usual super-Poincaré theory, while a novel ‘twisted’ theory of supergravity stems from the second (despotic) limit. We then propose boundary conditions such that the asymptotic symmetry algebras at null infinity correspond to supersymmetric extensions of the BMS algebras previously derived in connection to non- and ultra-relativistic limits of the N = 1 , 1 Virasoro algebra in two dimensions. Finally, we study the supersymmetric energy bounds and find the explicit form of the asymptotic and global Killing spinors of supersymmetric solutions in both flat space supergravity theories.

Enterohaemorrhagic Escherichia coli (EHEC) comprise a group of intestinal pathogens responsible for a range of illnesses, including kidney failure and neurological compromise. EHEC produce critical virulence factors, Shiga toxin (Stx) 1 or 2, and the synthesis of Stx2 is associated with worse disease manifestations. Infected patients only receive supportive treatment because some conventional antibiotics enable toxin production. Shiga toxin 2 genes ( stx2 ) are carried in λ-like bacteriophages ( stx2 -phages) inserted into the EHEC genome as prophages. Factors that cause DNA damage induce the lytic cycle of stx2 -phages, leading to Stx2 production. The phage Q protein is critical for transcription antitermination of stx2 and phage lytic genes. This study reports that deficiency of two endoribonucleases (RNases), E and G, significantly delayed cell lysis and impaired production of both Stx2 and stx2 -phages, unlike deficiency of either enzyme alone. Moreover, scarcity of both enzymes reduced the concentrations of Q and stx2 transcripts and slowed cell growth.

Dementia in Alzheimer’s disease progresses alongside neurodegeneration 1 – 4 , but the specific events that cause neuronal dysfunction and death remain poorly understood. During normal ageing, neurons progressively accumulate somatic mutations 5 at rates similar to those of dividing cells 6 , 7 which suggests that genetic factors, environmental exposures or disease states might influence this accumulation 5 . Here we analysed single-cell whole-genome sequencing data from 319 neurons from the prefrontal cortex and hippocampus of individuals with Alzheimer’s disease and neurotypical control individuals. We found that somatic DNA alterations increase in individuals with Alzheimer’s disease, with distinct molecular patterns. Normal neurons accumulate mutations primarily in an age-related pattern (signature A), which closely resembles ‘clock-like’ mutational signatures that have been previously described in healthy and cancerous cells 6 – 10 . In neurons affected by Alzheimer’s disease, additional DNA alterations are driven by distinct processes (signature C) that highlight C>A and other specific nucleotide changes. These changes potentially implicate nucleotide oxidation 4 , 11 , which we show is increased in Alzheimer’s-disease-affected neurons in situ. Expressed genes exhibit signature-specific damage, and mutations show a transcriptional strand bias, which suggests that transcription-coupled nucleotide excision repair has a role in the generation of mutations. The alterations in Alzheimer’s disease affect coding exons and are predicted to create dysfunctional genetic knockout cells and proteostatic stress. Our results suggest that known pathogenic mechanisms in Alzheimer’s disease may lead to genomic damage to neurons that can progressively impair function. The aberrant accumulation of DNA alterations in neurodegeneration provides insight into the cascade of molecular and cellular events that occurs in the development of Alzheimer’s disease. Analyses of single-cell whole-genome sequencing data show that somatic mutations are increased in the brain of individuals with Alzheimer’s disease compared to neurotypical individuals, with a pattern of genomic damage distinct from that of normal ageing.

Neurons live for decades in a postmitotic state, their genomes susceptible to DNA damage. Here we survey the landscape of somatic single-nucleotide variants (SNVs) in the human brain. We identified thousands of somatic SNVs by single-cell sequencing of 36 neurons from the cerebral cortex of three normal individuals. Unlike germline and cancer SNVs, which are often caused by errors in DNA replication, neuronal mutations appear to reflect damage during active transcription. Somatic mutations create nested lineage trees, allowing them to be dated relative to developmental landmarks and revealing a polyclonal architecture of the human cerebral cortex. Thus, somatic mutations in the brain represent a durable and ongoing record of neuronal life history, from development through postmitotic function.

Accretion onto black holes is an efficient mechanism in converting the gas mass-energy into energetic outputs as radiation, wind and jet. Tidal disruption events, in which stars are tidally torn apart and then accreted onto supermassive black holes, offer unique opportunities of studying the accretion physics as well as the wind and jet launching physics across different accretion regimes. In this review, we systematically describe and discuss the models that have been developed to study the accretion flows and jets in tidal disruption events. A good knowledge of these physics is not only needed for understanding the emissions of the observed events, but also crucial for probing the general relativistic space-time around black holes and the demographics of supermassive black holes via tidal disruption events.

The tidal forces close to massive black holes can rip apart stars that come too close to them. As the resulting stellar debris spirals toward the black hole, the debris heats up and emits x-rays. We report observations of a stable 131-second x-ray quasi-periodic oscillation from the tidal disruption event ASASSN-14li. Assuming the black hole mass indicated by host galaxy scaling relations, these observations imply that the periodicity originates from close to the event horizon and that the black hole is rapidly spinning. Our findings demonstrate that tidal disruption events can generate quasi-periodic oscillations that encode information about the physical properties of their black holes.

SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs) and multipotent neural progenitor cells (NPCs); however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal enhancer elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1) in ESCs, the related POU family member BRN2 (Pou3f2) co-occupied a large set of putative distal enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors.

Developmental programs are controlled by transcription factors and chromatin regulators, which maintain specific gene expression programs through epigenetic modification of the genome. These regulatory events at enhancers contribute to the specific gene expression programs that determine cell state and the potential for differentiation into new cell types. Although enhancer elements are known to be associated with certain histone modifications and transcription factors, the relationship of these modifications to gene expression and developmental state has not been clearly defined. Here we interrogate the epigenetic landscape of enhancer elements in embryonic stem cells and several adult tissues in the mouse. We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone. This indicates that the amount of actively used enhancers is lower than previously anticipated. Furthermore, poised enhancer networks provide clues to unrealized developmental programs. Finally, we show that enhancers are reset during nuclear reprogramming.

A bstract We analyze BPS black hole attractors in the conformal 4d gauged supergravity formalism and apply the technique known as supergravity localization in order to evaluate Sen’s quantum entropy function [1] in the AdS 2 ×S 2 near-horizon geometry. Under certain assumptions, we reduce the exact expression of the functional integral to a finite-dimensional integral for a number of supersymmetric black holes in gauged supergravity with AdS asymptotics subject to a holographic description via a dual field theory. Examples include the asymptotically AdS 4 ×S 7 Cacciatori-Klemm black holes [2] in M-theory and the asymptotically AdS 5 ×S 5 generalizations of Gutowski-Reall black holes [3] and Benini-Bobev black strings [4] in type IIB, as well as the recently constructed asymptotically AdS 4 ×S 6 solutions [5, 6] in massive type IIA. Our results provide an important first step towards a gravitational counterpart to the exact evaluation of supersymmetric partition functions at finite N for the holographically dual field theories in these examples.