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Cell
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Aug 28, 2014

Volume 158Issue 5p961-1212
Open Archive
On the cover: HIV-1 latent reservoirs are the major barrier to an effective cure. Viral reservoirs are formed early and are thought to be stable over time in the presence of antiretroviral therapy and can therefore lead to rapid viral rebound upon the cessation of therapy. In this issue, Halper-Stromberg et al. (pp. 989–999) show that, when administered early after infection or in combination with inducers of viral transcription in established infection, broadly neutralizing antibodies (bNAbs) are able to reduce the frequency of rebound viremia in humanized mice. This may represent a new therapeutic strategy to perturb the latent reservoir....
On the cover: HIV-1 latent reservoirs are the major barrier to an effective cure. Viral reservoirs are formed early and are thought to be stable over time in the presence of antiretroviral therapy and can therefore lead to rapid viral rebound upon the cessation of therapy. In this issue, Halper-Stromberg et al. (pp. 989–999) show that, when administered early after infection or in combination with inducers of viral transcription in established infection, broadly neutralizing antibodies (bNAbs) are able to reduce the frequency of rebound viremia in humanized mice. This may represent a new therapeutic strategy to perturb the latent reservoir.

Leading Edge

In This Issue

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  • An RNA Nexus in Neurodegeneration

    The causes of neuronal death in neurodegenerative diseases are multifaceted, but an emerging theme in a number of disorders is the role of RNA regulation and dynamics. In amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, RNAs arising from an expanded GGGGCC repeat are thought central to the pathogenic process, with recent data revealing why and offering a new strategy by which the deleterious RNA might be directly targeted. Likewise, a compelling potential therapeutic avenue for spinal muscular atrophy is illuminated by a new study in which small molecules are shown to selectively control alternative splicing of the survival of motor neuron 2 gene and ameliorate disease symptoms in mice.

Previews

  • Neutralizing the HIV Reservoir

    • Matthew D. Marsden,
    • Jerome A. Zack
    Halper-Stromberg et al. use a humanized mouse model to demonstrate that broadly neutralizing antibodies, when administered with a combination of HIV latency activators, can reduce persistent HIV reservoirs, as measured by plasma virus rebound. Their results support the use of broadly neutralizing antibodies in HIV-reservoir-purging strategies.
  • Sending Mixed Messages for Cell Population Control

    • Hyun Youk,
    • Wendell A. Lim
    Cells often receive signals to proliferate, but how population density is controlled is unclear. Hart et al. now show that a single secreted molecule that instructs both proliferation and death in T cells establishes a bistable response: the population is driven to either extinction or to a homeostatically defined density.
  • Monoculture Breeds Poor Social Skills

    • Gemma L. Staniforth,
    • Mick F. Tuite
    Two studies from Jarosz et al. describe how [GAR+], a protein-based epigenetic determinant found mainly in wild yeast strains, can be activated by microbial cross-kingdom communication. With the aid of genetically and ecologically diverse bacteria, yeast can override an ancient regulatory mechanism of glucose repression, promoting both microbial diversity and lifespan extension.
  • Building a Temperature-Sensitive Ion Channel

    • Ming-Feng Tsai,
    • Christopher Miller
    The biophysical basis of temperature-sensitive ion channel gating has been a tough nut to crack. Chowdhury, et al. use a protein engineering approach to render a temperature-insensitive voltage-gated channel cold- or heat-responsive to reveal principles for temperature-gating and a plausible model for molecularly enabling this mode of environmental responsiveness.

Review

  • Emerging Roles of RNA Modification: m6A and U-Tail

    • Mihye Lee,
    • Boseon Kim,
    • V. Narry Kim
    Although more than 100 types of RNA modification have been described thus far, most of them were thought to be rare in mRNAs and in regulatory noncoding RNAs. Recent developments have unveiled that at least some of the modifications are considerably abundant and widely conserved. This Minireview summarizes the molecular machineries and biological functions of methylation (N6-methyladenosine, m6A) and uridylation (U-tail).

Articles

Resource

Errata

SnapShot

  • SnapShot: Branching Morphogenesis

    • Cheng-Ming Chuong,
    • Ramray Bhat,
    • Randall B. Widelitz,
    • Mina J. Bissell
    Ectodermal appendages such as feathers, hair, mammary glands, salivary glands, and sweat glands form branches, allowing much-increased surface for functional differentiation and secretion. Here, the principles of branching morphogenesis are exemplified by the mammary gland and feathers.
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