Interactions between the Coxiella burnetii parasitophorous vacuole and the endoplasmic reticulum involve the host protein ORP1L

Coxiella burnetii is a gram-negative intracellular bacterium that forms a large, lysosome-like parasitophorous vacuole (PV) essential for bacterial replication. Host membrane lipids are critical for the formation and maintenance of this intracellular niche, yet the mechanisms by which Coxiella manipulates host cell lipid metabolism, trafficking and signalling are unknown. Oxysterol-binding protein-related protein 1 long (ORP1L) is a mammalian lipid-binding protein that plays a dual role in cholesterol-dependent endocytic trafficking as well as interactions between endosomes and the endoplasmic reticulum (ER). We found that ORP1L localized to the Coxiella PV within 12 h of infection through a process requiring the Coxiella Dot/Icm Type 4B secretion system, which secretes effector proteins into the host cell cytoplasm where they manipulate trafficking and signalling pathways. The ORP1L N-terminal ankyrin repeats were necessary and sufficient for PV localization, indicating that ORP1L binds a PV membrane protein. Strikingly, ORP1L simultaneously co-localized with the PV and ER, and electron microscopy revealed membrane contact sites between the PV and ER membranes. In ORP1L-depleted cells, PVs were significantly smaller than PVs from control cells. These data suggest that ORP1L is specifically recruited by the bacteria to the Coxiella PV, where it influences PV membrane dynamics and interactions with the ER

t' at the LHC: the physics of discovery

A search for a fourth family at the LHC is presently a low priority, but we argue that an effective search can be conducted early with only a few inverse femtobarns of data. We discuss a method based on invariant masses of single jets for identifying the $W$'s originating from heavy quark decays. This can significantly increase signal to background in the reconstruction of the $t'$ mass. We also study the various types of physics that can impact the background estimate, most notably higher order effects, initial state radiation, and models of the underlying event.Comment: 16 pages, 12 figures, small improvements, version to appear in JHE

Stable Atmospheric Boundary Layers and Diurnal Cycles – Challenges for Weather and Climate Models

The representation of the atmospheric boundary layer is an important part of weather and climate models and impacts many applications such as air quality and wind energy. Over the years, the performance in modeling 2-m temperature and 10-m wind speed has improved but errors are still significant. This is in particular the case under clear skies and low wind speed conditions at night as well as during winter in stably stratified conditions over land and ice. In this paper, the authors review these issues and provide an overview of the current understanding and model performance. Results from weather forecast and climate models are used to illustrate the state of the art as well as findings and recommendations from three intercomparison studies held within the Global Energy and Water Exchanges (GEWEX) Atmospheric Boundary Layer Study (GABLS). Within GABLS, the focus has been on the examination of the representation of the stable boundary layer and the diurnal cycle over land in clear-sky conditions. For this purpose, single-column versions of weather and climate models have been compared with observations, research models, and large-eddy simulations. The intercomparison cases are based on observations taken in the Arctic, Kansas, and Cabauw in the Netherlands. From these studies, we find that even for the noncloudy boundary layer important parameterization challenges remain.SB acknowledges the financial support received from the NationalScience Foundation by way of Grant AGS-1122315

Neuro-Rehabilitation OnLine (N-ROL): description and evaluation of a group-based telerehabilitation programme for acquired brain injury

Access to the published version of record is available free of charge at https://jnnp.bmj.com/content/92/12/1354Neuro-Rehabilitation OnLine was supported by a generous donation from the charity SameYou (charity number 1170102) and APL by National Institute of Health Research (RP-2015-06-012)