The Secreted Acid Phosphatase Domain-Containing GRA44 from Toxoplasma gondii Is Required for c-Myc Induction in Infected Cells.

During host cell invasion, the eukaryotic pathogen Toxoplasma gondii forms a parasitophorous vacuole to safely reside within the cell, while it is partitioned from host cell defense mechanisms. From within this safe niche, parasites sabotage multiple host cell systems, including gene expression, apoptosis, and intracellular immune recognition, by secreting a large arsenal of effector proteins. Many parasite proteins studied for active host cell manipulative interactions have been kinases. The translocation of effectors from the parasitophorous vacuole into the host cell is mediated by a putative translocon complex, which includes the proteins MYR1, MYR2, and MYR3. Whether other proteins are involved in the structure or regulation of this putative translocon is not known. We have discovered that the secreted protein GRA44, which contains a putative acid phosphatase domain, interacts with members of this complex and is required for host cell effects downstream of effector secretion. We have determined that GRA44 is processed in a region with homology to sequences targeted by protozoan proteases of the secretory pathway and that both major cleavage fragments are secreted into the parasitophorous vacuole. Immunoprecipitation experiments showed that GRA44 interacts with a large number of secreted proteins, including MYR1. Importantly, conditional knockdown of GRA44 resulted in a lack of host cell c-Myc upregulation, which mimics the phenotype seen when members of the translocon complex are genetically disrupted. Thus, the putative acid phosphatase GRA44 is crucial for host cell alterations during Toxoplasma infection and is associated with the translocon complex which Toxoplasma relies upon for success as an intracellular pathogen.IMPORTANCE Approximately one-third of humans are infected with the parasite Toxoplasma gondii Toxoplasma infections can lead to severe disease in those with a compromised or suppressed immune system. Additionally, infections during pregnancy present a significant health risk to the developing fetus. Drugs that target this parasite are limited, have significant side effects, and do not target all disease stages. Thus, a thorough understanding of how the parasite propagates within a host is critical in the discovery of novel therapeutic targets. Toxoplasma replication requires that it enter the cells of the infected organism. In order to survive the environment inside a cell, Toxoplasma secretes a large repertoire of proteins, which hijack a number of important cellular functions. How these Toxoplasma proteins move from the parasite into the host cell is not well understood. Our work shows that the putative phosphatase GRA44 is part of a protein complex responsible for this process

Observations of Musk Oxen on Banks Island, Northwest Territories, Canada

Notes summer 1963 observations of Ovibos moschatus. On a reconnaissance flight over the northern third of the island on Aug. 2 nearly sixty were seen, indicating greater abundance than hitherto supposed. Only two were seen south of the reconnaissance area during a two-month period; apparently they concentrate in the northern part at least during the summer

Initial test results on bolometers for the Planck high frequency instrument

We summarize the fabrication, flight qualification, and dark performance of bolometers completed at the Jet Propulsion Laboratory for the High Frequency Instrument (HFI) of the joint ESA/NASA Herschel/Planck mission to be launched in 2009. The HFI is a multicolor focal plane which consists of 52 bolometers operated at 100 mK. Each bolometer is mounted to a feedhorn-filter assembly which defines one of six frequency bands centered between 100-857 GHz. Four detectors in each of five bands from 143-857 GHz are coupled to both linear polarizations and thus measure the total intensity. In addition, eight detectors in each of four bands (100, 143, 217, and 353 GHz) couple only to a single linear polarization and thus provide measurements of the Stokes parameters, Q and U, as well as the total intensity. The measured noise equivalent power (NEP) of all detectors is at or below the background limit for the telescope and time constants are a few ms, short enough to resolve point sources as the 5 to 9 arc min beams move across the sky at 1 rpm

A framework for live host-based Bitcoin wallet forensics and triage

Organised crime and cybercriminals use Bitcoin, a popular cryptocurrency, to launder money and move it across borders with impunity. The UK and other countries have legislation to recover the proceeds of crime from criminals. Recent UK case law has recognised cryptocurrency assets as property that can be seized and realised under the Proceeds of Crime Act (POCA). To seize a cryptocurrency asset generally requires access to the private key. Anecdotal evidence suggests that if cryptocurrency is not seized quickly after enforcement action has taken place, it will be transferred to other wallets making it difficult to seize at a future time. We investigate how Bitcoin could be seized from an Electrum or Ledger hardware wallet, during a law enforcement search, using live forensic techniques and a dictionary attack.We conduct a literature review examining the state-of-the-art in Bitcoin application forensics and Bitcoin wallet attacks. Concluding, that there is a gap in research on Bitcoin wallet security and that a significant proportion of the available literature comes from a small group of academics working with industry and law enforcement (Volety et al. 2019; Van Der Horst et al., 2017; Zollner et al., 2019). We then forensically examine the Electrum software wallet and the Ledger Nano S hardware wallet, to establish what artefacts can be recovered to assist in the recovery of Bitcoin from the wallets. Our main contribution is a proposed framework for Bitcoin forensic triage, a collection tool to recover Bitcoin artefacts and identifiers, and two proof of concept dictionary-attack tools written in Python and OpenCL.We then evaluate these tools to establish if an attack is practicable using a low-cost cluster of public cloud-based Graphics Processing Unit (GPU) instances. During our investigation, we find a weakness in Electrum's storage of encrypted private keys in RAM. We leverage this to make around 2.4 trillion password guesses. We also demonstrate that we can conduct 16.6 billion guesses against a password protected Ledger seed phrase