Global landscape of HIV-human protein complexes

Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with ～40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection.     

IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics

Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas and cytogenetically normal acute myeloid leukaemias (AML). These alterations are gain-of-function mutations in that they drive the synthesis of the ‘oncometabolite’ R-2-hydroxyglutarate (2HG). It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukaemogenesis. Here we report the characterization of conditional knock-in (KI) mice in which the most common IDH1 mutation, IDH1(R132H), is inserted into the endogenous murine Idh1 locus and is expressed in all haematopoietic cells (Vav-KI mice) or specifically in cells of the myeloid lineage (LysM-KI mice). These mutants show increased numbers of early haematopoietic progenitors and develop splenomegaly and anaemia with extramedullary haematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells have hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1- or IDH2-mutant AML. To our knowledge, our study is the first to describe the generation and characterization of conditional IDH1(R132H)-KI mice, and also the first report to demonstrate the induction of a leukaemic DNA methylation signature in a mouse model. Our report thus sheds light on the mechanistic links between IDH1 mutation and human AML.     

Non-detection at Venus of high-frequency radio signals characteristic of terrestrial lightning

The detection of impulsive low-frequency (10 to 80 kHz) radio signals, and separate very-low-frequency (approximately 100 Hz) radio 'whistler' signals provided the first evidence for lightning in the atmosphere of Venus. Later, a small number of impulsive high-frequency (100 kHz to 5.6 MHz) radio signals, possibly due to lightning, were also detected. The existence of lightning at Venus has, however, remained controversial. Here we report the results of a search for high-frequency (0.125 to 16 MHz) radio signals during two close fly-bys of Venus by the Cassini spacecraft. Such signals are characteristic of terrestrial lightning, and are commonly heard on AM (amplitude-modulated) radios during thunderstorms. Although the instrument easily detected signals from terrestrial lightning during a later fly-by of Earth (at a global flash rate estimated to be 70 s(-1), which is consistent with the rate expected for terrestrial lightning), no similar signals were detected from Venus. If lightning exists in the venusian atmosphere, it is either extremely rare, or very different from terrestrial lightning.     

Kreisende kortikale Potentialfelder beim epileptischen Anfall

Summary The circular movement of cortical potential fields during epileptic seizures of the rabbit, evoked by intracortical application of penicillin, is described.     

Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family

Magnesium is an essential ion involved in many biochemical and physiological processes. Homeostasis of magnesium levels is tightly regulated and depends on the balance between intestinal absorption and renal excretion. However, little is known about specific proteins mediating transepithelial magnesium transport. Using a positional candidate gene approach, we identified mutations in TRPM6 (also known as CHAK2), encoding TRPM6, in autosomal-recessive hypomagnesemia with secondary hypocalcemia (HSH, OMIM 602014), previously mapped to chromosome 9q22 (ref. 3). The TRPM6 protein is a new member of the long transient receptor potential channel (TRPM) family and is highly similar to TRPM7 (also known as TRP-PLIK), a bifunctional protein that combines calcium- and magnesium-permeable cation channel properties with protein kinase activity. TRPM6 is expressed in intestinal epithelia and kidney tubules. These findings indicate that TRPM6 is crucial for magnesium homeostasis and implicate a TRPM family member in human disease.     

Control of Jupiter's radio emission and aurorae by the solar wind

Radio emissions from Jupiter provided the first evidence that this giant planet has a strong magnetic field and a large magnetosphere. Jupiter also has polar aurorae, which are similar in many respects to Earth's aurorae. The radio emissions are believed to be generated along the high-latitude magnetic field lines by the same electrons that produce the aurorae, and both the radio emission in the hectometric frequency range and the aurorae vary considerably. The origin of the variability, however, has been poorly understood. Here we report simultaneous observations using the Cassini and Galileo spacecraft of hectometric radio emissions and extreme ultraviolet auroral emissions from Jupiter. Our results show that both of these emissions are triggered by interplanetary shocks propagating outward from the Sun. When such a shock arrives at Jupiter, it seems to cause a major compression and reconfiguration of the magnetosphere, which produces strong electric fields and therefore electron acceleration along the auroral field lines, similar to the processes that occur during geomagnetic storms at the Earth.     

Metabolism of pyridine and 3-hydroxypyridine under aerobic,denitrifying and sulfate-reducing conditions

Summary The transformation of pyridine and several hydroxypyridines was investigated under different physiological conditions. Pyridine and 2-, 3- and 4-hydroxypyridine were metabolized aerobically within 9 days in a mineral salt medium inoculated with 10% sewage sludge. Under anaerobic conditions in the presence of nitrate or sulfate, pyridine and 3-hydroxypyridine were metabolized after a lag period of 2 months, while no transformation of 2- or 4-hydroxypyridine was detected. Experiments with¹⁴C-labeled-pyridine showed that under denitrifying as well as under sulfate-reducing conditions pyridine was oxidized to carbon dioxide. Disappearance of nitrate and sulfate under anaerobic conditions was 79% and 85%, respectively, of the amount predicted from the stoichiometric equation for the complete transformation of pyridine.