An asymmetric distribution of positrons in the Galactic disk revealed by gamma-rays

Gamma-ray line radiation at 511 keV is the signature of electron-positron annihilation. Such radiation has been known for 30 years to come from the general direction of the Galactic Centre, but the origin of the positrons has remained a mystery. Stellar nucleosynthesis, accreting compact objects, and even the annihilation of exotic dark-matter particles have all been suggested. Here we report a distinct asymmetry in the 511-keV line emission coming from the inner Galactic disk ( approximately 10-50 degrees from the Galactic Centre). This asymmetry resembles an asymmetry in the distribution of low mass X-ray binaries with strong emission at photon energies >20 keV ('hard' LMXBs), indicating that they may be the dominant origin of the positrons. Although it had long been suspected that electron-positron pair plasmas may exist in X-ray binaries, it was not evident that many of the positrons could escape to lose energy and ultimately annihilate with electrons in the interstellar medium and thus lead to the emission of a narrow 511-keV line. For these models, our result implies that up to a few times 10(41) positrons escape per second from a typical hard LMXB. Positron production at this level from hard LMXBs in the Galactic bulge would reduce (and possibly eliminate) the need for more exotic explanations, such as those involving dark matter.     

Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells

Lymph nodes prevent the systemic dissemination of pathogens such as viruses that infect peripheral tissues after penetrating the body's surface barriers. They are also the staging ground of adaptive immune responses to pathogen-derived antigens. It is unclear how virus particles are cleared from afferent lymph and presented to cognate B cells to induce antibody responses. Here we identify a population of CD11b+CD169+MHCII+ macrophages on the floor of the subcapsular sinus (SCS) and in the medulla of lymph nodes that capture viral particles within minutes after subcutaneous injection. Macrophages in the SCS translocated surface-bound viral particles across the SCS floor and presented them to migrating B cells in the underlying follicles. Selective depletion of these macrophages compromised local viral retention, exacerbated viraemia of the host, and impaired local B-cell activation. These findings indicate that CD169+ macrophages have a dual physiological function. They act as innate 'flypaper' by preventing the systemic spread of lymph-borne pathogens and as critical gatekeepers at the lymph-tissue interface that facilitate the recognition of particulate antigens by B cells and initiate humoral immune responses.     

RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels

Therapeutics that discriminate between the genetic makeup of normal cells and tumour cells are valuable for treating and understanding cancer. Small molecules with oncogene-selective lethality may reveal novel functions of oncoproteins and enable the creation of more selective drugs. Here we describe the mechanism of action of the selective anti-tumour agent erastin, involving the RAS-RAF-MEK signalling pathway functioning in cell proliferation, differentiation and survival. Erastin exhibits greater lethality in human tumour cells harbouring mutations in the oncogenes HRAS, KRAS or BRAF. Using affinity purification and mass spectrometry, we discovered that erastin acts through mitochondrial voltage-dependent anion channels (VDACs)--a novel target for anti-cancer drugs. We show that erastin treatment of cells harbouring oncogenic RAS causes the appearance of oxidative species and subsequent death through an oxidative, non-apoptotic mechanism. RNA-interference-mediated knockdown of VDAC2 or VDAC3 caused resistance to erastin, implicating these two VDAC isoforms in the mechanism of action of erastin. Moreover, using purified mitochondria expressing a single VDAC isoform, we found that erastin alters the permeability of the outer mitochondrial membrane. Finally, using a radiolabelled analogue and a filter-binding assay, we show that erastin binds directly to VDAC2. These results demonstrate that ligands to VDAC proteins can induce non-apoptotic cell death selectively in some tumour cells harbouring activating mutations in the RAS-RAF-MEK pathway.     

Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes

N-methyl-D-aspartate (NMDA) receptors mediate excitatory neurotransmission in the mammalian brain. Two glycine-binding NR1 subunits and two glutamate-binding NR2 subunits each form highly Ca2(+)-permeable cation channels which are blocked by extracellular Mg2(+) in a voltage-dependent manner. Either GRIN2B or GRIN2A, encoding the NMDA receptor subunits NR2B and NR2A, was found to be disrupted by chromosome translocation breakpoints in individuals with mental retardation and/or epilepsy. Sequencing of GRIN2B in 468 individuals with mental retardation revealed four de novo mutations: a frameshift, a missense and two splice-site mutations. In another cohort of 127 individuals with idiopathic epilepsy and/or mental retardation, we discovered a GRIN2A nonsense mutation in a three-generation family. In a girl with early-onset epileptic encephalopathy, we identified the de novo GRIN2A mutation c.1845C>A predicting the amino acid substitution p.N615K. Analysis of NR1-NR2A(N615K) (NR2A subunit with the p.N615K alteration) receptor currents revealed a loss of the Mg2(+) block and a decrease in Ca2(+) permeability. Our findings suggest that disturbances in the neuronal electrophysiological balance during development result in variable neurological phenotypes depending on which NR2 subunit of NMDA receptors is affected.     

Risks posed by obesity to body-surface narrowband wireless communication

Little work has been done on the effect of being overweight on the wireless narrowband radio propagation of wearable medical instruments. In this paper, by applying a finite-difference time-domain technique and a statistical learning method, the authors find that being overweight might be an obstacle to body-surface wireless communication. The findings have certain instructive meanings for those engineers who are designing on-body medical instruments for patients, especially those patients who are overweight.     

High Temperature Properties and Microstructures of Si_3N_4 with AZ-Type Non-Toxic, Non-Oxide Additives

A new type of Si3N4 ceramics (ZAN) is developed in our laboratory. Densification of ZAN is promoted by non-toxic, non-oxide AZ-type additives. In this work high temperature (HT) properties and microstructures of ZAN are investigated.     

The effect of bovine myelin basic protein on uptake and release of H3-labelled 5-hydroxytryptamine,L-noradrenalin and γ-aminobutyric acid in rat cortex slices

Summary At concentrations above 10^–5 M myelin basic protein (MBP) induced a small inhibition of the uptake of H³-5HT and H³-NA into rat cortex slices. Release of 5HT, NA and Gaba was not affected by 10^–5 M MBP.Acknowledgment. The authors wish to thank W. Bucher for the preparation of MBP.