Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit

Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit, the inflammatory reflex, inhibits tumor necrosis factor-α production in spleen by a mechanism requiring acetylcholine signaling through the α7 nicotinic acetylcholine receptor expressed on cytokine-producing macrophages. Nerve fibers in spleen lack the enzymatic machinery necessary for acetylcholine production; therefore, how does this neural circuit terminate in cholinergic signaling? We identified an acetylcholine-producing, memory phenotype T cell population in mice that is integral to the inflammatory reflex. These acetylcholine-producing T cells are required for inhibition of cytokine production by vagus nerve stimulation. Thus, action potentials originating in the vagus nerve regulate T cells, which in turn produce the neurotransmitter, acetylcholine, required to control innate immune responses.     

Stable carbon cycle-climate relationship during the Late Pleistocene

A record of atmospheric carbon dioxide (CO2) concentrations measured on the EPICA (European Project for Ice Coring in Antarctica) Dome Concordia ice core extends the Vostok CO2 record back to 650,000 years before the present (yr B.P.). Before 430,000 yr B.P., partial pressure of atmospheric CO2 lies within the range of 260 and 180 parts per million by volume. This range is almost 30% smaller than that of the last four glacial cycles; however, the apparent sensitivity between deuterium and CO2 remains stable throughout the six glacial cycles, suggesting that the relationship between CO2 and Antarctic climate remained rather constant over this interval.     

Detection of GTP-tubulin conformation in vivo reveals a role for GTP remnants in microtubule rescues

Microtubules display dynamic instability, with alternating phases of growth and shrinkage separated by catastrophe and rescue events. The guanosine triphosphate (GTP) cap at the growing end of microtubules, whose presence is essential to prevent microtubule catastrophes in vitro, has been difficult to observe in vivo. We selected a recombinant antibody that specifically recognizes GTP-bound tubulin in microtubules and found that GTP-tubulin was indeed present at the plus end of growing microtubules. Unexpectedly, GTP-tubulin remnants were also present in older parts of microtubules, which suggests that GTP hydrolysis is sometimes incomplete during polymerization. Observations in living cells suggested that these GTP remnants may be responsible for the rescue events in which microtubules recover from catastrophe.     

A physical map of the 1-gigabase bread wheat chromosome 3B

As the staple food for 35% of the world's population, wheat is one of the most important crop species. To date, sequence-based tools to accelerate wheat improvement are lacking. As part of the international effort to sequence the 17-billion-base-pair hexaploid bread wheat genome (2n = 6x = 42 chromosomes), we constructed a bacterial artificial chromosome (BAC)-based integrated physical map of the largest chromosome, 3B, that alone is 995 megabases. A chromosome-specific BAC library was used to assemble 82% of the chromosome into 1036 contigs that were anchored with 1443 molecular markers, providing a major resource for genetic and genomic studies. This physical map establishes a template for the remaining wheat chromosomes and demonstrates the feasibility of constructing physical maps in large, complex, polyploid genomes with a chromosome-based approach.     

On the origin of interictal activity in human temporal lobe epilepsy in vitro

The origin and mechanisms of human interictal epileptic discharges remain unclear. Here, we describe a spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy. Synchronous events were similar to interictal discharges of patient electroencephalograms. They were suppressed by antagonists of either glutamatergic or gamma-aminobutyric acid (GABA)-ergic signaling. The network of neurons discharging during population events comprises both subicular interneurons and a subgroup of pyramidal cells. In these pyramidal cells, GABAergic synaptic events reversed at depolarized potentials. Depolarizing GABAergic responses in neurons downstream to the sclerotic CA1 region contribute to human interictal activity.     

Conical intersection dynamics in NO2 probed by homodyne high-harmonic spectroscopy

Conical intersections play a crucial role in the chemistry of most polyatomic molecules, ranging from the simplest bimolecular reactions to the photostability of DNA. The real-time study of the associated electronic dynamics poses a major challenge to the latest techniques of ultrafast measurement. We show that high-harmonic spectroscopy reveals oscillations in the electronic character that occur in nitrogen dioxide when a photoexcited wave packet crosses a conical intersection. At longer delays, we observe the onset of statistical dissociation dynamics. The present results demonstrate that high-harmonic spectroscopy could become a powerful tool to highlight electronic dynamics occurring along nonadiabatic chemical reaction pathways.     

Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I

Small nuclear RNAs (snRNAs) are essential factors in messenger RNA splicing. By means of homozygosity mapping and deep sequencing, we show that a gene encoding U4atac snRNA, a component of the minor U12-dependent spliceosome, is mutated in individuals with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), a severe developmental disorder characterized by extreme intrauterine growth retardation and multiple organ abnormalities. Functional assays showed that mutations (30G>A, 51G>A, 55G>A, and 111G>A) associated with MOPD I cause defective U12-dependent splicing. Endogenous U12-dependent but not U2-dependent introns were found to be poorly spliced in MOPD I patient fibroblast cells. The introduction of wild-type U4atac snRNA into MOPD I cells enhanced U12-dependent splicing. These results illustrate the critical role of minor intron splicing in human development.     

Rubidium-87/strontium-87 age of juvinas basaltic achondrite and early igneous activity in the solar system

A (4.60+/-0.07)x10(9) year internal isochron has been drawn for the achondrite Juvinas by the rubidium-87/strontium-87 method. Earlier petrographic investigation of achondrites supplemented by a new ion microprobe study of Juvinas strongly suggest an igneous origin for this class of meteorites. The results thus indicate that igneous activity may have rapidly followed the formation of the achondrites' parent body 4.6x10(9) years ago.