Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis

Intestinal epithelial cells (IECs) provide a primary physical barrier against commensal and pathogenic microorganisms in the gastrointestinal (GI) tract, but the influence of IECs on the development and regulation of immunity to infection is unknown. Here we show that IEC-intrinsic IkappaB kinase (IKK)-beta-dependent gene expression is a critical regulator of responses of dendritic cells and CD4+ T cells in the GI tract. Mice with an IEC-specific deletion of IKK-beta show a reduced expression of the epithelial-cell-restricted cytokine thymic stromal lymphopoietin in the intestine and, after infection with the gut-dwelling parasite Trichuris, fail to develop a pathogen-specific CD4+ T helper type 2 (T(H)2) response and are unable to eradicate infection. Further, these animals show exacerbated production of dendritic-cell-derived interleukin-12/23p40 and tumour necrosis factor-alpha, increased levels of CD4+ T-cell-derived interferon-gamma and interleukin-17, and develop severe intestinal inflammation. Blockade of proinflammatory cytokines during Trichuris infection ablates the requirement for IKK-beta in IECs to promote CD4+ T(H)2 cell-dependent immunity, identifying an essential function for IECs in tissue-specific conditioning of dendritic cells and limiting type 1 cytokine production in the GI tract. These results indicate that the balance of IKK-beta-dependent gene expression in the intestinal epithelium is crucial in intestinal immune homeostasis by promoting mucosal immunity and limiting chronic inflammation.     

Early optical emission from the gamma-ray burst of 4 October 2002

Observations of the long-lived emission--or 'afterglow'--of long-duration gamma-ray bursts place them at cosmological distances, but the origin of these energetic explosions remains a mystery. Observations of optical emission contemporaneous with the burst of gamma-rays should provide insight into the details of the explosion, as well as into the structure of the surrounding environment. One bright optical flash was detected during a burst, but other efforts have produced negative results. Here we report the discovery of the optical counterpart of GRB021004 only 193 seconds after the event. The initial decline is unexpectedly slow and requires varying energy content in the gamma-ray burst blastwave over the course of the first hour. Further analysis of the X-ray and optical afterglow suggests additional energy variations over the first few days.     

A common origin for cosmic explosions inferred from calorimetry of GRB030329

Past studies have suggested that long-duration gamma-ray bursts have a 'standard' energy of E(gamma) approximately 10(51) erg in the ultra-relativistic ejecta, after correcting for asymmetries in the explosion ('jets'). But a group of sub-energetic bursts, including the peculiar GRB980425 associated with the supernova SN1998bw (E(gamma) approximately 10(48) erg), has recently been identified. Here we report radio observations of GRB030329 that allow us to undertake calorimetry of the explosion. Our data require a two-component explosion: a narrow (5 degrees opening angle) ultra-relativistic component responsible for the gamma-rays and early afterglow, and a wide, mildly relativistic component that produces the radio and optical afterglow more than 1.5 days after the explosion. The total energy release, which is dominated by the wide component, is similar to that of other gamma-ray bursts, but the contribution of the gamma-rays is energetically minor. Given the firm link of GRB030329 with SN2003dh, our result indicates a common origin for cosmic explosions in which, for reasons not yet understood, the energy in the highest-velocity ejecta is extremely variable.     

The bright optical afterglow of the nearby gamma-ray burst of 29 March 2003

Past studies of cosmological gamma-ray bursts (GRBs) have been hampered by their extreme distances, resulting in faint afterglows. A nearby GRB could potentially shed much light on the origin of these events, but GRBs with a redshift z 相似文献   

Direct frequency comb spectroscopy in the extreme ultraviolet

The development of the optical frequency comb (a spectrum consisting of a series of evenly spaced lines) has revolutionized metrology and precision spectroscopy owing to its ability to provide a precise and direct link between microwave and optical frequencies. A further advance in frequency comb technology is the generation of frequency combs in the extreme-ultraviolet spectral range by means of high-harmonic generation in a femtosecond enhancement cavity. Until now, combs produced by this method have lacked sufficient power for applications, a drawback that has also hampered efforts to observe phase coherence of the high-repetition-rate pulse train produced by high-harmonic generation, which is an extremely nonlinear process. Here we report the generation of extreme-ultraviolet frequency combs, reaching wavelengths of 40?nanometres, by coupling a high-power near-infrared frequency comb to a robust femtosecond enhancement cavity. These combs are powerful enough for us to observe single-photon spectroscopy signals for both an argon transition at 82?nanometres and a neon transition at 63?nanometres, thus confirming the combs' coherence in the extreme ultraviolet. The absolute frequency of the argon transition has been determined by direct frequency comb spectroscopy. The resolved ten-megahertz linewidth of the transition, which is limited by the temperature of the argon atoms, is unprecedented in this spectral region and places a stringent upper limit on the linewidth of individual comb teeth. Owing to the lack of continuous-wave lasers, extreme-ultraviolet frequency combs are at present the only promising route to extending ultrahigh-precision spectroscopy to the spectral region below 100?nanometres. At such wavelengths there is a wide range of applications, including the spectroscopy of electronic transitions in molecules, experimental tests of bound-state and many-body quantum electrodynamics in singly ionized helium and neutral helium, the development of next-generation 'nuclear' clocks and searches for variation of fundamental constants using the enhanced sensitivity of highly charged ions.     

Conserved function for embryonic nodal cilia

How left right handedness originates in the body plan of the developing vertebrate embryo is a subject of considerable debate. In mice, a left right bias is thought to arise from a directional extracellular flow (nodal flow) that is generated by dynein-dependent rotation of monocilia on the ventral surface of the embryonic node. Here we show that the existence of node monocilia and the expression of a dynein gene that is implicated in ciliary function are conserved across a wide range of vertebrate classes, indicating that a similar ciliary mechanism may underlie the establishment of handedness in all vertebrates.     

The sub-energetic gamma-ray burst GRB 031203 as a cosmic analogue to the nearby GRB 980425

Over the six years since the discovery of the gamma-ray burst GRB 980425, which was associated with the nearby (distance approximately 40 Mpc) supernova 1998bw, astronomers have debated fiercely the nature of this event. Relative to bursts located at cosmological distance (redshift z approximately 1), GRB 980425 was under-luminous in gamma-rays by three orders of magnitude. Radio calorimetry showed that the explosion was sub-energetic by a factor of 10. Here we report observations of the radio and X-ray afterglow of the recent GRB 031203 (refs 5-7), which has a redshift of z = 0.105. We demonstrate that it too is sub-energetic which, when taken together with the low gamma-ray luminosity, suggests that GRB 031203 is the first cosmic analogue to GRB 980425. We find no evidence that this event was a highly collimated explosion viewed off-axis. Like GRB 980425, GRB 031203 appears to be an intrinsically sub-energetic gamma-ray burst. Such sub-energetic events have faint afterglows. We expect intensive follow-up of faint bursts with smooth gamma-ray light curves (common to both GRB 031203 and 980425) to reveal a large population of such events.