Author Correction: Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.

Change history: In this Letter, author M. Akhlaghi should be associated with affiliation (2) rather than (3). This error has been corrected online.

Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.

Galaxies are surrounded by large reservoirs of gas, mostly hydrogen, that are fed by inflows from the intergalactic medium and by outflows from galactic winds. Absorption-line measurements along the lines of sight to bright and rare background quasars indicate that this circumgalactic medium extends far beyond the starlight seen in galaxies, but very little is known about its spatial distribution. The Lyman-α transition of atomic hydrogen at a wavelength of 121.6 nanometres is an important tracer of warm (about 104 kelvin) gas in and around galaxies, especially at cosmological redshifts greater than about 1.6 at which the spectral line becomes observable from the ground. Tracing cosmic hydrogen through its Lyman-α emission has been a long-standing goal of observational astrophysics1-3, but the extremely low surface brightness of the spatially extended emission is a formidable obstacle. A new window into circumgalactic environments was recently opened by the discovery of ubiquitous extended Lyman-α emission from hydrogen around high-redshift galaxies4,5. Such measurements were previously limited to especially favourable systems6-8 or to the use of massive statistical averaging9,10 because of the faintness of this emission. Here we report observations of low-surface-brightness Lyman-α emission surrounding faint galaxies at redshifts between 3 and 6. We find that the projected sky coverage approaches 100 per cent. The corresponding rate of incidence (the mean number of Lyman-α emitters penetrated by any arbitrary line of sight) is well above unity and similar to the incidence rate of high-column-density absorbers frequently detected in the spectra of distant quasars11-14. This similarity suggests that most circumgalactic atomic hydrogen at these redshifts has now been detected in emission.

Signatures of cool gas fueling a star-forming galaxy at redshift 2.3.

Galaxies are thought to be fed by the continuous accretion of intergalactic gas, but direct observational evidence has been elusive. The accreted gas is expected to orbit about the galaxy's halo, delivering not just fuel for star formation but also angular momentum to the galaxy, leading to distinct kinematic signatures. We report observations showing these distinct signatures near a typical distant star-forming galaxy, where the gas is detected using a background quasar passing 26 kiloparsecs from the host. Our observations indicate that gas accretion plays a major role in galaxy growth because the estimated accretion rate is comparable to the star-formation rate.

Cell encapsulation technology as a novel strategy for human anti-tumor immunotherapy.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant in autologous cell-based anti-tumor immunotherapy has recently been approved for clinical application. To avoid the need for individualized processing of autologous cells, we developed a novel strategy based on the encapsulation of GM-CSF-secreting human allogeneic cells. GM-CSF-producing K562 cells showed high, stable and reproducible cytokine secretion when enclosed into macrocapsules. For clinical development, the cryopreservation of these devices is critical. Thawing of capsules frozen at different time points displayed differences in GM-CSF release shortly after thawing. However, similar secretion values to those of non-frozen control capsules were obtained 8 days after thawing at a rate of >1000 ng GM-CSF per capsule every 24 h. For future human application, longer and reinforced capsules were designed. After irradiation and cryopreservation, these capsules produced >300 ng GM-CSF per capsule every 24 h 1 week after thawing. The in vivo implantation of encapsulated K562 cells was evaluated in mice and showed preserved cell survival. Finally, as a proof of principle of biological activity, capsules containing B16-GM-CSF allogeneic cells implanted in mice induced a prompt inflammatory reaction. The ability to reliably achieve high adjuvant release using a standardized procedure may lead to a new clinical application of GM-CSF in cell-based cancer immunization.

High molecular gas fractions in normal massive star-forming galaxies in the young Universe.

Stars form from cold molecular interstellar gas. As this is relatively rare in the local Universe, galaxies like the Milky Way form only a few new stars per year. Typical massive galaxies in the distant Universe formed stars an order of magnitude more rapidly. Unless star formation was significantly more efficient, this difference suggests that young galaxies were much more molecular-gas rich. Molecular gas observations in the distant Universe have so far largely been restricted to very luminous, rare objects, including mergers and quasars, and accordingly we do not yet have a clear idea about the gas content of more normal (albeit massive) galaxies. Here we report the results of a survey of molecular gas in samples of typical massive-star-forming galaxies at mean redshifts of about 1.2 and 2.3, when the Universe was respectively 40% and 24% of its current age. Our measurements reveal that distant star forming galaxies were indeed gas rich, and that the star formation efficiency is not strongly dependent on cosmic epoch. The average fraction of cold gas relative to total galaxy baryonic mass at z = 2.3 and z = 1.2 is respectively about 44% and 34%, three to ten times higher than in today's massive spiral galaxies. The slow decrease between z approximately 2 and z approximately 1 probably requires a mechanism of semi-continuous replenishment of fresh gas to the young galaxies.

An in vivo culture system for human embryos using an encapsulation technology: a pilot study.

BACKGROUND: Animal studies have demonstrated better embryo development in vivo than in vitro. This pilot study tested the feasibility of using a novel in utero culture system (IUCS) to obtain normal human fertilization and embryo development. METHODS: The IUCS device comprised a perforated silicone hollow tube. The study included 13 patients (<36 years) undergoing a first intracytoplasmic sperm injection (ICSI) treatment and 167 metaphase II oocytes in three groups. In Group 1, 1-2 h after ICSI, sibling oocytes were assigned to IUCS or conventional in vitro culture. The device was retrieved on Day 1, and all zygotes were cultured in vitro till Day 5. In Group 2, fertilized oocytes were assigned on Day 1, embryos retrieved on Day 3 and all embryos cultured till Day 5. In Group 3, after Day 0 assignment, embryos were retrieved on Day 3 for blastomere biopsy and fluorescence in situ hybridization (FISH) and cultured until Day 5. The highest quality blastocysts were transferred on Day 5. RESULTS: Fertilization and embryo development were comparable in the in vitro and IUCS arms, with a tendency towards better embryo quality in the IUCS. FISH analysis in Group 3 revealed more normal embryos using the IUCS (P = 0.049). Three clinical pregnancies and live births were obtained: two from the IUCS arm and one from the in vitro arm. CONCLUSIONS: Our pilot study shows that this new IUCS appears to be feasible and safe, supporting normal fertilization, embryo development and normal chromosomal segregation. Furthermore, live births are possible after the transient presence of a silicone device in the uterus. Clinicaltrials.gov: NCT00480103.

The rapid formation of a large rotating disk galaxy three billion years after the Big Bang.

Observations and theoretical simulations have established a framework for galaxy formation and evolution in the young Universe. Galaxies formed as baryonic gas cooled at the centres of collapsing dark-matter haloes; mergers of haloes and galaxies then led to the hierarchical build-up of galaxy mass. It remains unclear, however, over what timescales galaxies were assembled and when and how bulges and disks--the primary components of present-day galaxies--were formed. It is also puzzling that the most massive galaxies were more abundant and were forming stars more rapidly at early epochs than expected from models. Here we report high-angular-resolution observations of a representative luminous star-forming galaxy when the Universe was only 20% of its current age. A large and massive rotating protodisk is channelling gas towards a growing central stellar bulge hosting an accreting massive black hole. The high surface densities of gas, the high rate of star formation and the moderately young stellar ages suggest rapid assembly, fragmentation and conversion to stars of an initially very gas-rich protodisk, with no obvious evidence for a major merger.

In vivo calcium deposition on polyvinyl alcohol matrix used in hollow fiber cell macroencapsulation devices.

The encapsulation of genetically modified cells represents a promising approach for the delivery of therapeutic proteins. The functionality of the device is dependent on the characteristics of the biomaterials, the procedures used in its confection and the adaptability of the encapsulated cells in the host. We report conditions leading to the development of calcifications on the polyvinyl alcohol (PVA) matrix introduced in hollow fiber devices for the encapsulation of primary human fibroblasts implanted in mice. The manufacturing procedures, batches of PVA matrix and cell lineages were assessed for their respective role in the development of the phenomenon. The results showed that the calcification is totally prevented by substituting phosphate-buffer saline with ultra-pure sterile water in the rinsing procedure of the matrix. Moreover, a positive correlation was found, when comparing two fibroblast cell lineages, between the level of lactate dehydrogenase (LDH) activity measured in the cells and the degree of calcium deposition. Higher LDH activity may decrease calcium depositions because it generates in the device a more acidic microenvironment inhibiting calcium precipitation. The present study defines optimized conditions for the encapsulation of primary human fibroblasts in order to avoid potentially detrimental calcifications and to allow long-term survival of encapsulated cells.

Nerve growth factor- and neurotrophin-3-releasing guidance channels promote regeneration of the transected rat dorsal root.

Dorsal roots have a limited regeneration capacity after transection. To improve nerve regeneration, the growth-promoting effects of the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were evaluated. The proteins were continuously released by synthetic nerve guidance channels bridging a 4-mm gap in the transected dorsal root. Four weeks after lesion, the regenerated nerve cables were analyzed for the presence of myelinated and unmyelinated axons. While BDNF showed a limited effect on axonal regeneration (863 +/- 39 axons/regenerated nerve, n = 6), NGF (1843 +/- 482) and NT-3 (1495 +/- 449) powerfully promoted regeneration of myelinated axons compared to channels releasing the control protein bovine serum albumin (293 +/- 39). In addition, NGF, but not BDNF nor NT-3, had a potent effect on the regeneration of unmyelinated axons (NGF, 55 +/- 1.4; BDNF, 4 +/- 0.3; NT-3, 4.7 +/- 0.3 axons/100 microm(2); n = 6). The present study suggests that synthetic nerve guidance channels slowly and continuously releasing the neurotrophins NGF and NT-3 can overcome the limited regeneration of transected dorsal root.

Arabidopsis gene knockout: phenotypes wanted.

Gene knockout is considered to be a major component of the functional genomics toolbox, and is aimed at revealing the function of genes discovered through large-scale sequencing programs. In the past few years, several Arabidopsis populations mutagenized with insertion elements, such as the T-DNA of Agrobacterium or transposons, have been produced. These large populations are routinely screened for insertions into specific genes, allowing mass-isolation of knockout lines. Although many Arabidopsis knockouts have already been obtained, few of them have been reported to present informative phenotypes that provide a direct clue to gene function. Although functional redundancy explains the lack of phenotypical alterations in some cases, it also appears that many mutations are conditional and/or do not alter plant morphology even in the presence of severe physiological defects. Consequently, gene knockout per se is not sufficient to assess gene function and must be integrated into a more global approach for determining biological functions.

Expression of a truncated tobacco NtCBP4 channel in transgenic plants and disruption of the homologous Arabidopsis CNGC1 gene confer Pb2+ tolerance.

Recently we reported on a plasma membrane tobacco protein (designated NtCBP4) that binds calmodulin. When overexpressed in transgenic plants, NtCBP4 confers Pb2+ hypersensitivity associated with enhanced accumulation of this toxic metal. To further investigate possible modulation of Pb2+ tolerance in plants, we prepared transgenic plants that express a truncated version of this protein (designated NtCBP4DeltaC) from which its C-terminal, with the calmodulin-binding domain and part of the putative cyclic nucleotide-binding domain, was removed. In contrast to the phenotype of transgenic plants expressing the full-length gene, transgenic plants expressing the truncated gene showed improved tolerance to Pb2+, in addition to attenuated accumulation of this metal. Furthermore, disruption by T-DNA insertion mutagenesis of the Arabidopsis CNGC1 gene, which encodes a homologous protein, also conferred Pb2+ tolerance. We suggest that NtCBP4 and AtCNGC1 are components of a transport pathway responsible for Pb2+ entry into plant cells.

Hydrogel-based three-dimensional matrix for neural cells.

The ability to organize cells in three dimensions (3D) is an important component of tissue engineering. This study sought to develop an extracellular matrix (ECM) equivalent with a physicochemical structure capable of supporting neurite extension from primary neural cells in 3D. Rat embryonic day 14 striatal cells and chick embryonic day 9 dorsal root ganglia extended neurites in 3D in agarose hydrogels in a gel concentration-dependent manner. Primary neural cells did not extend neurites above a threshold agarose gel concentration of 1.25% wt/vol. Gel characterization by hydraulic permeability studies revealed that the average pore radius of a 1.25% agarose gel was 150 mm. Hydraulic permeability studies for calculating average gel pore radius and gel morphology studies by environmental and scanning electron micrography showed that the average agarose gel por size decreased exponentially as the gel concentration increased. It is hypothesized that the average gel porosity plays an important role in determining the ability of agarose gels to support neurite extension. Lamination of alternating nonpermissive, permissive, and nonpermissive gel layers facilitated the creation of 3D neural tracts in vitro. This ability of agarose hydrogels to organize, support, and direct neurite extension from neural cells may be useful for applications such as 3D neural cell culture and nerve regeneration. Agarose hydrogel substrates also offer the possibility of manipulating cells in 3D, and may be used as 3D templates for tissue engineering efforts in vitro and in vivo.