A Microfluidic Device for Whole-Animal Drug Screening Using Electrophysiological Measures in the Nematode C. Elegans

This paper describes the fabrication and use of a microfluidic device for performing whole-animal chemical screens using non-invasive electrophysiological readouts of neuromuscular function in the nematode worm, C. elegans. The device consists of an array of microchannels to which electrodes are attached to form recording modules capable of detecting the electrical activity of the pharynx, a heart-like neuromuscular organ involved in feeding. The array is coupled to a tree-like arrangement of distribution channels that automatically delivers one nematode to each recording module. The same channels are then used to perfuse the recording modules with test solutions while recording the electropharyngeogram (EPG) from each worm with sufficient sensitivity to detect each pharyngeal contraction. The device accurately reported the acute effects of known anthelmintics (anti-nematode drugs) and also correctly distinguished a specific drug-resistant mutant strain of C. elegans from wild type. The approach described here is readily adaptable to parasitic species for the identification of novel anthelmintics. It is also applicable in toxicology and drug discovery programs for human metabolic and degenerative diseases for which C. elegans is used as a model.Chemistry and Chemical Biolog

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Synchronous diversification of Sulawesis iconic artiodactyls driven by recent geological events.

The high degree of endemism on Sulawesi has previously been suggested to have vicariant origins, dating back to 40 Ma. Recent studies, however, suggest that much of Sulawesis fauna assembled over the last 15 Myr. Here, we test the hypothesis that more recent uplift of previously submerged portions of land on Sulawesi promoted diversification and that much of its faunal assemblage is much younger than the island itself. To do so, we combined palaeogeographical reconstructions with genetic and morphometric datasets derived from Sulawesis three largest mammals: the babirusa, anoa and Sulawesi warty pig. Our results indicate that although these species most likely colonized the area that is now Sulawesi at different times (14 Ma to 2-3 Ma), they experienced an almost synchronous expansion from the central part of the island. Geological reconstructions indicate that this area was above sea level for most of the last 4 Myr, unlike most parts of the island. We conclude that emergence of land on Sulawesi (approx. 1-2 Myr) may have allowed species to expand synchronously. Altogether, our results indicate that the establishment of the highly endemic faunal assemblage on Sulawesi was driven by geological events over the last few million years

Integrated Ocean Drilling Program Expedition 327 Preliminary Report: Juan de Fuca Ridge-Flank Hydrogeology The hydrogeologic architecture of basaltic oceanic crust: compartmentalization, anisotropy, microbiology, and crustal-scale properties on the eastern flank of Juan de Fuca Ridge, eastern Pacific Ocean, 5 July–5 September 2010

Integrated Ocean Drilling Program (IODP) Expedition 327 and related experiments focus on understanding fluid–rock interactions in young, upper ocean crust on the eastern flank of the Juan de Fuca Ridge, delineating the magnitude and distribution of hydrologic properties; the extent to which crustal compartments are connected or isolated (laterally and with depth); the rates and spatial extent of ridge-flank fluid circulation; and links between ridge-flank circulation, crustal alteration, and geomicrobial processes. Expedition 327 built on the achievements of IODP Expedition 301 and subsequent submersible and remotely operated vehicle (ROV) expeditions. Both drilling expeditions installed subseafloor borehole observatories ("CORKs") in basement holes to allow borehole conditions to recover to a more natural state after the dissipation of disturbances caused by drilling, casing, and other operations; provide a long-term monitoring and sampling presence for determining fluid pressure, temperature, composition, and microbiology; and facilitate the completion of active experiments to resolve crustal hydrogeologic conditions and processes.During Expedition 327, two basement holes were cored and drilled at Site U1362. Hole U1362A was cored and drilled to 528 meters below seafloor (mbsf) (292 meters subbasement [msb]), subjected to geophysical logging and hydrologic testing, and instrumented with a multilevel CORK observatory. Hole U1362B was drilled to 359 mbsf (117 msb), subjected to a 24 h pumping and tracer injection experiment, and instrumented with a single-level CORK observatory. Both CORK observatories include monitoring of pressure and temperature and downhole fluid and microbiology sampling. Wellhead samplers will be added and a long-term cross-hole test will be initiated during a postdrilling ROV expedition scheduled for Summer 2011. In addition, part of an instrument string deployed in Hole U1301B during Expedition 301 was recovered, and a replacement string of thermal sensors was installed. Finally, a program of shallow sediment coring was completed adjacent to Grizzly Bare outcrop, a suspected site of regional hydrothermal recharge. Thermal measurements and analyses of pore fluid and microbiological samples from a series of holes aligned radially from the outcrop edge will elucidate rates of fluid transport and evolution during the initial stages of ridge-flank hydrothermal circulation

Data from: Synchronous diversification of Sulawesi's iconic artiodactyls driven by recent geological events

The high degree of endemism on Sulawesi has previously been suggested to have vicariant origins, dating back 40 Myr ago. Recent studies, however, suggest that much of Sulawesi’s fauna assembled over the last 15 Myr. Here, we test the hypothesis that more recent uplift of previously submerged portions of land on Sulawesi promoted diversification, and that much of its faunal assemblage is much younger than the island itself. To do so, we combined palaeogeographical reconstructions with genetic and morphometric data sets derived from Sulawesi’s three largest mammals: the Babirusa, Anoa, and Sulawesi warty pig. Our results indicate that although these species most likely colonized the area that is now Sulawesi at different times (14 Myr ago to 2-3 Myr ago), they experienced an almost synchronous expansion from the central part of the island. Geological reconstructions indicate that this area was above sea level for most of the last 4 Myr, unlike most parts of the island. We conclude that emergence of land on Sulawesi (~1–2 Myr) may have allowed species to expand synchronously. Altogether, our results indicate that the establishment of the highly endemic faunal assemblage on Sulawesi was driven by geological events over the last few million years