A comparison of immunohistochemical assays and FISH in detecting the ALK translocation in diagnostic histological and cytological lung tumor material.

Introduction:Detection of the ALK rearrangement in a solid tumor gives these patients the option of crizotinib as an oral form of anticancer treatment. The current test of choice is fluorescence in situ hybridization (FISH), but various cheaper and more convenient immunohistochemical (IHC) assays have been proposed as alternatives.Methods:Fifteen FISH-positive cases from patients, seven with data on crizotinib therapy and clinical response, were evaluated for the presence of ALK protein using three different commercially available antibodies: D5F3, using the proprietary automated system (Ventana), ALK1 (Dako), and 5A4 (Abcam). A further 14 FISH-negative and three uncertain (<15% rearrangement detected) cases were also retrieved. Of the total 32 specimens, 17 were excisions and 15 were computed tomography-guided biopsies or cytological specimens. All three antibodies were applied to all cases. Antibodies were semiquantitatively scored on intensity, and the proportion of malignant cells stained was documented. Cutoffs were set by receiver operating curve analysis for positivity to optimize correct classification.Results:All three IHC assays were 100% specific but sensitivity did vary: D5F3 86%, ALK 79%, 5A4 71%. Intensity was the most discriminating measure overall, with a combination of proportion and intensity not improving the test. No FISH-negative IHC-positive cases were seen. Two FISH-positive cases were negative with all three IHC assays. One of these had been treated with crizotinib and had failed to show clinical response. The other harbored a second driving mutation in the EGFR gene.Conclusions:IHC with all three antibodies is especially highly specific (100%) although variably sensitive (71%-86%), specifically in cases with scanty material. D5F3 assay was most sensitive in these latter cases. Occasional cases are IHC-positive but FISH-negative, suggesting either inaccuracy of one assay or occasional tumors with ALK rearrangement that do not express high levels of ALK protein

2,000-year-long temperature and hydrology reconstructions from the Indo-Pacific warm pool

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 460 (2009): 1113-1116, doi:10.1038/nature08233.Northern Hemisphere surface temperature reconstructions suggest that the late twentieth century was warmer than any other time during the past 500 years and possibly any time during the past 1,300 years. These temperature reconstructions are based largely on terrestrial records from extra-tropical or highelevation sites; however, global average surface temperature changes closely follow those of the global tropics, which are 75% ocean. In particular, the tropical Indo- Pacific warm pool (IPWP) represents a major heat reservoir that both influences global atmospheric circulation and responds to remote northern latitude forcings. Here we present a decadally resolved continuous sea surface temperature (SST) reconstruction from the IPWP that spans the past two millennia and overlaps the instrumental record, enabling both a direct comparison of proxy data to the instrumental record and an evaluation of past changes in the context of twentieth century trends. Our record from the Makassar Strait, Indonesia, exhibits trends that are similar to a recent Northern Hemisphere temperature reconstruction. Reconstructed SST was, however, within error of modern values during the Medieval Warm Period from about AD 1000 to AD 1250, towards the end of the Medieval Warm Period. SSTs during the Little Ice Age (approximately ad 1550–1850) were variable, and 0.5 to 1°C colder than modern values during the coldest intervals. A companion reconstruction of δ18O of sea water—a sea surface salinity and hydrology indicator— indicates a tight coupling with the East Asian monsoon system and remote control of IPWP hydrology on centennial–millennial timescales, rather than a dominant influence from local SST variation.This work was financially supported by the US NSF and the Ocean Climate Change Institute of WHOI

Auxin pretreatment promotes regeneration of sugarcane (Saccharum spp. hybrids) midrib segment explants

We have developed a new, simple, quick and genotype-independent method for direct regeneration of sugarcane using novel midrib segment explants. Our protocol involves two steps: the pretreatment of starting material on MS (Murashige and Skoog (1962) Physiol Plant 15:473–497) medium containing 3.0 mg/l 2,4- dichlorophenoxyacetic acid (2,4-D) for 8 days under continuous dark and subsequent transfer of the explants to MS medium augmented with 0.1 mg/l benzyladenine (BA) and 0.1 mg/l naphthaleneacetic acid (NAA) under light-dark conditions. On the regeneration medium, numerous globular structures appeared from the explants and subsequently differentiated into shoots. Regenerated shoots attained 2–5 cm height within 30 days of culture initiation and readily rooted on MS basal medium. Hardened plants were successfully established in the greenhouse. The regulation of sugarcane morphogenesis by auxin pretreatment is discussed

Asian dust-storm activity dominated by Chinese dynasty changes since 2000 BP

The Asian monsoon (AM) played an important role in the dynastic history of China, yet it remains unknown whether AM-mediated shifts in Chinese societies affect earth surface processes to the point of exceeding natural variability. Here, we present a dust storm intensity record dating back to the first unified dynasty of China (the Qin Dynasty, 221–207 B.C.E.). Marked increases in dust storm activity coincided with unified dynasties with large populations during strong AM periods. By contrast, reduced dust storm activity corresponded to decreased population sizes and periods of civil unrest, which was co-eval with a weakened AM. The strengthened AM may have facilitated the development of Chinese civilizations, destabilizing the topsoil and thereby increasing the dust storm frequency. Beginning at least 2000 years ago, human activities might have started to overtake natural climatic variability as the dominant controls of dust storm activity in eastern China