Deletion mutants in COP9/Signalosome subunits in fission yeast Schizosaccharomyces pombe display distinct phenotypes

The COP9/signalosome complex is highly conserved in evolution and possesses significant structural similarity to the 19S regulatory lid complex of the proteasome. It also shares limited similarity to the translation initiation factor eIF3. The signalosome interacts with multiple cullins in mammalian cells. In the fission yeast Schizosaccharomyces pombe, the Csn1 subunit is required for the removal of covalently attached Nedd8 from Pcu1, one of three S. pombe cullins. It remains unclear whether this activity is required for all the functions ascribed to the signalosome. We previously identified Csn1 and Csn2 as signalosome subunits in S. pombe. csn1 and csn2 null mutants are DNA damage sensitive and exhibit slow DNA replication. Two further putative subunits, Csn4 and Csn5, were identified from the S. pombe genome database. Herein, we characterize null mutations of csn4 and csn5 and demonstrate that both genes are required for removal of Nedd8 from the S. pombe cullin Pcu1 and that their protein products associate with Csn1 and Csn2. However, neither csn4 nor csn5 null mutants share the csn1 and csn2 mutant phenotypes. Our data suggest that the subunits of the signalosome cannot be considered as a distinct functional unit and imply that different subunits of the signalosome mediate distinct functions

Satellite observations of mesoscale features in lower Cook Inlet and Shelikof Strait, Gulf of Alaska

The Seasat satellite launched in Summer 1978 carried a synthetic aperture radar (SAR). Although Seasat failed after 105 days in orbit, it provided observations that demonstrate the potential to examine and monitor upper oceanic processes. Seasat made five passes over lower Cook Inlet and Shelikof Strait, Alaska, during Summer 1978. SAR images from the passes show oceanographic features, including a meander in a front, a pair of mesoscale eddies, and internal waves. These features are compared with contemporary and representative images from a satellite-borne Advanced Very High Resolution Radiometer (AVHRR) and Coastal Zone Color Scanner (CZCS), with water property data, and with current observations from moored instruments. The results indicate that SAR data can be used to monitor mesoscale oceanographic features

Wavelet Analysis of SAR Images for Coastal Monitoring

The mapping of mesoscale ocean features in the coastal zone is a major potential application for satellite data. The evolution of mesoscale features such as oil slicks, fronts, eddies, and ice edge can be tracked by the wavelet analysis using satellite data from repeating paths. The wavelet transform has been applied to satellite images, such as those from Synthetic Aperture Radar (SAR), Advanced Very High-Resolution Radiometer (AVHRR), and ocean color sensor for feature extraction. In this paper, algorithms and techniques for automated detection and tracking of mesoscale features from satellite SAR imagery employing wavelet analysis have been developed. Case studies on two major coastal oil spills have been investigated using wavelet analysis for tracking along the coast of Uruguay (February 1997), and near Point Barrow, Alaska (November 1997). Comparison of SAR images with SeaWiFS (Sea-viewing Wide Field-of-view Sensor) data for coccolithophore bloom in the East Bering Sea during the fall of 1997 shows a good match on bloom boundary. This paper demonstrates that this technique is a useful and promising tool for monitoring of coastal waters

An essential function for the ATR-Activation-Domain (AAD) of TopBP1 in mouse development and cellular senescence

ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins – Dpb11TopBP1, Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR. Each contains an ATR activation domain (ADD) that interacts directly with the Mec1ATR:Ddc2ATRIP complex. Any of the Dpb11TopBP1, Ddc1Rad9 or Dna2 ADDs is sufficient to activate Mec1ATR in vitro. All three can also independently activate Mec1ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development

Internal solitons in the northeastern south China Sea. Part I: sources and deep water propagation

Author Posting. © IEEE, 2004. This article is posted here by permission of IEEE for personal use, not for redistribution. The definitive version was published in IEEE Journal of Oceanic Engineering 29 (2004): 1157-1181, doi:10.1109/JOE.2004.840839.A moored array of current, temperature, conductivity, and pressure sensors was deployed across the Chinese continental shelf and slope in support of the Asian Seas International Acoustics Experiment. The goal of the observations was to quantify the water column variability in order to understand the along- and across-shore low-frequency acoustic propagation in shallow water. The moorings were deployed from April 21–May 19, 2001 and sampled at 1–5 min intervals to capture the full range of temporal variability without aliasing the internal wave field. The dominant oceanographic signal by far was in fact the highly nonlinear internal waves (or solitons) which were generated near the Batan Islands in the Luzon Strait and propagated 485 km across deep water to the observation region. Dubbed trans-basin waves, to distinguish them from other, smaller nonlinear waves generated locally near the shelf break, these waves had amplitudes ranging from 29 to greater than 140 m and were among the largest such waves ever observed in the world’s oceans. The waves arrived at the most offshore mooring in two clusters lasting 7–8 days each separated by five days when no waves were observed.Within each cluster, two types of waves arrived which have been named type-a and type-b. The type-a waves had greater amplitude than the type-b waves and arrived with remarkable regularity at the same time each day, 24 h apart. The type-b waves were weaker than the type-a waves, arrived an hour later each day, and generally consisted of a single soliton growing out of the center of the wave packet. Comparison with modeled barotropic tides from the generation region revealed that: 1) The two clusters were generated around the time of the spring tides in the Luzon strait; and 2) The type-a waves were generated on the strong side of the diurnal inequality while the type-b waves were generated on the weaker beat. The position of the Kuroshio intrusion into the Luzon Strait may modulate the strength of the waves being produced. As the waves shoaled, the huge lead solitons first split into two solitons then merged together into a broad region of thermocline depression at depths less than 120 m. Elevation waves sprang up behind them as they continued to propagate onshore. The elevation waves also grew out of regions where the locally-generated internal tide forced the main thermocline down near the bottom. The “critical point” where the upper and lower layers were equal was a good indicator of when the depression or elevation waves would form, however this was not a static point, but rather varied in both space and time according to the presence or absence of the internal tides and the incoming trans-basin waves themselves.The planning, execution, and analysis of this work was supported by the U.S. Office of Naval Research Ocean Acoustics and Physical Oceanography Programs. Significant funding contributions were also made by the National Science Council of Taiwan

NADPH oxidase 5 (NOX5)-induced reactive oxygen signaling modulates normoxic HIF-1α and p27

NADPH oxidase 5 (NOX5) generated reactive oxygen species (ROS) have been implicated in signaling cascades that regulate cancer cell proliferation. To evaluate and validate NOX5 expression in human tumors, we screened a broad range of tissue microarrays (TMAs), and report substantial overexpression of NOX5 in malignant melanoma and cancers of the prostate, breast, and ovary. In human UACC-257 melanoma cells that possesses high levels of functional endogenous NOX5, overexpression of NOX5 resulted in enhanced cell growth, increased numbers of BrdU positive cells, and increased γ-H2AX levels. Additionally, NOX5-overexpressing (stable and inducible) UACC-257 cells demonstrated increased normoxic HIF-1α expression and decreased p2

Compounds from an Unbiased Chemical Screen Reverse Both Er-to-Golgi Trafficking Defects and Mitochondrial Dysfunction in Parkinson's Disease Models

α-Synuclein (α-syn) is a small lipid-binding protein involved in vesicle trafficking whose function is poorly characterized. It is of great interest to human biology and medicine because α-syn dysfunction is associated with several neurodegenerative disorders, including Parkinson’s disease (PD). We previously created a yeast model of α-syn pathobiology, which established vesicle trafficking as a process that is particularly sensitive to α-syn expression. We also uncovered a core group of proteins with diverse activities related to α-syn toxicity that is conserved from yeast to mammalian neurons. Here, we report that a yeast strain expressing a somewhat higher level of α-syn also exhibits strong defects in mitochondrial function. Unlike our previous strain, genetic suppression of endoplasmic reticulum (ER)-to-Golgi trafficking alone does not suppress α-syn toxicity in this strain. In an effort to identify individual compounds that could simultaneously rescue these apparently disparate pathological effects of α-syn, we screened a library of 115,000 compounds. We identified a class of small molecules that reduced α-syn toxicity at micromolar concentrations in this higher toxicity strain. These compounds reduced the formation of α-syn foci, re-established ER-to-Golgi trafficking and ameliorated α-syn-mediated damage to mitochondria. They also corrected the toxicity of α-syn in nematode neurons and in primary rat neuronal midbrain cultures. Remarkably, the compounds also protected neurons against rotenone-induced toxicity, which has been used to model the mitochondrial defects associated with PD in humans. That single compounds are capable of rescuing the diverse toxicities of α-syn in yeast and neurons suggests that they are acting on deeply rooted biological processes that connect these toxicities and have been conserved for a billion years of eukaryotic evolution. Thus, it seems possible to develop novel therapeutic strategies to simultaneously target the multiple pathological features of PD.MGH/MIT Morris Udall Center of Excellence in Parkinson Disease Research (NS038372)Michael J. Fox Foundation for Parkinson's ResearchHoward Hughes Medical InstituteUnited States. National Institutes of Health (NS049221)American Parkinson Disease Association, Inc

Ultraviolet Laser Action in Ferromagnetic Zn1−xFexO Nanoneedles

Fe-doped ZnO nanoneedles (NDs) were fabricated by an Ar+ ion sputtering technique operated at room temperature. The as-grown samples show both ferromagnetic and lasing properties. The saturated magnetization moment was measured from 0.307 to 0.659 emu cm−3 at the field of 10 kOe with various Fe concentrations. Intense ultraviolet random lasing emission was observed from Zn1 − xFexO NDs at room temperature. The X-ray photoelectron spectroscopy result reveals that the doped Fe atoms occupy the Zn sites and lead to a decrease in oxygen deficiency

Transcriptome Analysis of the Chinese White Wax Scale Ericerus pela with Focus on Genes Involved in Wax Biosynthesis

BACKGROUND: The Chinese white wax scale, Ericerus pela Chavannes is economically significant for its role in wax production. This insect has been bred in China for over a thousand years. The wax secreted by the male scale insect during the second-instar larval stage has been widespread used in wax candle production, wax printing, engraving, Chinese medicine, and more recently in the chemical, pharmaceutical, food, and cosmetics industries. However, little is known about the mechanisms responsible for white wax biosynthesis. The characterization of its larval transcriptome may promote better understanding of wax biosynthesis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, characterization of the transcriptome of E. pela during peak wax secretion was performed using Illumina sequencing technology. Illumina sequencing produced 41,839 unigenes. These unigenes were annotated by blastx alignment against the NCBI Non-Redundant (NR), Swiss-Prot, KEGG, and COG databases. A total of 104 unigenes related to white wax biosynthesis were identified, and 15 of them were selected for quantitative real-time PCR analysis. We evaluated the variations in gene expression across different development stages, including egg, first/second instar larvae, male pupae, and male and female adults. Then we identified five genes involved in white wax biosynthesis. These genes were expressed most strongly during the second-instar larval stage of male E. pela. CONCLUSION/SIGNIFICANCE: The transcriptome analysis of E. pela during peak wax secretion provided an overview of gene expression information at the transcriptional level and a resource for gene mining. Five genes related to white wax biosynthesis were identified