bluuebunny/crossref_metadata_2025 huggingface dataset:
Dense water formation on the northwestern shelf of the Okhotsk Sea: 1. Direct observations of brine rejection
Authors: Shcherbina Andrey Y. , Talley Lynne D. , Rudnick Daniel L.
Published: June 2004

Dense Shelf Water (DSW) formation due to brine rejection in the coastal polynya on the northwestern shelf of the Okhotsk Sea was studied using two bottom moorings during the winter of 1999–2000. A steady salinity and density increase that continued for over a month was observed at the shallower mooring. The maximum density of σθ = 26.92 kg m−3 was reached during this period. The density increase terminated abruptly in late February, while the active brine rejection continued for several more weeks based on indirect evidence from water properties and ice cover. This termination was possibly due to the onset of baroclinic instability of the density front at the polynya edge facilitating offshore eddy transport of the density anomaly. Observed periodic baroclinic tide intensification events are hypothesized to be an indicator of the presence of such baroclinic eddies. No significant density increase was observed at the deeper, offshore mooring, indicating a robust demarcation of the offshore extent of newly formed DSW. The relatively fresh water of the tidally mixed zone inshore of the shelf front was the precursor of the DSW, aided by the late‐autumn offshore transition of the front.
Discrimination experiments with the U.S. Army's standard metal detector
Authors: Riggs Lloyd , Chilaka Sailaja , Collins Leslie , Lowe Larry , Weaver Richard
Published: June 2004

Discrimination experiments with the U.S. Army's standard hand‐held metal detector (AN/PSS‐12) are described. An appendix describes the functioning of the device as a metal detector, and the body of the paper discusses modifications to the device necessary to carry out the discrimination experiments. Half of the mines in a large blind test grid were correctly identified with nearly zero false alarms, but the false alarm rate increased substantially for detection probabilities greater than one half. Degradation in performance is attributed to low signal‐to‐noise ratio from low metallic content mines buried deep in the soil. One measurement was taken with the object centered with respect to the search coils and four more with the object between the concentric search coils in the north, south, east, and west directions. Discrimination performance using all spatial measurements was shown to be superior to that obtained when using only the centered measurement, indicating that spatial measurement diversity is needed to adequately define all the unique modes of a target's polarizability tensor.
Cenozoic plate boundary evolution in the South Island of New Zealand: New thermochronological constraints
Authors: Batt Geoffrey E. , Baldwin Suzanne L. , Cottam Michael A. , Fitzgerald Paul G. , Brandon Mark T. , Spell Terry L.
Published: July 2004

Thermochronological investigations of samples collected west of the Alpine Fault zone provide new insight into the early development of the Australian‐Pacific (AUS‐PAC) plate boundary through New Zealand that is not preserved elsewhere in the modern orogenic system of the South Island. The40Ar/39Ar, fission track, and (U‐Th)/He ages for these samples span the Cenozoic and provide direct constraints on the timing and character of two discrete episodes in the evolution of this tectonic boundary. The initial propagation of the AUS‐PAC boundary through the South Island in the early Miocene is expressed as short‐lived, geographically localized cooling, which we infer to be due to exhumation, beginning at 23–25 Ma. This is consistent with development of this boundary as an initially distributed zone of deformation, progressively localizing onto discrete fault structures developing primacy of strain accommodation over time. Regionally synchronous development of rapid cooling at 8 Ma corroborates the association of the present obliquely convergent character of the AUS‐PAC boundary through the South Island with a marked change in Pacific plate motion at that time. Subsequent increases in cooling rate and a regionally prominent 5 Ma thermochronologic signal illuminate the progressive adaptation of the plate boundary to this new tectonic system over a period of ∼3 Myr, culminating in development of the extant tectonic regime.
Topiramate modulates pH of hippocampal CA3 neurons by combined effects on carbonic anhydrase and Cl−/HCO3− exchange
Authors: Leniger Tobias , Thöne Jan , Wiemann Martin
Published: July 2004

Topiramate (TPM) is an anticonvulsant whose impact on firing activity and intracellular pH (pHi) regulation of CA3 neurons was investigated.

Using the 4‐aminopyridine‐treated hippocampal slice model bathed in bicarbonate‐buffered solution, TPM (25–50 μM) reduced the frequency of epileptiform bursts and action potentials without affecting membrane potential or input resistance. Inhibitory effects of TPM were reversed by trimethylamine‐induced alkalinization.

TPM also lowered the steady‐state pHi of BCECF‐AM‐loaded neuronal somata by 0.18±0.07 pH units in CO2/HCO3−‐buffered solution. Subsequent to an ammonium prepulse, TPM reduced the acidotic peak but clearly slowed pHi recovery. These complex changes were mimicked by the protein phosphatase inhibitor okadaic acid.

Alkalosis upon withdrawal of extracellular Cl− was augmented by TPM. Furthermore, at decreased pHi due to the absence of extracellular Na+, TPM reversibly increased pHi. These findings demonstrate that TPM modulates Na+‐independent Cl−/HCO3− exchange.

In the nominal absence of extracellular CO2/HCO3− buffer, both steady‐state pHi and firing of epileptiform bursts remained unchanged upon adding TPM. However, pHi recovery subsequent to an ammonium prepulse was slightly increased, as was the case in the presence of the carbonic anhydrase (CA) inhibitor acetazolamide. Thus, a slight reduction of intracellular buffer capacity by TPM may be due to an inhibitory effect on intracellular CA.

Together, these findings show that TPM lowers neuronal pHi most likely due to a combined effect on Na+‐independent Cl−/HCO3− exchange and CA. The apparent decrease of steady‐state pHi may contribute to the anticonvulsive property of TPM.

British Journal of Pharmacology (2004) 142, 831–842. doi:10.1038/sj.bjp.0705850
Stimulus‐specific defect in the phagocytic pathways of annexin 1 null macrophages
Authors: Yona Simon , Buckingham Julia C , Perretti Mauro , Flower Roderick J
Published: July 2004

The role of the glucocorticoid‐regulated protein annexin 1 during the process of phagocytosis has been studied using annexin 1 null peritoneal macrophages. Wild type and annexin 1 null macrophages were incubated with several distinct phagocytic targets. No differences were observed in rate or the maximal response with respect to IgG complexes or opsonised zymosan phagocytosis, as assessed by monitoring the production of reactive oxygen species.

When annexin 1 null macrophages were incubated with non‐opsonised zymosan particles, they exhibited impaired generation of reactive oxygen species, which was linked to a defect in binding of cells to the particles, as determined with fluorescent zymosan. This phenomenon was further confirmed by electron microscopy analysis, where annexin 1 null macrophages internalised fewer non‐opsonised zymosan particles.

Specific alterations in macrophage plasma membrane markers were observed in the annexin 1 null cells. Whereas no differences in dectin‐1 and FcγR II/III expression were measured between the two genotypes, decreased membrane CD11b and F4/80 levels were measured selectively in macrophages lacking annexin 1.

These cells also responded with an enhanced release of PGE2 and COX‐2 protein expression following addition of the soluble stimulants, LPS and heat‐activated IgG.

In conclusion, these results suggest that participation of endogenous annexin 1 during zymosan phagocytosis is critical and that this protein plays a tonic inhibitory role during macrophage activation.

British Journal of Pharmacology (2004) 142, 890–898. doi:10.1038/sj.bjp.0705858
Molecular pharmacological profile of the nonredox‐type 5‐lipoxygenase inhibitor CJ‐13,610
Authors: Fischer Lutz , Steinhilber Dieter , Werz Oliver
Published: July 2004

5‐Lipoxygenase (5‐LO) is a crucial enzyme in the synthesis of the bioactive leukotrienes (LTs) from arachidonic acid (AA), and inhibitors of 5‐LO are thought to prevent the untowarded pathophysiological effects of LTs.

In this study, we present the molecular pharmacological profile of the novel nonredox‐type 5‐LO inhibitor CJ‐13,610 that was evaluated in various in vitro assays.

In intact human polymorphonuclear leukocytes (PMNL), challenged with the Ca2+‐ionophore A23187, CJ‐13,610 potently suppressed 5‐LO product formation with an IC50=0.07 μM. Supplementation of exogenous AA impaired the efficacy of CJ‐13,610, implying a competitive mode of action.

In analogy to ZM230487 and L‐739.010, two closely related nonredox‐type 5‐LO inhibitors, CJ‐13,610 up to 30 μM failed to inhibit 5‐LO in cell‐free assay systems under nonreducing conditions, but inclusion of peroxidase activity restored the efficacy of CJ‐13,610 (IC50=0.3 μM).

In contrast to ZM230487 and L‐739.010, the potency of CJ‐13,610 does not depend on the cell stimulus or the activation pathway of 5‐LO. Thus, 5‐LO product formation in PMNL induced by phosphorylation events was equally suppressed by CJ‐13,610 as compared to Ca2+‐mediated 5‐LO activation. In transfected HeLa cells, CJ‐13,610 only slightly discriminated between phosphorylatable wild‐type 5‐LO and a 5‐LO mutant that lacks phosphorylation sites.

In summary, CJ‐13,610 may possess considerable potential as a potent orally active nonredox‐type 5‐LO inhibitor that lacks certain disadvantages of former representatives of this class of 5‐LO inhibitors.

British Journal of Pharmacology (2004) 142, 861–868. doi:10.1038/sj.bjp.0705860
How does parkin ligate ubiquitin to Parkinson's disease?
Authors: Kahle Philipp J , Haass Christian
Published: July 2004

Recessive mutations in the human PARKIN gene are the most common cause of hereditary parkinsonism, which arises from the degeneration of dopaminergic neurons in the substantia nigra. However, the molecular mechanisms by which the loss of parkin causes dopaminergic neurodegeneration are not well understood. Parkin is an enzyme that ubiquitinates several candidate substrate proteins and thereby targets them for proteasomal degradation. Hypothesis‐driven searches have led to the discovery of aggregation‐prone protein substrates of parkin. Moreover, the enzyme is upregulated when under unfolded protein stress. Thus, loss‐of‐function mutations of parkin might impair the removal of potentially toxic protein aggregates. However, the limited neuropathological information that is available from parkin‐proven patients, as well as the recent knockout of the parkin gene in fruit flies and mice, may indicate a more complex disease mechanism, possibly involving the misfolding of parkin itself or of additional substrates. The risk factors that predispose dopaminergic neurons to degenerate on parkin failure are yet to be identified.
Gravity, radiation, and coflow effects on partially premixed flames
Authors: Qin Xiao , Puri Ishwar K. , Aggarwal Suresh K. , Katta Viswanath R.
Published: June 2004

Our objective is to characterize gravity effects on the structure of laminar methane–air partially premixed flames through detailed simulations. We examine the heat loss due to radiation from similar flames that are established at various gravitational accelerations and coflow velocities. Radiation is modeled using the optically thin assumption that provides a limiting value for the radiation heat transfer. We have validated the simulations with measurements in a representative 1-g flame. The predictions are in good agreement with the measured reaction zone topologies and temperature distributions. The simulations show that when the gravitational acceleration for a representative 1-g partially premixed double flame is instantaneously decreased to zero, it is possible to establish a nearly steady 0-g flame in roughly 2.2 s. The overall effect of radiation on the structure of the 1-g flame is relatively insignificant in contrast to the corresponding 0-g flame. Due to radiation effects, the heights of both the inner premixed and outer nonpremixed reaction zones in the 0-g double flame increase, and the heat release rate intensity near the premixed reaction zone tip decreases. When radiation effects are not included in the simulations, the peak temperatures are nearly the same for the 1-g and 0-g flames. However, with radiation the difference in these temperatures is significant. The decrease in the peak temperature due to radiation for the 0-g flame is nearly five times larger than for the 1-g flame. The value of the radiation fraction for 0-g flames without coflow can be as large as 50%, although it drops significantly in the presence of a coflow. While the flowfields upstream of the inner premixed reaction zone are nearly identical for 1-g and 0-g double flames, they are markedly different in the regions between the two reaction zones as well as downstream of the outer nonpremixed reaction zone. The maximum flame temperatures and local heat-release rates increase as the gravitational acceleration increases, while the radiation fractions and inner flame heights decrease. The flickering frequency also increases from 14.7 Hz at 1-g to 41.4 Hz at 10-g and follows the correlation St∝Fr−0.57 that is in accord with a previous compilation of normal gravity data. The radiation Damköhler number is inversely proportional to the Froude number. The radiation fraction decreases with increasing coflow, and the differences between the maximum flame temperatures and heat-release rates for 1-g and 0-g flames become less pronounced. Results for triple flames are in accord with those for double flames.
Two-phase viscous modeling of compaction of granular materials
Authors: Powers Joseph M.
Published: June 2004

An inviscid model for deflagration-to-detonation transition in granular energetic materials is extended by addition of explicit intraphase momenta and energy diffusion so as to (1) enable the use of a straightforward numerical scheme, (2) avoid prediction of structures with smaller length scales than the component grains, and (3) have a model prepared to describe long time scale transients that are present in some slow processes which can lead to detonation. The model is shown to be parabolic, frame invariant, and dissipative. Consideration of the characteristics for cases with and without intraphase diffusion indicate what boundary conditions are necessary for a well posed problem. A simple numerical method, based on a method of lines applied to the nonconservative form of the equations, is shown to predict convergence at the proper rate to unique solutions which agree well with known solutions for an unsteady inviscid shock tube and a steady piston-driven viscous shock. A series of simulations of inert piston-driven subsonic compaction waves in which the additional mechanisms of interphase compaction, drag, and heat transfer are systematically introduced at an order of magnitude suggested by experiments reveals that interphase drag and heat transfer equilibrate velocities and temperatures, and that compaction equilibrates solid and configurational stresses. At higher piston velocities, supersonic shock and compaction waves are induced; comparison of predictions with and without viscosity demonstrate some of the computational advantages of explicit inclusion of diffusion. The local dissipation rates for each mechanism are quantified, and it is seen that dissipation due to compaction dominates that due to intraphase and interphase transport of linear momenta and energy, suggesting that compaction is the key mechanism in inducing the transition to detonation in piston-driven experiments.
Raman spectroscopy of cubic boron nitride under high temperature and pressure conditions: A new optical pressure marker
Authors: Kawamoto Tatsuhiko , Matsukage Kyoko N. , Nagai Takaya , Nishimura Koshi , Mataki Takeshi , Ochiai Shukichi , Taniguchi Takashi
Published: June 2004

The pressure dependence of Raman peaks of cubic boron nitride (cBN) is determined at 100, 200 and 300 °C using pressure scales of ruby and gold. At pressures lower than 6 GPa, the pressure dependences of cBN Raman determined with the ruby pressure scale for transverse-optical (TO) and longitudinal-optical modes are 3.45±0.02 and 3.36±0.02 cm−1/GPa at 100 °C and 3.43±0.02 and 3.44±0.07 cm−1/GPa at 300 °C, respectively. These values are consistent with those in a previous study conducted at room temperature using the ruby pressure scale. Synchrotron x-ray diffraction experiments using a gold pressure marker also yield 3.45±0.03 cm−1/GPa for TO mode at 200 °C in a range of pressure up to 32 GPa. Under the present pressure and temperature conditions, the pressure dependence of Raman peaks of cBN seems to be independent of the temperature conditions. cBN can be used as an optical pressure marker under high temperature conditions.
Microwave design and characterization of a cryogenic dip probe for time-domain measurements of nanodevices
Authors: Jun M. S. , Hwang S. W. , Jeong D. Y. , Ahn D.
Published: June 2004

We present microwave (MW) design, characterization, and modeling of a dip probe that can deliver ultrashort electrical pulses to semiconductor nanodevices at cryogenic temperatures (T). Systematic MW measurements, equivalent circuit modeling, and parameter extraction of the superconducting coaxial cable, in which there is a T gradient from 300 to 4.2 K, are successfully performed. De-embedding of the MW sample mounting stage (SMS) characteristic from measurement results of the dip probe dipped in liquid He is achieved using this cable modeling. The de-embedded 4.2 K characteristic of the MW SMS is in reasonable agreement with the result of three-dimensional field simulation. Finally, transmission of short electrical pulses from the pulse generator at 300 K to the MW SMS at 4.2 K, with minimal degradation, is successfully demonstrated using our dip probe. Our design and characterization technique can be applied to almost all cryogenic equipment for MW characterization.
Work functions of individual single-walled carbon nanotubes
Authors: Suzuki Satoru , Watanabe Yoshio , Homma Yoshikazu , Fukuba Shin-ya , Heun Stefan , Locatelli Andrea
Published: June 2004

Work functions of individual single-walled carbon nanotubes (SWNTs) were studied by means of photoemission electron microscopy. Work function differences between the nanotubes were clearly observed in secondary electron images. The work functions of 93 SWNTs were found to range within 0.6eV, but most distributed in a much narrower energy range of 0.2eV. The work functions of single-walled nanotubes do not seem to have large structural dependence.
Familiarity Influences Judgments of Sex: The Case of Voice Recognition
Authors: Burton A Mike , Bonner Lesley
Published: July 2004

Two experiments are reported in which subjects made judgments about the sex or the familiarity of a voice. In experiment 1, subjects were fans of the BBC-radio soap opera, The Archers, and familiar voice clips were taken from this programme. Subjects showed a large reduction in response times when making sex judgments to familiar voices, despite the fact that sex judgments are generally much faster than familiarity judgments. In experiment 2, the same familiar clips were played to subjects unfamiliar with the soap opera, and no difference was observed in times to make sex judgments to Archers or non- Archers voices. We conclude that, unlike the case of face recognition, sex and identity processing of voices are not independent. The findings constrain models of person recognition across multiple modalities.
Bacterial Contamination and Submarine Groundwater Discharge—A Possible Link
Authors: Paytan Adina , Boehm Alexandria B. , Shellenbarger Gregory G.
Published: July 2004

Environmental Context.Pathogenic bacteria and viruses are sometimes detected in coastal waters, high levels of which correlate with occurrence of acute gastrointestinal illness in recreational beach users. The source of the bacterial and viral contamination to the beach is not always easy to decipher, and therefore efforts to prevent these occurrences are limited by lack of full understanding of their cause.

Abstract.Beach water contamination by pathogenic agents is monitored by Fecal Indicator Bacteria (FIB) levels. A source of these agents may be submarine groundwater discharge. At Huntington Beach, California high FIB levels in the surf zone are shown to be associated with high 224Ra and 223Ra activities, indicators of groundwater discharge.
Determining the History and Sources of Contaminants in Sediments in the Tamar Estuary, Tasmania, Using 210Pb Dating and Stable Pb Isotope Analyses
Authors: Seen Andrew , Townsend Ashley , Atkinson Bonnie , Ellison Joanna , Harrison Jennifer , Heijnis Henk
Published: July 2004

Environmental Context.Dating estuary sediments provides insights into the materials entering the estuary and can pinpoint when the contamination occurred. Heavy metal contamination is a known health risk but attributing it to a source can be contentious. For a sample sourced downstream of a city and a mining region, lead-210 dating and stable lead isotope analyses uncovered the sources of lead inputs. These methods quantified the extent that upstream mining activities and, for the first time, the extent that non-mining inputs (vehicles, industry) contributed to the estuary’s pollution.

Abstract.210Pb dating and heavy metal analyses (Cd, Cu, Pb, Zn) have been combined to establish an historical profile of pollutant levels in sediments in the Tamar Estuary (Tasmania, Australia) over the past century. Heavy metal profiles through the core show a strong correlation with mining activities and industrialization during the past century, reflecting catchment disturbance in one of Australia’s earliest settled areas. A source apportionment of Pb in the sediment core using stable Pb isotope ratios (204Pb, 206Pb, 207Pb, 208Pb) shows that mine pollution has been contributing 10–25 mg kg–1 to Tamar Estuary sediments since the start of mining in the early 1890s, whilst non-mining inputs were not significant until post-1930 and became increasingly significant post-World War II. Since the 1950s–1960s, non-mining anthropogenic Pb inputs have become as significant as Pb from mining activities, although there does appear to be a decline in non-mining inputs during the past 20 years, which is consistent with findings elsewhere where reductions in atmospheric Pb levels have been observed and are attributed to the phasing-out of leaded gasoline. The source apportionment does, however, suggest that Pb from mine pollution at Storys and Aberfoyle Creeks continues to impact upon upper Tamar Estuary sediment quality.
Effects of seeding ryegrass (Lolium multiflorum) on vegetation recovery following fire in a ponderosa pine (Pinus ponderosa) forest
Authors: Barclay Angela D. , Betancourt Julio L. , Allen Craig D.
Published: June 2004

Forty-nine vegetation transects were measured in 1997 and 1998 to determine the impact of grass seeding after the 1996 Dome Fire, which burned almost 6900 ha of ponderosa pine (Pinus ponderosa Lawson) forest in the Jemez Mountains of north-central New Mexico. High- and moderate-burned areas in Santa Fe National Forest were seeded with a mixture that included the exotic ryegrass (Lolium multiflorum Lam.). Adjacent burned areas of Bandelier National Monument were not seeded, and were used as a control in the post-seeding study. On the seeded plots, foliar cover of ryegrass declined from 1997 to 1998 due to self-inhibition and/or reduced precipitation from 1997 to 1998. Foliar cover and diversity of native forbs were greater in 1997 than 1998, probably due to a wet growing season in 1997. Cover, species richness, and diversity of native forbs were highest in non-seeded areas of moderate- and high-burn intensities. Regeneration and survivorship of conifer seedlings decreased as ryegrass cover increased, particularly in areas of high-burn intensity. Exotic plant cover, mostly horseweed [Conyza canadensis (L.) Cronq.], increased from 1997 to 1998 in non-seeded areas of moderate- and high-burn intensity. Both the initial success of seeding and the eventual impacts on native vegetation were strongly modulated by climate variability.
Direct interaction between FcγRI (CD64) and periplakin controls receptor endocytosis and ligand binding capacity
Authors: Beekman Jeffrey M. , Bakema Jantine E. , van de Winkel Jan G. J. , Leusen Jeanette H. W.
Published: July 2004

FcγRI depends for its biological function on both the intracellular domain of the α-chain and associated Fc receptor (FcR) γ-chains. However, functional protein effectors of FcγRI's intracellular domain have not been identified. In this study, we identified periplakin (PPL) as a selective interacting protein for the intracellular tail of FcγRI but no other activatory FcRs. The interaction was confirmed by coimmunoprecipitation and blot-overlay assays. PPL and FcγRI colocalized at the plasma membrane in monocytes and cell transfectants, and both were up-regulated by IFN-γ. By expressing C-terminal PPL in transfectants, we established a pivotal role for this protein in FcγRI ligand binding, endocytosis, and antigen presentation. These data illustrate that intracellular protein interactions with a multisubunit FcR α-chain can confer unique properties to the receptor.
Mitochondrial “swirls” induced by oxygen stress and in theDrosophilamutanthyperswirl
Authors: Walker David W. , Benzer Seymour
Published: July 2004

Mitochondrial dysfunction and reactive oxygen species have been implicated in the aging process as well as a wide range of hereditary and age-related diseases. Identifying primary events that result from acute oxidative stress may provide targets for therapeutic interventions that preclude aging. By using electron microscopy, we have discovered a striking initial pattern of degeneration of the mitochondria inDrosophilaflight muscle under hyperoxia (100% O2). Within individual mitochondria, the cristae become locally rearranged in a pattern that we have termed a “swirl.” Serial sections through individual mitochondria reveal the reorganization of the cristae in three dimensions. The cristae involved in a swirl are deficient in respiratory enzyme cytochromecoxidase activity, within an otherwise cytochromecoxidase-positive mitochondrion. In addition, under hyperoxia cytochromecundergoes a conformational change, manifested by display of an otherwise hidden epitope. The conformational change is correlated with widespread apoptotic cell death in the flight muscle, as revealed byin situterminal deoxynucleotidyltransferase-mediated dUTP nick end labeling. In normal flies, mitochondrial swirls accumulate slowly with age. To investigate the molecular mechanisms involved in oxygen toxicity, we conducted a genetic screen for mutants that display altered survival under hyperoxia, and we identified both sensitive and resistant mutants. We describe a mutant,hyperswirl, which displays an overabundance of swirls with associated respiratory and flight defects and a greatly reduced lifespan. Such mutants can identify genes that are needed to maintain mitochondrial homeostasis throughout the lifespan.
Nucleoporins as Components of the Nuclear Pore Complex Core Structure and Tpr as the Architectural Element of the Nuclear Basket
Authors: Krull Sandra , Thyberg Johan , Björkroth Birgitta , Rackwitz Hans-Richard , Cordes Volker C.
Published: July 2004

The vertebrate nuclear pore complex (NPC) is a macromolecular assembly of protein subcomplexes forming a structure of eightfold radial symmetry. The NPC core consists of globular subunits sandwiched between two coaxial ring-like structures of which the ring facing the nuclear interior is capped by a fibrous structure called the nuclear basket. By postembedding immunoelectron microscopy, we have mapped the positions of several human NPC proteins relative to the NPC core and its associated basket, including Nup93, Nup96, Nup98, Nup107, Nup153, Nup205, and the coiled coil-dominated 267-kDa protein Tpr. To further assess their contributions to NPC and basket architecture, the genes encoding Nup93, Nup96, Nup107, and Nup205 were posttranscriptionally silenced by RNA interference (RNAi) in HeLa cells, complementing recent RNAi experiments on Nup153 and Tpr. We show that Nup96 and Nup107 are core elements of the NPC proper that are essential for NPC assembly and docking of Nup153 and Tpr to the NPC. Nup93 and Nup205 are other NPC core elements that are important for long-term maintenance of NPCs but initially dispensable for the anchoring of Nup153 and Tpr. Immunogold-labeling for Nup98 also results in preferential labeling of NPC core regions, whereas Nup153 is shown to bind via its amino-terminal domain to the nuclear coaxial ring linking the NPC core structures and Tpr. The position of Tpr in turn is shown to coincide with that of the nuclear basket, with different Tpr protein domains corresponding to distinct basket segments. We propose a model in which Tpr constitutes the central architectural element that forms the scaffold of the nuclear basket.
Over-Expression of Rififylin, a New RING Finger and FYVE-like Domain-containing Protein, Inhibits Recycling from the Endocytic Recycling Compartment
Authors: Coumailleau Franck , Das Vincent , Alcover Andres , Raposo Graça , Vandormael-Pournin Sandrine , Le Bras Stéphanie , Baldacci Patricia , Dautry-Varsat Alice , Babinet Charles , Cohen-Tannoudji Michel
Published: July 2004

Endocytosed membrane components are recycled to the cell surface either directly from early/sorting endosomes or after going through the endocytic recycling compartment (ERC). Studying recycling mechanisms is difficult, in part due to the fact that specific tools to inhibit this process are scarce. In this study, we have characterized a novel widely expressed protein, named Rififylin (Rffl) for RING Finger and FYVE-like domain-containing protein, that, when overexpressed in HeLa cells, induced the condensation of transferrin receptor-, Rab5-, and Rab11-positive recycling tubulovesicular membranes in the perinuclear region. Internalized transferrin was able to access these condensed endosomes but its exit from this compartment was delayed. Using deletion mutants, we show that the carboxy-terminal RING finger of Rffl is dispensable for its action. In contrast, the amino-terminal domain of Rffl, which shows similarities with the phosphatidylinositol-3-phosphate–binding FYVE finger, is critical for the recruitment of Rffl to recycling endocytic membranes and for the inhibition of recycling, albeit in a manner that is independent of PtdIns(3)-kinase activity. Rffl overexpression represents a novel means to inhibit recycling that will help to understand the mechanisms involved in recycling from the ERC to the plasma membrane.
Polarized Membrane Traffic and Cell Polarity Development Is Dependent on Dihydroceramide Synthase-Regulated Sphinganine Turnover
Authors: van IJzendoorn Sven C.D. , van der Wouden Johanna M. , Liebisch Gerhard , Schmitz Gerd , Hoekstra Dick
Published: July 2004

Sphingoid bases have been implicated in various cellular processes including cell growth, apoptosis and cell differentiation. Here, we show that the regulated turnover of sphingoid bases is crucial for cell polarity development, i.e., the biogenesis of apical plasma membrane domains, in well-differentiated hepatic cells. Thus, inhibition of dihydroceramide synthase or sphinganine kinase activity with fumonisin B1 or N,N-dimethylsphingosine, respectively, dramatically perturbs cell polarity development, which is due to increased levels of sphinganine. Consistently, reduction of free sphinganine levels stimulates cell polarity development. Moreover, dihydroceramide synthase, the predominant enzyme responsible for sphinganine turnover, is a target for cell polarity stimulating cAMP/protein kinase A (PKA) signaling cascades. Indeed, electrospray ionization tandem mass spectrometry analyses revealed a significant reduction in sphinganine levels in cAMP/PKA-stimulated cells. These data suggest that sphinganine turnover is critical for and is actively regulated during HepG2 cell polarity development. Previously, we have identified an apical plasma membrane-directed trafficking pathway from the subapical compartment. This transport pathway, which is part of the basolateral-to-apical transcytotic itinerary, plays a crucial role in apical plasma membrane biogenesis. Here, we show that, as a part of the underlying mechanism, the inhibition of dihydroceramide synthase activity and ensuing increased sphinganine levels specifically perturb the activation of this particular pathway in the de novo apical membrane biogenesis.
Recognition of multiple patterns in unaligned sets of sequences: comparison of kernel clustering method with other methods
Authors: Kel A. , Tikunov Y. , Voss N. , Wingender E.
Published: July 2004

Motivation: Transcription factor binding sites often differ significantly in their primary sequence and can hardly be aligned. Often one set of sites can contain several subsets of sequences that follow not just one but several different patterns. There is a need for sensitive methods to reveal multiple patterns in unaligned sets of sequences.

Results: We developed a novel method for analysis of unaligned sets of sequences based on kernel estimation. The method is able to reveal ‘multiple local patterns’—a set of weight matrices. Every weight matrix characterizes a pattern that can be found in a significant subset of sequences under analysis. The method developed has been compared with several other methods of pattern discovery such as Gibbs sampling, MEME, CONSENSUS, MULTIPROFILER and PROJECTION. The kernel method showed the best performance in terms of how close the revealed weight matrices are to the original ones. We applied the kernel method to analyze three samples of promoters (cell-cycle, T-cells and muscle-specific). We compared the multiple patterns revealed with the TRANSFAC library of weight matrices and found a strong similarity to several weight matrices for transcription factors known to be involved in the mentioned specific gene regulation.

Availability: The program is available for on-line use at: http://www.biobase.de/cgi-bin/biobase/cbs2/bin/template.cgi?template=cbscall.html
New methods for joint analysis of biological networks and expression data
Authors: Sohler Florian , Hanisch Daniel , Zimmer Ralf
Published: July 2004

Summary: Biological networks, such as protein interaction, regulatory or metabolic networks, derived from public databases, biological experiments or text mining can be useful for the analysis of high-throughput experimental data. We present two algorithms embedded in the ToPNet application that show promising performance in analyzing expression data in the context of such networks. First, the Significant Area Search algorithm detects subnetworks consisting of significantly regulated genes. These subnetworks often provide hints on which biological processes are affected in the measured conditions. Second, Pathway Queries allow detection of networks including molecules that are not necessarily significantly regulated, such as transcription factors or signaling proteins. Moreover, using these queries, the user can formulate biological hypotheses and check their validity with respect to experimental data. All resulting networks and pathways can be explored further using the interactive analysis tools provided by ToPNet program.
Efficient similarity search in protein structure databases by k-clique hashing
Authors: Weskamp Nils , Kuhn Daniel , Hüllermeier Eyke , Klebe Gerhard
Published: July 2004

Motivation: Graph-based clique-detection techniques are widely used for the recognition of common substructures in proteins. They permit the detection of resemblances that are independent of sequence or fold homologies and are also able to handle conformational flexibility. Their high computational complexity is often a limiting factor and prevents a detailed and fine-grained modeling of the protein structure.

Results: We present an efficient two-step method that significantly speeds up the detection of common substructures, especially when used to screen larger databases. It combines the advantages from both clique-detection and geometric hashing. The method is applied to an established approach for the comparison of protein binding-pockets, and some empirical results are presented.

Availability: Upon request from the authors.
Vascular Endothelial Growth Factor Overexpression Increases Vascularization by Murine But Not Human Endothelial Cells in Cultured Skin Substitutes Grafted to Athymic Mice
Authors: Supp Dorothy M. , Karpinski Andrea C. , Boyce Steven T.
Published: July 2004

Cultured skin substitutes (CSS) consisting of fibroblasts, keratinocytes, and biopolymers are an adjunctive treatment for large burns. Because CSS lack a vascular plexus, they vascularize more slowly than split-thickness autografts. Previously, CSS were prepared with dermal microvascular endothelial cells (ECs), which formed vascular analogs at a low frequency but did not contribute to increased vascularization after grafting. The present study addressed whether keratinocytes genetically modified to overexpress vascular endothelial growth factor (VEGF), an endothelial cell mitogen, could improve the persistence and organization of ECs in CSS. CSS were prepared with control or VEGF-modified keratinocytes, with (CSS + ECs) or without added ECs, and were grafted to full-thickness wounds in athymic mice. Elevated VEGF expression was detected in VEGF-modified CSS and CSS + ECs compared with controls, but no significant difference in EC density in vitro was observed. After grafting, VEGF-modified CSS and CSS + ECs showed enhanced vascularization, and organization of human ECs into multicellular structures in CSS + ECs was observed. However, VEGF overexpression did not significantly enhance the proliferation of human ECs, suggesting that other factors may be required. Improved persistence and organization of human ECs in vitro will likely be required for their participation in vascularization of CSS + ECs after grafting.
Buses as Fire Hazards: A Swedish Problem Only? Suggestions for Fire-Prevention Measures
Authors: Huss Fredrik R. M. , Erlandsson U. , Sjöberg F.
Published: July 2004

In Sweden, approximately 6% of all human transportation is made via buses. The Swedish Board of Accident Investigation and the Swedish Rescue Services Agency have pointed out repeatedly that buses are potential fire and burn hazards, not only when involved in collisions but also in other circumstances. The number of fire incidents is increasing, especially in newer buses. In conjunction with the Swedish Rescue Services Agency, we examined some of the recent bus fires in Sweden. We did not find any casualties, but the results of our study suggest that casualties as a result of bus fires are imminent unless preventive measures are taken. We also studied experiences from previous bus fires and suggest preventive measures.
A History of the Development of Muscle Perforator Flaps and Their Specific Use in Burn Reconstruction
Authors: Hallock G. G.
Published: July 2004

Only rarely does coverage in the burn patient require the use of a vascularized flap. However, when mandatory, a knowledge of all alternatives is essential because common donor sites may have been badly burned and unavailable. The recent development of the muscle perforator flap may prove to be another valuable option. These flaps are nourished by the familiar musculocutaneous perforators but differ in that their complete intramuscular dissection is required during flap elevation so that no muscle need be included with the flap. A review of six cases using muscle perforator free flaps specifically for burn reconstruction or rehabilitation demonstrates how the same large cutaneous territory of a musculocutaneous flap can still be captured while the muscle and therefore its function is preserved.
Use of Free Serratus Anterior Muscle Slips for the Reconstruction of Dorsal-Side Defects of the Hand Resulting From Hot Press Injury
Authors: Topalan Murat , Özden Burcu Çelet , Aydin Atakan , Erer Metin
Published: July 2004

Mutilation of the hand as a result of hot press injury, the common characteristics of which are extensive soft tissue and extensor tendon loss, metacarpal and phalangeal necrosis, exposition of multiple joints, and infection, presents a serious challenge to the hand surgeon. Free transfer of the inferior three slips of the serratus anterior muscle is a useful surgical option for the reconstruction of dorsal-side defects in the hand. The versatility of the three separate slips, which are easily divisible for contouring, enables individual reconstruction of the different digits. Long vascular pedicle, low donor-site morbidity, and durability are other advantages. Four male patients with hot press injury of the dorsal side of the hand were treated with free transfer of serratus anterior muscle slips and split-thickness skin grafts. Follow-up period ranged between 5 and 12 years. Late functional and cosmetic results are presented.
Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport
Authors: Blacque Oliver E. , Reardon Michael J. , Li Chunmei , McCarthy Jonathan , Mahjoub Moe R. , Ansley Stephen J. , Badano Jose L. , Mah Allan K. , Beales Philip L. , Davidson William S. , Johnsen Robert C. , Audeh Mark , Plasterk Ronald H.A. , Baillie David L. , Katsanis Nicholas , Quarmby Lynne M. , Wicks Stephen R. , Leroux Michel R.
Published: July 2004

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Importantly, we demonstrate that BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11, and to a notably lesser extent, CHE-2. We propose that BBS proteins play important, selective roles in the assembly and/or function of IFT particle components. Our findings also suggest that some of the cardinal and secondary symptoms of BBS, such as obesity, diabetes, cardiomyopathy, and learning defects may result from cilia dysfunction.
The Normal Holonomy Group of Kähler Submanifolds
Authors: Alekseevsky Dmitri V. , Di Scala Antonio J.
Published: June 2004

We study the (restricted) holonomy group Hol(∇⊥) of the normal connection ∇⊥ (shortened to normal holonomy group) of a Kähler submanifold of a complex space form. We prove that if the normal holonomy group acts irreducibly on the normal space then it is linear isomorphic to the holonomy group of an irreducible Hermitian symmetric space. In particular, it is a compact group and the complex structure J belongs to its Lie algebra.

We prove that the normal holonomy group acts irreducibly if the submanifold is full (that is, it is not contained in a totally geodesic proper Kähler submanifold) and the second fundamental form at some point has no kernel. For example, a Kähler–Einstein submanifold of CPn has this property.

We define a new invariant μ of a Kähler submanifold of a complex space form. For non‐full submanifolds, the invariant μ measures the deviation of J from belonging to the normal holonomy algebra. For a Kähler–Einstein submanifold, the invariant μ is a rational function of the Einstein constant. By using the invariant μ, we prove that the normal holonomy group of a not necessarily full Kähler–Einstein submanifold of CPn is compact, and we give a list of possible holonomy groups.

The approach is based on a definition of the holonomy algebra hol(P) of an arbitrary curvature tensor field P on a vector bundle with a connection and on a De Rham type decomposition theorem for hol(P). 2000 Mathematics Subject Classification 53C40 (primary), 53B25 (secondary).
The Normal Function of a Speciation Gene,
Odysseus
, and Its Hybrid Sterility Effect
Authors: Sun Sha , Ting Chau-Ti , Wu Chung-I
Published: July 2004

To understand how postmating isolation is connected to the normal process of species divergence and why hybrid male sterility is often the first sign of speciation, we analyzed the
Odysseus
(
OdsH
) gene of hybrid male sterility in
Drosophila
. We carried out expression analysis, transgenic study, and gene knockout. The combined evidence suggests that the sterility phenotype represents a novel manifestation of the gene function rather than the reduction or loss of the normal one. The gene knockout experiment identified the normal function of
OdsH
as a modest enhancement of sperm production in young males. The implication of a weak effect of
OdsH
on the normal phenotype but a strong influence on hybrid male sterility is discussed in light of Haldane's rule of postmating isolation.
Neural Activity Triggers Neuronal Oxidative Metabolism Followed by Astrocytic Glycolysis
Authors: Kasischke Karl A. , Vishwasrao Harshad D. , Fisher Patricia J. , Zipfel Warren R. , Webb Watt W.
Published: July 2004

We have found that two-photon fluorescence imaging of nicotinamide adenine dinucleotide (NADH) provides the sensitivity and spatial three-dimensional resolution to resolve metabolic signatures in processes of astrocytes and neurons deep in highly scattering brain tissue slices. This functional imaging reveals spatiotemporal partitioning of glycolytic and oxidative metabolism between astrocytes and neurons during focal neural activity that establishes a unifying hypothesis for neurometabolic coupling in which early oxidative metabolism in neurons is eventually sustained by late activation of the astrocyte-neuron lactate shuttle. Our model integrates existing views of brain energy metabolism and is in accord with known macroscopic physiological changes in vivo.
Mitotic Golgi Partitioning Is Driven by the Membrane-Fissioning Protein CtBP3/BARS
Authors: Carcedo Cristina Hidalgo , Bonazzi Matteo , Spanò Stefania , Turacchio Gabriele , Colanzi Antonino , Luini Alberto , Corda Daniela
Published: July 2004

Organelle inheritance is an essential feature of all eukaryotic cells. As with other organelles, the Golgi complex partitions between daughter cells through the fission of its membranes into numerous tubulovesicular fragments. We found that the protein CtBP3/BARS (BARS) was responsible for driving the fission of Golgi membranes during mitosis in vivo. Moreover, by in vitro analysis, we identified two stages of this Golgi fragmentation process: disassembly of the Golgi stacks into a tubular network, and BARS-dependent fission of these tubules. Finally, this BARS-induced fission of Golgi membranes controlled the G
2
-to-prophase transition of the cell cycle, and hence cell division.
Was the Culprit Climate or Culture?
Authors: Klein Richard G.
Published: July 2004

Neanderthals and Modern Humans
An Ecological and Evolutionary Perspective. by Clive Finlayson. Cambridge University Press, New York, 2004. 265 pp. $85, £60. ISBN 0-521-82087-1.

The author argues that the disappearance of the Neanderthals was driven by changing climate rather than competitive advantages enjoyed by early modern humans.