bluuebunny/crossref_metadata_2025 huggingface dataset:
Interchange instabilities in a partially ionized plasma
Authors: Daughton W. , Catto Peter J. , Coppi B. , Krasheninnikov S. I.
Published: July 2002

In a partially ionized plasma, the charged particle population is coupled to the neutrals through charge exchange, ionization and recombination. An interchange instability is identified in which the driving factor is the neutral pressure gradient and the dominant collisional process is charge exchange. Regimes are considered in which the mean free path for neutral collisions with ions λni is small in comparison to the macroscopic length scales. The instability is analogous to a gravitational interchange mode with an effective gravity geff=νinVn where νin is the collision frequency of ions with neutrals. The neutral flow Vn=−(Mniνin)−1dpn/dx results from a balance between the neutral pressure gradient and collisional friction with the ions. An arbitrary kyλni dispersion relation is derived using fluid equations to describe the ions and the Boltzmann equation to describe the neutrals. This dispersion relation contains viscous and inertial effects and is substantially altered in the presence of realistic parallel wavelength due to a coupling between the unstable interchange mode and a stabilizing shear Alfvén mode. Reasonable conditions under which the modes may exist are examined and the possible relevance to divertor plasmas is considered.
Cylindrical implosion experiments using laser direct drive
Authors: Tubbs David L. , Barnes Cris W. , Beck J. Bradley , Hoffman Nelson M. , Oertel John A. , Watt Robert G. , Boehly Thomas , Bradley David , Jaanimagi Paul , Knauer James
Published: July 2002

Direct-drive cylindrical-implosion experiments are performed to study perturbed hydrodynamic flows in convergent geometry. Two experimental campaigns have been conducted, to demonstrate the advantages of direct over indirect drive and to validate numerical simulations of zeroth-order hydrodynamics and single-mode perturbation growth. Results and analysis of three unperturbed-target shots and two perturbed-target shots are discussed in detail. For unperturbed-target implosions, positions of inner and outer shell edges agree between simulation and experiment during the laser pulse. However, observed shell thickness is greater than simulated in unperturbed targets during deceleration and rebound; the effect appears only at the shell’s exterior edge. For perturbed-target implosions, growth factors ∼10–14 are observed, whereas growth factors near 30 are expected from simulation. Rayleigh–Taylor growth appears to differ between simulation and experiment. Observed zeroth-order flow at the exterior edge of imploding, perturbed targets appears to differ from simulation, even during acceleration. A possible physical model to explain such apparent differences is identified.
Thermal and plasma wave depth profiling in silicon
Authors: Opsal Jon , Rosencwaig Allan
Published: July 2002

We describe a depth-profiling concept using the critically damped plasma wave corresponding to the propagation of the free-carrier plasma density generated by a modulated laser in a semiconductor.
Far-infrared emission from two-dimensional plasmons in AlGaAs/GaAs heterointerfaces
Authors: Okisu Noriyuki , Sambe Yasuo , Kobayashi Takeshi
Published: July 2002

A modified dispersion formula describing two-dimensional (2D) plasmons in AlGaAs/GaAs heterointerfaces was derived and its validity was experimentally checked by observation of the far-infrared signal from grating coupled 2D plasmons in selectively doped AlGaAs/GaAs heterointerfaces. The plasmon resonance frequency shift towards higher energy observed by Höpfel et al. [Surf. Sci. 113, 118 (1982)] can be explained by our present dispersion formula.
Attenuation of far-infrared surface plasmons on overcoated metal
Authors: Steijn K. W. , Seymour R. J. , Stegeman G. I.
Published: July 2002

The attenuation of far-infrared (λ=0.119 mm) surface plasmons has been measured as a function of the thickness of a silicon overlayer on top of silver. Good agreement with theory was obtained indicating that the Drüde model for the dielectric constant of silver is valid out to these wavelengths.
20.2% efficiency Al0.4Ga0.6As/GaAs tandem solar cells grown by molecular beam epitaxy
Authors: Amano Chikara , Sugiura Hideo , Yamamoto Akio , Yamaguchi Masafumi
Published: July 2002

We report on the fabrication and the characteristics of Al0.4Ga0.6As/GaAs tandem solar cells. The annealing characteristics of GaAs tunnel diodes are studied. It is found that the degradation of the tunnel peak current density by the annealing is suppressed for the diodes composed of a GaAs tunnel junction sandwiched between AlGaAs layers. The tunnel junction is applied to the interconnect between the Al0.4Ga0.6As top cell and the GaAs bottom cell for the tandem solar cell. The cell has a short-circuit current density of 13.8 mA/cm2, an open-circuit voltage of 2.10 V, a fill factor of 70.0%, and a conversion efficiency of 20.2% at 1 sun, AM1.5. This efficiency is the highest ever reported at 1 sun for tandem solar cells.
Electron trap center generation due to hole trapping in SiO2 under Fowler–Nordheim tunneling stress
Authors: Uchida Hidetsugu , Ajioka Tsuneo
Published: July 2002

The relation between generation of neutral electron trap centers and hole trapping in thermally grown SiO2 under Fowler–Nordheim tunneling stress has been investigated. The experimental results show that the density of neutral electron trap centers is proportional to the density of trapped holes under Fowler–Nordheim tunneling stress with various electric fields and the total number of electrons injected into the oxide. The generation mechanism is explained by a model based on strained bonds.
Characterization of frequency dispersion in Ti-indiffused lithium niobate optical devices
Authors: Nightingale J. L. , Becker R. A. , Willis P. C. , Vrhel J. S.
Published: July 2002

The frequency dispersion of integrated optic interferometers fabricated on different lithium niobate substrate orientations is characterized. Dispersion in the dielectric constants and the electro-optic coefficients causes most device configurations to have a significantly different electro-optic response at frequencies above and below the acoustic resonances. Only the configuration that uses the r33 electro-optic coefficient displays a broadband, well behaved frequency response.
Neutron production from a shell-confined carbon-deuterium plasma by 1.06 μm laser irradiation
Authors: Daido Hiroyuki , Yamanaka Masanobu , Mima Kunioki , Nishihara Katsunobu , Nakai Sadao , Kitagawa Yoneyoshi , Miura Eisuke , Yamanaka Chiyoe , Hasegawa Akira
Published: July 2002

We demonstrate for the first time the production of more than 108 neutrons per shot from a carbon-deuterium plasma confined in a 100-μm-thick gold shell without an implosion using six beams from a GEKKO XII glass laser system at a laser wavelength of 1.06 μm. The equivalent neutron of the deuterium-tritium reaction is estimated to be 1010–1011.
Stacking-fault-induced defect creation in SiO2 on Si(100)
Authors: Liehr M. , Bronner G. B. , Lewis J. E.
Published: July 2002

Decomposition of SiO2 films on Si(100) during ultrahigh-vacuum anneal has been shown previously to be preceded, at low anneal temperatures, by electrical defect creation in metal-oxide-semiconductor structures. In this letter, the presence of stacking faults in a Si substrate is shown to be related to enhanced oxide decomposition during high-temperature anneal. Decomposition is enhanced because of the creation of a larger number of nucleation centers for the formation of volatile SiO. These nucleation centers are the result of the metals gettered in the stacking faults close to the SiO2/Si interface.
Elimination of residual signals and reduction of noise in a low-frequency magnetic fiber sensor
Authors: Dagenais Dominique M. , Bucholtz Frank , Koo Kee P.
Published: July 2002

Low-frequency sensitivities of interferometric magnetic fiber optic sensors have been limited by the presence of a large residual signal at the dither frequency which limits the dynamic range and upconverts low-frequency noise into sideband noise around the carrier. We present an operating regime that enables us to eliminate residual signals associated with the ac carrier. By choosing the proper carrier frequency and amplitude we obtain a nulled residual signal, strong magnetomechanical coupling, and an increase in signal-to-noise ratio of approximately 13 dB over previously reported results. A minimum detectable field of 45 pT/(Hz)1/2 at 0.1 Hz is demonstrated.
Role of poly(ADP-ribose) polymerase in rapid intracellular acidification induced by alkylating DNA damage
Authors: Affar El Bachir , Shah Rashmi G. , Dallaire Annie-Karine , Castonguay Vincent , Shah Girish M.
Published: July 2002

In response to high levels of DNA damage, catalytic activation of
the nuclear enzyme poly(ADP-ribose) polymerase (PARP) triggers necrotic
death because of rapid consumption of its substrate β-nicotinamide
adenine dinucleotide and consequent depletion of ATP. We examined
whether there are other consequences of PARP activation that could
contribute to cell death. Here, we show that PARP activation reaction
in vitro
becomes acidic with release of protons during
hydrolysis of β-nicotinamide adenine dinucleotide. In the cellular
context, we show that Molt 3 cells respond to DNA damage by the
alkylating agent
N
-methyl-
N
′-nitro-
N
-nitrosoguanidine
(MNNG) with a dose-dependent acidification within 30 min. Whereas
acidification by 0.15 pH units induced by 10 μM MNNG is reversed
within 1 h, 100 μM MNNG-induced acidification by 0.5–0.6 pH
units is persistent up to 7 h. Acidification is a general DNA
damage response because H
2
O
2
exposure also
acidifies Molt 3 cells, and MNNG causes acidification in Jurkat, U937,
or HL-60 leukemia cells and in PARP
+/+
fibroblasts.
Acidification is significantly decreased in the presence of PARP
inhibitors or in PARP
−/−
fibroblasts, suggesting a major
role for PARP activation in acidification. Inhibition of proton export
through ATP-dependent Na
+
/H
+
exchanger is
another major cause of acidification. Using the pH clamp method to
either suppress or introduce changes in cellular pH, we show that brief
acidification by 0.5–0.6 pH units may be a negative regulator of
apoptosis while permitting necrotic death of cells with
extensively damaged DNA.
Lymph nodal prion replication and neuroinvasion in mice devoid of follicular dendritic cells
Authors: Prinz Marco , Montrasio Fabio , Klein Michael A. , Schwarz Petra , Priller Josef , Odermatt Bernhard , Pfeffer Klaus , Aguzzi Adriano
Published: July 2002

Variant Creutzfeldt–Jakob disease and scrapie are typically initiated by extracerebral exposure to prions, and exhibit early prion accumulation in germinal centers. Follicular dendritic cells (FDCs), whose development and maintenance in germinal centers depends on tumor necrosis factor (TNF) and lymphotoxin (LT) signaling, are thought to be indispensable for extraneural prion pathogenesis. Here, we administered prions intraperitoneally to mice deficient for TNF and LT signaling components. LTα−/−, LTβ−/−, LTβR−/−, and LTα−/−× TNFα−/−mice resisted infection and contained no infectivity in spleens and lymph nodes (when present). However, TNFR1−/−, TNFR2−/−, and some TNFα−/−mice developed scrapie similarly to wild-type mice. High prion titers were detected in lymph nodes, but not spleens, of TNFR1−/−and TNFα−/−mice despite absence of FDCs and germinal centers. Transfer of TNFR1−/−fetal liver cells into lethally irradiatedPrnp0/0mice restored infectivity mainly in lymph nodes. Prion protein (PrP) colocalized with a minority of macrophages in tumor necrosis factor receptor (TNFR) 1−/−lymph nodes. Therefore, prion pathogenesis can be restricted to lymphoreticular subcompartments, and mature follicular dendritic cells are dispensable for this process. Macrophage subsets are plausible candidates for lymphoreticular prion pathogenesis and neuroinvasion in the absence of FDCs, and may represent a novel target for postexposure prophylaxis.
The fibrinolytic receptor for urokinase activates the G protein-coupled chemotactic receptor FPRL1/LXA4R
Authors: Resnati M. , Pallavicini I. , Wang J. M. , Oppenheim J. , Serhan C. N. , Romano M. , Blasi F.
Published: July 2002

The function of urokinase and its receptor is essential for cell migration in pathological conditions, as shown by the analysis of knockout mice phenotypes. How a protease of a fibrinolytic pathway can induce migration is not understood and no link between this protease and migration-promoting G protein-coupled receptors has been described. We now show that FPRL1/LXA4R, a G protein-coupled receptor for a number of polypeptides and for the endogenous lipoxin A4 (LXA4), is the link between urokinase-type plasminogen activator (uPA) and migration as it directly interacts with an activated, soluble, cleaved form of uPA receptor (uPAR) (D2D3
88–274
) to induce chemotaxis. In this article we show that (
i
) both uPAR and FPRL1/LXA4R are necessary for the chemotactic activity of uPA whereas FPRL1/LXA4R is sufficient to mediate D2D3
88–274
-induced cell migration. (
ii
) Inhibition or desensitization of FPRL1/LXA4R by antibodies or specific ligands specifically prevents chemotaxis induced by D2D3
88–274
in THP-1 cells and human peripheral blood monocytes. (
iii
) Desensitization of FPRL1/LXA4R prevents the activation of tyrosine kinase Hck induced by D2D3
88–274
. (
iv
) D2D3
88–274
directly binds to FPRL1/LXA4R and is competed by two specific FPRL1/LXA4R agonists, the synthetic MMK-1 peptide and a stable analog of LXA4. Thus, a naturally produced cleaved form of uPAR is a unique endogenous chemotactic agonist for FPRL1/LXA4R receptor and its activity can be antagonized by specific ligands. These results provide the first direct link, to our knowledge, between the fibrinolytic machinery and the inflammatory response, demonstrating that uPA-derived peptide fragments can activate a specific chemotactic receptor.
Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons
Authors: Vanderklish Peter W. , Edelman Gerald M.
Published: July 2002

Changes in the morphology of dendritic spines are correlated with synaptic plasticity and may relate mechanistically to its expression and stabilization. Recent work has shown that spine length can be altered by manipulations that affect intracellular calcium, and spine length is abnormal in genetic conditions affecting protein synthesis in neurons. We have investigated how ligands of group 1 metabotropic glutamate receptors (mGluRs) affect spine shape; stimulation of these receptors leads both to calcium release from intracellular stores and to dendritic protein synthesis. Thirty-minute incubation of cultured hippocampal slices and dissociated neurons with the selective group 1 mGluR agonist (
S
)-3,5-dihydroxyphenylglycine (DHPG) induced a significant increase in the average length of dendritic spines. This elongation resulted mainly from the growth of existing spines and was also seen even in the presence of antagonists of ionotropic receptors, indicating that activation of these receptors by mGluR-induced glutamate release was not required. Prolonged antagonism of group 1 mGluRs with (
S
)-α-methyl-4-carboxyphenylglycine (MCPG) did not result in shorter average spine length. Elongation of dendritic spines induced by DHPG was blocked by calcium chelation and by preincubation with the protein synthesis inhibitor puromycin. The results suggest that
in vivo
activation of group 1 mGluRs by synaptically released glutamate affects spine shape in a protein synthesis-dependent manner.
Lifespan depends on month of birth
Authors: Doblhammer Gabriele , Vaupel James W.
Published: July 2002

Month of birth influences adult life expectancy at ages 50+. Why?
In two countries of the Northern Hemisphere–Austria and
Denmark–people born in autumn (October–December) live longer than
those born in spring (April–June). Data for Australia show that, in
the Southern Hemisphere, the pattern is shifted by half a year. The
lifespan pattern of British immigrants to Australia is similar to that
of Austrians and Danes and significantly different from that of
Australians. These findings are based on population data with more than
a million observations and little or no selectivity. The differences in
lifespan are independent of the seasonal distribution of deaths and the
social differences in the seasonal distribution of births. In the
Northern Hemisphere, the excess mortality in the first year of life of
infants born in spring does not support the explanation of selective
infant survival. Instead, remaining life expectancy at age 50 appears
to depend on factors that arise
in utero
or early in
infancy and that increase susceptibility to diseases later in life.
This result is consistent with the finding that, at the turn of the
last century, infants born in autumn had higher birth weights than
those born in other seasons. Furthermore, differences in adult lifespan
by month of birth decrease over time and are significantly smaller in
more recent cohorts, which benefited from substantial improvements in
maternal and infant health.
An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids
Authors: Xie Wen , Radominska-Pandya Anna , Shi Yanhong , Simon Cynthia M. , Nelson Michael C. , Ong Erwin S. , Waxman David J. , Evans Ronald M.
Published: July 2002

Hepatic hydroxylation is an essential step in the metabolism and
excretion of bile acids and is necessary to avoid pathologic conditions
such as cholestasis and liver damage. In this report, we demonstrate
that the human xenobiotic receptor SXR (steroid and xenobiotic
receptor) and its rodent homolog PXR (pregnane X receptor) serve as
functional bile acid receptors in both cultured cells and animals. In
particular, the secondary bile acid derivative lithocholic acid (LCA)
is highly hepatotoxic and, as we show here, a metabolic substrate for
CYP3A hydroxylation. By using combinations of knockout and transgenic
animals, we show that activation of SXR/PXR is necessary and
sufficient to both induce CYP3A enzymes and confer resistance to
toxicity by LCA, as well as other xenotoxicants such as tribromoethanol
and zoxazolamine. Therefore, we establish SXR and PXR as bile acid
receptors and a role for the xenobiotic response in the detoxification
of bile acids.
Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity
Authors: Schmidt Darja , Müller Stefan
Published: July 2002

The activity of the p53 tumor suppressor protein and the c-Jun protooncogene is regulated by posttranslational modifications, such as phosphorylation or ubiquitination. In addition, covalent attachment of the ubiquitin-like modifier SUMO appears to modulate their transcriptional activity. Sumoylation proceeds via an enzymatic pathway that is mechanistically analogous to ubiquitination, but requires a different E1-activating enzyme and Ubc9, a SUMO-specific E2-conjugating enzyme. Here, we show that two members of the PIAS family, PIAS1 and PIASxβ, act as specific E3-like ligases that promote sumoylation of p53 and c-Jun
in vitro
and
in vivo
. The PIAS proteins physically interact with both p53 and c-Jun. In addition, they bind to Ubc9, suggesting that they recruit the E2 enzyme to their respective substrate. The SUMO ligase activity requires the conserved zinc-finger domain, which is distantly related to the essential RING-finger motif, found in a subset of ubiquitin ligases. Furthermore, similar to RING-type ubiquitin ligases, PIASxβ can catalyze its own modification. Hence, these data further extend the analogy between the ubiquitin and SUMO pathway. Strikingly, PIAS proteins strongly repress the transcriptional activity of p53, suggesting that the PIAS–SUMO pathway plays a crucial role in the regulation of p53 and presumably other transcription factors.
Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation
Authors: Ambruso Daniel R. , Knall Cindy , Abell Amy N. , Panepinto Julie , Kurkchubasche Arlet , Thurman Gail , Gonzalez-Aller Carolina , Hiester Andrew , deBoer Martin , Harbeck Ronald J. , Oyer Ryan , Johnson Gary L. , Roos Dirk
Published: July 2002

A 5-week-old male infant presented with severe bacterial infections and poor wound healing, suggesting a neutrophil defect. Neutrophils from this patient exhibited decreased chemotaxis, polarization, azurophilic granule secretion, and superoxide anion (O2−) production but had normal expression and up-regulation of CD11b. Rac2, which constitutes >96% of the Rac in neutrophils, is a member of the Rho family of GTPases that regulates the actin cytoskeleton and O2−production. Western blot analysis of lysates from patient neutrophils demonstrated decreased levels of Rac2 protein. Addition of recombinant Rac to extracts of the patient neutrophils reconstituted O2−production in anin vitroassay system. Molecular analysis identified a point mutation in one allele of the Rac2 gene resulting in the substitution of Asp57 by an Asn (Rac2D57N). Asp57 is invariant in all defined GTP-binding proteins. Rac2D57Nbinds GDP but not GTP and inhibits oxidase activation and O2−productionin vitro. These data represent the description of an inhibitory mutation in a member of the Rho family of GTPases associated with a human immunodeficiency syndrome.
Guest-induced organization of an optimal receptor from a dynamic receptor library: Spectroscopic screening
Authors: Kubota Yasuo , Sakamoto Shigeru , Yamaguchi Kentaro , Fujita Makoto
Published: July 2002

Complexation of a cis-protected palladium ion and a family of exo-bidentate and -tridentate ligands results in the formation of an equilibrium mixture of numerous metal-linked receptors that are referred to as a dynamic receptor library. We found that a guest induced the selective formation of the optimal receptor of its own. Screening of the library by using difference NMR facilitates the search for new receptors because in difference NMR only receptors interacting with the guest can be observed. An unpredictable heterotopic receptor was discovered by this screening method. Interestingly, the new receptor thus found was assembled quantitatively only in the presence of its optimal guest.
What was natural in the coastal oceans?
Authors: Jackson Jeremy B. C.
Published: July 2002

Humans transformed Western Atlantic coastal marine ecosystems
before modern ecological investigations began. Paleoecological,
archeological, and historical reconstructions demonstrate incredible
losses of large vertebrates and oysters from the entire Atlantic coast.
Untold millions of large fishes, sharks, sea turtles, and manatees were
removed from the Caribbean in the 17th to 19th centuries. Recent
collapses of reef corals and seagrasses are due ultimately to losses of
these large consumers as much as to more recent changes in climate,
eutrophication, or outbreaks of disease. Overfishing in the 19th
century reduced vast beds of oysters in Chesapeake Bay and other
estuaries to a few percent of pristine abundances and promoted
eutrophication. Mechanized harvesting of bottom fishes like cod set off
a series of trophic cascades that eliminated kelp forests and then
brought them back again as fishers fished their way down food webs to
small invertebrates. Lastly, but most pervasively, mechanized
harvesting of the entire continental shelf decimated large, long-lived
fishes and destroyed three-dimensional habitats built up by sessile
corals, bryozoans, and sponges. The universal pattern of losses
demonstrates that no coastal ecosystem is pristine and few wild
fisheries are sustainable along the entire Western Atlantic coast.
Reconstructions of ecosystems lost only a century or two ago
demonstrate attainable goals of establishing large and effective marine
reserves if society is willing to pay the costs. Historical
reconstructions provide a new scientific framework for manipulative
experiments at the ecosystem scale to explore the feasibility and
benefits of protection of our living coastal resources.
Intervening in evolution: Ethics and actions
Authors: Ehrlich Paul R.
Published: July 2002

Biologists should help to guide a process of cultural evolution in which society determines how much effort, if any, is ethically required to preserve options in biological evolution. Evolutionists, conservation biologists, and ecologists should be doing more research to determine actions that would best help to avoid foreclosing evolutionary options.
Reduced immunopathology and mortality despite tissue persistence in aMycobacterium tuberculosismutant lacking alternative σ factor, SigH
Authors: Kaushal Deepak , Schroeder Benjamin G. , Tyagi Sandeep , Yoshimatsu Tetsuyuki , Scott Cherise , Ko Chiew , Carpenter Liane , Mehrotra Jyoti , Manabe Yukari C. , Fleischmann Robert D. , Bishai William R.
Published: July 2002

The pathogenesis of tuberculosis involves multiple phases and is believed to involve both a carefully deployed series of adaptive bacterial virulence factors and inappropriate host immune responses that lead to tissue damage. A definedMycobacterium tuberculosismutant strain lacking thesigH-encoded transcription factor showed a distinctive infection phenotype. In resistant C57BL/6 mice, the mutant achieved high bacterial counts in lung and spleen that persisted in tissues in a pattern identical to those of wild-type bacteria. Despite a high bacterial burden, the mutant produced a blunted, delayed pulmonary inflammatory response, and recruited fewer CD4+and CD8+T cells to the lung in the early stages of infection. In susceptible C3H mice, the mutant again showed diminished immunopathology and was nonlethal at over 170 days after intravenous infection, in contrast to isogenic wild-type bacilli, which killed with a median time to death of 52 days. Complete genomic microarray analysis revealed thatM. tuberculosis sigHmay mediate the transcription of at least 31 genes directly and that it modulates the expression of about 150 others; the SigH regulon governs thioredoxin recycling and may be involved in the maintenance of intrabacterial reducing capacity. These data show that theM. tuberculosis sigHgene is dispensable for bacterial growth and survival within the host, but is required for the production of immunopathology and lethality. This phenotype demonstrates that beyond an ability to grow and persist within the host,M. tuberculosishas distinct virulence mechanisms that elicit deleterious host responses and progressive pulmonary disease.
Integrated fossil and molecular data reconstruct bat echolocation
Authors: Springer Mark S. , Teeling Emma C. , Madsen Ole , Stanhope Michael J. , de Jong Wilfried W.
Published: July 2002

Molecular and morphological data have important roles in
illuminating evolutionary history. DNA data often yield well resolved
phylogenies for living taxa, but are generally unattainable for
fossils. A distinct advantage of morphology is that some types of
morphological data may be collected for extinct and extant taxa.
Fossils provide a unique window on evolutionary history and may
preserve combinations of primitive and derived characters that are not
found in extant taxa. Given their unique character complexes, fossils
are critical in documenting sequences of character transformation over
geologic time and may elucidate otherwise ambiguous patterns of
evolution that are not revealed by molecular data alone. Here, we
employ a methodological approach that allows for the integration of
molecular and paleontological data in deciphering one of the most
innovative features in the evolutionary history of mammals—laryngeal
echolocation in bats. Molecular data alone, including an expanded data
set that includes new sequences for the A2AB gene, suggest that
microbats are paraphyletic but do not resolve whether laryngeal
echolocation evolved independently in different microbat lineages or
evolved in the common ancestor of bats and was subsequently lost in
megabats. When scaffolds from molecular phylogenies are incorporated
into parsimony analyses of morphological characters, including
morphological characters for the Eocene taxa
Icaronycteris
,
Archaeonycteris
,
Hassianycteris
, and
Palaeochiropteryx
,
the resulting trees suggest that laryngeal echolocation evolved in the
common ancestor of fossil and extant bats and was subsequently lost in
megabats. Molecular dating suggests that crown-group bats last shared a
common ancestor 52 to 54 million years ago.
Opiates inhibit neurogenesis in the adult rat hippocampus
Authors: Eisch Amelia J. , Barrot Michel , Schad Christina A. , Self David W. , Nestler Eric J.
Published: July 2002

Recent work implicates regulation of neurogenesis as a form of plasticity in the adult rat hippocampus. Given the known effects of opiates such as morphine and heroin on hippocampal function, we examined opiate regulation of neurogenesis in this brain region. Chronic administration of morphine decreased neurogenesis by 42% in the adult rat hippocampal granule cell layer. A similar effect was seen in rats after chronic self-administration of heroin. Opiate regulation of neurogenesis was not mediated by changes in circulating levels of glucocorticoids, because similar effects were seen in rats that received adrenalectomy and corticosterone replacement. These findings suggest that opiate regulation of neurogenesis in the adult rat hippocampus may be one mechanism by which drug exposure influences hippocampal function.
Site-specific chemical modification with polyethylene glycol of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) improves antitumor activity and reduces animal toxicity and immunogenicity
Authors: Tsutsumi Yasuo , Onda Masanori , Nagata Satoshi , Lee Byungkook , Kreitman Robert J. , Pastan Ira
Published: July 2002

Chemical modification of proteins with polyethylene glycol (PEGylation) can increase plasma half-lives, stability, and therapeutic potency. To make a PEGylated recombinant immunotoxin with improved therapeutic properties, we prepared a mutant of anti-Tac(Fv)-PE38 (LMB-2), a recombinant immunotoxin composed of a single-chain Fv fragment of the anti-human Tac monoclonal antibody to the IL-2 receptor α subunit fused to a 38-kDa fragment ofPseudomonasexotoxin. For site-specific PEGylation of LMB-2, one cysteine residue was introduced into the peptide connector (ASGCGPE) between the Fv and the toxin. This mutant LMB-2 (cys1-LMB-2), which retained full cytotoxic activity, was then site-specifically conjugated with 5 or 20 kDa of polyethylene glycol-maleimide. When compared with unmodified LMB-2, both PEGylated immunotoxins showed similar cytotoxic activitiesin vitrobut superior stability at 37°C in mouse serum, a 5- to 8-fold increase in plasma half-lives in mice, and a 3- to 4-fold increase in antitumor activity. This was accompanied by a substantial decrease in animal toxicity and immunogenicity. Site-specific PEGylation of recombinant immunotoxins may increase their therapeutic potency in humans.
Presence of mitochondria-type ribosomes outside mitochondria in germ plasm of
Drosophila
embryos
Authors: Amikura Reiko , Kashikawa Maki , Nakamura Akira , Kobayashi Satoru
Published: July 2002

Mitochondrially encoded large and small ribosomal RNAs (mtlrRNA and mtsrRNA) are transported out of mitochondria to polar granules, the distinctive organelles of germ plasm in
Drosophila
. Reduction of the extramitochondrial mtlrRNA amount leads to the failure of embryos to form the germ-line progenitors, or pole cells, suggesting that mtlrRNA, along with mtsrRNA, functions on the polar granules to specify the germ line. In this study, we provide several lines of evidence showing that there are mitochondria-type ribosomes on the polar granules during a short period before pole cell formation. Our ultrastructural analysis reveals that these ribosomes include both mitochondrial rRNAs and at least two mitochondrial ribosomal proteins (S12 and L7/L12). Furthermore, these ribosomes are integrated into well developed polysomes on the surface of polar granules. We propose that translation dependent on mitochondria-type ribosomes is an important mechanism underlying germ-line formation.
Mediation of tubuloglomerular feedback by adenosine: Evidence from mice lacking adenosine 1 receptors
Authors: Sun Daqing , Samuelson Linda C. , Yang Tianxin , Huang Yuning , Paliege Alex , Saunders Thom , Briggs Josie , Schnermann Jurgen
Published: July 2002

Adenosine is a determinant of metabolic control of organ function
increasing oxygen supply through the A2 class of adenosine receptors
and reducing oxygen demand through A1 adenosine receptors (A1AR). In
the kidney, activation of A1AR in afferent glomerular arterioles has
been suggested to contribute to tubuloglomerular feedback (TGF), the
vasoconstriction elicited by elevations in [NaCl] in the macula densa
region of the nephron. To further elucidate the role of A1AR in TGF, we
have generated mice in which the entire A1AR coding sequence was
deleted by homologous recombination. Homozygous A1AR mutants that do
not express A1AR mRNA transcripts and do not respond to A1AR agonists
are viable and without gross anatomical abnormalities. Plasma and
urinary electrolytes were not different between genotypes. Likewise,
arterial blood pressure, heart rates, and glomerular filtration rates
were indistinguishable between A1AR
+/+
,
A1AR
+/−
, and A1AR
−/−
mice. TGF responses to
an increase in loop of Henle flow rate from 0 to 30 nl/min, whether
determined as change of stop flow pressure or early proximal flow rate,
were completely abolished in A1AR
−/−
mice (stop flow
pressure response, −6.8 ± 0.55 mmHg and −0.4 ± 0.2 in
A1AR
+/+
and A1AR
−/−
mice; early proximal flow
rate response, −3.4 ± 0.4 nl/min and +0.02 ± 0.3
nl/min in A1AR
+/+
and A1AR
−/−
mice).
Absence of TGF responses in A1AR-deficient mice suggests that adenosine
is a required constituent of the juxtaglomerular signaling pathway.
A1AR null mutant mice are a promising tool to study the functional role
of A1AR in different target tissues.
Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice
Authors: Miller Douglas L. , Quddus Jawaid
Published: July 2002

Interaction of diagnostic ultrasound with gas bodies produces a useful contrast effect in medical images, but the same interaction also represents a mechanism for bioeffects. Anesthetized hairless mice were scanned by using a 2.5-MHz transducer (610-ns pulses with 3.6-kHz repetition frequency and 61-Hz frame rate) after injection of Optison and Evans blue dye. Petechial hemorrhages (PHs) in intestine and abdominal muscle were counted 15 min after exposure to characterize capillary rupture, and Evans blue extravasation was evaluated in samples of muscle tissue. For 5 ml⋅kg
-1
contrast agent and exposure to 10 alternating 10-s on and off periods, PH counts in muscle were approximately proportional to the square of peak negative pressure amplitude and were statistically significant above 0.64 MPa. PH counts in intestine and Evans blue extravasation into muscle tissue were significant above 1.0 MPa. The PH effect in muscle was proportional to contrast dose and was statistically significant for the lowest dose of 0.05 ml⋅kg
-1
. The effects decreased nearly to sham levels if the exposure was delayed 5 min. The PH effect in abdominal muscle was significant and statistically indistinguishable for uninterrupted 100-s exposure, 10-s exposure, 100 scans repeated at 1 Hz, and even for a single scan. The results confirms a previous report of PH induction by diagnostic ultrasound with contrast agent in mammalian skeletal muscle [Skyba, D. M., Price, R. J., Linka, A. Z., Skalak, T. C. & Kaul, S. (1998)
Circulation
98, 290–293].
Caspase-10 is an initiator caspase in death receptor signaling
Authors: Wang Jin , Chun Hyung J. , Wong Wilson , Spencer David M. , Lenardo Michael J.
Published: July 2002

A role for caspase-10, previously implicated in the autoimmune lymphoproliferative syndrome, in death receptor signaling has not been directly shown. Here we show that caspase-10 can function independently of caspase-8 in initiating Fas- and tumor necrosis factor-related apoptosis-inducing ligand-receptor-mediated apoptosis. Moreover, Fas crosslinking in primary human T cells leads to the recruitment and activation of caspase-10. Fluorescent resonance energy transfer analysis indicates that the death-effector domains of caspase-8 and -10 both interact with the death-effector domain of FADD. Nonetheless, we find that caspase-8 and -10 may have different apoptosis substrates and therefore potentially distinct roles in death receptor signaling or other cellular processes.
Helicobacter pyloriarginase inhibits nitric oxide production by eukaryotic cells: A strategy for bacterial survival
Authors: Gobert Alain P. , McGee David J. , Akhtar Mahmood , Mendz George L. , Newton Jamie C. , Cheng Yulan , Mobley Harry L. T. , Wilson Keith T.
Published: July 2002

The antimicrobial effect of nitric oxide (NO) is an essential part of innate immunity. The vigorous host response to the human gastric pathogenHelicobacter pylorifails to eradicate the organism, despite up-regulation of inducible NO synthase (iNOS) in the gastric mucosa. Here we report that wild-type strains ofH. pyloriinhibit NO production by activated macrophages at physiologic concentrations ofl-arginine, the common substrate for iNOS and arginase. Inactivation of the generocF, encoding constitutively expressed arginase inH. pylori, restored high-output NO production by macrophages. By using HPLC analysis, we show thatl-arginine is effectively consumed in the culture medium by wild-type but not arginase-deficientH. pylori. The substantially higher levels of NO generated by macrophages cocultured withrocF-deficientH. pyloriresulted in efficient killing of the bacteria, whereas wild-typeH. pyloriexhibited no loss of survival under these conditions. Killing of the arginase-deficientH. pyloriwas NO-dependent, because peritoneal macrophages from iNOS−/−mice failed to affect the survival of therocFmutant. Thus, bacterial arginase allowsH. pylorito evade the immune response by down-regulating eukaryotic NO production.
Pattern formation in
Escherichia coli
: A model for the pole-to-pole oscillations of Min proteins and the localization of the division site
Authors: Meinhardt Hans , de Boer Piet A. J.
Published: July 2002

Proper cell division requires an accurate definition
of the division plane. In bacteria, this plane is determined by a
polymeric ring of the FtsZ protein. The site of Z ring assembly in turn
is controlled by the Min system, which suppresses FtsZ polymerization
at noncentral membrane sites. The Min proteins in
Escherichia
coli
undergo a highly dynamic localization cycle, during which
they oscillate between the membrane of both cell halves. By
using computer simulations we show that Min protein dynamics can be
described accurately by using the following assumptions:
(
i
) the MinD ATPase self-assembles on the membrane and
recruits both MinC, an inhibitor of Z ring formation, and MinE, a
protein required for MinC/MinD oscillation, (
ii
) a
local accumulation of MinE is generated by a pattern formation reaction
that is based on local self-enhancement and a long range antagonistic
effect, and (
iii
) it displaces MinD from the membrane
causing its own local destabilization and shift toward higher MinD
concentrations. This local destabilization results in a wave of
high MinE concentration traveling from the cell center to a pole, where
it disappears. MinD reassembles on the membrane of the other cell half
and attracts a new accumulation of MinE, causing a wave-like
disassembly of MinD again. The result is a pole-to-pole oscillation of
MinC/D. On time average, MinC concentration is highest at the poles,
forcing FtsZ assembly to the center. The mechanism is self-organizing
and does not require any other hypothetical topological determinant.
A second iron-regulatory system in yeast independent of Aft1p
Authors: Rutherford Julian C. , Jaron Shulamit , Ray Esha , Brown Patrick O. , Winge Dennis R.
Published: July 2002

Iron homeostasis in the yeast
Saccharomyces
cerevisiae
is regulated at the transcriptional level by Aft1p,
which activates the expression of its target genes in response to
low-iron conditions. The yeast genome contains a paralog of
AFT1,
which has been designated
AFT2
. To
establish whether
AFT1
and
AFT2
have
overlapping functions, a mutant containing a double
aft1
Δ
aft2
Δ deletion was generated.
Growth assays established that the single
aft2
Δ strain
exhibited no iron-dependent phenotype. However, the double-mutant
aft1
Δ
aft2
Δ strain was more sensitive
to low-iron growth conditions than the single-mutant
aft1
Δ strain. A mutant allele of
AFT2
(
AFT2
-
1

up

), or
overexpression of the wild-type
AFT2
gene, led to
partial complementation of the respiratory-deficient phenotype of the
aft1
Δ strain. The
AFT2
-
1

up

allele also
increased the uptake of
59
Fe in an
aft1Δ
strain. DNA microarrays were used to identify genes regulated by
AFT2
. Some of the
AFT2
-regulated genes
are known to be regulated by Aft1p; however,
AFT2
-
1

up

-dependent
activation was independent of Aft1p. The kinetics of induction of two
genes activated by the
AFT2
-
1

up

allele are
consistent with Aft2p acting as a direct transcriptional factor.
Truncated forms of Aft1p and Aft2p bound to a DNA duplex containing the
Aft1p binding site
in vitro
. The wild-type allele of
AFT2
activated transcription in response to growth under
low-iron conditions. Together, these data suggest that yeast has a
second regulatory pathway for the iron regulon, with
AFT1
and
AFT2
playing partially redundant
roles.
cAMP compartmentation is responsible for a local activation of cardiac Ca2+ channels by beta-adrenergic agonists.
Authors: Jurevicius J , Fischmeister R
Published: July 2002

The role of cAMP subcellular compartmentation in the progress of beta-adrenergic stimulation of cardiac L-type calcium current (ICa) was investigated by using a method based on the use of whole-cell patch-clamp recording and a double capillary for extracellular microperfusion. Frog ventricular cells were sealed at both ends to two patch-clamp pipettes and positioned approximately halfway between the mouths of two capillaries that were separated by a 5-micron thin wall. ICa could be inhibited in one half or the other by omitting Ca2+ from one solution or the other. Exposing half of the cell to a saturating concentration of isoprenaline (ISO, 1 microM) produced a nonmaximal increase in ICa (347 +/- 70%; n = 4) since a subsequent application of ISO to the other part induced an additional effect of nearly similar amplitude to reach a 673 +/- 130% increase. However, half-cell exposure to forskolin (FSK, 30 microM) induced a maximal stimulation of ICa (561 +/- 55%; n = 4). This effect was not the result of adenylyl cyclase activation due to FSK diffusion in the nonexposed part of the cell. To determine the distant effects of ISO and FSK on ICa, the drugs were applied in a zero-Ca solution. Adding Ca2+ to the drug-containing solutions allowed us to record the local effect of the drugs. Dose-response curves for the local and distant effects of ISO and FSK on ICa were used as an index of cAMP concentration changes near the sarcolemma. We found that ISO induced a 40-fold, but FSK induced only a 4-fold, higher cAMP concentration close to the Ca2+ channels, in the part of the cell exposed to the drugs, than it did in the rest of the cell. cAMP compartmentation was greatly reduced after inhibition of phosphodiesterase activity with 3-isobutyl-methylxanthine, suggesting the colocalization of enzymes involved in the cAMP cascade. We conclude that beta-adrenergic receptors are functionally coupled to nearby Ca2+ channels via local elevations of cAMP.
Genetic interactions among cytoplasmic dynein, dynactin, and nuclear distribution mutants of Neurospora crassa.
Authors: Bruno K S , Tinsley J H , Minke P F , Plamann M
Published: July 2002

Cytoplasmic dynein is a multisubunit, microtubule-associated, mechanochemical enzyme that has been identified as a retrograde transporter of various membranous organelles. Dynactin, an additional multisubunit complex, is required for efficient dynein-mediated transport of vesicles in vitro. Recently, we showed that three genes defined by a group of phenotypically identical mutants of the filamentous fungus Neurospora crassa encode proteins that are apparent subunits of either cytoplasmic dynein or dynactin. These mutants, designated ropy (ro), display abnormal hyphal growth and are defective in nuclear distribution. We propose that mutations in other genes encoding dynein/dynactin subunits are likely to result in a ropy phenotype and have devised a genetic screen for the isolation of additional ro mutants. Cytoplasmic dynein/dynactin is the largest and most complex of the cytoplasmic motor proteins, and the genetic system described here is unique in its potentiality for identifying mutations in undefined genes encoding dynein/dynactin subunits or regulators. We used this screen to isolate > 1000 ro mutants, which were found to define 23 complementation groups. Unexpectedly, interallelic complementation was observed with some allele pairs of ro-1 and ro-3, which are predicted to encode the largest subunits of cytoplasmic dynein and dynactin, respectively. The results suggest that the Ro1 and Ro3 polypeptides may consist of multiple, functionally independent domains. In addition, approximately 10% of all newly isolated ro mutantsdisplay unlinked noncomplementation with two or more of the mutants that define the 23 complementation groups. The frequent appearance of ro mutants showing noncomplementation with multiple ro mutants having unlinked mutations suggests that nuclear distribution in filamentous fungi is a process that is easily disrupted by affecting either dosage or activity of cytoplasmic dynein, dynactin, and perhaps other cytoskeletal proteins or regulators.
Constitutive overexpression of Cu/Zn superoxide dismutase exacerbates kainic acid-induced apoptosis of transgenic-Cu/Zn superoxide dismutase neurons.
Authors: Bar-Peled O , Korkotian E , Segal M , Groner Y
Published: July 2002

Cu/Zn superoxide dismutase (Cu/Zn SOD) is a key enzyme in the metabolism of oxygen free radicals. The gene resides on chromosome 21 and is overexpressed in patients with Down syndrome. Cultured neurons of transgenic Cu/Zn SOD (Tg-Cu/Zn SOD) mice with elevated activity of Cu/Zn SOD were used to determine whether constitutive overexpression of Cu/Zn SOD creates an indigenous oxidative stress that predisposes the Tg-Cu/Zn SOD neurons to added insults. Neurons from three independently derived Tg-Cu/Zn SOD strains showed higher susceptibility than nontransgenic neurons to kainic acid (KA)-mediated excitotoxicity, reflected by an earlier onset and enhanced apoptotic cell death. This higher susceptibility of transgenic neurons to KA-mediated apoptosis was associated with a chronic prooxidant state that was manifested by reduced levels of cellular glutathione and altered [Ca2+]i homeostasis. The data are compatible with the thesis that overexpression of Cu/Zn SOD creates chronic oxidative stress in the transgenic neurons, which exacerbates their susceptibility to additional insults such as KA-mediated excitotoxicity.
Fibroblast growth factor (FGF) homologous factors: new members of the FGF family implicated in nervous system development.
Authors: Smallwood P M , Munoz-Sanjuan I , Tong P , Macke J P , Hendry S H , Gilbert D J , Copeland N G , Jenkins N A , Nathans J
Published: July 2002

Four new members of the fibroblast growth factor (FGF) family, referred to as fibroblast growth factor homologous factors (FHFs), have been identified by a combination of random cDNA sequencing, data base searches, and degenerate PCR. Pairwise comparisons between the four FHFs show between 58% and 71% amino acid sequence identity, but each FHF shows less than 30% identity when compared with other FGFs. Like FGF-1 (acidic FGF) and FGF-2 (basic FGF), the FHFs lack a classical signal sequence and contain clusters of basic residues that can act as nuclear localization signals. In transiently transfected 293 cells FHF-1 accumulates in the nucleus and is not secreted. Each FHF is expressed in the developing and adult nervous systems, suggesting a role for this branch of the FGF family in nervous system development and function.