bluuebunny/crossref_metadata_2025 huggingface dataset:
40
Ar/
39
Ar Dates from the West Siberian Basin: Siberian Flood Basalt Province Doubled
Authors: Reichow Marc K. , Saunders Andrew D. , White Rosalind V. , Pringle Malcolm S. , Al'Mukhamedov Alexander I. , Medvedev Alexander I. , Kirda Nikolay P.
Published: July 2002

Widespread basaltic volcanism occurred in the region of the West Siberian Basin in central Russia during Permo-Triassic times. New
40
Ar/
39
Ar age determinations on plagioclase grains from deep boreholes in the basin reveal that the basalts were erupted 249.4 ± 0.5 million years ago. This is synchronous with the bulk of the Siberian Traps, erupted further east on the Siberian Platform. The age and geochemical data confirm that the West Siberian Basin basalts are part of the Siberian Traps and at least double the confirmed area of the volcanic province as a whole. The larger area of volcanism strengthens the link between the volcanism and the end-Permian mass extinction.
Prokaryotic Diversity--Magnitude, Dynamics, and Controlling Factors
Authors: Torsvik Vigdis , Øvreås Lise , Thingstad Tron Frede
Published: July 2002

There are probably millions of species in the microorganismal domains Bacteria and Archaea (the prokaryotes), and we are only just beginning to work out the basic principles governing their distribution and abundance in natural environments. One characteristic that has become clear is that prokaryote diversity in aquatic environments is orders of magnitude less than in sediments and soils. Hypotheses and models explaining such differences are under development and are beginning to offer promising insights into the mechanisms governing prokaryote diversity and ecosystem function.
Hierarchical Control of Lymphocyte Survival
Authors: Boise Lawrence H. , Thompson Craig B.
Published: July 2002

After an immune response, the body must eliminate the excess cells generated to fight the foreign invader. Recent work indicates that this removal occurs as a result of an intricate network of regulatory processes. In their Perspective, Boise and Thompson synthesize this new evidence for the control of lymphocyte number by proteases, Bcl-2-related proteins, cytokines, and adhesion factors.
Preserved Collisional Crustal Structure of the Southern Urals Revealed by Vibroseis Profiling
Authors: Echtler H. P. , Stiller M. , Steinhoff F. , Krawczyk C. , Suleimanov A. , Spiridonov V. , Knapp J. H. , Menshikov Y. , Alvarez-Marrón J. , Yunusov N.
Published: July 2002

The vibroseis reflection profiling component of the URSEIS '95 experiment provides a high-resolution crustal-scale image of the unextended southern Uralide orogen. A marked lateral and vertical variation of reflectivity throughout the entire crust differentiates the former margin of the East European craton to the west from accreted terranes to the east. Between these regions is a less reflective zone corresponding to the Magnitogorsk volcanic arc and the crustal root zone. Continuous reflections and reflective domains that correlate at the surface with major tectonic features define a bivergent orogen in which the Paleozoic collisional structure has been largely preserved.
Lithosphere-Scale Seismic Image of the Southern Urals from Explosion-Source Reflection Profiling
Authors: Knapp J. H. , Steer D. N. , Brown L. D. , Berzin R. , Suleimanov A. , Stiller M. , Lüschen E. , Brown D. L. , Bulgakov R. , Kashubin S. N. , Rybalka A. V.
Published: July 2002

Explosive-source deep seismic reflection data from the southern Ural Mountains of central Russia provided a lithosphere-scale image of the central Eurasian plate that reveals deep reflections (35 to 45 seconds in travel time; ∼130 to 170 kilometers deep) from the mantle. The data display laterally variable reflectivity at the base of the crust that deepens beneath the central part of the profile, documenting a crustal thickness of ∼55 to 60 kilometers beneath the axis of the orogen. These data provide an image of the structure of the crust and underlying mantle lithosphere in a preserved collisional orogen, perhaps to the base of the lithosphere.
The Crystal Structure of a Five-Stranded Coiled Coil in COMP: A Prototype Ion Channel?
Authors: Malashkevich Vladimir N. , Kammerer Richard A. , Efimov Vladimir P. , Schulthess Therese , Engel Jürgen
Published: July 2002

Oligomerization by the formation of α-helical bundles is common in many proteins. The crystal structure of a parallel pentameric coiled coil, constituting the oligomerization domain in the cartilage oligomeric matrix protein (COMP), was determined at 2.05 angstroms resolution. The same structure probably occurs in two other extracellular matrix proteins, thrombospondins 3 and 4. Complementary hydrophobic interactions and conserved disulfide bridges between the α helices result in a thermostable structure with unusual properties. The long hydrophobic axial pore is filled with water molecules but can also accommodate small apolar groups. An “ion trap” is formed inside the pore by a ring of conserved glutamines, which binds chloride and probably other monatomic anions. The oligomerization domain of COMP has marked similarities with proposed models of the pentameric transmembrane ion channels in phospholamban and the acetylcholine receptor.
Structure of the A Site of
Escherichia coli
16
S
Ribosomal RNA Complexed with an Aminoglycoside Antibiotic
Authors: Fourmy Dominique , Recht Michael I. , Blanchard Scott C. , Puglisi Joseph D.
Published: July 2002

Aminoglycoside antibiotics that bind to 30
S
ribosomal A-site RNA cause misreading of the genetic code and inhibit translocation. The aminoglycoside antibiotic paromomycin binds specifically to an RNA oligonucleotide that contains the 30
S
subunit A site, and the solution structure of the RNA-paromomycin complex was determined by nuclear magnetic resonance spectroscopy. The antibiotic binds in the major groove of the model A-site RNA within a pocket created by an A-A base pair and a single bulged adenine. Specific interactions occur between aminoglycoside chemical groups important for antibiotic activity and conserved nucleotides in the RNA. The structure explains binding of diverse aminoglycosides to the ribosome, their specific activity against prokaryotic organisms, and various resistance mechanisms, and provides insight into ribosome function.
Interplane Tunneling Magnetoresistance in a Layered Manganite Crystal
Authors: Kimura T. , Tomioka Y. , Kuwahara H. , Asamitsu A. , Tamura M. , Tokura Y.
Published: July 2002

The current-perpendicular-to-plane magnetoresistance (CPP-MR) has been investigated for the layered manganite, La

2−2
x

Sr

1+2
x

Mn
2
O
7
(
x
= 0.3), which is composed of the ferromagnetic-metallic MnO
2
bilayers separated by nonmagnetic insulating block layers. The CPP-MR is extremely large (10
4
percent at 50 kilo-oersted) at temperatures near above the three-dimensional ordering temperature (
T
c
≈ 90 kelvin) because of the field-induced coherent motion between planes of the spin-polarized electrons. Below
T
c
, the interplane magnetic domain boundary on the insulating block layer serves as the charge-transport barrier, but it can be removed by a low saturation field, which gives rise to the low-field tunneling MR as large as 240 percent.
Sex-Specific Assembly of a Dosage Compensation Complex on the Nematode X Chromosome
Authors: Chuang Pao-Tien , Lieb Jason D. , Meyer Barbara J.
Published: July 2002

In nematodes, flies, and mammals, dosage compensation equalizes X-chromosome gene expression between the sexes through chromosome-wide regulatory mechanisms that function in one sex to adjust the levels of X-linked transcripts. Here, a dosage compensation complex was identified in the nematode
Caenorhabditis elegans
that reduces transcript levels from the two X chromosomes in hermaphrodites. This complex contains at least four proteins, including products of the dosage compensation genes
dpy-26
and
dpy-27
. Specific localization of the complex to the hermaphrodite X chromosomes is conferred by XX-specific regulatory genes that coordinately control both sex determination and dosage compensation.
Rotation and Magnetism of Earth's Inner Core
Authors: Glatzmaier Gary A. , Roberts Paul H.
Published: July 2002

Three-dimensional numerical simulations of the geodynamo suggest that a superrotation of Earth's solid inner core relative to the mantle is maintained by magnetic coupling between the inner core and an eastward thermal wind in the fluid outer core. This mechanism, which is analogous to a synchronous motor, also plays a fundamental role in the generation of Earth's magnetic field.
A Free Cyclotrigermenium Cation with a 2π-Electron System
Authors: Sekiguchi Akira , Tsukamoto Masanori , Ichinohe Masaaki
Published: July 2002

The reaction of tetrakis(tri-
tert
-butylsilyl)cyclotrigermene with trityl tetraphenylborate in benzene produces tris(tri-
tert
-butylsilyl)cyclotrigermenium tetraphenylborate [(
tert
-Bu
3
SiGe)
3
+
BPh
4
−
], which can be isolated as a yellow solid that is stable in the absence of air. The crystal structure of the cyclotrigermenium ion reveals a free germyl cation with a 2π

-electron system. The three germanium atoms form an equilateral triangle similar to the carbon analog, the cyclopropenium ion.
Activation of SAPK/JNK by TNF Receptor 1 Through a Noncytotoxic TRAF2-Dependent Pathway
Authors: Natoli Gioacchino , Costanzo Antonio , Ianni Angelo , Templeton Dennis J. , Woodgett James R. , Balsano Clara , Levrero Massimo
Published: July 2002

Interaction of the p55 tumor necrosis factor receptor 1 (TNF-R1)-associated signal transducer TRADD with FADD signals apoptosis, whereas the TNF receptor-associated factor 2 protein (TRAF2) is required for activation of the nuclear transcription factor nuclear factor kappa B. TNF-induced activation of the stress-activated protein kinase (SAPK) was shown to occur through a noncytotoxic TRAF2-dependent pathway. TRAF2 was both sufficient and necessary for activation of SAPK by TNF-R1; conversely, expression of a dominant-negative FADD mutant, which blocks apoptosis, did not interfere with SAPK activation. Therefore, SAPK activation occurs through a pathway that is not required for TNF-R1-induced apoptosis.
A General Strategy for Selecting High-Affinity Zinc Finger Proteins for Diverse DNA Target Sites
Authors: Greisman Harvey A. , Pabo Carl O.
Published: July 2002

A method is described for selecting DNA-binding proteins that recognize desired sequences. The protocol involves gradually extending a new zinc finger protein across the desired 9- or 10-base pair target site, adding and optimizing one finger at a time. This procedure was tested with a TATA box, a p53 binding site, and a nuclear receptor element, and proteins were obtained that bind with nanomolar dissociation constants and discriminate effectively (greater than 20,000-fold) against nonspecific DNA. This strategy may provide important information about protein-DNA recognition as well as powerful tools for biomedical research.
Twentieth-Century Sea Surface Temperature Trends
Authors: Cane Mark A. , Clement Amy C. , Kaplan Alexey , Kushnir Yochanan , Pozdnyakov Dmitri , Seager Richard , Zebiak Stephen E. , Murtugudde Ragu
Published: July 2002

An analysis of historical sea surface temperatures provides evidence for global warming since 1900, in line with land-based analyses of global temperature trends, and also shows that over the same period, the eastern equatorial Pacific cooled and the zonal sea surface temperature gradient strengthened. Recent theoretical studies have predicted such a pattern as a response of the coupled ocean-atmosphere system to an exogenous heating of the tropical atmosphere. This pattern, however, is not reproduced by the complex ocean-atmosphere circulation models currently used to simulate the climatic response to increased greenhouse gases. Its presence is likely to lessen the mean 20th-century global temperature change in model simulations.
Mass Survival of Birds Across the Cretaceous- Tertiary Boundary: Molecular Evidence
Authors: Cooper Alan , Penny David
Published: July 2002

The extent of terrestrial vertebrate extinctions at the end of the Cretaceous is poorly understood, and estimates have ranged from a mass extinction to limited extinctions of specific groups. Molecular and paleontological data demonstrate that modern bird orders started diverging in the Early Cretaceous; at least 22 avian lineages of modern birds cross the Cretaceous-Tertiary boundary. Data for several other terrestrial vertebrate groups indicate a similar pattern of survival and, taken together, favor incremental changes during a Cretaceous diversification of birds and mammals rather than an explosive radiation in the Early Tertiary.
PTG, a Protein Phosphatase 1-Binding Protein with a Role in Glycogen Metabolism
Authors: Printen John A. , Brady Matthew J. , Saltiel Alan R.
Published: July 2002

Protein dephosphorylation by phosphatase PP1 plays a central role in mediating the effects of insulin on glucose and lipid metabolism. A PP1C-targeting protein expressed in 3T3-L1 adipocytes (called PTG, for protein targeting to glycogen) was cloned and characterized. PTG was expressed predominantly in insulin-sensitive tissues. In addition to binding and localizing PP1C to glycogen, PTG formed complexes with phosphorylase kinase, phosphorylase a, and glycogen synthase, the primary enzymes involved in the hormonal regulation of glycogen metabolism. Overexpression of PTG markedly increased basal and insulin-stimulated glycogen synthesis in Chinese hamster ovary cells overexpressing the insulin receptor, which do not express endogenous PTG. These results suggest that PTG is critical for glycogen metabolism, possibly functioning as a molecular scaffold.
Protein Prenylation, et cetera--Signal Transduction in Two Dimensions
Authors: Gelb Michael H.
Published: July 2002

Many signaling proteins, including the proto-oncogene Ras, require the covalent addition of a lipid chain for proper function. This prenylated protein is then earmarked for further proteolysis and methylation. In his Perspective, Gelb discusses two reports in this issue that illuminate how the lipid is initially attached to the protein [Park
et al
. (
p. 1800
)] and how the later proteolytic modifications are accomplished [Boyartchuk
et al
. (
p. 1796
)]
PTEN
, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer
Authors: Li Jing , Yen Clifford , Liaw Danny , Podsypanina Katrina , Bose Shikha , Wang Steven I. , Puc Janusz , Miliaresis Christa , Rodgers Linda , McCombie Richard , Bigner Sandra H. , Giovanella Beppino C. , Ittmann Michael , Tycko Ben , Hibshoosh Hanina , Wigler Michael H. , Parsons Ramon
Published: July 2002

Mapping of homozygous deletions on human chromosome 10q23 has led to the isolation of a candidate tumor suppressor gene,
PTEN
, that appears to be mutated at considerable frequency in human cancers. In preliminary screens, mutations of
PTEN
were detected in 31% (13/42) of glioblastoma cell lines and xenografts, 100% (4/4) of prostate cancer cell lines, 6% (4/65) of breast cancer cell lines and xenografts, and 17% (3/18) of primary glioblastomas. The predicted
PTEN
product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions. These homologies suggest that
PTEN
may suppress tumor cell growth by antagonizing protein tyrosine kinases and may regulate tumor cell invasion and metastasis through interactions at focal adhesions.
Coordination of
Drosophila
Metamorphosis by Two Ecdysone-Induced Nuclear Receptors
Authors: White Kevin P. , Hurban Patrick , Watanabe Toshiki , Hogness David S.
Published: July 2002

The functions of the ecdysone-induced DHR3 and E75B orphan nuclear receptors in the early stages of Drosophila metamorphosis were investigated. DHR3 represses the ecdysone induction of early genes turned on by the pulse of ecdysone that triggers metamorphosis. It also induces βFTZF1, an orphan nuclear receptor that is essential for the appropriate response to the subsequent prepupal pulse of ecdysone. The E75B receptor, which lacks a complete DNA binding domain, inhibits this inductive function by forming a complex with DHR3 on the
β
FTZF1 promoter, thereby providing a timing mechanism for βFTZF1 induction that is dependent on the disappearance of E75B.
Atomistic Processes in the Early Stages of Thin-Film Growth
Authors: Zhang Zhenyu , Lagally Max G.
Published: July 2002

Growth of thin films from atoms deposited from the gas phase is intrinsically a nonequilibrium phenomenon governed by a competition between kinetics and thermodynamics. Precise control of the growth and thus of the properties of deposited films becomes possible only after an understanding of this competition is achieved. Here, the atomic nature of the most important kinetic mechanisms of film growth is explored. These mechanisms include adatom diffusion on terraces, along steps, and around island corners; nucleation and dynamics of the stable nucleus; atom attachment to and detachment from terraces and islands; and interlayer mass transport. Ways to manipulate the growth kinetics in order to select a desired growth mode are briefly addressed.
Nanoporous Molecular Sandwiches: Pillared Two-Dimensional Hydrogen-Bonded Networks with Adjustable Porosity
Authors: Russell Victoria A. , Evans Cara C. , Li Wenjie , Ward Michael D.
Published: July 2002

Crystal engineering of molecular materials is commonly frustrated by the absence of reliable structural paradigms that are needed for systematic design of crystal lattices with predictable structure and desirable function. This problem can be attributed, at least partially, to the absence of robust supramolecular motifs that serve as synthons for the assembly of crystal lattices. A novel class of molecular crystals based on two-dimensional hydrogen (H)-bonded networks comprising guanidinium ions and the sulfonate groups of alkane- or arenedisulfonate ions is described. The disulfonate ions act as pillars that connect opposing H-bonded sheets and form nanoporous galleries with one-dimensional channels. The flexibility of the H-bonded network allows the galleries to adapt to changes in the steric requirements of guest molecules that occupy the channels. This robustness reduces crystal engineering to the last remaining dimension, enabling rational adjustment of the gallery heights by choice of the disulfonate pillar.
The Initial Domestication of
Cucurbita pepo
in the Americas 10,000 Years Ago
Authors: Smith Bruce D.
Published: July 2002

Squash seeds, peduncles, and fruit rind fragments from Archaic period stratigraphic zones of Guilá Naquitz cave in Oaxaca, Mexico, are assigned to
Cucurbita pepo
on the basis of diagnostic morphological characters and identified as representing a domesticated plant on the basis of increased seed length and peduncle diameter, as well as changes in fruit shape and color, in comparison to wild
Cucurbita
gourds. Nine accelerator mass spectrometer radiocarbon dates on these specimens document the cultivation of
C. pepo
by the inhabitants of Guilá Naquitz cave between 10,000 to 8000 calendar years ago (9000 to 7000 carbon-14 years before the present), which predates maize, beans, and other directly dated domesticates in the Americas by more than 4000 years.
Reversible Unfolding of Individual Titin Immunoglobulin Domains by AFM
Authors: Rief Matthias , Gautel Mathias , Oesterhelt Filipp , Fernandez Julio M. , Gaub Hermann E.
Published: July 2002

Single-molecule atomic force microscopy (AFM) was used to investigate the mechanical properties of titin, the giant sarcomeric protein of striated muscle. Individual titin molecules were repeatedly stretched, and the applied force was recorded as a function of the elongation. At large extensions, the restoring force exhibited a sawtoothlike pattern, with a periodicity that varied between 25 and 28 nanometers. Measurements of recombinant titin immunoglobulin segments of two different lengths exhibited the same pattern and allowed attribution of the discontinuities to the unfolding of individual immunoglobulin domains. The forces required to unfold individual domains ranged from 150 to 300 piconewtons and depended on the pulling speed. Upon relaxation, refolding of immunoglobulin domains was observed.
Engineering Chemical Reactivity on Cell Surfaces Through Oligosaccharide Biosynthesis
Authors: Mahal Lara K. , Yarema Kevin J. , Bertozzi Carolyn R.
Published: July 2002

Cell surface oligosaccharides can be engineered to display unusual functional groups for the selective chemical remodeling of cell surfaces. An unnatural derivative of
N
-acetylmannosamine, which has a ketone group, was converted to the corresponding sialic acid and incorporated into cell surface oligosaccharides metabolically, resulting in the cell surface display of ketone groups. The ketone group on the cell surface can then be covalently ligated under physiological conditions with molecules carrying a complementary reactive functional group such as the hydrazide. Cell surface reactions of this kind should prove useful in the introduction of new recognition epitopes, such as peptides, oligosaccharides, or small organic molecules, onto cell surfaces and in the subsequent modulation of cell-cell or cell–small molecule binding events. The versatility of this technology was demonstrated by an example of selective drug delivery. Cells were decorated with biotin through selective conjugation to ketone groups, and selectively killed in the presence of a ricin A chain–avidin conjugate.
Trichodesmium
, a Globally Significant Marine Cyanobacterium
Authors: Capone Douglas G. , Zehr Jonathan P. , Paerl Hans W. , Bergman Birgitta , Carpenter Edward J.
Published: July 2002

Planktonic marine cyanobacteria of the genus
Trichodesmium
occur throughout the oligotrophic tropical and subtropical oceans. Their unusual adaptations, from the molecular to the macroscopic level, contribute to their ecological success and biogeochemical importance.
Trichodesmium
fixes nitrogen gas (N
2
) under fully aerobic conditions while photosynthetically evolving oxygen. Its temporal pattern of N
2
fixation results from an endogenous daily cycle that confines N
2
fixation to daylight hours.
Trichodesmium
colonies provide a unique pelagic habitat that supports a complex assemblage of consortial organisms. These colonies often represent a large fraction of the plant biomass in tropical, oligotrophic waters and contribute substantially to primary production. N
2
fixation by
Trichodesmium
is likely a major input to the marine and global nitrogen cycle.
Shared Motor Error for Multiple Eye Movements
Authors: Krauzlis R. J. , Basso M. A. , Wurtz R. H.
Published: July 2002

Most natural actions are accomplished with a seamless combination of individual movements. Such coordination poses a problem: How does the motor system orchestrate multiple movements to produce a single goal-directed action? The results from current experiments suggest one possible solution. Oculomotor neurons in the superior colliculus of a primate responded to mismatches between eye and target positions, even when the animal made two different types of eye movements. This neuronal activity therefore does not appear to convey a command for a specific type of eye movement but instead encodes an error signal that could be used by multiple movements. The use of shared inputs is one possible strategy for ensuring that different movements share a common goal.
HSV-TK Gene Transfer into Donor Lymphocytes for Control of Allogeneic Graft-Versus-Leukemia
Authors: Bonini Chiara , Ferrari Giuliana , Verzeletti Simona , Servida Paolo , Zappone Elisabetta , Ruggieri Luciano , Ponzoni Maurilio , Rossini Silvano , Mavilio Fulvio , Traversari Catia , Bordignon Claudio
Published: July 2002

In allogeneic bone marrow transplantation (allo-BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia (GvL) and immune reconstitution. However, their use is limited by the risk of severe graft-versus-host disease (GvHD). Eight patients who relapsed or developed Epstein-Barr virus–induced lymphoma after T cell–depleted BMT were then treated with donor lymphocytes transduced with the herpes simplex virus thymidine kinase (HSV-TK) suicide gene. The transduced lymphocytes survived for up to 12 months, resulting in antitumor activity in five patients. Three patients developed GvHD, which could be effectively controlled by ganciclovir-induced elimination of the transduced cells. These data show that genetic manipulation of donor lymphocytes may increase the efficacy and safety of allo-BMT and expand its application to a larger number of patients.
Giant Planet Formation by Gravitational Instability
Authors: Boss Alan P.
Published: July 2002

The recent discoveries of extrasolar giant planets, coupled with refined models of the compositions of Jupiter and Saturn, prompt a reexamination of theories of giant planet formation. An alternative to the favored core accretion hypothesis is examined here; gravitational instability in the outer solar nebula leading to giant planet formation. Three-dimensional hydrodynamic calculations of protoplanetary disks show that giant gaseous protoplanets can form with locally isothermal or adiabatic disk thermodynamics. Gravitational instability appears to be capable of forming giant planets with modest cores of ice and rock faster than the core accretion mechanism can.
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Authors: Polymeropoulos Mihael H. , Lavedan Christian , Leroy Elisabeth , Ide Susan E. , Dehejia Anindya , Dutra Amalia , Pike Brian , Root Holly , Rubenstein Jeffrey , Boyer Rebecca , Stenroos Edward S. , Chandrasekharappa Settara , Athanassiadou Aglaia , Papapetropoulos Theodore , Johnson William G. , Lazzarini Alice M. , Duvoisin Roger C. , Di Iorio Giuseppe , Golbe Lawrence I. , Nussbaum Robert L.
Published: July 2002

Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.
Activation of Corticotropin-Releasing Factor in the Limbic System During Cannabinoid Withdrawal
Authors: Rodrı́guez de Fonseca Fernando , Carrera M. Rocı́o A. , Navarro Miguel , Koob George F. , Weiss Friedbert
Published: July 2002

Corticotropin-releasing factor (CRF) has been implicated in the mediation of the stress-like and negative affective consequences of withdrawal from drugs of abuse, such as alcohol, cocaine, and opiates. This study sought to determine whether brain CRF systems also have a role in cannabinoid dependence. Rats were treated daily for 2 weeks with the potent synthetic cannabinoid HU-210. Withdrawal, induced by the cannabinoid antagonist SR 141716A, was accompanied by a marked elevation in extracellular CRF concentration and a distinct pattern of Fos activation in the central nucleus of the amygdala. Maximal increases in CRF corresponded to the time when behavioral signs resulting from cannabinoid withdrawal were at a maximum. These data suggest that long-term cannabinoid administration alters CRF function in the limbic system of the brain, in a manner similar to that observed with other drugs of abuse, and also induces neuroadaptive processes that may result in future vulnerability to drug dependence.
Niemann-Pick C1 Disease Gene: Homology to Mediators of Cholesterol Homeostasis
Authors: Carstea Eugene D. , Morris Jill A. , Coleman Katherine G. , Loftus Stacie K. , Zhang Dana , Cummings Christiano , Gu Jessie , Rosenfeld Melissa A. , Pavan William J. , Krizman David B. , Nagle James , Polymeropoulos Mihail H. , Sturley Stephen L. , Ioannou Yiannis A. , Higgins Maureen E. , Comly Marcella , Cooney Adele , Brown Anthony , Kaneski Christine R. , Blanchette-Mackie E. Joan , Dwyer Nancy K. , Neufeld Edward B. , Chang Ta-Yuan , Liscum Laura , Strauss Jerome F. , Ohno Kousaku , Zeigler Marsha , Carmi Rivka , Sokol Jacob , Markie David , O'Neill Raymond R. , van Diggelen O. P. , Elleder Milan , Patterson Marc C. , Brady Roscoe O. , Vanier Marie T. , Pentchev Peter G. , Tagle Danilo A.
Published: July 2002

Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)–derived cholesterol. By positional cloning methods, a gene (
NPC1)
with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection of NP-C fibroblasts with wild-type
NPC1
cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking. The 1278–amino acid NPC1 protein has sequence similarity to the morphogen receptor PATCHED and the putative sterol-sensing regions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.
Surface Energies and Thermodynamic Phase Stability in Nanocrystalline Aluminas
Authors: McHale J. M. , Auroux A. , Perrotta A. J. , Navrotsky A.
Published: July 2002

Corundum, α-Al
2
O
3
, is the thermodynamically stable phase of coarsely crystalline aluminum oxide, but syntheses of nanocrystalline Al
2
O
3
usually result in γ-Al
2
O
3
. Adsorption microcalorimetry, thermogravimetric analyses, and Brunauer-Emmett-Teller adsorption experiments, coupled with recently reported high-temperature solution calorimetry data, prove that γ-Al
2
O
3
has a lower surface energy than α-Al
2
O
3
and becomes energetically stable at surface areas greater than 125 square meters per gram and thermodynamically stable at even smaller surface areas (for example, 75 square meters per gram at 800 kelvin). The results are in agreement with recent molecular dynamics simulations and provide conclusive experimental evidence that differences in surface energy can favor the formation of a particular polymorph.
Identification of the Tuberous Sclerosis Gene
TSC1
on Chromosome 9q34
Authors: Slegtenhorst Marjon van , Hoogt Ronald de , Hermans Caroline , Nellist Mark , Janssen Bart , Verhoef Senno , Lindhout Dick , Ouweland Ans van den , Halley Dicky , Young Janet , Burley Mariwyn , Jeremiah Steve , Woodward Karen , Nahmias Joseph , Fox Margaret , Ekong Rosemary , Osborne John , Wolfe Jonathan , Povey Sue , Snell Russell G. , Cheadle Jeremy P. , Jones Alistair C. , Tachataki Maria , Ravine David , Sampson Julian R. , Reeve Mary Pat , Richardson Paul , Wilmer Friederike , Munro Cheryl , Hawkins Trevor L. , Sepp Tiina , Ali Johari B. M. , Ward Susannah , Green Andrew J. , Yates John R. W. , Kwiatkowska Jolanta , Henske Elizabeth P. , Short M. Priscilla , Haines Jonathan H. , Jozwiak Sergiusz , Kwiatkowski David J.
Published: July 2002

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 (
TSC1
) and 16p13 (
TSC2
). The
TSC1
gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase
TSC1
transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified in
TSC1
, 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.
AIB1, a Steroid Receptor Coactivator Amplified in Breast and Ovarian Cancer
Authors: Anzick Sarah L. , Kononen Juha , Walker Robert L. , Azorsa David O. , Tanner Minna M. , Guan Xin-Yuan , Sauter Guido , Kallioniemi Olli-P. , Trent Jeffrey M. , Meltzer Paul S.
Published: July 2002

Members of the recently recognized SRC-1 family of transcriptional coactivators interact with steroid hormone receptors to enhance ligand-dependent transcription. AIB1, a member of the SRC-1 family, was cloned during a search on the long arm of chromosome 20 for genes whose expression and copy number were elevated in human breast cancers. AIB1 amplification and overexpression were observed in four of five estrogen receptor–positive breast and ovarian cancer cell lines. Subsequent evaluation of 105 unselected specimens of primary breast cancer found AIB1 amplification in approximately 10 percent and high expression in 64 percent of the primary tumors analyzed. AIB1 protein interacted with estrogen receptors in a ligand-dependent fashion, and transfection of AIB1 resulted in enhancement of estrogen-dependent transcription. These observations identify AIB1 as a nuclear receptor coactivator whose altered expression may contribute to development of steroid-dependent cancers.
Competing Interactions and Levels of Ordering in Self-Organizing Polymeric Materials
Authors: Muthukumar M. , Ober C. K. , Thomas E. L.
Published: July 2002

The sophisticated use of self-organizing materials, which include liquid crystals, block copolymers, hydrogen- and π-bonded complexes, and many natural polymers, may hold the key to developing new structures and devices in many advanced technology industries. Synthetic materials are usually designed with only one structure-forming process in mind. However, combination of both complementary and antagonistic interactions in macromolecular systems can create order in materials over many length scales. Here polymer materials that make use of competing molecular interactions are summarized, and the prospects for the further development of such materials through both synthetic and processing pathways are highlighted.
A Critical Role for Tapasin in the Assembly and Function of Multimeric MHC Class I-TAP Complexes
Authors: Ortmann Bodo , Copeman James , Lehner Paul J. , Sadasivan Bhanu , Herberg Jethro A. , Grandea Andeas G. , Riddell Stanley R. , Tampé Robert , Spies Thomas , Trowsdale John , Cresswell Peter
Published: July 2002

Newly assembled major histocompatibility complex (MHC) class I molecules, together with the endoplasmic reticulum chaperone calreticulin, interact with the transporter associated with antigen processing (TAP) through a molecule called tapasin. The molecular cloning of tapasin revealed it to be a transmembrane glycoprotein encoded by an MHC-linked gene. It is a member of the immunoglobulin superfamily with a probable cytoplasmic endoplasmic reticulum retention signal. Up to four MHC class I–tapasin complexes were found to bind to each TAP molecule. Expression of tapasin in a negative mutant human cell line (220) restored class I–TAP association and normal class I cell surface expression. Tapasin expression also corrected the defective recognition of virus-infected 220 cells by class I–restricted cytotoxic T cells, establishing a critical functional role for tapasin in MHC class I–restricted antigen processing.
Cdc25 Mitotic Inducer Targeted by Chk1 DNA Damage Checkpoint Kinase
Authors: Furnari Beth , Rhind Nicholas , Russell Paul
Published: July 2002

Arrest of the cell cycle at the G
2
checkpoint, induced by DNA damage, requires inhibitory phosphorylation of the kinase Cdc2 in both fission yeast and human cells. The kinase Wee1 and the phosphatase Cdc25, which regulate Cdc2 phosphorylation, were evaluated as targets of Chk1, a kinase essential for the checkpoint. Fission yeast
cdc2-3w Δcdc25
cells, which express activated Cdc2 and lack Cdc25, were responsive to Wee1 but insensitive to Chk1 and irradiation. Expression of large amounts of Chk1 produced the same phenotype as did loss of the
cdc25
gene in
cdc2-3w
cells. Cdc25 associated with Chk1 in vivo and was phosphorylated when copurified in Chk1 complexes. These findings identify Cdc25, but not Wee1, as a target of the DNA damage checkpoint.
Antagonism of Central Melanocortin Receptors in Vitro and in Vivo by Agouti-Related Protein
Authors: Ollmann Michael M. , Wilson Brent D. , Yang Ying-Kui , Kerns Julie A. , Chen Yanru , Gantz Ira , Barsh Gregory S.
Published: July 2002

Expression of Agouti protein is normally limited to the skin where it affects pigmentation, but ubiquitous expression causes obesity. An expressed sequence tag was identified that encodes Agouti-related protein, whose RNA is normally expressed in the hypothalamus and whose levels were increased eightfold in
ob/ob
mice. Recombinant Agouti-related protein was a potent, selective antagonist of Mc3r and Mc4r, melanocortin receptor subtypes implicated in weight regulation. Ubiquitous expression of human
AGRP
complementary DNA in transgenic mice caused obesity without altering pigmentation. Thus, Agouti-related protein is a neuropeptide implicated in the normal control of body weight downstream of leptin signaling.
Caspase-3-Generated Fragment of Gelsolin: Effector of Morphological Change in Apoptosis
Authors: Kothakota Srinivas , Azuma Toshifumi , Reinhard Christoph , Klippel Anke , Tang Jay , Chu Keting , McGarry Thomas J. , Kirschner Marc W. , Koths Kirston , Kwiatkowski David J. , Williams Lewis T.
Published: July 2002

The caspase-3 (CPP32, apopain, YAMA) family of cysteinyl proteases has been implicated as key mediators of apoptosis in mammalian cells. Gelsolin was identified as a substrate for caspase-3 by screening the translation products of small complementary DNA pools for sensitivity to cleavage by caspase-3. Gelsolin was cleaved in vivo in a caspase-dependent manner in cells stimulated by Fas. Caspase-cleaved gelsolin severed actin filaments in vitro in a Ca
2+
-independent manner. Expression of the gelsolin cleavage product in multiple cell types caused the cells to round up, detach from the plate, and undergo nuclear fragmentation. Neutrophils isolated from mice lacking gelsolin had delayed onset of both blebbing and DNA fragmentation, following apoptosis induction, compared with wild-type neutrophils. Thus, cleaved gelsolin may be one physiological effector of morphologic change during apoptosis.
Measurement of the Force-Velocity Relation for Growing Microtubules
Authors: Dogterom Marileen , Yurke Bernard
Published: July 2002

Forces generated by protein polymerization are important for various forms of cellular motility. Assembling microtubules, for instance, are believed to exert pushing forces on chromosomes during mitosis. The force that a single microtubule can generate was measured by attaching microtubules to a substrate at one end and causing them to push against a microfabricated rigid barrier at the other end. The subsequent buckling of the microtubules was analyzed to determine both the force on each microtubule end and the growth velocity. The growth velocity decreased from 1.2 micrometers per minute at zero force to 0.2 micrometer per minute at forces of 3 to 4 piconewtons. The force-velocity relation fits well to a decaying exponential, in agreement with theoretical models, but the rate of decay is faster than predicted.
Contribution of Stream Channel Erosion to Sediment Yield from an Urbanizing Watershed
Authors: Trimble Stanley W.
Published: July 2002

Stream channel erosion has long been suspected as the major contributor to long-term sediment yield from urbanizing watersheds. For San Diego Creek in southern California, measurements from 1983 to 1993 showed that stream channel erosion furnished 10
5
megagrams per year of sediment, or about two-thirds of the total sediment yield. Thus, because channel erosion can be a major source of sediment yield from urbanizing areas, channel stabilization should be a priority in managing sediment yield.
Interior Structure and Seasonal Mass Redistribution of Mars from Radio Tracking of Mars Pathfinder
Authors: Folkner W. M. , Yoder C. F. , Yuan D. N. , Standish E. M. , Preston R. A.
Published: July 2002

Doppler and range measurements to the Mars Pathfinder lander made using its radio communications system have been combined with similar measurements from the Viking landers to estimate improved values of the precession of Mars' pole of rotation and the variation in Mars' rotation rate. The observed precession of –7576 ± 35 milliarc seconds of angle per year implies a dense core and constrains possible models of interior composition. The estimated annual variation in rotation is in good agreement with a model of seasonal mass exchange of carbon dioxide between the atmosphere and ice caps.
Characterization of the Martian Surface Deposits by the Mars Pathfinder Rover, Sojourner
Authors: Team Rover
Published: July 2002

Sojourner, the Mars Pathfinder rover, discovered pebbles on the surface and in rocks that may be sedimentary—not volcanic—in origin. Surface pebbles may have been rounded by Ares flood waters or liberated by weathering of sedimentary rocks called conglomerates. Conglomerates imply that water existed elsewhere and earlier than the Ares flood. Most soil-like deposits are similar to moderately dense soils on Earth. Small amounts of dust are currently settling from the atmosphere.
Promotion of the Cycling of Diet-Enhancing Nutrients by African Grazers
Authors: McNaughton S. J. , Banyikwa F. F. , McNaughton M. M.
Published: July 2002

Experiments in Serengeti National Park, Tanzania, provide direct evidence that large, free-ranging mammalian grazers accelerate nutrient cycling in a natural ecosystem in a way that enhances their own carrying capacity. Both nitrogen and sodium were at considerably higher plant-available levels in soils of highly grazed sites than in soils of nearby areas where animal density is sparse. Fencing that uncoupled grazers and soils indicated that the animals promote nitrogen availability on soils of inherently similar fertility and select sites of higher sodium availability as well as enhancing that availability.
Hydrogen Radicals, Nitrogen Radicals, and the Production of O
3
in the Upper Troposphere
Authors: Wennberg P. O. , Hanisco T. F. , Jaeglé L. , Jacob D. J. , Hintsa E. J. , Lanzendorf E. J. , Anderson J. G. , Gao R.-S. , Keim E. R. , Donnelly S. G. , Negro L. A. Del , Fahey D. W. , McKeen S. A. , Salawitch R. J. , Webster C. R. , May R. D. , Herman R. L. , Proffitt M. H. , Margitan J. J. , Atlas E. L. , Schauffler S. M. , Flocke F. , McElroy C. T. , Bui T. P.
Published: July 2002

The concentrations of the hydrogen radicals OH and HO
2
in the middle and upper troposphere were measured simultaneously with those of NO, O
3
, CO, H
2
O, CH
4
, non-methane hydrocarbons, and with the ultraviolet and visible radiation field. The data allow a direct examination of the processes that produce O
3
in this region of the atmosphere. Comparison of the measured concentrations of OH and HO
2
with calculations based on their production from water vapor, ozone, and methane demonstrate that these sources are insufficient to explain the observed radical concentrations in the upper troposphere. The photolysis of carbonyl and peroxide compounds transported to this region from the lower troposphere may provide the source of HO

x

required to sustain the measured abundances of these radical species. The mechanism by which NO affects the production of O
3
is also illustrated by the measurements. In the upper tropospheric air masses sampled, the production rate for ozone (determined from the measured concentrations of HO
2
and NO) is calculated to be about 1 part per billion by volume each day. This production rate is faster than previously thought and implies that anthropogenic activities that add NO to the upper troposphere, such as biomass burning and aviation, will lead to production of more O
3
than expected.
Sensitivity of CaM Kinase II to the Frequency of Ca
2+
Oscillations
Authors: De Koninck Paul , Schulman Howard
Published: July 2002

The transduction of many cellular stimuli results in oscillations in the intracellular concentration of calcium ions (Ca
2+
). Although information is thought to be encoded in the frequency of such oscillations, no frequency decoder has been identified. Rapid superfusion of immobilized Ca
2+
- and calmodulin-dependent protein kinase II (CaM kinase II) in vitro showed that the enzyme can decode the frequency of Ca
2+
spikes into distinct amounts of kinase activity. The frequency response of CaM kinase II was modulated by several factors, including the amplitude and duration of individual spikes as well as the subunit composition and previous state of activation of the kinase. These features should provide specificity in the activation of this multifunctional enzyme by distinct cellular stimuli and may underlie its pivotal role in activity-dependent forms of synaptic plasticity.
Functional Expression of a Mammalian Odorant Receptor
Authors: Zhao Haiqing , Ivic Lidija , Otaki Joji M. , Hashimoto Mitsuhiro , Mikoshiba Katsuhiro , Firestein Stuart
Published: July 2002

Candidate mammalian odorant receptors were first cloned some 6 years ago. The physiological function of these receptors in initiating transduction in olfactory receptor neurons remains to be established. Here, a recombinant adenovirus was used to drive expression of a particular receptor gene in an increased number of sensory neurons in the rat olfactory epithelium. Electrophysiological recording showed that increased expression of a single gene led to greater sensitivity to a small subset of odorants.
Absence of a Spin Gap in the Superconducting Ladder Compound Sr
2
Ca
12
Cu
24
O
41
Authors: Mayaffre H. , Auban-Senzier P. , Nardone M. , Jérome D. , Poilblanc D. , Bourbonnais C. , Ammerahl U. , Dhalenne G. , Revcolevschi A.
Published: July 2002

Transport and copper-63 nuclear magnetic resonance measurements of the Knight shift and relaxation time
T
1
performed on the two-leg spin ladders of Sr
2
Ca
12
Cu
24
O
41
single crystals as a function of pressure show a collapse of the gap in ladder spin excitations when superconductivity is stabilized at 31 kilobars. This result suggests that the superconducting phase in these materials may be connected to this transition and the collapse of the spin gap, and support the prediction made with exact diagonalization techniques in two-leg isotropic
t
−
J
ladder models of a transition between a low-doping spin gap phase and a gapless regime.
Alopecia Universalis Associated with a Mutation in the Human
hairless
Gene
Authors: Ahmad Wasim , Faiyaz ul Haque Muhammad , Brancolini Valeria , Tsou Hui C. , ul Haque Sayed , Lam HaMut , Aita Vincent M. , Owen Jason , deBlaquiere Michelle , Frank Jorge , Cserhalmi-Friedman Peter B. , Leask Andrew , McGrath John A. , Peacocke Monica , Ahmad Mahmud , Ott Jurg , Christiano Angela M.
Published: July 2002

There are several forms of hereditary human hair loss, known collectively as alopecias, the molecular bases of which are entirely unknown. A kindred with a rare, recessively inherited type of alopecia universalis was used to search for a locus by homozygosity mapping, and linkage was established in a 6-centimorgan interval on chromosome 8p12 (the logarithm of the odds favoring linkage score was 6.19). The human homolog of a murine gene,
hairless
, was localized in this interval by radiation hybrid mapping, and a missense mutation was found in affected individuals. Human
hairless
encodes a putative single zinc finger transcription factor protein with restricted expression in the brain and skin.