bluuebunny/crossref_metadata_2025 huggingface dataset:
Proposals That Would Limit Visas Strike Fear at Universities
Authors: Glanz James
Published: October 2006

Next week the Senate will begin debating a bill to reform immigration law that could transform the cosmopolitan world of American research universities. Science and engineering programs depend heavily on foreign graduate students and postdocs—an arrangement that rests on an intricate array of visa categories. Several measures, which were defeated or withdrawn in the Senate Judiciary Committee but are likely to be resurrected in the floor debate, would eliminate certain visa categories and place stricter requirements and shorter time limits on others. (See the 22 March 1996 Editorial.)
Premature Aging Gene Discovered
Authors: Pennisi Elizabeth
Published: October 2006

Patients who have the rare hereditary condition known as Werner's syndrome begin aging dramatically while still in their twenties. Their hair goes gray, their skin loses its suppleness, and worse, they also develop cancer, heart disease, and many other diseases that usually don't strike until later in life. On page
258
of this issue, researchers now report that they have identified the gene at fault in Werner's syndrome, which apparently encodes a DNA-unwinding enzyme called a helicase. This suggests that the premature aging, cancer, and other problems associated with the syndrome may be due to failure of normal DNA repair, replication, or one of the other DNA activities that require a helicase.
New Role for HIV: A Vehicle for Moving Genes Into Cells
Authors: Cohen Jon
Published: October 2006

A big problem that has dogged the nascent field of gene therapy is the lack of an effective means for shuttling genes into target cells. Most current transfer vehicles, or vectors, only work with dividing cells, for example, making it hard to get therapeutic genes into neurons and stem cells. Now a team from the Salk Institute reports on page
263
using a highly modified form of the AIDS virus, HIV, to transfect nondividing cells. The work is a long way from clinical application, but it may point the way to better vectors.
Is There a Role for Benefit-Cost Analysis in Environmental, Health, and Safety Regulation?
Authors: Arrow Kenneth J. , Cropper Maureen L. , Eads George C. , Hahn Robert W. , Lave Lester B. , Noll Roger G. , Portney Paul R. , Russell Milton , Schmalensee Richard , Smith V. Kerry , Stavins Robert N.
Published: October 2006

Benefit-cost analysis can play an important role in legislative and regulatory policy debates on protecting and improving health, safety, and the natural environment. Although formal benefit-cost analysis should not be viewed as either necessary or sufficient for designing sensible public policy, it can provide an exceptionally useful framework for consistently organizing disparate information, and in this way, it can greatly improve the process and, hence, the outcome of policy analysis. If properly done, benefit-cost analysis can be of great help to agencies participating in the development of environmental, health, and safety regulations, and it can likewise be useful in evaluating agency decision-making and in shaping statutes.
Protein Sorting by Transport Vesicles
Authors: Rothman James E. , Wieland Felix T.
Published: October 2006

Eukaryotic life depends on the spatial and temporal organization of cellular membrane systems. Recent advances in understanding the machinery of vesicle transport have established general principles that underlie a broad variety of physiological processes, including cell surface growth, the biogenesis of distinct intracellular organelles, endocytosis, and the controlled release of hormones and neurotransmitters.
Global Observations of Oceanic Rossby Waves
Authors: Chelton Dudley B. , Schlax Michael G.
Published: October 2006

Rossby waves play a critical role in the transient adjustment of ocean circulation to changes in large-scale atmospheric forcing. The TOPEX/POSEIDON satellite altimeter has detected Rossby waves throughout much of the world ocean from sea level signals with ≲10-centimeter amplitude and ≳500-kilometer wavelength. Outside of the tropics, Rossby waves are abruptly amplified by major topographic features. Analysis of 3 years of data reveals discrepancies between observed and theoretical Rossby wave phase speeds that indicate that the standard theory for free, linear Rossby waves is an incomplete description of the observed waves.
History of Ancient Copper Smelting Pollution During Roman and Medieval Times Recorded in Greenland Ice
Authors: Hong Sungmin , Candelone Jean-Pierre , Patterson Clair C. , Boutron Claude F.
Published: October 2006

Determination of copper concentrations in Greenland ice dated from seven millennia ago to the present showed values exceeding natural levels, beginning about 2500 years ago. This early large-scale pollution of the atmosphere of the Northern Hemisphere is attributed to emissions from the crude, highly polluting smelting technologies used for copper production during Roman and medieval times, especially in Europe and China. This study opens the way to a quantitative assessment of the history of early metal production, which was instrumental in the development of human cultures during ancient eras.
Positional Cloning of the Werner's Syndrome Gene
Authors: Yu Chang-En , Oshima Junko , Fu Ying-Hui , Wijsman Ellen M. , Hisama Fuki , Alisch Reid , Matthews Shellie , Nakura Jun , Miki Tetsuro , Ouais Samir , Martin George M. , Mulligan John , Schellenberg Gerard D.
Published: October 2006

Werner's syndrome (WS) is an inherited disease with clinical symptoms resembling premature aging. Early susceptibility to a number of major age-related diseases is a key feature of this disorder. The gene responsible for WS (known as
WRN
) was identified by positional cloning. The predicted protein is 1432 amino acids in length and shows significant similarity to DNA helicases. Four mutations in WS patients were identified. Two of the mutations are splice-junction mutations, with the predicted result being the exclusion of exons from the final messenger RNA. One of these mutations, which results in a frameshift and a predicted truncated protein, was found in the homozygous state in 60 percent of Japanese WS patients examined. The other two mutations are nonsense mutations. The identification of a mutated putative helicase as the gene product of the WS gene suggests that defective DNA metabolism is involved in the complex process of aging in WS patients.
Short-Term Plasticity of a Thalamocortical Pathway Dynamically Modulated by Behavioral State
Authors: Castro-Alamancos Manuel A. , Connors Barry W.
Published: October 2006

The neocortex receives information about the environment and the rest of the brain through pathways from the thalamus. These pathways have frequency-dependent properties that can strongly influence their effect on the neocortex. In 1943 Morison and Dempsey described “augmenting responses,” a form of short-term plasticity in some thalamocortical pathways that is triggered by 8- to 15-hertz activation. Results from anesthetized rats showed that the augmenting response is initiated by pyramidal cells in layer V. The augmenting response was also observed in awake, unrestrained animals and was found to be dynamically modulated by their behavioral state.
Rho1p, a Yeast Protein at the Interface Between Cell Polarization and Morphogenesis
Authors: Drgonová Jana , Drgon Tomás , Tanaka Kazuma , Kollár Roman , Chen Guang-Chao , Ford Richard A. , Chan Clarence S. M. , Takai Yoshimi , Cabib Enrico
Published: October 2006

The enzyme that catalyzes the synthesis of the major structural component of the yeast cell wall, β(1→3)-D-glucan synthase (also known as 1,3-β-glucan synthase), requires a guanosine triphosphate (GTP) binding protein for activity. The GTP binding protein was identified as Rho1p. The
rho1
mutants were defective in GTP stimulation of glucan synthase, and the defect was corrected by addition of purified or recombinant Rho1p. A protein missing in purified preparations from a
rho1
strain was identified as Rho1p. Rho1p also regulates protein kinase C, which controls a mitogen-activated protein kinase cascade. Experiments with a dominant positive
PKC1
gene showed that the two effects of Rho1p are independent of each other. The colocalization of Rho1p with actin patches at the site of bud emergence and the role of Rho1p in cell wall synthesis emphasize the importance of Rho1p in polarized growth and morphogenesis.
Identification of Yeast Rho1p GTPase as a Regulatory Subunit of 1,3-β-Glucan Synthase
Authors: Qadota Hiroshi , Python Christophe P. , Inoue Shunsuke B. , Arisawa Mikio , Anraku Yasuhiro , Zheng Yi , Watanabe Takahide , Levin David E. , Ohya Yoshikazu
Published: October 2006

1,3-β-D-Glucan synthase [also known as β(1→3)glucan synthase] is a multi-enzyme complex that catalyzes the synthesis of 1,3-β-linked glucan, a major structural component of the yeast cell wall. Temperature-sensitive mutants in the essential Rho-type guanosine triphosphatase (GTPase), Rho1p, displayed thermolabile glucan synthase activity, which was restored by the addition of recombinant Rho1p. Glucan synthase from mutants expressing constitutively active Rho1p did not require exogenous guanosine triphosphate for activity. Rho1p copurified with β(1→3)glucan synthase and associated with the Fks1p subunit of this complex in vivo. Both proteins were localized predominantly at sites of cell wall remodeling. Therefore, it appears that Rho1p is a regulatory subunit of β(1→3)glucan synthase.
URI Tries Downsizing by Formula
Authors: Roush Wade
Published: October 2006

Kingston, Rhode Island—Lots of universities are talking about slimming down. The University of Rhode Island (URI) is doing it. In these times of tight budgets, the school is cutting departments based on a novel self-audit that accounts for each hour of faculty time and all associated costs and revenues. Only the best and most cost-effective will survive, says the school. Already admissions have been stopped in 47 degree-granting programs, including 16 in science and engineering. The effort could prove a model for the rest of the academic world, which is watching with keen interest
How Much Is a Program Worth?
Authors: Roush Wade
Published: October 2006

Kingston, Rhode Island—With coffers draining faster than they could be filled, administrators at the University of Rhode Island (URI) needed to find all their financial leaks and caulk them. The caulking gun: URI's Program Contribution Analysis. Although complex in details, the analysis had the single goal of determining whether faculty time was being spent efficiently. Here's how it worked for one professor in the Department of Human Development, Counseling, and Family Studies.
A 24-Hour Circadian Clock Is Found in the Mammalian Retina
Authors: Morrell Virginia
Published: October 2006

By developing a clever technique for studying a hamster's retina in culture, investigators have found that it hosts a biological clock, secreting varying amounts of the hormone melatonin over a 24-hour cycle. The finding, reported on page
419
, brings to two the number of biological clocks known in mammals—the other is in a brain structure called the suprachiasmatic nucleus—and brings mammals into line with other vertebrates, which have multiple clocks. It will also provide investigators trying to tease apart the workings of these clocks with a valuable experimental model.
Molecularly Adsorbed Oxygen Species on Si(111)-(7×7): STM-Induced Dissociative Attachment Studies
Authors: Martel R. , Avouris Ph. , Lyo I.-W.
Published: October 2006

Scanning tunneling microscope (STM)-induced selective bond breaking in individual molecules and conventional STM imaging are combined to determine the nature of chemisorbed O
2
species formed during the initial stages of silicon (111)-(7×7) oxidation. A selective atomic-scale modification mechanism that involves dissociative electron attachment of tip-emitted electrons to empty adsorbate orbitals is introduced. Two molecular species were found: one involves O
2
bonded to an already oxidized silicon adatom, and the other involves an O
2
molecule that is bonded to a second-layer rest atom and interacting with two silicon adatoms.
Independent Modes of Natural Killing Distinguished in Mice Lacking

Lag3
Authors: Miyazaki Toru , Dierich Andrée , Benoist Christophe , Mathis Diane
Published: October 2006

The LAG3 protein has several features in common with CD4, suggesting that it may be important in controlling T cell reactivity. However, mice with a
Lag3
null mutation have now been shown to exhibit a defect in the natural killer cell, rather than the T cell, compartment. Killing of certain tumor targets by natural killer cells from these mice was inhibited or even abolished, whereas lysis of cells displaying major histocompatibility complex class I disparities remained intact. It appears that LAG3 is a receptor or coreceptor that defines different modes of natural killing.
A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p
Authors: Taunton Jack , Hassig Christian A. , Schreiber Stuart L.
Published: October 2006

Trapoxin is a microbially derived cyclotetrapeptide that inhibits histone deacetylation in vivo and causes mammalian cells to arrest in the cell cycle. A trapoxin affinity matrix was used to isolate two nuclear proteins that copurified with histone deacetylase activity. Both proteins were identified by peptide microsequencing, and a complementary DNA encoding the histone deacetylase catalytic subunit (HD1) was cloned from a human Jurkat T cell library. As the predicted protein is very similar to the yeast transcriptional regulator Rpd3p, these results support a role for histone deacetylase as a key regulator of eukaryotic transcription.
Regulation of an Early Developmental Checkpoint in the B Cell Pathway by Igβ
Authors: Gong Shiaoching , Nussenzweig Michel C.
Published: October 2006

Many of the cell fate decisions in precursor B cells and more mature B cells are controlled by membrane immunoglobulin (Ig) M heavy chain (mμ) and the Igα-Igβ signal transducers. The role of Igβ in regulating early B cell development was examined in mice that lack Igβ (Igβ
−/−
). These mice had a complete block in B cell development at the immature CD43
+
B220
+
stage. Immunoglobulin heavy chain diversity (D
H
) and joining (J
H
) segments rearranged, but variable (V
H
) to DJ
H
recombination and immunoglobulin messenger RNA expression were compromised. These experiments define an unexpected, early requirement for Igβ to produce B cells that can complete VDJ
H
recombination.
CNS Gene Encoding Astrotactin, Which Supports Neuronal Migration Along Glial Fibers
Authors: Zheng Chen , Heintz Nathaniel , Hatten Mary E.
Published: October 2006

Vertebrate central nervous system (CNS) histogenesis depends on glia-guided migration of postmitotic neurons to form neuronal laminae. Previous studies have established that the neuronal protein astrotactin functions in murine cerebellar granule cell migration in vitro. The gene encoding astrotactin predicts a protein with three epidermal growth factor repeats and two fibronectin type III repeats. Astrotactin messenger RNA is expressed in postmitotic neuronal precursors in the cerebellum, hippocampus, cerebrum, and olfactory bulb, where migration establishes laminar structures. Fab fragments of antibodies to a recombinant astrotactin peptide blocked migration of cerebellar granule neurons in vitro along astroglial fibers. Transfection of astrotactin complementary DNA into 3T3 cells indicated that astrotactin acts as a ligand for neuron-glia binding during neuronal migration.
Circadian Rhythms in Cultured Mammalian Retina
Authors: Tosini Gianluca , Menaker Michael
Published: October 2006

Many retinal functions are circadian, but in most instances the location of the clock that drives the rhythm is not known. Cultured neural retinas of the golden hamster (
Mesocricetus auratus
) exhibited circadian rhythms of melatonin synthesis for at least 5 days at 27°C. The rhythms were entrained by light cycles applied in vitro and were free-running in constant darkness. Retinas from hamsters homozygous for the circadian mutation
tau
, which shortens the free-running period of the circadian activity rhythm by 4 hours, showed a shortened free-running period of melatonin synthesis. The mammalian retina contains a genetically programmed circadian oscillator that regulates its synthesis of melatonin.
Rare Sightings Beguile Physicists
Authors: Taubes Gary
Published: October 2006

Over the past few months, particle physics experiments have yielded a crop of events that seem to conflict with standard theory. Only one of these anomalies has been published so far; the others have been disseminated only at conferences or via pervasive rumor. But they are attracting extraordinary attention. Theorists, long starved for surprising new results, are hailing them as possible glimpses of the next great theory of particles and forces—in particular, a theory called supersymmetry, which could provide a unified explanation for all the quantum forces and for the range of particle masses. But some physicists caution that these anomalies might be no more than statistical fluctuations or experimental glitches.
NASA Shuffle Seen as Harming Science
Authors: Lawler Andrew
Published: October 2006

Researchers are up in arms about a reorganization at the National Aeronautics and Space Administration (NASA) that could threaten the research agenda of the international space station. The change transfers control of the $2.1 billion annual space station budget from NASA headquarters in Washington to the Johnson Space Center in Houston, and scientists are worried that it could also force science facilities and experiments to take a back seat to the station's engineering requirements and undermine efforts to improve the credibility of the agency's life sciences research.
ASM Report Sees a Mixed Future
Authors: Jacobson Louis
Published: October 2006

A survey conducted by the American Society for Microbiology (ASM) paints a rosy overall view of employment prospects for microbiology Ph.D.s., with a projected 6% annual increase in jobs for the next 3 years. But most of that growth will be in industry and undergraduate teaching, rather than the more traditional academic and government research positions.
Yeast Genome Sequence Ferments New Research
Authors: Williams Nigel
Published: October 2006

In simultaneous press conferences in Brussels and Washington, researchers unveiled the complete genome of the most complex organism yet sequenced—brewer's yeast. The 12-million-base sequence, the result of a European Union-funded collaboration of more than 100 laboratories, is the first for a member of the eukaryotes—organisms that, unlike bacteria, have nucleated cells, among them all multicelled animals and plants. The similarities of yeast genes to those of more complex organisms, including humans, is already drawing a host of researchers eager to exploit the sequence.
Saturn's Rings: Life at the Edge
Authors: Murray Carl D.
Published: October 2006

Over the past year, astronomers have been able to study Saturn's rings in detail with the Hubble Space Telescope. In his Perspective, Murray discusses three accompanying papers that describe new results, including observation of OH molecules above the rings, high-quality images of the braided F ring, and the finding that two of the satellites that affect the ring dynamics—Prometheus and Atlas—are out of their expected positions.
Observations of Saturn's Ring-Plane Crossings in August and November 1995
Authors: Nicholson Philip D. , Showalter Mark R. , Dones Luke , French Richard G. , Larson Stephen M. , Lissauer Jack J. , McGhee Colleen A. , Seitzer Patrick , Sicardy Bruno , Danielson G. Edward
Published: October 2006

Observations of Saturn's ring system with the Hubble Space Telescope during the 10 August 1995 Earth crossing and the 17 to 21 November 1995 solar crossing indicate that the F ring dominates their apparent edge-on thickness of 1.2 to 1.5 kilometers. The F ring is slightly inclined with respect to the A ring, which may explain the approximately 50-minute difference in apparent crossing times for the east and west ring ansae in August. Prometheus lags its predicted position by about 19 degrees in longitude. The faint G ring is neutral or reddish in color and is confined to a radial range of 2.72 to 2.85 Saturn radii. The broad, distinctly blue E ring flares outward to a maximum thickness of about 15,000 kilometers at 7.5 Saturn radii and appears to have a spatially uniform particle size distribution.
Observations of Saturn's Inner Satellites During the May 1995 Ring-Plane Crossing
Authors: Bosh Amanda S. , Rivkin Andrew S.
Published: October 2006

The 22 May 1995 Saturn ring-plane crossing was observed with the Hubble Space Telescope; the markedly reduced scattered light from the rings at this time allowed study of the small inner satellites of the Saturn system. Prometheus was further from its predicted location than expected based on uncertainties in the 1981 ephemerides propagated forward by 15 years. A body found orbiting near or within Saturn's F ring is either an F-ring shepherd or a transient clump of dust within the F ring; given its approximate brightness, the clump theory is more likely.
Probing Electrical Transport in Nanomaterials: Conductivity of Individual Carbon Nanotubes
Authors: Dai Hongjie , Wong Eric W. , Lieber Charles M.
Published: October 2006

A general approach has been developed to determine the conductivity of individual nanostructures while simultaneously recording their structure. Conventional lithography has been used to contact electrically single ends of nanomaterials, and a force microscope equipped with a conducting probe tip has been used to map simultaneously the structure and resistance of the portion of the material protruding from the macroscopic contact. Studies of individual carbon nanotubes demonstrate that the structurally most perfect nanotubes have resistivities an order of magnitude lower than those found previously and that defects in the nanotube structure cause substantial increases in the resistivity.
Role of Type I Myosins in Receptor-Mediated Endocytosis in Yeast
Authors: Geli M. Isabel , Riezman Howard
Published: October 2006

Type I myosins are thought to drive actin-dependent membrane motility, but the direct demonstration in vivo of their involvement in specific cellular processes has been difficult. Deletion of the genes
MYO3
and
MYO5
, which encode the yeast type I myosins, almost abolished growth. A double-deleted mutant complemented with a
MYO5
temperature-sensitive allele (
myo5-1
) showed a strong defect in the internalization step of receptor-mediated endocytosis, whereas the secretory pathway remained apparently unaffected. Thus, myosin I activity is required for a budding event in endocytosis but not for several other aspects of membrane traffic.
Selective Activation of NF-κB by Nerve Growth Factor Through the Neurotrophin Receptor p75
Authors: Carter Bruce D. , Kaltschmidt Christian , Kaltschmidt Barbara , Offenhäuser Nina , Böhm-Matthaei Renate , Baeuerle Patrick A. , Barde Yves-Alain
Published: October 2006

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) selectively bind to distinct members of the Trk family of tyrosine kinase receptors, but all three bind with similar affinities to the neurotrophin receptor p75 (p75
NTR
). The biological significance of neurotrophin binding to p75
NTR
in cells that also express Trk receptors has been difficult to ascertain. In the absence of TrkA, NGF binding to p75
NTR
activated the transcription factor nuclear factor kappa B (NF-κB) in rat Schwann cells. This activation was not observed in Schwann cells isolated from mice that lacked p75
NTR
. The effect was selective for NGF; NF-κB was not activated by BDNF or NT-3.
Cerebellum Implicated in Sensory Acquisition and Discrimination Rather Than Motor Control
Authors: Gao Jia-Hong , Parsons Lawrence M. , Bower James M. , Xiong Jinhu , Li Jinqi , Fox Peter T.
Published: October 2006

Recent evidence that the cerebellum is involved in perception and cognition challenges the prevailing view that its primary function is fine motor control. A new alternative hypothesis is that the lateral cerebellum is not activated by the control of movement per se, but is strongly engaged during the acquisition and discrimination of sensory information. Magnetic resonance imaging of the lateral cerebellar output (dentate) nucleus during passive and active sensory tasks confirmed this hypothesis. These findings suggest that the lateral cerebellum may be active during motor, perceptual, and cognitive performances specifically because of the requirement to process sensory data.
Transcription-Coupled Repair Deficiency and Mutations in Human Mismatch Repair Genes
Authors: Mellon Isabel , Rajpal Deepak K. , Koi Minoru , Boland C. Richard , Champe Gregory N.
Published: October 2006

Deficiencies in mismatch repair have been linked to a common cancer predisposition syndrome in humans, hereditary nonpolyposis colorectal cancer (HNPCC), and a subset of sporadic cancers. Here, several mismatch repair-deficient tumor cell lines and HNPCC-derived lymphoblastoid cell lines were found to be deficient in an additional DNA repair process termed transcription-coupled repair (TCR). The TCR defect was corrected in a mutant cell line whose mismatch repair deficiency had been corrected by chromosome transfer. Thus, the connection between excision repair and mismatch repair previously described in
Escherichia coli
extends to humans. These results imply that deficiencies in TCR and exposure to carcinogens present in the environment may contribute to the etiology of tumors associated with genetic defects in mismatch repair.
Linkage of Replication to Start by the Cdk Inhibitor Sic1
Authors: Schneider B. L. , Yang Q.-H. , Futcher A. B.
Published: October 2006

In
Saccharomyces cerevisiae
, three G
1
cyclins (Clns) are important for Start, the event committing cells to division. Sic1, an inhibitor of Clb-Cdc28 kinases, became phosphorylated at Start, and this phosphorylation depended on the activity of Clns. Sic1 was subsequently lost, which depended on the activity of Clns and the ubiquitin-conjugating enzyme Cdc34. Inactivation of Sic1 was the only nonredundant essential function of Clns, because a
sic1
deletion rescued the inviability of the
cln1 cln2 cln3
triple mutant. In
sic1
mutants, DNA replication became uncoupled from budding. Thus, Sic1 may be a substrate of Cln-Cdc28 complexes, and phosphorylation and proteolysis of Sic1 may regulate commitment to replication at Start.
Smart Genes Use Many Cues to Set Cell Fate
Authors: Roush Wade
Published: October 2006

Undifferentiated cells in an early embryo may be like an orchestra without a leader, depending on the biochemical music of their neighbors—secreted regulatory factors—for cues about whether to play the part of a muscle cell, for instance, or a neuron. Yet there hasn't been much evidence that genes in these cells are “smart” enough to pick up the multitude of nuanced biochemical notes surrounding them. Now, however, researchers have found a sophisticated biochemical ear in a sea urchin gene. The gene's “on-off switches” and “volume controls” consist of seven modules, or collections of binding sites, that respond to 13 different regulatory factors. Various combinations of modules can be put together to change the time and place of the gene's activation, and hence the cell's fate
New Skeleton Gives Path From Trees to Ground an Odd Turn
Authors: Shreeve James
Published: October 2006

Durham, North Carolina—Our human forerunners, during the past 5 million years, are thought to have gradually adapted from a life in the trees to one on the ground. But new information about one of these forerunners,
Australopithecus africanus
, may show that adaptive path to be rather crooked. Hundreds of
africanus
specimens—many of them “kept on the back burner” by the boycott against South Africa's old apartheid government—are just now coming under scrutiny. They include the mo st complete australopithecine skeleton found since “Lucy,” the famous representative of an
africanus
predecessor,
Australopithecus afarensis
. And at the recent meeting of the American Association of Physical Anthropologists, resear chers used these bones to show that the body proportions of africanus were more apelike—and perhaps more suited to a life in the trees—than those of
afarensis
, its presumed ancestor. This could mean africanus doubled back on its evo lutionary tracks for some reason. Or perhaps Lucy wasn't the ancestor of
africanus
—or us—after all.
Frontiers in Biomedicine: Cardiovascular Medicine
Authors: Kiberstis Paula , Marx Jean
Published: October 2006

While cardiovascular disease is still the number one killer in the Western world, researchers have been making major inroads on the problem, as this Special Issue shows. Indeed, as detailed on our
Editorial
page by pioneer cholesterol researchers M. S. Brown and J. L. Goldstein, insights into how the body handles cholesterol have already led to the development of new drugs that show great promise in reducing deaths from heart attack. And that may be only the beginning.

In recent work, researchers have identified a host of additional genetic factors that help determine whether the cardiovascular system stays healthy or breaks down. In this Special Issue, experts from this molecular frontier review some of the latest of this research:
E. N. Olson and D. Srivastava
look at the genes controlling the formation of the heart;
R. P. Lifton
surveys the genes that contribute to the development of high blood pressure, a strong risk factor for stroke and heart disease; and
M. T. Keating and M. S. Sanguinetti
examine the genes responsible for inherited cardiac arrhythmias and cardiomyopathies. In addition,
G. H. Gibbons and V. J. Dzau
review the ever-expanding list of potential targets for molecularly based therapies for vascular diseases, while
J. L. Breslow
surveys genetically engineered mouse models of atherosclerosis. (Also see the Report by
Geisterfer-Lowrance
et al.
on a new mouse model of familial hypertrophic cardiomyopathy.)

The News report offers a discussion of emerging new therapies for stroke and what they mean for the health care system, as well as reports on new devices for treating diseased hearts and on the difficulties faced by Moscow's premier cardiology research institute since the Soviet Union dissolved.

Finally, we direct you to
Beyond the Printed Page
, where we provide a movie showing the development of the chick heart, and to
Cardiology Compass
, a guide to help you navigate through the many sights and sounds of cardiology on the Internet.
Molecular Pathways Controlling Heart Development
Authors: Olson Eric N. , Srivastava Deepak
Published: October 2006

Heart formation requires complex interactions among cells from multiple embryonic origins. Recent studies have begun to reveal the genetic pathways that control cardiac morphogenesis. Many of the genes within these pathways are conserved across vast phylogenetic distances, which has allowed cardiac development to be dissected in organisms ranging from flies to mammals. Studies of cardiac development have also revealed the molecular defects underlying several congenital cardiac malformations in humans and may ultimately provide opportunities for genetic testing and intervention.
Molecular Genetics of Human Blood Pressure Variation
Authors: Lifton Richard P.
Published: October 2006

Hypertension is a common multifactorial vascular disorder of largely unknown cause. Recognition that hypertension is in part genetically determined has motivated studies to identify mutations that confer susceptibility. Thus far, mutations in at least 10 genes have been shown to alter blood pressure; most of these are rare mutations imparting large quantitative effects that either raise or lower blood pressure. These mutations alter blood pressure through a common pathway, changing salt and water reabsorption in the kidney. These findings demonstrate the utility of molecular genetic approaches to the understanding of blood pressure variation and may provide insight into the physiologic mechanisms underlying common forms of hypertension.
Diabetes Complications: Why Is Glucose Potentially Toxic?
Authors: Porte Daniel , Schwartz Michael W.
Published: October 2006

Individuals with diabetes can lead quite normal lives when their blood sugar is controlled by insulin injections. But these injections cannot maintain blood glucose at concentrations as low and stable as they are in normal individuals. The resulting highe r glucose concentrations eventually lead to the complications of diabetes—damage to blood vessels, heart disease, blindness, stroke, and kidney failure. In a report in this week's issue (Ishii
et al.
, p. 728), a new inhibitor of protein kinase C is shown to inhibit some indices of glucose toxicity in an animal model of diabetes. In their Perspective, Porte and Schwartz discuss how close we are to being able to treat these complication s in patients.
In Vitro Development of Primitive and Definitive Erythrocytes from Different Precursors
Authors: Nakano Toru , Kodama Hiroaki , Honjo Tasuku
Published: October 2006

During mouse embryogenesis the production of “primitive” erythrocytes (EryP) precedes the production of “definitive” erythrocytes (EryD) in parallel with the transition of the hematopoietic site from the yolk sac to the fetal liver. On a macrophage colony-stimulating factor-deficient stromal cell line OP9, mouse embryonic stem cells were shown to give rise to EryP and EryD sequentially with a time course similar to that seen in murine ontogeny. Studies of the different growth factor requirements and limiting dilution analysis of precursor frequencies indicate that most EryP and EryD probably developed from different precursors by way of distinct differentiation pathways.
Homologous Association of Oppositely Imprinted Chromosomal Domains
Authors: LaSalle Janine M. , Lalande Marc
Published: October 2006

Human chromosome 15q11-q13 encompasses the Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) loci, which are subject to parental imprinting, a process that marks the parental origin of certain chromosomal subregions. A temporal and spatial association between maternal and paternal chromosomes 15 was observed in human T lymphocytes by three-dimensional fluorescence in situ hybridization. This association occurred specifically at the imprinted 15q11-q13 regions only during the late S phase of the cell cycle. Cells from PWS and AS patients were deficient in association, which suggests that normal imprinting involves mutual recognition and preferential association of maternal and paternal chromosomes 15.
A Mouse Model of Familial Hypertrophic Cardiomyopathy
Authors: Geisterfer-Lowrance Anja A. T. , Christe Michael , Conner David A. , Ingwall Joanne S. , Schoen Frederick J. , Seidman Christine E. , Seidman J. G.
Published: October 2006

A mouse model of familial hypertrophic cardiomyopathy (FHC) was generated by the introduction of an Arg
403
→ Gln mutation into the α cardiac myosin heavy chain (MHC) gene. Homozygous αMHC
403/403
mice died 7 days after birth, and sedentary heterozygous αMHC
403/+
mice survived for 1 year. Cardiac histopathology and dysfunction in the αMHC
403/+
mice resembled human FHC. Cardiac dysfunction preceded histopathologic changes, and myocyte disarray, hypertrophy, and fibrosis increased with age. Young male αMHC
403/+
mice showed more evidence of disease than did their female counterparts. Preliminary results suggested that exercise capacity may have been compromised in the αMHC
403/+
mice. This mouse model may help to define the natural history of FHC.
A New Reason for Being: Science
Authors: Lawler Andrew
Published: October 2006

Dan Goldin is crisscrossing the country telling audiences that NASA's mission should be to seek answers to such age-old questions as the origins of life and our solar system. Building the hardware should be simply a means to that end, he says, not the driving force behind the agency's activities.
Added Weight for Neutrino Mass Claim
Authors: Glanz James
Published: October 2006

Indianapolis—Eight months ago a group of experimenters at Los Alamos National Laboratory met with skepticism when they claimed to have found evidence of a positive mass for the neutrino—a wispy subatomic particle generally assumed to be massless. Now they're back, with twice the evidence. Last week the Liquid Scintillator Neutrino Detector (LSND) experiment reported that it has picked up 22 events in which neutrinos generated at the end of an accelerator changed identity before reaching the detector. That process can only take place if the neutrino has mass. If the LSND group is right—and some other researchers are warming to the claim—conventional physics may be in need of revision.
A First Glimpse of Strange Matter?
Authors: Taubes Gary
Published: October 2006

Two particles of strange matter may have made a fleeting appearance in a detector at Brookhaven National Laboratory. All matter in the universe seems to be composed of just two of the six available kinds of quarks, the up and the down, but theoretical calculations suggest that mixing in a fair share of strange quarks, the next heaviest type, should yield another family of stable particles—strange matter. The Brookhaven result might be the first detection of the lightest form of strange matter, a six-quark particle called the H. But with just two events, the physicists aren't ready to claim a discovery.
Impact of DNA Replication Errors Put to the Test
Authors: Normile Dennis
Published: October 2006

Tokyo—Molecular biologist Mitsuru Furusawa and embryologist Hirofumi Doi have developed a theoretical model showing that the very process of DNA synthesis spreads mutations unevenly across a population. The process may help keep populations robust by preserving a stable genetic baseline, yet pave the way for rapid evolutionary change when environmental conditions shift. Now a team of Austrian scientists will look for the kinds of evolutionary changes the model predicts in two experimental organisms. If they succeed, the results will not only increase understanding of evolutionary processes but also elevate the status of evolutionary biology as an experimental science.
Uncharacteristic Earthquakes on the San Andreas Fault
Authors: Grant Lisa B.
Published: October 2006

One model of earthquake recurrence holds that large quakes exhibit regular or characteristic rupture patterns. Combined with a simple picture of how elastic strain accumulates in the faults, this implies that characteristic earthquakes occur at regular intervals. In her Perspective, Grant proposes that recent data from study sites along the San Andreas fault are difficult to understand with this model. The earthquake activity is more irregular and more clustered than the model would suggest.
Dengue Hemorrhagic Fever
Authors: James Anthony A.
Published: October 2006

New results in this issue of
Science
by Olson
et al.
(
p. 884
) report a way to genetically engineer mosquitoes so they cannot transmit dengue fever to humans. This first successful effort to express an exogenous gene that confers resistance to an important human pathogen is discussed by James in his Perspective.
Galileo Probe: In Situ Observations of Jupiter's Atmosphere
Authors: Young Richard E. , Smith Martha A. , Sobeck Charles K.
Published: October 2006

The Galileo probe performed the first in situ measurements of the atmosphere of Jupiter on 7 December 1995. The probe returned data until it reached a depth corresponding to an atmospheric pressure of ∼24 bars. This report presents a brief overview of the origins and purpose of the mission. Science objectives, entry parameters and mission events, and results are described. The remaining reports address in more detail the individual experiments summarized here.
The Galileo Probe Mass Spectrometer: Composition of Jupiter's Atmosphere
Authors: Niemann Hasso B. , Atreya Sushil K. , Carignan George R. , Donahue Thomas M. , Haberman John A. , Harpold Dan N. , Hartle Richard E. , Hunten Donald M. , Kasprzak Wayne T. , Mahaffy Paul R. , Owen Tobias C. , Spencer Nelson W. , Way Stanley H.
Published: October 2006

The composition of the jovian atmosphere from 0.5 to 21 bars along the descent trajectory was determined by a quadrupole mass spectrometer on the Galileo probe. The mixing ratio of He (helium) to H
2
(hydrogen), 0.156, is close to the solar ratio. The abundances of methane, water, argon, neon, and hydrogen sulfide were measured; krypton and xenon were detected. As measured in the jovian atmosphere, the amount of carbon is 2.9 times the solar abundance relative to H
2
, the amount of sulfur is greater than the solar abundance, and the amount of oxygen is much less than the solar abundance. The neon abundance compared with that of hydrogen is about an order of magnitude less than the solar abundance. Isotopic ratios of carbon and the noble gases are consistent with solar values. The measured ratio of deuterium to hydrogen (D/H) of (5 ± 2) × 10
−5
indicates that this ratio is greater in solar-system hydrogen than in local interstellar hydrogen, and the
3
He/
4
He ratio of (1.1 ± 0.2) × 10
−4
provides a new value for protosolar (solar nebula) helium isotopes. Together, the D/H and
3
He/
4
He ratios are consistent with conversion in the sun of protosolar deuterium to present-day
3
He.
Results of the Galileo Probe Nephelometer Experiment
Authors: Ragent Boris , Colburn David S. , Avrin Philip , Rages Kathy A.
Published: October 2006

The nephelometer experiment carried on the Galileo probe was designed to measure the jovian cloud structure and its microphysical characteristics from entry down to atmospheric pressure levels greater than 10 bars. Before this mission there was no direct evidence for the existence of the clouds below the uppermost cloud layer, and only theoretical models derived from remote sensing observations were available for describing such clouds. Only one significant cloud structure with a base at about 1.55 bars was found along the probe descent trajectory below an ambient pressure of about 0.4 bar, although many indications of small densities of particle concentrations were noted during much of the descent.
High-Energy Charged Particles in the Innermost Jovian Magnetosphere
Authors: Fischer H. M. , Pehlke E. , Wibberenz G. , Lanzerotti L. J. , Mihalov J. D.
Published: October 2006

The energetic particles investigation carried by the Galileo probe measured the energy and angular distributions of the high-energy particles from near the orbit of Io to probe entry into the jovian atmosphere. Jupiter's inner radiation region had extremely large fluxes of energetic electrons and protons; intensities peaked at ∼2.2
R
J
(where
R
J
is the radius of Jupiter). Absorption of the measured particles was found near the outer edge of the bright dust ring. The instrument measured intense fluxes of high-energy helium ions (∼62 megaelectron volts per nucleon) that peaked at ∼1.5
R
J
inside the bright dust ring. The abundances of all particle species decreased sharply at ∼1.35
R
J
; this decrease defines the innermost edge of the equatorial jovian radiation.
Radio Frequency Signals in Jupiter's Atmosphere
Authors: Lanzerotti L. J. , Rinnert K. , Dehmel G. , Gliem F. O. , Krider E. P. , Uman M. A. , Bach J.
Published: October 2006

During the Galileo probe's descent through Jupiter's atmosphere, under the ionosphere, the lightning and radio emission detector measured radio frequency signals at levels significantly above the probe's electromagnetic noise. The signal strengths at 3 and 15 kilohertz were relatively large at the beginning of the descent, decreased with depth to a pressure level of about 5 bars, and then increased slowly until the end of the mission. The 15-kilohertz signals show arrival direction anisotropies. Measurements of radio frequency wave forms show that the probe passed through an atmospheric region that did not support lightning within at least 100 kilometers and more likely a few thousand kilometers of the descent trajectory. The apparent opacity of the jovian atmosphere increases sharply at pressures greater than about 4 bars.
Two Genetically Separable Steps in the Differentiation of Thymic Epithelium
Authors: Nehls Michael , Kyewski Bruno , Messerle Martin , Waldschütz Ralph , Schüddekopf Kerstin , Smith Andrew J. H. , Boehm Thomas
Published: October 2006

The development of the thymus depends initially on epithelial-mesenchymal and subsequently on reciprocal lympho-stromal interactions. The genetic steps governing development and differentiation of the thymic microenvironment are unknown. With the use of a targeted disruption of the
whn
gene, which recapitulates the phenotype of the athymic nude mouse, the WHN transcription factor was shown to be the product of the
nude
locus. Formation of the thymic epithelial primordium before the entry of lymphocyte progenitors did not require the activity of WHN. However, subsequent differentiation of primitive precursor cells into subcapsular, cortical, and medullary epithelial cells of the postnatal thymus did depend on activity of the
whn
gene. These results define the first genetically separable steps during thymic epithelial differentiation.
Determination of Life-Span in

Caenorhabditis elegans

by Four Clock Genes
Authors: Lakowski Bernard , Hekimi Siegfried
Published: October 2006

The nematode worm
Caenorhabditis elegans
is a model system for the study of the genetic basis of aging. Maternal-effect mutations in four genes—
clk-1, clk-2
,
clk-3,
and
gro-1
— interact genetically to determine both the duration of development and life-span. Analysis of the phenotypes of these mutants suggests the existence of a general physiological clock in the worm. Mutations in certain genes involved in dauer formation (an alternative larval stage induced by adverse conditions in which development is arrested) can also extend life-span, but the life extension of Clock mutants appears to be independent of these genes. The
daf-2(e1370) clk-1(e2519)
worms, which carry life-span-extending mutations from two different pathways, live nearly five times as long as wild-type worms.
Increase in Single L-Type Calcium Channels in Hippocampal Neurons During Aging
Authors: Thibault Olivier , Landfield Philip W.
Published: October 2006

Voltage-activated calcium (Ca
2+
) influx is increased in mammalian CA1 hippocampal neurons during aging. However, the molecular basis for this elevation is not known. The partially dissociated hippocampal (“zipper'') slice preparation was used to analyze single Ca
2+
channel activity in CA1 neurons of adult and aged rats. Total L-type Ca
2+
channel activity in patches was found to increase with aging, primarily because of an increase in the density of functional channels. Learning in aged animals was inversely correlated with channel density. This increase in functional Ca
2+
channels with aging could underlie the vulnerability of neurons to age-associated neurodegenerative conditions.
Binding of GSK3β to the APC-β-Catenin Complex and Regulation of Complex Assembly
Authors: Rubinfeld Bonnee , Albert Iris , Porfiri Emilio , Fiol Carol , Munemitsu Susan , Polakis Paul
Published: October 2006

The adenomatous polyposis coli gene (
APC
) is mutated in most colon cancers. The APC protein binds to the cellular adhesion molecule β-catenin, which is a mammalian homolog of ARMADILLO, a component of the WINGLESS signaling pathway in
Drosophila
development. Here it is shown that when β-catenin is present in excess, APC binds to another component of the WINGLESS pathway, glycogen synthase kinase 3β (GSK3β), a mammalian homolog of
Drosophila
ZESTE WHITE 3. APC was a good substrate for GSK3β in vitro, and the phosphorylation sites were mapped to the central region of APC. Binding of β-catenin to this region was dependent on phosphorylation by GSK3β.