bluuebunny/crossref_metadata_2025 huggingface dataset:
Commitment of CNS Progenitors Along the Dorsoventral Axis of
Drosophila
Neuroectoderm
Authors: Udolph Gerald , Lüer Karin , Bossing Torsten , Technau Gerhard M.
Published: October 2006

In the
Drosophila
embryo, the central nervous system (CNS) develops from a population of neural stem cells (neuroblasts) and midline progenitor cells. Here, the fate and extent of determination of CNS progenitors along the dorsoventral axis was assayed. Dorsal neuroectodermal cells transplanted into the ventral neuroectoderm or into the midline produced CNS lineages consistent with their new position. However, ventral neuroectodermal cells and midline cells transplanted to dorsal sites of the neuroectoderm migrated ventrally and produced CNS lineages consistent with their origin. Thus, inductive signals at the ventral midline and adjacent neuroectoderm may confer ventral identities to CNS progenitors as well as the ability to assume and maintain characteristic positions in the developing CNS. Furthermore, ectopic transplantations of wild-type midline cells into
single minded
(
sim
) mutant embryos suggest that the ventral midline is required for correct positioning of the cells.
Reciprocal stimulation of GTP hydrolysis by two directly interacting GTPases
Authors: Powers Ted , Walter Peter
Published: October 2006

The
Escherichia coli
guanosine triphosphate (GTP)-binding proteins Ffh and FtsY have been proposed to catalyze the cotranslational targeting of proteins to the bacterial plasma membrane. A mutation was introduced into the GTP-binding domain of FtsY that altered its nucleotide specificity from GTP to xanthosine triphosphate (XTP). The mutant FtsY protein stimulated GTP hydrolysis by a ribonucleoprotein consisting of Ffh and 4.5S RNA in a reaction that required XTP, and it hydrolyzed XTP in a reaction that required both the Ffh-4.5S ribonucleoprotein and GTP. Thus, nucleotide triphosphate hydrolysis by Ffh and FtsY is likely to occur in reciprocally coupled reactions in which the two interacting guanosine triphosphatases act as regulatory proteins for each other.
Inducible Gene Targeting in Mice
Authors: Kühn Ralf , Schwenk Frieder , Aguet Michel , Rajewsky Klaus
Published: October 2006

A method of gene targeting that allows the inducible inactivation of a target gene in mice is presented. The method uses an interferon-responsive promoter to control the expression of Cre recombinase. Here, Cre was used to delete a segment of the DNA polymerase β gene flanked by
IoxP
recombinase recognition sites. Deletion was complete in liver and nearly complete in lymphocytes within a few days, whereas partial deletion was obtained in other tissues. This method can be used for the inducible inactivation of any other gene in vivo.
Elongin (SIII): A Multisubunit Regulator of Elongation by RNA Polymerase II
Authors: Aso Teijiro , Lane William S. , Conaway Joan Weliky , Conaway Ronald C.
Published: October 2006

The Elongin (SIII) complex activates elongation by mammalian RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin is a heterotrimer composed of A, B, and C subunits of 110, 18, and 15 kilodaltons, respectively. Here, the mammalian Elongin A gene was isolated and expressed, and the Elongin (SIII) complex reconstituted with recombinant subunits. Elongin A is shown to function as the transcriptionally active component of Elongin (SIII) and Elongin B and C as regulatory subunits. Whereas Elongin C assembles with Elongin A to form an AC complex with increased specific activity, Elongin B, a member of the ubiquitin-homology gene family, appears to serve a chaperone-like function, facilitating assembly and enhancing stability of the Elongin (SIII) complex.
Binding of the von Hippel-Lindau Tumor Suppressor Protein to Elongin B and C
Authors: Kibel Adam , Iliopoulos Othon , DeCaprio James A. , Kaelin William G.
Published: October 2006

Germ-line mutations of the von Hippel-Lindau tumor suppressor gene (
VHL
) predispose individuals to a variety of human tumors, and somatic mutations of this gene have been identified in sporadic renal cell carcinomas and cerebellar hemangioblastomas. Two transcriptional elongation factors, Elongin B and C, were shown to bind in vitro and in vivo to a short, colinear region of the VHL protein (pVHL) that is frequently mutated in human tumors. A peptide replica of this region inhibited binding of pVHL to Elongin B and C, whereas a point-mutant derivative, corresponding to a naturally occurring VHL missense mutation, had no effect. These results suggest that the tumor suppression function of pVHL may be linked to its ability to bind to Elongin B and C.
Integrins and Modulation of Transmitter Release from Motor Nerve Terminals by Stretch
Authors: Chen Bo-Ming , Grinnell Alan D.
Published: October 2006

The stretch of a frog muscle within the physiological range can more than double the spontaneous and evoked release of neurotransmitter from its motor nerve terminals. Here, stretch enhancement of release was suppressed by peptides containing the sequence arginine-glycine-aspartic acid (RGD), which blocks integrin binding. Integrin antibodies also inhibited the enhancement obtained by stretching. Stretch enhancement depended on intraterminal calcium derived both from external calcium and from internal stores. Muscle stretch thus might enhance the release of neurotransmitters either by elevating internal calcium concentrations or by increasing the sensitivity of transmitter release to calcium in the nerve terminal.
Requirement of Mip-1α for an Inflammatory Response to Viral Infection
Authors: Cook Donald N. , Beck Melinda A. , Coffman Thomas M. , Kirby Suzanne L. , Sheridan John F. , Pragnell lan B. , Smithies Oliver
Published: October 2006

Macrophage inflammatory protein-1α (MIP-1α) is a chemokine that has pro-inflammatory and stem cell inhibitory activities in vitro. Its biologic role in vivo was examined in mice in which the gene encoding MIP-1α had been disrupted. Homozygous MIP-1α mutant (-/-) mice were resistant to Coxsackievirus-induced myocarditis seen in infected wild-type (+/+) mice. Influenza virus-infected -/- mice had reduced pneumonitis and delayed clearance of the virus compared with infected +/+ mice. The -/- mice had no overt hematopoietic abnormalities. These results demonstrate that MIP-1α is an important mediator of virus-induced inflammation in vivo.
Human H-Y: a Male-Specific Histocompatibility Antigen Derived from the SMCY Protein
Authors: Wang Wei , Meadows Leslie R. , den Haan Joke M. M. , Sherman Nicholas E. , Chen Ye , Blokland Els , Shabanowitz Jeffrey , Agulnik Alexander I. , Hendrickson Ronald C. , Bishop Colin E. , Hunt Donald F. , Goulmy Els , Engelhard Victor H.
Published: October 2006

H-Y is a transplantation antigen that can lead to rejection of male organ and bone marrow grafts by female recipients, even if the donor and recipient match at the major histocompatibility locus of humans, the HLA (human leukocyte antigen) locus. However, the origin and function of H-Y antigens has eluded researchers for 40 years. One human H-Y antigen presented by HLA-B7 was identified as an 11-residue peptide derived from SMCY, an evolutionarily conserved protein encoded on the Y chromosome. The protein from the homologous gene on the X chromosome,
SMCX
, differs by two amino acid residues in the same region. The identification of H-Y may aid in transplantation prognosis, prenatal diagnosis, and fertilization strategies.
Signatures of the Martian Atmosphere in Glass of the Zagami Meteorite
Authors: Marti K. , Kim J. S. , Thakur A. N. , McCoy T. J. , Keil K.
Published: October 2006

Isotopic signatures of nitrogen, argon, and xenon have been determined in separated millimeter-sized pockets of shock-melted glass in a recently identified lithology of the meteorite Zagami, a shergottite. The ratio of nitrogen-15 to nitrogen-14, which is at least 282 per mil larger than the terrestrial value, the ratio of xenon-129 to xenon-132 = 2.40, and the argon isotopic abundances match the signatures previously observed in the glassy lithology of the Antarctic shergottite EETA 79001. These results show that the signatures in EETA 79001 are not unique but characterize the trapped gas component in shock-melted glass of shergottites. The isotopic and elemental ratios of nitrogen, argon, and xenon closely resemble the Viking spacecraft data for the martian atmosphere and provide compelling evidence for a martian origin of the two shergottites and, by extension, of the meteorites in the shergottites-nakhlites-chassignites (SNC) group.
Crystal Structure of the β Chain of a T Cell Antigen Receptor
Authors: Bentley Graham A. , Boulot Ginette , Karjalainen Klaus , Mariuzza Roy A.
Published: October 2006

The crystal structure of the extracellular portion of the β chain of a murine T cell antigen receptor (TCR), determined at a resolution of 1.7 angstroms, shows structural homology to immunoglobulins. The structure of the first and second hypervariable loops suggested that, in general, they adopt more restricted sets of conformations in TCR β chains than those found in immunoglobulins; the third hypervariable loop had certain structural characteristics in common with those of immunoglobulin heavy chain variable domains. The variable and constant domains were in close contact, presumably restricting the flexibility of the β chain. This may facilitate signal transduction from the TCR to the associated CD3 molecules in the TCR-CD3 complex.
Requirement of Serine Phosphorylation for Formation of STAT-Promoter Complexes
Authors: Zhang Xiaokui , Blenis John , Li Heng-Chun , Schindler Chris , Chen-Kiang Selina
Published: October 2006

Members of the interleukin-6 family of cytokines bind to and activate receptors that contain a common subunit, gp130. This leads to the activation of Stat3 and Stat1, two cytoplasmic signal transducers and activators of transcription (STATs), by tyrosine phosphorylation. Serine phosphorylation of Stat3 was constitutive and was enhanced by signaling through gp130. In cells of lymphoid and neuronal origins, inhibition of serine phosphorylation prevented the formation of complexes of DNA with Stat3-Stat3 but not with Stat3-Stat1 or Stat1-Stat1 dimers. In vitro serine dephosphorylation of Stat3 also inhibited DNA binding of Stat3-Stat3. The requirement of serine phosphorylation for Stat3- Stat3⋅DNA complex formation was inversely correlated with the affinity of Stat3-Stat3 for the binding site. Thus, serine phosphorylation appears to enhance or to be required for the formation of stable Stat3-Stat3⋅DNA complexes.
Rapid Adaptation of Cardiac Ryanodine Receptors: Modulation by Mg
2+
and Phosphorylation
Authors: Valdivia Hector H. , Kaplan Jack H. , Ellis-Davies Graham C. R. , Lederer W. Jonathan
Published: October 2006

Channel adaptation is a fundamental feature of sarcoplasmic reticulum calcium release channels (called ryanodine receptors, RyRs). It permits successive increases in the intracellular concentration of calcium (Ca
2+
) to repeatedly but transiently activate channels. Adaptation of RyRs in the absence of magnesium (Mg2+) and adenosine triphosphate is an extremely slow process (taking seconds). Photorelease of Ca
2+
from nitrophenyl-EGTA, a photolabile Ca
2+
chelator, demonstrated that RyR adaptation is rapid (milliseconds) in canine heart muscle when physiological Mg
2+
concentrations are present. Phosphorylation of the RyR by protein kinase A increased the responsiveness of the channel to Ca
2+
and accelerated the kinetics of adaptation. These properties of the RyR from heart may also be relevant to other cells in which multiple agonist-dependent triggering events regulate cellular functions.
High-Frequency Motility of Outer Hair Cells and the Cochlear Amplifier
Authors: Dallos Peter , Evans Burt N.
Published: October 2006

Outer hair cells undergo somatic elongation-contraction cycles in vitro when electrically stimulated. This "electromotile" response is assumed to underlie the high sensitivity and frequency selectivity of amplification in the mammalian cochlea. This process, presumably operating on a cycle-by-cycle basis at the frequency of the stimulus, is believed to provide mechanical feedback in vivo. However, if driven by the receptor potential of the cell, the mechanical feedback is expected to be severely attenuated at high frequencies because of electrical low-pass filtering by the outer hair cell basolateral membrane. It is proposed that electromotility at high frequencies is driven instead by extracellular potential gradients across the hair cell, and it is shown that this driving voltage is not subject to low-pass filtering and is sufficiently large. It is further shown that if the filtering properties of the cell membrane are canceled, taking advantage of the electrical characteristics of isolated outer hair cells in a partitioning glass microchamber, then the lower bound of the motor's bandwidth is approximately 22 kilohertz, a number determined only by the limitations of our instrumentation.
Structure of the Cell Wall Anchor of Surface Proteins in
Staphylococcus aureus
Authors: Schneewind Olaf , Fowler Audree , Faull Kym F.
Published: October 2006

Many surface proteins are anchored to the cell wall of Gram-positive bacteria and are involved in the pathogenesis of these organisms. A hybrid molecule was designed that, when expressed in
Staphylococcus aureus
, was anchored to the cell wall and could be released by controlled enzymatic digestion. By a combination of molecular biology and mass spectrometry techniques, the structure of the cell wall anchor of surface proteins in
S. aureus
was revealed. After cleavage of surface proteins between threonine and glycine of the conserved LPXTG motif, the carboxyl of threonine is amide-linked to the free amino group of the pentaglycine crossbridge in the staphylococcal cell wall.
Processing of Complex Sounds in the Macaque Nonprimary Auditory Cortex
Authors: Rauschecker Josef P. , Tian Biao , Hauser Marc
Published: October 2006

Neurons in the superior temporal gyrus of anesthetized rhesus monkeys were exposed to complex acoustic stimuli. Bandpassed noise bursts with defined center frequencies evoked responses that were greatly enhanced over those evoked by pure tones. This finding led to the discovery of at least one new cochleotopic area in the lateral belt of the nonprimary auditory cortex. The best center frequencies of neurons varied along a rostrocaudal axis, and the best bandwidths of the noise bursts varied along a mediolateral axis. When digitized monkey calls were used as stimuli, many neurons showed a preference for some calls over others. Manipulation of the calls' frequency structure and playback of separate components revealed different types of spectral integration. The lateral areas of the monkey auditory cortex appear to be part of a hierarchical sequence in which neurons prefer increasingly complex stimuli and may form an important stage in the preprocessing of communication sounds.
Diversification and Extinction in the History of Life
Authors: Benton M. J.
Published: October 2006

Analysis of the fossil record of microbes, algae, fungi, protists, plants, and animals shows that the diversity of both marine and continental life increased exponentially since the end of the Precambrian. This diversification was interrupted by mass extinctions, the largest of which occurred in the Early Cambrian, Late Ordovician, Late Devonian, Late Permian, Early Triassic, Late Triassic, and end-Cretaceous. Most of these extinctions were experienced by both marine and continental organisms. As for the periodicity of mass extinctions, no support was found: Seven mass extinction peaks in the last 250 million years are spaced 20 to 60 million years apart.
Classical and Quantum Magnetic Phenomena in Natural and Artificial Ferritin Proteins
Authors: Gider S. , Awschalom D. D. , Douglas T. , Mann S. , Chaparala M.
Published: October 2006

Artificial ferritin has been synthesized with control of both the magnetic state (antiferromagnetic or ferrimagnetic) and the particle size over an order of magnitude in the number of iron atoms. The magnetic properties of the artificial ferritin were compared with those of natural horse spleen ferritin in a range of temperatures (20 millikelvin to 300 kelvin) and fields (1 nanotesla to 27 tesla). In the classical regime, the blocking temperature was found to correlate with the average particle size. A correlation was also observed in the quantum regime between the resonance frequency of macroscopic quantum tunneling of the Neel vector and the particle size. At high magnetic fields (to 27 tesla), a spin flop transition with a strong dependence on orientation was seen in the natural ferritin, providing evidence of antiferromagnetism in this system.
Muscle Efficiency and Elastic Storage in the Flight Motor of
Drosophila
Authors: Dickinson Michael H. , Lighton John R. B.
Published: October 2006

Insects could minimize the high energetic costs of flight in two ways: by employing high-efficiency muscles and by using elastic elements within the thorax to recover energy expended accelerating the wings. However, because muscle efficiency and elastic storage have proven difficult variables to measure, it is not known which of these strategies is actually used. By comparison of mechanical power measurements based on gas exchange with simultaneously measured flight kinematics in Drosophila, a method was developed for determining both the mechanical efficiency and the minimum degree of elastic storage within the flight motor. Muscle efficiency values of 10 percent suggest that insects may minimize energy use in flight by employing an elastic flight motor rather than by using extraordinarily efficient muscles. Further, because of the trade-off between inertial and aerodynamic power throughout the wing stroke, an elastic storage capacity as low as 10 percent may be enough to minimize the energetic costs of flight.
A Morbillivirus that Caused Fatal Fisease in Horses and Humans
Authors: Murray Keith , Selleck Paul , Hooper Peter , Hyatt Alex , Gould Allan , Gleeson Laurie , Westbury Harvey , Hiley Lester , Selvey Linda , Rodwell Barry , Ketterer Peter
Published: October 2006

A morbillivirus has been isolated and added to an increasing list of emerging viral diseases. This virus caused an outbreak of fatal respiratory disease in horses and humans. Genetic analyses show it to be only distantly related to the classic morbilliviruses rinderpest, measles, and canine distemper. When seen by electron microscopy, viruses had 10- and 18-nanometer surface projections that gave them a "double-fringed" appearance. The virus induced syncytia that developed in the endothelium of blood vessels, particularly the lungs.
Calcium Signaling in Neurons: Molecular Mechanisms and Cellular Consequences
Authors: Ghosh Anirvan , Greenberg Michael E.
Published: October 2006

Neuronal activity can lead to marked increases in the concentration of cytosolic calcium, which then functions as a second messenger that mediates a wide range of cellular responses. Calcium binds to calmodulin and stimulates the activity of a variety of enzymes, including calcium-calmodulin kinases and calcium-sensitive adenylate cyclases. These enzymes transduce the calcium signal and effect short-term biological responses, such as the modification of synaptic proteins and long-lasting neuronal responses that require changes in gene expression. Recent studies of calcium signal-transduction mechanisms have revealed that, depending on the route of entry into a neuron, calcium differentially affects processes that are central to the development and plasticity of the nervous system, including activity-dependent cell survival, modulation of synaptic strength, and calcium-mediated cell death.
Cytokine Signaling Through Nonreceptor Protein Tyrosine Kinases
Authors: Taniguchi Tadatsugu
Published: October 2006

Cytokines are a family of soluble mediators of cell-to-cell communication that includes interleukins, interferons, and colony-stimulating factors. The characteristic features of cytokines lie in their functional redundancy and pleiotropy. Most of the cytokine receptors that constitute distinct superfamilies do not possess intrinsic protein tyrosine kinase (PTK) domains, yet receptor stimulation usually invokes rapid tyrosine phosphorylation of intracellular proteins, including the receptors themselves. It is now clear that these receptors are capable of recruiting or activating (or both) a variety of nonreceptor PTKs to induce downstream signaling pathways. Thus, the intracytoplasmic structure of cytokine receptors has evolved so as to allow the combined action of different PTK family members expressed in different cell types, which may ultimately determine the activity of cytokines.
Killing of Trypanosomes by the Human Haptoglobin-Related Protein
Authors: Smith Andrea B. , Esko Jeffrey D. , Hajduk Stephen L.
Published: October 2006

African trypanosomes cause disease in humans and animals.
Trypanosoma brucei brucei
affects cattle but not humans because of its sensitivity to a subclass of human high density lipoproteins (HDLs) called trypanosome lytic factor (TLF). TLF contains two apolipoproteins that are sufficient to cause lysis of
T. b. brucei
in vitro. These proteins were identified as the human haptoglobin-related protein and paraoxonase-arylesterase. An antibody to haptoglobin inhibited TLF activity. TLF was shown to exhibit peroxidase activity and to be inhibited by catalase. These results suggest that TLF kills trypanosomes by oxidative damage initiated by its peroxidase activity.
Recruitment and Activation of PTP1C in Negative Regulation of Antigen Receptor Signaling by FcγRIIB1
Authors: D'Ambrosio Daniele , Hippen Keli L. , Minskoff Stacey A. , Mellman Ira , Pani Giovanni , Siminovitch Kathy A. , Cambier John C.
Published: October 2006

Coligation of the Fc receptor on B cells, FcγRIIB1, with the B cell antigen receptor (BCR) leads to abortive BCR signaling. Here it was shown that the FcγRIIB1 recruits the phosphotyrosine phosphatase PTP1C after BCR coligation. This association is mediated by the binding of a 13-amino acid tyrosine-phosphorylated sequence to the carboxyl-terminal Src homology 2 domain of PTP1C and activates PTP1C. Inhibitory signaling and PTP1C recruitment are dependent on the presence of the tyrosine within the 13-amino acid sequence. Inhibitory signaling mediated by FcγRIIB1 is deficient in
motheaten
mice which do not express functional PTP1C. Thus, PTP1C is an effector of BCR-FcγRIIB1 negative signal cooperativity.
Superantigen-Dependent, Cell-Mediated Cytotoxicity Inhibited by MHC Class I Receptors on T Lymphocytes
Authors: Phillips Joseph H. , Gumperz Jenny E. , Parham Peter , Lanier Lewis L.
Published: October 2006

Bacterial superantigens bind with high affinity to major histocompatibility complex (MHC) class II antigens on antigen-presenting cells and with T cell antigen receptor (TCR) β chains on T lymphocytes, which results in the T cell activation responsible for toxic shock syndrome and food poisoning. Many cytotoxic T lymphocyte (CTL) clones were shown to have receptors for human leukocyte antigen (HLA) class I molecules that inhibited superantigen-induced cytotoxicity against appropriate class I-bearing target cells. One type of inhibitory receptor, NKB1, was present on CD4
+
and CD8
+
TCRαβ
+
CTL clones and blocked the killing of staphylococcal enterotoxin B (SEB)-coated targets bearing certain polymorphic HLA-B molecules. Expression of HLA-A, -B, and -C molecules on the SEB-coated targets also protected against cytolysis mediated by many NKB1-negative T cell clones, suggesting the presence of additional inhibitory MHC class I receptors. These HLA class I receptors may limit tissue destruction and possibly autoimmunity caused by activated T lymphocytes.
Evidence that F Plasmid Transfer Replication Underlies Apparent Adaptive Mutation
Authors: Galitski Timothy , Roth John R.
Published: October 2006

An
Escherichia coli
K12 strain, FC40, has been used extensively in the analysis of adaptive mutability. This strain carries a revertible mutant
lac
allele on an F plasmid and accumulates Lac
+
(lactose utilizing) revertants, but not unselected mutants, when placed on selective medium. These adaptive mutations are a subset of spontaneous types and their formation depends on the RecABC functions. Data presented here suggest that this phenomenon depends on transfer functions of the F factor. Fertility inhibition eliminates RecA-dependent adaptive reversion. Thus, "adaptive" revertants may form during replication from the transfer origin, whereas loci in the nonreplicating chromosome show little mutation.
Nicotinic Receptor Binding Site Probed with Unnatural Amino Acid Incorporation in Intact Cells
Authors: Nowak Mark W. , Kearney Patrick C. , Sampson  , Saks Margaret E. , Labarca Cesar G. , Silverman Scott K. , Zhong Wenge , Thorson Jon , Abelson John N. , Davidson Norman , Schultz Peter G. , Dougherty Dennis A. , Lester Henry A.
Published: October 2006

The nonsense codon suppression method for unnatural amino acid incorporation has been applied to intact cells and combined with electrophysiological analysis to probe structure-function relations in the nicotinic acetylcholine receptor. Functional receptors were expressed in
Xenopus
oocytes when tyrosine and phenylalanine derivatives were incorporated at positions 93, 190, and 198 in the binding site of the α subunit. Subtle changes in the structure of an individual side chain produced readily detectable changes in the function of this large channel protein. At each position, distinct features of side chain structure dominated the dose-response relation, probably by governing the agonist-receptor binding.
Crystal Structure of the 20
S
Proteasome from the Archaeon
T. acidophilum
at 3.4 Å Resolution
Authors: Löwe Jan , Stock Daniela , Jap Bing , Zwickl Peter , Baumeister Wolfgang , Huber Robert
Published: October 2006

Three archaeological sites at Katanda on the Upper Semliki River in the Western Rift Valley of Zaire have provided evidence for a well-developed bone industry in a Middle Stone Age context. Artifacts include both barbed and unbarbed points as well as a daggerlike object. Dating by both direct and indirect means indicate an age of ∼90,000 years or older. Together with abundant fish (primarily catfish) remains, the bone technology indicates that a complex subsistence specialization had developed in Africa by this time. The level of behavioral competence required is consistent with that of upper Paleolithic
Homo sapiens sapiens
. These data support an African origin of behaviorally as well as biologically modern humans.
Dating and Context of Three Middle Stone Age Sites with Bone Points in the Upper Semliki Valley, Zaire
Authors: Brooks Alison S. , Helgren David M. , Cramer Jon S. , Franklin Alan , Hornyak William , Keating Jody M. , Klein Richard G. , Rink William J. , Schwarcz Henry , Smith J. N. Leith , Stewart Kathlyn , Todd Nancy E. , Verniers Jacques , Yellen John E.
Published: October 2006

The extent to which the earliest anatomically modern humans in Africa exhibited behavioral and cognitive traits typical ofHomo sapiens sapiensis controversial. In eastern Zaire, archaeological sites with bone points have yielded dates older than 89-15+22thousand years ago by several techniques. These include electron spin resonance, thermoluminescence, optically stimulated luminescence, uranium series, and amino acid racemization. Faunal and stratigraphic data are consistent with this age.
A Middle Stone Age Worked Bone Industry from Katanda, Upper Semliki Valley, Zaire
Authors: Yellen John E. , Brooks Alison S. , Cornelissen Els , Mehlman Michael J. , Stewart Kathlyn
Published: October 2006

Three archaeological sites at Katanda on the Upper Semliki River in the Western Rift Valley of Zaire have provided evidence for a well-developed bone industry in a Middle Stone Age context. Artifacts include both barbed and unbarbed points as well as a daggerlike object. Dating by both direct and indirect means indicate an age of approximately 90,000 years or older. Together with abundant fish (primarily catfish) remains, the bone technology indicates that a complex subsistence specialization had developed in Africa by this time. The level of behavioral competence required is consistent with that of upper Paleolithic Homo sapiens sapiens. These data support an African origin of behaviorally as well as biologically modern humans.
How Baseball Outfielders Determine Where to Run to Catch Fly Balls
Authors: McBeath Michael K. , Shaffer Dennis M. , Kaiser Mary K.
Published: October 2006

Current theory proposes that baseball outfielders catch fly balls by selecting a running path to achieve optical acceleration cancellation of the ball. Yet people appear to lack the ability to discriminate accelerations accurately. This study supports the idea that outfielders convert the temporal problem to a spatial one by selecting a running path that maintains a linear optical trajectory (LOT) for the ball. The LOT model is a strategy of maintaining "control" over the relative direction of optical ball movement in a manner that is similar to simple predator tracking behavior.
Potentiated Necrosis of Cultured Cortical Neurons by Neurotrophins
Authors: Koh Jae-Young , Gwag Byoung J. , Lobner Doug , Choi Dennis W.
Published: October 2006

The effects of neurotrophins on several forms of neuronal degeneration in murine cortical cell cultures were examined. Consistent with other studies, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 all attenuated the apoptotic death induced by serum deprivation or exposure to the calcium channel antagonist nimodipine. Unexpectedly, however, 24-hour pretreatment with these same neurotrophins markedly potentiated the necrotic death induced by exposure to oxygen-glucose deprivation or
N
-methyl-D-aspartate. Thus, certain neurotrophins may have opposing effects on different types of death in the same neurons.
Proteasome from
Thermoplasma acidophilum
: a Threonine Protease
Authors: Seemüller Erika , Lupas Andrei , Stock Daniela , Löwe Jan , Huber Robert , Baumeister Wolfgang
Published: October 2006

The catalytic mechanism of the 20
S
proteasome from the archaebacterium
Thermoplasma acidophilum
has been analyzed by site-directed mutagenesis of the β subunit and by inhibitor studies. Deletion of the amino-terminal threonine or its mutation to alanine led to inactivation of the enzyme. Mutation of the residue to serine led to a fully active enzyme, which was over ten times more sensitive to the serine protease inhibitor 3,4-dichloroisocoumarin. In combination with the crystal structure of a proteasome-inhibitor complex, the data show that the nucleophilic attack is mediated by the amino-terminal threonine of processed β subunits. The conservation pattern of this residue in eukaryotic sequences suggests that at least three of the seven eukaryotic β-type subunit branches should be proteolytically inactive.
Phytochromes: Photosensory Perception and Signal Transduction
Authors: Quail Peter H. , Boylan Margaret T. , Parks Brian M. , Short Timothy W. , Xu Yong , Wagner Doris
Published: October 2006

The phytochrome family of photoreceptors monitors the light environment and dictates patterns of gene expression that enable the plant to optimize growth and development in accordance with prevailing conditions. The enduring challenge is to define the biochemical mechanism of phytochrome action and to dissect the signaling circuitry by which the photoreceptor molecules relay sensory information to the genes they regulate. Evidence indicates that individual phytochromes have specialized photosensory functions. The amino-terminal domain of the molecule determines this photosensory specificity, whereas a short segment in the carboxyl-terminal domain is critical for signal transfer to downstream components. Heterotrimeric GTP-binding proteins, calcium-calmodulin, cyclic guanosine 5′-phosphate, and the COP-DET-FUS class of master regulators are implicated as signaling intermediates in phototransduction.
Translational Suppression by Trinucleotide Repeat Expansion at
FMR1
Authors: Feng Yue , Zhang Fuping , Lokey Laurie K. , Chastain Jane L. , Lakkis Lisa , Eberhart Derek , Warren Stephen T.
Published: October 2006

Fragile X syndrome is the result of the unstable expansion of a trinucleotide repeat in the 5′-untranslated region of the
FMR1
gene. Fibroblast subclones from a mildly affected patient, each containing stable
FMR1
alleles with 57 to 285 CGG repeats, were shown to exhibit normal steady-state levels of
FMR1
messenger RNA. However, FMR protein was markedly diminished from transcript with more than 200 repeats. Such transcripts were associated with stalled 40
S
ribosomal subunits. These results suggest that a structural RNA transition beyond 200 repeats impedes the linear 40
S
migration along the 5′-untranslated region. This results in translational inhibition by trinucleotide repeat expansion.
Release of Ca
2+
from Individual Plant Vacuoles by Both InsP
3
and Cyclic ADP-Ribose
Authors: Allen Gethyn J. , Muir Shelagh R. , Sanders Dale
Published: October 2006

Calcium mobilization from intracellular pools couples many stimuli to responses in plant cells. Cyclic adenosine 5′-diphosphoribose (cADPR), which interacts with a ryanodine receptor in certain animal cells, was shown to elicit calcium release at the vacuolar membrane of beet storage root. The vacuolar calcium release pathway showed similarities to cADPR-gated calcium release in animal cells, including inhibition by ruthenium red, ryanodine activation, and high affinity for cADPR [Michaelis constant (
K
m
) = 24 ± 7 nanomolar]. Analysis by patch-clamping demonstrated that the cADPR-gated pathway in beet is voltage-dependent over the physiological range, does not spontaneously desensitize, and is colocalized with an inositol 1,4,5-trisphosphate (InsP
3
)-gated calcium release pathway in individual vacuoles.
Conversion of
Xenopus
Ectoderm into Neurons by NeuroD, a Basic Helix-Loop-Helix Protein
Authors: Lee Jacqueline E. , Hollenberg Stanley M. , Snider Lauren , Turner David L. , Lipnick Naomi , Weintraub Harold
Published: October 2006

Basic helix-loop-helix (bHLH) proteins are instrumental in determining cell type during development. A bHLH protein, termed NeuroD, for neurogenic differentiation, has now been identified as a differentiation factor for neurogenesis because (i) it is expressed transiently in a subset of neurons in the central and peripheral nervous systems at the time of their terminal differentiation into mature neurons and (ii) ectopic expression of
neuroD
in
Xenopus
embryos causes premature differentiation of neuronal precursors. Furthermore,
neuroD
can convert presumptive epidermal cells into neurons and also act as a neuronal determination gene. However, unlike another previously identified proneural gene (XASH-3),
neuroD
seems competent to bypass the normal inhibitory influences that usually prevent neurogenesis in ventral and lateral ectoderm and is capable of converting most of the embryonic ectoderm into neurons. The data suggest that
neuroD
may participate in the terminal differentiation step during vertebrate neuronal development.
Gene Trap Tagging of
PROLIFERA
, an Essential
MCM2-3-5
-Like Gene in
Arabidopsis
Authors: Springer Patricia S. , McCombie W. Richard , Sundaresan Venkatesan , Martienssen Robert A.
Published: October 2006

Gene trap transposon mutagenesis can identify essential genes whose functions in later development are obscured by an early lethal phenotype. In higher plants, many genes are required for haploid gametophyte viability, so that the phenotypic effects of their disruption cannot be readily observed in the diploid plant body. The
PROLIFERA
(
PRL
) gene, identified by gene trap transposon mutagenesis in
Arabidopsis
, is required for megagametophyte and embryo development. Reporter gene expression patterns revealed that PRL was expressed in dividing cells throughout the plant.
PRL
is related to the
MCM2-3-5
family of yeast genes that are required for the initiation of DNA replication.
Long-Range Motional Restrictions in a Multidomain Zinc-Finger Protein from Anisotropic Tumbling
Authors: Brüschweiler Rafael , Liao Xiubei , Wright Peter E.
Published: October 2006

Structural characterization of biomolecules in solution by nuclear magnetic resonance (NMR) spectroscopy is based primarily on the use of interproton distances derived from homonuclear cross-relaxation experiments. Information about short time-scale dynamics, on the other hand, is obtained from relaxation rates of heteronuclear spin pairs such as
15
N-
1
H. By combining the two types of data and utilizing the dependence of heteronuclear NMR relaxation rates on anisotropic diffusional rotational tumbling, it is possible to obtain structural information about long-range motional correlations between protein domains. This approach was applied to characterize the relative orientations and mobilities of the first three zinc-finger domains of the
Xenopus
transcription factor TFIIIA in aqueous solution. The data indicate that the motions of the individual zinc-finger domains are highly correlated on time scales shorter than 10 nanoseconds and that the average conformation of the three-finger polypeptide is elongated.
A Region of Adenylyl Cyclase 2 Critical for Regulation by G Protein βγ Subunits
Authors: Chen Jianqiang , DeVivo Michael , Dingus Jane , Harry Anya , Li Jingrong , Sui Jinliang , Carty Donna J. , Blank Jonathan L. , Exton John H. , Stoffel Robert H. , Inglese James , Lefkowitz Robert J. , Logothetis Diomedes E. , Hildebrandt John D. , lyengar Ravi
Published: October 2006

Receptor-mediated activation of heterotrimeric guanine nucleotide-binding proteins (G proteins) results in the dissociation of α from βγ subunits, thereby allowing both to regulate effectors. Little is known about the regions of effectors required for recognition of Gβγ. A peptide encoding residues 956 to 982 of adenylyl cyclase 2 specifically blocked Gβγ stimulation of adenylyl cyclase 2, phospholipase C-β3, potassium channels, and β-adrenergic receptor kinase as well as inhibition of calmodulin-stimulated adenylyl cyclases, but had no effect on interactions between Gβγ and Gα
o
. Substitutions in this peptide identified a functionally important motif, Gln-X-X-Glu-Arg, that is also conserved in regions of potassium channels and β-adrenergic receptor kinases that participate in Gβγ interactions. Thus, the region defined by residues 956 to 982 of adenylyl cyclase 2 may contain determinants important for receiving signals from Gβγ.
Crystal Structure of the T4 regA Translational Regulator Protein at 1.9 Å Resolution
Authors: Kang ChulHee , Chan Rodney , Berger Imre , Lockshin Curtis , Green Louis , Gold Larry , Rich Alexander
Published: October 2006

The translational regulator protein regA is encoded by the T4 bacteriophage and binds to a region of messenger RNA (mRNA) that includes the initiator codon. RegA is unusual in that it represses the translation of about 35 early T4 mRNAs but does not affect nearly 200 other mRNAs. The crystal structure of regA was determined at 1.9 Å resolution; the protein was shown to have an α-helical core and two regions with antiparallel β sheets. One of these β sheets has four antiparallel strands and has some sequence homology to RNP-1 and RNP-2, which are believed to be RNA-binding motifs and are found in a number of known RNA-binding proteins. Structurally guided mutants may help to uncover the basis for this variety of RNA interaction.
Distinct Binding Specificities and Functions of Higher Eukaryotic Polypyrimidine Tract-Binding Proteins
Authors: Singh Ravinder , Valcárcel J , Green Michael R.
Published: October 2006

In higher eukaryotes, the polypyrimidine-tract (Py-tract) adjacent to the 3′ splice site is recognized by several proteins, including the essential splicing factor U2AF
65
, the splicing regulator Sex-lethal (Sxl), and polypyrimidine tract-binding protein (PTB), whose function is unknown. Iterative in vitro genetic selection was used to show that these proteins have distinct sequence preferences. The uridine-rich degenerate sequences selected by U2AF
65
are similar to those present in the diverse array of natural metazoan Py-tracts. In contrast, the Sxl-consensus is a highly specific sequence, which can help explain the ability of Sxl to regulate splicing of
transformer
pre-mRNA and autoregulate splicing of its own pre-mRNA. The PTB-consensus is not a typical Py-tract; it can be found in certain alternatively spliced pre-mRNAs that undergo negative regulation. Here it is shown that PTB can regulate alternative splicing by selectively repressing 3′ splice sites that contain a PTB-binding site.
Inducible Gene Expression in Trypanosomes Mediated by a Prokaryotic Repressor
Authors: Wirtz Elizabeth , Clayton Christine
Published: October 2006

An inducible expression system was developed for the protozoan parasite
Trypanosoma brucei
. Transgenic trypanosomes expressing the tetracycline repressor of
Escherichia coli
exhibited inducer (tetracycline)-dependent expression of chromosomally integrated reporter genes under the control of a procyclic acidic repetitive protein (PARP) promoter bearing a
tet
operator. Reporter expression could be controlled over a range of four orders of magnitude in response to tetracycline concentration, a degree of regulation that exceeds those exhibited by other eukaryotic repression-based systems. The tet repressor-controlled PARP promoter should be a valuable tool for the study of trypanosome biochemistry, pathogenicity, and cell and molecular biology.
Cardiac Function in Mice Overexpressing the β-Adrenergic Receptor Kinase or a βARK Inhibitor
Authors: Koch Walter J. , Rockman Howard A. , Samama Philippe , Hamilton RaeAnn , Bond Richard A. , Milano Carmelo A. , Lefkowitz Robert J.
Published: October 2006

Transgenic mice were created with cardiac-specific overexpression of the β-adrenergic receptor kinase-1 (βARK1) or a βARK inhibitor. Animals overexpressing βARK1 demonstrated attenuation of isoproterenol-stimulated left ventricular contractility in vivo, dampening of myocardial adenylyl cyclase activity, and reduced functional coupling of β-adrenergic receptors. Conversely, mice expressing the βARK inhibitor displayed enhanced cardiac contractility in vivo with or without isoproterenol. These animals demonstrate the important role of βARK in modulating in vivo myocardial function. Because increased amounts of βARK1 and diminished cardiac β-adrenergic responsiveness characterize heart failure, these animals may provide experimental models to study the role of βARK in heart disease.
Sensorimotor Encoding by Synchronous Neural Ensemble Activity at Multiple Levels of the Somatosensory System
Authors: Nicolelis Miguel A. L. , Baccala Luiz A. , Lin Rick C. S. , Chapin John K.
Published: October 2006

Neural ensemble processing of sensorimotor information during behavior was investigated by simultaneously recording up to 48 single neurons at multiple relays of the rat trigeminal somatosensory system. Cortical, thalamic, and brainstem neurons exhibited widespread 7- to 12-hertz synchronous oscillations, which began during attentive immobility and reliably predicted the imminent onset of rhythmic whisker twitching. Each oscillatory cycle began as a traveling wave of neural activity in the cortex that then spread to the thalamus. Just before the onset of rhythmic whisker twitching, the oscillations spread to the spinal trigeminal brainstem complex. Thereafter, the oscillations at all levels were synchronous with whisker protraction. Neural structures manifesting these rhythms also exhibited distributed spatiotemporal patterns of neuronal ensemble activity in response to tactile stimulation. Thus, multilevel synchronous activity in this system may encode not only sensory information but also the onset and temporal domain of tactile exploratory movements.
Stable Transfection of Malaria Parasite Blood Stages
Authors: van Dijk M. R. , Waters A. P. , Janse C. J.
Published: October 2006

Genetic manipulation of malaria parasites would revolutionize the study of this group of pathogens and have implications for vaccine and drug development. This report describes the stable, drug-selectable genetic transformation of the clinically relevant intracellular blood stages of a malaria parasite. A plasmid transfection vector carrying the gene locus that encodes a drug-resistant form of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase from the rodent malaria parasite
Plasmodium berghei
was constructed. Derivatives of this vector were introduced into merozoites of
P. berghei
by electroporation, and parasites were selected for successful transformation in the rodent host on the basis of resistance to pyrimethamine. The plasmids were present in a circular, unrearranged form that replicated episomally to an observed maximum of 15 copies per cell in drug-resistant populations.
Progesterone Synthesis and Myelin Formation by Schwann Cells
Authors: Koenig Herbert L. , Schumacher Michael , Ferzaz Badia , Thi Anh N. Do , Ressouches Annie , Guennoun Rachida , Jung-Testas Ingrid , Robel Paul , Akwa Yvette , Baulieu Etienne-Emile
Published: October 2006

Progesterone is shown here to be produced from pregnenolone by Schwann cells in peripheral nerves. After cryolesion of the sciatic nerve in male mice, axons regenerate and become myelinated. Blocking either the local synthesis or the receptor-mediated action of progesterone impaired remyelination. Administration of progesterone or its precursor, pregnenolone, to the lesion site increased the extent of myelin sheath formation. Myelination of axons was also increased when progesterone was added to cultures of rat dorsal root ganglia. These observations indicate a role for locally produced progesterone in myelination, demonstrate that progesterone is not simply a sex steroid, and suggest a new therapeutic approach to promote myelin repair.
Extreme Discordant Sib Pairs for Mapping Quantitative Trait Loci in Humans
Authors: Risch Neil , Zhang Heping
Published: October 2006

Analysis of differences between siblings (sib pair analysis) is a standard method of genetic linkage analysis for mapping quantitative trait loci, such as those contributing to hypertension and obesity, in humans. In traditional designs, pairs are selected at random or with one sib having an extreme trait value. The majority of such pairs provide little power to detect linkage; only pairs that are concordant for high values, low values, or extremely discordant pairs (for example, one in the top 10 percent and the other in the bottom 10 percent of the distribution) provide substantial power. Focus on discordant pairs can reduce the amount of genotyping necessary over conventional designs by 10- to 40-fold.
Identification of a Stimulator of Steroid Hormone Synthesis Isolated from Testis
Authors: Boujrad Noureddine , Ogwuegbu Stephen O. , Garnier Martine , Lee Choong-Hyun , Martin Brian M. , Papadopoulos Vassilios
Published: October 2006

Gonadal steroidogenesis is regulated by pituitary gonadotropins and a locally produced, unidentified factor. A 70-kilodalton (kD) protein complex secreted from rat Sertoli cells was isolated. The complex, composed of 28- and 38-kD proteins, stimulated steroidogenesis by Leydig cells and ovarian granulosa cells in a dose-dependent and adenosine 3′,5′-monophosphate-independent manner. The follicle-stimulating hormone-induced 28-kD protein appeared to be responsible for the bioactivity, but the 38-kD protein was indispensable for maximal activity. The 28- and 38-kD proteins were shown to be identical to the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the proenzyme form of cathepsin L, respectively. Thus, a TIMP-1-procathepsin L complex is a potent activator of steroidogenesis and may regulate steroid concentrations and, thus, germ cell development in both males and females.