bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmed Cell Death and the Control of Cell Survival: Lessons from the Nervous System
Authors: Raff Martin C. , Barres Barbara A. , Burne Julia F. , Coles Harriet S. , Ishizaki Yasuki , Jacobson Michael D.
Published: October 2006

During the development of the vertebrate nervous system, up to 50 percent or more of many types of neurons normally die soon after they form synaptic connections with their target cells. This massive cell death is thought to reflect the failure of these neurons to obtain adequate amounts of specific neurotrophic factors that are produced by the target cells and that are required for the neurons to survive. This neurotrophic strategy for the regulation of neuronal numbers may be only one example of a general mechanism that helps to regulate the numbers of many other vertebrate cell types, which also require signals from other cells to survive. These survival signals seem to act by suppressing an intrinsic cell suicide program, the protein components of which are apparently expressed constitutively in most cell types.
Alterations of a Zinc Finger-Encoding Gene,
BCL-6
, in Diffuse Large-Cell Lymphoma
Authors: Ye Bihui H. , Lista Florigio , Lo Coco Francesco , Knowles Daniel M. , Offit Kenneth , Chaganti R. S. K. , Dalla-Favera Riccardo
Published: October 2006

The molecular pathogenesis of diffuse large-cell lymphoma (DLCL), the most frequent and clinically relevant type of lymphoma, is unknown. A gene was cloned from chromosomal translocations affecting band 3q27, which are common in DLCL. This gene,
BCL-6
, codes for a 79-kilodalton protein that is homologous with zinc finger-transcription factors. In 33 percent (13 of 39) of DLCL samples, but not in other types of lymphoid malignancies, the
BCL-6
gene is truncated within its 5′ noncoding sequences, suggesting that its expression is deregulated. Thus,
BCL-6
may be a proto-oncogene specifically involved in the pathogenesis of DLCL.
A Switch Between Two-, Three-, and Four-stranded Coiled Coils in GCN4 Leucine Zipper Mutants
Authors: Harbury Pehr B. , Zhang Tao , Kim Peter S. , Alber Tom
Published: October 2006

Coiled-coil sequences in proteins consist of heptad repeats containing two characteristic hydrophobic positions. The role of these buried hydrophobic residues in determining the structures of coiled coils was investigated by studying mutants of the GCN4 leucine zipper. When sets of buried residues were altered, two-, three-, and four-helix structures were formed. The x-ray crystal structure of the tetramer revealed a parallel, four-stranded coiled coil. In the tetramer conformation, the local packing geometry of the two hydrophobic positions in the heptad repeat is reversed relative to that in the dimer. These studies demonstrate that conserved, buried residues in the GCN4 leucine zipper direct dimer formation. In contrast to proposals that the pattern of hydrophobic and polar amino acids in a protein sequence is sufficient to determine three-dimensional structure, the shapes of buried side chains in coiled coils are essential determinants of the global fold.
Photoactivated Conformational Changes in Rhodopsin: A Time-Resolved Spin Label Study
Authors: Farahbakhsh Zohreh Toossi , Hideg Kálmán , Hubbell Wayne L.
Published: October 2006

Rhodopsin has been selectively spin-labeled near the cytoplasmic termini of helices C and G. Photoactivation with a light flash induces an electron paramagnetic resonance spectral change in the millisecond time domain, coincident with the appearance of the active metarhodopsin II intermediate. The spectral change is consistent with a small movement near the cytoplasmic termination of the C helix and reverses upon formation of the MIII state. These results provide an important link between the optical changes associated with the retinal chromophore and protein conformational states.
The Influence of Antigen Organization on B Cell Responsiveness
Authors: Bachmann Martin F. , Rohrer Urs Hoffmann , Kündig Thomas M. , Bürki Kurt , Hengartner Hans , Zinkernagel Rolf M.
Published: October 2006

The influence of antigen epitope density and order on B cell induction and antibody production was assessed with the glycoprotein of vesicular stomatitis virus serotype Indiana [VSV-G (IND)]. VSV-G (IND) can be found in a highly repetitive form in the envelope of VSV-IND and in a poorly organized form on the surface of infected cells. In VSV-G (IND) transgenic mice, B cells were unresponsive to the poorly organized VSV-G (IND) present as self antigen but responded promptly to the same antigen presented in the highly organized form. Thus, antigen organization influences B cell tolerance.
Visualization of Single Molecules of RNA Polymerase Sliding Along DNA
Authors: Kabata Hiroyuki , Kurosawa Osamu , Arai Ichiro , Washizu Masao , Margarson Stefanie A. , Glass Robert E. , Shimamoto Nobuo
Published: October 2006

Transcription requires that RNA polymerase binds to promoters buried in nonspecific sites on DNA. The search for promoters may be facilitated if the polymerase slides along the molecule of DNA. Single molecules of
Escherichia coli
RNA polymerase were visualized, and their movements on immobilized bacteriophage λ and T7 DNAs were examined. Deviating from drifts by bulk flow, about 40 percent of the enzyme molecules moved along the extended DNA. The results provide direct evidence for sliding as a mechanism for relocation of the enzyme on DNA.
Protein Design by Binary Patterning of Polar and Nonpolar Amino Acids
Authors: Kamtekar Satwik , Schiffer Jarad M. , Xiong Huayu , Babik Jennifer M. , Hecht Michael H.
Published: October 2006

A general strategy is described for the de novo design of proteins. In this strategy the sequence locations of hydrophobic and hydrophilic residues were specified explicitly, but the precise identities of the side chains were not constrained and varied extensively. This strategy was tested by constructing a large collection of synthetic genes whose protein products were designed to fold into four-helix bundle proteins. Each gene encoded a different amino acid sequence, but all sequences shared the same pattern of polar and nonpolar residues. Characterization of the expressed proteins indicated that most of the designed sequences folded into compact α-helical structures. Thus, a simple binary code of polar and nonpolar residues arranged in the appropriate order can drive polypeptide chains to collapse into globular α-helical folds.
Mutations that Allow Disulfide Bond Formation in the Cytoplasm of
Escherichia coli
Authors: Derman Alan I. , Prinz William A. , Belin Dominique , Beckwith Jon
Published: October 2006

Disulfide bonds are rarely found in cytoplasmic proteins. Mutations were selected for in
Escherichia coli
that allow disulfide bond formation in the cytoplasm. In the presence of these mutations, export-defective versions of alkaline phosphatase and mouse urokinase were able to fold into their enzymatically active conformations in the cytoplasm because their disulfide bonds were formed. The mutations were mapped to the gene for thioredoxin reductase and diminish or eliminate the activity of this enzyme. Thioredoxin itself was found to be unnecessary for this disulfide bond formation. Thioredoxin reductase, but not thioredoxin, is thus implicated in keeping cysteines reduced in cytoplasmic proteins.
Yeast Origin Recognition Complex Functions in Transcription Silencing and DNA Replication
Authors: Bell Stephen P. , Kobayashi Ryuji , Stillman Bruce
Published: October 2006

The genes encoding two of the subunits of the
Saccharomyces cerevisiae
origin recognition complex (ORC) have been isolated. Characterization of a temperature-sensitive mutation in the gene encoding the 72-kD subunit of ORC (
ORC2
) indicates that this protein complex functions early in the DNA replication process. Moreover, ORC derived from

orc2
ts

cells is defective for DNA binding. Others have shown a defect in

orc2
ts

cells in transcriptional silencing at the silent mating-type loci. Consistent with this finding, ORC specifically binds to each of the four mating-type silencers identified in yeast. These findings support the hypothesis that ORC acts as an initiator protein at yeast origins of DNA replication and suggest that ORC also functions in the determination of transcriptional domains.
Isolation of
ORC6
, a Component of the Yeast Origin Recognition Complex by a One-Hybrid System
Authors: Li Joachim J. , Herskowitz Ira
Published: October 2006

Here a method is described to identify genes encoding proteins that recognize a specific DNA sequence. A bank of random protein segments tagged with a transcriptional activation domain is screened for proteins that can activate a reporter gene containing the sequence in its promoter. This strategy was used to identify an essential protein that interacts in vivo with the yeast origin of DNA replication. Matches between its predicted amino acid sequence and peptide sequence obtained from the 50-kilodalton subunit of the yeast origin recognition complex (ORC) established that the gene isolated here,
ORC6
, encodes this subunit. These observations provide evidence that ORC recognizes yeast replication origins in vivo.
Sharing of the Interleukin-2 (IL-2) Receptor γ Chain Between Receptors for IL-2 and IL-4
Authors: Kondo Motonari , Takeshita Toshikazu , Ishii Naoto , Nakamura Masataka , Watanabe Sumiko , Arai Ken-ichi , Sugamura Kazuo
Published: October 2006

The γ chain of the interleukin-2 (IL-2) receptor is an indispensable subunit for IL-2 binding and intracellular signal transduction. A monoclonal antibody to the γ chain, TUGm2, inhibited IL-2 binding to the functional IL-2 receptors and also inhibited IL-4-induced cell growth and the high-affinity binding of IL-4 to the CTLL-2 mouse T cell line. Another monoclonal antibody, TUGm3, which reacted with the γ chain cross-linked with IL-2, also immunoprecipitated the γ chain when cross-linked with IL-4. These results suggest that the IL-2 receptor γ chain is functionally involved in the IL-4 receptor complex.
Separate GTP Binding and GTPase Activating Domains of a Gα Subunit
Authors: Markby David W. , Onrust René , Bourne Henry R.
Published: October 2006

Most members of the guanosine triphosphatase (GTPase) superfamily hydrolyze guanosine triphosphate (GTP) quite slowly unless stimulated by a GTPase activating protein or GAP. The α subunits (Gα) of the heterotrimeric G proteins hydrolyze GTP much more rapidly and contain an ∼120-residue insert not found in other GTPases. Interactions between a Gα insert domain and a Gα GTP-binding core domain, both expressed as recombinant proteins, show that the insert acts biochemically as a GAP. The results suggest a general mechanism for GAP-dependent hydrolysis of GTP by other GTPases.
The U5 and U6 Small Nuclear RNAs as Active Site Components of the Spliceosome
Authors: Sontheimer Erik J. , Steitz Joan A.
Published: October 2006

Five small nuclear RNAs (U1, U2, U4, U5, and U6) participate in precursor messenger RNA (pre-mRNA) splicing. To probe their interactions within the active center of the mammalian spliceosome, substrates containing a single photoactivatable 4-thiouridine residue adjacent to either splice site were synthesized, and crosslinks were induced during the course of in vitro splicing. An invariant loop sequence in U5 small nuclear RNA contacts exon 1 before and after the first step of splicing because a crosslink between U5 and the last residue of exon 1 appeared in the pre-mRNA and then in the cutoff exon 1 intermediate. Both of these crosslinked species could undergo subsequent splicing, indicating that the crosslinks reflect a functional interaction that is maintained through both reaction steps. The same U5 loop aligns the two exons for ligation since the first residue of exon 2 also became crosslinked to U5 in the lariat intermediate. An invariant sequence in U6 RNA became crosslinked to the conserved second position of the intron within both the lariat intermediate and the lariat intron product. On the basis of these results, several conformational arrangements of small nuclear RNAs within the spliceosomal active center can be distinguished, and additional mechanistic parallels between the spliceosome and self-splicing introns can be drawn.
Peptide Translocation by Variants of the Transporter Associated with Antigen Processing
Authors: Heemels Marie-Thérèse , Schumacher Ton N. M. , Wonigeit Kurt , Ploegh Hidde L.
Published: October 2006

Major histocompatibility complex (MHC) class I molecules associate with peptides that are delivered from the cytosol to the lumen of the endoplasmic reticulum by the transporter associated with antigen processing (TAP). Liver microsomes of SHR and Lewis rats, which express different alleles of TAP (
cim
b
and
cim
a
, respectively), accumulate different sets of peptides. Use of MHC congenic rats assigned this difference to the MHC, independent of the class I products expressed. Both the
cim
a
and
cim
b
TAP complexes translocate peptides with a hydrophobic carboxyl terminus, but translocation of peptides with a carboxyl-terminal His, Lys, or Arg residue is unique to
cim
a
. Thus, the specificity of the TAP peptide translocator restricts the peptides available for antigen presentation.
Rational Design of Potent, Bioavailable, Nonpeptide Cyclic Ureas as HIV Protease Inhibitors
Authors: Lam Patrick Y. S. , Jadhav Prabhakar K. , Eyermann Charles J. , Hodge C. Nicholas , Ru Yu , Bacheler Lee T. , Meek James L. , Otto Michael J. , Rayner Marlene M. , Wong Y. Nancy , Chang Chong-Hwan , Weber Patricia C. , Jackson David A. , Sharpe Thomas R. , Erickson-Viitanen Susan
Published: October 2006

Mechanistic information and structure-based design methods have been used to design a series of nonpeptide cyclic ureas that are potent inhibitors of human immunodeficiency virus (HIV) protease and HIV replication. A fundamental feature of these inhibitors is the cyclic urea carbonyl oxygen that mimics the hydrogen-bonding features of a key structural water molecule. The success of the design in both displacing and mimicking the structural water molecule was confirmed by x-ray crystallographic studies. Highly selective, preorganized inhibitors with relatively low molecular weight and high oral bioavailability were synthesized.
Hybrid Cricket Auditory Behavior: Evidence for Genetic Coupling in Animal Communication
Authors: Hoy Ronald R. , Hahn Janet , Paul Robert C.
Published: October 2006

Male field crickets produce species-specific and stereotyped calling songs. Conspecific females are attracted to the call. Reciprocal F
1
hybrid females prefer the calls of sibling hybrids to reciprocal hybrids. Discrimination is probably based on temporal pattern and not carrier frequency of the call. The results imply that production of song by males and its detection by females have a common genetic basis.
Selective and ATP-Dependent Translocation of Peptides by the MHC-Encoded Transporter
Authors: Neefjes Jacques J. , Momburg Frank , Hämmerling Günter J.
Published: October 2006

Major histocompatibility complex (MHC) class I molecules present peptides derived from nuclear and cytosolic proteins to CD8
+
T cells. These peptides are translocated into the lumen of the endoplasmic reticulum (ER) to associate with class I molecules. Two MHC-encoded putative transporter proteins, TAP1 and TAP2, are required for efficient assembly of class I molecules and presentation of endogenous peptides. Expression of TAP1 and TAP2 in a mutant cell line resulted in the delivery of an 11-amino acid oligomer model peptide to the ER. Peptide translocation depended on the sequence of the peptide, was adenosine triphosphate (ATP)-dependent, required ATP hydrolysis, and was inhibited in a concentration-dependent manner.
Reconstitution of T Cell Receptor ζ-Mediated Calcium Mobilization in Nonlymphoid Cells
Authors: Hall Craig G. , Sancho Jaime , Terhorst Cox
Published: October 2006

T cell antigen receptor (TCR) activation involves interactions between receptor subunits and nonreceptor protein tyrosine kinases (PTKs). Early steps in signaling through the ζ chain of the TCR were examined in transfected COS-1 cells. Coexpression of the PTK p59

fynT

, but not p56

lck

, with ζ or with a homodimeric TCRβ-ζ fusion protein produced tyrosine phosphorylation of both ζ and phospholipase C (PLC)-γ1, as well as calcium ion mobilization in response to receptor cross-linking. CD45 coexpression enhanced these effects. No requirement for the PTKZAP-70 was observed. Thus, p59

fynT

may link ζ directly to the PLC-γ1 activation pathway.
Lack of N Regions in Antigen Receptor Variable Region Genes of TdT-Deficient Lymphocytes
Authors: Komori Toshihisa , Okada Ami , Stewart Valerie , Alt Frederick W.
Published: October 2006

During the assembly of immunoglobulin and T cell receptor variable region genes from variable (V), diversity (D), and joining (J) segments, the germline-encoded repertoire is further diversified by processes that include the template-independent addition of nucleotides (N regions) at gene segment junctions. Terminal deoxynucleotidyl transferase (TdT)-deficient lymphocytes had no N regions in their variable region genes, which shows that TdT is responsible for N region addition. In addition, certain variable region genes appeared at increased frequency in TdT-deficient thymocytes, which indicates that N region addition also influences repertoire development by alleviating sequence-specific constraints imposed on the joining of particular V, D, and J segments.
GABA-Activated Chloride Channels in Secretory Nerve Endings
Authors: Zhang Shuanglin J. , Jackson Meyer B.
Published: October 2006

Neurotransmitters acting on presynaptic terminals regulate synaptic transmission and plasticity. Because of the difficulty of direct electrophysiological recording from small presynaptic terminals, little is known about the ion channels that mediate these actions or about the mechanisms by which transmitter secretion is altered. The patch-clamp technique is used to show that the predominant inhibitory presynaptic neurotransmitter, γ-aminobutyric acid (GABA), activates a GABA
A
receptor and gates a chloride channel in the membranes of peptidergic nerve terminals of the posterior pituitary. The opening of a chloride channel by GABA weakly depolarizes the nerve terminal membrane and blocks action potentials. In this way, GABA limits secretion by retarding the spread of excitation into the terminal arborization.
β-Adrenergic Receptor Kinase-2 and β-Arrestin-2 as Mediators of Odorant-Induced Desensitization
Authors: Dawson Ted M. , Arriza Jeffrey L. , Jaworsky Donna E. , Borisy Felice F. , Attramadal Håvard , Lefkowitz Robert J. , Ronnett Gabriele V.
Published: October 2006

β-Adrenergic receptor kinase (βARK) and β-arrestin function in the homologous or agonist-activated desensitization of G protein-coupled receptors. The isoforms βARK-2 and β-arrestin-2 are highly enriched in and localized to the dendritic knobs and cilia of the olfactory receptor neurons where the initial events of olfactory signal transduction occur. Odorants induce a rapid and transient elevation of adenosine 3′,5′-monophosphate (cAMP), which activates a nonspecific cation channel and produces membrane depolarization. Preincubation of rat olfactory cilia with antibodies raised against βARK-2 and β-arrestin-2 increased the odorant-induced elevation of cAMP and attenuated desensitization. These results suggest that βARK-2 and β-arrestin-2 mediate agonist-dependent desensitization in olfaction.
An Adenovirus Vector for Gene Transfer into Neurons and Glia in the Brain
Authors: La Salle G. Le Gal , Robert J. J. , Berrard S. , Ridoux V. , Stratford-Perricaudet L. D. , Perricaudet M. , Mallet J.
Published: October 2006

The efficient introduction of genetic material into quiescent nerve cells is important in the study of brain function and for gene therapy of neurological disorders. A replication-deficient adenoviral vector that contained a reporter gene encoding β-galactosidase infected rat nerve cells in vitro and in vivo. β-Galactosidase was expressed in almost all sympathetic neurons and astrocytes in culture. After stereotactic inoculations into the rat hippocampus and the substantia nigra, β-galactosidase activity was detected for 2 months. Infected cells were identified as microglial cells, astrocytes, or neurons with anatomical, morphological, and immunohistochemical criteria. No obvious cytopathic effect was observed.
Increased Frequency of Calcium Waves in
Xenopus laevis
Oocytes that Express a Calcium-ATPase
Authors: Camacho Patricia , Lechleiter James D.
Published: October 2006

When inositol 1,4,5-trisphosphate (IP
3
) receptors are activated, calcium is released from intracellular stores in excitatory propagating waves that annihilate each other upon collision. The annihilation phenomenon suggests the presence of an underlying refractory period that controls excitability. Enhanced calcium-adenosine triphosphatase (ATPase) activity might alter the refractory period of calcium release. Expression of messenger RNA encoding the avian calcium-ATPase (SERCA1) in
Xenopus laevis
oocytes increased the frequency of IP
3
-induced calcium waves and narrowed the width of individual calcium waves. The effect of SERCA1 expression on calcium wave frequency was dependent on the concentration of IP
3
and was larger at higher (1 μM) than at lower (0.1 μM) concentrations of IP
3
. The results demonstrate that calcium pump activity can control IP
3
-mediated calcium signaling.
Neuroprotective Effects of Glutamate Antagonists and Extracellular Acidity
Authors: Kaku David A. , Giffard Rona G. , Choi Dennis W.
Published: October 2006

Glutamate antagonists protect neurons from hypoxic injury both in vivo and in vitro, but in vitro studies have not been done under the acidic conditions typical of hypoxia-ischemia in vivo. Consistent with glutamate receptor antagonism, extracellular acidity reduced neuronal death in murine cortical cultures that were deprived of oxygen and glucose. Under these acid conditions,
N
-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-kainate antagonists further reduced neuronal death, such that some neurons tolerated prolonged oxygen and glucose deprivation almost as well as did astrocytes. Neuroprotection induced by this combination exceeded that induced by glutamate antagonists alone, suggesting that extracellular acidity has beneficial effects beyond the attenuation of ionotropic glutamate receptor activation.
Conditioned Narcotic Withdrawal in Humans
Authors: O'Brien Charles P. , Testa Thomas , O'Brien Thomas J. , Brady John Paul , Wells Barbara
Published: October 2006

Subjective and physiological manifestations of the narcotic withdrawal syndrome were produced as a conditioned response. Withdrawal reactions precipitated by the narcotic antagonist naloxone in methadone-dependent volunteers were the unconditioned response. These data support clinical anecdotes of withdrawal symptoms occurring in former addicts when they return to their drug-related environment.
Fat-Containing Uterine Smooth Muscle Cells in "Toxemia": Possible Relevance to Atherosclerosis?
Authors: Haust M. Daria , Las Heras Jorge , Harding Paul G.
Published: October 2006

Uterine smooth muscle cells in "toxemia of pregnancy" contain varying amounts of fat—a feature to date believed to characterize only the arterial smooth muscle cells in atherosclerotic lesions. Thus, the smooth muscle cells at these two sites do not differ essentially in their reactivity to certain forms of injury: hypoxia may represent an injurious factor common to both "toxemia" and atherosclerosis. These observations imply that the view that the arterial smooth muscle cells are biologically different than are those elsewhere may no longer be tenable.
Characterization of a New Human Diploid Cell Strain, IMR-90
Authors: Nichols W. W. , Murphy D. G. , Cristofalo V. J. , Toji L. H. , Greene A. E. , Dwight S. A.
Published: October 2006

A new human diploid fibroblast-like cell line has been established from lung tissue of a female fetus. This has been frozen away in large quantity and characterized for use in research and related purposes. This is the first of a planned series of human cell lines to be established, characterized, and banked in large quantity in support of the National Institute on Aging research and general cell biology.
N
-Nitrosodiethanolamine in Synthetic Cutting Fluids: A Part-Per-Hundred Impurity
Authors: Fan Tsai Y. , Morrison John , Rounbehler David P. , Ross Ronald , Fine David H. , Miles Walter , Sen N. P.
Published: October 2006

N
-nitrosodiethanolamine has been found to be present at a concentration of 0.02 to 3 percent in several brands of synthetic cutting fluids. Its identity was confirmed by three independent techniques: (i) by measuring the retention times on two different high-performance liquid-chromatography columns, (ii) by dehydration to
N
-nitrosomorpholine, and (iii) by preparation of the
O
-methyl ether derivative.
Cyclic ADP-Ribose in Insulin Secretion from Pancreatic βCells
Authors: Takasawa Shin , Nata Koji , Yonekura Hideto , Okamoto Hiroshi
Published: October 2006

Inositol 1,4,5-trisphosphate (IP
3
) is thought to be a second messenger for intracellular calcium mobilization. However, in a cell-free system of islet microsomes, cyclic adenosine diphosphate-ribose (cADP-ribose), a nicotinamide adenine dinucleotide (NAD
+
) metabolite, but not IP
3
, induced calcium release. In digitonin-permeabilized islets, cADP-ribose and calcium, but not IP
3
, induced insulin secretion. Islet microsomes released calcium when combined with the extract from intact islets that had been incubated with high concentrations of glucose. Sequential additions of cADP-ribose inhibited the calcium release response to extracts from islets treated with high concentrations of glucose. Conversely, repeated additions of the islet extract inhibited the calcium release response to a subsequent addition of cADP-ribose. These results suggest that cADP-ribose is a mediator of calcium release from islet microsomes and may be generated in islets by glucose stimulation, serving as a second messenger for calcium mobilization in the endoplasmic reticulum.
Higher Level Organization of Individual Gene Transcription and RNA Splicing
Authors: Xing Yigong , Johnson Carol V. , Dobner Paul R. , Lawrence Jeanne Bentley
Published: October 2006

Visualization of fibronectin and neurotensin messenger RNAs within mammalian interphase nuclei was achieved by fluorescence hybridization with genomic, complementary DNA, and intron-specific probes. Unspliced transcripts accumulated in one or two sites per nucleus. Fibronectin RNA frequently accumulated in elongated tracks that overlapped and extended well beyond the site of transcription. Splicing appears to occur directly within this RNA track, as evidenced by an unambiguous spatial separation of intron-containing and spliced transcripts. Excised introns for neurotensin RNA appear free to diffuse. The transcription and processing site of the fibronectin gene localized to the nuclear interior and was associated with larger transcript domains in over 88 percent of the cells. These results support a view of nuclear function closely integrated with structure.
Ancient Conserved Regions in New Gene Sequences and the Protein Databases
Authors: Green Philip , Lipman David , Hillier LaDeana , Waterston Robert , States David , Claverie Jean-Michel
Published: October 2006

Sets of new gene sequences from human, nematode, and yeast were compared with each other and with a set of
Escherichia coli
genes in order to detect ancient evolutionarily conserved regions (ACRs) in the encoded proteins. Nearly all of the ACRs so identified were found to be homologous to sequences in the protein databases. This suggests that currently known proteins may already include representatives of most ACRs and that new sequences not similar to any database sequence are unlikely to contain ACRs. Preliminary analyses indicate that moderately expressed genes may be more likely to contain ACRs than rarely expressed genes. It is estimated that there are fewer than 900 ACRs in all.
Molecular Mechanism of Transcription-Repair Coupling
Authors: Selby Christopher P. , Sancar Aziz
Published: October 2006

Lesions in the transcribed strand block transcription and are repaired more rapidly than lesions in the nontranscribed (coding) strand which do not block RNA polymerase (RNAP). It has been shown previously that in
Escherichia coli
the
mfd
(mutation frequency decline) gene is necessary for strand-specific repair. The
mfd
gene was cloned and sequenced and the Mfd protein was purified and used to reconstitute strand-specific repair in a completely defined system. The
mfd
gene encodes a protein of 130 kilodaltons and contains the so-called "helicase motifs," a leucine zipper motif, and regions of sequence similarity to UvrB and RecG proteins. The Mfd protein was shown to (i) displace RNAP stalled at a lesion in an adenosine triphosphate-dependent reaction, (ii) bind to the damage recognition subunit (UvrA) of the excision nuclease, and (iii) stimulate the repair of the transcribed strand only when transcription is taking place. Thus, Mfd appears to target the transcribed strand for repair by recognizing a stalled RNAP and actively recruiting the repair enzyme to the transcription blocking lesion as it dissociates the stalled RNAP.
Electrostatic Screening of Charge and Dipole Interactions with the Helix Backbone
Authors: Lockhart David J. , Kim Peter S.
Published: October 2006

Electrostatic interactions in proteins are potentially quite strong, but these interactions are mitigated by the screening effects of water, ions, and nearby protein atoms. The early work of Kirkwood and Westheimer on small organic molecules showed that the extent of the screening may depend on whether charged or dipolar groups are involved. The dielectric and ionic screening of the interactions between the dipolar backbone amide groups of monomeric α helices and either (i) solvent-exposed charges or (ii) solvent-exposed dipoles at the amino terminus was measured. The dielectric screening effects are an order of magnitude greater for the backbone-charge interactions than for the backbone-dipole interactions, and the ionic strength dependence is substantially different in the two cases. These results suggest that interactions that involve the dipolar groups of proteins may be relatively more important for stability and function than is generally thought.
Tyrosine Kinase-Stimulated Guanine Nucleotide Exchange Activity of Vav in T Cell Activation
Authors: Gulbins Erich , Coggeshall K. Mark , Baier Gottfried , Katzav Shulamit , Burn Paul , Altman Amnon
Published: October 2006

The hematopoietically expressed product of the
vav
proto-oncogene, Vav, shares homology with guanine nucleotide releasing factors (GRFs) [also called guanosine diphosphate-dissociation stimulators (GDSs)] that activate Ras-related small guanosine triphosphate (GTP)-binding proteins. Human T cell lysates or Vav immunoprecipitates possessed GRF activity that increased after T cell antigen receptor (TCR)-CD3 triggering; an in vitro-translated Vav fragment that contained the putative GRF domain was also active. Vav-associated GRF stimulation after TCR-CD3 ligation paralleled its tyrosine phosphorylation; both were blocked by a protein tyrosine kinase (PTK) inhibitor. Vav also was a substrate for the p56

lck

PTK. Thus, Vav is a PTK-regulated GRF that may be important in TCR-CD3-initiated signal transduction through the activation of Ras.
Localization of a Memory Trace in the Mammalian Brain
Authors: Krupa David J. , Thompson Judith K. , Thompson Richard F.
Published: October 2006

The localization of sites of memory formation within the brain has proven to be a formidable task even for simple forms of learning and memory. In order to localize a particular site of memory formation within the brain, the rabbit eyeblink response was classically conditioned while regions of the cerebellum or red nucleus were temporarily inactivated by microinfusions of the γ-aminobutyric acid agonist muscimol. Cerebellar inactivation completely blocked learning but had no effect on subsequent learning after inactivation, whereas red nucleus inactivation did not prevent learning but did block the expression of conditioned responses. The site of memory formation for this learned response thus appears to be localized within the cerebellum.
Identification of the von Hippel-Lindau Disease Tumor Suppressor Gene
Authors: Latif Farida , Tory Kalman , Gnarra James , Yao Masahiro , Duh Fuh-Mei , Orcutt Mary Lou , Stackhouse Thomas , Kuzmin Igor , Modi William , Geil Laura , Schmidt Laura , Zhou Fangwei , Li Hua , Wei Ming Hui , Chen Fan , Glenn Gladys , Choyke Peter , Walther McClellan M. , Weng Yongkai , Duan Dah-Shuhn R. , Dean Michael , Glavač Damjan , Richards Frances M. , Crossey Paul A. , Ferguson-Smith Malcolm A. , Le Paslier Denis , Chumakov llya , Cohen Daniel , Chinault A. Craig , Maher Eamonn R. , Linehan W. Marston , Zbar Berton , Lerman Michael I.
Published: October 2006

A gene discovered by positional cloning has been identified as the von Hippel-Lindau (VHL) disease tumor suppressor gene. A restriction fragment encompassing the gene showed rearrangements in 28 of 221 VHL kindreds. Eighteen of these rearrangements were due to deletions in the candidate gene, including three large nonoverlapping deletions. Intragenic mutations were detected in cell lines derived from VHL patients and from sporadic renal cell carcinomas. The VHL gene is evolutionarily conserved and encodes two widely expressed transcripts of approximately 6 and 6.5 kilobases. The partial sequence of the inferred gene product shows no homology to other proteins, except for an acidic repeat domain found in the procyclic surface membrane glycoprotein of
Trypanosoma brucei
.
High Spontaneous Intrachromosomal Recombination Rates in Ataxia-Telangiectasia
Authors: Meyn M. Stephen
Published: October 2006

Ataxia-telangiectasia (A-T) is an inherited human disease associated with neurologic degeneration, immune dysfunction, and high cancer risk. It has been proposed that the underlying abnormality in A-T is a defect in genetic recombination that interferes with immune gene rearrangements and the repair of DNA damage. Recombination was studied in A-T and control human fibroblast lines by means of two recombination vectors. Unexpectedly, spontaneous intrachromosomal recombination rates were 30 to 200 times higher in A-T fibroblast lines than in normal cells, whereas extrachromosomal recombination frequencies were near normal. Increased recombination is thus a component of genetic instability in A-T and may contribute to the cancer risk seen in A-T patients.
Divergence in Proteins, Mitochondrial DNA, and Reproductive Compatibility Across the Isthmus of Panama
Authors: Knowlton Nancy , Weigt Lee A. , Solórzano Luis Aníbal , Mills DeEtta K. , Bermingham Eldredge
Published: October 2006

It is widely believed that gene flow connected many shallow water populations of the Caribbean and eastern Pacific until the Panama seaway closed 3.0 to 3.5 million years ago. Measurements of biochemical and reproductive divergence for seven closely related, transisthmian pairs of snapping shrimps (
Alpheus
) indicate, however, that isolation was staggered rather than simultaneous. The four least divergent pairs provide the best estimate for rates of molecular divergence and speciation. Ecological, genetic, and geological data suggest that gene flow was disrupted for the remaining three pairs by environmental change several million years before the land barrier was complete.
Echo-Detecting Characteristics of Neurons in Inferior Colliculus of Unanesthetized Bats
Authors: Pollak George , Marsh David , Bodenhamer Robert , Souther Arthur
Published: October 2006

Neurons in the inferior colliculus of echolocating bats responded well to two stimuli presented in close temporal sequence. Favorable recovery of responsiveness was seen with stimuli having durations, intensities, and interpulse intervals similar to the natural biosonar signals reaching the ears during the various phases of echolocation. Some units responded to a subthreshold simulated echo but only when preceded by a loud initial pulse. These units appear to be specialized for echo-detection.
Lithium Ion Entry Through the Sodium Channel of Cultured Mouse Neuroblastoma Cells: A Biochemical Study
Authors: Richelson Elliott
Published: October 2006

Lithium ion entry at low concentrations (1 to 5 mM) into an electrically active adrenergic clone of mouse neuroblastoma cells was stimulated by veratridine; and this stimulation was blocked by tetrodotoxin, These data provide biochemical evidence that lithium ions enter by way of the sodium channel which may be a major pathway for entry of this ion into electrically active cells.
Bombesin: Potent Effects on Thermoregulation in the Rat
Authors: Brown Marvin , Rivier Jean , Vale Wylie
Published: October 2006

Several vasoactive peptides administered intracisternally have been assessed for the effect of lowering the core temperature of rats exposed to cold. Peptides structurally related to neurotensin lower core temperature while those related to substance P do not. The tetradecapeptide bombesin, originally isolated from the extracts of the skin of the frog
Bombina bombina
, is 10
4
times more potent than neurotensin in lowering core temperature, with a minimal effective dose less than or equal to 1 nanogram per 200 grams of body weight. Thus bombesin is one of the most potent peptides reported to affect the central nervous system.
Infrared Reflectance in Leaf-Sitting Neotropical Frogs
Authors: Schwalm Patricia A. , Starrett Priscilla H. , McDiarmid Roy W.
Published: October 2006

Two members of the glass-frog family Centrolenidae (
Centrolenella fleischmanni
,
C. prosoblepon
) and the hylid subfamily Phyllomedusinae (
Agalychnis moreletii
,
Pachymedusa dacnicolor
) reflect near-infrared light (700 to 900 nanometers) when examined by infrared color photography. Infrared reflectance may confer adaptive advantage to these arboreal frogs both in thermoregulation and infrared cryptic coloration.
Suppression of Sympathetic Nervous System During Fasting
Authors: Young James B. , Landsberg Lewis
Published: October 2006

Two days of fasting in rats significantly reduces the turnover of norepinephrine in the heart. In contrast to the effects of ganglionic blockade in fed controls, similar blockade in fasted animals is without significant effect on [3H]-norepinephrine retention or endogenous norepinephrine in the heart. These data are consistent with suppression of centrally mediated sympathetic activity in the fasted state. The decrease in norepinephrine turnover during fasting is completely reversed by 1 day of refeeding.
Ammonia in the Human Airways: Neutralization of Inspired Acid Sulfate Aerosols
Authors: Larson Timothy V. , Covert David S. , Frank Robert , Charlson Robert J.
Published: October 2006

In the human being, expired ammonia concentrations from 7 to 520 micrograms per cubic meter are controlled by the last airway segment traversed by the air, and such concentrations are higher in the mouth than nose. Inspired submicrometric sulfuric acid aerosol at a mass concentration of 600 ± 100 micrograms per cubic meter was found to be an ammonium salt with an average ammonium to sulfate molar ratio of ≥1, when sampled within 0.5 second after exhalation.
Fatty Acids and Their Prostaglandin Derivatives: Inhibitors of Proliferation in Aortic Smooth Muscle Cells
Authors: Huttner J. J. , Gwebu E. T. , Panganamala R. V. , Milo G. E. , Cornwell D. G. , Sharma H. M. , Geer J. C.
Published: October 2006

Prostaglandins are synthesized from eicosa-8,11,14-trienoic acid and eicosa-5,8,11,14-tetraenoic acid by smooth muscle cell cultures from guinea pig aorta. Production is inhibited by indomethacin. The precursor fatty acids and their prostaglandin derivatives inhibit proliferation of the cell cultures. The relative availability of fatty acids for prostaglandin biosynthesis may represent a control mechanism for cell proliferation.
Dopamine Receptor Binding Enhancement Accompanies Lesion-Induced Behavioral Supersensitivity
Authors: Creese Ian , Burt David R. , Snyder Solomon H.
Published: October 2006

The binding of [
3
H]haloperidol to rat striatal dopamine receptors increases after lesion (made by injection of 6-hydroxydopamine) of the nigrostriatal dopamine pathway in those rats which are behaviorally supersensitive, as reflected by apomorphine-induced contralateral rotations. The enhanced binding is associated with an increased number of receptor sites with no change in their affinity.
Structure of a Molluscan Cardioexcitatory Neuropeptide
Authors: Price David A. , Greenberg Michael J.
Published: October 2006

A cardioexcitatory substance from ganglia of the clam Macrocallista nimbosa, formerly designated peak C, is the tetrapeptide amide Phe-Met-Arg-Phe-NH
2
. Its structure was determined by the combined use of Edman dansyl degradation and tryptic digestion. The structure was confirmed by synthesis. This neuropeptide is active at about 10
-8
M
when assayed on molluscan muscle.
Neurogenesis in the Adult Rat: Electron Microscopic Analysis of Light Radioautographs
Authors: Kaplan Michael S. , Hinds James W.
Published: October 2006

Three-month-old rats were injected intraperitoneally with [
3
H]thymidine (4.3 microcuries per gram of body weight) and allowed to survive for 30 days. Radioautography of 1-μm sections revealed labeled cells in the granular layers of dentate gyrus and olfactory bulb; these were confirmed as neurons by electron microscopy of reembedded 1-μm sections.
Phototoxic Keratoconjunctivitis from Coal-Tar Pitch Volatiles
Authors: Emmett Edward A. , Stetzer Lloyd , Taphorn Barbara
Published: October 2006

Roofers working with coal-tar pitch develop burning eyes and conjunctivitis which they subjectively associate with sun exposure. A coal-tar pitch distillate instilled in the conjunctivae of rabbits produced minimal or mild irritation in the absence of ultraviolet radiation, but irradiation with long-ultraviolet produced marked photophobia and severe keratoconjunctivitis.
Eye Contact and Face Scanning in Early Infancy
Authors: Haith Marshall M. , Bergman Terry , Moore Michael J.
Published: October 2006

Visual fixations of 3- to 5-week-old, 7-week-old, and 9- to 11-week-old infants were recorded as they scanned an adult's face which was stationary, moving, or talking. A dramatic increase in face fixations occurred between 5 and 7 weeks for all conditions. Talking produced an intensification of scanning in the eye area in the two older groups.
Mapping the Locus of the
H-Y
Gene on the Human Y Chromosome
Authors: Koo Gloria C. , Wachtel Stephen S. , Krupen-Brown Karen , Mittl Lillian R. , Breg W. Roy , Genel Myron , Rosenthal Ira M. , Borgaonkar Digamber S. , Miller Dorothy A. , Tantravahi Ramana , Schreck Rhona R. , Erlanger Bernard F. , Miller Orlando J.
Published: October 2006

The
H-Y
locus is on the short arm of the human Y chromosome in most individuals but on the long arm in at least one of 17 individuals with structural abnormalities of the Y.
Cross-Linking of DNA in Situ as a Probe for Chromatin Structure
Authors: Hanson Carl Veith , Shen Che-kun , Hearst John E.
Published: October 2006

The photochemical cross-linking of DNA in situ in chromatin is blocked over short intervals. Electron microscopy of DNA cross-linked in chromatin reveals the lengths of protected regions and provides a map of their sites along the DNA. Protected regions occur most frequently in tandem and have a basic length of 160 to 200 base pairs.
Abolition of Direction Selectivity in the Visual Cortex of the Cat
Authors: Cynader Max , Chernenko Garry
Published: October 2006

Cats were reared in a stroboscopically illuminated environment, which deprived them of experience with visual movement but allowed them form vision. In these cats, neurons of the visual cortex displayed normal orientation selectivity, but direction selectivity was virtually abolished. The effect remained unaltered by long periods of normal visual exposure.
Fertilization of Sea Urchins Needs Magnesium Ions in Seawater
Authors: Sano Kiyoshi , Mohri Hideo
Published: October 2006

When sea urchin eggs were inseminated in seawater free of magnesium, the fertilization rate was very low. Spermatozoa that had been treated with egg jelly to induce the acrosome reaction also failed to fertilize eggs in seawater free of magnesium. These results indicate that magnesium is indispensable for some process or processes at fertilization, such as membrane fusion or sperm penetration.
Orientation Anisotropy: Incidence and Magnitude in Caucasian and Chinese Subjects
Authors: Timney B. N. , Muir D. W.
Published: October 2006

Cutoff spatial frequencies for sine-wave gratings were measured at four orientations for 100 Caucasian and 24 Chinese subjects, all of whom were raised in carpentered environments. For the Caucasian subjects, average acuity for horizontal and vertical gratings was superior to that for obliques by about one-quarter of an octave. However, about 10 percent of subjects failed to show the effect. The Chinese subjects showed an anisotropy of about one-eighth of an octave. The carpentered environment explanation of orientation anisotropy cannot, in its present form, account for the wide variety of response patterns obtained, nor the differences between Chinese and Caucasian subjects.
Extended Helical Conformation Newly Observed in Protein Folding
Authors: Srinivasan R. , Balasubramanian R. , Rajan S. S.
Published: October 2006

A new secondary structure, which shows regularity within the experimental error, is noticed in α-chymotrypsin, and considering its extended nature, the name ε-helix has been suggested for the same. The average observed values of φ and ψ for this conformation are -93° and +146°, respectively. The helical parameters turn out to be
n
= -2.7 and
h
= 3.3 angstroms.
Stereochemical Requirements for Intercalation of Platinum Complexes into Double-Stranded DNA's
Authors: Lippard Stephen J. , Bond Peter J. , Wu Kun C. , Bauer William R.
Published: October 2006

The complexes 1,10-phenanthrolineethylenediamineplatinum(II) and 2,2′-bipyridineethylenediamineplatinum(II) have a planar, aromatic ligand system that facilitates intercalation, as shown by their ability to unwind closed circular duplex DNA. Nonbonded steric interactions can rotate the pyridine ligands out of the coordination plane in bis(pyridine)ethylenediamineplatinum(II), thus preventing intercalation. Fiber x-ray diffraction patterns of the two metallointercalators indicate that the binding is governed by the neighbor exclusion principle.
Hypoxanthine-Guanine Phosphoribosyltransferase Mutant Glioma Cells: Diminished Monoamine Oxidase Activity
Authors: Skaper Stephen D. , Seegmiller J. Edwin
Published: October 2006

A defective capability of cultured rat glioma cells to reutilize purine bases (hypoxanthine-guanine phosphoribosyltransferase deficiency) was associated with a reduced capacity to oxidatively deaminate serotonin and tryptamine. The mutant glioma cells were also more sensitive to the cytotoxic effects of serotonin than were normal cells.
How do respiratory state and measurement method affect bra size calculations?
Authors: McGhee D E , Steele J R
Published: October 2006

Objectives:To investigate the effects of respiratory state and measurement method on bra size calculation.

Methods:The bra sizes of 16 large-breasted women were measured during two respiratory states, end voluntary inspiration and relaxed voluntary expiration, and using two sizing methods, which were compared against subject-reported bra sizes.

Results:Both respiratory state and measurement method significantly affected bra size estimations, whereby measuring chest circumference during inspiration increased both band and decreased cup size. However, whereas bra size calculated using the standard method differed significantly from subject-reported bra size, cup size calculated using the breast hemi-circumference method did not differ significantly from subject-reported cup size.

Conclusions:As respiratory state significantly affects bra sizes, it should be standardised during bra size measurements. A more valid and reliable bra sizing method should be developed, possibly using the breast hemi-circumference method for cup size estimations and raw under-bust chest circumference values for band size.