bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Decreases in Atrial Natriuretic Peptide and Salt-Sensitive Hypertension
Authors: John Simon W. M. , Krege John H. , Oliver Paula M. , Hagaman John R. , Hodgin Jeffrey B. , Pang Stephen C. , Flynn T. Geoffrey , Smithies Oliver
Published: October 2006

To determine if defects in the atrial natriuretic peptide (ANP) system can cause hypertension, mice were generated with a disruption of the
proANP
gene. Homozygous mutants had no circulating or atrial ANP, and their blood pressures were elevated by 8 to 23 millimeters of mercury when they were fed standard (0.5 percent sodium chloride) and intermediate (2 percent sodium chloride) salt diets. On standard salt diets, heterozygotes had normal amounts of circulating ANP and normal blood pressures. However, on high (8 percent sodium chloride) salt diets they were hypertensive, with blood pressures elevated by 27 millimeters of mercury. These results demonstrate that genetically reduced production of ANP can lead to salt-sensitive hypertension.
Association Between X-Linked Mixed Deafness and Mutations in the POU Domain Gene
POU3F4
Authors: de Kok Yvette J. M. , van der Maarel Silvère M. , Bitner-Glindzicz Maria , Huber Irene , Monaco Anthony P. , Malcolm Susan , Pembrey Marcus E. , Ropers Hans-Hilger , Cremers Frans P. M.
Published: October 2006

Deafness with fixation of the stapes (DFN3) is the most frequent X-linked form of hearing impairment. The underlying gene has been localized to a 500-kilobase segment of the Xq21 band. Here, it is reported that a candidate gene for this disorder,
Brain 4
(
POU3F4
), which encodes a transcription factor with a POU domain, maps to the same interval. In five unrelated patients with DFN3 but not in 50 normal controls, small mutations were found that result in truncation of the predicted protein or in nonconservative amino acid substitutions. These findings indicate that
POU3F4
mutations are a molecular cause of DFN3.
Requirement of MADS Domain Transcription Factor D-MEF2 for Muscle Formation in
Drosophila
Authors: Lilly Brenda , Zhao Bin , Ranganayakulu Gogineni , Paterson Bruce M. , Schulz Robert A. , Olson Eric N.
Published: October 2006

Members of the myocyte enhancer binding factor-2 (MEF2) family of MADS (MCM1, agamous, deficiens, and serum response factor) box transcription factors are expressed in the skeletal, cardiac, and smooth muscle lineages of vertebrate and
Drosophila
embryos. These factors bind an adenine-thymidine-rich DNA sequence associated with muscle-specific genes. The function of MEF2 was determined by generating a loss-of-function of the single
mef2
gene in
Drosophila
(
D-mef2
). In loss-of-function embryos, somatic, cardiac, and visceral muscle cells did not differentiate, but myoblasts were normally specified and positioned. These results demonstrate that different muscle cell types share a common myogenic differentiation program controlled by MEF2.
Potentiation of Transmitter Release by Ciliary Neurotrophic Factor Requires Somatic Signaling
Authors: Stoop Ron , Poo Mu-Ming
Published: October 2006

Neurotrophic factors participate in the development and maintenance of the nervous system. Application of ciliary neurotrophic factor (CNTF), a protein that promotes survival of motor neurons, resulted in an immediate potentiation of spontaneous and impulse-evoked transmitter release at developing neuromuscular synapses in
Xenopus
cell cultures. When CNTF was applied at the synapse, the onset of the potentiation was slower than that produced by application at the cell body of the presynaptic neuron. The potentiation effect was abolished when the neurite shaft was severed from the cell body. Thus, transmitter secretion from the nerve terminals is under immediate somatic control and can be regulated by CNTF.
In Vivo Evidence of Structural Brain Asymmetry in Musicians
Authors: Schlaug Gottfried , Jäncke Lutz , Huang Yanxiong , Steinmetz Helmuth
Published: October 2006

Certain human talents, such as musical ability, have been associated with left-right differences in brain structure and function. In vivo magnetic resonance morphometry of the brain in musicians was used to measure the anatomical asymmetry of the planum temporale, a brain area containing auditory association cortex and previously shown to be a marker of structural and functional asymmetry. Musicians with perfect pitch revealed stronger leftward planum temporale asymmetry than nonmusicians or musicians without perfect pitch. The results indicate that outstanding musical ability is associated with increased leftward asymmetry of cortex subserving music-related functions.
High Sex Ratios in China's Future
Authors: Tuljapurkar Shripad , Li Nan , Feldman Marcus W.
Published: October 2006

In China in recent years, male live births have exceeded those of females by amounts far greater than those that occur naturally in human populations, a trend with significant demographic consequences. The resulting imbalance in the first-marriage market is estimated to be about 1 million males per year after 2010. These "excess" males were not easily accommodated in models with substantial changes in first-marriage patterns. The current sex ratio at birth has little effect on a couple's probability of having at least one son, so future increases in the sex ratio may well occur, especially given increasing access to sex-selective abortion.
Casein Kinase IIα Transgene-Induced Murine Lymphoma: Relation to Theileriosis in Cattle
Authors: Seldin David C. , Leder Philip
Published: October 2006

Infection of cattle with the protozoan parasite
Theileria parva
results in a fatal lymphoproliferative syndrome that is associated with the overexpression of casein kinase II. The role of this enzyme in the pathogenesis of lymphoproliferative disorders was investigated by expressing the catalytic subunit in lymphocytes of transgenic mice. Adult transgenic mice displayed a stochastic propensity to develop lymphoma; co-expression of a c-
myc
transgene in addition to casein kinase II resulted in neonatal leukemia. Thus, the casein kinase II gene can serve as an oncogene, and its dysregulated expression is capable of transforming lymphocytes in a two-step pathway with c-
myc
.
Selfish Behavior of Restriction-Modification Systems
Authors: Naito Taku , Kusano Kohji , Kobayashi Ichizo
Published: October 2006

Plasmids carrying gene pairs encoding type II DNA restriction endonucleases and their cognate modification enzymes were shown to have increased stability in
Escherichia coli
. The descendants of cells that had lost these genes appeared unable to modify a sufficient number of recognition sites in their chromosomes to protect them from lethal attack by the remaining restriction enzyme molecules. The capacity of these genes to act as a selfish symbiont is likely to have contributed to the evolution of restriction-modification gene pairs.
Head-On Collision Between a DNA Replication Apparatus and RNA Polymerase Transcription Complex
Authors: Liu Bin , Alberts Bruce M.
Published: October 2006

An in vitro system reconstituted from purified proteins has been used to examine what happens when the DNA replication apparatus of bacteriophage T4 collides with an
Escherichia coli
RNA polymerase ternary transcription complex that is poised to move in the direction opposite to that of the moving replication fork. In the absence of a DNA helicase, the replication fork stalls for many minutes after its encounter with the RNA polymerase. However, when the T4 gene 41 DNA helicase is present, the replication fork passes the RNA polymerase after a pause of a few seconds. This brief pause is longer than the pause observed for a codirectional collision between the same two polymerases, suggesting that there is an inherent disadvantage to having replication and transcription directions oriented head to head. As for a codirectional collision, the RNA polymerase remains competent to resume faithful RNA chain elongation after the DNA replication fork passes; most strikingly, the RNA polymerase has switched from its original template strand to use the newly synthesized daughter DNA strand as the template.
A Role for Exonuclease I from
S. pombe
in Mutation Avoidance and Mismatch Correction
Authors: Szankasi Philippe , Smith Gerald R.
Published: October 2006

Exonuclease I (Exo I) from
Schizosaccharomyces pombe
, a 5′→3′ double-stranded DNA exonuclease, is induced during meiotic prophase I. The
exo1
gene is a member of a family of related DNA repair genes, including
RAD2/rad13/xpgc
and
YKL510/rad2
, conserved from yeast to humans. An
exo1
mutant displays a mutator phenotype and alters activity of the
ade6-M387
marker effect. These results suggest that Exo I acts in a pathway that corrects mismatched base pairs.
Peptide Specificity in the Recognition of MHC Class I by Natural Killer Cell Clones
Authors: Malnati Mauro S. , Peruzzi Marta , Parker Kenneth C. , Biddison William E. , Ciccone Ermanno , Moretta Alessandro , Long Eric O.
Published: October 2006

Recognition by natural killer (NK) cells of major histocompatibility complex (MHC) class I molecules on target cells inhibits NK-mediated lysis. Here, inhibition of NK clones by HLA-B*2705 molecules mutated at single amino acids in the peptide binding site varied among HLA-B*2705-specific NK clones. In addition, a subset of such NK clones was inhibited by only one of several self peptides loaded onto HLA-B*2705 molecules expressed in peptide transporter-deficient cells, showing that recognition was peptide-specific. These data demonstrate that specific self peptides, complexed with MHC class I, provide protection from NK-mediated lysis.
Collision of Comet Shoemaker-Levy 9 with Jupiter Observed by the NASA Infrared Telescope Facility
Authors: Orton G. , A'Hearn M. , Baines K. , Deming D. , Dowling T. , Goguen J. , Griffith C. , Hammel H. , Hoffmann W. , Hunten D. , Jewitt D. , Kostiuk T. , Miller S. , Noll K. , Zahnle K. , Achilleos N. , Dayal A. , Deutsch L. , Espenak F. , Esterle P. , Friedson J. , Fast K. , Harrington J. , Hora J. , Joseph R. , Kelly D. , Knacke R. , Lacy J. , Lisse C. , Rayner J. , Sprague A. , Shure M. , Wells K. , Yanamandra-Fisher P. , Zipoy D. , Bjoraker G. , BuhI D. , Golisch W. , Griep D. , Kaminski C. , Arden C. , Chaikin A. , Goldstein J. , Gilmore D. , Fazio G. , Kanamori T. , Lam H. , Livengood T. , MacLow M.-M. , Marley M. , Momary T. , Robertson D. , Romani P. , Spitale J. , Sykes M. , Tennyson J. , Wellnitz D. , Ying S.-W.
Published: October 2006

The National Aeronautics and Space Administration (NASA) Infrared Telescope Facility was used to investigate the collision of comet Shoemaker-Levy 9 with Jupiter from 12 July to 7 August 1994. Strong thermal infrared emission lasting several minutes was observed after the impacts of fragments C, G, and R. All impacts warmed the stratosphere and some the troposphere up to several degrees. The abundance of stratospheric ammonia increased by more than 50 times. Impact-related particles extended up to a level where the atmospheric pressure measured several millibars. The north polar near-infrared aurora brightened by nearly a factor of 5 a week after the impacts.
The Neuron-Restrictive Silencer Factor (NRSF): A Coordinate Repressor of Multiple Neuron-Specific Genes
Authors: Schoenherr Christopher J. , Anderson David J.
Published: October 2006

The neuron-restrictive silencer factor (NRSF) binds a DNA sequence element, called the neuron-restrictive silencer element (NRSE), that represses neuronal gene transcription in nonneuronal cells. Consensus NRSEs have been identified in 18 neuron-specific genes. Complementary DNA clones encoding a functional fragment of NRSF were isolated and found to encode a novel protein containing eight noncanonical zinc fingers. Expression of NRSF mRNA was detected in most nonneuronal tissues at several developmental stages. In the nervous system, NRSF mRNA was detected in undifferentiated neuronal progenitors, but not in differentiated neurons. NRSF represents the first example of a vertebrate silencer protein that potentially regulates a large battery of cell type-specific genes, and therefore may function as a master negative regulator of neurogenesis.
Glutamate Receptor RNA Editing in Vitro by Enzymatic Conversion of Adenosine to Inosine
Authors: Rueter Susan M. , Burns Colleen M. , Coode Sarah A. , Mookherjee Paramita , Emeson Ronald B.
Published: October 2006

RNA encoding the B subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptor (GluR-B) undergoes a posttranscriptional modification in which a genomically encoded adenosine is represented as a guanosine in the GluR-B complementary DNA. In vitro editing of GluR-B RNA transcripts with HeLa cell nuclear extracts was found to result from an activity that converts adenosine to inosine in regions of double-stranded RNA by enzymatic base modification. This activity is consistent with that of a double-stranded RNA-specific adenosine deaminase previously described in
Xenopus
oocytes and widely distributed in mammalian tissues.
Pineal Opsin: a Nonvisual Opsin Expressed in Chick Pineal
Authors: Max Marianna , McKinnon Peter J. , Seidenman Kenneth J. , Barrett R. Keith , Applebury Meredithe L. , Takahashi Joseph S. , Margolskee Robert F.
Published: October 2006

Pineal opsin (P-opsin), an opsin from chick that is highly expressed in pineal but is not detectable in retina, was cloned by the polymerase chain reaction. It is likely that the P-opsin lineage diverged from the retinal opsins early in opsin evolution. The amino acid sequence of P-opsin is 42 to 46 percent identical to that of the retinal opsins. P-opsin is a seven-membrane spanning, G protein-linked receptor with a Schiff-base lysine in the seventh membrane span and a Schiff-base counterion in the third membrane span. The primary sequence of P-opsin suggests that it will be maximally sensitive to ∼500-nanometer light and produce a slow and prolonged phototransduction response consistent with the nonvisual function of pineal photoreception.
Evidence from 18
S
Ribosomal DNA that the Lophophorates Are Protostome Animals
Authors: Halanych Kenneth M. , Bacheller John D. , Aguinaldo Anna Marie A. , Liva Stephanie M. , Hillis David M. , Lake James A.
Published: October 2006

The suspension-feeding metazoan subkingdom Lophophorata exhibits characteristics of both deuterostomes and protostomes. Because the morphology and embryology of lophophorates are phylogenetically ambiguous, their origin is a major unsolved problem of metazoan phylogenetics. The complete 18
S
ribosomal DNA sequences of all three lophophorate phyla were obtained and analyzed to clarify the phylogenetic relationships of this subkingdom. Sequence analyses show that lophophorates are protostomes closely related to mollusks and annelids. This conclusion deviates from the commonly held view of deuterostome affinity.
Sodefrin: a Female-Attracting Peptide Pheromone in Newt Cloacal Glands
Authors: Kikuyama S. , Toyoda F. , Ohmiya Y. , Matsuda K. , Tanaka S. , Hayashi H.
Published: October 2006

A decapeptide called sodefrin was isolated from the abdominal gland of the cloaca of the male red-bellied newt,
Cynops pyrrhogaster
. The native peptide, as well as the synthetic one, had a female-attracting activity. Sodefrin was found in the apical portion of the epithelial cells of the abdominal gland. Sodefrin is apparently species specific because it did not attract females of
Cynops ensicauda
. This is the first amphibian pheromone to be identified and the first peptide pheromone identified in a vertebrate.
Epithelial Antibiotics Induced at Sites of Inflammation
Authors: Schonwetter Barry S. , Stolzenberg Ethan D. , Zasloff Michael A.
Published: October 2006

The role of antimicrobial peptides in epithelial defense is not fully understood. An epithelial β-defensin, lingual antimicrobial peptide (LAP), was isolated from bovine tongue and the corresponding complementary DNA cloned. LAP showed a broad spectrum of antibacterial and antifungal activities. LAP messenger RNA abundance was markedly increased in the epithelium surrounding naturally occurring tongue lesions. This increase coincided with the cellular hallmarks of acute and chronic inflammation in the underlying lamina propria, supporting a role for epithelial antimicrobial peptides as integral components of the inflammatory response.
Inhibition of Ocular Dominance Column Formation by Infusion of NT-4/5 or BDNF
Authors: Cabelli Robert J. , Hohn Andreas , Shatz Carla J.
Published: October 2006

During the development of the visual system of higher mammals, axons from the lateral geniculate nucleus (LGN) become segregated into eye-specific patches (the ocular dominance columns) within their target, layer 4 of the primary visual cortex. This occurs as a consequence of activity-dependent synaptic competition between axons representing the two eyes. The possibility that this competition could be mediated through neurotrophin-receptor interactions was tested. Infusion of neurotrophin-4/5 (NT-4/5) or brain-derived neurotrophic factor (BDNF) into cat primary visual cortex inhibited column formation within the immediate vicinity of the infusion site but not elsewhere in the visual cortex. Infusion of nerve growth factor, neurotrophin 3 (NT-3), or vehicle solution did not affect column formation. These observations implicate TrkB, the common receptor for BDNF and NT-4/5, in the segregation of LGN axons into ocular dominance columns in layer 4. Moreover, they suggest that in addition to their better known roles in the prevention of cell death, neurotrophins may also mediate the activity-dependent control of axonal branching during development of the central nervous system.
Tyrosine Kinase Inhibition: An Approach to Drug Development
Authors: Levitzki Alexander , Gazit Aviv
Published: October 2006

Protein tyrosine kinases (PTKs) regulate cell proliferation, cell differentiation, and signaling processes in the cells of the immune system. Uncontrolled signaling from receptor tyrosine kinases and intracellular tyrosine kinases can lead to inflammatory responses and to diseases such as cancer, atherosclerosis, and psoriasis. Thus, inhibitors that block the activity of tyrosine kinases and the signaling pathways they activate may provide a useful basis for drug development. This article summarizes recent progress in the development of PTK inhibitors and demonstrates their potential use in the treatment of disease.
Demonstration of Positionally Disordered Water Within a Protein Hydrophobic Cavity by NMR
Authors: Ernst James A. , Clubb Robert T. , Zhou Huan-Xiang , Gronenborn Angela M. , Clore G. Marius
Published: October 2006

The presence and location of water of hydration (that is, bound water) in the solution structure of human interleukin-1β (hIL-1β) was investigated with water-selective two-dimensional heteronuclear magnetic resonance spectroscopy. It is shown here that in addition to water at the surface of the protein and ordered internal water molecules involved in bridging hydrogen bonds, positionally disordered water is present within a large, naturally occurring hydrophobic cavity located at the center of the molecule. These water molecules of hydration have residency times in the range of 1 to 2 nanoseconds to 100 to 200 microseconds and can be readily detected by nuclear magnetic resonance (NMR). Thus, large hydrophobic cavities in proteins may not be truly empty, as analysis of crystal structures appears to show, but may contain mobile water molecules that are crystallographically invisible but detectable by NMR.
Pathogenicity of Live, Attenuated SIV After Mucosal Infection of Neonatal Macaques
Authors: Baba Timothy W. , Jeong Yong Seok , Pennick Dominique , Bronson Rod , Greene Michael F. , Ruprecht Ruth M.
Published: October 2006

Adult macaques do not develop disease after infection with a
nef
deletion mutant of the simian immunodeficiency virus (SIV) and are protected against challenge with pathogenic virus. This finding led to the proposal to use
nef
-deleted viruses as live, attenuated vaccines to prevent human acquired immunodeficiency syndrome (AIDS). In contrast, neonatal macaques developed persistently high levels of viremia after oral exposure to an SIV
nef
,
vpr
, and negative regulatory element (NRE) deletion mutant. Severe hemolytic anemia, thrombocytopenia, and CD4
+
T cell depletion were observed, indicating that neither
nef
nor
vpr
determine pathogenicity in neonates. Because such constructs have retained their pathogenic potential, they should not be used as candidate live, attenuated virus vaccines against human AIDS.
Cardiac Malformation in Neonatal Mice Lacking Connexin43
Authors: Reaume Andrew G. , de Sousa Paul A. , Kulkarni Sarang , Langille B. Lowell , Zhu Daguang , Davies Tyler C. , Juneja Subhash C. , Kidder Gerald M. , Rossant Janet
Published: October 2006

Gap junctions are made up of connexin proteins, which comprise a multigene family in mammals. Targeted mutagenesis of connexin43 (Cx43), one of the most prevalent connexin proteins, showed that its absence was compatible with survival of mouse embryos to term, even though mutant cell lines showed reduced dye coupling in vitro. However, mutant embryos died at birth, as a result of a failure in pulmonary gas exchange caused by a swelling and blockage of the right ventricular outflow tract from the heart. This finding suggests that Cx43 plays an essential role in heart development but that there is functional compensation among connexins in other parts of the developing fetus.
Pseudovascular adenoid squamous-cell carcinoma of the oral cavity—a report of two cases
Authors: Zidar N , Gale N , Z̆upevc A , Dovšak D
Published: October 2006

Informed consent was obtained for the publication of the patients’ details in this report. Two cases of pseudovascular adenoid squamous-cell carcinoma (SCC) in the oral cavity are described, which were characterised by acantholysis of the tumour cells, with formation of anastomosing spaces and channels mimicking an angiosarcoma. Both tumours contained foci of SCC suggesting the correct diagnosis: in one patient conventional SCC, and in the other, a spindle-cell carcinoma.

The pathogenesis of pseudovascular adenoid SCC is unknown. Our cases were characterised by loss of immunohistochemical expression of E-cadherin, one of the major adhesion molecules of epithelial cells. Pseudovascular adenoid SCC is suggested to be pathogenetically related to the loss of E-cadherin expression, leading to the loss of tumour cell–cell adhesion.
Dedifferentiated chondrosarcoma with telangiectatic osteosarcoma-like features
Authors: Okada K , Hasegawa T , Tateishi U , Endo M , Itoi E
Published: October 2006

A 35-year-old Japanese man was admitted to the National Cancer Center, Tokyo, Japan, in December 2000, with a 2-month history of pain around the left thigh. Radiographs showed a poorly demarcated osteolytic lesion with focal mineralisation and endosteal scalloping in the left proximal femur. Biopsy showed a proliferation of highly anaplastic cells without any cartilaginous component. A wide excision of the left proximal femur with a replacement by endoprosthesis was carried out in February 2001 after treatment with methotrexate and 20 Gy radiation therapy. Pathological examination of the surgical specimen showed a focus of low-grade chondrosarcoma and the coexistence of telangiectatic osteosarcoma-like features. The patient was diagnosed with dedifferentiated chondrosarcoma with telangiectatic osteosarcoma-like features. Lung metastasis appeared in July 2001 despite an adjuvant chemotherapy including methotrexate,cis-platinum and doxorubicin. The latest follow-up study in June 2004 showed multiple lung metastases. Establishing a definitive diagnosis of dedifferentiated chondrosarcoma may be difficult with limited small biopsy specimens. Dedifferentiated chondrosarcoma should be included in the differential diagnosis of osteolytic tumours with focal calcification and endosteal scalloping even if an extraosseous tumour component is not identified.
Alveolar soft-part sarcoma: a review and update
Authors: Folpe A L , Deyrup A T
Published: October 2006

Alveolar soft-part sarcoma (ASPS) is a rare, distinctive sarcoma, typically occurring in young patients. Although it displays a relatively indolent clinical course, the ultimate prognosis is poor and is often characterised by late metastases. Recently, our understanding of the genetic events underlying the pathogenesis of ASPS has greatly increased. The historical, histopathological, ultrastructural, immunohistochemical and genetic aspects of ASPS are reviewed in this article.
RECENT RESULTS ON THERMAL CASIMIR FORCE BETWEEN DIELECTRICS AND RELATED PROBLEMS
Authors: GEYER B. , KLIMCHITSKAYA G. L. , MOSTEPANENKO V. M.
Published: October 2006

We review recent results obtained in the physics of the thermal Casimir force acting between two dielectrics, dielectric and metal, and between metal and semiconductor. The detailed derivation for the low-temperature behavior of the Casimir free energy, pressure and entropy in the configuration of two real dielectric plates is presented. For dielectrics with finite static dielectric permittivity it is shown that the Nernst heat theorem is satisfied. Hence, the Lifshitz theory of the van der Waals and Casimir forces is demonstrated to be consistent with thermodynamics. The nonzero dc conductivity of dielectric plates is proved to lead to a violation of the Nernst heat theorem and, thus, is not related to the phenomenon of dispersion forces. The low-temperature asymptotics of the Casimir free energy, pressure and entropy are derived also in the configuration of one metal and one dielectric plate. The results are shown to be consistent with thermodynamics if the dielectric plate possesses a finite static dielectric permittivity. If the dc conductivity of a dielectric plate is taken into account this results in the violation of the Nernst heat theorem. We discuss both the experimental and theoretical results related to the Casimir interaction between metal and semiconductor with different charge carrier density. Discussions in the literature on the possible influence of spatial dispersion on the thermal Casimir force are analyzed. In conclusion, the conventional Lifshitz theory taking into account only the frequency dispersion remains the reliable foundation for the interpretation of all present experiments.
CHARGE ORBITS OF SYMMETRIC SPECIAL GEOMETRIES AND ATTRACTORS
Authors: BELLUCCI STEFANO , FERRARA SERGIO , GÜNAYDIN MURAT , MARRANI ALESSIO
Published: October 2006

We study the critical points of the black hole scalar potential V BH in N = 2, d = 4 supergravity coupled to nV vector multiplets, in an asymptotically flat extremal black hole background described by a 2(nV+1)-dimensional dyonic charge vector and (complex) scalar fields which are coordinates of a special Kähler manifold.

For the case of homogeneous symmetric spaces, we find three general classes of regular attractor solutions with nonvanishing Bekenstein–Hawking entropy. They correspond to three (inequivalent) classes of orbits of the charge vector, which is in a 2(nV+1)-dimensional representation RV of the U-duality group. Such orbits are nondegenerate, namely they have nonvanishing quartic invariant (for rank-3 spaces). Other than the ½-BPS one, there are two other distinct non-BPS classes of charge orbits, one of which has vanishing central charge.

The three species of solutions to the N = 2 extremal black hole attractor equations give rise to different mass spectra of the scalar fluctuations, whose pattern can be inferred by using invariance properties of the critical points of V BH and some group theoretical considerations on homogeneous symmetric special Kähler geometry.
A. K. RAYCHAUDHURI AND HIS EQUATION
Authors: EHLERS J.
Published: October 2006

Amal Kumar Raychaudhuri died on June 18, 2005. This essay follows the lecture which was given in honor of this great Indian scientist and teacher on December 26, 2005 in Puri, India.
GRAVITY: A NEW HOLOGRAPHIC PERSPECTIVE
Authors: PADMANABHAN T.
Published: October 2006

A general paradigm for describing classical (and semiclassical) gravity is presented. This approach brings to the center-stage a holographic relationship between the bulk and surface terms in a general class of action functionals and provides a deeper insight into several aspects of classical gravity which have no explanation in the conventional approach. After highlighting a series of unresolved issues in the conventional approach to gravity, we show that (i) principle of equivalence, (ii) general covariance and (iii) a reasonable condition on the variation of the action functional, suggest a generic Lagrangian for semiclassical gravity of the form L = QabcdRabcd with ∇b Qabcd = 0. The expansion of Qabcd in terms of the derivatives of the metric tensor determines the structure of the theory uniquely. The zeroth order term gives the Einstein–Hilbert action and the first order correction is given by the Gauss–Bonnet action. Any such Lagrangian can be decomposed into surface and bulk terms which are related holographically. The equations of motion can be obtained purely from a surface term in the gravity sector. Hence the field equations are invariant under the transformation Tab → Tab + λgab and gravity does not respond to the changes in the bulk vacuum energy density. The cosmological constant arises as an integration constant in this approach. The implications are discussed.
COSMOLOGICAL QUESTS IN THE CMB SKY
Authors: SOURADEEP TARUN
Published: October 2006

Observational cosmology has indeed made a very rapid progress in recent years. The ability to quantify the universe has largely improved due to observational constraints coming from structure formation measurements of CMB anisotropy and, more recently, polarization has played a very important role. Besides precise determination of various parameters of the "standard" cosmological model, observations have also established some important basic tenets that underlie models of cosmology and structure formation in the universe — "acausally" correlated initial perturbations in a flat, statistically isotropic universe, adiabatic nature of primordial density perturbations. These are consistent with the expectation of the paradigm of inflation and the generic prediction of the simplest realization of inflationary scenario in the early universe. Further, gravitational instability is the established mechanism for structure formation from these initial perturbations. In the next decade, future experiments promise to strengthen these deductions and uncover the remaining crucial signature of inflation — the primordial gravitational wave background.
Acute caffeine ingestion does not impair glucose tolerance in persons with tetraplegia
Authors: Battram D. S. , Bugaresti J. , Gusba J. , Graham T. E.
Published: October 2006

Acute caffeine (Caf) ingestion impairs glucose tolerance in able-bodied humans during an oral glucose tolerance test (OGTT). The mechanism responsible for this effect remains unclear, however, it is suggested to be due to the accompanying increase in epinephrine concentration. We examined whether or not Caf would elicit a glucose intolerance in persons with tetraplegia (TP) who do not exhibit an increased epinephrine response following Caf ingestion. All TP [ n = 14; 9 incomplete (Inc) lesion, 5 complete (Com) lesion] completed two OGTT 1 h after consuming either gelatin (Pl) or Caf capsules (dose = 4 mg/kg). Blood samples were collected at baseline (time = 0 min), 1 h after capsule ingestion (time = 60 min), and every 30 min during the OGTT (time = 90–180 min). Glucose, insulin, proinsulin, and C-peptide responses were similar ( P > 0.05) between treatments, demonstrating no effect of Caf on glucose tolerance. This lack of a Caf effect may be due to the low epinephrine concentration that remained unchanged ( P > 0.05) throughout all experiments. Interestingly, the Com exhibited a 50% higher glucose response ( P ≤ 0.05) and a 46% ( P > 0.05) lower insulin response (vs. Inc), suggesting a more pronounced glucose intolerance within this subgroup. Furthermore, nine TP (5 Com, 4 Inc) had glucose levels of ≥ 7.8 mM at the end of the OGTT (time = 180 min), classifying them as glucose intolerant. In summary, acute Caf ingestion does not increase epinephrine concentration or impair glucose tolerance in TP.
Transforming growth factor-β following skeletal muscle strain injury in rats
Authors: Smith Cheryl A. , Stauber Franciose , Waters Christopher , Alway Stephen E. , Stauber William T.
Published: October 2006

Transforming growth factor-β (TGF-β) is a multifunctional cytokine implicated in inflammatory processes, wound healing, and fibrosis. In muscle diseases (i.e., dystrophy and inflammatory myopathy) and in animal models of muscle injury (i.e., produced by cardiotoxin, laceration, and eccentric contractions), increased TGF-β was associated with muscle fibrosis and healing. Although TGF-β transcript abundance was increased following injury, many studies presume that TGF-β protein was also active as evident by increases in collagen transcript abundance. The purpose was to determine whether TGF-β protein is present and active 48 h following injury. Using female rats, muscle strains were produced by stretching (50 stretches) the plantar flexor muscles. Forty-eight hours following injury, the medial gastrocnemius was removed and compartmentalized into five equal segments. Damaged myofibers with intracellular concanavalin A staining were counted. The percentage of damaged myofibers was significantly greater in the distal-most segment. TGF-β was assessed by using immunohistochemistry, RT-PCR, and immunoblot analysis. Immunohistochemistry revealed the presence of TGF-β1in areas of myofiber injury, whereas TGF-β2was not detected. Increases in TGF-β1and TGF-β2transcript abundance following strain injury were documented by RT-PCR analysis. Increases in TGF-β1and TGF-β2precursor abundance were observed following strain injury by using immunoblot analysis but there was no change in active TGF-β abundance. Although there was no correlation between the amount of cellular injury and TGF-β transcript and protein abundance, elevated levels of TGF-β1and TGF-β2precursor proteins were present in strain-injured skeletal muscles 48 h after injury.
Proteomic Analysis of the Cerebrospinal Fluid of Patients with Creutzfeldt-Jakob Disease
Authors: Cepek Lukas , Brechlin Peter , Steinacker Petra , Mollenhauer Brit , Klingebiel Enrico , Bibl Mirko , Kretzschmar Hans A. , Wiltfang Jens , Otto Markus
Published: October 2006

So far, only the detection of 14-3-3 proteins in cerebrospinal fluid (CSF) has been accepted as diagnostic criterion for Creutzfeldt-Jakob disease (CJD). However, this assay cannot be used for screening because of the high rate of false-positive results, whereas patients with variant CJD are often negative for 14-3-3 proteins. The aim of this study was to compare the spot patterns of CSF by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to search for a CJD-specific spot pattern. We analyzed the CSF of 28 patients [11 CJD, 9 Alzheimer’s disease (AD), 8 nondemented controls (NDC)] employing 2D-PAGE which was optimized for minimal volumes of CSF (0.1 ml; 7-cm strips). All samples were run at least three times, gels were silver stained and analyzed by an analysis software and manually revised. We could consistently match 268 spots which were then compared between all groups. By the use of 5 spots, we were able to differentiate CJD from AD or NDC with a sensitivity of 100%. CJD could also be distinguished from both groups by using a heuristic clustering algorithm of 2 spots. We conclude that this proteomic approach can differentiate CJD from other diseases and may serve as a model for other neurodegenerative diseases.
Food Allergies and Eosinophilic Esophagitis – Two Case Studies
Authors: Martín-Muñoz María F. , Lucendo Alfredo J. , Navarro Marta , Letrán Antonio , Martín-Chávarri Sonia , Burgos Emilio , Martín-Esteban M.
Published: October 2006

Eosinophilic esophagitis (EE) is a clinical-pathological disorder which is being increasingly diagnosed. It is etiologically associated with hypersensitivity to airborne allergens and/or dietary components. However, immediate hypersensitivity to foods has rarely been proven as the etiologic cause of the disorder. Two patients are presented with a history of rhinoconjunctivitis, allergic asthma, atopic dermatitis and food allergies which are currently under control and who show specific IgE to pulses and chicken respectively. These patients developed acute dysphagia and vomiting immediately after ingesting these foods and following appropriate examination were diagnosed as suffering from EE. The study also showed signs of blood hypereosinophilia while the esophageal manometry revealed a motor disorder characterized by aperistalsis and non-propulsive simultaneous waves affecting the lower two-thirds of the organ composed of smooth muscle. Topical treatment with fluticasone propionate was administered over a period of 3 months, in addition to a diet abstaining from the aforementioned foods and this led to remission of dysphagia and normalization of the endoscopic, histological and manometric studies of the esophagus. This situation remained stable for a considerable length of time after steroid treatment was discontinued, which showed that exposure to foods seemed to be the cause of the esophageal disorder. Similarly, allergies to inhalants and other digestive symptoms which appear upon immediate ingestion of the foods involved would not justify the sudden onset of dysphagia. We offer a pathophysiological explanation for the mechanisms of the disease based on the activation of eosinophils and mast cells by IgE and their ability to disturb the dynamic behavior of the neural and muscle components of the esophageal wall.
Small Heat-Shock Protein Hsp20 Attenuates β-Agonist–Mediated Cardiac Remodeling Through Apoptosis Signal–Regulating Kinase 1
Authors: Fan Guo-Chang , Yuan Qunying , Song Guojie , Wang Yigang , Chen Guoli , Qian Jiang , Zhou Xiaoyang , Lee Yong J. , Ashraf Muhammad , Kranias Evangelia G.
Published: October 2006

Chronic stimulation of the β-adrenergic neurohormonal axis contributes to the progression of heart failure and mortality in animal models and human patients. In cardiomyocytes, activation of the β-adrenergic pathway has been shown to result in transiently increased expression of a cardiac small heat-shock protein Hsp20. The present study shows that cardiac overexpression (10-fold) of Hsp20 may protect the heart against β-agonist–induced cardiac remodeling, associated with isoproterenol (50 μg/g per day) infusion for 14 days. Hsp20 attenuated the cardiac hypertrophic response, markedly reduced interstitial fibrosis, and decreased apoptosis. Contractility was also preserved in hearts with increased Hsp20 levels. These beneficial effects were associated with attenuation of the ASK1-JNK/p38 (apoptosis signal–regulating kinase 1/c-Jun NH
2
-terminal kinase/p38) signaling cascade triggered by isoproterenol, whereas there was no difference in either extracellular signal-related kinase 1/2 or Akt activation. Parallel in vitro experiments supported the inhibitory role of Hsp20 on enforced ASK1-JNK/p38 activation in both H9c2 cells and adult rat cardiomyocytes. Immunostaining studies also demonstrated that Hsp20 colocalizes with ASK1 in cardiomyocytes. Taken together, our findings indicate that (1) β-agonist–induced cardiac injury is associated with activation of the ASK1-JNK/p38 cascade; (2) increased expression of Hsp20 attenuates the induction of remodeling, dysfunction, and apoptosis in response to sustained β-adrenergic stimulation; and (3) the beneficial effects of Hsp20 are at least partially attributable to inhibition of the ASK1-signaling cascade.
Oximetry-Guided Reoxygenation Improves Neurological Outcome After Experimental Cardiac Arrest
Authors: Balan Irina S. , Fiskum Gary , Hazelton Julie , Cotto-Cumba Cynthia , Rosenthal Robert E.
Published: October 2006

Background and Purpose—

Current guidelines suggest that cardiac arrest (CA) survivors should be ventilated with 100% O
2
after resuscitation. Breathing 100% O
2
may worsen neurological outcome after experimental CA. This study tested the hypothesis that graded reoxygenation, with oximetry guidance, can safely reduce FiO
2
after resuscitation, avoiding hypoxia while promoting neurological recovery.

Methods—

Mature dogs underwent 10 minutes of CA and restoration of spontaneous circulation with100% O
2.
Animals were randomized to 1-hour additional ventilation on 100% FiO
2
or to rapid lowering of arterial O
2
saturation to <96% but >94% with pulse oximeter guidance. Animals were awakened at hour 23, and the neurological deficit score (0=normal; 100=brain-dead) was measured. Reanesthetized animals were perfusion-fixed and the brains removed for histopathology.

Results—

The neurological deficit score was significantly better in oximetry (O) dogs. O dogs appeared aware of their surroundings, whereas most hyperoxic (H) animals were stuporous (neurological deficit score=43.0±5.9 [O] versus 61.0±4.2 [H]; n=8,
P
<0.05). Stereological analysis revealed fewer injured CA1 neurons in O animals (cresyl violet: 35.5±4.3% [O] versus 60.5±3.3% [H];
P
<0.05). There were also fewer fluoro–Jade B–stained degenerating CA1 neurons in O animals (3320±267 [O] versus 6633±356 [H] per 0.1 mm
3
;
P
<0.001).

Conclusions—

A clinically applicable protocol designed to reduce postresuscitative hyperoxia after CA results in significant neuroprotection. Clinical trials of controlled normoxia after CA/restoration of spontaneous circulation should strongly be considered.
Can Multivariable Risk-Benefit Profiling Be Used to Select Treatment-Favorable Patients for Thrombolysis in Stroke in the 3- to 6-Hour Time Window?
Authors: Kent David M. , Selker Harry P. , Ruthazer Robin , Bluhmki Erich , Hacke Werner
Published: October 2006

Background and Purpose—

The Stroke-Thrombolytic Predictive Instrument (Stroke-TPI) uses multivariate equations to predict outcomes with and without thrombolysis. We sought to examine whether such a multivariate predictive instrument might be useful in selecting patients with a favorable risk-benefit treatment profile for therapy after 3 hours.

Methods—

We explored outcomes in patients from 5 major randomized clinical trials testing intravenous recombinant tissue plasminogen activator (rt-PA) classified by the Stroke-TPI as “treatment-favorable” or “treatment-unfavorable.” We used iterative bootstrap re-sampling to estimate how such a model would perform on independent test data.

Results—

Among patients treated within the 3- to 6-hour window, 67% of patients were classified by Stroke-TPI predicted outcomes as “treatment-favorable” and 33% were classified as “treatment-unfavorable.” Outcomes in the treatment-favorable group demonstrated benefit for thrombolysis (modified Rankin Scale score ≤1: 44.0% with rt-PA versus 34.2 with placebo,
P
=0.005), whereas harm was demonstrated in the treatment-unfavorable group (modified Rankin Scale score ≤1: 31.3% with rt-PA versus 38.3% with placebo;
P
=0.004). Bootstrap resampling with complete cross-validation showed that the absolute margin of benefit in the treatment-favorable group diminished on average by 36% between derivation and independent validation sets, but still represented a significant tripling of improvement in benefit compared with conventional inclusion criteria (5.2% [interquartile range, 1.7% to 8.6%] versus 1.8% [interquartile range, −0.5 to 4.1],
P
<0.0001).

Conclusions—

Such multivariable risk-benefit profiling may be useful in the selection of acute stroke patients for rt-PA therapy even more than 3 hours after symptom onset. Prospective testing is indicated.
Visual Grouping and the Focusing of Attention Induce Gamma-band Oscillations at Different Frequencies in Human Magnetoencephalogram Signals
Authors: Vidal Juan R. , Chaumon Maximilien , O'Regan J. Kevin , Tallon-Baudry Catherine
Published: October 2006

Neural oscillatory synchrony could implement grouping processes, act as an attentional filter, or foster the storage of information in short-term memory. Do these findings indicate that oscillatory synchrony is an unspecific epiphenomenon occurring in any demanding task, or that oscillatory synchrony is a fundamental mechanism involved whenever neural cooperation is requested? If the latter hypothesis is true, then oscillatory synchrony should be specific, with distinct visual processes eliciting different types of oscillations. We recorded magnetoencephalogram (MEG) signals while manipulating the grouping properties of a visual display on the one hand, and the focusing of attention to memorize part of this display on the other hand. Grouping-related gamma oscillations were present in all conditions but modulated by the grouping properties of the stimulus (one or two groups) in the high gamma-band (70–120 Hz) at central occipital locations. Attention-related gamma oscillations appeared as an additional component whenever attentional focusing was requested in the low gamma-band (44–66 Hz) at parietal locations. Our results thus reveal the existence of a functional specialization in the gamma range, with grouping-related oscillations showing up at higher frequencies than attention-related oscillations. The pattern of oscillatory synchrony is thus specific of the visual process it is associated with. Our results further suggest that both grouping processes and focused attention rely on a common implementation process, namely, gamma-band oscillatory synchrony, a finding that could account for the fact that coherent percepts are more likely to catch attention than incoherent ones.
Neural Correlates of Modality-specific Spatial Extinction
Authors: Hillis Argye E. , Chang Shannon , Heidler-Gary Jennifer , Newhart Melissa , Kleinman Jonathan T. , Davis Cameron , Barker Peter B. , Aldrich Eric , Ken Lynda
Published: October 2006

Sites of lesions responsible for visual, tactile, and/or motor extinction have not been clearly identified. We sought to determine the frequency of extinction in various modalities immediately after acute ischemic stroke, the rate of co-occurrence of extinction across modalities, and areas of infarct and/or hypoperfusion associated with each modality of extinction. A total of 148 patients with right supratentorial stroke were studied. In Study 1, 88 patients without hemiplegia, hemianesthesia, or visual field cuts were tested within 24 hours of onset for visual, tactile, and motor extinction, and underwent magnetic resonance diffusion and perfusion imaging. Associations between modality of extinction and areas of neural dysfunction (hypoperfusion/infarct) were identified. Of the 88 patients, 19 had only tactile extinction, 8 had only visual extinction, 12 had only motor extinction, 14 had extinction in two or more modalities, and 35 had no extinction. Tactile extinction was associated with neural dysfunction in the inferior parietal lobule; visual extinction was associated with dysfunction in the visual association cortex; and motor extinction was associated with neural dysfunction in the superior temporal gyrus. In Study 2, data from 60 patients who were excluded from Study 1 because of motor deficits were analyzed in the same way to determine whether frontal lesions contributed to visual or tactile extinction. Results again demonstrated that tactile extinction is associated with inferior parietal dysfunction, and visual extinction is associated with dysfunction of the visual association cortex. Potential accounts of the results, based on the “hemisphere rivalry” model of extinction and the limited attentional capacity model, are considered.