bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of the Medial Upper Arm Fascia to Bridge Biceps Tendon Defects
Authors: AL-QATTAN M. M.
Published: March 2006

Options to bridge biceps tendon defects which have been described in the literature include fascia lata, semitendinosus tendon, flexor carpi radialis, Achilles tendon–calcaneus composite allografts and Achilles tendon allografts. In this study, the author reports the use of the upper arm fascia. This option is considered most suitable for patients who require simultaneous pedicled latissimus dorsi flap coverage of concurrent traumatic complex anterior elbow defects.
Epithelioid haemangioendothelioma in the parapharyngeal space
Authors: Lee J-C , Lee B-J , Wang S-G , Kim H-W
Published: March 2006

Epithelioid haemangioendothelioma (EHE) is an uncommon vascular neoplasm which occurs rarely in the head and neck and has an unpredictable clinical behaviour. It is characterized by round or spindle-shaped endothelial cells with cytoplasmic vacuolation. Most often, EHE arises from the soft tissues of the upper and lower extremities, and it has borderline malignant potential. We describe the first reported case of EHE in the parapharyngeal space, which was treated successfully via a transcervical–transparotid approach (following angiography with embolization), without massive intra-operative bleeding or facial nerve damage.
Deafness in Vogt–Koyanagi–Harada syndrome
Authors: Sil A , Chatrath P , Gatland D J
Published: March 2006

Sudden onset sensorineural hearing loss is a well recognized entity frequently encountered in otolaryngological practice. However, the combination of such deafness as part of a wider systemic disorder is fortunately rare. Almost 100 years after the syndrome was classified, we describe a case of Vogt–Koyanagi–Harada syndrome occurring unusually in a Caucasian woman and characterized by sudden hearing loss. A brief review of this rare condition is presented.
Coexistent acute pyogenic and tubercular petrous apicitis: a diagnostic dilemma
Authors: Sethi A , Sethi D , Mrig S , Passey J C , Srivastav N
Published: March 2006

We report the case of a 16-year-old boy who presented to us with acute otitis media, facial weakness and retro-orbital pain. Computed tomography and magnetic resonance imaging (MRI) scans of the head and temporal bone revealed otitis media with petrous apicitis. The patient responded to broad-spectrum, parenteral antibiotics, with disappearance of facial weakness and reduction in pain. One month following the completion of treatment, the patient continued to have dull retro-orbital pain and developed ear discharge. A repeat MRI of the temporal bone revealed a persistent inflammatory lesion in the petrous apex, with a nodular, ring-enhancing lesion in the cerebellum, strongly suggestive of tuberculosis. The ear discharge stained positive for acid-fast bacilli and the patient's serum enzyme-linked immunosorbent assay for tuberculosis was reactive. The patient responded well to anti-tubercular treatment and was disease free eight months following the completion of treatment.
Ätiologie und Verlauf kindlichen dissozialen Verhaltens - Risikofaktoren für die Entwicklung einer antisozialen Persönlichkeitsstörung
Authors: Vloet Timo D. , Herpertz Sabine , Herpertz-Dahlmann Beate
Published: March 2006

Zusammenfassung: Gegenstand: Störungen des Sozialverhaltens gehören zu den häufigsten Erkrankungen in unserem Fachgebiet. Methode: Die an der Entstehung von Störungen des Sozialverhaltens wesentlich beteiligten biologischen und psychosozialen Faktoren sowie deren Interaktion werden in dieser Übersichtsarbeit dargestellt. Dabei wird speziell auf Veränderungen der autonomen Reagibilität eingegangen. Ergebnis: Bei den unterschiedlichen Entwicklungspfaden hin zu einer antisozialen Persönlichkeitsstörung kommt frühen Formen von Störungen des Sozialverhaltens und dem psychopathischen Subtyp eine besondere Aussagekraft zu. Schlussfolgerung: Es wird die Bedeutung einer frühzeitigen Förderung gefährdeter Kinder zur Vermeidung einer dissozialen Entwicklung herausgestellt.
Beeinträchtigen subklinische epileptische Entladungen wirklich das Kurzzeitgedächtnis von Kindern?
Authors: Tremmel Laura , Holtmann Martin , Schmidt Martin H. , Brandl Ulrich
Published: March 2006

Zusammenfassung: Fragestellung: Trotz Anfallsfreiheit ist das schulische Vorankommen epilepsiekranker Kinder und Jugendlicher oft durch Konzentrationsschwierigkeiten, Teilleistungsstörungen und Verhaltensauffälligkeiten beeinträchtigt. Welche Rolle dabei die auch bei guter medikamentöser Einstellung häufig weiterbestehenden subklinischen epilepsietypischen Potentiale spielen, ist noch nicht hinreichend geklärt. Es wurden Hinweise darauf gefunden, dass es während subklinischer Potentiale zu zeitgleich auftretenden, vorübergehenden kognitiven Störungen (transitory cognitive impairment) im Kurzzeitgedächtnis kommt. Der mögliche Einfluss dieser Potentiale wird in der vorliegenden Studie untersucht. Methodik: 40 Kinder (10,3 ± 3,5 Jahre) mit bekannten subklinischen epilepsietypischen Potentialen im EEG wurden mit zwei computerisierten, EEG-gekoppelten Testsystemen zum visuell-räumlichen und verbalen Kurzzeitgedächtnis untersucht, die die Betrachtung der Leistung in zeitlich exaktem Zusammenhang mit den subklinischen epilepsietypischen Entladungen ermöglichen. Ergebnisse: Es fanden sich keine signifikanten Unterschiede der kognitiven Leistung in Phasen mit und ohne epilepsietypische Entladungen, weder bei subklinischen Entladungen über 1.5 sec., noch bei multiplen Entladungen innerhalb eines Testzyklus. Auch Lokalisation und Zeitpunkt des Auftretens der subklinischen epilepsietypischen Entladungen im Testverlauf wirkten sich nicht bedeutsam auf die Leistung aus. Schlussfolgerungen: Unsere Untersuchung ergab keinen Anhalt für bedeutsame Zusammenhänge zwischen epilepsietypischen Potentialen und Fehlerraten als Ausdruck vorübergehender kognitiver Beeinträchtigungen im verbalen und visuell-räumlichen Kurzzeitgedächtnis. Für die bekannten kognitiven Leistungsdefizite bei Epilepsie-Patienten sind andere Erklärungsmöglichkeiten zu suchen.
Automatic Generation of Quantitative Reasoning Items
Authors: Arendasy Martin , Sommer Markus , Gittler Georg , Hergovich Andreas
Published: March 2006

This paper deals with three studies on the computer-based, automatic generation of algebra word problems. The cognitive psychology based generative/quality control frameworks of the item generator are presented. In Study I the quality control framework is empirically tested using a first set of automatically generated items. Study II replicates the findings of Study I using a larger set of automatically generated algebra word problems. Study III deals with the generative framework of the item generator by testing construct validity aspects of the item generator produced items. Using nine Rasch-homogeneous subscales of the new intelligence structure battery (INSBAT, Hornke et al., 2004 ), a hierarchical confirmatory factor analysis is reported, which provides first evidence of convergent as well as divergent validity of the automatically generated items. The end of the paper discusses possible advantages of automatic item generation in general ranging from test security issues and the possibility of a more precise psychological assessment to mass testing and economical questions of test construction.
Relativistic calculation of nuclear magnetic shieldings of xenon difluoride
Authors: Kudo K. , Ootani Y. , Funaki M. , Fukui H.
Published: March 2006

A new method for calculating relativistic nuclear magnetic shieldings at the coupled Hartree-Fock (CHF) level, which is based on the theory of Barysz-Sadlej-Snijders (BSS), was applied to the evaluation of the shieldings in XeF2. Our calculation results were compared with the experimental results for the xenon and fluorine nuclear magnetic shielding anisotropies, obtained by using solid-state Xe129 and F19 NMR spectroscopies. It was shown that the relativistic effects are considerable and that the relativistic BSS-CHF calculation can reproduce well the experimental values of the shielding anisotropies for Xe and F in XeF2.
Pair formation and global ordering of strongly interacting ferrocolloid mixtures: An integral equation study
Authors: Range Gabriel M. , Klapp Sabine H. L.
Published: March 2006

Using the reference hypernetted chain (RHNC) integral equation theory and an accompanying stability analysis we investigate the structural and phase behaviors of model bidisperse ferrocolloids based on correlations of the homogeneous isotropic high-temperature phase. Our model consists of two species of dipolar hard spheres (DHSs) which dipole moments are proportional to the particle volume. At small packing fractions our results indicate the onset of chain formation, where the (more strongly coupled) A species behaves essentially as a one-component DHS fluid in a background of B particles. At high packing fractions, on the other hand, the RHNC theory indicates the appearance of isotropic-to-ferromagnetic transitions (volume ratios close to one) and demixing transitions (smaller volume ratios). However, contrary with the related case of monodisperse DHS mixtures previously studied by us [Phys. Rev. E 70, 031201 (2004)], none of the present bidisperse systems exhibit demixing within the isotropic phase, rather we observe coupled ferromagnetic/demixing phase transitions.
On Burnett coefficients in periodic media
Authors: Conca Carlos , Orive Rafael , Vanninathan Muthusamy
Published: March 2006

The aim of this work is to demonstrate a curious property of general periodic structures. It is well known that the corresponding homogenized matrix is positive definite. We calculate here the next order Burnett coefficients associated with such structures. We prove that these coefficients form a tensor which is negative semidefinite. We also provide some examples showing degeneracy in multidimension.
On the Birman-Schwinger principle applied to −Δ+m2−m
Authors: Maceda M.
Published: March 2006

The condition for E=0 to be an eigenvalue of the operator −Δ+m2−m+λV is obtained through the use of the Birman-Schwinger principle (Theorem 3.2). By setting E=−α2 and using the analyticity of the corresponding Birman-Schwinger kernel (Theorem 3.1), the series development of λ−1 is obtained up to second order on α (Theorem 4.1).
Group-III intermixing in InAs∕InGaAlAs quantum dots-in-well
Authors: Wang Y. , Djie H. S. , Ooi B. S.
Published: March 2006

We report selective postgrowth band gap tuning of InAs∕InGaAlAs quantum dots-in-well grown on InP substrate using impurity-free group-III intermixing. In contrast to most reported intermixing results, SixNy annealing cap results in a larger band gap blueshift than SiO2 annealing cap with a differential shift of 92nm after annealing at 800°C for 30s. Intermixing also results in large wavelength tuning from 1.6to1.37μm at room temperature, accompanied by luminescence linewidth reduction and intensity improvement. According to our theoretical model, we postulate that the unusual In(GaAl)As intermixing is governed by different interdiffusion rates of group-III atoms.
Patterning of silica microsphere monolayers with focused femtosecond laser pulses
Authors: Cai Wenjian , Piestun Rafael
Published: March 2006

We demonstrate the patterning of monolayer silica microsphere lattices with tightly focused femtosecond laser pulses. We selectively removed microspheres from a lattice and characterized the effect on the lattice and the substrate. The proposed physical mechanism for the patterning process is laser-induced breakdown followed by ablation of material. We show that a microsphere focuses radiation in its interior and in the near field. This effect plays an important role in the patterning process by enhancing resolution and accuracy and by reducing the pulse energy threshold for damage. Microsphere patterning could create controlled defects within self-assembled opal photonic crystals.
Structural and magnetic properties of Mn5Ge3 clusters in a dilute magnetic germanium matrix
Authors: Bihler C. , Jaeger C. , Vallaitis T. , Gjukic M. , Brandt M. S. , Pippel E. , Woltersdorf J. , Gösele U.
Published: March 2006

We have characterized the structural and magnetic properties of low-temperature molecular-beam epitaxy grown Ge:Mn by means of high-resolution transmission electron microscopy (HR-TEM), energy dispersive x-ray spectroscopy, and superconducting quantum interference device (SQUID) magnetometry. We find a coherent incorporation of Mn5Ge3 clusters in an epitaxially grown Ge:Mn matrix, which shows the characteristics of a diluted magnetic semiconductor phase of Mn-doped Ge. The clusters are preferentially oriented with the hexagonal [0001] direction parallel to the [001] growth direction of the Ge:Mn matrix, as determined from both HR-TEM and SQUID measurements.
Area dependence of high-frequency spin-transfer resonance in giant magnetoresistance contacts up to 300nm diameter
Authors: Mancoff F. B. , Rizzo N. D. , Engel B. N. , Tehrani S.
Published: March 2006

We measured high-frequency spin-transfer resonances from <8GHz to >26GHz excited by dc currents through giant magnetoresistance point contacts with diameters d from <50 to almost 300nm. The slope of resonance frequency versus current decreased with increased d and was fit best by a spin-transfer model where the effective d extends ⩾50nm past the contact edge into the surrounding magnetic film. An increased resonance critical current versus contact area was also fit well by this model including a surrounding ring of excited area. Spin-transfer resonance in large devices eliminates the need for electron-beam lithography in applications.
Carbon nanotube thermal transport: Ballistic to diffusive
Authors: Wang Jian , Wang Jian-Sheng
Published: March 2006

We propose the expression ℓ0∕(ℓ0+L) for the energy transmission covering both ballistic and diffusive regimes, where ℓ0 is mean free path and L is system length. With this formula, calculations of thermal conduction in carbon nanotubes (CNTs) show: (1) Thermal conductance at room temperature is proportional to the diameter for single-walled CNTs (SWCNTs) and to the square of diameter for multiwalled CNTs. (2) Interfaces play an important role in thermal conduction in CNTs due to their symmetry of vibrational modes. (3) For CNTs in ballistic-diffusive regime, thermal conductivity κ goes as Lα. The exponent α is found to decrease with increasing temperature and is insensitive to the diameter of SWCNTs for the Umklapp process, α≈0.8 for short SWCNTs at room temperature. These results are consistent with recent experimental findings.
Laser-induced Ni(Ti) silicide formation
Authors: Setiawan Y. , Lee P. S. , Pey K. L. , Wang X. C. , Lim G. C.
Published: March 2006

Effects of Ti alloying during laser-induced Ni silicide formation is studied. Unique triple layer microstructures were found with the presence of supercell in the NiSi2 grains formed at the interface. This supercell formation was caused by a local ordering of Ni and Si atoms that favor lower free energy during rapid solidification. Ti rapidly segregates from the alloy melt and forms a protective TiOx overlayer on the surface during solidification. Melt front progressing towards the Ni-rich region leads to quenching of an amorphous layer sandwiched between NiSi2 grains and the TiOx overlayer.
The effect of p doping in InAs quantum dot lasers
Authors: Sandall I. C. , Smowton P. M. , Walker C. L. , Badcock T. , Mowbray D. J. , Liu H. Y. , Hopkinson M.
Published: March 2006

We directly measure the modal gain and spontaneous emission spectra in three quantum dot structures that are nominally identical except for the level of p doping to ascertain the effect that p doping has on quantum dot lasers. The maximum modal gain increases at fixed quasi-Fermi level separation as the level of p doping increases from 0 to 15 to 50 acceptors per dot. The internal optical mode loss is similar for all three samples but the measured nonradiative current is larger for the p-doped structures.
Electrical characteristics of bulk GaN-based Schottky rectifiers with ultrafast reverse recovery
Authors: Zhou Yi , Li Mingyu , Wang Dake , Ahyi Claude , Tin Chin-Che , Williams John , Park Minseo , Williams N. Mark , Hanser Andrew
Published: March 2006

A vertical Schottky diode rectifier was fabricated using a bulk n−GaN wafer. Pt Schottky contacts were prepared on the Ga face and full backside ohmic contact was prepared on the N face by using Ti∕Al. The root mean square surface roughnesses of the Ga and N faces are 0.61 and 4.7nm, respectively. A relatively high breakdown field of 5.46kV∕cm was achieved with no additional edge termination. The breakdown field decreases as the size of the device increases. The background electron concentration of the bulk GaN wafer was low (5×1015cm−3), which may lead to a relatively high breakdown field even with no special edge termination. The forward turn-on voltage was as low as 2.4V at the current density of 100A∕cm2. The device exhibited an ultrafast reverse recovery characteristics (reverse recovery time <20ns).
Crack detection and analyses using resonance ultrasonic vibrations in full-size crystalline silicon wafers
Authors: Belyaev A. , Polupan O. , Dallas W. , Ostapenko S. , Hess D. , Wohlgemuth J.
Published: March 2006

An experimental approach for fast crack detection and length determination in full-size solar-grade crystalline silicon wafers using a resonance ultrasonic vibrations (RUV) technique is presented. The RUV method is based on excitation of the longitudinal ultrasonic vibrations in full-size wafers. Using an external piezoelectric transducer combined with a high sensitivity ultrasonic probe and computer controlled data acquisition system, real-time frequency response analysis can be accomplished. On a set of identical crystalline Si wafers with artificially introduced periphery cracks, it was demonstrated that the crack results in a frequency shift in a selected RUV peak to a lower frequency and increases the resonance peak bandwidth. Both characteristics were found to increase with the length of the crack. The frequency shift and bandwidth increase serve as reliable indicators of the crack appearance in silicon wafers and are suitable for mechanical quality control and fast wafer inspection.
Digital-holography refractive-index-profile measurement of phase gratings
Authors: de Angelis M. , De Nicola S. , Finizio A. , Pierattini G. , Ferraro P. , Pelli S. , Righini G. , Sebastiani S.
Published: March 2006

A phase grating is produced in an iron-doped lithium niobate photorefractive crystal by two-beam holographic configuration. Digital holography is used to investigate the two-dimensional profile of index of refraction produced by the photorefractive process. The proposed technique gives a direct and quantitative two-dimensional profile of index of refraction in photorefractive structures, can monitor defects and can be used for in situ visualization during the photorefractive process.
Serum response factor MADS box serine -162 phosphorylation switches proliferation and myogenic gene programs
Authors: Iyer Dinakar , Chang David , Marx Joe , Wei Lei , Olson Eric N. , Parmacek Michael S. , Balasubramanyam Ashok , Schwartz Robert J.
Published: March 2006

Phosphorylation of a cluster of amino acids in the serum response factor (SRF) “MADS box” αI coil DNA binding domain regulated the transcription of genes associated with proliferation or terminal muscle differentiation. Mimicking phosphorylation of serine-162, a target of protein kinase C-α, with an aspartic acid substitution (SRF-S162D) completely inhibited SRF–DNA binding and blocked α-actin gene transcription even in the presence of potent myogenic cofactors, while preserving c-
fos
promoter activity because of stabilization of the ternary complex via Elk-1. Introduction of SRF-S162D into
SRF
null ES cells permitted transcription of the c-
fos
gene but was unable to rescue expression of myogenic contractile genes. Transition of proliferating C2C12 myoblasts to postfusion myocytes after serum withdrawal was associated with a progressive decline in SRF-S162 phosphorylation and an increase in α-actin gene expression. Hence, the phosphorylation status of serine-162 in the αI coil may constitute a novel switch that directs target gene expression into proliferation or differentiation programs.
Reveromycin A, an agent for osteoporosis, inhibits bone resorption by inducing apoptosis specifically in osteoclasts
Authors: Woo Je-Tae , Kawatani Makoto , Kato Masanori , Shinki Toshimasa , Yonezawa Takayuki , Kanoh Naoki , Nakagawa Hiroshi , Takami Masamichi , Lee Kun Hyung , Stern Paula H. , Nagai Kazuo , Osada Hiroyuki
Published: March 2006

Mature bone-resorbing osteoclasts (OCs) mediate excessive bone loss seen in several bone disorders, including osteoporosis. Here, we showed that reveromycin A (RM-A), a small natural product with three carboxylic groups in its structure, induced apoptosis specifically in OCs, but not in OC progenitors, nonfunctional osteoclasts, or osteoblasts. RM-A inhibited protein synthesis in OCs by selectively blocking enzymatic activity of isoleucyl-tRNA synthetase. The proapoptotic effect of RM-A was inhibited by neutralization or disruption of the acidic microenvironment, a prominent characteristic of OCs. RM-A was incorporated in OCs but not in nonfunctional osteoclasts and OC progenitors in neutral culture medium. Effects of RM-A on OC apoptosis increased under acidic culture conditions. RM-A not only was incorporated, but also induced apoptosis in OC progenitors in acidic culture medium. RM-A inhibited osteoclastic pit formation, decreased prelabeled
45
Ca release in organ cultures, and antagonized increased bone resorption in ovariectomized mice. These results suggested that preventive effects of RM-A on bone resorption
in vitro
and
in vivo
were caused by apoptosis through inhibition of isoleucyl-tRNA synthetase in OCs and that specific sensitivity of OCs to RM-A was due to the acidic microenvironment, which increased cell permeability of RM-A by suppressing dissociation of protons from carboxylic acid moieties, making them less polar. This unique mechanism suggested that RM-A might represent a type of therapeutic agent for treating bone disorders associated with increased bone loss.
Interplay between replication and recombination in
Escherichia coli
: Impact of the alternative DNA polymerases
Authors: Delmas Stéphane , Matic Ivan
Published: March 2006

Homologous recombination (HR) and translesion synthesis (TLS) are two pathways involved in the tolerance of lesions that block the replicative DNA polymerase. However, whereas TLS is frequently error-prone and, therefore, can be deleterious, HR is generally error-free. Furthermore, because the recombination enzymes and alternative DNA polymerases that perform TLS may use the same substrate, their coordination might be important to assure cell fitness and survival. This study aimed to determine whether and how these pathways are coordinated in
Escherichia coli
cells by using conjugational replication and recombination as a model system. The role of the three alternative DNA polymerases that are regulated by the SOS system was tested in DNA polymerase III holoenzyme-proficient and -deficient mutants. When PolIII is inactive, the alternative DNA polymerases copy DNA in the following order: PolII, PolIV, and PolV. The observed hierarchy corresponds to the selective constraints imposed on the genes coding for alternative DNA polymerases observed in natural populations of
E. coli
, suggesting that this hierarchy depends on the frequency of specific damages encountered during the evolutionary history of
E. coli
. We also found that DNA replication and HR are in competition and that they can precede each other. Our results suggest that there is probably not an active choice of which pathway to use, but, rather, the nature and concentration of lesions that lead to formation of ssDNA and the level of SOS induction that they engender might determine the outcome of the competition between HR and alternative DNA polymerases.
Imaging cellular signals in the heart
in vivo
: Cardiac expression of the high-signal Ca
2+
indicator GCaMP2
Authors: Tallini Yvonne N. , Ohkura Masamichi , Choi Bum-Rak , Ji Guangju , Imoto Keiji , Doran Robert , Lee Jane , Plan Patricia , Wilson Jason , Xin Hong-Bo , Sanbe Atsushi , Gulick James , Mathai John , Robbins Jeffrey , Salama Guy , Nakai Junichi , Kotlikoff Michael I.
Published: March 2006

Genetically encoded sensor proteins provide unique opportunities to advance the understanding of complex cellular interactions in physiologically relevant contexts; however, previously described sensors have proved to be of limited use to report cell signaling
in vivo
in mammals. Here, we describe an improved Ca
2+
sensor, GCaMP2, its inducible expression in the mouse heart, and its use to examine signaling in heart cells
in vivo
. The high brightness and stability of GCaMP2 enable the measurement of myocyte Ca
2+
transients in all regions of the beating mouse heart and prolonged pacing and mapping studies in isolated, perfused hearts. Transgene expression is efficiently temporally regulated in cardiomyocyte GCaMP2 mice, allowing recording of
in vivo
signals 4 weeks after transgene induction. High-resolution imaging of Ca
2+
waves in GCaMP2-expressing embryos revealed key aspects of electrical conduction in the preseptated heart. At embryonic day (e.d.) 10.5, atrial and ventricular conduction occur rapidly, consistent with the early formation of specialized conduction pathways. However, conduction is markedly slowed through the atrioventricular canal in the e.d. 10.5 heart, forming the basis for an effective atrioventricular delay before development of the AV node, as rapid ventricular activation occurs after activation of the distal AV canal tissue. Consistent with the elimination of the inner AV canal muscle layer at e.d. 13.5, atrioventricular conduction through the canal was abolished at this stage. These studies demonstrate that GCaMP2 will have broad utility in the dissection of numerous complex cellular interactions in mammals,
in vivo
.
Cranial remains of an Eocene tarsier
Authors: Rossie James B. , Ni Xijun , Beard K. Christopher
Published: March 2006

The phylogenetic position of tarsiers relative to anthropoids and Paleogene omomyids remains a subject of lively debate that lies at the center of research into anthropoid origins. Omomyids have long been regarded as the nearest relatives of tarsiers, but a sister group relationship between anthropoids and tarsiers has also been proposed. These conflicting phylogenetic reconstructions rely heavily on comparisons of cranial anatomy, but until now, the fossil record of tarsiers has been limited to a single jaw and several isolated teeth. In this article, we describe cranial material of a fossil tarsiid from the middle-Eocene Shanghuang fissure-fillings in southern Jiangsu Province, China. This facial fragment, which is allocated toTarsius eocaenus, is virtually identical to the corresponding anatomy in living tarsiers and differs substantially from that of early anthropoids such asBahinia,Phenacopithecus, andParapithecus. This new specimen indicates that tarsiers already possessed greatly enlarged orbits and a haplorhine oronasal configuration by the time they are first documented in the fossil record during the middle Eocene.
Mixed-lineage kinase 3 regulates B-Raf through maintenance of the B-Raf/Raf-1 complex and inhibition by the NF2 tumor suppressor protein
Authors: Chadee Deborah N. , Xu Dazhong , Hung Gene , Andalibi Ali , Lim David J. , Luo Zhijun , Gutmann David H. , Kyriakis John M.
Published: March 2006

The Ras → Raf → MEK1/2 → extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway couples mitogenic signals to cell proliferation. B-Raf and Raf-1 function within an oligomer wherein they are regulated in part by mutual transactivation. The MAPK kinase kinase (MAP3K) mixed-lineage kinase 3 (MLK3) is required for mitogen activation of B-Raf and cell proliferation. Here we show that the kinase activity of MLK3 is not required for support of B-Raf activation. Instead, MLK3 is a component of the B-Raf/Raf-1 complex and is required for maintenance of the integrity of this complex. We show that the activation of ERK and the proliferation of human schwannoma cells bearing a loss-of-function mutation in theneurofibromatosis 2(NF2) gene require MLK3. We find that merlin, the product ofNF2, blunts the activation of both ERK and c-Jun N-terminal kinase (JNK). Finally, we demonstrate that merlin and MLK3 can interactin situand that merlin can disrupt the interactions between B-Raf and Raf-1 or those between MLK3 and either B-Raf or Raf-1. Thus, MLK3 is part of a multiprotein complex and is required for ERK activation. The levels of this complex may be negatively regulated by merlin.
Molecular flexibility can influence the stimulatory ability of receptor–ligand interactions at cell–cell junctions
Authors: Qi Shuyan , Krogsgaard Michelle , Davis Mark M. , Chakraborty Arup K.
Published: March 2006

Direct cell–cell communication is crucial for many processes in biology, particularly embryogenesis, interactions between hematopoetic cells, and in the nervous system. This communication is often mediated by the binding of receptors to cognate ligands at a cell–cell junction. One such interaction that is very important for the development of many immune responses is the binding of the αβ T cell receptor for antigen (TCR) on T lymphocytes with peptide–MHC complexes on other cells. In general, the stability (e.g., half-life) of TCR–peptide–MHC binding measured in solution correlates with functional responses. Several anomalies have been reported, however. For example, for some anomalous ligands, large changes in heat capacity can apparently substitute for a lack of stability in TCR–ligand interactions. Here, we show that, when there are significant conformational changes during receptor–ligand binding and the receptor/ligand have relatively rigid molecular subdomains, the difference between the half-life of this receptor–ligand complex at a cell–cell junction and that measured using soluble molecules is large. Thus, receptors/ligands with these specific molecular features do not follow correlations between stimulatory potency in the cellular environment and half-lives measured with soluble molecules. Our “first-principles” prescription for correcting the half-life measured in solution to obtain the pertinent value at a cell–cell junction illuminates the origin of correlations of T cell response with thermodynamic properties. Application of our ideas to diverse systems where receptor–ligand interactions occur across juxtaposed cells may help avoid debates about “anomalies” that may simply arise from receptor/ligand-specific differences between half-lives in solution and in the cellular environment.
Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions
Authors: Sidhaye Venkataramana K. , Güler Ali D. , Schweitzer Kelly S. , D’Alessio Franco , Caterina Michael J. , King Landon S.
Published: March 2006

Aquaporin-5 (AQP5) is expressed in epithelia of lung, cornea, and various secretory glands, sites where extracellular osmolality is known to fluctuate. Hypertonic aquaporin (AQP) induction has been described, but little is known about the effects of a hypotonic environment on AQP abundance. We report that, when mouse lung epithelial cells were exposed to hypotonic medium, a dose-responsive decrease in AQP5 abundance was observed. Hypotonic reduction of AQP5 was blocked by ruthenium red, methanandamide, and miconazole, agents that inhibit the cation channel transient receptor potential vanilloid (TRPV) 4 present in lung epithelial cells. Several observations indicate that TRPV4 participates in hypotonic reduction of AQP5, including a requirement for extracellular calcium to achieve AQP5 reduction; an increase in intracellular calcium in mouse lung epithelial (MLE) cells after hypotonic stimulation; and reduction of AQP5 abundance after addition of the TRPV4 agonist 4α-Phorbol-12,13-didecanoate (4α-PDD). Similarly, addition of hypotonic PBS to mouse trachea
in vivo
decreased AQP5 within 1 h, an effect blocked by ruthenium red. To confirm a functional interaction, AQP5 was expressed in control or TRPV4-expressing human embryonic kidney (HEK) cells. Hypotonic reduction of AQP5 was observed only in the presence of TRPV4 and was blocked by ruthenium red. Combined with earlier studies, these observations indicate that AQP5 abundance is tightly regulated along a range of osmolalities and that AQP5 reduction by extracellular hypotonicity can be mediated by TRPV4. These findings have direct relevance to regulation of membrane water permeability and water homeostasis in epithelia of the lung and other organs.
Kupffer cell-dependent TNF-α signaling mediates injury in the arterialized small-for-size liver transplantation in the mouse
Authors: Tian Yinghua , Jochum Wolfram , Georgiev Panco , Moritz Wolfgang , Graf Rolf , Clavien Pierre-Alain
Published: March 2006

Implantation of small liver grafts causes liver injury and defective regeneration leading to graft failure. We investigated whether Kupffer cell-dependent TNF-α signaling contributes to this poor outcome. Partial 30% liver transplantation was performed in C57BL/6 wild-type mice (control group), and in three groups with down-regulation of the TNF-α pathway: (
i
) TNF receptor 1 knockout [TNFR-1(−/−)] mice, and mice pretreated with (
ii
) gadolinium chloride or (
iii
) pentoxifylline (PTX). Fifty-percent partial liver transplantation, a model associated with full recovery, and transplantation in IL-6 knockout [IL-6(−/−)] mice were performed in some experiments. Graft injury, regeneration, portal flow, liver microcirculation, leukocyte adhesion, and animal survival were assessed. Animal survival rates were 14% in the control group vs. 43% in the gadolinium chloride group, 57% for the TNFR-1(−/−) group, and 86% in the PTX group (
P
< 0.001). Markers of liver injury were reduced in all treated groups when compared with controls. Each treated group disclosed better portal flow and sinusoid perfusion, decreased leukocyte adherence, particularly in the PTX group. Liver regeneration occurred only in the treated groups. IL-6 and IL-10 levels were dramatically up-regulated (50×) in the PTX group, and at lower levels in other experimental groups. The protective effect of PTX was lost in IL-6(−/−) mice and protection was restored by a single dose of r-IL-6. In conclusion, interruption of TNF-α signaling or depletion of Kupffer cells improves survival after 30% liver transplantation, reduces liver injury, and enhances regeneration. The superior effects of PTX are mediated by IL-6.
Thermodynamic and kinetic modeling of transcriptional pausing
Authors: Tadigotla Vasisht R. , Maoiléidigh Dáibhid Ó , Sengupta Anirvan M. , Epshtein Vitaly , Ebright Richard H. , Nudler Evgeny , Ruckenstein Andrei E.
Published: March 2006

We present a statistical mechanics approach for the prediction of backtracked pauses in bacterial transcription elongation derived from structural models of the transcription elongation complex (EC). Our algorithm is based on the thermodynamic stability of the EC along the DNA template calculated from the sequence-dependent free energy of DNA–DNA, DNA–RNA, and RNA–RNA base pairing associated with (
i
) the translocational and size fluctuations of the transcription bubble; (
ii
) changes in the associated DNA–RNA hybrid; and (
iii
) changes in the cotranscriptional RNA secondary structure upstream of the RNA exit channel. The calculations involve no adjustable parameters except for a cutoff used to discriminate paused from nonpaused complexes. When applied to 100 experimental pauses in transcription elongation by
Escherichia coli
RNA polymerase on 10 DNA templates, the approach produces statistically significant results. We also present a kinetic model for the rate of recovery of backtracked paused complexes. A crucial ingredient of our model is the incorporation of kinetic barriers to backtracking resulting from steric clashes of EC with the cotranscriptionally generated RNA secondary structure, an aspect not included explicitly in previous attempts at modeling the transcription elongation process.
Form deprivation modulates retinal neurogenesis in primate experimental myopia
Authors: Tkatchenko Andrei V. , Walsh Pamela A. , Tkatchenko Tatiana V. , Gustincich Stefano , Raviola Elio
Published: March 2006

Juvenile primates develop myopia when their visual experience is degraded by lid fusion. In response to this abnormal visual input, retinal neural networks cause an excessive growth of the postequatorial segment of the eye, but the mechanism underlying this axial elongation is unknown. After fusion of the lids in one eye of juvenile rhesus macaques and green monkeys, we combined cDNA subtractions, microarray profiling, and real-time PCR to compare gene expression in the retinas of the closed and open eyes. This molecular analysis showed up-regulation of a number of genes associated with cell division in the retina of the closed eye and differential expression of six genes localized to chromosomal loci linked to forms of human hereditary myopia. In addition, it substantiated a previous observation, based on immunocytochemistry, that synthesis of vasoactive intestinal polypeptide was increased upon lid fusion. Injection of 5-bromo-2′-deoxyuridine and immunocytochemistry showed that the primate retinal periphery harbors mitotically active neuroprogenitor cells that increase in number when the visual experience is altered by lid fusion. Furthermore, the number of dividing cells is highly correlated with axial elongation of the eye and the resulting myopic refractive error. Thus, the retina undergoes active growth during the postnatal development of the primate eye. This growth is modulated by the visual input and accelerates considerably when the eye develops axial myopia. Vasoactive intestinal polypeptide may be the molecule that stimulates retinal growth.
Recovery of an arenavirus entirely from RNA polymerase I/II-driven cDNA
Authors: Flatz Lukas , Bergthaler Andreas , de la Torre Juan Carlos , Pinschewer Daniel D.
Published: March 2006

The prototypic arenavirus lymphocytic choriomeningitis virus has been a primary workhorse of viral immunologists for almost a century, and it has served as an important model for studying basic principles of arenavirus molecular biology. Its negative-stranded bisegmented RNA genome has, however, posed a major obstacle to attempts at manipulating the infectious virus by reverse genetic techniques. Here, we report the recovery of infectious lymphocytic choriomeningitis virus (the immunosuppressive strain clone 13) entirely from cDNA. Intracellular transcription of the short and the long viral genome segment from polymerase (pol) I-driven vectors and coexpression of the minimal viral-transacting factors NP and L from pol II-driven plasmids resulted in the efficient formation of infectious virus with genetic tags in both genome segments. The cDNA-derived viruses behaved identically to wild-type virus in both cell culture and infected mice. Importantly, they caused a chronic infection and suppressed the adaptive immune response to an unrelated third-party virus. This technology provides an important basis for investigating viral determinants of persistent infection and immunosuppression. In addition, our findings demonstrate that pol I/II-based vector systems may represent an efficient alternative strategy for the recovery of cytoplasmic negative-strand RNA viruses from cDNA.
Systemic antithrombotic effects of ADAMTS13
Authors: Chauhan Anil K. , Motto David G. , Lamb Colin B. , Bergmeier Wolfgang , Dockal Michael , Plaimauer Barbara , Scheiflinger Friedrich , Ginsburg David , Wagner Denisa D.
Published: March 2006

The metalloprotease ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats 13) cleaves highly adhesive large von Willebrand factor (VWF) multimers after their release from the endothelium. ADAMTS13 deficiency is linked to a life-threatening disorder, thrombotic thrombocytopenic purpura (TTP), characterized by platelet-rich thrombi in the microvasculature. Here, we show spontaneous thrombus formation in activated microvenules of Adamts13−/− mice by intravital microscopy. Strikingly, we found that ADAMTS13 down-regulates both platelet adhesion to exposed subendothelium and thrombus formation in injured arterioles. An inhibitory antibody to ADAMTS13 infused in wild-type mice prolonged adhesion of platelets to endothelium and induced thrombi formation with embolization in the activated microvenules. Absence of ADAMTS13 did not promote thrombi formation in αIIbβ3 integrin-inhibited blood. Recombinant ADAMTS13 reduced platelet adhesion and aggregation in histamine-activated venules and promoted thrombus dissolution in injured arterioles. Our findings reveal that ADAMTS13 has a powerful natural antithrombotic activity and recombinant ADAMTS13 could be used as an antithrombotic agent.
Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function
Authors: Yawata Makoto , Yawata Nobuyo , Draghi Monia , Little Ann-Margaret , Partheniou Fotini , Parham Peter
Published: March 2006

Interactions between killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands regulate the development and response of human natural killer (NK) cells. Natural selection drove an allele-level group A KIR haplotype and the HLA-C1 ligand to unusually high frequency in the Japanese, who provide a particularly informative population for investigating the mechanisms by which KIR and HLA polymorphism influence NK cell repertoire and function. HLA class I ligands increase the frequencies of NK cells expressing cognate KIR, an effect modified by gene dose, KIR polymorphism, and the presence of other cognate ligand–receptor pairs. The five common Japanese KIR3DLI allotypes have distinguishable inhibitory capacity, frequency of cellular expression, and level of cell surface expression as measured by antibody binding. Although KIR haplotypes encoding 3DL1*001 or 3DL1*005, the strongest inhibitors, have no activating KIR, the dominant haplotype encodes a moderate inhibitor, 3DL1*01502, plus functional forms of the activating receptors 2DL4 and 2DS4. In the population, certain combinations of KIR and HLA class I ligand are overrepresented or underrepresented in women, but not men, and thus influence female fitness and survival. These findings show how KIR–HLA interactions shape the genetic and phenotypic KIR repertoires for both individual humans and the population.
The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04
Authors: Salomon Rachelle , Franks John , Govorkova Elena A. , Ilyushina Natalia A. , Yen Hui-Ling , Hulse-Post Diane J. , Humberd Jennifer , Trichet Michel , Rehg Jerold E. , Webby Richard J. , Webster Robert G. , Hoffmann Erich
Published: March 2006

H5N1 influenza viruses transmitted from poultry to humans in Asia cause high mortality and pose a pandemic threat. Viral genes important for cell tropism and replication efficiency must be identified to elucidate and target virulence factors. We applied reverse genetics to generate H5N1 reassortants combining genes of lethal A/Vietnam/1203/04 (VN1203), a fatal human case isolate, and nonlethal A/chicken/Vietnam/C58/04 (CH58) and tested their pathogenicity in ferrets and mice. The viruses' hemagglutinins have six amino acids differences, identical cleavage sites, and avian-like α-(2,3)–linked receptor specificity. Surprisingly, exchanging hemagglutinin and neuraminidase genes did not alter pathogenicity, but substituting CH58 polymerase genes completely attenuated VN1203 virulence and reduced viral polymerase activity. CH58's NS gene partially attenuated VN1203 in ferrets but not in mice. Our findings suggest that for high virulence in mammalian species an avian H5N1 virus with a cleavable hemagglutinin requires adaptive changes in polymerase genes to overcome the species barrier. Thus, novel antivirals targeting polymerase proteins should be developed.
Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens
Authors: Suffia Isabelle J. , Reckling Stacie K. , Piccirillo Ciriaco A. , Goldszmid Romina S. , Belkaid Yasmine
Published: March 2006

Natural regulatory T (T reg) cells are involved in control of the immune response, including response to pathogens. Previous work has demonstrated that the repertoire of natural T reg cells may be biased toward self-antigen recognition. Whether they also recognize foreign antigens and how this recognition contributes to their function remain unknown. Our studies addressed the antigenic specificity of natural T reg cells that accumulate at sites of chronic infection with Leishmania major in mice. Our results support the idea that natural T reg cells are able to respond specifically to foreign antigens in that they strongly proliferate in response to Leishmania-infected dendritic cells, they maintain Foxp3 expression, and Leishmania-specific T reg cell lines can be generated from infected mice. Surprisingly, the majority of natural T reg cells at the infected site are Leishmania specific. Further, we showed that parasite-specific natural T reg cells are restricted to sites of infection and that their survival is strictly dependent on parasite persistence.
Immune responses and HIV: a little order from the chaos
Authors: O'Connor David H. , Burton Dennis R.
Published: March 2006

HIV is evolution gone mad and bad. The virus infects a person and rapidly diversifies to become a huge swarm of viruses, each equipped differently to resist the onslaught of diverse T cells and antibodies. We can't expect to predict details of the struggle between virus and immunity, right? Wrong—maybe we can make some predictions, say two new landmark studies with potentially huge consequences for AIDS vaccine design.
A Single P-loop Glutamate Point Mutation to either Lysine or Arginine Switches the Cation–Anion Selectivity of the CNGA2 Channel
Authors: Qu Wei , Moorhouse Andrew J. , Chandra Meenak , Pierce Kerrie D. , Lewis Trevor M. , Barry Peter H.
Published: March 2006

Cyclic nucleotide-gated (CNG) channels play a critical role in olfactory and visual transduction. Site-directed mutagenesis and inside-out patch-clamp recordings were used to investigate ion permeation and selectivity in two mutant homomeric rat olfactory CNGA2 channels expressed in HEK293 cells. A single point mutation of the negatively charged pore loop (P-loop) glutamate (E342) to either a positively charged lysine or arginine resulted in functional channels, which consistently responded to cGMP, although the currents were generally extremely small. The concentration–response curve of the lysine mutant channel was very similar to that of wild-type (WT) channels, suggesting no major structural alteration to the mutant channels. Reversal potential measurements, during cytoplasmic NaCl dilutions, showed that the lysine and the arginine mutations switched the selectivity of the channel from cations (PCl/PNa = 0.07 [WT]) to anions (PCl/PNa = 14 [Lys] or 10 [Arg]). Relative anion permeability sequences for the two mutant channels, measured with bi-ionic substitutions, were NO3− > I− > Br− > Cl− > F− > acetate−, the same as those obtained for anion-selective GABA and glycine channels. The mutant channels also seem to have an extremely small single-channel conductance, measured using noise analysis of about 1–2 pS, compared to a WT value of about 29 pS. The results showed that it is predominantly the charge of the E342 residue in the P-loop, rather than the pore helix dipoles, which controls the cation–anion selectivity of this channel. However, the outward rectification displayed by both mutant channels in symmetrical NaCl solutions suggests that the negative ends of the pore helix dipoles may play a role in reducing the outward movement of Cl− ions through these anion-selective channels. These results have potential implications for the determinants of anion–cation selectivity in the large family of P-loop–containing channels.