bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mechanisms of Acute Ischemic Injury in the Cell Processes of Developing White Matter Astrocytes
Authors: Salter Michael G , Fern Robert
Published: October 2007

Astrocytes are fundamentally important to the maintenance and proper functioning of the central nervous system. During the period of development when myelination is occurring, white matter astrocytes are particularly sensitive to ischemic injury and their failure to regulate glutamate during ischemic conditions may be an important factor in excitotoxic injury. Here, we have identified key mechanisms of injury that operate on the processes of immature white matter astrocytes during oxygen-glucose deprivation (OGD) using GFAP-GFP mice. Oxygen-glucose deprivation produced a parallel loss of astrocyte processes and somata, assessed by both the retention of GFP fluorescence within these structures and by quantitative electron microscopy. Oxygen-glucose deprivation-induced process loss was Ca2+ independent and had two distinct mechanisms. Substituting either extracellular Na+ or Cl−, or perfusion with the Na—K–Cl co-transport blocker bumetanide, provided protection up to 40 mins of OGD but not beyond that point. HCO−3 substitution or perfusion with 4,4′-diisothiocyanostilbene-2,2′-disulphonic acid provided complete protection of the processes up to 60 mins of OGD. Zero-Na+/zero-K+ conditions provided complete protection from OGD-induced injury of processes and somata at all time points. We conclude that acute ischemic-type injury of immature astrocytes follows a cytotoxic ion influx mediated in part by Na—K–Cl co-transport and in part by Na+- and K+-dependent HCO−3 transport, a mechanism that is common to both cell processes and somata. This work provides a basis on which preventative strategies may be developed to protect white matter astrocytes from ischemic injury in susceptible individuals.
A Concerted Role of Na+—K+—Cl−Cotransporter and Na+/Ca2+Exchanger in Ischemic Damage
Authors: Luo Jing , Wang Yanping , Chen Hai , Kintner Douglas B , Cramer Sam W , Gerdts Josiah K , Chen Xinzhi , Shull Gary E , Philipson Kenneth D , Sun Dandan
Published: October 2007

Na+–K+–Cl−cotransporter isoform 1 (NKCC1) and Na+/Ca2+exchanger isoform 1 (NCX1) were expressed in cortical neurons. Three hours of oxygen and glucose deprivation (OGD) significantly increased expression of full-length NCX1 protein (∼116 kDa), which remained elevated during 1 to 21 h reoxygenation (REOX) and was accompanied with concurrent cleavage of NCX1. Na+/Ca2+exchanger isoform 1 heterozygous (NCX1+/−) neurons with ∼50% less of NCX1 protein exhibited ∼64% reduction in NCX-mediated Ca2+influx. Expression of NCX1 and NKCC1 proteins was reduced in double heterozygous (NCX1+/−/NKCC1+/−) neurons. NCX-mediated Ca2+influx was nearly abolished in these neurons. Three-hour OGD and 21-h REOX caused ∼80% mortality rate in NCX1+/+neurons and in NCX1+/−neurons. In contrast, NKCC1+/−neurons exhibited ∼45% less cell death. The lowest mortality rate was found in NCX1+/−/NKCC1+/−neurons (∼65% less neuronal death). The increased tolerance to ischemic damage was also observed in NCX1+/−/NKCC1+/−brains after transient cerebral ischemia. NCX1+/−/NKCC1+/−mice had a significantly reduced infarct volume at 24 and 72 h reperfusion. In conclusion, these data suggest that NKCC1 in conjunction with NCX1 plays a role in reperfusion-induced brain injury after ischemia.
Total Cerebral Blood Flow, White Matter Lesions and Brain Atrophy: The SMART-MR Study
Authors: Appelman Auke PA , van der Graaf Yolanda , Vincken Koen L , Tiehuis Audrey M , Witkamp Theo D , Mali Willem PTM , Geerlings Mirjam I ,   SMART Study Group
Published: October 2007

We investigated whether total cerebral blood flow (CBF) was associated with brain atrophy, and whether this relation was modified by white matter lesions (WML). Within the Second Manifestations of ARTerial disease-magnetic resonance (SMART-MR) study, a prospective cohort study among patients with arterial disease, cross-sectional analyses were performed in 828 patients (mean age 58±10 years, 81% male) with quantitative flow, atrophy, and WML measurements on magnetic resonance imaging (MRI). Total CBF was measured with MR angiography and was expressed per 100 mL brain volume. Total brain volume and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF) and ventricular fraction (VF). Lower BPF indicates more global brain atrophy, whereas higher VF indicates more subcortical brain atrophy. Mean CBF was 52.0±10.2 mL/min per 100 mL, mean BPF was 79.2±2.9%, and mean VF was 2.03±0.96%. Linear regression analyses showed that lower CBF was associated with more subcortical brain atrophy, after adjusting for age, sex, vascular risk factors, intima-media thickness, and lacunar infarcts, but only in patients with moderate to severe WML (upper quartile of WML): Change in VF per s.d. decrease in CBF 0.18%, 95% CI: 0.02 to 0.34%. Our findings suggest that cerebral hypoperfusion in the presence of WML may be associated with subcortical brain atrophy.
IT Alignment: An Annotated Bibliography
Authors: Chan Yolande E , Reich Blaize Horner
Published: October 2007

We provide summaries of over 150 alignment articles. The information is intended to assist faculty and graduate students who are conducting IT alignment-related research. The findings presented should interest practitioners also. We hope that the article will facilitate the ongoing study and practice of IT alignment.
Force fluctuations and polymerization dynamics of intracellular microtubules
Authors: Brangwynne Clifford P. , MacKintosh F. C. , Weitz David A.
Published: October 2007

Microtubules are highly dynamic biopolymer filaments involved in a wide variety of biological processes including cell division, migration, and intracellular transport. Microtubules are very rigid and form a stiff structural scaffold that resists deformation. However, despite their rigidity, inside of cells they typically exhibit significant bends on all length scales. Here, we investigate the origin of these bends using a Fourier analysis approach to quantify their length and time dependence. We show that, in cultured animal cells, bending is suppressed by the surrounding elastic cytoskeleton, and even large intracellular forces only cause significant bending fluctuations on short length scales. However, these lateral bending fluctuations also naturally cause fluctuations in the orientation of the microtubule tip. During growth, these tip fluctuations lead to microtubule bends that are frozen-in by the surrounding elastic network. This results in a persistent random walk of the microtubule, with a small apparent persistence length of ≈30 μm, ≈100 times smaller than that resulting from thermal fluctuations alone. Thus, large nonthermal forces govern the growth of microtubules and can explain the highly curved shapes observed in the microtubule cytoskeleton of living cells.
Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial
Authors: Siddle Hannah V. , Kreiss Alexandre , Eldridge Mark D. B. , Noonan Erin , Clarke Candice J. , Pyecroft Stephen , Woods Gregory M. , Belov Katherine
Published: October 2007

A fatal transmissible tumor spread between individuals by biting has emerged in the Tasmanian devil (Sarcophilus harrisii), a carnivorous marsupial. Here we provide genetic evidence establishing that the tumor is clonal and therefore foreign to host devils. Thus, the disease is highly unusual because it is not just a tumor but also a tissue graft, passed between individuals without invoking an immune response. The MHC plays a key role in immune responses to both tumors and grafts. The most common mechanism of immune evasion by tumors is down-regulation of classical cell surface MHC molecules. Here we show that this mode of immune escape does not occur. However, because the tumor is a graft, it should still be recognized and rejected by the host's immune system due to foreign cell surface antigens. Mixed lymphocyte responses showed a lack of alloreactivity between lymphocytes of different individuals in the affected population, indicating a paucity of MHC diversity. This result was verified by genotyping, providing a conclusive link between a loss of MHC diversity and spread of a disease through a wild population. This novel disease arose as a direct result of loss of genetic diversity and the aggressive behavior of the host species. The neoplastic clone continues to spread although the population, and, without active disease control by removal of affected animals and the isolation of disease-free animals, the Tasmanian devil faces extinction.
Native language governs interpretation of salient speech sound differences at 18 months
Authors: Dietrich Christiane , Swingley Daniel , Werker Janet F.
Published: October 2007

One of the first steps infants take in learning their native language is to discover its set of speech-sound categories. This early development is shown when infants begin to lose the ability to differentiate some of the speech sounds their language does not use, while retaining or improving discrimination of language-relevant sounds. However, this aspect of early phonological tuning is not sufficient for language learning. Children must also discover which of the phonetic cues that are used in their language serve to signal lexical distinctions. Phonetic variation that is readily discriminable to all children may indicate two different words in one language but only one word in another. Here, we provide evidence that the language background of 1.5-year-olds affects their interpretation of phonetic variation in word learning, and we show that young children interpret salient phonetic variation in language-specific ways. Three experiments with a total of 104 children compared Dutch- and English-learning 18-month-olds' responses to novel words varying in vowel duration or vowel quality. Dutch learners interpreted vowel duration as lexically contrastive, but English learners did not, in keeping with properties of Dutch and English. Both groups performed equivalently when differentiating words varying in vowel quality. Thus, at one and a half years, children's phonological knowledge already guides their interpretation of salient phonetic variation. We argue that early phonological learning is not just a matter of maintaining the ability to distinguish language-relevant phonetic cues. Learning also requires phonological interpretation at appropriate levels of linguistic analysis.
Structure of outer membrane protein G by solution NMR spectroscopy
Authors: Liang Binyong , Tamm Lukas K.
Published: October 2007

The bacterial outer membrane protein G (OmpG), a monomeric pH-gated porin, was overexpressed in
Escherichia coli
and refolded in β-octyl glucoside micelles. After transfer into dodecylphosphocholine micelles, the solution structure of OmpG was determined by solution NMR spectroscopy at pH 6.3. Complete backbone assignments were obtained for 234 of 280 residues based on CA, CB, and CO connection pathways determined from a series of TROSY-based 3D experiments at 800 MHz. The global fold of the 14-stranded β-barrel was determined based on 133 long-range NOEs observed between neighboring strands and local chemical shift and NOE information. The structure of the barrel is very similar to previous crystal structures, but the loops of the solution structure are quite flexible.
Human combinatorial libraries yield rare antibodies that broadly neutralize hepatitis C virus
Authors: Johansson Daniel X. , Voisset Cécile , Tarr Alexander W. , Aung Mie , Ball Jonathan K. , Dubuisson Jean , Persson Mats A. A.
Published: October 2007

One way to dissect the antibody response to an invading microorganism is to clone the antibody repertoire from immune donors and subsequently characterize the specific antibodies. Recently, methodological advances have allowed investigations of neutralizing antibodies against hepatitis C virus (HCV)
in vitro
. We have investigated three human mAbs, previously isolated from an individual infected with HCV of genotype 2b, that are known to cross-react in a binding assay to the envelope E2 protein of genotypes 1a and 1b. We now report that two of them have a neutralizing activity with a breadth not previously observed. Indeed, mAbs 1:7 and A8 recognized E2 from all of the six major genotypes, and they neutralized retroviral pseudoparticles [HCV pseudoparticles (HCVpp)] carrying genetically equally diverse HCV envelope glycoproteins. Importantly, these antibodies were also able to neutralize the cell culture infectious HCV clone JFH-1
in vitro
, with IC
50
values of 60 ng/ml and 560 ng/ml, respectively. The conformational epitopes of these two broadly reactive antibodies were overlapping yet distinct and involved amino acid residues in the 523–535 region of E2, known to be important for the E2–CD81 interaction. The third antibody clone, representing a dominant population in the initial screen for these antibodies, was less broadly reactive and was unable to neutralize the genotype 2a infectious clone JFH-1. Our results confirm at the clonal level that broadly neutralizing human anti-HCV antibodies can be elicited and that the region amino acids 523–535 of the HCV envelope glycoprotein E2 carries neutralizing epitopes conserved across all genotypes.
Time course and calcium dependence of transmitter release at a single ribbon synapse
Authors: Goutman Juan D. , Glowatzki Elisabeth
Published: October 2007

At the first synapse in the auditory pathway, the receptor potential of mechanosensory hair cells is converted into a firing pattern in auditory nerve fibers. For the accurate coding of timing and intensity of sound signals, transmitter release at this synapse must occur with the highest precision. To measure directly the transfer characteristics of the hair cell afferent synapse, we implemented simultaneous whole-cell recordings from mammalian inner hair cells (IHCs) and auditory nerve fiber terminals that typically receive input from a single ribbon synapse. During a 1-s IHC depolarization, the synaptic response depressed >90%, representing the main source for adaptation in the auditory nerve. Synaptic depression was slightly affected by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor desensitization; however, it was mostly caused by reduced vesicular release. When the transfer function between transmitter release and Ca
2+
influx was tested at constant open probability for Ca
2+
channels (potentials >0 mV), a super linear relation was found. This relation is presumed to result from the cooperative binding of three to four Ca
2+
ions at the Ca
2+
sensor. However, in the physiological range for receptor potentials (−50 to −30 mV), the relation between Ca
2+
influx and afferent activity was linear, assuring minimal distortion in the coding of sound intensity. Changes in Ca
2+
influx caused an increase in release probability, but not in the average size of multivesicular synaptic events. By varying Ca
2+
buffering in the IHC, we further investigate how Ca
2+
channel and Ca
2+
sensor at this synapse might relate.
Toxofilin from
Toxoplasma gondii
forms a ternary complex with an antiparallel actin dimer
Authors: Lee Sung Haeng , Hayes David B. , Rebowski Grzegorz , Tardieux Isabelle , Dominguez Roberto
Published: October 2007

Many human pathogens exploit the actin cytoskeleton during infection, including
Toxoplasma gondii
, an apicomplexan parasite related to
Plasmodium
, the agent of malaria. One of the most abundantly expressed proteins of
T. gondii
is toxofilin, a monomeric actin-binding protein (ABP) involved in invasion. Toxofilin is found in rhoptry and presents an N-terminal signal sequence, consistent with its being secreted during invasion. We report the structure of toxofilin amino acids 69–196 in complex with the host mammalian actin. Toxofilin presents an extended conformation and interacts with an antiparallel actin dimer, in which one of the actins is related by crystal symmetry. Consistent with this observation, analytical ultracentrifugation analysis shows that toxofilin binds two actins in solution. Toxofilin folds into five consecutive helices, which form three relatively independent actin-binding sites. Helices 1 and 2 bind the symmetry-related actin molecule and cover its nucleotide-binding cleft. Helices 3–5 bind the other actin and constitute the primary actin-binding region. Helix 3 interacts in the cleft between subdomains 1 and 3, a common binding site for most ABPs. Helices 4 and 5 wrap around actin subdomain 4, and residue Gln-134 of helix 4 makes a hydrogen-bonding contact with the nucleotide in actin, both of which are unique features among ABPs. Toxofilin dramatically inhibits nucleotide exchange on two actin molecules simultaneously. This effect is linked to the formation of the antiparallel actin dimer because a construct lacking helices 1 and 2 binds only one actin and inhibits nucleotide exchange less potently.
Guanine riboswitch variants from
Mesoplasma florum
selectively recognize 2′-deoxyguanosine
Authors: Kim Jane N. , Roth Adam , Breaker Ronald R.
Published: October 2007

Several mRNA aptamers have been identified in
Mesoplasma florum
that have sequence and structural features resembling those of guanine and adenine riboswitches. Two features distinguish these RNAs from established purine-sensing riboswitches. All possess shortened hairpin-loop sequences expected to alter tertiary contacts known to be critical for aptamer folding. The RNAs also carry nucleotide changes in the core of each aptamer that otherwise is strictly conserved in guanine and adenine riboswitches. Some aptamers retain the ability to selectively bind guanine or adenine despite these mutations. However, one variant type exhibits selective and high-affinity binding of 2′-deoxyguanosine, which is consistent with its occurrence in the 5′ untranslated region of an operon containing ribonucleotide reductase genes. The identification of riboswitch variants that bind nucleosides and reject nucleobases reveals that natural metabolite-sensing RNA motifs can accrue mutations that expand the diversity of ligand detection in bacteria.
Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia
Authors: Jones Kristian L. , Mansell Ashley , Patella Shane , Scott Bernadette J. , Hedger Mark P. , de Kretser David M. , Phillips David J.
Published: October 2007

Activin A is a member of the transforming growth factor-β superfamily, which we have identified as having a role in inflammatory responses. We show that circulating levels of activin increase rapidly after LPS-induced challenge through activation of Toll-like receptor 4 and the key adaptor protein, MyD88. Treatment with the activin-binding protein, follistatin, alters the profiles of TNF, IL-1β, and IL-6 after LPS stimulation, indicating that activin modulates the release of several key proinflammatory cytokines. Further, mice administered one 10-μg dose of follistatin to block activin effects have increased survival after a lethal dose of LPS, and the circulating levels of activin correlate with survival outcome. These findings demonstrate activin A's crucial role in the inflammatory response and show that blocking its actions by the use of follistatin has significant therapeutic potential to reduce the severity of inflammatory diseases.
Gel-forming mucins appeared early in metazoan evolution
Authors: Lang Tiange , Hansson Gunnar C. , Samuelsson Tore
Published: October 2007

Mucins are proteins that cover and protect epithelial cells and are characterized by domains rich in proline, threonine, and serine that are heavily glycosylated (PTS or mucin domains). Because of their sequence polymorphism, these domains cannot be used for evolutionary analysis. Instead, we have made use of the von Willebrand D (VWD) and SEA domains, typical for mucins. A number of animal genomes were examined for these domains to identify mucin homologues, and domains of the resulting proteins were used in phylogenetic studies. The frog
Xenopus tropicalis
stands out because the number of gel-forming mucins has markedly increased to at least 25 as compared with 5 for higher animals. Furthermore, the frog Muc2 homologues contain unique PTS domains where cysteines are abundant. This animal also has a unique family of secreted mucin-like proteins with alternating PTS and SEA domains, a type of protein also identified in the fishes. The evolution of the Muc4 mucin seems to have occurred by recruitment of a PTS domain to AMOP, NIDO, and VWD domains from a sushi domain-containing family of proteins present in lower animals, and
Xenopus
is the most deeply branching animal where a protein similar to the mammalian Muc4 was identified. All transmembrane mucins seem to have appeared in the vertebrate lineage, and the MUC1 mucin is restricted to mammals. In contrast, proteins with properties of the gel-forming mucins were identified also in the starlet sea anemone
Nematostella vectensis
, demonstrating an early origin of this group of mucins.
Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death
Authors: Jang Sung-Wuk , Okada Masashi , Sayeed Iqbal , Xiao Ge , Stein Donald , Jin Peng , Ye Keqiang
Published: October 2007

Nerve growth factor (NGF) binds to TrkA receptor and triggers activation of numerous signaling cascades, which play critical roles in neuronal plasticity, survival, and neurite outgrowth. To mimic NGF functions pharmacologically, we developed a high-throughput screening assay to identify small-molecule agonists for TrkA receptor. The most potent compound, gambogic amide, selectively binds to TrkA, but not TrkB or TrkC, and robustly induces its tyrosine phosphorylation and downstream signaling activation, including Akt and MAPKs. Further, it strongly prevents glutamate-induced neuronal cell death and provokes prominent neurite outgrowth in PC12 cells. Gambogic amide specifically interacts with the cytoplasmic juxtamembrane domain of TrkA receptor and triggers its dimerization. Administration of this molecule in mice substantially diminishes kainic acid-triggered neuronal cell death and decreases infarct volume in the transient middle cerebral artery occlusion model of stroke. Thus, gambogic amide might not only establish a powerful platform for dissection of the physiological roles of NGF and TrkA receptor but also provide effective treatments for neurodegenerative diseases and stroke.
Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype
Authors: Harari Alexandre , Cellerai Cristina , Enders Felicitas Bellutti , Köstler Josef , Codarri Laura , Tapia Gonzalo , Boyman Onur , Castro Erika , Gaudieri Silvana , James Ian , John Mina , Wagner Ralf , Mallal Simon , Pantaleo Giuseppe
Published: October 2007

We studied CD8 T cell responses against HIV-1, cytomegalovirus, Epstein–Barr virus, and influenza in 128 subjects and demonstrate that polyfunctional CD8 T cell responses, also including IL-2 production and Ag-specific proliferation, are predominantly driven by virus epitopes restricted by HLA-B alleles. Interestingly, these protective CD8 T cells are equipped with low-avidity T cell receptors (TCRs) for the cognate virus epitope. Conversely, HLA-A-restricted epitopes are mostly associated with “only effector” IFN-γ-secreting, with cytotoxicity, and with the lack of IL-2 production and Ag-specific proliferation. These CD8 T cells are equipped with high-avidity TCR and express higher levels of the T cell exhaustion marker PD-1. Thus, the functional profile of the CD8 T cell response is strongly influenced by the extent to which there is stimulation of polyfunctional (predominantly restricted by HLA-B) versus only effector (restricted by HLA-A) T cell responses. These results provide the rationale for the observed protective role of HLA-B in HIV-1-infection and new insights into the relationship between TCR avidity, PD-1 expression, and the functional profile of CD8 T cells.
Ca
2+
influx is an essential component of the positive-feedback loop that maintains leading-edge structure and activity in macrophages
Authors: Evans John H. , Falke Joseph J.
Published: October 2007

In migrating eukaryotic cells, phosphatidylinositol 3-kinase (PI3K), filamentous actin (F-actin), and monomeric Rho GTPases are key components of a complex positive-feedback system that maintains and amplifies a phosphatidylinositol-3,4,5-trisphosphate signal at the leading edge of the cell. This lipid signal is required for cell polarization and movement. In leukocytes and
Dictyostelium
, activation or inhibition of any one of these components leads to the activation or inhibition, respectively, of the others via undefined feedback interactions. The role of Ca
2+
signals in migrating leukocytes is controversial, and there has been no indication that Ca
2+
participates in positive feedback. Here, we demonstrate that an extracellular Ca
2+
influx is required for positive feedback at the leading edge of spontaneously polarized macrophages. Inhibition of extracellular Ca
2+
influx leads to loss of leading-edge PI3K activity, disassembly of F-actin, cessation of ruffling, and decay of chemoattractant signals. Conversely, increasing cytosolic Ca
2+
enhances membrane ruffling, PI3K activity, and F-actin accumulation. Overall, these findings demonstrate that an extracellular Ca
2+
influx is an essential component, together with PI3K and F-actin, of the positive-feedback cycle that maintains leading-edge structure and ruffling activity and that supports the chemoattractant response. Strikingly, the Ca
2+
-sensitive enzyme protein kinase Cα (PKCα) is enriched at the leading edge, and its enrichment is sensitive to blockade of Ca
2+
influx, to inhibition of PI3K activity, and to F-actin depolymerization. These findings support the working hypothesis that a local, leading-edge Ca
2+
signal recruits PKCα as a central player in the positive-feedback loop.
Adaptations of guest and host in expanded self-assembled capsules
Authors: Ajami Dariush , Rebek Julius
Published: October 2007

Reversible encapsulation complexes create spaces where two or more molecules can be temporarily isolated. When the mobility of encapsulated molecules is restricted, different arrangements in space are possible, and new forms of isomerism (“social isomerism”) are created: the orientation of one encapsulated molecule influences that of the other in the confined space. Expansion of a capsule's length is possible through addition of small-molecule spacer elements. The expanded capsules have dimensions that permit the observation of social isomerism of two identical guests, and they adopt arrangements that properly fill the host's space. The host also can adapt to longer guests by incorporating additional spacers, much as protein modules are added to a viral capsid in response to larger genomes. Arachidonic and related fatty acid derivatives act in this way to induce the assembly of further extended capsules having sufficient length to accommodate them.
Plasma sodium stiffens vascular endothelium and reduces nitric oxide release
Authors: Oberleithner Hans , Riethmüller Christoph , Schillers Hermann , MacGregor Graham A. , de Wardener Hugh E. , Hausberg Martin
Published: October 2007

Dietary salt plays a major role in the regulation of blood pressure, and the mineralocorticoid hormone aldosterone controls salt homeostasis and extracellular volume. Recent observations suggest that a small increase in plasma sodium concentration may contribute to the pressor response of dietary salt. Because endothelial cells are (
i
) sensitive to aldosterone, (
ii
) in physical contact with plasma sodium, and (
iii
) crucial regulators of vascular tone, we tested whether acute changes in plasma sodium concentration, within the physiological range, can alter the physical properties of endothelial cells. The tip of an atomic force microscope was used as a nanosensor to measure stiffness of living endothelial cells incubated for 3 days in a culture medium containing aldosterone at a physiological concentration (0.45 nM). Endothelial cell stiffness was unaffected by acute changes in sodium concentration <135 mM but rose steeply between 135 and 145 mM. The increase in stiffness occurred within minutes. Lack of aldosterone in the culture medium or treatment with the epithelial sodium channel inhibitor amiloride prevented this response. Nitric oxide formation was found down-regulated in cells cultured in aldosterone-containing high sodium medium. The results suggest that changes in plasma sodium concentration
per se
may affect endothelial function and thus control vascular tone.
An interpretation of fluctuations in enzyme catalysis rate, spectral diffusion, and radiative component of lifetimes in terms of electric field fluctuations
Authors: Prakash Meher K. , Marcus R. A.
Published: October 2007

Time-dependent fluctuations in the catalysis rate (δ
k(t)
) observed in single-enzyme experiments were found in a particular study to have an autocorrelation function decaying on the same time scale as that of spectral diffusion δω
0
(
t
). To interpret this similarity, the present analysis focuses on a factor in enzyme catalysis, the local electrostatic interaction energy (
E
) at the active site and its effect on the activation free energy barrier. We consider the slow fluctuations of the electrostatic interaction energy (δ
E(t))
as a contributor to δ
k(t)
and relate the latter to δω
0
(
t
). The resulting relation between δ
k(t)
and δω
0
(
t
) is a dynamic analog of the solvatochromism used in interpreting solvent effects on organic reaction rates. The effect of the postulated δ
E(t)
on fluctuations in the radiative component (δγ
r
−1
(
t
)) of the fluorescence decay of chromophores in proteins also is examined, and a relation between δγ
r
−1
(
t
) and δω
0
(t) is obtained. Experimental tests will determine whether the correlation functions for δ
k(t)
, δω
0
(
t
), and δγ
r
−1
are indeed similar for any enzyme. Measurements of dielectric dispersion, ε(ω), for the enzyme discussed elsewhere will provide further insight into the correlation function for δ
E(t)
. They also will determine whether fluctuations in the nonradiative component γ
nr
−1
of the lifetime decay has a different origin, fluctuations in distance for example.
A surface on the androgen receptor that allosterically regulates coactivator binding
Authors: Estébanez-Perpiñá Eva , Arnold Leggy A. , Nguyen Phuong , Rodrigues Edson Delgado , Mar Ellena , Bateman Raynard , Pallai Peter , Shokat Kevan M. , Baxter John D. , Guy R. Kiplin , Webb Paul , Fletterick Robert J.
Published: October 2007

Current approaches to inhibit nuclear receptor (NR) activity target the hormone binding pocket but face limitations. We have proposed that inhibitors, which bind to nuclear receptor surfaces that mediate assembly of the receptor's binding partners, might overcome some of these limitations. The androgen receptor (AR) plays a central role in prostate cancer, but conventional inhibitors lose effectiveness as cancer treatments because anti-androgen resistance usually develops. We conducted functional and x-ray screens to identify compounds that bind the AR surface and block binding of coactivators for AR activation function 2 (AF-2). Four compounds that block coactivator binding in solution with IC
50
≈ 50 μM and inhibit AF-2 activity in cells were detected: three nonsteroidal antiinflammatory drugs and the thyroid hormone 3,3′,5-triiodothyroacetic acid. Although visualization of compounds at the AR surface reveals weak binding at AF-2, the most potent inhibitors bind preferentially to a previously unknown regulatory surface cleft termed binding function (BF)-3, which is a known target for mutations in prostate cancer and androgen insensitivity syndrome. X-ray structural analysis reveals that 3,3′,5-triiodothyroacetic acid binding to BF-3 remodels the adjacent interaction site AF-2 to weaken coactivator binding. Mutation of residues that form BF-3 inhibits AR function and AR AF-2 activity. We propose that BF-3 is a previously unrecognized allosteric regulatory site needed for AR activity
in vivo
and a possible pharmaceutical target.
A pilot study of Supplemental Instruction for at-risk students at an Historically Black University (HBU) in South Africa
Authors: Zulu Constance
Published: October 2007

This article discusses a pilot investigation conducted between February and May 2002. The aim of this investigation was to assess the efficacy of the Supplemental Instruction (SI) program — which has a proven track record elsewhere — at an historically black university in South Africa. SI is an academic assistance program which was developed at the University of Missouri- Kansas City in 1973 by Deanna C. Martin and subsequently adopted countrywide and in other parts of the world. The pilot was conducted on a population of first year law students registered for an introductory module, “Introduction to South African Legal Method and Theory”. Two questions were investigated: 1. Does SI have an effect on students’ mastery of content? 2. Does SI have an effect on students’ perceptions of their mastery of skills? Three measures were used to explore these questions, namely pre and posttests of content mastery; student perception of skill mastery and end of course grades. Although there was no significant difference on the mastery of course content between SI and Non-SI participants, it was found that higher SI attendance rates resulted in slightly higher mean grades, suggesting that SI may have had some impact on the final course end grades. A significant difference at the .03 level was found between the mean grades of students who attended 4 or more sessions and those who attended 1–3 sessions. The investigation also revealed that a number of barriers and challenges need to be addressed for a successful SI program to be implemented at the university.
Discourse, culture and the law
Authors: Thetela Pulie
Published: October 2007

The aim of this paper is to analyse the nature of the courtroom discourse in an African context. The nature of courtroom discourse has been extensively discussed and and analysed in non-African contexts. This paper, however, makes a unique contribution by analysing the nature of courtroom discourse in multilingual courts in Southern Africa. The contribution is unique because it investigates the probematic nature of courtroom interpretation, using the theoretical notion of crosstalk, in multilingual communities when the communicative styles of the participants are divergent and conflicting. More significantly the paper illustrates the potential impact of a special register hlonipha-the language of respect for women. The paper concludes by looking at ways in which through register we can intrerrogate power relations in courtroom discourse and examine the implications of such power discrepancy on the delivery of justice.
Phonological theory and the development of prosodic structure
Authors: Ota Mitsuhiko
Published: October 2007

This article presents a model of prosodic structure development that takes account of the fundamental continuity between child and adult systems, the surface level divergence of child forms from their adult target forms, and the overall developmental paths of prosodic structure. The main empirical base for the study comes from longitudinal data collected from three Japanese-speaking children (1; 0–2; 6). Evidence for word-internal prosodic constituents including the mora and the foot is found in compensatory lengthening phenomena, syllable size restrictions and word size restrictions in early word production. By implementing the representational principles that organize these prosodic categories as rankable and violable constraints, Optimality Theory can provide a systematic account of the differences in the prosodic structure of child and adult Japanese while assuming representational continuity between the two. A constraint-based model of prosodic structure acquisition is also shown to demarcate the learning paths in a way that is consistent with the data.
Bifurcating the verb particle construction
Authors: Sawyer Joan
Published: October 2007

In the literature, John threw the ball up and The baby threw his dinner up have both been treated as members of the set of verb particle constructions (VPC). Syntactic evidence from action nominalizations, insertion of degree adverbials, contrastive stress, and gapped constructions (Fraser, 1976) suggests that the VPC must be bifurcated into two classes: a verb adverb construction (VAC) containing a verb, a complement, and an adverb and a VPC with a verb, complement, and a particle. Literature on the acquisition of the VPC has not taken this distinction into account. This article focuses on the acquisition of the VAC. The patterning on syntactic tests is a result of the fact that adverbs are predicators and particles are not. Additional syntactic tests (initial coordination of adverbs and adverbs+PPs and placing locative adverbs in argument positions) suggest that adverbs (not particles) are phrasal constituents: the adverb takes the apparent object as its subject. The bifurcation of the VPC and the suggested structure are supported by evidence from child language acquisition. Children treat the two constructions differently from the earliest stages. Crucially, the overwhelming error (79%) in VAC use is dropping the grammatical object. The timing of this error corresponds to that of subject drop in the null subject stage.
A connection in lexical development
Authors: van Helden-Lankhaar Marja
Published: October 2007

The relationship is examined between two different domains of lexical development: innovative compounding and access to abstract lexical relations. The creation of novel compounds as appropriate labels for novel concepts requires the accessibility of relatively abstract relations between word meanings in the mental lexicon. In a picture naming task in which novel concepts have to be labeled (e.g., a vehicle that can both sail and drive) children’s production of appropriate novel compounds (e.g., car-boat) increases with age. This compound production is, independently of age, related to children’s ability to access coordinate lexical relations (such as between cat and dog) in a contrastive word association task (‘a cat is not a...?’). It is proposed that this connection between innovative compounding and access to coordinate relations is cognitive in nature and involves a common ability for lexical comparisons. Innovative compounding reflects comparison ‘on the spot’ between the novel concept and available related word meaning knowledge, and contrastive coordinate production reflects the results of developmentally earlier comparison processes evoked by adult contrastive input.
Derived words in the lexicon of Polish children
Authors: Haman Ewa
Published: October 2007

The present work is an attempt to explain how the structure of derived words influences the order of acquisition of word formation rules. Three main types of derivatives  transpositions, modifications and mutations  are investigated in Polish child language. The differences among the three categories (analyzed in nouns, verbs and adjectives) are discussed, regarding semantic and formal changes undergone in the process of forming complex words. It is claimed that semantic-formal correspondence is an essential factor influencing the order of acquisition of word formation rules. Modifications in which the correspondence is both preserved and has a simple character emerge earlier than the other types of derivatives  transpositions (the correspondence is broken) and mutations (the correspondence is complex). The proposal is said to be complementary to Clarks principles of acquisition of complex words (Clark, 1993).

Polish has a very rich word formation system (compared e.g. with English), thus the analysis of word formation acquisition in such a language seems to be especially important for developmental psycholinguistic research. The proposal is tested on four Polish childrens speech diaries available in CHILDES (Smoczynska, 1998). All data available from ages two to seven were analyzed. The analyses revealed that indeed modifications are acquired earlier than transpositions and mutations. The consequences of the finding for psycholinguistic theory are discussed.
Language discrimination by newborns
Authors: Ramus Franck
Published: October 2007

Speech rhythm has long been claimed to be a useful bootstrapping cue in the very first steps of language acquisition. Previous studies have suggested that newborn infants do categorize varieties of speech rhythm, as demonstrated by their ability to discriminate between certain languages. However, the existing evidence is not unequivocal: in previous studies, stimuli discriminated by newborns always contained additional speech cues on top of rhythm. Here, we conducted a series of experiments assessing discrimination between Dutch and Japanese by newborn infants, using a speech resynthesis technique to progressively degrade non-rhythmical properties of the sentences. When the stimuli are resynthesized using identical phonemes and artificial intonation contours for the two languages, thereby preserving only their rhythmic and broad phonotactic structure, newborns still seem to be able to discriminate between the two languages, but the effect is weaker than when intonation is present. This leaves open the possibility that the temporal correlation between intonational and rhythmic cues might actually facilitate the processing of speech rhythm.
Aspects de la traduction publicitaire
Authors: Guidere Mathieu
Published: October 2007

The proliferation of international advertising campaigns has brought the translator to the forefront and opened the way for the marked expansion of what can conveniently be styled “advertising translation”. This is increasingly emerging as a key factor in the business worldþs internationalization strategies. The present article gives a survey of the factors — both exogenous and endogenous — which exert an influence in this type of translation and provides a detailed study of the object and the method used to optimize interlinguistic transference. The specificity of the advertising text is manifest both from the communication standpoint and from the strictly semiotic angle and calls for distinctive treatment. Hence the translator of advertising material cannot afford any skimping in a linguistic analysis of the significant structure with which he has to deal. For it is the perceptiveness of his analysis that will determine the quality of the translationand the success of the advertising campaign.
Practice Orientation in the Teaching of LSP Translation
Authors: Holljen Maj-Britt
Published: October 2007

The issue of translator training has become one of FIT’s principal concerns, as it touches fundamental aspects of the future of the field of translation generally, and of LSP translation in particular. Quality assurance in connection with translation studies is not something that is built up over night. I have long been concerned with the problem of how to integrate into the students’ workload texts which not just reflect but rather challenge the different kinds of requirements demanded by their future employers. The POSI project — PraxisOrientierte Studieninhalte für die Ausbildung von Übersetzern und Dolmetschern – is approaching the same problem from a different angle, namely by focusing on the market’s need for qualified translators, and defining qualified as including not just the actual translating abilities, but indeed abilities to manage the entire translation process with all its extra-textual aspects. Theoretically I lean on Christiane Nord and the functionalist model of translation in my didactic approach to translator training.

The article is two sided: a)it is a report on a three-year research project involving the introduction of real external translation assignments into the curriculum of LSP translation studies, and b) it is a didactic reflection on this kind of practical orientation, on what we are able to achieve, how and why it is so vital to enlarge the scope of teaching translation in this direction.
La phraséologie en terminologie
Authors: Tryuk Malgorzata
Published: October 2007

In the context of terminology, phraseology is considered to be the linguistic study of particular terms and their environment, and terminological phraseologism is understood to be a combination of lexemes which is neither totally fixed nor completely free (e.g. of the type: N+Adj, N+V, V+N) , with the term as its stable core.

The author maintains that any research in the area of terminological phraseology should recognize the fact that all kinds of specialized texts are characterized in equal measure by terminology specific to the field in question, and by special phraseology both marked by frequency of usage, specific concentration, usage peculiar to a given field or discipline. Translators of specialized texts should be aware of these peculiarities. It is thus natural that they expect theoreticians authors of mono-, bi- and multilingual studies in the area of terminological phraseology to provide them with tools which would make it possible to identify these special entities; it is also understandable that they expect terminographers to supply them with phraseological data banks.
Vocabulary in LSP
Authors: Khuwaileh Abdulla Aied
Published: October 2007

The paper aims at exploring some of the conditions and ways in which LSP(Language for Special Purposes) adult learners perceive misleading vocabulary. Specifically, the paper represents an attempt to find out whether adult learners of English who know the meaning of certain words can or cannot work out the new meaning of phrases or collocation which would result from the combination of two or more words. on top of this, we will try to give reasons for the learners’ inaccurate guesses. The phrases and/or collocations used in this study were contextualised in sentences to show or mirror our learners’ ability in working out their collocational new meanings. To achieve this objective, two methods were followed. First, individual general words (not technical) were taught and then a combination of two or more of these words (to give specific meanings) was worked out by 80 LSP learners through context. Second, after testing the same learners in these words and grading their responses, both descriptive and inferential statistics were used to indicate both frequencies and statistical significance levels. The samples and teaching situation were taken from the Jordan University of Science and Technology.

The study showed that JUST learners found difficulties in working out or guessing the specific meanings of phrases and collocations when combined to form new meanings though they knew the meaning of each word individually. These phrases look deceptively easy to our Arabic speaking LSP learners at first sight, but their meanings can be radically different from what our learners might expect. The study ends up with a number of practical teaching implications including paraphrasing and idiomaticity in the first place. Finally, some other research recommendations were suggested.
Syntactic Competence as a Prerequisite for Translation
Authors: Homeidi Moheiddin A.
Published: October 2007

Two main points are discussed in this paper: first, a syntactic analysis of some of the verb complements in Arabic in the Government and Binding framework, henceforth GB. These include the following: the object , the absolute object, the causative object or the object of result, the comitative object, the locative object (adverb of place) and the temporal object (adverb of time). Second how such structures might be translated into English. Do they keep their syntactic categories as in Arabic or should they take some different syntactic forms but with the same meaning. The analysis shows quite clearly that syntactic categories cannot be kept through the process of translation although the meanings can be rendered quite properly.