bluuebunny/crossref_metadata_2025 huggingface dataset:
A Neuroimaging Study of Premotor Lateralization and Cerebellar Involvement in the Production of Phonemes and Syllables
Authors: Ghosh Satrajit S. , Tourville Jason A. , Guenther Frank H.
Published: July 2008

Purpose

This study investigated the network of brain regions involved in overt production of vowels, monosyllables, and bisyllables to test hypotheses derived from the Directions Into Velocities of Articulators (DIVA) model of speech production (Guenther, Ghosh, & Tourville, 2006). The DIVA model predicts left lateralized activity in inferior frontal cortex when producing a single syllable or phoneme and increased cerebellar activity for consonant–vowel syllables compared with steady-state vowels.

Method

Sparse sampling functional magnetic resonance imaging (fMRI) was used to collect data from 10 right-handed speakers of American English while producing isolated monosyllables (e.g., “ba,” “oo”). Data were analyzed using both voxel-based and participant-specific anatomical region-of-interest–based techniques.

Results

Overt production of single monosyllables activated a network of brain regions, including left ventral premotor cortex, left posterior inferior frontal gyrus, bilateral supplementary motor area, sensorimotor cortex, auditory cortex, thalamus, and cerebellum. Paravermal cerebellum showed greater activity for consonant-vowel syllables compared to vowels.

Conclusions

The finding of left-lateralized premotor cortex activity supports the DIVA model prediction that this area contains cell populations representing syllable motor programs without regard for semantic content. Furthermore, the superior paravermal cerebellum is more active for consonant–vowel syllables compared with vowels, perhaps due to increased timing constraints for consonant production.
Parameters to Maximize 2f2-f1 Distortion Product Otoacoustic Emission Levels
Authors: Horn Jennifer H. , Pratt Sheila R. , Durrant John D.
Published: July 2008

Purpose

Past research has established parameters for the 2f1-f2 distortion product otoacoustic emissions (DPOAEs) that enhance response levels (e.g., L1 – L2 = 10 dB; f2/f1 = 1.22; L1, L2 = 65, 55 dB SPL). These same parameters do not optimize 2f2-f1 DPOAEs. Therefore, this study was conducted to evaluate more completely those parameters that produce the most robust 2f2-f1 output.

Method

Input–output functions of the 2f2-f1 component were obtained from 20 normal-hearing adults (with f2 = 2000 Hz and 4000 Hz). Frequency ratios, level differences, and overall sound levels were manipulated with parameter combinations chosen to expand on information established in previous studies. The DPOAE signal-to-noise ratio (SNR), response presence, and output levels were measured.

Results

In general, mean SNRs and 2f2-f1 levels were greater, and DPOAEs were present more often for 2000 than for 4000 Hz across all parameter combinations. No single parameter combination resulted in pronounced maxima for 2f2-f1, which is consistent with past studies but is in sharp contrast to results for the more familiar 2f1-f2.

Conclusions

Overall, the results suggest that to maximize the 2f2-f1 level, lower test frequencies, low frequency ratio, essentially equal levels of primary tones, and moderate stimulus levels are best, and such parameters might be important for applying DPOAE measurement to assessment of normal and impaired auditory function.
Changes in Speech Production Associated With Alphabet Supplementation
Authors: Hustad Katherine C. , Lee Jimin
Published: July 2008

Purpose

This study examined the effect of alphabet supplementation (AS) on temporal and spectral features of speech production in individuals with cerebral palsy and dysarthria.

Method

Twelve speakers with dysarthria contributed speech samples using habitual speech and while using AS. One hundred twenty listeners orthographically transcribed speech samples. Differences between habitual and AS speech were examined for intelligibility, rate, word duration, vowel duration, pause duration, pause frequency, vowel space, and first and second formant frequency (F1 and F2) values for corner vowels.

Results

Descriptive results showed that intelligibility was higher, rate of speech was slower, and pause duration and pause frequency were greater for AS than for habitual speech. Inferential statistics showed that vowel duration, word duration, and vowel space increased significantly for AS. Vowel space did not differ for male and female speakers; however, there was an interaction between sex and speaking condition. Changes in vowel space were accomplished by reductions in F2 for /u/. Vowel space accounted for more variability in intelligibility than rate for AS; the opposite was true for habitual speech.

Conclusion

AS is associated with temporal and spectral changes in speech production. Spectral changes associated with corner vowels appear to be more important than temporal changes.
Broadband Auditory Stream Segregation by Hearing-Impaired and Normal-Hearing Listeners
Authors: Valentine Susie , Lentz Jennifer J.
Published: July 2008

Purpose

To investigate the effects of hearing loss on auditory stream segregation of broadband inharmonic sounds.

Method

Auditory stream segregation by listeners with normal and impaired hearing was measured for 6-component inharmonic sounds (“A” and “B”) using objective and subjective methods. Components in the A stimuli ranged between 1000 and 4000 Hz, whereas B stimuli were generated at the same frequency ratio but scaled upward in frequency relative to the A stimuli. In Experiment 1, streaming was measured by having listeners detect a delay inserted into a sequence of A and B stimuli (A_B_A_B_…) for B stimuli with different frequencies. In Experiment 2, streaming was measured using an ABA_ABA_… sequence, and the frequency of the B stimulus decreased until listeners reported that they could “no longer hear two separate streams.”

Results

Experiment 1 indicated no significant differences between groups in the size of the just detectable delay and no significant interactions between group and the scaling factor between the B and A stimuli. Experiment 2 revealed no significant differences in streaming abilities between normal-hearing and hearing-impaired groups.

Conclusions

Overall, results indicate that listeners with normal and impaired hearing have similar auditory streaming abilities for broadband inharmonic complex stimuli.
Quality of Life for Children With Cochlear Implants: Perceived Benefits and Problems and the Perception of Single Words and Emotional Sounds
Authors: Schorr Efrat A. , Roth Froma P. , Fox Nathan A.
Published: July 2008

Purpose

This study examined children’s self-reported quality of life with a cochlear implant as related to children’s actual perceptions of speech and the emotional information conveyed by sound. Effects of age at amplification with hearing aids and fitting of cochlear implants on perceived quality of life were also investigated.

Method

A self-reported quality of life questionnaire and assessments of speech perception (single words) and emotion identification were administered to a sample of 37 children with cochlear implants who were congenitally deaf, who were 5–14 years of age, and who all used spoken language.

Results

The children reported significant improvement in quality of life because of their cochlear implants, and they also reported low levels of concern about typical problems associated with wearing an implant. The children’s perceived quality of life did not significantly predict speech perception performance at the single word level. In contrast, increased quality of life predicted better performance on the emotion identification task. Age at first use of amplification predicted perceived quality of life.

Conclusions

The findings regarding age reinforce the importance of early detection and intervention for children’s positive quality of life with cochlear implants later in childhood.
Changes in Articulator Movement Variability During Phonemic Development: A Longitudinal Study
Authors: Grigos Maria I.
Published: July 2008

Purpose

The present study explored articulator movement variability during voicing contrast acquisition. The purpose was to examine whether oral articulator movement trajectories associated with the production of voiced/voiceless bilabial phonemes in children became less variable over time.

Method

Jaw, lower lip, and upper lip movements were recorded longitudinally in six, 19 month-old children as they began producing the voiceless phoneme /p/. Displacement signals were time and amplitude normalized. The spatiotemporal index (A. Smith, L. Goffman, H. Zelaznik, S. Ying, & C. McGillem, 1995) was computed to examine the variability in movement trajectories across repeated productions of target utterances.

Results

Spatiotemporal variability of lip and jaw movements significantly decreased as children began producing the voiceless phoneme /p/. A significant negative correlation between the STI and the length of voice onset time (VOT) was also found in the voiceless productions in 4 of the 6 participants.

Conclusions

Oral articulator movement variability is reduced in children across the stabilization of voicing contrast acquisition. Further, the relationship between VOT contrast production and movement variability suggests that a coordinate system between the oral and laryngeal articulators may be refined as children acquire the voicing contrast.
Voiced Initial Consonant Perception Deficits in Older Listeners With Hearing Loss and Good and Poor Word Recognition
Authors: Phillips Susan L. , Richter Scott J. , McPherson David
Published: July 2008

Purpose

This study examined differences in voiced consonant–vowel (CV) perception in older listeners with normal hearing and in 2 groups of older listeners with matched hearing losses: those with good and those with poor word recognition scores.

Method

Thirty-six participants identified CVs from an 8-item display from the natural voiced initial consonants /b, d, g, m, n, ð, v and z/ in three vowel contexts (/
a
, o, u/) spoken by a male and a female talker.

Results

The listeners with hearing loss and poor word recognition scores (WRS) made more of the same types of errors, as well as errors not made by listeners with hearing loss and good word recognition. Errors above chance rates for these listeners were highest in the context of /
a
/ and were similar in the contexts of /o/ and /u/. Sequential information analyses (SINFAs) verified that information was transmitted least efficiently in the context of /
a
/. The results yielded a list of consonant confusions unique to listeners with poor WRS.

Conclusions

Listeners with poor WRS have more difficulty identifying voiced initial consonants in CV syllables than do listeners with good WRS. These listeners made some systematic errors, but most errors were nonsystematic, perhaps due to the low level of feature information transmitted.
Simulating the Effects of Spread of Electric Excitation on Musical Tuning and Melody Identification With a Cochlear Implant
Authors: Spahr Anthony J. , Litvak Leonid M. , Dorman Michael F. , Bohanan Ashley R. , Mishra Lakshmi N.
Published: July 2008

Purpose

To determine why, in a pilot study, only 1 of 11 cochlear implant listeners was able to reliably identify a frequency-to-electrode map where the intervals of a familiar melody were played on the correct musical scale. The authors sought to validate their method and to assess the effect of pitch strength on musical scale recognition in normal-hearing listeners.

Method

Musical notes were generated as either sine waves or spectrally shaped noise bands, with a center frequency equal to that of a desired note and symmetrical (log-scale) reduction in amplitude away from the center frequency. The rate of amplitude reduction was manipulated to vary pitch strength of the notes and to simulate different degrees of current spread. The effect of the simulated degree of current spread was assessed on tasks of musical tuning/scaling, melody recognition, and frequency discrimination.

Results

Normal-hearing listeners could accurately and reliably identify the appropriate musical scale when stimuli were sine waves or steeply sloping noise bands. Simulating greater current spread degraded performance on all tasks.

Conclusions

Cochlear implant listeners with an auditory memory of a familiar melody could likely identify an appropriate frequency-to-electrode map but only in cases where the pitch strength of the electrically produced notes is very high.
Spontaneous local variations in ongoing neural activity bias perceptual decisions
Authors: Hesselmann Guido , Kell Christian A. , Eger Evelyn , Kleinschmidt Andreas
Published: July 2008

Neural variability in responding to identical repeated stimuli has been related to trial-by-trial fluctuations in ongoing activity, yet the neural and perceptual consequences of these fluctuations remain poorly understood. Using functional neuroimaging, we recorded brain activity in subjects who reported perceptual decisions on an ambiguous figure, Rubin's vase-faces picture, which was briefly presented at variable intervals of ≥20 s. Prestimulus activity in the fusiform face area, a cortical region preferentially responding to faces, was higher when subjects subsequently perceived faces instead of the vase. This finding suggests that endogenous variations in prestimulus neuronal activity biased subsequent perceptual inference. Furnishing evidence that evoked sensory responses, we then went on to show that the pre- and poststimulus activity interact in a nonlinear way and the ensuing perceptual decisions depend upon the prestimulus context in which they occur.
Cell proliferation at 122°C and isotopically heavy CH
4
production by a hyperthermophilic methanogen under high-pressure cultivation
Authors: Takai Ken , Nakamura Kentaro , Toki Tomohiro , Tsunogai Urumu , Miyazaki Masayuki , Miyazaki Junichi , Hirayama Hisako , Nakagawa Satoshi , Nunoura Takuro , Horikoshi Koki
Published: July 2008

We have developed a technique for cultivation of chemolithoautotrophs under high hydrostatic pressures that is successfully applicable to various types of deep-sea chemolithoautotrophs, including methanogens. It is based on a glass-syringe-sealing liquid medium and gas mixture used in conjunction with a butyl rubber piston and a metallic needle stuck into butyl rubber. By using this technique, growth, survival, and methane production of a newly isolated, hyperthermophilic methanogen
Methanopyrus kandleri
strain 116 are characterized under high temperatures and hydrostatic pressures. Elevated hydrostatic pressures extend the temperature maximum for possible cell proliferation from 116°C at 0.4 MPa to 122°C at 20 MPa, providing the potential for growth even at 122°C under an
in situ
high pressure. In addition, piezophilic growth significantly affected stable carbon isotope fractionation of methanogenesis from CO
2
. Under conventional growth conditions, the isotope fractionation of methanogenesis by
M. kandleri
strain 116 was similar to values (−34‰ to−27‰) previously reported for other hydrogenotrophic methanogens. However, under high hydrostatic pressures, the isotope fractionation effect became much smaller (<−12‰), and the kinetic isotope effect at 122°C and 40 MPa was −9.4‰, which is one of the smallest effects ever reported. This observation will shed light on the sources and production mechanisms of deep-sea methane.
Tracking the energy flow along the reaction path
Authors: Yan Shannon , Wu Yen-Tien , Liu Kopin
Published: July 2008

We report a comprehensive study of the quantum-state correlation property of product pairs from reactions of chlorine atoms with both the ground-state and the CH stretch-excited CHD
3
. In light of available
ab initio
theoretical results, this set of experimental data provides a conceptual framework to visualize the energy-flow pattern along the reaction path, to classify the activity of different vibrational modes in a reactive encounter, to gain deeper insight into the concept of vibrational adiabaticity, and to elucidate the intermode coupling in the transition-state region. This exploratory approach not only opens up an avenue to understand polyatomic reaction dynamics, even for motions at the molecular level in the fleeting transition-state region, but it also leads to a generalization of Polanyi's rules to reactions involving a polyatomic molecule.
Wnt signaling in
Pristionchus pacificus
gonadal arm extension and the evolution of organ shape
Authors: Rudel David , Tian Huiyu , Sommer Ralf J.
Published: July 2008

Changes in organ morphology have been essential to the evolution of novel body forms and in permitting organisms to invade new ecological niches. Changes in the arrangement of cells and tissues and in the regulation of morphological movements are fundamental to evolutionary transitions of organ shape and function. However, little is known about the genetic and developmental control of these changes. We use interspecific differences in the migration and extension of the nematode hermaphrodite gonadal arms to study the generation of morphological novelty. We show that the extending
Pristionchus pacificus
gonadal arms display a ventral migration that is unique to the Diplogastridae in comparison to the Rhabditidae, including
Caenorhabditis elegans
, and other nematodes. This results in the distal gonad residing along the ventral side of the body in
P. pacificus
in contrast to lying on the dorsal side of the body as in
C. elegans
. We show that at the cellular level this morphogenetic movement is regulated by signals from the developing vulva and the sister gonadal arm. We further show that in
P. pacificus
Wnt signaling is essential for this regulation. We show genetic and molecular evidence that suggest the Wnt ligands
Ppa-mom-2
and
Ppa-cwn-2
are components of the signaling mechanism. Supporting these findings, the hermaphrodite gonad of
Ppa-bar-1
mutant animals mimics the shape of the
C. elegans
hermaphrodite gonad; the arms fail to extend ventrally. Thus, this genetic analysis of gonad migration provides insight into the mechanisms underlying the generation of morphological novelty and organ shape.
A pH-stabilizing role of voltage-gated proton channels in IgE-mediated activation of human basophils
Authors: Musset Boris , Morgan Deri , Cherny Vladimir V. , MacGlashan Donald W. , Thomas Larry L. , Ríos Eduardo , DeCoursey Thomas E.
Published: July 2008

Eosinophils and other phagocytes use NADPH oxidase to kill bacteria. Proton channels in human eosinophils and neutrophils are thought to sustain NADPH oxidase activity, and their opening is greatly enhanced by a variety of NADPH oxidase activators, including phorbol myristate acetate (PMA). In nonphagocytic cells that lack NADPH oxidase, no clear effect of PMA on proton channels has been reported. The basophil is a granulocyte that is developmentally closely related to the eosinophil but nevertheless does not express NADPH oxidase. Thus, one might expect that stimulating basophils with PMA would not affect proton currents. However, stimulation of human basophils in perforated-patch configuration with PMA,N-formyl-methionyl-leucyl-phenylalanine, or anti-IgE greatly enhanced proton currents, the latter suggesting involvement of proton channels during activation of basophils by allergens through their highly expressed IgE receptor (FcεRI). The anti-IgE-stimulated response occurred in a fraction of cells that varied among donors and was less profound than that to PMA. PKC inhibition reversed the activation of proton channels, and the proton channel response to anti-IgE or PMA persisted in Ca2+-free solutions. Zn2+at concentrations that inhibit proton current inhibited histamine release elicited by PMA or anti-IgE. Studied with confocal microscopy by using SNARF-AM and the shifted excitation and emission ratioing of fluorescence approach, anti-IgE produced acidification that was exacerbated in the presence of 100 μM Zn2+. Evidently, proton channels are active in basophils during IgE-mediated responses and prevent excessive acidification, which may account for their role in histamine release.
Hierarchical organization of eglin c native state dynamics is shaped by competing direct and water-mediated interactions
Authors: Materese Christopher Kroboth , Goldmon Christa Charisse , Papoian Garegin A.
Published: July 2008

The native state dynamics of the small globular serine protease inhibitor eglin c has been studied in a long 336 ns computer simulation in explicit solvent. We have elucidated the energy landscape explored during the course of the simulation by using Principal Component Analysis. We observe several basins in the energy landscape in which the system lingers for extended periods. Through an iterative process we have generated a tree-like hierarchy of states describing the observed dynamics. We observe a range of divergent contact types including salt bridges, hydrogen bonds, hydrophilic interactions, and hydrophobic interactions, pointing to the frustration between competing interactions. Additionally, we find evidence of competing water-mediated interactions. Divergence in water-mediated interactions may be found to supplement existing direct contacts, but they are also found to be independent of such changes. Water-mediated contacts facilitate interactions between residues of like charge as observed in the simulation. Our results provide insight into the complexity of the dynamic native state of a globular protein and directly probe the residual frustration in the native state.
Transition state for protein–DNA recognition
Authors: Ferreiro Diego U. , Sánchez Ignacio E. , de Prat Gay Gonzalo
Published: July 2008

We describe the formation of protein–DNA contacts in the two-state route for DNA sequence recognition by a transcriptional regulator. Surprisingly, direct sequence readout establishes in the transition state and constitutes the bottleneck of complex formation. Although a few nonspecific ionic interactions are formed at this early stage, they mainly play a stabilizing role in the final consolidated complex. The interface is fairly plastic in the transition state, likely because of a high level of hydration. The overall picture of this two-state route largely agrees with a smooth energy landscape for binding that speeds up DNA recognition. This “direct” two-state route differs from the parallel multistep pathway described for this system, which involves nonspecific contacts and at least two intermediate species that must involve substantial conformational rearrangement in either or both macromolecules.
The proton donor for OO bond scission by cytochrome
c
oxidase
Authors: Gorbikova Elena A. , Belevich Ilya , Wikström Mårten , Verkhovsky Michael I.
Published: July 2008

Cytochrome
c
oxidase is the main catalyst of oxygen consumption in mitochondria and many aerobic bacteria. The key step in oxygen reduction is scission of the O

O bond and formation of an intermediate P
R
of the binuclear active site composed of heme
a
3
and Cu
B
. The donor of the proton required for this reaction has been suggested to be a unique tyrosine residue (Tyr-280) covalently cross-linked to one of the histidine ligands of Cu
B
. To test this idea we used the Glu-278–Gln mutant enzyme from
Paracoccus denitrificans
, in which the reaction with oxygen stops at the P
R
intermediate. Three different time-resolved techniques were used. Optical spectroscopy showed fast (≈60 μs) appearance of the P
R
species along with full oxidation of heme
a
, and FTIR spectroscopy revealed a band at 1,308 cm
−1
, which is characteristic for the deprotonated form of the cross-linked Tyr-280. The development of electric potential during formation of the P
R
species suggests transfer of a proton over a distance of ≈4 Å perpendicular to the membrane plane, which is close to the distance between the oxygen atom of the hydroxyl group of Tyr-280 and the bound oxygen. These results strongly support the hypothesis that the cross-linked tyrosine is the proton donor for O

O bond cleavage by cytochrome
c
oxidase and strengthens the view that this tyrosine also provides the fourth electron in O
2
reduction in conditions where heme
a
is oxidized.
Adaptive mutations in the signal peptide of the type 1 fimbrial adhesin of uropathogenic
Escherichia coli
Authors: Ronald Leah S. , Yakovenko Olga , Yazvenko Nina , Chattopadhyay Sujay , Aprikian Pavel , Thomas Wendy E. , Sokurenko Evgeni V.
Published: July 2008

Signal peptides (SPs) are critical for protein transport across cellular membranes, have a highly conserved structure, and are cleaved from the mature protein upon translocation. Here, we report that naturally occurring mutations in the SP of the adhesive, tip-associated subunit of type 1 fimbriae (FimH) are positively selected in uropathogenic
Escherichia coli
. On the one hand, these mutations have a detrimental effect, with reduced FimH transport across the inner membrane, fewer FimH and fimbriae expressed on the bacterial surface, and decreased bacterial adhesion under flow conditions. On the other hand, the fimbriae expressed by the mutants are significantly longer on average, with many fimbriae able to stretch to >20 μm in length. More surprisingly, the SP mutant bacteria display an increased ability to resist detachment from the surface upon a switch from high to low flow. This functional effect of longer fimbriae highlights the importance of the nonadhesive fimbrial rod for adhesive function. Also, whereas bacterial adhesion to bladder epithelial cells was preserved in most mutants, binding to and killing by human neutrophils was decreased, providing an additional reason the SP mutations are relatively common among uropathogenic strains. Thus, this study demonstrates how mutations in an SP, while decreasing transport function and not affecting the final structure of the translocated protein, can lead to functional gains of the extracellular organelles that incorporate the protein and overall adaptive changes in the organism's fitness.
Co-evolving stability and conformational homogeneity of the human adenosine A2areceptor
Authors: Magnani Francesca , Shibata Yoko , Serrano-Vega Maria J. , Tate Christopher G.
Published: July 2008

Structural studies on mammalian integral membrane proteins have long been hampered by their instability in detergent. This is particularly true for the agonist conformation of G protein-coupled receptors (GPCRs), where it is thought that the movement of helices that occurs upon agonist binding results in a looser and less stable packing in the protein. Here, we show that mutagenesis coupled to a specific selection strategy can be used to stabilize the agonist and antagonist conformations of the adenosine A2areceptor. Of the 27 mutations identified that improve the thermostability of the agonist conformation, only three are also present in the 17 mutations identified that improve the thermostability of the antagonist conformation, suggesting that the selection strategies used were specific for each conformation. Combination of the stabilizing mutations for the antagonist- or agonist-binding conformations resulted in mutants that are more stable at higher temperatures than the wild-type receptor by 17°C and 9°C, respectively. The mutant receptors both showed markedly improved stability in short-chain alkyl-glucoside detergents compared with the wild-type receptor, which will facilitate their structural analysis.
mTORC1 promotes survival through translational control of Mcl-1
Authors: Mills John R. , Hippo Yoshitaka , Robert Francis , Chen Samuel M. H. , Malina Abba , Lin Chen-Ju , Trojahn Ulrike , Wendel Hans-Guido , Charest Al , Bronson Roderick T. , Kogan Scott C. , Nadon Robert , Housman David E. , Lowe Scott W. , Pelletier Jerry
Published: July 2008

Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is a frequent occurrence in human cancers and a major promoter of chemotherapeutic resistance. Inhibition of one downstream target in this pathway, mTORC1, has shown potential to improve chemosensitivity. However, the mechanisms and genetic modifications that confer sensitivity to mTORC1 inhibitors remain unclear. Here, we demonstrate that loss of TSC2 in the
E
μ-
myc
murine lymphoma model leads to mTORC1 activation and accelerated oncogenesis caused by a defective apoptotic program despite compromised AKT phosphorylation. Tumors from
Tsc2
+/−
E
μ-
Myc
mice underwent rapid apoptosis upon blockade of mTORC1 by rapamycin. We identified myeloid cell leukemia sequence 1 (
Mcl-1
), a
bcl-2
like family member, as a translationally regulated genetic determinant of mTORC1-dependent survival. Our results indicate that the extent by which rapamycin can modulate expression of
Mcl-1
is an important feature of the rapamycin response.
Organ renewal and cell divisions by differentiated cells in
Drosophila
Authors: Guha Arjun , Lin Li , Kornberg Thomas B.
Published: July 2008

For many organs, the processes of renewal and regeneration recruit stem cells to replace differentiated, postmitotic cells, but the capacity of an organ's differentiated cells to divide and contribute is uncertain. Most cells of the
Drosophila
adult are the descendants of dedicated precursors that divide and replace larval cells that are histolyzed during metamorphosis. We investigated the provenance of cells that reconstitute the second thoracic metamere of the tracheal system (Tr2). These cells contribute the precursors for Branchless(FGF)-dependent growth of the dorsal air sacs, the major tracheal organs of the adult fly. We found that, in contrast to the cells in other tracheal metameres that proceed through many cycles of endoreplication, the cells that constitute the Tr2 branches in young larvae do not. Like the cells in other tracheal metameres, these cells arrest mitotic cycling in the embryo and form differentiated, air-filled tracheal branches of the larva. We report here that they reinitiate cell divisions during the third instar (L3) to increase the Tr2 population by ≈10-fold with multipotent cells.
Distal-less homeobox transcription factors regulate development and maturation of natural killer cells
Authors: Sunwoo John B. , Kim Sungjin , Yang Liping , Naik Tina , Higuchi Darryl A. , Rubenstein John L. , Yokoyama Wayne M.
Published: July 2008

Natural killer (NK) cells constitute a subpopulation of lymphocytes that develop from precursors in the bone marrow (BM), but the transcriptional regulation of their development and maturation is only beginning to be understood, in part due to their relatively rare abundance, especially of developmental subsets. Using a mouse model in which NK cells are arrested at an immature stage of development, and a gene expression profiling approach, we uncovered transient normal NK cell expression of a homeobox transcription factor (TF) family, called
Distal-less
(
Dlx
), which had been primarily implicated in murine CNS, craniofacial, limb, and skin development. Our studies demonstrate that
Dlx1
,
Dlx2
, and
Dlx3
are transiently expressed in immature Mac-1
lo
NK cells within the BM, with
Dlx3
being the predominantly expressed member. These genes are expressed in a temporally regulated pattern with overlapping waves of expression, and they display functional redundancy. Expression is extinguished in fully mature splenic NK cells, and persistent expression of
Dlx
genes leads to functionally immature NK cells arrested at the Mac-1
lo
stage. Whereas conventional splenic NK cells develop but are arrested at an immature stage, there appears to be a complete failure to develop CD127
+
thymic NK cells when
Dlx
genes are persistently expressed. We also observed that T and B cells fail to develop in the context of persistent
Dlx1
expression. Thus, these studies indicate that Dlx TFs play a functional role in lymphocyte development.
Combinatorial surrobody libraries
Authors: Xu Li , Yee Helena , Chan Christina , Kashyap Arun K. , Horowitz Lawrence , Horowitz Michael , Bhatt Ramesh R. , Lerner Richard A.
Published: July 2008

A unique type of combinatorial protein libraries has been constructed. These libraries are based on the pre-B cell receptor (pre-BCR). The pre-BCR is a protein that is produced during normal development of the antibody repertoire. Unlike that of canonical antibodies, the pre-BCR subunit is a trimer that is composed of an antibody heavy chain paired with two surrogate light chain (SLC) components. Combinatorial libraries based on these pre-BCR proteins in which diverse heavy chains are paired with a fixed SLC were expressed in mammalian,
Escherichia coli
, and phagemid systems. These libraries contain members that have nanomolar affinity for antigen. We term this type of antigen-binding protein a “surrobody” to distinguish it from the canonical antibody molecule.
Summary of the 5th IAEA Technical Meeting on Steady State Operation of Magnetic Fusion Devices (Daejeon, Republic of Korea, 14–17 May 2007)
Authors: Lee G.S. , Na Yong-Su , Becoulet A. , Ide S. , Kessel C.E. , Komori A. , Kuteev B.V. , Mank G. , Olstad R.A. , Sarkar B. , Sips A.C.C. , van Houtte D. , Vdovin V.L.
Published: July 2008

This report summarizes the contributions presented at the 5th IAEA Technical Meeting on Steady State Operation of Magnetic Fusion Devices, held in Daejeon, Republic of Korea, 14–17 May 2007. The main topics of the meeting were overview and superconducting devices, long pulse operation and advanced tokamak, steady state fusion technology, heating and current drive, particle control and power exhaust and ITER-related issues.
Two Microtubule-associated Proteins of Arabidopsis MAP65s Promote Antiparallel Microtubule Bundling
Authors: Gaillard Jérémie , Neumann Emmanuelle , Van Damme Daniel , Stoppin-Mellet Virginie , Ebel Christine , Barbier Elodie , Geelen Danny , Vantard Marylin
Published: July 2008

The Arabidopsis MAP65s are a protein family with similarity to the microtubule-associated proteins PRC1/Ase1p that accumulate in the spindle midzone during late anaphase in mammals and yeast, respectively. Here we investigate the molecular and functional properties of AtMAP65-5 and improve our understanding of AtMAP65-1 properties. We demonstrate that, in vitro, both proteins promote the formation of a planar network of antiparallel microtubules. In vivo, we show that AtMAP65-5 selectively binds the preprophase band and the prophase spindle microtubule during prophase, whereas AtMAP65-1-GFP selectively binds the preprophase band but does not accumulate at the prophase spindle microtubules that coexists within the same cell. At later stages of mitosis, AtMAP65-1 and AtMAP65-5 differentially label the late spindle and phragmoplast. We present evidence for a mode of action for both proteins that involves the binding of monomeric units to microtubules that “zipper up” antiparallel arranged microtubules through the homodimerization of the N-terminal halves when adjacent microtubules encounter.
Modelling non-stationary gene regulatory processes with a non-homogeneous Bayesian network and the allocation sampler
Authors: Grzegorczyk Marco , Husmeier Dirk , Edwards Kieron D. , Ghazal Peter , Millar Andrew J.
Published: July 2008

Method: The objective of the present article is to propose and evaluate a probabilistic approach based on Bayesian networks for modelling non-homogeneous and non-linear gene regulatory processes. The method is based on a mixture model, using latent variables to assign individual measurements to different classes. The practical inference follows the Bayesian paradigm and samples the network structure, the number of classes and the assignment of latent variables from the posterior distribution with Markov Chain Monte Carlo (MCMC), using the recently proposed allocation sampler as an alternative to RJMCMC.

Results: We have evaluated the method using three criteria: network reconstruction, statistical significance and biological plausibility. In terms of network reconstruction, we found improved results both for a synthetic network of known structure and for a small real regulatory network derived from the literature. We have assessed the statistical significance of the improvement on gene expression time series for two different systems (viral challenge of macrophages, and circadian rhythms in plants), where the proposed new scheme tends to outperform the classical BGe score. Regarding biological plausibility, we found that the inference results obtained with the proposed method were in excellent agreement with biological findings, predicting dichotomies that one would expect to find in the studied systems.

Availability: Two supplementary papers on theoretical (T) and experi-mental (E) aspects and the datasets used in our study are available from http://www.bioss.ac.uk/associates/marco/supplement/

Contact:  marco@bioss.ac.uk, dirk@bioss.ac.uk
Three ocean state indices implemented in the Mercator-Ocean operational suite
Authors: Crosnier L. , Drévillon M. , Ramos Buarque S. , Soulat F.
Published: July 2008

Crosnier, L., Drévillon, M., Ramos Buarque, S., and Soulat, F. 2008. Three ocean state indices implemented in the Mercator-Ocean operational suite. – ICES Journal of Marine Science, 65: 1504–1507. We present three indices for the state of the ocean, all computed using the Mercator-Ocean analyses and ocean forecast system: an upwelling index based on sea surface temperature (SST), the tropical cyclone heat potential, showing the thermal energy available in the ocean to enhance or decrease the power of cyclones, and the Indian Ocean dipole mode index based on SST. Such indices are updated on a weekly or monthly basis.
Peeking into Pit Fields: A Multiple Twinning Model of Secondary Plasmodesmata Formation in Tobacco
Authors: Faulkner Christine , Akman Ozgur E. , Bell Karen , Jeffree Chris , Oparka Karl
Published: July 2008

In higher plants, plasmodesmata (PD) are major conduits for cell–cell communication. Primary PD are laid down at cytokinesis, while secondary PD arise during wall extension. During leaf development, the basal cell walls of trichomes extend radially without division, providing a convenient system for studying the origin of secondary PD. We devised a simple freeze-fracture protocol for examining large numbers of PD in surface view. In the postcytokinetic wall, simple PD were distributed randomly. As the wall extended, PD became twinned at the cell periphery. Additional secondary pores were inserted at right angles to these, giving rise to pit fields composed of several paired PD. During wall extension, the number of PD increased fivefold due to the insertion of secondary PD. Our data are consistent with a model in which a subset of the original primary PD pores function as templates for the insertion of new secondary PD, spatially fixing the position of future pit fields. Many of the new PD shared the same wall collar as the original PD pore, suggesting that new PD pores may arise by fissions of existing PD progenitors. Different models of secondary PD formation are discussed. Our data are supported by a computational model, Plasmodesmap, which accurately simulates the formation of radial pit fields during cell wall extension based on the occurrence of multiple PD twinning events in the cell wall. The model predicts PD distributions with striking resemblance to those seen on fractured wall faces.
XopD SUMO Protease Affects Host Transcription, Promotes Pathogen Growth, and Delays Symptom Development inXanthomonas-Infected Tomato Leaves
Authors: Kim Jung-Gun , Taylor Kyle W. , Hotson Andrew , Keegan Mark , Schmelz Eric A. , Mudgett Mary Beth
Published: July 2008

We demonstrate that XopD, a type III effector from Xanthomonas campestris pathovar vesicatoria (Xcv), suppresses symptom production during the late stages of infection in susceptible tomato (Solanum lycopersicum) leaves. XopD-dependent delay of tissue degeneration correlates with reduced chlorophyll loss, reduced salicylic acid levels, and changes in the mRNA abundance of senescence- and defense-associated genes despite high pathogen titers. Subsequent structure-function analyses led to the discovery that XopD is a DNA binding protein that alters host transcription. XopD contains a putative helix-loop-helix domain required for DNA binding and two conserved ERF-associated amphiphilic motifs required to repress salicylic acid– and jasmonic acid–induced gene transcription in planta. Taken together, these data reveal that XopD is a unique virulence factor in Xcv that alters host transcription, promotes pathogen multiplication, and delays the onset of leaf chlorosis and necrosis.
ArabidopsisPUB22 and PUB23 Are Homologous U-Box E3 Ubiquitin Ligases That Play Combinatory Roles in Response to Drought Stress
Authors: Cho Seok Keun , Ryu Moon Young , Song Charlotte , Kwak June M. , Kim Woo Taek
Published: July 2008

Ubiquitination is involved in diverse cellular processes in higher plants. In this report, we describe Arabidopsis thaliana PUB22 and PUB23, two homologous U-box–containing E3 ubiquitin (Ub) ligases. The PUB22 and PUB23 genes were rapidly and coordinately induced by abiotic stresses but not by abscisic acid. PUB22- and PUB23-overexpressing transgenic plants were hypersensitive to drought stress. By contrast, loss-of-function pub22 and pub23 mutant plants were significantly more drought-tolerant, and a pub22 pub23 double mutant displayed even greater drought tolerance. These results indicate that PUB22 and PUB23 function as negative regulators in the water stress response. Yeast two-hybrid, in vitro pull-down, and in vivo coimmunoprecipitation experiments revealed that PUB22 and PUB23 physically interacted with RPN12a, a subunit of the 19S regulatory particle (RP) in the 26S proteasome. Bacterially expressed RPN12a was effectively ubiquitinated in a PUB-dependent fashion. RPN12a was highly ubiquitinated in 35S:PUB22 plants, but not in pub22 pub23 double mutant plants, consistent with RPN12a being a substrate of PUB22 and PUB23 in vivo. In water-stressed wild-type and PUB-overexpressing plants, a significant amount of RPN12a was dissociated from the 19S RP and appeared to be associated with small-molecular-mass protein complexes in cytosolic fractions, where PUB22 and PUB23 are localized. Overall, our results suggest that PUB22 and PUB23 coordinately control a drought signaling pathway by ubiquitinating cytosolic RPN12a in Arabidopsis.
Forest history affects genetic diversity – molecular variation of Dryopteris dilatata (Dryopteridaceae) in ancient and recent forests
Authors: Reisch Christoph , Mayer Florian , Rüther Carsten , Nelle Oliver
Published: July 2008

In a pilot study presented here, the genetic diversity of Dryopteris dilatata in relation to the history of forest stands in the Western Bavarian Forest, Germany, was investigated using random amplified polymorphic DNA (RAPD) analysis. We selected three ancient and three recent sites, which were classified for age considering historical maps, stand age, vegetation composition and charcoal analysis. RAPD analysis of 118 individuals with ten primers resulted in 81 fragments. Mean genetic diversity, measured as percentage of polymorphic bands and Nei's gene diversity, was higher in ancient than in recent forests. Furthermore, we detected a higher total number of genotypes and more unique genotypes in ancient than in recent forests. An analysis of molecular variance (AMOVA) revealed significant genetic variation between the populations in the differently aged forests (6%), the populations within the forests (9%) and a high variation (85%) within populations. Populations from ancient forests were clearly differentiated from each other (14%), while populations from recent forests exhibited no significant differences (0%). Thus, forest history seems to have an impact both on genetic differentiation between and on diversity within populations of forest plants. In conclusion, the combination of population genetics and palaeoecology is a promising approach to analyse the impact of historical events on the genetic structure of plant populations.
Ranunculusanatolicus sp. nov. (Ranunculaceae) from northeast Turkey
Authors: Akkemik Ünal , Akalin Emine , Özhatay Neriman
Published: July 2008

Ranunculus
anatolicusÜ. Akkemik, E. Akalin & N. Özhatay sp. nov. from northeast Turkey is described and illustrated. The new species is related to R. fenzlii Boiss., R. caucasicus Bieb. subsp. subleiocarpus (Som. & Lev.) P. H. Davis, and R. dissectus Bieb. subsp. huetii (Boiss.) Davis, from which it mainly differs by its broadly cuneate leaflobes and multiplex petals (8–12).
Campylanthus hajarensis sp. nov. and a new record of Campylanthus (Scrophulariaceae) from Oman
Authors: Hjertson Mats , Henrot Jacqueline , Thulin Mats
Published: July 2008

Campylanthus hajarensis sp. nov. from a limestone gorge in the Hajar Mts in northern Oman, is described and illustrated. This is the first species of Campylanthus to be discovered in northern Oman. In addition, Campylanthus antonii, previously known only from Yemen, is recorded from the Dhofar Region in Oman.
Thirty‐eight years of change in a tropical forest: plot data from Mpanga Forest Reserve, Uganda
Authors: Taylor D. , Hamilton A. C. , Lewis S. L. , Nantale G.
Published: July 2008

Variations in the composition and structure of mid‐altitude, semi‐deciduous topical forest in a 0.64‐ha plot in Mpanga Forest Reserve, Uganda, are described for a 38‐year period to 2006. Repeat surveys of trees in the plot with a girth ≥30 cm at reference height in 1982, 1993 and 2006, following a baseline survey in 1968, indicate only relatively minor fluctuations in density, Shannon diversity, evenness, basal area (BA) and estimated above ground biomass. The largest trees [diameter at breast height (dbh) > 40 cm] and main canopy taxa (e.g. Celtis mildbraedii) accounted for the largest fraction of BA. Mortality was the highest amongst taxa classed as early seral, understorey and/or in the smallest size category (dbh = 9.5–20 cm), while new recruits were predominantly understorey taxa. Only one tree was recorded as felled for human use between the surveys of 1968 and 1993. In contrast, a considerable increase in anthropogenic disturbance was evident at the time of the 2006 survey, and illegal logging now poses a substantial threat to future resource availability and carbon storage in what was for a time one of the most protected areas of forest in Uganda.
Audit of motor weakness and premature catheter dislodgement after epidural analgesia in major abdominal surgery
Authors: Königsrainer I. , Bredanger S. , Drewel‐Frohnmeyer R. , Vonthein R. , Krueger W. A. , Königsrainer A. , Unertl K. E. , Schroeder T. H.
Published: July 2008

In a quality improvement audit on epidural analgesia in 300 patients after major abdominal surgery, we identified postoperative lower leg weakness and premature catheter dislodgement as the most frequent causes of premature discontinuation of postoperative epidural infusion. Lower limb motor weakness occurred in more than half of the patients with lumbar epidural analgesia. In a second period monitoring 177 patients, lumbar catheter insertion was abandoned in favour of exclusive thoracic placement for epidural catheters. Additionally, to prevent outward movement, the catheters were inserted deeper into the epidural space (mean (SD) 5.2 (1.5) cm in Period Two vs 4.6 (1.3) cm in Period One). Lower leg motor weakness declined from 14.7% to 5.1% (odds ratio 0.35; 95% confidence interval 0.16–0.74) between the two periods. Similarly, the frequency of premature catheter dislodgement was reduced from 14.5% to 5.7% (odds ratio 0.35; 95% confidence interval 0.17–0.72). With a stepwise logistic regression model we demonstrated that the odds of premature catheter dislodgement was reduced by 43% for each centimetre of additional catheter advancement in Period Two. We conclude that careful audit of specific complications can usefully guide changes in practice that improve success of epidural analgesia regimens.