bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Inducer Polarity and Contrast on the Perception of Illusory Figures
Authors: Matthews Nestor , Welch Leslie
Published: January 2007

A study designed to determine how inducer–surround contrast and inducer polarity affect the contour clarity and the lightness of illusory figures is reported. Using magnitude estimation procedures, ten naive subjects rated both the contour clarity and the lightness of Kanizsa squares. The magnitude of the inducer–surround contrast and the inducer polarity (all-black, all-white, or black-and-white) were varied randomly on each trial. The data indicate that contour clarity increases with contrast at the same rate across polarity conditions but that contour clarity at any given contrast level depends significantly on polarity. Contour clarity judgments were significantly lower when the inducers were all-white than when the inducers were all-black or black-and-white, and significantly greater in the ‘mixed’ polarity case (black-and-white inducers) than in the ‘same’ polarity case (the average of the all-black and all-white inducer conditions). Inducer contrast and polarity significantly affected the lightness of the illusory figure in a manner consistent with simultaneous spatial contrast. Also, for a given increment in contrast, contour clarity altered significantly more than surface lightness, regardless of inducer polarity. The findings suggest that the mechanism which mediates boundary formation is sensitive to the direction of contrast, and that the boundary formation mechanism is more sensitive than the surface lightness mechanism to changes in contrast magnitude. The results are considered within the context of neural network models of form perception.
Real and Virtual Borders in the Poggendorff Illusion
Authors: Westheimer Gerald , Wehrhahn Christian
Published: January 2007

The strength of the Poggendorff illusion has been determined by a nulling method for the classical as well as other configurations of the central inducing region. Compared to a uniform field, an inducing rectangle with very low contrast produces a marked illusion, which saturates at a Michelson contrast of about 0.1. With virtual borders of the Kanizsa type there is a weak illusion and this effect is attenuated when the ‘pacman’ sectors are occluded. Texture borders without luminance contrast induce a stronger illusion. These results are discussed in relation to earlier data for contrast dependence of Vernier acuity and for the orientation discrimination and tilt illusion with real and virtual borders.
Face Detection in Peripheral Vision: Do Faces Pop Out?
Authors: Brown Valerie , Huey Dale , Findlay John M
Published: January 2007

We examined whether faces can produce a ‘pop-out’ effect in visual search tasks. In the first experiment, subjects' eye movements and search latencies were measured while they viewed a display containing a target face amidst distractors. Targets were upright or inverted faces presented with seven others of the opposite polarity as an ‘around-the-clock’ display. Face images were either photographic or ‘feature only’, with the outline removed. Naive subjects were poor at locating an upright face from an array of inverted faces, but performance improved with practice. In the second experiment, we investigated systematically how training improved performance. Prior to testing, subjects were practised on locating either upright or inverted faces. All subjects benefited from training. Subjects practised on upright faces were faster and more accurate at locating upright target faces than inverted. Subjects practised on inverted faces showed no difference between upright and inverted targets. In the third experiment, faces with ‘jumbled’ features were used as distractors, and this resulted in the same pattern of findings. We conclude that there is no direct rapid ‘pop-out’ effect for faces. However, the findings demonstrate that, in peripheral vision, upright faces show a processing advantage over inverted faces.
Vergence Eye Movements Elicited by Stimuli without Corresponding Features
Authors: Liu Lei , Stevenson Scott B , Schor Clifton M
Published: January 2007

We have observed quantitative depth perception with a dichoptic stimulus which possessed no contrast-defined binocular corresponding features (phantom stereogram). The depth perception can be the result of appreciation of a partial-occlusion situation depicted by the stimulus, or the result of activities of low-level disparity detectors which are capable of combining dissimilar local features in the stimulus. Although both mechanisms predict similar depth perception, they predict different vergence eye-movement outputs, especially in the vertical dimension. To identify the underlying mechanisms of the phantom stereopsis, we recorded vergence tracking eye movements to four types of dichoptic stimuli: (a) conventional stereogram with horizontal disparity (HD); (b) horizontal phantom stereogram (HP); (c) conventional stereogram with vertical disparity (VD); and (d) vertical phantom stereogram (VP). We found that HD, HP, and VD stimuli could elicit robust vergence tracking eye movements but VP stimulus could not. While the success of HP stimulus in eliciting vergence tracking may be explained by proximal vergence, the failure of VP stimulus in eliciting vergence tracking clearly indicates that phantom stereogram could not elicit coherent responses among low-level disparity detectors. Partial occlusion, therefore, has to play an important role in the depth perception from the phantom stereogram.
Limiting Factors for the Detection of Orientation
Authors: Zanker Johannes M
Published: January 2007

First steps of visual-information processing in primates are characterised by a highly ordered representation of the outside world on the cortex. Two prominent features of cortical organisation are the retinotopic mapping of position in the visual field on the first stages of the visual stream, and the systematic variation of orientation preference in the same areas. In an attempt to understand the relation of position and orientation representation, we need to know the minimum spatial requirements for orientation detection. In the present paper, the spatial limits for detecting orientation are analysed by simulating simple orientation filters and testing the ability of human observers to detect the orientation of small lines at various positions in the visual field. At sufficiently high contrast levels, the minimum physical length of a line to discriminate orientation differences of 45°–90° is not constant when presented at various eccentricities, but covaries inversely with the cortical magnification factor. In consequence, a line needs to correspond to about 0.2 mm of cortical surface, independently of the actual eccentricity at which the stimulus is presented, in order to allow observers to recognise its orientation. This has consequences for our understanding of orientation detection, (i) In combination with simulation experiments, it becomes clear that the elementary process underlying orientation detection is a local operation, which seems to focus on small regions compared with cortical receptive fields, (ii) With respect to the number of inputs to the visual cortex, the performance of this local operation approaches the physical limits, requiring hardly more than three-four input LGN axons to be activated for detecting the orientation of a highly visible line segment. Comparing these spatial characteristics with the receptive fields of orientation-sensitive neurons in the primate visual system could suggest new insights into the neuronal circuits underlying orientation mapping in the human cortex.
The Golf-Ball Illusion: Evidence for Top-down Processing in Weight Perception
Authors: Ellis Robert R , Lederman Susan J
Published: January 2007

Theories of weight illusions have traditionally emphasised either the primary contribution of low-level sensory cues or the role of expectation based on knowledge and past experience. Current models of weight illusions lean quite strongly towards sensory-based interpretations. The current experiment raises a problem for such approaches by generating a weight illusion that is difficult to explain other than by the participants' knowledge. Golfers (who expect a weight difference between ball types) reliably judged practice golf balls to weigh more than real golf balls of the same weight. In contrast, non-golfers (who expect no weight difference between ball types) judged practice and real balls of equal weight to weigh the same. Furthermore, within the group of golfers, those who expected the weights of the two ball types to be the most discrepant prior to lifting tended to report the strongest illusions subsequent to lifting. Because there is no low-level sensory cue between ball types that on its own would signal a weight difference, the current finding suggests that there is a top-down component to weight perception that is based on experience with specific objects.
Independence of Contour and Biological-Motion Cues for Motion-Defined Animal Shapes
Authors: Bellefeuille Anne , Faubert Jocelyn
Published: January 2007

The effects of different kinds of cues on the perception of second-order motion-defined animal shapes were assessed. In the first experiment discrimination thresholds for motion-defined animals without biological motion (non-BioM) were compared with motion-defined animals with biological motion (BioM). The results show no significant difference between the two conditions, suggesting that BioM does not interact with simple contour motion. In order to isolate the relative strength and interaction between the motion cues a second experiment was conducted where four conditions were used. The first condition consisted of animal contours with non-BioM, the second condition consisted of animal contours with BioM, the third condition was composed of dots present at the joints of the animals with non-BioM, and the fourth condition was composed of dots with BioM. In all cases the animal shapes traveled across the screen for a given number of frames. As in the first experiment, the results of the second study show no interaction between cues. Furthermore, the data show that the thresholds are similar whether BioM or contour cues are presented. The only condition which is significantly different is the condition without either contour or BioM cues. It is concluded that the form representation generated from these cues in motion-defined animal shapes consists of separate mechanisms which appear equally efficient for discrimination and which do not interact with one another.
The Role of Binocular Viewing in a Spacing Illusion Arising in a Darkened Surround
Authors: Suzuki Kotaro
Published: January 2007

A study is reported of the binocular-oculomotor hypothesis of the moon illusion. In a dark hall, a pair of light points was presented straight ahead horizontally, and another pair was presented at the same distance but 50° upward. Twenty subjects compared the spacings of these two pairs. Half of the subjects viewed the stimuli first monocularly and then binocularly, and the other half viewed them in the reverse order. Eye position was also systematically varied, either level or elevated. A spacing illusion was consistently obtained during binocular viewing (with the upper spacing seen as smaller), but no illusion arose during monocular viewing unless it was preceded by binocular viewing. Furthermore, an enhancement of the illusion due to eye elevation was found only during binocular viewing. These findings replicate the report of Taylor and Boring (1942 American Journal of Psychology55 189–201), in which the moon was used as the stimulus, and support the binocular-oculomotor hypothesis as a partial explanation for the moon illusion.
Change in Visually Perceived Eye Level without Change in Perceived Pitch
Authors: Li Wenxun , Matin Leonard
Published: January 2007

Both the physical elevation that appears to correspond to eye level and the visually perceived pitch of a visual field are linear functions of the physical pitch of a normally illuminated, complexly structured visual field. One of the possible bases for the large effect of physical pitch on the elevation of visually perceived eye level (VPEL) is that the visual field generates a mental representation which specifies spatial coordinates and these determine the VPEL elevation (‘implicit-surface model’; ISM). The influence on the elevation of VPEL is nearly as large when the visual field contains either one or two long pitched-from-vertical or rolled-from-vertical lines in otherwise total darkness as when it consists of a well-illuminated and complexly structured pitched room (L Matin and W Li, 1994 Vision Research34 311–330), and, in order to examine the ISM, we employed a rolled-from-vertical, two-line configuration within a frontoparallel plane viewed in otherwise total darkness. Measurements of visually perceived pitch were made by a manual matching procedure and VPEL measurements were made by the psychophysical setting of the elevation of a small visual target to appear at eye level while each of three subjects viewed the two-line configuration at each of three horizontal eccentricities with the configuration at each of seven roll orientations. In direct contradiction to the ISM, the perceived pitch of the two-line configuration did not deviate significantly from the erect orientation (‘vertical’) for any roll at any eccentricity, but the elevation of VPEL changed systematically with the roll of the configuration both at left and at right eccentricities, and did not change at all with the two-line configuration centered on the median plane. Consistent with our previous work and with our previous interpretation regarding the basis for VPEL (L Matin and W Li, 1994 Vision Research34 2577 – 2598), the variation of VPEL for the two-line visual field equals the average of the VPEL variations produced by viewing each of the single lines separately.
The Influence of Stimulus Tilt on Haptic Curvature Matching and Discrimination by Dynamic Touch
Authors: Pont Sylvia C , Kappers Astrid M L , Koenderink Jan J
Published: January 2007

We investigated whether haptic comparison of the curvature of strips is influenced by the tilt (the average slope relative to the horizontal) of the curved strips. This particular stimulus manipulation was chosen to decide between two broad ways in which dynamic curvature comparison might be done: on the basis of the attitude (slope) differences over the surfaces or on the basis of the attitude (slope) differences between successively presented surfaces. For this purpose we conducted matching and discrimination experiments in which strips of constant curvature 9 cm long were touched dynamically and the tilts of the strips were varied. The results of the matching experiment showed some influence of tilt: the strips were judged to be slightly more curved if the tilt was nonzero than if it was zero. The results of the discrimination experiment did not show an effect of tilt. Because the attitude (slope) differences over the surfaces were independent of the tilt it is concluded that curvature comparison is based primarily on attitude differences over the curved surfaces.
Aftereffect of High-Speed Motion
Authors: Verstraten Frans A J , van der Smagt Maarten J , van de Grind Wim A
Published: January 2007

A visual illusion known as the motion aftereffect is considered to be the perceptual manifestation of motion sensors that are recovering from adaptation. This aftereffect can be obtained for a specific range of adaptation speeds with its magnitude generally peaking for speeds around 3 deg s−1. The classic motion aftereffect is usually measured with a static test pattern. Here, we measured the magnitude of the motion aftereffect for a large range of velocities covering also higher speeds, using both static and dynamic test patterns. The results suggest that at least two (sub)populations of motion-sensitive neurons underlie these motion aftereffects. One population shows itself under static test conditions and is dominant for low adaptation speeds, and the other is prevalent under dynamic test conditions after adaptation to high speeds. The dynamic motion aftereffect can be perceived for adaptation speeds up to three times as fast as the static motion aftereffect. We tested predictions that follow from the hypothesised division in neuronal substrates. We found that for exactly the same adaptation conditions (oppositely directed transparent motion with different speeds), the aftereffect direction differs by 180° depending on the test pattern. The motion aftereffect is opposite to the pattern moving at low speed when the test pattern is static, and opposite to the high-speed pattern for a dynamic test pattern. The determining factor is the combination of adaptation speed and type of test pattern.
Contrast Masking Reveals Spatial-Frequency Channels in Stereopsis
Authors: Prince Simon J D , Eagle Richard A , Rogers Brian J
Published: January 2007

Yang and Blake (1991 Vision Research31 1177–1189) investigated depth detection in stereograms containing spatially narrow-band signal and noise energies. The resulting masking functions led them to conclude that stereo vision was subserved by only two channels peaking at 3 and 5 cycles deg−1. Glennerster and Parker (1997 Vision Research37 2143 – 2152) re-analysed these data, taking into account the relative attenuation of low- and high-frequency noise masks as a consequence of the modulation transfer function (MTF) of the early visual system. They transformed the data using an estimated MTF and found that peak masking was always at the signal frequency across a 2.8 octave range. Here we determine the MTF of the early visual system for individual subjects by measuring contrast thresholds in a 2AFC orientation-discrimination task (horizontal vs vertical) using band-limited stimuli presented in a 7 deg x 7 deg window at 4 deg eccentricity. The filtered stimuli had a bandwidth of 1.5 octaves in frequency and 15° in orientation at half-height. In the subsequent stereo experiment, the same (vertical) filters were used to generate both signal and noise bands. The noise was binocularly uncorrelated and scaled by each subject's MTF. Subjects performed a 2AFC depth-discrimination task (crossed vs uncrossed disparity) to determine threshold signal contrast as a function of signal and mask frequency. The resulting functions showed that peak masking was at the signal frequency over the three octave range tested (0.4–3.2 cycles deg−1). Comparison with simple luminance-masking data from experiments with similar stimuli shows that bandwidths for stereo masking are considerably larger. These data suggest that there are multiple bandpass channels feeding into stereopsis but that their characteristics differ from luminance channels in pattern vision.
The Effect of Pre-Movement Delays on Pointing Accuracy in Middle Childhood
Authors: Graham Joanna K , Bradshaw Mark F , Davis Alyson
Published: January 2007

In adults, the introduction of a pre-response delay has been shown to affect accuracy in pointing tasks while leaving accuracy in perceptual matching tasks unaffected. Here, we report on the effect of pre-movement delays on pointing accuracy in 6–10-year-old children. Children of this age group are of particular interest as their reliance on visual cues to monitor and correct their reaches appears to change during this period of development. Nineteen children were asked to point to the location of a target light after a delay of 0, 1, 2, or 4 s following target extinction. Performance was measured in two conditions: (i) open-loop, where the child reproduced the target locations in complete darkness, and (ii) with visual feedback, where information about hand position was available. Errors in the direction and in the amplitude of each reaching movement were recorded separately. The results show that temporal delay significantly affects the pointing movements of these children. Accuracy (mean) deteriorated after only 1 s whereas the precision (standard deviation) of the responses deteriorated after 4 s. Errors in amplitude, but not errors in direction, were reduced by the provision of visual feedback. Taken together, the findings suggest that amplitude and directional components of pointing in childhood utilise different sources of information, which differ in the extent to which temporal constraints operate.
Emmert's Law in the Dark: Active and Passive Proprioceptive Effects on Positive Visual Afterimages
Authors: Bross Michael
Published: January 2007

The relationship between apparent size and apparent distance is given by Emmert's law, which states that a retinal image is proportional in size to the distance of the surface it is projected upon. This principle also applies to retinal afterimages in that they, too, will change in apparent size if distance cues suggest that the location of the object projected onto the retinal image has been altered. It has also been known for some time that non-retinal cues can produce quantitative and qualitative effects on an afterimage when it is viewed in the dark. In the present two studies, positive afterimages of an observer's hand, as well as objects held by that hand, were used as targets to investigate the effects on size-constancy scaling of moving the hand to and fro along the line of sight for different distances in the dark. Results show that, when observers focus on a held object, the changes in size predicted by Emmert's law occur in response to both active and passive proprioceptive or haptic cues. The most intriguing result consisted of the finding that, when only the hand is the target, there appears to be a limit to the decrease in apparent hand size. It appears that the visual system ‘refuses’ to size-scale the hand below a limit it accepts as representative or acceptable of ‘its’ hand.
The Effects of Age upon the Perception of Depth and 3-D Shape from Differential Motion and Binocular Disparity
Authors: Norman J Farley , Dawson Thomas E , Butler Amy K
Published: January 2007

The ability of younger and older adults to perceive the 3-D shape, depth, and curvature of smooth surfaces defined by differential motion and binocular disparity was evaluated in six experiments. The number of points defining the surfaces and their spatial and temporal correspondences were manipulated. For stereoscopic sinusoidal surfaces, the spatial frequency of the corrugations was also varied. For surfaces defined by motion, the lifetimes of the individual points in the patterns were varied, and comparisons were made between the perception of surfaces defined by points and that of more ecologically valid textured surfaces. In all experiments, the older observers were less sensitive to the depths and curvatures of the surfaces, although the deficits were much larger for motion-defined surfaces. The results demonstrate that older adults can extract depth and shape from optical patterns containing only differential motion or binocular disparity, but these abilities are often manifested at reduced levels of performance.
Aspects of growth performance and nutrient retention of starter broilers fed Mucuna cochinchinensis-based diets supplemented with methionine
Authors: Ukachukwu S. N. , Uzoech S. O. , Obiefuna J. N.
Published: January 2007

Aspects of growth performance and nutrient retention of starter broilers fed diets containing 10% boiled Mucuna cochinchinensis meal with graded levels of methionine supplementation (0, 0.25, 0.5 and 0.75%) were assessed using 120 unsexed ‘Anak’ strain day-old broiler chicks. The birds were randomly assigned to the four dietary treatments and each treatment was replicated three times with 10 birds per replicate. The experiment lasted 5 weeks, with three birds selected from each replicate and used for nutrient retention studies at the beginning of the fifth week. The 0.75% methionine supplement group had the highest (P < 0.05) daily feed intake and final liveweight. The 0.25% methionine supplement group had the best (P < 0.05) feed conversion ratio and net protein utilisation and the second best final liveweight. The mean dry matter, crude protein, ether extract and nitrogen-free extract retention and energy utilisation for birds fed diets supplemented with methionine at 0.25, 0.5 and 0.75% were similar but significantly higher (P < 0.05) than those of birds fed the unsupplemented diet. Based on efficiency of utilisation of the diets and projected economics of production, the 0.25% level of methionine supplementation appears to be ideal for use in 10% boiled M. cochinchinensis-based diets for starter broiler chicks.
Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine
Authors: Leonardi Roberta , Rock Charles O. , Jackowski Suzanne , Zhang Yong-Mei
Published: January 2007

The human isoform 2 of pantothenate kinase (PanK2) is localized to the mitochondria, and mutations in this protein are associated with a progressive neurodegenerative disorder. PanK2 inhibition by acetyl-CoA is so stringent (IC
50
< 1 μM) that it is unclear how the enzyme functions in the presence of intracellular CoA concentrations. Palmitoylcarnitine was discovered to be a potent activator of PanK2 that functions to competitively antagonize acetyl-CoA inhibition. Acetyl-CoA was a competitive inhibitor of purified PanK2 with respect to ATP. The interaction between PanK2 and acetyl-CoA was stable enough that a significant proportion of the purified protein was isolated as the PanK2·acetyl-CoA complex. The long-chain acylcarnitine activation of PanK2 explains how PanK2 functions
in vivo
, by providing a positive regulatory mechanism to counteract the negative regulation of PanK2 activity by acetyl-CoA. Our results suggest that PanK2 is located in the mitochondria to sense the levels of palmitoylcarnitine and up-regulate CoA biosynthesis in response to an increased mitochondrial demand for the cofactor to support β-oxidation.
Stimulation of endogenous neurogenesis by anti-EFRH immunization in a transgenic mouse model of Alzheimer's disease
Authors: Becker Maria , Lavie Vered , Solomon Beka
Published: January 2007

Neurogenesis is a subject of intense interest and extensive research, but it stands at the center of a bitter debate over ethical and practical problems. Neurodegenerative diseases, such as Alzheimer's disease (AD), accompanied by a shifting balance between neurogenesis and neurodegeneration, are suitable for stimulation of neurogenesis for the benefit of diseased patients. We have previously shown that Abs against the EFRH sequence of β-amyloid peptide (AβP) prevent aggregation and disaggregate AβP both
in vitro
and
in vivo
. EFRH, located in the soluble tail of the N-terminal region, acts as a regulatory site controlling both solubilization and disaggregation processes in the AβP molecule. Here we show that anti-EFRH immunotherapy of a platelet-derived amyloid precursor protein transgenic mouse model of AD stimulates endogenous neurogenesis, suggested by elevated numbers of BrdU-incorporated cells, most of which are colocalized with a marker of mature neurons, NeuN. These newly born neurons expressed the activity-dependent gene Zif268, indicating their functional integration and participation in response to synaptic input in the brain. These findings suggest that anti-amyloid immunotherapy may promote recovery from AD or other diseases related to AβP overproduction and neurotoxicity by restoring neuronal population, as well as cognitive functions in treated patients.
Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator,
uhrf1
Authors: Sadler Kirsten C. , Krahn Katherine N. , Gaur Naseem A. , Ukomadu Chinweike
Published: January 2007

In contrast to the deregulated hepatocellular division that is a feature of many hepatic diseases and malignancies, physiologic liver growth during embryonic development and after partial hepatectomy (PH) in adults is characterized by tightly controlled cell proliferation. We used forward genetic screening in zebrafish to test the hypothesis that a similar genetic program governs physiologic liver growth during hepatogenesis and regeneration after PH. We identified the
uhrf1
gene, a cell cycle regulator and transcriptional activator of
top2a
expression, as required for hepatic outgrowth and embryonic survival. By developing a methodology to perform PH on adult zebrafish, we found that liver regeneration in
uhrf1
+/−
adult animals is impaired.
uhrf1
transcript levels dramatically increase after PH in both mice, and zebrafish and
top2a
is not up-regulated in
uhrf1
+/−
livers after PH. This indicates that
uhrf1
is required for physiologic liver growth in both embryos and adults and illustrates that zebrafish livers regenerate.
I-Ssp6803I: the first homing endonuclease from the PD-(D/E)XK superfamily exhibits an unusual mode of DNA recognition
Authors: Orlowski Jerzy , Boniecki Michal , Bujnicki Janusz M.
Published: January 2007

Motivation: Restriction endonucleases (REases) and homing endonucleases (HEases) are biotechnologically important enzymes. Nearly all structurally characterized REases belong to the PD-(D/E)XK superfamily of nucleases, while most HEases belong to an unrelated LAGLIDADG superfamily. These two protein folds are typically associated with very different modes of protein-DNA recognition, consistent with the different mechanisms of action required to achieve high specificity. REases recognize short DNA sequences using multiple contacts per base pair, while HEases recognize very long sites using a few contacts per base pair, thereby allowing for partial degeneracy of the target sequence. Thus far, neither REases with the LAGLIDADG fold, nor HEases with the PD-(D/E)XK fold, have been found.

Results: Using protein fold recognition, we have identified the first member of the PD-(D/E)XK superfamily among homing endonucleases, a cyanobacterial enzyme I-Ssp6803I. We present a model of the I-Ssp6803I-DNA complex based on the structure of Type II restriction endonuclease R.BglI and predict the active site and residues involved in specific DNA sequence recognition by I-Ssp6803I. Our finding reveals a new unexpected evolutionary link between HEases and REases and suggests how PD-(D/E)XK nucleases may develop a ‘HEase-like’ way of interacting with the extended DNA sequence. This in turn may be exploited to study the evolution of DNA sequence specificity and to engineer nucleases with new substrate specificities.

Contact:  iamb@genesilico.pl
Acinetobacter baumannii lipopolysaccharides are potent stimulators of human monocyte activation via Toll-like receptor 4 signalling
Authors: Erridge Clett , Moncayo-Nieto Olga L. , Morgan Robert , Young Michelle , Poxton Ian R.
Published: January 2007

Acinetobacter baumanniiis a major nosocomial pathogen and frequent cause of hospital-acquired pneumonia, surgical wound infections and sepsis. As very little is known of the endotoxic potential ofA. baumanniilipopolysaccharide (LPS) with respect to human cells or of its ability to stimulate inflammatory signalling via human Toll-like receptors (TLRs), the biological activity of these endotoxins was investigated in human monocytic THP-1 cells and in TLR-deficient HEK-293 cells transfected with human TLR2 and TLR4 constructs. Endotoxins derived from five clinical isolates ofA. baumanniiand one ofAcinetobacter‘genomospecies 9’ showed high potency, which was comparable to that ofEscherichia colistrain R1 NCTC 13114 LPS, in the induction of the Limulus amoebocyte reaction and interleukin 8 and tumour necrosis factor alpha release from THP-1 cells. Whole UV-killed cells ofA. baumanniiandAcinetobacter‘genomospecies 9’ stimulated both TLR2- and TLR4-dependent signalling, whereas pure endotoxins of all investigated strains induced signalling via TLR4, but not TLR2.
Helicobacter pylori heat-shock protein 60 induces interleukin-8 via a Toll-like receptor (TLR)2 and mitogen-activated protein (MAP) kinase pathway in human monocytes
Authors: Zhao Ying , Yokota Kenji , Ayada Kiyoshi , Yamamoto Yumiko , Okada Tomayuki , Shen Lianhua , Oguma Keiji
Published: January 2007

Previous reports have indicated thatHelicobacter pyloriheat-shock protein 60 (H. pylori-HSP60), as an immunodominant antigen, induces interleukin (IL)-8 production in human monocytes. The exact mechanism by whichH. pylori-HSP60 induces IL-8 production in monocytes has not been fully elucidated. In the present study, the downstream pathway by whichH. pylori-HSP60 induces IL-8 secretion in human monocytic cell lines was investigated. IntactH. pylori, heat-killedH. pyloriandH. pylorirecombinant HSP60 (rHpHSP60) all induced the secretion of IL-8 and the activation of mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and p38, but not c-Jun N-terminal kinase (JNK), up to 24 h in NOMO1 cells. The specific inhibitors PD98059 and U0126 (for ERK1/2 signalling) and SB203580 (for p38 MAPK signalling) down-regulated IL-8 secretion from rHpHSP60-treated NOMO1 cells. An anti-Toll-like receptor (TLR)2 antibody or TLR2 small interfering RNA (siRNA) partially inhibited the secretion of IL-8, and anti-TLR2 antibody also suppressed activation of ERK and p38 MAPK in rHpHSP60-treated NOMO1 cells. These reactions were associated with nuclear factor-κB (NF-κB)-mediated transcriptional activation, since U0126, SB203580 and the anti-TLR2 antibody decreased NF-κB activation. Taken together, the results suggest that ERK and p38 MAPK signalling linked to the TLR2 recognition receptor in human monocytes may be an important pathway inH. pylori-HSP60-induced IL-8 secretion.
VIM1, a methylcytosine-binding protein required for centromeric heterochromatinization
Authors: Woo Hye Ryun , Pontes Olga , Pikaard Craig S. , Richards Eric J.
Published: January 2007

Epigenetic regulation in eukaryotes is executed by a complex set of signaling interactions among small RNA species and chromatin marks, including histone modification and DNA methylation. We identified vim1 (VARIANT IN METHYLATION 1), an Arabidopsis mutation causing cytosine hypomethylation and decondensation of centromeres in interphase. VIM1 is a member of a small gene family, encoding proteins containing PHD, RING, and SRA (SET- and RING-associated) domains, which are found together in mammalian proteins implicated in regulation of chromatin modification, transcription, and the cell cycle. VIM1 is an unconventional methylcytosine-binding protein that interacts in vitro with 5mCpG- and 5mCpHpG-modified DNA (via its SRA domain), as well as recombinant histones (H2B, H3, H4, and HTR12) in plant extracts. VIM1 associates with methylated genomic loci in vivo and is enriched in chromocenters. Our findings suggest that VIM1 acts at the DNA methylation–histone interface to maintain centromeric heterochromatin.
The crystal structure of leucyl/phenylalanyl‐tRNA‐protein transferase from Escherichia coli
Authors: Dong Xuesong , Kato‐Murayama Miyuki , Muramatsu Tomonari , Mori Hirotada , Shirouzu Mikako , Bessho Yoshitaka , Yokoyama Shigeyuki
Published: January 2007

Leucyl/phenylalanyl‐tRNA‐protein transferase (L/F‐transferase) is an N‐end rule pathway enzyme, which catalyzes the transfer of Leu and Phe from aminoacyl‐tRNAs to exposed N‐terminal Arg or Lys residues of acceptor proteins. Here, we report the 1.6 Å resolution crystal structure of L/F‐transferase (JW0868) from Escherichia coli, the first three‐dimensional structure of an L/F‐transferase. The L/F‐transferase adopts a monomeric structure consisting of two domains that form a bilobate molecule. The N‐terminal domain forms a small lobe with a novel fold. The large C‐terminal domain has a highly conserved fold, which is observed in the GCN5‐related N‐acetyltransferase (GNAT) family. Most of the conserved residues of L/F‐transferase reside in the central cavity, which exists at the interface between the N‐terminal and C‐terminal domains. A comparison of the structures of L/F‐transferase and the bacterial peptidoglycan synthase FemX, indicated a structural homology in the C‐terminal domain, and a similar domain interface region. Although the peptidyltransferase function is shared between the two proteins, the enzymatic mechanism would differ. The conserved residues in the central cavity of L/F‐transferase suggest that this region is important for the enzyme catalysis.
Population structure at the S‐locus of Sorbus aucuparia L. (Rosaceae: Maloideae)
Authors: RASPÉ OLIVIER , KOHN JOSHUA R.
Published: January 2007

Low sequence divergence within functional alleles is predicted for the self‐incompatibility locus because of strong negative frequency‐dependent selection. Nevertheless, sequence variation within functional alleles is essential for current models of the evolution of new mating types. We genotyped the stylar self‐incompatibility RNase of 20 Sorbus aucuparia from a population in the Pyrenees mountains of France in order to compare alleles found there to those previously sampled in a Belgian population. Both populations returned 20 different alleles from samples of 20 individuals, providing maximum‐likelihood estimates of 24.4 (95% CI 20–34) alleles in each. Ten alleles occurred in both samples. The maximum likelihood (ML) estimate of the overlap in the alleles present in both populations was 16, meaning that an estimated eight alleles are private to each population, and a total of 32 alleles occur across the two populations examined. We used Fisher's (1961) missing plot method to estimate that 40 alleles occur in the species. In accord with population genetics theory, we observed at most one synonymous sequence difference between copies of alleles sampled from the different populations and no variation within populations. Phylogenetic analysis shows that nearly every allele in S. aucuparia arose prior to divergence of this species from members of three different genera of the Rosaceae subfamily, Maloideae. Lack of observable sequence variation within alleles, coupled with the slow pace of allelic relative to taxonomic diversification, implies that finding intermediate stages in the process of new allele creation will be difficult in this group.
A novel mutation at the DFNA36 hearing loss locus reveals a critical function and potential genotype–phenotype correlation for amino acid‐572 of TMC1
Authors: Kitajiri S , Makishima T , Friedman TB , Griffith AJ
Published: January 2007

We ascertained a North American Caucasian family (LMG248) segregating autosomal dominant, non‐syndromic, post‐lingual, progressive sensorineural hearing loss. The hearing loss begins in the second decade of life and initially affects high frequencies. It progresses to profound deafness at all frequencies by the fourth or fifth decade. The phenotype co‐segregates with short‐tandem repeat markers flanking the TMC1 gene at the DFNA36 locus on chromosome 9q31‐q21. The affected individuals carry a novel missense substitution, p.D572H (c.G1714C), of the TMC1 gene. This mutation is at the same nucleotide and amino acid position as the only other reported DFNA36 mutation, p.D572N (c.G1714A). Our observations implicate a critical function for amino acid‐572 for wild‐type TMC1 function or the pathogenesis of DFNA36 hearing loss. The slower progression of hearing loss associated with p.D572H, in comparison with that caused by p.D572N, may reflect a correlation of DFNA36 phenotype with TMC1 genotype.
Interferon‐beta treatment and active replication of the JC virus in relapsing‐remitting multiple sclerosis patients
Authors: Álvarez‐Lafuente R. , García‐Montojo M. , De Las Heras V. , Bartolomé M. , Arroyo R.
Published: January 2007

We analyzed the effect of beta‐interferon (beta‐IFN) treatment over the active replication of JC virus (JCV) through the evaluation of JCV DNA prevalence and viral load in peripheral blood mononuclear cells (PBMCs) and serum samples, and mRNA prevalence and viral load, in relapsing‐remitting multiple sclerosis (RRMS) patients. DNA extracted from PBMCs and serum, and mRNA extracted from PBMCs were analyzed in 146 RRMS patients (73 treated with beta‐IFN, and 73 untreated patients), and 73 matched healthy blood donors for the presence of JCV genomes by quantitative real‐time PCR assay. We found the same DNA prevalence in PBMC samples in RRMS patients treated with beta‐IFN and in untreated ones: 6.8% (5/73). When we analyzed the viral active replication in both groups through the analysis of DNA prevalence in serum samples and the mRNA extracted from PBMCs, we did not find any positive sample. Regarding the viral load of those positive samples, we did not find any statistical significant difference between treated and untreated RRMS patients: 28.6 ± 7.2 and 32.3 ± 8.4 copies/μg of DNA, respectively. These results lead us to conclude that beta‐IFN treatment in monotherapy has not any effect on JCV active replication.
Effects of human apolipoprotein E isoforms on the amyloid β‐protein concentration and lipid composition in brain low‐density membrane domains
Authors: Morishima‐Kawashima Maho , Han Xianlin , Tanimura Yu , Hamanaka Hiroki , Kobayashi Mariko , Sakurai Takashi , Yokoyama Minesuke , Wada Koji , Nukina Nobuyuki , Fujita Shinobu C. , Ihara Yasuo
Published: January 2007

Apolipoprotein E4 (apoE4) encoded by ε4 allele is a strong genetic risk factor for Alzheimer’s disease (AD). ApoE4 carriers have accelerated amyloid β‐protein (Aβ) deposition in their brains, which may account for their unusual susceptibility to AD. We hypothesized that the accelerated Aβ deposition in the brain of apoE4 carriers is mediated through cholesterol‐enriched low‐density membrane (LDM) domains. Thus, the concentrations of Aβ and various lipids in LDM domains were quantified in the brains of homozygous apoE3 and apoE4 knock‐in (KI) mice, and in the brains of those mice bred with β‐amyloid precursor protein (APP) transgenic mice (Tg2576). The Aβ40 and Aβ42 concentrations and the Aβ42 proportions in LDM domains did not differ between apoE3 and apoE4 KI mice up to 18 months of age. The Aβ40 concentration in the LDM domains was slightly, but significantly higher in apoE3/APP mice than in apoE4/APP mice. The lipid composition of LDM domains was modulated in an apoE isoform‐specific manner, but its significance for Aβ deposition remains unknown. These data show that the apoE isoform‐specific effects on the Aβ concentration in LDM domains do not occur in KI mouse models.
Amyotrophic lateral sclerosis: all roads lead to Rome
Authors: Aguilar Jose‐Luis Gonzalez de , Echaniz‐Laguna Andoni , Fergani Anissa , René Frédérique , Meininger Vincent , Loeffler Jean‐Philippe , Dupuis Luc
Published: January 2007

Amyotrophic lateral sclerosis (ALS) is the most frequent adult‐onset motor neuron disease characterized by degeneration of upper and lower motor neurons, generalized weakness and muscle atrophy. Most cases of ALS appear sporadically but some forms of the disease result from mutations in the gene encoding the antioxidant enzyme Cu/Zn superoxide dismutase (SOD1). Several other mutated genes have also been found to predispose to ALS including, among others, one that encodes the regulator of axonal retrograde transport dynactin. As all roads lead to the proverbial Rome, we discuss here how distinct molecular pathways may converge to the same final result that is motor neuron death. We critically review the basic research on SOD1‐linked ALS to propose a pioneering model of a ‘systemic’ form of the disease, causally involving multiple cell types, either neuronal or non‐neuronal. Contrasting this, we also postulate that other neuron‐specific defects, as those triggered by dynactin dysfunction, may account for a primary motor neuron disease that would represent ‘pure’ neuronal forms of ALS. Identifying different disease subtypes is an unavoidable step toward the understanding of the physiopathology of ALS and will hopefully help to design specific treatments for each subset of patients.
A pooling approach to detect signatures of selective sweeps in genome scans using microsatellites
Authors: THOMAS MEIKE , MÖLLER FRIEDRICH , WIEHE THOMAS , TAUTZ DIETHARD
Published: January 2007

We have evaluated a pooling approach that can reduce the number of polymerase chain reactions in a screen for selective sweeps by more than an order of magnitude. We show that the complex peak pattern that results from pooling of all samples from a given population is a faithful reflection of the composite pattern of the individual alleles, although with an under‐representation of the larger alleles. Candidate loci for selective sweeps can be identified by visual inspection of the pool patterns. We have also implemented a software tool, which can find suitable microsatellite loci in the vicinity of annotated genes.
Morphometric analysis of murine skin wound healing: Standardization of experimental procedures and impact of an advanced multitissue array technique
Authors: Gerharz Michael , Baranowsky Ankev , Siebolts Udo , Eming Sabine , Nischt Roswitha , Krieg Thomas , Wickenhauser Claudia
Published: January 2007

Morphometric data based on skin wounding offer important information for the characterization of the phenotype of transgenic mouse models. The goal of this study was the comparison of technical procedures concerning wounding, processing, and evaluation of samples in different mouse strains. The multitissue array technique was used to estimate its adaptability for standardized analysis in wound healing. Skin wounds between days 1 and 14 after wounding were analyzed. The influence of mouse strain (C57BI/6 vs. FVB/N mice), sex, size of the punch biopsies, and preparation of the tissue sections was investigated on 94 mice. The parameters distance between the migration tongues (δMT) and surface not covered by epithelium were evaluated to describe the reepithelialization, and the distance between the adnexa was chosen to measure wound contraction. In addition, the techniques to measure the area of granulation tissue (GT) were evaluated. The data illustrate the requirement of standardized conditions for skin wound‐healing experiments and demonstrate that histological preparation in serial sections is mandatory to detect slight differences in wound contraction. For the analysis of cellular composition in GT, multitissue arrays are useful tools in wound‐healing studies.
Erythropoietin after a century of research: younger than ever
Authors: Jelkmann Wolfgang
Published: January 2007

In the light of the enthusiasm regarding the use of recombinant human erythropoietin (Epo) and its analogues for treatment of the anaemias of chronic renal failure and malignancies it is worth remembering that today's success has been based on a century of laborious research. The concept of the humoral regulation of haematopoiesis was first formulated in 1906. The term ‘erythropoietin’ for the erythropoiesis‐stimulating hormone was introduced in 1948. Native human Epo was isolated in 1977 and its gene cloned in 1985. During the last 15 yr, major progress has been made in identifying the molecules controlling Epo gene expression, primarily the hypoxia‐inducible transcription factors (HIF) that are regulated by specific O2 and oxoglutarate requiring Fe2+‐containing dioxygenases. With respect to the action of Epo, its dimeric receptor (Epo‐R) has been characterised and shown to signal through protein kinases, anti‐apoptotic proteins and transcription factors. The demonstration of Epo‐R in non‐haematopoietic tissues indicates that Epo is a pleiotropic viability and growth factor. The neuroprotective and cardioprotective potentials of Epo are reviewed with a focus on clinical research. In addition, studies utilising the Epo derivatives with prolonged half‐life, peptidic and non‐peptidic Epo mimetics, orally active drugs stimulating endogenous Epo production and Epo gene transfer are reviewed.