bluuebunny/crossref_metadata_2025 huggingface dataset:
Anterior vaginal wall reconstruction: anterior colporrhaphy reinforced with tension free vaginal tape underneath bladder base
Authors: TANTANASIS T. , GIANNOULIS C. , DANIILIDIS A. , PAPATHANASIOU K. , LOUFOPOULOS A. , TZAFETTAS J.
Published: April 2008

Objective. To assess the effectiveness of the polypropylene tape in preventing cystocele recurrence. Methods. Fifty Caucasian women aged 50‐77 years (mean age 66.6 years), with stage II–IV pelvic organ prolapse, enrolled into the study. Vaginal reconstructive surgery included an anterior colporrhaphy on all patients, posterior colpoperineorrhaphy on 28 patients and hysterectomy on 36 patients. Patients were divided into a study group of 28 women and a control group of 22 women. As reinforcement to the anterior colporrhaphy procedure, in the study group a polypropylene tape (TVT‐O) was placed underneath the bladder base and fixed with polyglactin sutures. Postoperative follow‐up was carried out every 4 months (total 48 months). The assessment of the anatomic result included both clinical evaluation of the operated sites and perineal sonography. Results. The mean postoperative distance of the bladder base to the inferior edge of the symphysis pubis was 1.5 cm (range: 1.0–2.2 cm) in the study group and 2.8 cm (range: 2.0–3.8) in the control group. Postoperatively, there were two cases of stress incontinence and two cases of urge incontinence, one in each group. No case of tape erosion was noted, no dyspareunia and no recurrent cystocele in the study group. Four cases of recurrent cystocele (20%) were reported in the control group. Conclusion. While the preliminary results of our study are encouraging, larger series of patients and longer follow‐up are required to verify the effectiveness of the aforementioned modification.
What Does the Rise of China Do for Industrialisation in Sub-Saharan Africa?
Authors: Power Raphael
Published: April 2008

China's rapid growth and deepening global presence in Africa creates a major challenge for the conventional wisdom of industrialisation as a core component of development strategy. These challenges are expressed through a combination of direct impacts (expressed in bilateral country-to-country relations) and indirect impacts (reflected in competition in third country markets). In current structures, these impacts are predominantly harmful for SSA's industrial growth, as expressed through its recent experience in the exports of clothing to the US under AGOA (African Growth & Opportunity Act). If Washington Consensus policies prevail, these harmful impacts will be sustained and deepened.
China & India as Africa's New Donors: The Impact of Aid on Development
Authors: McCormick Dorothy
Published: April 2008

Using a two-analytical framework and drawing on a wide range of secondary data, this article attempts to assess the likely impact of aid from China and India on the development of Africa. The framework treats aid as one of four main channels through which China and India influence the shape and performance of particular sectors and, through them, development outcomes. The first stage of analysis examines the varying patterns of Chinese and Indian aid and the multiple impacts such aid has on one key sector: manufacturing. The main findings from this level of analysis have to do with the differing patterns of Indian and Chinese aid, differences between Chinese and Indian aid, and aid from western countries, and the interconnections between the impact channels.

India and China have different patterns of aid. India concentrates on non-monetary aid mainly in the form of technical assistance and scholarships, while China offers a wider range of monetary and non-monetary aid packages, which include grants and loans for infrastructure, plant and equipment, as well as scholarships, training opportunities, and technical assistance. Chinese monetary aid is tied to the use of Chinese goods and services, and requires adherence to the 'One China' policy, but does not carry the 'good governance' conditionalities that currently characterise western donors. The impact channels of trade, FDI, aid, and migration overlap to some degree, especially in the case of China. The line between FDI and aid is often blurred, as is the line between aid and trade. The second stage of the analysis looks at the implications of Chinese and Indian aid to manufacturing for development outcomes such as growth, distribution, governance, and environment. The analysis shows clearly that the potential impact of Chinese and Indian aid on Africa is significant, but that the actual effects of these emerging donors on particular countries depends to a large extent on the institutional and structural conditions of the recipients.
China & the Contradictions of ‘Non-interference’ in Sudan
Authors: Large Daniel
Published: April 2008

The core Chinese foreign policy principle of non-interference has recently come under increasing and more visible strain in China's relations with Sudan. Noninterference has been central to Beijing's relations with different governments in Khartoum since 1959. From the mid-1990s, however, the Chinese role in Sudan has become more embedded and consequential. Today China faces the challenge of accommodating its established policy of non-interference with the more substantive and growing complexity of Chinese involvement developed over the past decade in Sudan, amidst ongoing conflict in western Darfur and changing politics after the North-South peace agreement of January 2005.
Variations in Reflex Blink-Rate during Visual-Motor Tasks
Authors: Drew G. C.
Published: April 2008

The influence of the performance of various tasks on the reflex blink rate has been investigated repeatedly, but the results obtained have been somewhat contradictory. More recently, it has been suggested that the reflex blink rate may be a considerable factor in the accuracy with which visual-motor tasks are performed. The aim of the present experiment was to attempt to obtain further evidence on both these questions.

The experiment was carried out in two parts. The main part was done in the laboratory, while a validating experiment was carried out on the road. In the laboratory, subjects were required to steer a pencil along a moving track which varied in difficulty. The difficulty of the response was varied by using a direct control on some trials and a velocity control on others. Blink rate, errors, and control measurements were recorded throughout. In the road experiment, cine films were taken of the driver's eyes while driving in heavy traffic and in open country.

The results of both experiments show: (a) That there are marked individual differences in blink rate, the relative order of which is maintained in spite of variations in the actual blink rate. (b) That there is no relationship between the accuracy with which a particular individual carries out a task of this sort and his blink rate. The rapid “blinker” is no more and no less likely to be accurate than the infrequeiit I “blinker.” (c) That the actual blink rate for all individuals varies inversely with the difficulty of the task and the amount of control movement necessary. The blink rate decreases as the necessity for detailed visual control of movement increases. Blink rates when driving a car in heavy traffic, or when steering along an oscillating track, are considerably lower than when driving in open country or when following a straight track. (d) That the adjustment of the blink rate to the difficulty of the task is achieved not only by an alteration in overall blink rate, but also by a change in the distribution of blinking. The blink rate is approximately constant under constant conditions, but when the task is varying in difficulty, blinking occurs just before and just after periods of maximum difficulty, but is completely inhibited during the periods of maximum difficulty itself.
Further Experiments on the Olfactory Thresholds of Pure Chemical Substances, Using the “Sniff-Bottle Method”
Authors: Cheesman G. H. , Townsend M. J.
Published: April 2008

“Sniff-Bottle” method of determining olfactory thresholds under conditions of adaptation to a second olfactory stimulus, as described by Cheesman and Mayne (1953), has been further developed. Their study was limited to the mutual adaptation effects of three substances. The original matrix of nine quantities, described as degrees of community of odour property, has been revised and extended to include a fourth stimulus-substance. It is suggested that the matrix now obtained shows a definite pattern characteristic of consistent mutual relationships between the substances. A number of shortcomings in the original technique are discussed, and the appropriate emendations described.
Some Effects of Thiamine Deficiency and Reduced Caloric Intake on “Behaviour under Stress” and on Learning
Authors: Knopfelmacher F. , Khairy Melek , Russell R. W. , Yudkin John
Published: April 2008

The main purpose of the investigation was to determine the effects of thiamine deficiency in rats on behaviour under stress and on learning. Since thiamine deficiency reduces food intake, it was necessary to have two control groups. The first received adequate thiamine, but a food intake reduced to that of the vitamin-deficient animals; the second received adequate thiamine and an unrestricted food intake. It was thus possible to study the effects both of thiamine deficiency and of reduced caloric intake on the behaviour variables measured.

The experimental group was maintained on a thiamine-deficient diet throughout the entire experimental period. Because of the effects of thiamine deficiency on caloric intake, food-hunger was never used as a form of motivation. Behaviour in four different situations was studied: in Hall's open-field test, in two discrimination situations both involving exposure to insoluble and soluble problems, and in a water maze.

Contrary to the findings of several previous studies, there were no significant effects of thiamine deficiency on behaviour prior to the onset of polyneuritis with its debilitating effects on motor co-ordination. There was also no evidence of impairment in any of the behaviour studied which could be attributed to restrictions in caloric intake. This was the case even though the restrictions continued for a period of somewhat more than twelve months. Although these restrictions did not lead to impairment they were associated with certain changes in performance. Animals whose feeding was restricted were more active and, during the soluble phase of one discrimination situation, showed more vicarious trial and error and learned more readily than animals fed ad libitum on the same diet. It is suggested that these differences may be interpreted in terms of the effects of what previous investigators have referred to as “irrelevant drives”.
Experimental Determination of Luneburg's Constants σ and κ
Authors: Zajaczkowska A.
Published: April 2008

Visual space is, according to Luneburg, a non-Euclidean hyperbolic space of constant negative curvature. Two personal constants enter into the geometrical description of binocular subjective space. One is σ indicating the degree of depth perception characteristic to the observer. The second is K, the curvature; a value which denotes by how much the visual space of an individual departs from Euclidean space. The constants σ and K were determined experimentally for 30 untrained observers by Luneburg's 3- and 4-point tests. All values found for K were negative and support the hypothesis that the geometry of binocular space is hyperbolic. Some discrepancies between the theory and findings were observed, while the sensitivity of the experiments to the lack of training and even a slight measure of aniseikonia is evident.
Directional Information and Apparent Movement
Authors: Jeeves Malcolm A. , Bruner Jerome S.
Published: April 2008

The number of alternative directions that a point of light can take in the apparent movement produced by the successive exposure of two points of light may be considered its directional information. The present experiment is concerned with the relationship between such directional information and the threshold between apparent movement and apparent successiveness, the original hypothesis being that the greater the directional information, the higher the threshold of movement. In fact, contrary results were obtained. Thresholds were obtained under conditions where movement could occur in either eight directions or only in two directions, better and more persistent movement being found under the former conditions. But this result is obtained only when one measures thresholds by an ascending method: increasing the time separation between light points from optimal movement to successiveness. An hypothesis is proposed to explain the findings stated in terms of “attentional disarticulation”.
Different Thresholds for Recognition—Further Experiments on Interpolated Recall and Recognition
Authors: Kay Harry , Skemp Richard
Published: April 2008

Three experiments are described which have attempted to identify some of the difficulties in recognition after interpolated recall. In the first, complex picture material was used, and, though subjects were able to recognize the original after interpolated recall, they did in fact recognize fewer items. This posed the query, why should the recall of some items depress the recognition of other unrecalled items? The second experiment showed that in recognition the stronger (correct) memory has an inhibitory effect on a weaker (also correct) memory. The third experiment therefore examined the hypothesis that the juxtaposition of better and worse known items raises the threshold of recognition of the worse known, and confirmed that the threshold of recognition for an item varies according to its context. The theoretical significance of this finding is briefly indicated.
Like and cross modality responses in normal and subnormal children
Authors: Hermelin B. , O'connor N.
Published: April 2008

Experiments which investigated response behaviour in imbeciles and normals, in a conflict situation between a general verbal instruction and direct stimuli, were carried out. It was found that combined verbal-motor responses did not give better results than either verbal or motor responses alone. Results in accordance with the general instruction were significantly better if the subnormal children responded in a different modality from the one in which the signals were given. While normals and imbeciles differed markedly in their ability to perform the tasks in like-modality trials, this difference was less apparent in cross modality responses.
Apparatus: The Reflecting Shutter Principle and Mechanical Tachistoscopes
Authors: Deutsch J. A.
Published: April 2008

The principle employed in the two tachistoscopes described below is that of using a shutter which reflects light down one channel at the same time as it cuts it off from another. The principle has been applied to produce a high speed projection tachistoscope at a fraction of the cost of a comparable electronic model and a simple direct view classroom tachistoscope. The principle can be further adapted to a variety of uses.
Perceptual Capacity of the Isolated Visual Cortex in the Cat
Authors: Sperry R. W. , Myers R. E. , Schrier A. M.
Published: April 2008

The split-brain approach was utilized in 6 cats to test the degree of functional autonomy in the visual system. The central visual cortex of one hemisphere was isolated by the removal of most of the extravisual neocortex of the same hemisphere. Visual inflow was restricted to the isolated side in four cases by sectioning the crossed optic fibres at the chiasma and masking one eye and in two cases by section of the contralateral optic tract. The isolation produced severe deficits in visual performance, although all cases retained some ability to learn and to recall simple pattern discriminations. The results of two- and three-stage removals of the non-visual cortex, and of terminal section of the callosum, as well as histology of the lateral geniculate nucleus indicated that geniculo-striate damage was not the limiting factor. Removal of fronto-parietal cortex produced as much or more decrement in visual discrimination than did removal of temporal cortex.
Apparatus: A New Colour Mixer and Episcotister
Authors: Perry A. , Howard I. P.
Published: April 2008

The paper describes the construction of a differential system which can be used as a colour mixer or flicker apparatus. The use of sectored discs has been largely replaced by filters, wedges and polaroids in much visual work. However, our apparatus has two main applications, as a convenient, inexpensive colour mixer for student work and as a research tool in the study of flicker fusion and kindred phenomena.
A Contribution to the Study of Phenomenal Causation
Authors: Boyle D. G.
Published: April 2008

In his studies of the perception of causality, Michotte describes a number of “impressions” concomitant with precisely defined experimental conditions, of which “Launching” † and “Triggering” † are two of the most important. Two major factors influencing the nature of the impressions are the relative speeds of the two rectangles representing objects participating in dynamic inter-relationships, and the length of path of the more passive of the two objects. This investigation was an attempt to discover the quantitative relationships obtaining between these two independent variables and the dependent variable of the subjects’ responses to the experimental conditions.
The Use of Small Filament Lamps as Visual Stimuli
Authors: Carpenter A. , Leonard J. A.
Published: April 2008

The purpose of this note is to draw attention to the fact that the time needed for small filament lamps to reach full brightness is dependent upon the time for which they have been previously switched off. This dependence is a possible source of error in biassed choice reaction sequences, and a circuit is given which avoids the difficulty.
Transmembrane domain–dependent partitioning of membrane proteins within the endoplasmic reticulum
Authors: Ronchi Paolo , Colombo Sara , Francolini Maura , Borgese Nica
Published: April 2008

The length and hydrophobicity of the transmembrane domain (TMD) play an important role in the sorting of membrane proteins within the secretory pathway; however, the relative contributions of protein–protein and protein–lipid interactions to this phenomenon are currently not understood. To investigate the mechanism of TMD-dependent sorting, we used the following two C tail–anchored fluorescent proteins (FPs), which differ only in TMD length: FP-17, which is anchored to the endoplasmic reticulum (ER) membrane by 17 uncharged residues, and FP-22, which is driven to the plasma membrane by its 22-residue-long TMD. Before export of FP-22, the two constructs, although freely diffusible, were seen to distribute differently between ER tubules and sheets. Analyses in temperature-blocked cells revealed that FP-17 is excluded from ER exit sites, whereas FP-22 is recruited to them, although it remains freely exchangeable with the surrounding reticulum. Thus, physicochemical features of the TMD influence sorting of membrane proteins both within the ER and at the ER–Golgi boundary by simple receptor-independent mechanisms based on partitioning.
Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival
Authors: Van Damme Philip , Van Hoecke Annelies , Lambrechts Diether , Vanacker Peter , Bogaert Elke , van Swieten John , Carmeliet Peter , Van Den Bosch Ludo , Robberecht Wim
Published: April 2008

Recently, mutations in the progranulin (PGRN) gene were found to cause familial and apparently sporadic frontotemporal lobe dementia (FTLD). Moreover, missense changes in PGRN were identified in patients with motor neuron degeneration, a condition that is related to FTLD. Most mutations identified in patients with FTLD until now have been null mutations. However, it remains unknown whether PGRN protein levels are reduced in the central nervous system from such patients. The effects of PGRN on neurons also remain to be established. We report that PGRN levels are reduced in the cerebrospinal fluid from FTLD patients carrying a PGRN mutation. We observe that PGRN and GRN E (one of the proteolytic fragments of PGRN) promote neuronal survival and enhance neurite outgrowth in cultured neurons. These results demonstrate that PGRN/GRN is a neurotrophic factor with activities that may be involved in the development of the nervous system and in neurodegeneration.
Gone with the Wnt/Notch: stem cells in laminopathies, progeria, and aging
Authors: Meshorer Eran , Gruenbaum Yosef
Published: April 2008

Specific mutations in the human gene encoding lamin A or in the lamin A–processing enzyme, Zmpste24, cause premature aging. New data on mice and humans suggest that these mutations affect adult stem cells by interfering with the Notch and Wnt signaling pathways.
Gene placement and competition control T cell receptor γ variable region gene rearrangement
Authors: Xiong Na , Zhang Li , Kang Chulho , Raulet David H.
Published: April 2008

The production of distinct sets of T cell receptor (TCR) γδ+ T cells occurs in an ordered fashion in thymic development. The Vγ3 and Vγ4 genes, located downstream in the TCRγ Cγ1 gene cluster, are expressed by the earliest waves of developing TCRγδ+ T cells in the fetal thymus, destined for intraepithelial locations. Upstream Vγ2 and Vγ5 genes are expressed in later waves in the adult and constitute most TCRγδ+ T cells in secondary lymphoid tissue. This developmental pattern is caused in part by a preference for rearrangements of the downstream Vγ3 and Vγ4 genes in the early fetal stage, which switches to a preference for rearrangements of the upstream Vγ2 and Vγ5 gene rearrangements in the adult. Our gene targeting studies show that the downstream Vγ genes rearrange preferentially in the early fetal thymus because of their downstream location, independent of promoter or recombination signal sequences and unrelated to the extent of germline transcription. Remarkably, gene deletion studies show that the downstream Vγ genes competitively inhibit upstream Vγ rearrangements at the fetal stage. These data provide a mechanism for specialization of the fetal thymus for the production of T cells expressing specific Vγ genes.
A minimal binding footprint on CD1d-glycolipid is a basis for selection of the unique human NKT TCR
Authors: Wun Kwok S. , Borg Natalie A. , Kjer-Nielsen Lars , Beddoe Travis , Koh Ruide , Richardson Stewart K. , Thakur Meena , Howell Amy R. , Scott-Browne James P. , Gapin Laurent , Godfrey Dale I. , McCluskey James , Rossjohn Jamie
Published: April 2008

Although it has been established how CD1 binds a variety of lipid antigens (Ag), data are only now emerging that show how αβ T cell receptors (TCRs) interact with CD1-Ag. Using the structure of the human semiinvariant NKT TCR–CD1d–α-galactosylceramide (α-GalCer) complex as a guide, we undertook an alanine scanning mutagenesis approach to define the energetic basis of this interaction between the NKT TCR and CD1d. Moreover, we explored how analogues of α-GalCer affected this interaction. The data revealed that an identical energetic footprint underpinned the human and mouse NKT TCR–CD1d–α-GalCer cross-reactivity. Some, but not all, of the contact residues within the Jα18-encoded invariant CDR3α loop and Vβ11-encoded CDR2β loop were critical for recognizing CD1d. The residues within the Vα24-encoded CDR1α and CDR3α loops that contacted the glycolipid Ag played a smaller energetic role compared with the NKT TCR residues that contacted CD1d. Collectively, our data reveal that the region distant to the protruding Ag and directly above the F′ pocket of CD1d was the principal factor in the interaction with the NKT TCR. Accordingly, although the structural footprint at the NKT TCR–CD1d–α-GalCer is small, the energetic footprint is smaller still, and reveals the minimal requirements for CD1d restriction.
Leukocyte transmigration requires kinesin-mediated microtubule-dependent membrane trafficking from the lateral border recycling compartment
Authors: Mamdouh Zahra , Kreitzer Geri E. , Muller William A.
Published: April 2008

Diapedesis of leukocytes across endothelial cells is a crucial step in both the innate and adaptive immune responses. Surface molecules on leukocytes and endothelial cells critical for diapedesis have been identified, but the mechanisms underlying this process are not understood. Homophilic interaction between platelet/endothelial cell adhesion molecule (PECAM) on leukocytes and PECAM at the endothelial border triggers targeted recycling of membrane from a reticulum localized close to the endothelial cell lateral border. This membrane surrounds the transmigrating leukocyte (Mamdouh, Z., X. Chen, L.M. Pierini, F.R. Maxfield, and W.A. Muller. 2003. Nature. 421:748–753). How this process occurs and whether it is required for diapedesis independent of PECAM are not known. We now report that targeted recycling from this lateral border recycling compartment (LBRC) is required for diapedesis, is mediated by kinesin family molecular motors, and requires normally functioning endothelial microtubules. Selective disruption of microtubules or inhibition of kinesin motor domain blocked targeted recycling and diapedesis of monocytes. Furthermore, targeted recycling of membrane from the LBRC was required for transmigration of lymphocytes, which migrate independently of PECAM. Thus, trafficking of membrane from the LBRC to surround leukocytes may be a general requirement for migration of leukocytes across the endothelial cell border. Furthermore, these data provide the first demonstration of a role for endothelial microtubules and kinesins in promoting diapedesis, and a mechanism to explain targeted recycling.
12(S)-hydroxyheptadeca-5Z, 8E, 10E–trienoic acid is a natural ligand for leukotriene B4 receptor 2
Authors: Okuno Toshiaki , Iizuka Yoshiko , Okazaki Hiroshi , Yokomizo Takehiko , Taguchi Ryo , Shimizu Takao
Published: April 2008

Activated blood platelets and macrophages metabolize prostaglandin H2 into thromboxane A2 and 12(S)-hydroxyheptadeca-5Z, 8E, 10E–trienoic acid (12-HHT) in an equimolar ratio through the action of thromboxane synthase. Although it has been shown that 12-HHT is abundant in tissues and bodily fluids, this compound has long been viewed as a by-product lacking any specific function. We show that 12-HHT is a natural ligand for leukotriene B4 (LTB4) receptor-2 (BLT2), a G protein–coupled receptor that was originally identified as a low-affinity receptor for LTB4. BLT2 agonistic activity in lipid fractions from rat small intestine was identified as 12-HHT using high-performance liquid chromatography and mass spectrometry. Exogenously expressed BLT2 in mammalian cells was activated by synthetic 12-HHT, as assessed by guanosine 5′-O-(3-thio) triphosphate binding, the activation of intracellular signaling pathways, and chemotaxis assay. Displacement analysis using [3H]LTB4 showed that 12-HHT binds to BLT2 with a higher affinity than LTB4. Lipid extracts from cyclooxygenase 1–deficient mice failed to activate BLT2. Bone marrow–derived mast cells (BMMCs) isolated from wild-type mice migrated toward a low concentration of 12-HHT, whereas BMMCs from BLT2-deficient mice did not. We conclude that 12-HHT is a natural lipid agonist of BLT2 in vivo and induces chemotaxis of mast cells.
Comparison of radiating divertor behaviour in single-null and double-null plasmas in DIII-D
Authors: Petrie T.W. , Brooks N.H. , Fenstermacher M.E. , Groth M. , Hyatt A.W. , Isler R.C. , Lasnier C.J. , Leonard A.W. , Porter G.D. , Schaffer M.J. , Watkins J.G. , Wade M.R. , West W.P.
Published: April 2008

‘Puff-and-pump’ radiating divertor scenarios, applied to both upper single-null (SN) and double-null (DN) H-mode plasmas, result in a 30–60% increase in radiated power with little or no decrease in τE. Argon was injected into the private flux region of the upper divertor, and plasma flow into the upper divertor was enhanced by a combination of deuterium gas puffing upstream of the divertor targets and particle pumping at the targets. For the same constant deuterium injection rate, argon penetrated the main plasma of SNs more rapidly and reached a higher steady-state concentration when theB× ∇B-ion drift direction wastowardsthe divertor (V∇B↑) rather thanaway fromthe divertor (V∇B↓). We also found that the initial rate at which argon accumulated inside DN plasmas was more than twice that of comparable SN plasmas having the sameB× ∇B-ion drift direction. In DNs, the radiated power was not shared equally between divertors during argon injection. Only when theB× ∇Bion drift direction was away from the divertor were both significant increases in divertor radiated power and an accumulation of argon in the divertor observed, based on spectroscopic measurements of Ar II. Our data suggest that an unbalanced DN shape where theB× ∇B-ion drift is directedawayfrom the dominant divertor may provide the best chance of successfully coupling a radiating divertor approach with a higher performance H-mode plasma.
Probabilistic multi-class multi-kernel learning: on protein fold recognition and remote homology detection
Authors: Damoulas Theodoros , Girolami Mark A.
Published: April 2008

Motivation: The problems of protein fold recognition and remote homology detection have recently attracted a great deal of interest as they represent challenging multi-feature multi-class problems for which modern pattern recognition methods achieve only modest levels of performance. As with many pattern recognition problems, there are multiple feature spaces or groups of attributes available, such as global characteristics like the amino-acid composition (C), predicted secondary structure (S), hydrophobicity (H), van der Waals volume (V), polarity (P), polarizability (Z), as well as attributes derived from local sequence alignment such as the Smith–Waterman scores. This raises the need for a classification method that is able to assess the contribution of these potentially heterogeneous object descriptors while utilizing such information to improve predictive performance. To that end, we offer a single multi-class kernel machine that informatively combines the available feature groups and, as is demonstrated in this article, is able to provide the state-of-the-art in performance accuracy on the fold recognition problem. Furthermore, the proposed approach provides some insight by assessing the significance of recently introduced protein features and string kernels. The proposed method is well-founded within a Bayesian hierarchical framework and a variational Bayes approximation is derived which allows for efficient CPU processing times.

Results: The best performance which we report on the SCOP PDB-40D benchmark data-set is a 70% accuracy by combining all the available feature groups from global protein characteristics but also including sequence-alignment features. We offer an 8% improvement on the best reported performance that combines multi-class k-nn classifiers while at the same time reducing computational costs and assessing the predictive power of the various available features. Furthermore, we examine the performance of our methodology on the SCOP 1.53 benchmark data-set that simulates remote homology detection and examine the combination of various state-of-the-art string kernels that have recently been proposed.

Contact:  theo@dcs.gla.ac.uk

Supplementary information: Supplementary data are available at Bioinformatics online.
The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2
Authors: Park Sun-Mi , Gaur Arti B. , Lengyel Ernst , Peter Marcus E.
Published: April 2008

Cancer progression has similarities with the process of epithelial-to-mesenchymal transition (EMT) found during embryonic development, during which cells down-regulate E-cadherin and up-regulate Vimentin expression. By evaluating the expression of 207 microRNAs (miRNAs) in the 60 cell lines of the drug screening panel maintained by the Nation Cancer Institute, we identified the miR-200 miRNA family as an extraordinary marker for cells that express E-cadherin but lack expression of Vimentin. These findings were extended to primary ovarian cancer specimens. miR-200 was found to directly target the mRNA of the E-cadherin transcriptional repressors ZEB1 (TCF8/δEF1) and ZEB2 (SMAD-interacting protein 1 [SIP1]/ZFXH1B). Ectopic expression of miR-200 caused up-regulation of E-cadherin in cancer cell lines and reduced their motility. Conversely, inhibition of miR-200 reduced E-cadherin expression, increased expression of Vimentin, and induced EMT. Our data identify miR-200 as a powerful marker and determining factor of the epithelial phenotype of cancer cells.
DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes
Authors: Kuramochi-Miyagawa Satomi , Watanabe Toshiaki , Gotoh Kengo , Totoki Yasushi , Toyoda Atsushi , Ikawa Masahito , Asada Noriko , Kojima Kanako , Yamaguchi Yuka , Ijiri Takashi W. , Hata Kenichiro , Li En , Matsuda Yoichi , Kimura Tohru , Okabe Masaru , Sakaki Yoshiyuki , Sasaki Hiroyuki , Nakano Toru
Published: April 2008

Silencing of transposable elements occurs during fetal gametogenesis in males via de novo DNA methylation of their regulatory regions. The loss of MILI (miwi-like) and MIWI2 (mouse piwi 2), two mouse homologs of Drosophila Piwi, activates retrotransposon gene expression by impairing DNA methylation in the regulatory regions of the retrotransposons. However, as it is unclear whether the defective DNA methylation in the mutants is due to the impairment of de novo DNA methylation, we analyze DNA methylation and Piwi-interacting small RNA (piRNA) expression in wild-type, MILI-null, and MIWI2-null male fetal germ cells. We reveal that defective DNA methylation of the regulatory regions of the Line-1 (long interspersed nuclear elements) and IAP (intracisternal A particle) retrotransposons in the MILI-null and MIWI2-null male germ cells takes place at the level of de novo methylation. Comprehensive analysis shows that the piRNAs of fetal germ cells are distinct from those previously identified in neonatal and adult germ cells. The expression of piRNAs is reduced under MILI- and MIWI2-null conditions in fetal germ cells, although the extent of the reduction differs significantly between the two mutants. Our data strongly suggest that MILI and MIWI2 play essential roles in establishing de novo DNA methylation of retrotransposons in fetal male germ cells.
Control of cell fate by the formation of an architecturally complex bacterial community
Authors: Vlamakis Hera , Aguilar Claudio , Losick Richard , Kolter Roberto
Published: April 2008

Bacteria form architecturally complex communities known as biofilms in which cells are held together by an extracellular matrix. Biofilms harbor multiple cell types, and it has been proposed that within biofilms individual cells follow different developmental pathways, resulting in heterogeneous populations. Here we demonstrate cellular differentiation within biofilms of the spore-forming bacterium Bacillus subtilis, and present evidence that formation of the biofilm governs differentiation. We show that motile, matrix-producing, and sporulating cells localize to distinct regions within the biofilm, and that the localization and percentage of each cell type is dynamic throughout development of the community. Importantly, mutants that do not produce extracellular matrix form unstructured biofilms that are deficient in sporulation. We propose that sporulation is a culminating feature of biofilm formation, and that spore formation is coupled to the formation of an architecturally complex community of cells.
Acute predator stress impairs the consolidation and retrieval of hippocampus-dependent memory in male and female rats
Authors: Park Collin R. , Zoladz Phillip R. , Conrad Cheryl D. , Fleshner Monika , Diamond David M.
Published: April 2008

We have studied the effects of an acute predator stress experience on spatial learning and memory in adult male and female Sprague-Dawley rats. All rats were trained to learn the location of a hidden escape platform in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. In the control (non-stress) condition, female rats were superior to the males in the accuracy and consistency of their spatial memory performance tested over multiple days of training. In the stress condition, rats were exposed to the cat for 30 min immediately before or after learning, or before the 24-h memory test. Predator stress dramatically increased corticosterone levels in males and females, with females exhibiting greater baseline and stress-evoked responses than males. Despite these sex differences in the overall magnitudes of corticosterone levels, there were significant sex-independent correlations involving basal and stress-evoked corticosterone levels, and memory performance. Most importantly, predator stress impaired short-term memory, as well as processes involved in memory consolidation and retrieval, in male and female rats. Overall, we have found that an intense, ethologically relevant stressor produced a largely equivalent impairment of memory in male and female rats, and sex-independent corticosterone-memory correlations. These findings may provide insight into commonalities in how traumatic stress affects the brain and memory in men and women.
Involvement of basolateral amygdala α2-adrenoceptors in modulating consolidation of inhibitory avoidance memory
Authors: Ferry Barbara , McGaugh James L.
Published: April 2008

These experiments investigated the role of the α2-adrenoceptors of the basolateral nucleus of the amygdala (BLA) in modulating the retention of inhibitory avoidance (IA). In Experiment 1, male Sprague Dawley rats implanted with bilateral cannulae in the BLA received microinfusions of a selective α2-adrenoceptor antagonist idazoxan 20 min either before or immediately after training. Retention was tested 48 h later. Idazoxan induced a dose-dependent enhancement of retention performance and was more effective when administered post-training. In Experiment 2, animals received pre- or post-training intra-BLA infusions of a selective α2-adrenoceptor agonist UK 14,304. The agonist induced a dose-dependent impairment of retention performance and, as with the antagonist treatments, post-training infusions were more effective. These results provide additional evidence that consolidation of inhibitory avoidance memory depends critically on prolonged activation of the noradrenergic system in the BLA and indicate that this modulatory influence is mediated, in part, by pre-synaptic α2-adrenoceptors.
Choosing a Method for Phylogenetic Prediction
Authors: Mount David W.
Published: April 2008

INTRODUCTION

Three methods--maximum parsimony, distance, and maximum likelihood--are generally used to find the evolutionary tree or trees that best account for the observed variation in a group of sequences. Each of these methods uses a different type of analysis. Programs based on distance methods are commonly used in the molecular biology laboratory because they are straightforward and can be used with a large number of sequences. Maximum likelihood methods are more challenging and require a greater understanding of the evolutionary models on which they are based. Because they involve so many computational steps and because the number of steps increases dramatically with the number of sequences, maximum likelihood programs are limited to a smaller number of sequences. They can be implemented on a supercomputer in order to analyze a greater number of sequences. This article presents an overview for the researcher who has a set of related sequences and wants to analyze them to predict the best trees that depict the phylogenetic relationships among the sequences.
In Planta Visualization of Protein Interactions Using Bimolecular Fluorescence Complementation (BiFC)
Authors: Waadt Rainer , Kudla Jörg
Published: April 2008

INTRODUCTION

Bimolecular fluorescence complementation (BiFC) analysis enables direct visualization of protein-protein interactions in living cells. This method has been successfully adapted to a variety of expression systems in different organisms. BiFC is based on the formation of a fluorescent complex by fragments of the enhanced yellow fluorescent protein (eYFP) when brought together by the interaction of two associating proteins fused to these fragments. Interaction of these proteins restores fluorescence and allows the visualization of spatial localization patterns of protein complexes. Absence of interaction prevents reassembly of the fluorescent protein and results only in background fluorescence. The specificity of bimolecular fluorescence complementation must be confirmed by parallel analysis of proteins in which the interaction interface has been mutated. This protocol describes the Agrobacterium-mediated transient expression protocol for BiFC assays in Nicotiana benthamiana leaf cells. This method exhibits a high transformation rate (up to 90% of the cells) and allows the simultaneous expression of multiple proteins in single cells. Therefore, this expression system enables colocalization analyses of fluorescently labeled proteins with the formation of BiFC complexes for determination of cellular complex localization. In addition, protein interaction assays in N. benthamiana leaves permit the investigation of protein interactions at different time points of expression, allow analysis of proteins that are normally toxic in protoplasts, and enable comparative protein interaction investigation in epidermal cells as well as in mesophyll protoplasts.
Secretory leukocyte peptidase inhibitor and lung cancer
Authors: Nukiwa Toshihiro , Suzuki Takuji , Fukuhara Tatsuro , Kikuchi Toshiaki
Published: April 2008

Secretory leukocyte peptidase inhibitor (SLPI) belongs to the whey acidic protein four‐disulfide core family of proteins, and has antimicrobial and antiprotease functions. SLPI is produced by the epithelial cells lining the respiratory, digestive, and reproductive tracts. Gene‐targeting experiments in mice indicated that one function of SLPI is to protect proepithelin from elastase cleavage in wound healing. In addition to its antiprotease function, SLPI has an anti‐inflammatory function through the modulation of nuclear factor‐κB acting intracellularly, especially in macrophages. SLPI is also produced in cancer tissues, but its role in cancer is not well understood. SLPI genes are often upregulated under tumorigenic conditions. We found a negligible number of tumors in the lungs of SLPI knockout mice 20 or 40 weeks after administration of urethane, an interesting experimental model for investigating the function of SLPI in cancer. This review discusses the normal function of SLPI and its possible roles in cancer tissues. (Cancer Sci 2008; 99: 849–855)
Genetic and epigenetic changes in aberrant crypt foci and serrated polyps
Authors: Suehiro Yutaka , Hinoda Yuji
Published: April 2008

Aberrant crypt foci (ACF) in colorectal mucosa are the earliest known morphological precursors to colorectal cancer and can be subclassified as dysplastic, heteroplastic (non‐dysplastic), and mixed types. Serrated adenoma (SA) is a polyp with serrated architecture and dysplasia, and can be subclassified as traditional SA or sessile SA. Sessile SA is thought to be preneoplastic and differs from most lesions in the traditional SA category because of their flat morphology and general lack of cytological dysplasia. Serrated polyps include hyperplastic polyps (HP), SA, and admixed hyperplastic‐adenomatous polyps and are considered a morphological continuum encompassing heteroplastic ACF, HP, admixed hyperplastic‐adenomatous polyps, and SA. Recent studies have uncovered other developmental pathways including a heteroplastic ACF‐HP/SA‐carcinoma sequence and a heteroplastic ACF–adenoma–carcinoma sequence. Heteroplastic ACF histopathologically resemble HP and SA. Sporadic HP are usually present in the left colon, are small, and are considered benign. However, adenocarcinoma arising in the setting of colorectal HP or SA, especially in patients with hyperplastic polyposis, has been described. The relationship between heteroplastic ACF, HP, and colorectal cancer is less certain than that of dysplastic ACF. Here, we discuss the current understanding of genetic and epigenetic alterations in the development of colorectal cancer. Our goal is to provide a conceptual framework for understanding the heteroplastic ACF–HP/SA–carcinoma sequence. (Cancer Sci 2008; 99: 1071–1076)
Vascular endothelial growth factor expression is closely related to irinotecan‐mediated inhibition of tumor growth and angiogenesis in neuroblastoma xenografts
Authors: Kaneko Setsuko , Ishibashi Makiko , Kaneko Michio
Published: April 2008

In the present study, irinotecan (CPT‐11) was highly effective not only against the chemosensitive neuroblastoma (NB) xenografts SK‐N‐ASnu and TNB9, but also against the multidrug‐resistant NB xenograft TS‐N‐2nu. SK‐N‐ASnu and TNB9 were significantly more responsive to low‐dose daily CPT‐11 treatment than to intermittent administration of one‐third of the median lethal dose. For TS‐N‐2nu, there was no significant difference in tumor growth inhibition between the two treatment schedules. Treatment with CPT‐11 alone could not completely abolish tumor growth in mice. For TNB9, tumor regrowth seemed to result from an inability to regress host vessels in the stroma during treatment and an inability to suppress host‐derived vascular endothelial growth factor (VEGF) expression throughout therapy. In the multidrug‐resistant TS‐N‐2nu, VEGF was not suppressed by low‐dose therapy with CPT‐11, and neurofilament‐positive tumor cells escaped from apoptosis and were growth arrested at G0/G1 phase. These findings suggest a mechanism for the incomplete responsiveness of TS‐N‐2nu to CPT‐11. Our data demonstrate that diminished VEGF gene and protein expression is closely correlated with tumor growth inhibition and inhibition of angiogenesis by CPT‐11 in NB xenografts. Our results further suggest that a persistent blocker of stroma‐derived VEGF will need to be combined with CPT‐11 to completely inhibit the growth of chemosensitive NB, and that administration of CPT‐11 at higher doses will be required to inhibit the growth of multidrug‐resistant NB. (Cancer Sci 2008; 99: 1209–1217)
Single‐institute phase 2 study of thalidomide treatment for refractory or relapsed multiple myeloma: Prognostic factors and unique toxicity profile
Authors: Hattori Yutaka , Okamoto Shin‐ichiro , Shimada Naoki , Kakimoto Tsunayuki , Morita Kunihiko , Tanigawara Yusuke , Ikeda Yasuo
Published: April 2008

We previously reported a pilot study of thalidomide monotherapy for Japanese patients with refractory or relapsed multiple myeloma. In the present work, we have extended this clinical trial to a single‐institute phase 2 study with a larger number of patients and longer follow‐up time. New information on the optimal dose and prognostic factors as well as the correlation of toxicities with treatment schedule was obtained. Fifteen of 56 (27%) patients achieved a partial response, including three cases with near‐complete remission. Most patients suffered toxicities at a dose of 400 mg per day, but there was no clear dose–response relationship. Thus, a lower dose such as 200 mg per day or less is considered optimal. Multivariate analyses identified only lack of response to therapy as an adverse prognostic factor for progression‐free survival. Chromosomal abnormality, C‐reactive protein >10 mg/L, and more than six previous courses of chemotherapy were significantly associated with shorter overall survival. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 23 and 11% of patients, respectively. Grade 4 interstitial pneumonia and grade 5 pulmonary hypertension were observed; however, no patient suffered deep vein thrombosis, which has frequently been observed in other studies. Duration of therapy was closely related to the development of peripheral neuropathy. The efficacy and prognostic factors of this treatment were confirmed in long‐term observation. However, special attention should be paid to toxicities such as hematological and pulmonary complications as well as peripheral neuropathy in long‐term users. (Cancer Sci2008; 99: 1243–1250)