bluuebunny/crossref_metadata_2025 huggingface dataset:
Mining the secretome of the root‐knot nematode Meloidogyne chitwoodi for candidate parasitism genes
Authors: ROZE ERWIN , HANSE BRAM , MITREVA MAKEDONKA , VANHOLME BARTEL , BAKKER JAAP , SMANT GEERT
Published: October 2007

Parasite proteins secreted at the interface of nematode and host are believed to play an essential role in parasitism. Here, we present an efficient pipeline of bio‐informatic algorithms and laboratory experiments to identify candidate parasitism genes within nematode secretomes, i.e. the repertoire of secreted proteins in an organism. We performed our approach on 12 218 expressed sequence tags (ESTs) originating from three life stages of the plant parasitic nematode Meloidogyne chitwoodi—a molecularly unexplored root‐knot nematode species. The ESTs from M. chitwoodi were assembled into 5880 contigs and open reading frames translated from the consensus sequences were searched for features of putative signal peptides for protein secretion and trans‐membrane regions, resulting in the identification of 398 secretome members. The products of parasitism genes are secreted by a range of organs, including the oesophageal, amphidial and rectal glands, the intestine, and the hypodermis. To localize the site of expression in M. chitwoodi, we subjected the most abundant secretome members to in situ hybridization microscopy. We found hybridization of one tag in the dorsal oesophageal gland, seven in the two subventral oesophageal glands, two in the intestine and one tag hybridized to the tail tip in the proximity of the phasmids. Four sequences showed similarity to putative parasitism genes from other nematode species, whereas seven represented pioneering sequences. Our approach presents an efficient method to identify candidate parasitism genes, which does not require sophisticated cDNA isolation and selection protocols, and can therefore be used as a powerful starting point for the molecular investigation of parasites.
Mining the genomes of plant pathogenic bacteria: how not to drown in gigabases of sequence
Authors: VINATZER BORIS A. , YAN SHUANGCHUN
Published: October 2007

Hundreds of bacterial genomes including the genomes of dozens of plant pathogenic bacteria have been sequenced. These genomes represent an invaluable resource for molecular plant pathologists. In this review, we describe different approaches that can be used for mining bacterial genome sequences and examples of how some of these approaches have been used to analyse plant pathogen genomes so far. We review how genomes can be mined one by one and how comparative genomics of closely related genomes releases the true power of genomics. Databases and tools useful for genome mining that are publicly accessible on the Internet are also described. Finally, the need for new databases and tools to efficiently mine today's plant pathogen genomes and hundreds more in the near future is discussed.
Bone marrow trephine findings in acute myeloid leukaemia with multilineage dysplasia
Authors: Ngo Nyethane , Lampert Irvin A , Naresh Kikkeri N
Published: October 2007

Acute myeloid leukaemia (AML) with multilineage dysplasia (MD) is one of the four main categories of AML in the World Health Organization (WHO) classification. The role of bone marrow trephine biopsy (BMTB) histology and immunohistochemistry in the diagnosis of AML‐MD is currently unclear. BMTBs were studied in 11 cases of AML‐MD and two cases of myelodysplasia that subsequently transformed to AML. Among them, six cases showed trilineage dysplasia and seven showed bilineage dysplasia. With respect to conforming to the WHO definition of AML, documentation of an increased proportion of immature myeloid cells was possible on morphology and counting of immature cells following immunostaining with CD34, CD117 or HLA‐DR antibodies. Recognition and quantification of dysplastic features in the haemopoietic lineages was made easier by immunohistochemistry with antibodies to ret40f (glycophorin C), myeloperoxidase, CD61 and/or CD42b, CD34, CD117 and HLA‐DR. Based on this relatively small series of cases we show the utility of BMTB and immunohistochemistry as an aid to the diagnosis of AML‐MD. This has to be seen not just in light of its utility at diagnosis, but also the role the diagnostic BMTB would play for purposes of comparison when follow‐up BMTBs are submitted in this group of patients.
Retracted: Effect of progestins with different glucocorticoid activity on bone metabolism
Authors: Ishida Yoichiro , Mine Takatomo , Taguchi Toshihiko
Published: October 2007

Objective  Progestins are commonly prescribed for hormone replacement therapy (HRT) and contraception. However, the effects of progestins on bone metabolism remain unclear and are often controversial.

Design and patients  This study was conducted to test the hypothesis that progestins with no significant glucocorticoid activity may be a better choice for HRT to achieve increased beneficial effects on bone metabolism than progestins with strong glucocorticoid activity. A total of 104 postmenopausal women aged 50–75 years with osteoporosis were allocated randomly to three groups: (1) conjugated oestrogen plus medroxyprogesterone acetate (HRT‐MPA, with significant glucocorticoid activity); (2) conjugated oestrogen plus norethisterone (HRT‐NET, with no significant glucocorticoid activity); and (3) control (no treatment).

Measurements  Vertebral X‐rays and bone mineral density (BMD) at distal 1/3 radius were assessed at baseline and every 6 months during the 2‐year study period, along with markers of bone turnover. The occurrence of new nonvertebral fractures was identified by X‐ray.

Results  After the 2‐year treatment, mean BMD changes relative to baseline in the HRT‐MPA, HRT‐NET and control groups were 1·6%, 2·3% and –1·9%, respectively. In addition, the rate of increase in HRT‐NET was significantly greater than that in HRT‐MPA (P = 0·019). The incidence of new fractures during the 2‐year treatment in the control group was 26% (9/34). HRT‐NET treatment significantly inhibited the occurrence of new fractures (RR 0·14, 95% CI 0·02–0·93, P = 0·04), while HRT‐MPA treatment failed to show a statistically significant reduction (RR 0·41, 95% CI 0·14–1·24, P = 0·11). Both HRT‐MPA and HRT‐NET treatments significantly decreased serum osteocalcin levels by 29·4% and 23·5%, respectively, after 6 months of treatment, with the decrease in HRT‐MPA being significantly greater than that in HRT‐NET (P = 0·042).

Conclusions  These findings suggest that progestins with no significant glucocorticoid activity may be a better choice for HRT, resulting in increased beneficial effects on bone metabolism compared with progestins with strong glucocorticoid activity.
The management of high‐risk patients with primary hyperparathyroidism – minimally invasive parathyroidectomy vs. medical treatment
Authors: Fang Wen‐Liang , Tseng Ling‐Ming , Chen Jui‐Yu , Chiou See‐Ying , Chou Yi‐Hong , Wu Chew‐Wun , Lee Chen‐Hsen
Published: October 2007

Objective  Parathyroidectomy (PTx) for high‐risk primary hyperparathyroidism (PHPT) patients poses a surgical challenge. We hypothesize that a minimally invasive parathyroidectomy (MIP) under local anaesthesia may minimize the perioperative risks and facilitate easier clinical care than medical treatment for these patients.

Design and patients  We performed a prospective, nonrandomized, controlled study of 33 PHPT patients evaluated as poor general anaesthesia risks. The outline of the diseased parathyroids and the thyroid were mapped by Tc99m sestamibi scan and focused sonogram. MIPs were performed under local anaesthesia (group 1, 19 patients). Medical treatment with bisphosphonates was continued for patients refusing operation (group 2, 14 patients).

Measurements  Serum Ca, PO4, and i‐PTH were measured the following morning, every 6 months in the first postoperative year and then yearly for group 1 patients, or every 3 months for group 2 patients. American Society of Anaesthesiologists (ASA) and New York Heart Association (NYHA) class designations were re‐evaluated every 3 months.

Results  In group 1, there were no operative complications, mortality or recurrent hypercalcaemia during a mean follow‐up of 35·5 months. Group 2 patients had a significantly higher incidence of episodes of hypercalcaemic crisis, deteriorating renal function and weight‐bearing bone fractures, while group 1 patients had a higher incidence of improved ASA and NYHA class, better 3‐year overall survival rate (83·1%vs. 60·8%, P = 0·032), and less medical costs.

Conclusion  MIP can be safely performed under local anaesthesia and it facilitates clinical care in high‐risk PHPT patients. It is recommended for those selected by image localization.
Inversion of time‐dependent nuclear well‐logging data using neural networks
Authors: Carmine Laura , Aristodemou Elsa , Pain Christopher , Muggeridge Ann , De Oliveira Cassiano
Published: October 2007

The purpose of this work was to investigate a new and fast inversion methodology for the prediction of subsurface formation properties such as porosity, salinity and oil saturation, using time‐dependent nuclear well logging data. Although the ultimate aim is to apply the technique to real‐field data, an initial investigation as described in this paper, was first required; this has been carried out using simulation results from the time‐dependent radiation transport problem within a borehole. Simulated neutron and γ‐ray fluxes at two sodium iodide (NaI) detectors, one near and one far from a pulsed neutron source emitting at ∼14 MeV, were used for the investigation. A total of 67 energy groups from the BUGLE96 cross section library together with 567 property combinations were employed for the original flux response generation, achieved by solving numerically the time‐dependent Boltzmann radiation transport equation in its even parity form. Material property combinations (scenarios) and their correspondent teaching outputs (flux response at detectors) are used to train the Artificial Neural Networks (ANNs) and test data is used to assess the accuracy of the ANNs. The trained networks are then used to produce a surrogate model of the expensive, in terms of computational time and resources, forward model with which a simple inversion method is applied to calculate material properties from the time evolution of flux responses at the two detectors.

The inversion technique uses a fast surrogate model comprising 8026 artificial neural networks, which consist of an input layer with three input units (neurons) for porosity, salinity and oil saturation; and two hidden layers and one output neuron representing the scalar photon or neutron flux prediction at the detector. This is the first time this technique has been applied to invert pulsed neutron logging tool information and the results produced are very promising. The next step in the procedure is to apply the methodology to real data.
Varicocelectomy: semen parameters and protamine deficiency
Authors: Nasr‐Esfahani M. H. , Abasi H. , Razavi S. , Ashrafi S. , Tavalaee M.
Published: October 2007

Different methods have been used to evaluate the beneficial effect of varicocelectomy; these include semen parameters and pregnancy rate. Because of high biological variability of semen parameters, sperm functional tests have been considered as an efficient end point in assessment of fertility. Therefore, the aim of this study was to evaluate the effect of varicocelectomy on semen parameters and sperm protamine deficiency in 192 patients. The results of the present study show that all the three semen parameters and percentage of sperms with normal protamine content have improved post‐surgery. The cumulative pregnancy rate was 34.6%. Comparing the results of the semen parameters and protamine content between patients whose partner became pregnant to those who did not benefit from varicocelectomy before and 6 months after surgery, show that patients may benefit from varicocelectomy that had higher initial semen density and better sperm morphology prior to surgery. Detailed analyses of sperm morphology, along with aforementioned results reveal that the factors which account for pregnancy difference are: (i) improvement in early events of spermatogenesis, possibly during spermatocytogensis and reduction division; and (ii) late spermiogenesis events. Thus, it can be suggested that patients with low initial sperm count may benefit more from assisted reproductive techniques or varicocelectomy followed by assisted reproduction.
Purinergic modulation of human corpus cavernosum relaxation
Authors: Lau D. H. W. , Metcalfe M. J. , Mumtaz F. H. , Mikhailidis D. P. , Thompson C. S.
Published: October 2007

The activation of P2Y6 receptors has been previously reported to cause vascular smooth muscle constriction and relaxation. The aim of our study was to determine the effect of P2Y6 receptor subtype activation on human cavernosal function. Cavernosal tissue was obtained from 23 patients undergoing gender reassignment surgery. Immunohistochemistry (IHC) and Western blotting were used to determine the presence of P2Y6 receptors in corpus cavernosal tissue. The effects of UDP (a selective P2Y6 receptor agonist) before and after the addition of distilled water (control), cibacron blue 3GA (CB, a P2Y6 receptor antagonist; 10−4 m) or N‐nitro‐l‐arginine methyl esther (l‐NAME, a NO synthase inhibitor; 10−4 m) were assessed on phenylephrine (PE; 10−4 m) pre‐contracted cavernosal strips using organ baths. Electrical field stimulation (EFS; 0.5–32 Hz) was performed in the absence and presence of CB to determine neuronal‐mediated P2Y6 receptor responses. IHC and Western blotting revealed the presence of P2Y6 receptors on cavernosal sections. UDP at 10−4 m and 10−3 m induced a 5% and 16% relaxation of the PE‐mediated response (both p < 0.0001), respectively, which was significantly blocked by CB (48% reduction of the UDP 10−3 m response, p < 0.002) but not affected by l‐NAME. EFS‐induced relaxations of pre‐contraction strips were not significantly altered by CB. We have found the presence of P2Y6 receptors in human cavernosal tissues, that when activated induce cavernosal smooth muscle cell relaxation via non‐neuronal and non‐nitric oxide dependent mechanism. Further investigation is needed to establish whether P2Y6 receptors play a physiological role in penile erection.
Bisphenol‐A disruption of the endocrine pancreas and blood glucose homeostasis
Authors: Ropero A. B. , Alonso‐Magdalena P. , García‐García E. , Ripoll C. , Fuentes E. , Nadal A.
Published: October 2007

The link between endocrine disruptors and altered blood glucose homeostasis has been recently suggested. Epidemiological studies have correlated levels of phthalates, dioxins and persistent organic pollutants with alterations of blood glucose homeostasis in humans. Environmentally relevant doses of the ubiquitous endocrine disruptor bisphenol‐A (BPA) have profound effects on mice endocrine pancreas – an essential tissue involved in glucose metabolism. BPA exerts rapid non‐genomic effects on insulin releasing β‐cells and glucagon releasing α‐cells within freshly isolated islets of Langerhans. In vivo, a single BPA injection of 10μg/kg rapidly increases plasma insulin and concomitantly decreases glycaemia. When mice were treated with BPA 100μg/kg/day for 4 days, the environmental oestrogen produced an increase in β‐cell insulin content along with a post‐prandial hyperinsulinaemia and insulin resistance. The results reviewed here demonstrate that doses well below the current lowest observed adverse effect level considered by the US‐EPA, disrupt pancreatic β‐cell function producing insulin resistance in male mice. Therefore, this altered blood glucose homeostasis by BPA exposure may enhance the risk of developing type II diabetes.
The KiSS‐1/GPR54 system: putative target for endocrine disruption of reproduction at hypothalamic–pituitary unit?
Authors: Navarro Victor M. , Tena‐Sempere Manuel
Published: October 2007

The hypothalamic–pituitary (HP) unit, key element in the control of development and function of the reproductive axis, is highly sensitive to the organizing and activational effects of endogenous and exogenous compounds with sex steroid activity. Thus, inappropriate sex steroid input during early critical periods of their maturation can induce immediate or delayed defects in the neuroendocrine systems governing reproduction, which might eventually lead to alterations in the timing of puberty onset and/or infertility. Similarly, later inadequate exposures can cause dysfunctions of the gonadotropic axis. In recent years, kisspeptins (the products of KiSS‐1 gene that operate through the G protein‐coupled receptor 54) have emerged as fundamental regulators of puberty onset and gonadotropin secretion, and neurons in the hypothalamus expressing KiSS‐1 have been demonstrated as essential conduits for the dynamic control of the gonadotropic axis by a number of hormonal factors. In this context, the hypothalamic KiSS‐1 system has been proven sensitive to the early organizing effects, as well as to the acute regulatory actions, of gonadal steroids: phenomena which are likely to play fundamental roles in the sexual differentiation of gonadotropin secretion, and its feedback regulation by androgen and oestrogen. These observations raise the question on whether the hypothalamic KiSS‐1 system might constitute a potential target for endocrine disruption of puberty onset and reproductive function at the HP unit by compounds with oestrogenic, androgenic or anti‐androgenic activity. We review herein the physiological basis and initial, albeit so far scarce, experimental evidence supporting such possibility.
Neoplasia as development gone awry: the role of endocrine disruptors
Authors: Soto Ana M. , Maffini Maricel V. , Sonnenschein Carlos
Published: October 2007

The hypothesis that prenatal exposure to endocrine disruptors might cause cancer arose from challenging two well‐accepted notions: (i) mammalian development is merely the unfolding of a genetic programme and (ii) only mutagenic agents can cause cancer. This hypothesis required challenging genetic determinism. The ecological developmental biology (eco‐devo) movement revitalized the concept of developmental plasticity through the occurrence of polyphenisms (a single genotype produces diverse phenotypes which are determined by environmental cues). Based on the principles of eco‐devo and the tissue organization field theory of carcinogenesis and neoplasia, we tested the hypothesis that exposure to xenoestrogens during foetal development in rats increased the propensity to develop mammary cancer during adulthood. We chose exposure to bisphenol A (BPA) as a model for environmental oestrogen exposure. This endocrine disruptor induced the development of ductal hyperplasias and carcinoma in situ. These highly proliferative lesions contained an increased number of oestrogen receptor α‐positive cells. Thus, foetal BPA exposure was sufficient to induce the development of oestrogen‐sensitive pre‐neoplastic and neoplastic lesions in the mammary gland in the absence of any additional treatment aimed at increasing tumour incidence.
Characterization of a tightly controlled promoter of the halophilic archaeon Haloferax volcanii and its use in the analysis of the essential cct1 gene
Authors: Large Andrew , Stamme Claudia , Lange Christian , Duan Zhenhong , Allers Thorsten , Soppa Jörg , Lund Peter A.
Published: October 2007

A system where archaeal gene expression could be controlled by simple manipulation of growth conditions would enable the construction of conditional lethal mutants in essential genes, and permit the controlled overproduction of proteins in their native host. As tools for the genetic manipulation of Haloferax volcanii are well developed, we set out to identify promoters with a wide dynamic range of expression in this organism. Tryptophan is the most costly amino acid for the cell to make, so we reasoned that tryptophan‐regulated promoters might be good candidates. Microarray analysis of H. volcanii gene expression in the presence and absence of tryptophan identified a tryptophanase gene (tna) that showed strong induction in the presence of tryptophan. qRT‐PCR revealed a very fast response and an up to 100‐fold induction after tryptophan addition. This result has been confirmed using three independent reporter genes (cct1, pyrE2 and bgaH). Vectors containing this promoter will be very useful for investigating gene function in H. volcanii and potentially in other halophilic archaea. To demonstrate this, we used the promoter to follow the consequences of depletion of the essential chaperonin protein CCT1, and to determine the ability of heterologous CCT proteins to function in H. volcanii.
Individual chitin synthase enzymes synthesize microfibrils of differing structure at specific locations in the Candida albicans cell wall
Authors: Lenardon Megan D. , Whitton Rhian K. , Munro Carol A. , Marshall Deborah , Gow Neil A. R.
Published: October 2007

The shape and integrity of fungal cells is dependent on the skeletal polysaccharides in their cell walls of which β(1,3)‐glucan and chitin are of principle importance. The human pathogenic fungus Candida albicans has four genes, CHS1, CHS2, CHS3 and CHS8, which encode chitin synthase isoenzymes with different biochemical properties and physiological functions. Analysis of the morphology of chitin in cell wall ghosts revealed two distinct forms of chitin microfibrils: short microcrystalline rodlets that comprised the bulk of the cell wall; and a network of longer interlaced microfibrils in the bud scars and primary septa. Analysis of chitin ghosts of chs mutant strains by shadow‐cast transmission electron microscopy showed that the long‐chitin microfibrils were absent in chs8 mutants and the short‐chitin rodlets were absent in chs3 mutants. The inferred site of chitin microfibril synthesis of these Chs enzymes was corroborated by their localization determined in Chsp–YFP‐expressing strains. These results suggest that Chs8p synthesizes the long‐chitin microfibrils, and Chs3p synthesizes the short‐chitin rodlets at the same cellular location. Therefore the architecture of the chitin skeleton of C. albicans is shaped by the action of more than one chitin synthase at the site of cell wall synthesis.
A small non‐coding RNA of the invasion gene island (SPI‐1) represses outer membrane protein synthesis from the Salmonella core genome
Authors: Pfeiffer Verena , Sittka Alexandra , Tomer Raju , Tedin Karsten , Brinkmann Volker , Vogel Jörg
Published: October 2007

The Salmonella pathogenicity island (SPI‐1) encodes ∼35 proteins involved in assembly of a type III secretion system (T3SS) which endows Salmonella with the ability to invade eukaryotic cells. We have discovered a novel SPI‐1 gene, invR, which expresses an abundant small non‐coding RNA (sRNA). The invR gene, which we identified in a global search for new Salmonella sRNA genes, is activated by the major SPI‐1 transcription factor, HilD, under conditions that favour host cell invasion. The RNA chaperone, Hfq, is essential for the in vivo stability of the ∼80 nt InvR RNA. Hfq binds InvR with high affinity in vitro, and InvR co‐immunoprecipitates with FLAG epitope‐tagged Hfq in Salmonella extracts. Surprisingly, deletion/overexpression of invR revealed no phenotype in SPI‐1 regulation. In contrast, we find that InvR represses the synthesis of the abundant OmpD porin encoded by the Salmonella core genome. As invR is conserved in the early branching Salmonella bongori, we speculate that porin repression by InvR may have aided successful establishment of the SPI‐1 T3SS after horizontal acquisition in the Salmonella lineage. This study identifies the first regulatory RNA of an enterobacterial pathogenicity island, and new roles for Hfq and HilD in SPI‐1 gene expression.
Immunohistochemical analysis of receptor tyrosine kinase signal transduction activity in chordoma
Authors: Fasig J. H. , Dupont W. D. , LaFleur B. J. , Olson S. J. , Cates J. M. M.
Published: October 2007

Aims: Currently, there are no effective chemotherapeutic protocols for chordoma. Reports of receptor tyrosine kinase (RTK) expression in chordoma suggest that these tumours may respond to kinase inhibitor therapy. However, RTK signalling activity has not been extensively investigated in chordoma. Methods: A tissue microarray containing 21 cases of chordoma was analysed for expression of a number of proteins involved in signal transduction from RTKs by immunohistochemistry. Results: Platelet‐derived growth factor receptor‐β, epidermal growth factor receptor (EGFR), KIT and HER2 were detected in 100%, 67%, 33% and 0% of cases, respectively. Platelet‐derived growth factor receptor‐β staining was of moderate‐to‐strong intensity in 20 of 21 cases. In contrast, KIT immunoreactivity was weak and focal in each of the seven positive cases. Total EGFR staining was variable; weak staining for phosphorylated EGFR was detected in nine cases. Phosphorylated isoforms of p44/42 mitogen‐activated protein kinase, Akt and STAT3, indicative of tyrosine kinase activity, were detected in 86%, 76% and 67% of cases, respectively. Conclusions: Chordomas commonly express RTKs and activated signal transduction molecules. Although there were no statistically significant correlations between the expression of any of the markers studied and disease‐free survival or tumour location, the results nonetheless indicate that chordomas may respond to RTK inhibitors or modulators of other downstream signalling molecules.
The expression of osteopontin is increased in vessels with blood–brain barrier impairment
Authors: Iwanaga Y. , Ueno M. , Ueki M. , Huang C.‐L. , Tomita S. , Okamoto Y. , Ogawa T. , Ueda N. , Maekawa N. , Sakamoto H.
Published: October 2007

Aims: We previously reported that the blood–brain barrier (BBB) function was deteriorated in vessels located along hippocampal fissures in stroke‐prone spontaneously hypertensive rats (SHRSP). In this study, we examined changes of gene expression in the BBB‐damaged vessels of SHRSP. Methods: Vascular samples were microdissected from the hippocampi of SHRSP and Wistar‐Kyoto (WKY) as a control and the difference in gene expression between the BBB‐damaged vessels in SHRSP and vessels without BBB damage in WKY was examined by a microarray. The differences in gene and protein expression between brain tissues in the two strains of rats were examined using real‐time quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR), Western blotting and immunohistochemistry. Results: The microarray assay revealed that the ratio of osteopontin gene expression in the vascular tissue of the hippocampi of SHRSP to that of WKY was the highest among 8435 genes. Real‐time RT‐PCR analysis revealed that the gene expression of osteopontin was significantly increased in the hippocampal samples of SHRSP compared with that in the hippocampal samples of WKY rats or with that in the cortical samples of SHRSP. Immunohistochemical and Western blot analyses showed that the osteopontin protein expression was seen in perivascular ED1‐positive macrophages/microglial cells located around hippocampal fissures and significantly increased in the hippocampi of SHRSP compared with that of WKY. Conclusions: These findings indicate that the expression of osteopontin is increased in BBB‐damaged vessels in hypertensive SHRSP compared with that in vessels without BBB impairment in WKY rats, suggesting a role for osteopontin in BBB function.
Limbic structures are prone to age‐related impairments in proteasome activity and neuronal ubiquitinated inclusions in SAMP10 mouse: a model of cerebral degeneration
Authors: Shimada A. , Keino H. , Kawamura N. , Chiba Y. , Hosokawa M.
Published: October 2007

Aims: Neurodegenerative diseases are characterized by ubiquitinated inclusions in selective brain regions. Here we investigated whether the dysfunction of the ubiquitin proteasome system might be involved in the pathogenesis and regional selectivity of neuronal ubiquitinated inclusions using the SAMP10 strain of mouse, an inbred model of age‐related cerebral degeneration. Methods: By comparing SAMP10 mice at various ages with SAMR1 and C57BL mice as normal brain ageing controls, we studied morphological features and distribution of inclusions. We measured tissue proteasome activity in different brain regions of mice at various ages by fluorogenic substrate assays. We induced inclusions in cultured neurones by inhibiting the proteasome and analysed changes in the dendritic morphology. Results: Inclusions were formed in association with lipofuscin in neuronal perikarya and occurred most frequently in the limbic‐related forebrain structures. There were sparse inclusion‐bearing neurones in the non‐limbic forebrain. In aged SAMR1 and C57BL, there were far fewer inclusions in the limbic‐related forebrain than in aged SAMP10. The proteasome activity in the limbic‐related forebrain decreased much more rapidly and remarkably upon ageing (26% activity was detected in 17‐month‐old compared with 3‐month‐old mice) in SAMP10 than in SAMR1. The proteasome activity in the non‐limbic forebrain did not change significantly with advancing age in either SAMP10 or SAMR1. Proteasomal inhibition enhanced the formation of ubiquitinated inclusions in cultured neurones. Neurones bearing inclusions had shortened neurites. Conclusions: We propose that the regional selectivity of proteasomal impairment is causally related to the selectivity of inclusion formation and associated dendritic degeneration in neurones of ageing SAMP10 mice.
Angiotensin‐converting enzyme (ACE) levels and activity in Alzheimer's disease, and relationship of perivascular ACE‐1 to cerebral amyloid angiopathy
Authors: Miners J. S. , Ashby E. , Van Helmond Z. , Chalmers K. A. , Palmer L. E. , Love S. , Kehoe P. G.
Published: October 2007

Aims: Several observations point to the involvement of angiotensin‐converting enzyme‐1 (ACE‐1) in Alzheimer's disease (AD): ACE‐1 cleaves amyloid‐β peptide (Aβ) in vitro, the level and activity of ACE‐1 are reportedly increased in AD, and variations in the ACE‐1 gene are associated with AD. We analysed ACE‐1 activity and expression in AD and control brains, particularly in relation to Aβ load and cerebral amyloid angiopathy (CAA). Methods: ACE‐1 activity was measured in the frontal cortex from 58 control and 114 AD cases of known Aβ load and CAA severity. The distribution of ACE‐1 was examined immunohistochemically. In five AD cases with absent or mild CAA, five with moderate to severe CAA and five controls with absent or mild CAA, levels of vascular ACE‐1 were assessed by quantitative immunofluorescence. Results: ACE‐1 activity was increased in AD (P < 0.001) and correlated directly with parenchymal Aβ load (P = 0.05). Immunohistochemistry revealed ACE‐1 in neurones and cortical blood vessels – in the intima but most abundant perivascularly. Cases with moderate to severe CAA had significantly more vessel‐associated ACE‐1 than did those with little or no CAA. Perivascular ACE‐1 did not colocalize with Aβ, smooth muscle actin, glial fibrillary acidic protein, collagen IV, vimentin or laminin, but was similarly distributed to extracellular matrix (ECM) proteins fibronectin and decorin. Conclusions: Our findings indicate that ACE‐1 activity is increased in AD, in direct relationship to parenchymal Aβ load. Increased ACE‐1, probably of neuronal origin, accumulates perivascularly in severe CAA and colocalizes with vascular ECM. The possible relationship of ACE‐1 to the deposition of perivascular ECM remains to be determined.
The effect of oxygenation level on cerebral post‐traumatic apoptotsis is modulated by the 18‐kDa translocator protein (also known as peripheral‐type benzodiazepine receptor) in a rat model of cortical contusion
Authors: Soustiel J. F. , Palzur E. , Vlodavsky E. , Veenman L. , Gavish M.
Published: October 2007

Aims: Hyperbaric hyperoxia has been shown to reduce apoptosis in brain injury. As the 18‐kDa translocator protein (TSPO), also known as peripheral‐type benzodiazepine receptor, is closely associated with the mitochondrial transition pore and because of its role in mitochondrial respiration and apoptosis, we hypothesized that reduction of apoptosis by hyperoxia may involve the TSPO. Methods: TSPO and transferase‐mediated dUTP nick end labelling (TUNEL) immunopositivity was first assessed in cortical contusion, created by dynamic cortical deformation, by immunohistochemistry in rats exposed to normoxia [(dynamic cortical deformation (DCD)], normobaric hyperoxia or hyperbaric hyperoxia [hyperbaric oxygen therapy (HBO)]. In a second step, transmembrane mitochondrial potential (ΔψM) and caspase 9 activity were assessed in the injured area in comparison with the noninjured hemisphere. Measurements were performed in DCD and HBO groups. A third group receiving both HBO and the TSPO ligand PK11195 was investigated as well. Results: TSPO correlated quantitatively and regionally with TUNEL immunopositivity in the perilesional area. Hyperoxia reduced both the number of TSPO expressing and TUNEL positive cells in the perilesional area, and this effect proved to be pressure dependent. After contusion, we demonstrated a dissipation of ΔψM in isolated mitochondria and an elevation of caspase 9 activity in tissue homogenates from the contused area, both of which could be substantially reversed by hyperbaric hyperoxia. This protective effect of hyperoxia was reversed by PK11195. Conclusions: The present findings suggest that the protective effect of hyperoxia may be due to a negative regulation of the proapoptotic function of mitochondrial TSPO, including conservation of the mitochondrial membrane potential.
Fine mapping study in Scandinavian families suggests association between coeliac disease and haplotypes in chromosome region 5q32
Authors: Adamovic S. , Amundsen S. S. , Lie B. A. , Hellqvist Å. , Gudjónsdóttir A. H. , Ek J. , Nilsson S. , Wahlström J. , Ascher H. , Sollid L. M. , Naluai Å. T.
Published: October 2007

The previous genome‐wide scan in Scandinavian families supported earlier evidence for linkage of a region on chromosome 5 (5q31–33) to coeliac disease. This study deals with further genetic mapping of an 18 cM region, spanning from marker GAh18A (131.87 Mb) to D5S640 (149.96 Mb). Linkage and association analyses were performed in a two‐step approach. First, seven microsatellites were added. Strong evidence for linkage was obtained with a Zlr score of 3.96, Pnc = 4 × 10−5 at marker D5S436. The strongest association was with a haplotype consisting of the markers D5S2033 and D5S2490 (Pnc < 0.001). In the second step, we added 17 microsatellites and 69 single nucleotide polymorphisms (SNPs) to the analysis. These markers were located close to or within candidate genes across the region of approximately 7 Mb beneath the linkage peak marked by D5S2017 and D5S812. A substantial increase of the linkage signal with a maximum Zlr score of 4.6 at marker rs1972644 (Pnc = 2 × 10−6) was obtained and several SNPs showed association. Seven SNPs that individually showed the strongest association were genotyped in a second independent family sample set (225 trios). In the trio family sample as well as in the multiplex family sample, the strongest association was found with SNPs within the region flanked by the associated microsatellites D5S2033 and D5S2490 at 5q32.
Characterization of seven new HLA alleles from the Henan and Gansu Provinces of China
Authors: Zhang B. , Lazaro A. M. , Xing P. , Cheng S. , Hurley C. K.
Published: October 2007

Four new class I and three class II alleles have been found in Chinese individuals.
SNP mapping and candidate gene sequencing in the class I region of the HLA complex: searching for multiple sclerosis susceptibility genes in Tasmanians
Authors: Burfoot R. K. , Jensen C. J. , Field J. , Stankovich J. , Varney M. D. , Johnson L. J. , Butzkueven H. , Booth D. , Bahlo M. , Tait B. D. , Taylor B. V. , Speed T. P. , Heard R. , Stewart G. J. , Foote S. J. , Kilpatrick T. J. , Rubio J. P.
Published: October 2007

This study is an extension to previously published work that has linked variation in the human leukocyte antigen (HLA) class I region with susceptibility to multiple sclerosis (MS) in Australians from the Island State of Tasmania. Single nucleotide polymorphism (SNP) mapping was performed on an 865‐kb candidate region (D6S1683–D6S265) in 166 Tasmanian MS families, and seven candidate genes [ubiquitin D (UBD), olfactory receptor 2H3 (OR2H3), gamma‐aminobutyric acid B receptor 1 (GABBR1), myelin oligodendrocyte glycoprotein (MOG), HLA‐F, HLA complex group 4 (HCG4) and HLA‐G] were resequenced. SNPs tagging the extended MS susceptibility haplotype were genotyped in an independent sample of 356 Australian MS trios and SNPs in the MOG gene were significantly over‐transmitted to MS cases. We identified significant effects on MS susceptibility of HLA‐A*2 (OR: 0.51; P = 0.05) and A*3 (OR: 2.85; P = 0.005), and two coding polymorphisms in the MOG gene (V145I: P = 0.01, OR: 2.2; V142L: P = 0.04, OR: 0.45) after full conditioning on HLA‐DRB1. We have therefore identified plausible candidates for the causal MS susceptibility allele, and although not conclusive at this stage, our data provide suggestive evidence for multiple class I MS susceptibility genes.
HLA‐DPB1 polymorphism in Blang and Puyi ethnic groups of Southwest China inferred from sequence‐based typing
Authors: Wang B. , Hu W. , Wang J. , Li S. , Yu H. , Tang W. , Tan S. , Shou W. , Zhang J. , Xiao C.
Published: October 2007

In the present study, DNA typing for HLA‐DPB1 was performed using polymerase chain reaction (PCR)–sequence‐based typing method in two isolated Chinese populations: the Blangs (n = 94) in Shuangjiang County and the Puyis (n = 76) in Luoping County from Yunnan province of Southwest China. These two populations exhibited certain similarity in their allelic distributions of the HLA‐DPB1 gene. A total of 11 and 12 alleles at the DPB1 locus were found in the Blang and Puyi groups, respectively. In the Blang group, the most frequent alleles were DPB1*0501 (51.0%) and DPB1*1301 (17.0%). DPB1*030101 was also common with a frequency of 6.4%. In the Puyi group, the most frequent allele was also DPB1*0501 with a frequency of 47.5%, followed by DPB1*1301 (21.1%). Two alleles DPB1*2101 and DPB1*0202 followed, with frequencies ranging between 5% and 8%. The alleles DPB1*4101, DPB1*3301, DPB1*6801 and DPB1*8401 were found for the first time in Chinese populations. A dendrogram constructed by neighbor‐joining method showed that the Blang and Puyi ethnic minorities, which had the closest relationship belonged to the southern Chinese.
Monocular deprivation enhances the nuclear signalling of extracellular signal‐regulated kinase in the developing visual cortex
Authors: Takamura Hironori , Ichisaka Satoshi , Hayashi Chihiro , Maki Hirotoshi , Hata Yoshio
Published: October 2007

Monocular deprivation (MD) of vision leads to a loss of cortical response to the deprived eye in the early postnatal period (ocular dominance plasticity). The activity of several signal molecules, including extracellular signal‐regulated kinase (ERK), has been reported as playing a crucial role in the ocular dominance plasticity. Although pharmacological inhibition of ERK disturbed the ocular dominance plasticity, it remains to be elucidated how the ERK activity is modulated by MD. We herein report the effects of MD on ERK activation in the visual cortex of young and adult rats. Phosphorylated ERK (pERK)‐immunopositive cells are mainly distributed in layers II/III of the visual cortex. Following MD, we found a significant decrease in the density of pERK‐immunopositive cells in the cortex receiving deprived‐eye inputs in both young and adult animals. The amount of pERK protein also decreased in the input‐deprived cortex as revealed by Western blotting. Regarding the subcellular localization of pERK, we found a significant increase in the pERK‐immunopositive nucleus following MD in young animals. In these animals, the amount of pERK protein in the nuclear fraction of cortical tissue was significantly increased. No up‐regulation of the nuclear pERK was observed in adults or following binocular deprivation. These findings suggest that ERK activation may therefore be regulated by different mechanisms between young and adult animals, and MD during the developing period may thus specifically up‐regulate the nuclear signalling of ERK.
Temporal profile of circadian clock gene expression in a transplanted suprachiasmatic nucleus and peripheral tissues
Authors: Sujino Mitsugu , Nagano Mamoru , Fujioka Atsuko , Shigeyoshi Yasufumi , Inouye Shin‐Ichi T.
Published: October 2007

The mammalian hypothalamic suprachiasmatic nucleus (SCN) is the master oscillator that regulates the circadian rhythms of the peripheral oscillators. Previous studies have demonstrated that the transplantation of embryonic SCN tissues into SCN‐lesioned arrhythmic mice restores the behavioral circadian rhythms of these animals. In our present study, we examined the clock gene expression profiles in a transplanted SCN and peripheral tissues, and also analysed the circadian rhythm of the locomotor activity in SCN‐grafted mice. These experiments were undertaken to elucidate whether the transplanted SCN generates a dynamic circadian oscillation and maintains the phase relationships that can be detected in intact mice. The grafted SCN indeed showed dynamic circadian expression rhythms of clock genes such as mPeriod1 (mPer1) and mPeriod2 (mPer2). Furthermore, the phase differences between the expression rhythms of these genes in the grafted SCN and the locomotor activity rhythms of the transplanted animals were found to be very similar to those in intact animals. Moreover, in the liver, kidney and skeletal muscles of the transplanted animals, the phase angles between the circadian rhythm of the grafted SCN and that of the peripheral tissues were maintained as in intact animals. However, in the SCN‐grafted animals, the amplitudes of the mPer1 and mPer2 rhythms were attenuated in the peripheral tissues. Our current findings therefore indicate that a transplanted SCN has the capacity to generate a dynamic intrinsic circadian oscillation, and can also lock the normal phase angles among the SCN, locomotor activity and peripheral oscillators in a similar manner as in intact control animals.
Ovarian and oviductal morphology of a brood parasitic bird,Molothrus bonariensis(Passeriformes, Icteridae)
Authors: Rueda‐Cediel Pamela , Kattan Gustavo , Ramírez‐Pinilla Martha Patricia
Published: October 2007

Brood parasitic birds such as cowbirds (Molothrusspp., Icteridae) lay their eggs in the nests of other species, abandoning them to be incubated and raised by the hosts. Lack of investment in parental care results in high annual fecundities of female parasitic birds. Brood parasites lay eggs in series or clutches, separated by gaps or non‐laying intervals of a few days, but they may continuously lay for prolonged periods. In tropical latitudes, the fecundity of female shiny cowbirds (Molothrus bonariensis) has been estimated to be 120 eggs per year in a six‐month breeding season, a fecundity that is paralleled only by domestic fowl. However, no detailed morphological descriptions of the reproductive tracts of brood parasites are available. We studied the reproductive tract of female shiny cowbirds in northeastern Colombia, searching for morphological features that might be related to this high fecundity. The reproductive tracts of female shiny cowbird showed no departures from the standard morphology or follicular dynamics known for birds with different postural patterns and fecundities, suggesting that high fecundity in cowbirds does not require a specialized reproductive tract. Instead, explanations must be sought at physiological levels.
The Effects of Transformational Leadership on Organizational Performance through Knowledge and Innovation*
Authors: García‐Morales Víctor J. , Lloréns‐Montes Francisco Javier , Verdú‐Jover Antonio J.
Published: October 2007

Today's information and knowledge society requires new leaders who can confront a reality based on knowledge and foster innovation to achieve improvements in organizational performance. However, organizations sometimes fail to achieve sustainable competitive advantage due to their limited understanding of the relationships between these strategic variables. To date, very little research has analysed the direct and indirect relationships between these variables. Our study seeks to fill this research gap by analysing theoretically and empirically how the leader's perceptions of different intermediate strategic variables related to knowledge (knowledge slack, absorptive capacity, tacitness, organizational learning) and innovation influence the relation between transformational leadership and organizational performance. Based on the literature, we develop a theoretical model that shows the interrelations between these variables. We then test the model using data from 408 Spanish organizations, discuss the findings and provide several implications for business practitioners.
A General Multi‐step Algorithm for Voxel Traversing Along a Line
Authors: Liu Y. K. , Song H. Y. , Žalik B.
Published: October 2007

Traversing voxels along a three dimensional (3D) line is one of the most fundamental algorithms for voxel‐based applications. This paper presents a new 6‐connectivity integer algorithm for this task. The proposed algorithm accepts voxels having different sizes in x, y and z directions. To explain the idea of the proposed approach, a 2D algorithm is firstly considered and then extended in 3D. This algorithm is a multi‐step as up to three voxels may be added in one iteration. It accepts both integer and floating‐point input.

The new algorithm was compared to other popular voxel traversing algorithms. Counting the number of arithmetic operations showed that the proposed algorithm requires the least amount of operations per traversed voxel. A comparison of spent CPU time using either integer or floating‐point arithmetic confirms that the proposed algorithm is the most efficient. This algorithm is simple, and in compact form which also makes it attractive for hardware implementation.
A Sketch‐Based User Interface for Reconstructing Architectural Drawings
Authors: Lee Sangwon , Feng David , Grimm Cindy , Gooch Bruce
Published: October 2007

We present a framework for interactive sketching that allows users to create three‐dimensional (3D) architectural models quickly and easily from a source drawing. The sketching process has four steps. (1) The user calibrates a viewing camera by specifying the origin and vanishing points of the drawing. (2) The user outlines surface polygons in the drawing. (3) A 3D reconstruction algorithm uses perceptual constraints to determine the closest visual fit for the polygon. (4) The user can then adjust aesthetic controls to produce several stylistic effects in the scene: a smooth transition between day and night rendering, a horizon knockout effect and entourage figures. The major advantage of our approach lies in the combination of perception‐based techniques, which allow us to minimize unnecessary interactions, and a hinging‐angle scheme, which shows significant improvement in numerical stability over previous optimization‐based 3D reconstruction algorithms. We also demonstrate how our reconstruction algorithm can be extended to work with perspective images, a feature unavailable in previous approaches.
Object‐Space Visibility Ordering for Point‐Based and Volume Rendering
Authors: Hofsetz C. , Max N. , Bastos R.
Published: October 2007

This paper presents a method to accelerate algorithms that need a correct and complete visibility ordering of their data for rendering. The technique works by pre‐sorting primitives in object‐space using three lists (one for each axis: X, Y and Z), and then combining the lists using graphics hardware by rendering each list to a texture and merging the textures in the end. We validate our algorithm by applying it to the splatting technique using several types of rendering, including point‐based rendering and volume rendering. We also detail our hardware implementation for volume rendering using point sprites.