bluuebunny/crossref_metadata_2025 huggingface dataset:
Conservation of the pentanucleotide motif at the top of the yellow fever virus 17D 3′ stem–loop structure is not required for replication
Authors: Silva Patrícia A. G. C. , Molenkamp Richard , Dalebout Tim J. , Charlier Nathalie , Neyts Johan H. , Spaan Willy J. M. , Bredenbeek Peter J.
Published: May 2007

The pentanucleotide (PN) sequence 5′-CACAG-3′ at the top of the 3′ stem–loop structure of the flavivirus genome is well conserved in the arthropod-borne viruses but is more variable in flaviviruses with no known vector. In this study, the sequence requirements of the PN motif for yellow fever virus 17D (YFV) replication were determined. In general, individual mutations at either the second, third or fourth positions were tolerated and resulted in replication-competent virus. Mutations at the fifth position were lethal. Base pairing of the nucleotide at the first position of the PN motif and a nucleotide four positions downstream of the PN (ninth position) was a major determinant for replication. Despite the fact that the majority of the PN mutants were able to replicate efficiently, they were outcompeted by parental YFV-17D virus following repeated passages in double-infected cell cultures. Surprisingly, some of the virus mutants at the first and/or the ninth position that maintained the possibility of forming a base pair were found to have a similar fitness to YFV-17D under these conditions. Overall, these experiments suggest that YFV is less dependent on sequence conservation of the PN motif for replication in animal cells than West Nile virus. However, in animal cell culture, YFV has a preference for the wt CACAG PN sequence. The molecular mechanisms behind this preference remain to be elucidated.
Strong suppression of tumor growth by insulin‐like growth factor‐binding protein‐related protein 1/tumor‐derived cell adhesion factor/mac25
Authors: Sato Yuichiro , Chen Zhaoxin , Miyazaki Kaoru
Published: May 2007

Insulin‐like growth factor binding protein‐related protein 1 (IGFBP‐rP1) has been shown to induce cellular senescence or apoptosis of breast and prostate cancer cell lines in vitro. To examine whether IGFBP‐rP1 acts as a tumor‐suppressive protein in vivo, we established two model systems. Expression of IGFBP‐rP1 in the human bladder carcinoma cell line EJ‐1 was blocked by RNA interference. Human colon cancer cell line DLD‐1, which did not express endogenous IGFBP‐rP1, was transfected with an IGFBP‐rP1 expression vector. When injected intraperitoneally or subcutaneously into nude mice, the IGFBP‐rP1‐expressing EJ‐1 and DLD‐1 cell lines grew poorly, whereas the IGFBP‐rP1 non‐producers grew rapidly and produced large tumors. In monolayer culture the IGFBP‐rP1 producers and non‐producers grew similarly in each model, whereas in soft agar culture the former produced far less colonies than the latter. The IGFBP‐rP1 producers had IGFBP‐rP1 bound to the cell surface, and adhered more efficiently to fibronectin and laminin‐5 than the respective non‐producers. Expression of IGFBP‐rP1 did not affect the efficiency of insulin signaling. These results demonstrate that IGFBP‐rP1 strongly suppresses tumor growth by an insulin‐independent or insulin‐like growth factor‐independent mechanism. Cell surface IGFBP‐rP1 may reduce the anchorage‐independent growth ability, leading to the marked loss of tumorigenicity. (Cancer Sci 2007; 98: 1055–1063)
Complex ABCC8 DNA variations in congenital hyperinsulinism: lessons from functional studies
Authors: Muzyamba Morris , Farzaneh Tabasum , Behe Phillip , Thomas Alison , Christesen Henrik B. T. , Brusgaard Klaus , Hussain Khalid , Tinker Andrew
Published: May 2007

Objective  Congenital hyperinsulinism (CHI) is a cause of persistent and severe hypoglycaemia in infancy. Mutations in the genes ABCC8 and KCNJ11 encoding SUR1 and Kir6·2, respectively, are the commonest cause of CHI. We investigated whether the possession of two DNA variants leading to coding changes in a single allele of ABCC8 can affect the potential mechanism of disease pathogenesis.

Design and patients  We studied two patients with complex mutations in the ABCC8 gene with CHI and used in vitro studies to explore the potential disease mechanism and the contribution of the various mutant allelles.

Results  The first case had diffuse disease and was homozygous for the mutations D1193V and R1436Q in SUR1. Channel complexes containing the D1193V mutant were delivered to the plasma membrane and were functional and those containing R1436Q were also present at the plasma membrane but were nonfunctional. Combining the two mutations (SUR1D1193V/R1436Q) led to intracellular retention of the channel complex. In a second family, the patient had histologically focal disease and was heterozygous for two mutations from his father (G228D and D1471N) and one from his mother (V1572I). SUR1 G228D and D1471N singly or in combination led to intracellular retention of the channel complex and loss of function. By contrast, V1572I is trafficked appropriately and is functional, consistent with a mechanism of reduction to hemizygosity of paternal ABCC8 in focal disease. V1572I is likely to be a benign DNA variant.

Conclusion  In one patient the combination of two coding variants led to intracellular retention of channel complex. In a second patient, functional studies allowed us to unravel the DNA variants likely to be causing the abrogation of ATP‐sensitive K+ channel function.
Perioperative plasma active and total ghrelin levels are reduced in acromegaly when compared with in nonfunctioning pituitary tumours even after normalization of serum GH
Authors: Kawamata Takakazu , Inui Akio , Hosoda Hiroshi , Kangawa Kenji , Hori Tomokatsu
Published: May 2007

Objective Ghrelin is a novel gastric peptide known to stimulate GH secretion, but the relationship between ghrelin and the GH‐insulin‐like growth factor (IGF)‐1 axis in GH excess or deficiency is poorly understood. This study investigated dysregulation of ghrelin secretion in acromegaly and its short‐term postoperative recovery.

Methods A prospective study was conducted on eight patients who underwent complete transsphenoidal resection of GH‐producing pituitary adenomas (acromegaly group) and 22 for endocrinologically nonfunctioning pituitary tumours (control group). Active and total plasma ghrelin levels were measured serially before and after surgery.

Results Preoperative active and total plasma ghrelin concentrations (mean ± SD; fmol/ml) were significantly reduced in acromegalic patients when compared with those in the controls (9·6 ± 4·3 and 157·4 ± 65·6vs.21·8 ± 13·0 and 267·1 ± 111·4;P = 0·023 andP = 0·021, respectively). Both levels were still significantly suppressed on postoperative Day 7 in the acromegaly group when compared with those in the control group (11·7 ± 4·3 and 197·8 ± 68·9vs.22·5 ± 12·6 and 302·7 ± 100·0;P = 0·038 andP = 0·018, respectively). The ratios of active to total ghrelin were not significantly different between the two groups before and after operation. In acromegalic patients, active and total ghrelin levels remained significantly suppressed even after normalization of serum GH levels.

Conclusions The putative negative feedback mechanism of GH on ghrelin secretion may in part account for the low ghrelin levels observed in acromegalic patients, and the mechanism may persist even after normalization of serum GH.
Adaptive versus non‐adaptive phenotypic plasticity and the potential for contemporary adaptation in new environments
Authors: GHALAMBOR C. K. , McKAY J. K. , CARROLL S. P. , REZNICK D. N.
Published: May 2007

The role of phenotypic plasticity in evolution has historically been a contentious issue because of debate over whether plasticity shields genotypes from selection or generates novel opportunities for selection to act. Because plasticity encompasses diverse adaptive and non‐adaptive responses to environmental variation, no single conceptual framework adequately predicts the diverse roles of plasticity in evolutionary change.

Different types of phenotypic plasticity can uniquely contribute to adaptive evolution when populations are faced with new or altered environments. Adaptive plasticity should promote establishment and persistence in a new environment, but depending on how close the plastic response is to the new favoured phenotypic optimum dictates whether directional selection will cause adaptive divergence between populations. Further, non‐adaptive plasticity in response to stressful environments can result in a mean phenotypic response being further away from the favoured optimum or alternatively increase the variance around the mean due to the expression of cryptic genetic variation. The expression of cryptic genetic variation can facilitate adaptive evolution if by chance it results in a fitter phenotype.

We conclude that adaptive plasticity that places populations close enough to a new phenotypic optimum for directional selection to act is the only plasticity that predictably enhances fitness and is most likely to facilitate adaptive evolution on ecological time‐scales in new environments. However, this type of plasticity is likely to be the product of past selection on variation that may have been initially non‐adaptive.

We end with suggestions on how future empirical studies can be designed to better test the importance of different kinds of plasticity to adaptive evolution.
Fault locking, block rotation and crustal deformation in the Pacific Northwest
Authors: McCaffrey Robert , Qamar Anthony I. , King Robert W. , Wells Ray , Khazaradze Giorgi , Williams Charles A. , Stevens Colleen W. , Vollick Jesse J. , Zwick Peter C.
Published: May 2007

We interpret Global Positioning System (GPS) measurements in the northwestern United States and adjacent parts of western Canada to describe relative motions of crustal blocks, locking on faults and permanent deformation associated with convergence between the Juan de Fuca and North American plates. To estimate angular velocities of the oceanic Juan de Fuca and Explorer plates and several continental crustal blocks, we invert the GPS velocities together with seafloor spreading rates, earthquake slip vector azimuths and fault slip azimuths and rates. We also determine the degree to which faults are either creeping aseismically or, alternatively, locked on the block-bounding faults. The Cascadia subduction thrust is locked mainly offshore, except in central Oregon, where locking extends inland. Most of Oregon and southwest Washington rotate clockwise relative to North America at rates of 0.4–1.0 ° Myr−1. No shear or extension along the Cascades volcanic arc has occurred at the mm/yr level during the past decade, suggesting that the shear deformation extending northward from the Walker Lane and eastern California shear zone south of Oregon is largely accommodated by block rotation in Oregon. The general agreement of vertical axis rotation rates derived from GPS velocities with those estimated from palaeomagnetic declination anomalies suggests that the rotations have been relatively steady for 10–15 Ma. Additional permanent dextral shear is indicated within the Oregon Coast Range near the coast. Block rotations in the Pacific Northwest do not result in net westward flux of crustal material—the crust is simply spinning and not escaping. On Vancouver Island, where the convergence obliquity is less than in Oregon and Washington, the contractional strain at the coast is more aligned with Juan de Fuca—North America motion. GPS velocities are fit significantly better when Vancouver Island and the southern Coast Mountains move relative to North America in a block-like fashion. The relative motions of the Oregon, western Washington and Vancouver Island crustal blocks indicate that the rate of permanent shortening, the type that causes upper plate earthquakes, across the Puget Sound region is 4.4 ± 0.3 mm yr−1. This shortening is likely distributed over several faults but GPS data alone cannot determine the partitioning of slip on them. The transition from predominantly shear deformation within the continent south of the Mendocino Triple Junction to predominantly block rotations north of it is similar to changes in tectonic style at other transitions from shear to subduction. This similarity suggests that crustal block rotations are enhanced in the vicinity of subduction zones possibly due to lower resisting stress.
Significant high expression of CD23 in follicular lymphoma of the inguinal region
Authors: Thorns C , Kalies K , Fischer U , Höfig K , Krokowski M , Feller A C , Merz H , Bernd H‐W
Published: May 2007

Aims:  Inguinal lymph nodes are considered to be problematic for the diagnosis of lymphoma due to architectural changes resulting from previous inflammatory processes. The aim was to investigate the morphology and immunophenotype of follicular lymphomas (FL) in order to clarify whether FL presenting in inguinal nodes differs from FL biopsies from other sites.

Methods and results:  A total of 219 FLs were studied, comprising 78 biopsy specimens of inguinal lymph nodes and 141 from other sites. All samples were assessed for growth pattern, grade, sclerosis and immunophenotype (Bcl‐2, CD10, CD23, Mib‐1). Cases negative for Bcl‐2 were analysed by polymerase chain reaction and fluorescence in situ hybridization. In comparison with the biopsies from other regions, we found a significantly increased number of CD23+ FLs in samples of inguinal lymph nodes (38% versus 21%). Expression of CD23 was more frequently detected in grade 1 FLs than in other grades (grade 1, 37%; grade 2, 18%; grade 3, 23%; transformed, 6%). Other immunohistochemical parameters, however, did not differ between the two groups.

Conclusion:  There is an unexpectedly high frequency of CD23 expression in FL in general, which is even more pronounced in inguinal nodes.
Histopathology of graft versus host disease of the liver
Authors: Quaglia A , Duarte R , Patch D , Ngianga‐Bakwin K , Dhillon A P
Published: May 2007

Aims:  To analyse the histological features of 33 patients (48 biopsy specimens) with a clinicopathological diagnosis of graft vs. host disease of the liver (L‐GVHD).

Results:  The time of biopsy post‐haematopoietic stem cell transplantation (HSCT) ranged from 22 to 1082 days (median 144 days). Bile duct damage (BDD) was present in all biopsies except one. The bile duct to portal ratio ranged from 0.3 to 1 (median 0.8). Moderate/severe lobular hepatitis was present in 11 biopsies. Endotheliitis was present in four biopsies (8%). The majority of the biopsies showed none [25 (52%)] or mild [17 (35%)] fibrosis. The only significant difference between biopsies earlier (‘acute’) or later (‘chronic’ GVHD) than 100 days post‐HSCT was the presence of portal inflammation in the ‘chronic’ GVHD group.

Conclusion:  BDD is the predominant change in L‐GVHD. In about a quarter of biopsies the appearance may be of a lobular hepatitis. L‐GVHD is not a fibrogenic process. The significance of separating acute versus chronic L‐GVHD based on a cut‐off of 100 days post‐HSCT is questionable. Further studies are needed to understand the relationships between the mechanisms of BDD, bile duct loss and regeneration.
Cytoarchitectural and kinetic features in the histological evaluation of follicular thyroid neoplasms
Authors: Arif S , Patel J , Blanes A , Diaz‐Cano S J
Published: May 2007

Aims:  The diagnosis of follicular thyroid carcinomas is mainly based on capsular and vascular invasion. The aim of this study was to determine the diagnostic relevance of nuclear features, inflammation and stromal changes.

Methods and results:  Anisokaryosis, chromatin pattern, nucleolus, nuclear pleomorphism, nuclear/cytoplasmic ratio, necrosis, stromal changes and tumour interstitial lymphocytes (TIL) were analysed in adenomatous hyperplastic nodules (39), adenomas (43) and carcinomas (28 minimally invasive, 48 widely invasive and 27 anaplastic). Ki67 immunostaining, in situ end labelling (ISEL) for apoptosis and the Ki67/ISEL index were analysed by topographical compartments. Variables were compared by histological diagnosis using Fisher's exact test, analysis of variance and Student's t‐tests and considered significant if P < 0.05. TIL were absent in 96% of neoplasms and 54% of adenomatous hyperplastic nodules. Conspicuous nucleoli, increased nuclear–cytoplasmic ratio and coexistent apoptosis–myxoid changes distinguished minimally invasive carcinomas from adenomas. The most specific variables of high‐grade carcinoma were vasculonecrotic patterns, nuclear hyperchromatism and pleomorphism. A kinetic advantage predominated in the internal compartments of benign lesions and in the peripheral compartments of malignant lesions.

Conclusions:  Follicular carcinomas show up‐regulation of proliferation markers and the distinctive topographical kinetic profiles provide a basis for the distinction between benign and malignant and an explanation for the circumscription and encapsulation of benign lesions.
BALB/c mice resistant to Toxoplasma gondii infection proved to be highly susceptible when previously infected with Myocoptes musculinus fur mites
Authors: Welter Áurea , Mineo José Roberto , De Oliveira Silva Deise Aparecida , Lourenço Elaine Vicente , Vieira Ferro Eloísa Amália , Roque‐Barreira Maria Cristina , Maria da Silva Neide
Published: May 2007

The immune response induced by Toxoplasma gondii is characterized by Th1 immune mechanisms. We previously demonstrated that C57BL/6 mice infested with Myocoptes musculinus and infected with T. gondii by intraperitoneal route undergo accelerated mortality according to Th2 immune mechanisms induced by the acarian. To evaluate whether infection with M. musculinus influences T. gondii‐induced Th1 response in a resistant mouse lineage, BALB/c, which develops latent chronic toxoplasmosis in a way similar to that observed in immunocompetent humans, this study was done. The animals were infected with T. gondii ME‐49 strain 1 month after M. musculinus infestation, being the survival and the immune response monitored. The double‐infected displayed higher mortality rate if compared with the mono‐infected mice. In addition, infection with M. musculinus changed the T. gondii‐specific immune response, converting BALB/c host to a susceptible phenotype. Spleen cells had increased the levels of IL‐4 in double‐infected mice. This alteration was associated with severe pneumonia, encephalitis and wasting condition. In addition, a higher tissue parasitism was observed in double‐infected animals. It can be concluded that infection with these two contrasting parasites, M. musculinus and T. gondii, may convert an immunocompetent host into a susceptible one, and such a host will develop severe toxoplasmosis.
Central nervous system capillary haemangioblastoma: the pathologist's viewpoint
Authors: Hussein Mahmoud R.
Published: May 2007

Haemangioblastomas are rare neoplasms of uncertain histogenesis. They represent 1.5–2.5% of intracranial tumours. While the cerebellum is by far the most frequent site, these lesions also tend to occur in the medulla and spinal cord. Most haemangioblastomas are sporadic but up to one quarter are associated with Von Hippel–Lindau disease (VHL). Although a fairly good number of haemangioblastomas were reported, a lack of side‐by‐side analysis of these reports has resulted in tentative conclusions that merely offer a first glimpse at their clinicopathologic diversity and histogenesis. To remedy this issue, this study presents a literature review concerning these lesions. Medline literature including both relevant monographs and clinicopathological case series. Haemangioblastomas occur either as a part of VHL disease (25–30%, inherited mutation of VHL gene on 3p25–26 chromosome) or as sporadic tumours (often with somatic mutation of VHL gene). They have diverse clinicopathologic presentations with cerebellar lesions having a better prognosis than their brainstem counterparts. Immunostaining is important for separation of haemangioblastomas from other tumours with similar histology. The rich vascularity of haemangioblastomas is due to overexpression of vascular endothelial growth factors. Moreover, ‘stromal’ cells represent the neoplastic cells of haemangioblastomas and are capable of forming blood islands with extramedullary haematopoiesis.
Subterranean rodents of the genusCtenomys(Caviomorpha, Ctenomyidae) follow the converse to Bergmann's rule
Authors: Medina Alonso I. , Martí Dardo A. , Bidau Claudio J.
Published: May 2007

Aim We analysed body‐size variation in relation to latitude, longitude, elevation and environmental variables inCtenomys(tuco‐tucos), subterranean rodents in the Ctenomyidae (Caviomorpha). We tested the existence of inter‐ and intraspecific size clines to determine if these rodents follow Bergmann's rule, to compare intra‐ and interspecific size trends and to assess the relevance of the subterranean lifestyle on these trends.

Location South America, south of 15° latitude.

Methods This paper is based on 719 specimens of tuco‐tucos from 133 localities of Argentina, Bolivia, Chile, Paraguay, Peru and Uruguay, representing 47 named species and 32 undescribed forms. Intraspecific analyses were performed forCtenomys talarumThomas, 1898 and theCtenomys perrensiThomas, 1896 species complex. Head and body length and weight were used for estimating body size. Geographical independent variables included latitude, longitude and altitude. Environmental independent variables were mean minimal and maximal monthly temperature, mean annual temperature, mean minimal and maximal precipitation, and total annual precipitation. To estimate seasonality, the annual variability of the climatic factors was calculated as their coefficients of variation and the difference between maximum and minimum values. Mean annual actual evapotranspiration (AET), and mean annual, January (summer) and July (winter) potential evapotranspiration (PET) values were also calculated for each locality, as well as annual, summer and winter water balance (WB). Statistical analyses consisted of simple and multiple regression and nonparametric correlation.

Results Body size ofCtenomysdecreases interspecifically from 15°00′ S to 48°15′ S and from 56°33′ W to 71°46′ W, and is positively correlated with ambient temperature and precipitation. The best predictors of body size according to multiple regression analyses were mean annual temperature, the difference between mean maximum and minimum annual temperatures, annual PET, the difference between summer and winter PET, and annual and winter water balance. These patterns are repeated, but not identically, at a smaller geographical scale within the speciesC. talarumand the superspeciesC. perrensi.

Main conclusions Tuco‐tucos follow the converse to Bergmann's rule at the interspecific level. At the intraspecific level some parallel trends were observed, but the smaller scale of these analyses, involving a very reduced variation of environmental factors, necessitates caution in interpreting results. The subterranean lifestyle probably insulates these rodents from the external temperature. The observed latitudinal body‐size gradients are more probably related to seasonality, ambient energy, primary productivity and/or intensity of predation.
Geographical distribution and extinction risk: lessons from Triassic–Jurassic marine benthic organisms
Authors: Kiessling Wolfgang , Aberhan Martin
Published: May 2007

Aim To evaluate the influence of geographical distribution on the extinction risk of benthic marine invertebrates using data from the fossil record, both during times of background extinction and across a mass‐extinction episode. Total geographical range is contrasted with proxies of global abundance to assess the relationships between the two essential components of geographical distribution and extinction risk.

Location A global occurrence data base of fossil benthic macro‐organisms from the Triassic and Jurassic periods was used for this study.

Methods Geographical distributions and biodiversity dynamics were assessed for each genus (all taxa) or species (bivalves) based on a sample‐standardized data set and palaeogeographical reconstructions. Geographical ranges were measured by the maximum great circle distance of a taxon within a stratigraphic interval. Global abundance was assessed by the number of localities at which a taxon was recorded. Widespread and rare taxa were separated using median and percentile values of the frequency distributions of occurrences.

Results The frequency distribution of geographical ranges is very similar to that for modern taxa. Although no significant correlation could be established between local abundance and geographical range, proxies of global abundance are strongly correlated with geographical range. Taxon longevities are correlated with both mean geographical range and mean global abundance, but range size appears to be more critical than abundance in determining extinction risk. These results are valid when geographical distribution is treated as a trait of taxa and when assessed for individual geological stages.

Main conclusions Geographical distribution is a key predictor of extinction risk of Triassic and Jurassic benthic marine invertebrates. An important exception is in the end‐Triassic mass extinction, which equally affected geographically restricted and widespread genera, as well as common and rare genera. This suggests that global diversity crises may curtail the role of geographical distribution in determining extinction risk.
Local–regional boundary shifts in oribatid mite (Acari: Oribatida) communities: species–area relationships in arboreal habitat islands of a coastal temperate rain forest, Vancouver Island, Canada
Authors: Lindo Zoë , Winchester Neville N.
Published: May 2007

Aim This study investigates the species–area relationship (SAR) for oribatid mite communities of isolated suspended soil habitats, and compares the shape and slope of the SAR with a nested data set collected over three spatial scales (core, patch and tree level). We investigate whether scale dependence is exhibited in the nested sampling design, use multivariate regression models to elucidate factors affecting richness and abundance patterns, and ask whether the community composition of oribatid mites changes in suspended soil patches of different sizes.

Location Walbran Valley, Vancouver Island, Canada.

Methods A total of 216 core samples were collected from 72 small, medium and large isolated suspended soil habitats in six western redcedar trees in June 2005. The relationship between oribatid species richness and habitat volume was modelled for suspended soil habitat isolates (type 3) and a nested sampling design (type 1) over multiple spatial scales. Nonlinear estimation parameterized linear, power and Weibull function regression models for both SAR designs, and these were assessed for best fit usingR2and Akaike's information criteria (ΔAIC) values. Factors affecting oribatid mite species richness and standardized abundance (number per g dry weight) were analysed byanovaand linear regression models.

Results Sixty‐seven species of oribatid mites were identified from 9064 adult specimens. Surface area and moisture content of suspended soils contributed to the variation in species richness, while overall oribatid mite abundance was explained by moisture and depth. A power‐law function best described the isolate SAR (S = 3.97 × A0.12,R2 = 0.247,F1,70 = 22.450,P < 0.001), although linear and Weibull functions were also valid models. Oribatid mite species richness in nested samples closely fitted a power‐law model (S = 1.96 × A0.39,R2 = 0.854,F1,18 = 2693.6,P < 0.001). The nested SAR constructed over spatial scales of core, patch and tree levels proved to be scale‐independent.

Main conclusions Unique microhabitats provided by well developed suspended soil accumulations are a habitat template responsible for the diversity of canopy oribatid mites. Species–area relationships of isolate vs. nested species richness data differed in the rate of accumulation of species with increased area. We suggest that colonization history, stability of suspended soil environments, and structural habitat complexity at local and regional scales are major determinants of arboreal oribatid mite species richness.
Intra‐seasonal precipitation patterns and above‐ground productivity in three perennial grasslands
Authors: SWEMMER ANTHONY M. , KNAPP ALAN K. , SNYMAN HENNIE A.
Published: May 2007

Relationships between above‐ground net primary productivity (ANPP) of grasslands and annual precipitation are often weak at the site level, with much of the inter‐annual variation in ANPP left unexplained. A potential reason for this is that the distribution of precipitation within a growing season affects productivity in addition to the total amount.

 We analysed long‐term ANPP data for three southern African temperate grasslands (mean annual precipitation ranging from 538 mm to 798 mm) to determine the effects of precipitation event size, number and spacing relative to seasonal totals.

 Ungrazed, non‐manipulated treatments at each site showed contrasting results despite sharing a common, dominant species. At the driest site, a model combining average event size and number of events per growing season provided a substantially better fit to the ANPP data than precipitation amount (seasonal total). At the wettest site, the interval between events was the most important precipitation variable. Precipitation distribution was not important at the intermediate site where amount was the best predictor of ANPP. A limit to the size of precipitation events efficiently utilized for ANPP was evident for the driest site only.

 At each site, experimental treatments that altered species composition and soil fertility had little effect on precipitation–ANPP relationships. The lack of consistency in the relative importance of the precipitation variables among sites suggests that local, edaphic factors modify precipitation–ANPP relationships.

 This analysis demonstrates that the distribution and size of precipitation events can affect ANPP independent of precipitation amount. As altered precipitation regimes are forecast by global climate models, the sensitivity of ecosystems to precipitation distribution should be considered when predicting responses to climate change.

 While mean values of precipitation, and other ecosystem drivers, are typically used to predict function at the level of whole ecosystems, our results show that more complex measures of environmental variability may be required to understand ecosystem function, and to increase the accuracy of predictions of ecosystem responses to global change.
The cost‐effectiveness of long‐term antiviral therapy in the management of HBeAg‐positive and HBeAg‐negative chronic hepatitis B in Singapore
Authors: Lacey L. F. , Gane E.
Published: May 2007

Summary.  The purpose of this study was the economic evaluation of short‐duration treatments of chronic hepatitis B (CHB) and longer duration antiviral treatment for up to 5 years. Two 10‐health state Markov models were developed for hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative CHB patients respectively. The perspective of this economic evaluation was the Singapore healthcare system and CHB patient. The models followed cohorts of HBeAg‐positive and HBeAg‐negative CHB patients, respectively, over a period of 40 years, by which time the majority of the cohorts would have died if left untreated. Costs and benefits were discounted at 5% per annum. Annual rates of disease progression and the magnitude of treatment effects were obtained from the literature, with a focus on data obtained in Asian patients and meeting the criteria for therapy as described in internationally recognized management guidelines. Short‐course therapy with α‐interferon, or 1‐year treatment with pegylated interferon α‐2a, lamivudine or adefovir had limited impact on disease progression. In contrast, treatment of CHB with antiviral therapy for 5 years substantially decreased the rate of disease progression. Treatment with lamivudine for 1‐year is highly cost‐effective compared with no treatment of CHB but has limited effect on reducing the rate of disease progression. Compared with 1‐year treatment with lamivudine, sequential antiviral therapies for up to 5 years (i.e. lamivudine plus adefovir on emergence of lamivudine resistance or adefovir plus lamivudine on emergence of adefovir resistance) are highly cost‐effective by international standards. These conclusions are robust to uncertainties in model inputs and are consistent with the findings of other recently published studies.
Aiolos Controls Gene Conversion and Cell Death in DT40 B Cells
Authors: Narvi E. , Nera K.‐P. , Terho P. , Mustonen L. , Granberg J. , Lassila O.
Published: May 2007

The Ikaros family transcription factor Aiolos is important for B cell function, since B cells of Aiolos‐null mutant mice exhibit an activated phenotype, enhanced B‐cell receptor (BCR) signalling response and develop a systemic lupus erythematosus (SLE) type autoimmune disease. Aiolos has also been reported to interact with anti‐apoptotic Bcl‐2 and Bcl‐xL in T cells, but whether Aiolos regulates cell death has not been studied in B cells. Here we show that the disruption of Aiolos in the DT40 B cell line induces a cell death sensitive phenotype, as the Aiolos−/− cells are more prone to apoptosis by nutritional stress, BCR cross‐linking, UV‐ or γ‐irradiation. Furthermore, the Aiolos−/− cells have defective Ig gene conversion providing evidence that Aiolos is needed for the somatic diversification of the BCR repertoire. The re‐expression of DNA‐binding isoform Aio‐1 was able to restore the gene conversion defect of the Aiolos‐deficient cells, whereas the introduction of dominant negative isofom Aio‐2 had no effect on gene conversion, thus demonstrating the functional importance of alternative splicing within Ikaros family. Although the Aiolos−/− cells exhibit reduced expression of activation‐induced cytidine deaminase (AID), ectopic AID overexpression did not restore the gene conversion defect in the Aiolos−/− cells. Our findings indicate that Aiolos may regulate gene conversion in an AID independent manner.
A Dual Altered Peptide Ligand Inhibits Myasthenia Gravis Associated Responses by Inducing Phosphorylated Extracellular‐regulated Kinase 1,2 that Upregulates CD4+CD25+Foxp3+ Cells
Authors: Ben‐David H. , Venkata Aruna B. , Sela M. , Mozes E.
Published: May 2007

Myasthenia gravis (MG) and its animal model experimental autoimmune MG (EAMG), are T‐cell dependent, antibody‐mediated autoimmune disorders. A dual altered peptide ligand (APL) composed of the tandemly arranged two single amino acids analogs of two myasthenogenic peptides, p195–212 and p259–271, was demonstrated to downregulate, in vitro and in vivo, MG‐associated autoimmune responses. Upregulation of regulatory CD4+CD25+ cells plays a key role in the mechanism of action of the dual APL. The objectives of the present study were to address the involvement of extracellular‐regulated kinase (ERK)1,2 in the mechanisms by which the dual APL‐induced CD4+CD25+ cells suppress MG‐associated autoimmune responses. We demonstrate here that administration of the dual APL increased activated ERK1,2 in the CD4+CD25+‐enriched population. Further, inhibition of ERK1,2 by its inhibitor, U0126, in dual APL‐induced CD4+CD25+ cells, abrogated their ability to suppress interferon (IFN)‐γ secretion by lymph node (LN) cells of mice that were immunized with the myasthenogenic peptide. Moreover, inhibition of ERK1,2 in the dual APL‐induced regulatory CD4+CD25+ cells, resulted in downregulation of the forkhead box p3 (Foxp3) gene and protein expression levels, as well as in the downregulation of CD4+CD25+ development, suggesting that the active suppression exerted by the dual APL via CD4+CD25+ cells depends on ERK1,2 activity.
Protective Acquired Immunity to Enteromyxum scophthalmi (Myxozoa) is Related to Specific Antibodies in Psetta maxima (L.) (Teleostei)
Authors: Sitjà‐Bobadilla A. , Palenzuela O. , Riaza A. , Macías M. A. , Alvarez‐Pellitero P.
Published: May 2007

The acquired protection of three groups of turbot that had survived enteromyxosis outbreaks was tested by challenging with E. scophthalmi in three different experiments. The relation of such a response with the kinetics and duration of antibody production (determined by an ELISA) was studied. The progression of the infection was evaluated by PCR. In experiments 1 and 2, in which turbot had cohabited with highly infected fish during outbreaks, parasite prevalence and mortality were very low or null, and there was a progressive and statistically significant increase in the mean antibody production up to 350 and 152 days post‐exposure respectively. By contrast, in experiment 3, fish (coming from non‐infected tanks during the initial outbreak), both infection prevalence and cumulative mortality reached 92.8%, and specific antibodies were detected only in two fish. The observed differences in mortality after challenge appear to be related to the production of specific antibodies and it is probably accompanied by a repertoire of mechanisms of innate immunity. The exploitation of the immune system through breeding selection programmes as a possible strategy to control the disease is discussed.
Annular atrophic lichen planus
Authors: Ponce‐Olivera Rosa María , Tirado‐Sánchez Andrés , Montes‐de‐Oca‐Sánchez Griselda , León‐Dorantes Gladys , Mercadillo‐Pérez Patricia
Published: May 2007

A 30‐year‐old woman presented with a 1‐year history of a pruritic eruption on the extremities, characterized by several annular plaques. The patient had been treated unsuccessfully with medium‐potency topical steroids. The lesions had an erythematous papular border with an atrophic center (width, 1–4 cm) (Fig. 1). No oral, genital, or nail lesions were observed.

Annular lesion with an infiltrated border and atrophic center

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A skin biopsy from one of the plaques was performed. Histopathologic examination of the raised border showed hyperkeratosis of the stratum corneum, focal thickening of the granular layer, basal liquefaction degeneration of the epidermis, and a band‐like subepidermal infiltration with numerous Civatte bodies. In the center of the lesion, the epidermis became thinner (Fig. 2). Elastic fibers were reduced or absent in the papillary dermis.

(a) Biopsy of the border of a plaque with the typical changes of lichen planus (hematoxylin and eosin, ×10), with flattened epidermis in the center of the plaque; (b) medium power of the border of the plaque with details of the changes of lichen planus (hematoxylin and eosin, ×40)

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The patient was treated with high‐potency topical steroids for 2 months with clinical improvement.
Comparative study of fig tree efficacy in the treatment of common warts (Verruca vulgaris) vs. cryotherapy
Authors: Bohlooli Shahab , Mohebipoor Alireza , Mohammadi Sadollah , Kouhnavard Mina , Pashapoor Sedigheh
Published: May 2007

Background  A traditional method for the treatment of warts in some rural areas of Iran comprises the use of fig tree (ficus carica) latex as a local treatment; however, there is no scientific evaluation of its efficacy.

Methods  A prospective, open right/left comparative trial of fig tree latex therapy vs. local standard of cryotherapy was carried out. Twenty‐five patients with common warts were recruited into the study from an outpatient clinic. The patients were instructed in self‐application of fig tree latex to warts on one side of the body. The wart on the opposite side was treated using standard cryotherapy. A 6‐month follow‐up study was planned.

Results  In 11 (44%) of the 25 patients complete resolution of fig tree latex‐treated warts was observed. The remaining 14 patients (56%) had a complete cure following cryotherapy. Two patients had complete remission on both sides. Two patients failed to respond to either cryotherapy or fig tree latex. It was found that fig tree latex therapy was marginally less effective than cryotherapy. Adverse effects were observed only in cryo‐treated warts. At the 6‐month follow‐up study there was an 18% recurrence rate.

Conclusion  Fig tree latex therapy of warts offers several beneficial effects including short‐duration therapy, no reports of any side‐effects, ease‐of‐use, patient compliance, and a low recurrence rate. The exact mechanism of the antiwart activity of fig tree latex is unclear but is likely to be the result of the proteolytic activity of the latex enzymes.
A framework for measuring the social impact of food allergy across Europe: a EuroPrevall state of the art paper
Authors: De Blok B. M. J. , Vlieg‐Boerstra B. J. , Oude Elberink J. N. G. , Duiverman E. J. , DunnGalvin A. , Hourihane J. O'B. , Cornelisse‐Vermaat J. R. , Frewer L. , Mills C. , Dubois A. E. J.
Published: May 2007

This state of the art paper has been developed through EuroPrevall, a European multicentre research project funded by the European Union which aims to improve quality of life for food allergic individuals. Food allergy (whether clinically diagnosed or self‐perceived) represents a major health issue in Western societies and may have a considerably greater impact on society than was previously believed. However, the social impact of food allergy has never been systematically investigated using validated instruments. Combining the information from studies on health‐related quality of life (HRQoL) with epidemiological data on prevalence will ultimately give some indication of the magnitude of the social impact of food allergy in Europe. HRQoL can be assessed with disease‐specific questionnaires, which are being developed in EuroPrevall. These instruments will be used to identify HRQoL problems associated with food allergy, and to assess the effectiveness of interventions and to guide the development of regulatory policies.
Differences in psychosocial profiles between men and women living kidney donors
Authors: Achille Marie , Soos John , Fortin Marie‐Chantal , Pâquet Michel , Hébert Marie‐Josée
Published: May 2007

Abstract:  Background:  The expansion of kidney transplantation by living donation has led to a disproportional increase in the women to men ratio among donors and this difference cannot be explained on the basis of medical exclusion. The present study was designed to test whether women donors are more likely to (i) display altruistic and gender‐typed nurturing behaviour and (ii) be subtly influenced by family pressure to donate and less able to resist this pressure.

Methods:  All 71 (61% women) individuals who had donated a kidney at our centre between 1995 and 2005 were sent a survey. Thirty‐nine individuals (71% response rate; 64% female participation) filled out and returned the survey, which included standardized measures of altruism, self‐esteem, family dynamics and endorsement of gender‐stereotyped roles, as well as sociodemographic questions and questions about donation.

Results:  Findings show no difference between women and men in terms of the psychological attributes measured. One woman and two men reported having felt pressure to donate, and 92% of women compared with 54% of men reported having felt free to change their mind. Men took longer than women to make the decision to donate.

Conclusions:  Results suggest that among individuals who have already donated, there is no evidence that women may be more inclined to donate than man because of differences in their psychosocial profiles or because they may be more vulnerable to family pressure. Future research may gain from focusing on men and women donors and non‐donors in families where transplantation is being considered.
Macrophage migration inhibitory factor gene influences the risk of developing tuberculosis in northwestern Colombian population
Authors: Gómez L. M. , Sánchez E. , Ruiz‐Narvaez E. A. , López‐Nevot M. A. , Anaya J.‐M. , Martín J.
Published: May 2007

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that regulates innate and adaptative immunity responses against pathogens. The MIF gene, at 22q11.2, is polymorphic. Functional promoter variants in the MIF gene influence susceptibility to inflammatory diseases in Caucasians and Africans. An association study was carried out to examine the influence of MIF−173 single nucleotide polymorphism and the MIF−794 microsatellite on the susceptibility to develop human tuberculosis (TB) in a well‐defined Latin‐American population. To this purpose, 230 northwestern Colombian patients with pulmonary TB, negative for human immunodeficiency virus infection, and 235 matched healthy individuals stratified by the tuberculin skin test were examined. Multivariate analysis showed that MIF−173C allele was associated with disease (odds ratio = 1.64, 95% confidence interval 1.07–2.52) in a dominant pattern. No allele in the MIF−794 CATT microsatellite was associated with risk of TB. These results indicate that MIF gene influences the risk of developing TB in the studied population.
Identification of four novel MHC‐C alleles in chimpanzees
Authors: Caggiari L. , Rehermann B. , Folgori A. , De Re V.
Published: May 2007

Sequence‐based typing strategy is used to identify polymorphism of Patr‐C. Four new Patr‐C alleles are described.
Characterization of a new HLA‐DRB1*1405 variant, HLA‐DRB1*140503, identified by sequence‐based typing
Authors: Kwon O.‐J. , Park S.‐Y. , Oh J.‐W. , Nah S.‐Y. , Jeong S. M.
Published: May 2007

A new human leukocyte antigen‐DRB1*140503 differs from DRB1*140501 with T to C transition at codon 78 (TAT→TAC) of exon 2 without coding change.
Detection of the solanum fruit fly, Bactrocera latifrons (Hendel) in Tanzania (Dipt., Tephritidae)
Authors: Mwatawala M. , De Meyer M. , White I. M. , Maerere A. , Makundi R. H.
Published: May 2007

Abstract:  The presence of the Solanum fruit fly, Bactrocera latifrons, in Africa is reported for the first time, based on trapped and reared specimens in Tanzania. Two new host records, Solanum aethiopicum and Solanum macrocarpon, are reported.
Isolation of Cryptococcus neoformans from hollows of living trees in the city of Alfenas, MG, Brazil
Authors: Reimão Juliana Quero , Drummond Elislene Dias , Terceti Mateus de Souza , Lyon Juliana Pereira , Franco Marília Caixeta , De Siqueira Antônio Martins
Published: May 2007

Cryptococcus neoformans is an encapsulated yeast, aetiological agent of cryptococcosis, commonly associated with pigeon droppings and plant materials. The species has also been associated with tree hollows. The aim of the present work was to verify the presence of the yeast in hollows of living trees and identify the isolates obtained in varieties and serotypes. Three samples were collected from 18 trees of five different species totalling 54 samples. Wood samples were collected by scraping the surface of the trunks and the inner face of the hollows. Samples were inoculated on to agar Niger medium for fungal isolation. The serotypes were determined by PCR using specific primers. Among the 54 samples evaluated, two were positive for the presence of C. n. var. neoformans (serotype A and MATα). The trees belonged to Caesalpinia peltophoroides and Anadenanthera peregrina species. The results of this study suggest that decayed wood obtained from hollows of C. peltophoroides and A. peregrina can be used as natural habitat for C. n. var. neoformans.