bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural basis for reversible photobleaching of a green fluorescent protein homologue
Authors: Henderson J. Nathan , Ai Hui-wang , Campbell Robert E. , Remington S. James
Published: April 2007

Fluorescent protein (FP) variants that can be reversibly converted between fluorescent and nonfluorescent states have proven to be a catalyst for innovation in the field of fluorescence microscopy. However, the structural basis of the process remains poorly understood. High-resolution structures of a FP derived from
Clavularia
in both the fluorescent and the light-induced nonfluorescent states reveal that the rapid and complete loss of fluorescence observed upon illumination with 450-nm light results from cis–trans isomerization of the chromophore. The photoinduced change in configuration from the well ordered cis isomer to the highly nonplanar and disordered trans isomer is accompanied by a dramatic rearrangement of internal side chains. Taken together, the structures provide an explanation for the loss of fluorescence upon illumination, the slow light-independent recovery, and the rapid light-induced recovery of fluorescence. The fundamental mechanism appears to be common to all of the photoactivatable and reversibly photoswitchable FPs reported to date.
Exceptional transmission of plastids and mitochondria from the transplastomic pollen parent and its impact on transgene containment
Authors: Svab Zora , Maliga Pal
Published: April 2007

Plastids in
Nicotiana tabacum
are normally transmitted to the progeny by the maternal parent only. However, low-frequency paternal plastid transmission has been reported in crosses involving parents with an alien cytoplasm. Our objective was to determine whether paternal plastids are transmitted in crosses between parents with the normal cytoplasm. The transplastomic father lines carried a spectinomycin resistance (
aadA
) transgene incorporated in the plastid genome. The mother lines in the crosses were either (
i
) alloplasmic, with the
Nicotiana undulata
cytoplasm that confers cytoplasmic male sterility (CMS92) or (
ii
) normal, with the fertile
N
.
tabacum
cytoplasm. Here we report that plastids from the transplastomic father were transmitted in both cases at low (10
−4
-10
−5
) frequencies; therefore, rare paternal pollen transmission is not simply due to breakdown of normal controls caused by the alien cytoplasm. Furthermore, we have found that the entire plastid genome was transmitted by pollen rather than small plastid genome (ptDNA) fragments. Interestingly, the plants, which inherited paternal plastids, also carried paternal mitochondrial DNA, indicating cotransmission of plastids and mitochondria in the same pollen. The detection of rare paternal plastid transmission described here was facilitated by direct selection for the transplastomic spectinomycin resistance marker in tissue culture; therefore, recovery of rare paternal plastids in the germline is less likely to occur under field conditions.
In vivo
selection for metastasis promoting genes in the mouse
Authors: Gumireddy Kiranmai , Sun Fangxian , Klein-Szanto Andres J. , Gibbins Jonathan M. , Gimotty Phyllis A. , Saunders Aleister J. , Schultz Peter G. , Huang Qihong
Published: April 2007

Here, we report the identification of a metastasis promoting factor by a forward genetic screen in mice. A retroviral cDNA library was introduced into the nonmetastatic cancer cell line 168FARN, which was then orthotopically transplanted into mouse mammary fat pads, followed by selection for cells that metastasize to the lung. The genes encoding the disulfide isomerase ERp5 and β-catenin were found to promote breast cancer invasion and metastasis. Disulfide isomerases (thiol isomerases), which catalyze disulfide bond formation, reduction, and isomerization, have not previously been implicated in cancer cell signaling and tumor metastasis. Overexpression of ERp5 promotes both
in vitro
migration and invasion and
in vivo
metastasis of breast cancer cells. These effects were shown to involve activation of ErbB2 and phosphoinositide 3-kinase (PI3K) pathways through dimerization of ErbB2. Activation of ErbB2 and PI3K subsequently stimulates RhoA and β-catenin, which mediate the migration and invasion of tumor cells. Inhibition of ErbB2 and PI3K reverses the phenotypes induced by ERp5. Finally, ERp5 was shown to be up-regulated in human surgical samples of invasive breast cancers. These data identify a link between disulfide isomerases and tumor development, and provide a mechanism that modulates ErbB2 and PI3K signaling in the promotion of cancer progression.
Identity of a pathway for saccadic suppression
Authors: Lee Psyche H. , Sooksawate Thongchai , Yanagawa Yuchio , Isa Kaoru , Isa Tadashi , Hall William C.
Published: April 2007

Neurons in the superficial gray layer (SGS) of the superior colliculus receive visual input and excite intermediate layer (SGI) neurons that play a critical role in initiating rapid orienting movements of the eyes, called saccades. In the present study, two types of experiments demonstrate that a population of SGI neurons gives rise to a reciprocal pathway that inhibits neurons in SGS. First, in GAD67-GFP knockin mice, GABAergic SGI neurons that expressed GFP fluorescence were injected with the tracer biocytin to reveal their axonal projections. Axons arising from GFP-positive neurons in SGI terminated densely in SGS. Next, SGI neurons in rats and mice were stimulated by using the photolysis of caged glutamate, and
in vitro
whole-cell patch-clamp recordings were used to measure the responses evoked in SGS cells. Large, synaptically mediated outward currents were evoked in SGS neurons. These currents were blocked by gabazine, confirming that they were GABA
A
receptor-mediated inhibitory postsynaptic currents. This inhibitory pathway from SGI transiently suppresses visual activity in SGS, which in turn could have multiple effects. These effects could include reduction of perceptual blurring during saccades as well as prevention of eye movements that might be spuriously triggered by the sweep of the visual field across the retina.
Regulation of CNS synapses by neuronal MHC class I
Authors: Goddard C. Alex , Butts Daniel A. , Shatz Carla J.
Published: April 2007

Until recently, neurons in the healthy brain were considered immune-privileged because they did not appear to express MHC class I (MHCI). However, MHCI mRNA was found to be regulated by neural activity in the developing visual system and has been detected in other regions of the uninjured brain. Here we show that MHCI regulates aspects of synaptic function in response to activity. MHCI protein is colocalized postsynaptically with PSD-95 in dendrites of hippocampal neurons.
In vitro
, whole-cell recordings of hippocampal neurons from β2m/TAP1 knockout (KO) mice, which have reduced MHCI surface levels, indicate a 40% increase in mini-EPSC (mEPSC) frequency. mEPSC frequency is also increased 100% in layer 4 cortical neurons. Similarly, in KO hippocampal cultures, there is a modest increase in the size of presynaptic boutons relative to WT, whereas postsynaptic parameters (PSD-95 puncta size and mEPSC amplitude) are normal. In EM of intact hippocampus, KO synapses show a corresponding increase in vesicles number. Finally, KO neurons
in vitro
fail to respond normally to TTX treatment by scaling up synaptic parameters. Together, these results suggest that postsynaptically localized MHCl acts in homeostatic regulation of synaptic function and morphology during development and in response to activity blockade. The results also imply that MHCI acts retrogradely across the synapse to translate activity into lasting change in structure.
A conserved phosphatase cascade that regulates nuclear membrane biogenesis
Authors: Kim Youngjun , Gentry Matthew S. , Harris Thurl E. , Wiley Sandra E. , Lawrence John C. , Dixon Jack E.
Published: April 2007

A newly emerging family of phosphatases that are members of the haloacid dehalogenase superfamily contains the catalytic motif DXDX(T/V). A member of this DXDX(T/V) phosphatase family known as Dullard was recently shown to be a potential regulator of neural tube development in
Xenopus
[Satow R, Chan TC, Asashima M (2002)
Biochem Biophys Res Commun
295:85–91]. Herein, we demonstrate that human Dullard and the yeast protein Nem1p perform similar functions in mammalian cells and yeast cells, respectively. In addition to similarity in primary sequence, Dullard and Nem1p possess similar domains and show similar substrate preferences, and both localize to the nuclear envelope. Additionally, we show that human Dullard can rescue the aberrant nuclear envelope morphology of
nem1
Δ yeast cells, functionally replacing Nem1p. Finally, Nem1p, has been shown to deposphorylate the yeast phosphatidic acid phosphatase Smp2p [Santos-Rosa H, Leung J, Grimsey N, Peak-Chew S, Siniossoglou S (2005)
EMBO J
24:1931–1941], and we show that Dullard dephosphorylates the mammalian phospatidic acid phosphatase, lipin. Therefore, we propose that Dullard participates in a unique phosphatase cascade regulating nuclear membrane biogenesis, and that this cascade is conserved from yeast to mammals.
Cis binding between inhibitory receptors and MHC class I can regulate mast cell activation
Authors: Masuda Ai , Nakamura Akira , Maeda Tsutomu , Sakamoto Yuzuru , Takai Toshiyuki
Published: April 2007

Allergy is caused by immune effector cells, including mast cells and basophils. Cellular signaling that activates these effector cells is regulated by different inhibitory receptors on their surface. We show that human leukocyte immunoglobulin (Ig)-like receptor (LILR) B2 and its mouse orthologue, paired Ig-like receptor (PIR)–B, constitutively associate to major histocompatibility complex (MHC) class I on the same cell surface (in cis). The IgE-mediated effector responses were augmented in β2-microglobulin (β2m) and PIR-B–deficient mast cells. In addition, the increased cytokine production of β2m-deficient mast cells was not affected by the co-culture with MHC class I–positive mast cells, showing that less cis interaction between PIR-B and MHC class I on mast cells led to the increased cytokine release. Thus, the constitutive cis binding between LILRB2 or PIR-B and MHC class I has an essential role in regulating allergic responses.
The discovery value of “Big Science”
Authors: Esparza José , Yamada Tadataka
Published: April 2007

The increasing complexity of biomedical research is leading to the exploration of new models for large-scale collaborative research. This Big Science approach, however, has created anxieties and potential tensions between investigator-driven research, and research guided by a more organized, collaborative effort. Another potential tension exists between research conducted purely in search of new knowledge and research aimed at finding solutions. We argue that big biomedicine—the work of coordinated multidisciplinary groups that use the latest technologies to solve complex problems—can be an important way to harness the creativity of individual investigators, stimulate innovation, and supply the infrastructure, experimental systems, and resources needed to solve the urgent health problems confronted by our global society. We discuss this using the example of the Global HIV Vaccine Enterprise.
CpG methylation is targeted to transcription units in an invertebrate genome
Authors: Suzuki Miho M. , Kerr Alastair R.W. , De Sousa Dina , Bird Adrian
Published: April 2007

DNA is methylated at the dinucleotide CpG in genomes of a wide range of plants and animals. Among animals, variable patterns of genomic CpG methylation have been described, ranging from undetectable levels (e.g., in Caenorhabditis elegans) to high levels of global methylation in the vertebrates. The most frequent pattern in invertebrate animals, however, is mosaic methylation, comprising domains of methylated DNA interspersed with unmethylated domains. To understand the origin of mosaic DNA methylation patterns, we examined the distribution of DNA methylation in the Ciona intestinalis genome. Bisulfite sequencing and computational analysis revealed methylated domains with sharp boundaries that strongly colocalize with ∼60% of transcription units. By contrast, promoters, intergenic DNA, and transposons are not preferentially targeted by DNA methylation. Methylated transcription units include evolutionarily conserved genes, whereas the most highly expressed genes preferentially belong to the unmethylated fraction. The results lend support to the hypothesis that CpG methylation functions to suppress spurious transcriptional initiation within infrequently transcribed genes.
Effects of paradigm and inter-stimulus interval on age differences in eyeblink classical conditioning in rabbits
Authors: Woodruff-Pak Diana S. , Seta Susan E. , Roker LaToya A. , Lehr Melissa A.
Published: April 2007

The aim of this study was to examine parameters affecting age differences in eyeblink classical conditioning in a large sample of young and middle-aged rabbits. A total of 122 rabbits of mean ages of 4 or 26 mo were tested at inter-stimulus intervals (ISIs) of 600 or 750 msec in the delay or trace paradigms. Paradigm affected both age groups dramatically, with superior performance in the delay paradigm. ISI was salient as middle-aged rabbits were significantly impaired in 750-msec compared with 600-msec delays, and young rabbits were significantly less impaired in 600-msec than in 750-msec trace. Young rabbits performed equally well at both delay ISIs, and consequently, there were significant age differences in 750-msec but not in 600-msec delays. Middle-aged rabbits performed poorly at both 600- and 750-msec trace, resulting in significant age differences in 600-msec but not in 750-msec trace. Timing of the conditioned response has been associated with cerebellar cortical function. Normal aging of the cerebellar cortex likely contributed to the magnitude of the effect of ISI in delay conditioning in middle-aged rabbits. Results demonstrate that the magnitude of age differences in eyeblink conditioning can be enlarged or eliminated by ISI and paradigm.
Crystal structure of the tetrameric inositol 1‐phosphate phosphatase (TM1415) from the hyperthermophile, Thermotoga maritima
Authors: Stieglitz Kimberly A. , Roberts Mary F. , Li Weizhong , Stec Boguslaw
Published: April 2007

The structure of the first tetrameric inositol monophosphatase (IMPase) has been solved. This enzyme, from the eubacterium Thermotoga maritima, similarly to its archaeal homologs exhibits dual specificity with both IMPase and fructose‐1,6‐bisphosphatase activities. The tetrameric structure of this unregulated enzyme is similar, in its quaternary assembly, to the allosterically regulated tetramer of fructose‐1,6‐bisphosphatase. The individual dimers are similar to the human IMPase. Additionally, the structures of two crystal forms of IMPase show significant differences. In the first crystal form, the tetrameric structure is symmetrical, with the active site loop in each subunit folded into a β‐hairpin conformation. The second form is asymmetrical and shows an unusual structural change. Two of the subunits have the active site loop folded into a β‐hairpin structure, whereas in the remaining two subunits the same loop adopts an α‐helical conformation.
Randomized exposure‐controlled trials; impact of randomization and analysis strategies
Authors: Karlsson Kristin E. , Grahnén Anders , Karlsson Mats O. , Jonsson E. Niclas
Published: April 2007

What is already known about this subject

• When characterizing an exposure–response relationship it has been suggested that the randomized concentration‐controlled trial (RCCT) is potentially a more informative design than a randomized dose‐controlled trial design (RDCT).

• Traditionally, these trials have been analysed by group‐wise comparison or similar statistics.

• The aim of this study was to compare different randomization schemes when a model‐based analysis has been performed.

What this study adds

• Alternative randomization schemes may not have the proposed advantages if a model‐based analysis is employed.

Aims

In the literature, five potential benefits of randomizing clinical trials on concentration levels, rather than dose, have been proposed: (i) statistical study power will increase; (ii) study power will be less sensitive to high variability in the pharmacokinetics (PK); (iii) the power of establishing an exposure–response relationship will be robust to correlations between PK and pharmacodynamics (PD); (iv) estimates of the exposure–response relationship are likely to be less biased; and (v) studies will provide a better control of exposure in situations with toxicity issues. The main aim of this study was to investigate if these five statements are valid when the trial results are evaluated using a model‐based analysis.

Methods

Quantitative relationships between drug dose, concentration, biomarker and clinical end‐point were defined using pharmacometric models. Three randomization schemes for exposure‐controlled trials, dose‐controlled (RDCT), concentration‐controlled (RCCT) and biomarker‐controlled (RBCT), were simulated and analysed according to the models.

Results

(i) The RCCT and RBCT had lower statistical power than RDCT in a model‐based analysis; (ii) with a model‐based analysis the power for an RDCT increased with increasing PK variability; (iii) the statistical power in a model‐based analysis was robust to correlations between CL and EC50 or Emax; (iv) under all conditions the bias was negligible (<3%); and (v) for studies with equal power RCCT could produce either more or fewer adverse events compared with an RDCT.

Conclusion

Alternative randomization schemes may not have the proposed advantages if a model‐based analysis is employed.
Is attachment style a source of resilience against health inequalities at work?
Authors: Reading Richard
Published: April 2007

Bartley, M.,
Head, J. &
Stansfeld, S.
(
2007
)

,
64
,
765
–
775
.
 
DOI: 10.1016/j.socscimed.2006.09.033.
A randomized comparison of the effect of two prelinguistic communication interventions on the acquisition of spoken communication in preschoolers with ASD
Authors: Temple Kathryn
Published: April 2007

.
 
Yoder, P. &
Stone, W. P.
(
2006
)

,
49
,
698
–
711
.

Purpose  This randomized group experiment compared the efficacy of two communication interventions [Responsive Education and Prelinguistic Milieu Teaching (RPMT) and the Picture Exchange Communication System (PECS)] on spoken communication in 36 pre‐schoolers with autism spectrum disorders (ASD).

Method  Each treatment was delivered to children for a maximum total of 24 h over a 6‐month period. Spoken communication was assessed in a rigorous test of generalization at pretreatment, post‐treatment and 6‐month follow‐up periods.

Results  Picture Exchange Communication System was more successful than RPMT in increasing the number of non‐imitative spoken communication acts and the number of different non‐imitative words used at the post‐treatment period. Considering growth over all three measurement periods, an exploratory analysis showed that growth rate of the number of different non‐imitative words was faster in the PECS group than in the RPMT group for children who began treatment with relatively high object exploration. In contrast, analogous slopeswere steeper in the RPMT group than in the PECS group for children who began treatment with relatively low object exploration.
Impact of a theoretically based sex education programme (SHARE) delivered by teachers on NHS registered conceptions and terminations: final results of cluster randomised trial
Authors: Reading Richard
Published: April 2007

.
 
Henderson, M.,
Wight, D.,
Raab, G. M.,
Abraham, C.,
Parkes, A.,
Scott, S. &
Hart, G.
(
2007
)

,
334
,
133
–
6
.
 
DOI: 10.1136/bmj.39014.503692.55.

Objective  To assess the impact of a theoretically based sex education programme (SHARE) delivered by teachers compared with conventional education in terms of conceptions and terminations registered by the National Health Service.

Design  Follow‐up of cluster randomized trial 4.5 years after intervention.

Setting  National Health Service records of women who had attended 25 secondary schools in east Scotland.

Participants  A total of 4196 women (99.5% of those eligible).

Intervention  SHARE programme (intervention group) vs. existing sex education (control group).

Main outcome measure  National Health Service recorded conceptions and terminations for the achieved sample linked at age 20 years.

Results  In an ‘intention to treat’ analysis, there were no significant differences between the groups in registered conceptions per 1000 pupils (300 SHARE vs. 274 control; difference 26, 95% CI −33 to 86) and terminations per 1000 pupils (127 vs. 112; difference 15, −13 to 42) between ages 16 and 20 years.

Conclusions  This specially designed sex education programme did not reduce conceptions or terminations by age 20 years compared with conventional provision. The lack of effect was not due to quality of delivery. Enhancing teacher‐led school sex education beyond conventional provision in eastern Scotland is unlikely to reduce terminations in teenagers.
Physical activity to prevent obesity in young children: cluster randomised controlled trial
Authors: Reading Richard
Published: April 2007

.
 
Reilly, J. J.,
Kelly, L.,
Montgomery, C.,
Williamson, A.,
Fisher, A.,
McColl, J. H.,
Lo Conte, R.,
Paton, J. Y. &
Grant, S.
(
2006
)

,
333
,
1041
 
DOI: 10.1136/bmj.38979.623773.55.

Objective  To assess whether a physical activity intervention reduces body mass index in young children.

Design  Cluster randomized controlled single blinded trial over 12 months.

Setting  Thirty‐six nurseries in Glasgow, Scotland.

Participants  In total, 545 children in their pre‐school year, mean age 4.2 years (SD 0.2) at baseline.

Intervention  Enhanced physical activity programme in nursery (three 30‐minute sessions a week over 24 weeks) plus home‐based health education aimed at increasing physical activity through play and reducing sedentary behaviour.

Main outcome measure  Body mass index, expressed as a standard deviation score relative to UK 1990 reference data. Secondary measures were objectively measured physical activity and sedentary behaviour; fundamental movement skills; and evaluation of the process.

Results  Group allocation had no significant effect on the primary outcome measure at 6 and 12 months or on measures of physical activity and sedentary behaviour by accelerometry. Children in the intervention group had significantly higher performance in movement skills tests than control children at 6‐month follow‐up (P = 0.0027; 95% CI 0.3–1.3) after adjustment for sex and baseline performance.

Conclusions  Physical activity can significantly improve motor skills but did not reduce body mass index in young children in this trial.
Clinical review: chronic constipation in children
Authors: Reading Richard
Published: April 2007

.
 
Rubin, G. &
Dale, A.
(
2006
)

,
333
,
1051
–
1055
.
 
DOI: 10.1136/bmj.39007.760174.47.
Older and wiser: improvements in breeding success are linked to better foraging performance in European shags
Authors: DAUNT F. , WANLESS S. , HARRIS M. P. , MONEY L. , MONAGHAN P.
Published: April 2007

An increase in average breeding performance with age and experience among younger age classes has been recorded in numerous studies of iteroparous breeders. An important component of this pattern is thought to be improvements in foraging performance, resulting in delivery of more or better quality food to offspring by older, more experienced individuals.

Young, inexperienced breeders may exhibit lower foraging efficiency or foraging effort, and it has been predicted that differences in foraging performance with age and experience will be more marked when environmental conditions are poor. However, as the timing of breeding generally differs with age and experience, intrinsic differences in foraging abilities are typically confounded by variation in extrinsic conditions, and hence food availability.

To disentangle these effects, we experimentally manipulated the timing of breeding in European shags, Phalacrocorax aristotelis Linnaeus. We used a cross‐fostering protocol, such that naive, young birds reared their chicks at the same time as older, experienced individuals. Our design produced simultaneous chick rearing during two periods in the same breeding season that differed markedly in environmental conditions: early, when conditions were good; and late, when conditions were poorer. We examined foraging efficiency, foraging effort and amount of food delivered to offspring by the two classes of breeder. We predicted that any differences in foraging performance would be more marked under the poorer conditions later in the season.

We found that experienced parents delivered more food than naive parents, irrespective of the time of season. This was due partly to the consistently higher foraging efficiency of the experienced parents. In addition, experienced parents adjusted their foraging effort to the environmental conditions. Early in the breeding season, they made less foraging effort than naive parents. Under the poorer foraging conditions, experienced parents increased their foraging effort but naive parents did not, being either unable or unwilling to do so.

Our results suggest that an increase in foraging efficiency, and the capacity to adjust foraging effort in response to food availability, are important components of the observed improvements in breeding performance with age and experience.
Secondary forest growth deviation from chronosequence predictions in central Amazonia
Authors: FELDPAUSCH TED R. , PRATES‐CLARK CASSIA da CONCEICAO , FERNANDES ERICK C.M. , RIHA SUSAN J.
Published: April 2007

Nearly all published rates of secondary forest (SF) regrowth for Amazonia are inferred from chronosequences. We examined SF regrowth on abandoned pastures over a 4‐year period to determine if measured rates of forest recovery differ from chronosequence predictions. We studied the emergence, development and death of over 1300 stems in 10 SFs representing three age classes (<1–5, 6–10 and 11–14 years old). Mean tree biomass accumulation in both the <1–5 and 6–10 years old (4.4 and 5.7 Mg ha−1 yr−1, respectively) abandoned pastures was lower than predicted and deviated significantly (57% and 41%) from rates estimated from the chronosequence. The older SFs, with a mean growth rate of 9.9 Mg ha−1 yr−1 followed the rate predicted by the chronosequence. Understocking was the primary cause of low biomass recovery rates in the youngest forests; although the youngest stands had a diameter at breast height increment three times the oldest stands, the youngest stands lacked sufficient density to cumulatively produce high biomass accumulation rates. Four years of measurement indicated that the youngest stands had developed 59% of the stems measured in the older stands during the same time period. The 6–10‐year‐old stands were rapidly self‐thinning and approached stem density values measured in the same aged stands at the onset of the study. Mortality was high for all stands, with 54% of the original stems remaining after 4 years in intermediate‐aged stands. The forests were dominated by the tree Vismia, which represented 55–66% of the biomass in all stands. The Vismia share of the biomass was decreasing over time, with other genera replacing the pioneer. Our measured rates of regrowth indicate that generalized estimates of forest regrowth through chronosequence studies will overestimate forest regrowth for the youngest forests that were under land use for longer time‐periods before abandonment. Certified Emission Reductions under the Clean Development Mechanism of the Kyoto protocol should consider these results when predicting and compensating for carbon sequestered under natural forest management.
Predicting naturalization of southern African Iridaceae in other regions
Authors: VAN KLEUNEN MARK , JOHNSON STEVEN D. , FISCHER MARKUS
Published: April 2007

One of the major challenges in invasion biology is to predict the likelihood of naturalization, and ultimately invasiveness, of species from properties that can be assessed in the native range prior to a species’ introduction elsewhere. This is particularly relevant as intentional introduction for horticultural usage has been predicted to be the over‐riding factor associated with naturalization.

 We compiled a data set on 1036 species of Iridaceae native to southern Africa to test whether traits differ between horticulturally used and unused species, whether the likelihood of naturalization elsewhere is higher for horticulturally used species, and whether it differs according to species’ taxonomic affinities, geographical range size, altitudinal range, number of subtaxa and plant size.

 Our results show that at least 306 southern African Iridaceae species are used in horticulture elsewhere. Of the 67 that have become naturalized elsewhere, no less than 62 are in horticulture, indicating horticultural trade as the main source of naturalized Iridaceae.

 Global horticultural usage differs among the three subfamilies and among the genera. In addition, horticultural usage is more likely for species with a larger distributional range, a lower maximum altitude, more subtaxa and a taller height. This indicates that species introduced elsewhere for horticultural usage have a biased set of biogeographical and biological characteristics that should be corrected for in analyses of naturalization.

 After correction for horticultural usage, naturalization differs between genera, and is more likely for species with lower maximum altitude, species with higher numbers of subtaxa and taller species.

 Cross‐validation of our predictive logistic regression model revealed a low kappa (0·279 ± 0·069, mean ± SE) that was significantly different from zero. This indicates that the estimates from our logistic regression model can be used to predict naturalization of Iridaceae but that the accuracy is relatively low.

Synthesis and applications. Our study shows that screening protocols for potential invasiveness of species of Iridaceae should include international horticultural usage, and taxonomic, biogeographical and biological characteristics in the native range, as predictors. Moreover, for the development of more accurate predictive models, experimental assessment of other plant characteristics associated with naturalization is still required.
Effects of habitat quality and fishing on Caribbean spotted spiny lobster populations
Authors: WYNNE STUART P. , CÔTÉ ISABELLE M.
Published: April 2007

Overfishing has had detrimental impacts on many marine populations. However, measurements of the effect of exploitation are often confounded by intersite differences in habitat quality.

To assess the effects of fishing and habitat quality on spotted spiny lobster Panulirus guttatus, the target of a luxury fishery in the Caribbean, lobster populations were assessed on 12 reefs around Anguilla, British West Indies. Habitat quality was measured by the availability of foraging habitat. Fishing intensity was estimated through interviews with fishers.

Spotted spiny lobster densities were significantly higher on reefs with good‐quality habitat than on poorer‐quality reefs. However, mean lobster size remained constant regardless of habitat quality.

 In contrast, lobsters were on average smaller in heavily fished than in unfished areas because of the removal of the largest size classes by fishers. Changes in densities as a result of fishing could not be detected, and there was no interaction between fishing pressure and habitat quality.

The lack of an observable effect of fishing on lobster population densities may be because fishers more intensively target high‐quality habitats. Fishing has probably reduced lobster densities on high‐quality reefs to a greater extent than on low‐quality reefs, but the high productivity of good‐quality sites is still sustaining more intense fishing.

Synthesis and applications. The importance of habitat quality in sustaining P. guttatus populations in the face of intense exploitation suggests that management efforts should be aimed at enhancing reef health. The latter may be achieved through the establishment of no‐take areas on good‐quality reefs. Such actions should, however, be expected to generate conflicts with stakeholders because these reefs are currently those most heavily exploited.
Epidemiology, genes and the environment: lessons learned from the Helsinki Birth Cohort Study
Authors: Eriksson J. G.
Published: April 2007

Nonoptimal growth during fetal life and infancy is associated with an increased risk of coronary heart disease and type 2 diabetes later in life. This early pattern of growth is associated with an increased disease risk especially when followed by a relative gain in body size later in childhood. Genetic factors are closely involved in growth and disease pathogenesis and gene‐early life environmental interactions will be described affecting adult health outcomes. This overview will primarily focus upon findings from the Helsinki Birth Cohort Study consisting of 15846 subjects born 1924–1944 on whom growth data and information on adult health are available.
Intraperitoneal immunization with oligomannose‐coated liposome‐entrapped soluble leishmanial antigen induces antigen‐specific T‐helper type immune response in BALB/c mice through uptake by peritoneal macrophages
Authors: SHIMIZU Y. , TAKAGI H. , NAKAYAMA T. , YAMAKAMI K. , TADAKUMA T. , YOKOYAMA N. , KOJIMA N.
Published: April 2007

The present study demonstrates that the intraperitoneal administration of soluble leishmanial antigen (SLA) entrapped in liposomes coated with neoglycolipids containing oligomannose residues (mannopentaose or mannotriose) strongly induces an antigen‐specific T‐helper type 1 (Th1) immune response in BALB/c mice. In response to in vitro stimulation with SLA, spleen cells from mice that had received oligomannose‐coated liposomes encasing SLA (SLA‐OML) displayed greater interferon (IFN)‐γ and interleukin (IL)‐2 production and lower IL‐4 and IL‐5 production than spleen cells from mice that had received SLA alone, indicating that the SLA‐specific Th1 immune response had predominantly been induced in the mice that had received SLA‐OML. After subsequent infection with Leishmania major, mice that had received SLA‐OML were effectively protected against the disease, with a predominant production of IFN‐γ. OML were preferentially and rapidly incorporated into peritoneal macrophages, and the transplantation of macrophages containing SLA‐OML into the peritoneal cavity also induced protection against L. major infection. Thus, SLA‐OML were shown to successfully induce a specific Th1 immune response capable of controlling L. major infection in BALB/c mice through the effective uptake of OML by peritoneal macrophages.
Differential immune regulation of activated T cells between cutaneous and mucosal leishmaniasis as a model for pathogenesis
Authors: CARVALHO L. P. , PASSOS S. , BACELLAR O. , LESSA M. , ALMEIDA R. P. , MAGALHÃES A. , DUTRA W. O. , GOLLOB K. J. , MACHADO P. , Ribeiro DE JESUS A.
Published: April 2007

Cutaneous (CL) and mucosal leishmaniasis (ML) are characterized by a predominant type 1 immune response (IFN‐γ and TNF‐α production) and strong inflammatory response in the lesions with few parasites. This exacerbated type 1 response is more evident in ML as compared to CL. Our main hypothesis is that a differential immune regulation of T cell activation leads to over reactive T cells in ML. In the present study, we investigated immunological factors that could explain the mechanisms behind it by comparing some immune regulatory mechanisms between ML and CL patients: frequency of cells expressing co‐stimulatory molecules, apoptotic markers, T cell activation markers; and ability of neutralizing antibodies to IL‐2, IL‐12 and IL‐15 do down‐regulate IFN‐γ production in leishmania antigen‐stimulated peripheral blood mononuclear cells (PBMC). Interestingly, in CL anti‐IL‐2 and anti‐IL‐15 significantly suppressed antigen‐specific IFN‐γ production, while in ML only anti‐IL‐2 suppressed IFN‐γ production. Finally, higher frequency of CD4+ T cells expressing CD28−, CD69+ and CD62L

low

were observed in ML as compared to CL. These data indicate that an exacerbated type 1 response in ML is differentially regulated and not appropriately down modulated, with increased frequencies of activated effectors T cells, maintaining the persistent inflammatory response and tissue damage observed in ML.
Chronic exposure to schistosome eggs reduces serum cholesterol but has no effect on atherosclerotic lesion development
Authors: LA FLAMME A. C. , HARVIE M. , KENWRIGHT D. , CAMERON K. , RAWLENCE N. , LOW Y. S. , MCKENZIE S.
Published: April 2007

Previous studies have shown that people infected with schistosomiasis have lower levels of serum cholesterol than uninfected controls. To better understand the impact of this parasitic infection on serum cholesterol levels and on atherosclerotic lesion development induced by hypercholesterolemia, apolipoprotein E (ApoE)‐deficient mice were chronically exposed to the eggs of Schistosoma mansoni over a period of 16 weeks. Total serum cholesterol and low‐density lipoprotein (LDL) were reduced in egg‐exposed ApoE‐deficient mice fed a diet high in cholesterol compared to unexposed controls. However, exposure to eggs had no effect on atherosclerotic lesion size or progression in ApoE‐deficient mice. Macrophages isolated from egg‐exposed mice had an enhanced ability to take up LDL but not acetylated LDL (acLDL). This study suggests that schistosome eggs alone may alter serum lipid profiles through enhancing LDL uptake by macrophages, but these changes do not ultimately affect atherosclerotic lesion development.
Problems encountered during immunofluorescent diagnosis of fireblight
Authors: ROBERTS PAULINE
Published: April 2007

An immunofiuorescent (fluorescent antibody or FA) staining technique was used to detect Erwinia amylovora (Burrill) Winslow et al. in plant tissue, but in preliminary trials it failed to do so in a majority of preparations from fireblight‐infected plants. Differential centrifugation greatly improved the rate of detection of E. amylovora in plant tissue. Ctiltures of E. herbicola subsp. ananas (Serrano) Dye, E. stewartii (Smith) Dye, E. rhapontici (Millard) Burkholder and two plant isolates (probably Pseudomonas fiuorescens (Trevisan) Migula and E. herbicola subsp. herbicola (Lohnis) Dye) cross‐reacted with E. amylovora in the FA stain. Of these only the Ps. fiuorescens isolate and a different plant isolate of E.h. subsp. herbicola cross‐reacted with E. amylovora anti‐serum in the slide agglutination test. Use of absorbed E. amylovora antiserum completely eliminated cross reactions in the slide agglutination test, but only partly removed cross reactions in the FA stain. Immunofluorescence appeared to be more sensitive but less reliable than conventional plating methods for fireblight diagnosis.
Comparison of virulence of isolates of Fusarium oxysporum f.sp. elaeidis from Africa and South America
Authors: FLOOD J. , MEPSTED R. , VELEZ A. , PAUL T. , COOPER R. M.
Published: April 2007

The virulences of three isolates of Fusarium oxysporum f.sp. elaeidis from West Africa were compared with that of a Brazilian isolate. The Brazilian strain was more virulent and caused disease in all oil‐palm lines tested, even those which had been selected for resistance to, and were generally unaffected by, African strains. Differential interactions between hosts and isolates of the pathogen could have serious implications for selection of breeding material and for the extension of oil‐palm cultivation in South America.
Effect of packed red blood cells transfusion on plasma fibronectin during liver resection
Authors: Kostopanagiotou G. , Pandazi A. , Matsota P. , Arkadopoulos N. , Dalamanga N. , Politou M. , Traulou O. , Smyrniotis V.
Published: April 2007

summary Our study aimed at evaluating the effect of blood transfusion – allogeneic or autologous – on plasma levels of fibronectin during liver resections. Thirty‐five patients scheduled for liver resection were randomly allocated to receive autologous (group autologous blood transfusion (ABT), n= 19) or allogeneic (homologous) (homologous blood transfusion (HBT), n= 16) packed red blood cell to maintain serum haemoglobin concentration above 9 g. Serum levels of fibronectin were measured before induction of anaesthesia, at the end of operation and at first, third and sixth postoperative day. Perioperative morbidity and survival rate were also recorded. Serum fibronectin levels were significantly higher (P < 0·05) in the autologous group than in the allogeneic, at the first (134 ± 49 μg mL−1 vs. 89 ± 31 μg mL−1) and third (178 ± 51 μg mL−1 vs. 96 ± 41 μg mL−1) postoperative day. No differences in survival and complication rate between the two groups were observed. Concentrations of serum fibronectin seem to be adversely affected by allogeneic blood transfusion during liver resection surgery, although this does not seem to affect patients’ morbidity and mortality.
Cardiac metastasis of renal pelvic cancer
Authors: Murakami Takayuki , Komiya Atsushi , Mikata Kunihisa , Kaneko Shigeki , Ikeda Ichiro
Published: April 2007

Abstract:  A 66‐year‐old man was referred to our hospital with chest discomfort and shortness of breath. Seven months previously he had undergone a laparoscopic left nephroureterectomy for a left renal pelvic tumor and was given two cycles of adjuvant chemotherapy (methotrexate, epirubicin and cisplatin). Echocardiogram showed an 8‐mm sized mass extending from the right atrium into the right ventricle. On computed tomography, multiple lung tumors, as well as the right atrial and ventricular mass, were seen. The patient died of acute heart failure caused by right ventricular outflow obstruction. On autopsy, a right atrial and ventricular metastasis of the initial transitional cell carcinoma was found. The patient’s cause of death was acute heart failure as a result of cardiac metastasis of his initial renal pelvic carcinoma.
Establishment and characterization of androgen‐independent human prostate cancer cell lines, LN‐REC4 and LNCaP‐SF, from LNCaP
Authors: Iwasa Yoichi , Mizokami Atsushi , Miwa Sotaro , Koshida Kiyoshi , Namiki Mikio
Published: April 2007

Aim:  To investigate the mechanisms of androgen‐independent growth in prostate cancer (PCa), we established two PCa cell lines, LN‐REC4 and LNCaP‐SF, from the androgen‐dependent PCa cell line, LNCaP.

Materials and methods:  LN‐Pre and LN‐REC4 cells were generated from LNCaP tumors grown on intact and castrated severe combined immunodeficient (SCID) mouse, respectively. After we cultured LNCaP cells under a steroid‐free conditions for 6 months in vitro, LNCaP‐SF cells were established. To show the character of LN‐REC4 and LNCaP‐SF cells, androgen sensitivity was investigated through examination of growth rate, and prostate‐specific antigen (PSA), androgen receptor (AR), p21, p27, and cyclin D1 expression were examined by reverse transcription‐polymerase chain reaction (RT‐PCR). Angiogenesis assay in vitro was carried out using conditioned medium. To examine the expression level of vascular endothelial growth factor (VEGF), RT‐PCR and enzyme‐linked immunosorbent assay were also done.

Results and conclusions:  LN‐REC4 cells proliferated better than LNCaP cells in castrated mice and did well irrespective of castration, although responsiveness for androgen of LN‐REC4 cells attenuated less than that of LNCaP cells in vitro. LNCaP‐SF cells in castrated mice proliferated more rapidly than in normal mice. The PSA expression in LNCaP‐SF cells was still induced by androgen. Expression of AR, p21, p27 and cyclin D1 were not changed in LN‐REC4 and LNCaP‐SF cells. Angiogenesis assay showed that both cells stimulated angiogenesis. LN‐REC4 induced VEGF more than LNCaP and LN‐Pre cells. However, expression of VEGF per cell in LNCaP‐SF was lower than LNCaP cells, suggesting that other factors might be involved in angiogenesis. These cell lines might be a useful tool for researching androgen‐independent growth and treatments of recurred PCa.
Leiomyoma of the corpus cavernosum of the penis
Authors: Liu Shih‐Ping , Shun Chia‐Tung , Chang Shang‐Jen , Chen Jun , Hsieh Ju‐Ton
Published: April 2007

Abstract:  While soft tissue tumors can occur in the penis, corpus cavernous tumors are rare. Reported cases of corpus cavernous tumors are from metastases of advanced malignancy, such as cancers of the bladder, prostate, rectosigmoid colon, kidney, pancreas, liver, testis and nasopharynx. Primary corpus cavernous tumors are extremely rare and have possibly never been reported before. Herein, we report a case of leiomyoma of the corpus cavernosum. After the diagnosis of leiomyoma was established, total excision of the tumor was not attempted and the tumor remained unchanged in size and shape over a follow‐up period of 15 months.
Ipsilateral right testicular metastasis from renal cell carcinoma in a responder patient to interleukine‐2 treatment
Authors: Camerini Andrea , Tartarelli Gianna , Martini Leonardo , Donati Sara , Puccinelli Paolo , Amoroso Domenico
Published: April 2007

Abstract:  We present a case of metastatic spreading to the testicle in a 46‐year‐old patient with renal cell carcinoma, ‘clear‐cell’ type, during interleukin‐2 combined subcutaneous plus aerosol treatment. Testicular metastasis occurred while the patient showed a response to the treatment with disappearance of lung lesions and reduction of lymph‐nodes lesions. After orchiectomy with spermatic cord resection and disease re‐evaluation confirming the previous response, the patient re‐started immunotherapy. The contrast between systemic disease response to treatment and disease testicular progression might be explained by a relative insensitivity of the testicle to interleukin‐2 immunotherapy as a result of a possible establishment of an immunosuppressive microenvironment. We believe that the rarity of this metastatic site and the intriguing possible mechanisms at its base, makes an interesting case for clinicians.
Complex urethral disruptions: In pursuit of a successful reconstruction
Authors: Pratap Akshay , Gupta Devendra Kumar , Agrawal Chandra Shekhar , Pandit Rakesh Kumar , Adhikary Shailesh , Kumar Anand , Tiwari Awadhesh , Singh Satyendra Narayan
Published: April 2007

Objectives:  We analyzed the methods and outcomes of urethroplasty in men with complex urethral disruptions.

Methods:  The medical records of 40 men with complex urethral disruptions were analyzed. Surgical methods were individualized according to stricture location, severity and length of the stricture, bladder neck characteristics and presence of complicating factors. Patients were divided into four groups based on the above characteristics.

Results:  End‐to‐end urethroplasty performed in six patients with short bulbar strictures (<3 cm) was successful in all. Elaborated perineal repair was performed in 10 patients with intermediate (3–6 cm) strictures with or without complicating factors. Elaborated perineal repair with urethral substitution was performed in nine patients with long segment stricture (>6 cm). Abdominal transpubic repair was successfully applied to patients with rectourethral fistula or lacerated bladder neck. Success rate of anastomotic urethroplasty was 95% while over all success rate was 85%.

Conclusion:  Guidelines for urethral reconstruction of complex urethral disruptions are predicated on stricture length, location, bladder neck characteristics and associated complicating factors. End‐to‐end urethroplasty with stricture excision is highly reliable for short strictures for which previous operative repair have failed. Elaborated perineal repair is extremely versatile for intermediate and longer strictures with associated complicating factors. Abdominal transpubic urethroplasty is effective for patients with rectourethral fistula or lacerated bladder neck.