bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of variation in CYP11B1 and CYP11B2 on corticosteroid phenotype and hypothalamic–pituitary–adrenal axis activity in hypertensive and normotensive subjects
Authors: Freel E. M. , Ingram M. , Wallace A. M. , White A. , Fraser R. , Davies E. , Connell J. M. C.
Published: April 2008

Background  Aldosterone is important in the development of hypertension. We have shown that a single nucleotide polymorphism (SNP) (–344T) in the 5′ regulatory region (UTR) of the gene encoding aldosterone synthase (CYP11B2) associates with aldosterone excess and hypertension as well as altered adrenal 11‐hydroxylation efficiency (deoxycortisol to cortisol). This conversion is carried out by the enzyme 11β‐hydroxylase, encoded by the adjacent gene, CYP11B1. We proposed that the effects of CYP11B2 are explained by linkage disequilibrium (LD) across the CYP11B locus. We have demonstrated high LD across this locus and identified two SNPs in the 5′ UTR of CYP11B1 (–1859 G/T, –1889 A/G) that associate with reduced transcription in vitro and altered 11‐hydroxylation efficiency in vivo. Accordingly, we hypothesized that the reduced adrenal 11‐hydroxylation may lead to chronic resetting of the pituitary–adrenal axis, with chronically increased ACTH drive resulting in aldosterone excess.

Methods  To test this, we examined hypothalamic–pituitary–adrenal (HPA) axis activity in hypertensive and normotensive individuals stratified according to genotype at CYP11B2 (–344T/C) and CYP11B1 (–1859 G/T, –1889 A/G). Fifty‐six subjects homozygous for CYP11B2 SNP (27 TT, 12 CC), and 38 homozygous for CYP11B1 SNPs (18 TTGG, 20 GGAA) were recruited. Diurnal variation and the effects of dexamethasone suppression and ACTH stimulation on plasma aldosterone, cortisol and ACTH under controlled conditions were studied.

Results  Subjects with SNPs associated with reduced 11‐hydroxylation efficiency (–344T CYP11B2; TTGG CYP11B1) showed reduced inhibition of ACTH after dexamethasone (P = 0·05) and an altered cortisol–ACTH relationship (decreased cortisol–ACTH ratio, P < 0·02). The same individuals also demonstrated close correlations between plasma cortisol and aldosterone (–344T CYP11B2 r = 0·508, P < 0·004; TTGG CYP11B1 r = 0·563, P < 0·003) suggesting that there was common regulation (possibly ACTH) of these hormones in genetically susceptible subjects.

Conclusions  Variation in CYP11B2 and CYP11B1 associates with chronic up‐regulation of the HPA axis. These novel data support the suggestion that chronic aldosterone excess, in genetically susceptible individuals, may be a consequence of increased ACTH drive to the adrenal and identify novel molecular mechanisms that may lead to the development of hypertension within the general population.
Pituitary adenomas in northern Sweden: a study on therapy choices and the risk of second primary tumours
Authors: Norberg Lars , Johansson Robert , Rasmuson Torgny
Published: April 2008

Objectives  To present the incidence of pituitary adenomas in northern Sweden and to determine whether the incidence of second primary tumours differs from the incidence in the general population or might be related to radiotherapy.

Design  A retrospective register study.

Patients  A total of 546 patients with pituitary adenomas were identified in the Cancer Registry of northern Sweden between 1958 and 2004. Only patients with histopathological verification and/or endocrine activity of the adenoma and more than 12 months of follow‐up were included, resulting in 376 patients in the study.

Measurements  The number of patients receiving surgery and/or radiotherapy and presenting second primary tumours were registered. Standard incidence ratios (SIRs) between the observed and the expected incidence of second primary tumours were calculated.

Results  The total number of person‐years at risk for a second primary tumour was 4730. Fifty‐four out of 376 (14%) patients had 63 second primary tumours. Forty patients had second primary tumours diagnosed more than 12 months after diagnosis of the pituitary adenoma (expected 42·6, SIR 0·94, 95% CI 0·67–1·28). A significantly increased incidence of second primary tumours was seen in 42 men with GH‐secreting adenomas. Ten second tumours were found (expected 4·55, SIR 2·20, 95% CI 1·05–4·04). A total of 261 patients received radiotherapy and 31 second primary tumours occurred after radiotherapy (expected 32·9, SIR 0·94, 95% CI 0·64–1·34). Three second primary intracranial tumours appeared within the irradiation volume (expected 0·85, SIR 3·51, 95% CI 0·71–10·36).

Conclusions  No significant increase was found in the incidence of second primary tumours in general in patients with pituitary adenomas. An increased incidence of second primary tumours was seen in men with GH‐secreting adenomas.
Preclinical cardiac involvement in phaeochromocytoma: a study with integrated backscatter
Authors: Galetta Fabio , Bernini Giampaolo , Franzoni Ferdinando , Tocchini Leonardo , Taurino Chiara , Bardini Michele , Rossi Marco , Salvetti Antonio , Santoro Gino
Published: April 2008

Objective  It is well known that vascular and cardiac structure may be influenced by circulating neurohormonal factors. Our aim was to study the myocardial wall texture by integrated backscatter (IBS) analysis in patients with phaeochromocytoma (PHEO).

Design  Fourteen patients with PHEO, 15 matched high‐normal blood pressure (BP) subjects, 15 mild essential hypertensives and 15 normotensive controls underwent two‐dimensional conventional ultrasonography and ultrasonic IBS of the myocardial wall. IBS analysis was performed at both interventricular septum and posterior wall levels. IBS values were expressed in decibels and corrected for the IBS values obtained within the pericardium (C‐IBS). The systo‐diastolic cyclical variations in IBS (CV‐IBS), an index of myocardial contractile performance, were also evaluated.

Results  Patients with PHEO showed C‐IBS values comparable to those of hypertensive patients, and significantly higher than those of high‐normal BP subjects and controls at both septum and posterior wall levels (P < 0·001 for all). In PHEO patients, CV‐IBS was lower than that of normotensive, high‐normal BP subjects and hypertensive patients, at both septum and posterior wall levels (P < 0·001 for all). An inverse relationship was found in the PHEO group between 24‐h urinary normetanephrine and CV‐IBS of both septum (r2 = –0·29, P < 0·05) and posterior wall (r2 = –0·46, P < 0·05).

Conclusions  Our results show that patients with PHEO have myocardial remodelling characterized by increased myocardial fibrosis, confirmed by an increase in the overall myocardial backscatter level measured. The observed decrease in the magnitude of CV‐IBS suggests an impairment of myocardial contractile performance. These results may provide insights into the role of catecholamines in left ventricular (LV) structure and function in PHEO.
Uncommon clinical presentations of pheochromocytoma and paraganglioma in two different patients affected by two distinct novel VHL germline mutations
Authors: Ercolino Tonino , Becherini Lucia , Valeri Andrea , Maiello Michele , Gaglianò Maria Sole , Parenti Gabriele , Ramazzotti Matteo , Piscitelli Elisa , Simi Lisa , Pinzani Pamela , Nesi Gabriella , Degl’Innocenti Donatella , Console Nico , Bergamini Carlo , Mannelli Massimo
Published: April 2008

Context  The von Hippel‐Lindau (VHL) syndrome is an inherited multitumour disorder characterized by clinical heterogeneity and high penetrance. Pheochromocytoma (Pheo) is present in 10%–15% of cases and can be isolated or associated with other lesions such as haemangioblastomas, kidney cysts or cancer and pancreatic lesions. In VHL patients, Pheos generally secrete norepinephrine and are located in the adrenals. Extra‐adrenal Pheos (paragangliomas, PGLs) are rare.

Objective  While performing genetic testing in patients affected by apparently sporadic Pheos or PGLs, we found two novel different VHL germline mutations in two females who presented with two distinct very uncommon clinical pictures. One patient was studied for the presence of an adrenal incidentaloma and the other for the presence of a neck tumour.

Methods and results  Patients coding regions and exon–intron boundaries of RET (exons 10, 11, 13–15), VHL, SDHD, SDHB and SDHC genes were amplified and sequenced. We identified two novel VHL point mutations: a L198V missense mutation in a 32‐year‐old female affected by a right adrenal compound and mixed tumour constituted by an epinephrine secreting Pheo, a ganglioneuroma and an adrenocortical adenoma, and a T152I missense mutation in a 24‐year‐old female affected by a left carotid body tumour. No other lesions were found in the patients or in the VHL mutation positive relatives.

Conclusions  These cases enlarge the list of VHL mutations and add new insights in the clinical variability of VHL disease, thus confirming the importance of genetic testing in patients affected by apparently sporadic Pheos or PGLs.
Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs
Authors: ORITO K. , SAITO M. , FUKUNAGA K. , MATSUO E. , TAKIKAWA S. , MUTO M. , MISHIMA K. , EGASHIRA N. , FUJIWARA M.
Published: April 2008

The purposes of the present study were to elucidate the pharmacokinetics of zonisamide, determine the presence of a drug interaction with phenobarbital, and evaluate how long any interaction lasted after discontinuation of phenobarbital in dogs. Five dogs received zonisamide (5 mg/kg, p.o. and i.v.) before and during repeated oral administration of phenobarbital (5 mg/kg, bid, for 30–35 days). Zonisamide (5 mg/kg, p.o.) was also administered 8, 10, and 12 weeks after discontinuation of phenobarbital. Blood was sampled until 24 h after each zonisamide administration and serum concentrations of zonisamide were determined. Repeated phenobarbital decreased the maximum serum concentration, area under the serum concentration vs. time curve, apparent elimination half‐life, and bioavailability of zonisamide. Total clearance increased. Time to maximum serum concentration and volume distribution were not changed. The maximum serum concentration and area under the serum concentration vs. time curve of zonisamide continued to be low until 10 weeks after the discontinuation of phenobarbital. They were restored to the same serum concentration as before phenobarbital administration 12 weeks after the discontinuation of phenobarbital. These data suggested that repeated administration of a clinical dose of phenobarbital enhanced the clearance of zonisamide and the enhanced clearance lasted at least 10 weeks after the discontinuation of phenobarbital. Caution may be necessary when zonisamide is given with phenobarbital and when antiepileptic therapy is changed from phenobarbital to zonisamide.
A prospective study on canine atopic dermatitis and food‐induced allergic dermatitis in Switzerland
Authors: Picco F. , Zini E. , Nett C. , Naegeli C. , Bigler B. , Rüfenacht S. , Roosje P. , Gutzwiller M. E. Ricklin , Wilhelm S. , Pfister J. , Meng E. , Favrot C.
Published: April 2008

Canine atopic dermatitissensu strictoand food‐induced allergic dermatitis are common canine skin conditions, which are often considered clinically undistinguishable. Several attempts have been made to describe populations of atopic dogs and determine breed predisposition but the results were often biased by the use of hospital populations as control group. The present study aims to describe a population of Swiss atopic and food‐allergic dogs and to compare it with a data set representing more than 85% of all Swiss dogs. The study, which was carried out during 1 year in several practices and teaching hospital in Switzerland, describes a group of 259 allergic dogs, determines breed predisposition for atopic dermatitis and food‐induced allergic dermatitis, compares the clinical signs and features of both conditions, and outlines the clinical picture of five frequently affected breeds.
An autopsy case of Fabry disease with neuropathological investigation of the pathogenesis of associated dementia
Authors: Okeda Riki , Nisihara Masahiro
Published: April 2008

The pathogenesis of dementia associated with Fabry disease was examined neuropathologically in an autopsy case. The patient was a 47‐year‐old computer programmer who developed renal failure at the age of 36, necessitating peritoneal dialysis, and thereafter suffered in succession episodic pulmonary congestion, bradyacusia, heart failure, and dementia, before dying of acute myocardial infarction. MRI of the brain demonstrated leuko‐araiosis. The CNS parenchyma showed widespread segmental hydropic swelling of axons in the bilateral cerebral and cerebellar deep white matter in addition to neuronal ballooning due to glycolipid storage in a few restricted nuclei and multiple tiny lacunae. Hydropic axonal swelling was also sparsely distributed in the pyramidal tract, pedunculus cerebellaris superior and brachium colliculi inferioris, but wallerian degeneration of these tracts was absent. Additional features included angiopathy of the subarachnoidal arteries due to Fabry disease, such as medial thickening resulting from glycolipid deposition in smooth muscle cells (SMCs) and adventitial fibrosis with lymphocytic infiltration, together with widespread subtotal or total replacement of medial SMCs by fibrosis, associated with prominent intimal fibrous thickening and undulation of the internal elastic membrane of medium‐sized (1000–100 μm diameter) arteries. The findings in this case suggest that axonopathic leukoencephalopathy due to multisegmental hydropic swelling of axons in the bilateral cerebral deep white matter is responsible for the dementia associated with Fabry disease, and may be caused by ischemia resulting from widespread narrowing and stiffening of medium‐sized subarachnoidal arteries and progressive heart failure.
Marinesco‐Sjögren syndrome with atrophy of the brain stem tegmentum and dysplastic cytoarchitecture in the cerebral cortex
Authors: Sakai Kenji , Tada Mari , Yonemochi Yosuke , Nakajima Takashi , Onodera Osamu , Takahashi Hitoshi , Kakita Akiyoshi
Published: April 2008

Marinesco‐Sjögren syndrome (MSS) is a progressive multisystem disease with autosomal recessive inheritance characterized by cataracts, mental retardation, and cerebellar ataxia. Recently, two causative genes for MSS, SIL1 and SARA2, have been identified. On the other hand, the histopathologic features of the CNS in this syndrome have not yet been clarified in detail. We report here the features of an autopsy case of MSS with progressive myopathy, in which atrophy of the cerebellum and brain stem tegmentum, retinal degeneration, and dysplastic cytoarchitecture in the cerebral cortex were evident. An elder brother of the patient showed quite similar symptoms, implying an autosomal recessive mode of inheritance. However, we detected no mutations in the available genes. This case appears to represent an unusual example of MSS manifesting widespread developmental anomaly and neuronal degeneration in the CNS.
Evaluation of the anti‐inflammatory effect of infliximab in a mouse model of acute asthma
Authors: DEVECI Figen , MUZ M. Hamdi , ILHAN Nevin , KİRKİL Gamze , TURGUT Teyfik , AKPOLAT Nusret
Published: April 2008

Background and objective: To evaluate the potential role of anti‐tumour necrosis factor (TNF)‐α mAb (infliximab) on the inflammatory response in a mouse model of acute asthma.

Methods: BALB/c mice received intraperitoneal (i.p.) ovalbumin (OVA) on days 0 and 14, 100 μg of OVA intranasally on day 14 and 50 μg of OVA intranasally on days 25, 26 and 27. The low‐dose (2.5 mg/kg) and high‐dose (6.25 mg/kg) infliximab groups received i.p. infliximab before each i.p. sensitization and on challenge days 1, 6, 13, 20 and 27. The control group received i.p. injections of normal saline with alum on days 0 and 14 and normal saline without alum on days 14, 25, 26 and 27.

Results: There were statistically significant decreases in the numbers of BAL fluid (BALF) neutrophils, eosinophils, as well as lung eosinophils in both the low‐ and high‐dose infliximab groups when compared with the control OVA sensitized/challenged group. The lower dose of infliximab did not alter lung neutrophil counts, but a marked decrease was seen with the high dose of infliximab. After treatment with low and high doses of infliximab, BALF levels of regulated on activation normal T cell expressed and secreted (RANTES), granulocyte macrophage‐colony stimulating factor (GM‐CSF), TNF‐α, IL‐6, macrophage inflammatory protein (MIP)‐2, and levels of RANTES, IL‐4, GM‐CSF, TNF‐α, IL‐6 and MIP‐2 in lung tissue were significantly decreased when compared with the control OVA sensitized/challenged group. There was a significant decrease in BALF IL‐4 only in the high‐dose infliximab group.

Conclusions: These results show that an anti‐TNF‐α mAb has a considerable anti‐inflammatory effect on allergen‐induced lung inflammation in an animal model of acute asthma.
Common functional polymorphisms in the cathepsin S promoter in Japanese subjects: Possible contribution to pulmonary emphysema
Authors: MINEMATSU Naoto , NAKAMURA Hidetoshi , FURUUCHI Momoyo , NAKAJIMA Takahiro , TAKAHASHI Saeko , TSUJIMURA Shuko , TATENO Hiroki , ISHIZAKA Akitoshi
Published: April 2008

Background and objective:  Cathepsin S is involved in the pathogenesis of COPD in murine models overexpressing interferon (IFN)‐γ and IL‐13. It is widely accepted that genetic factors partly influence susceptibility to COPD; however, the association of genetic polymorphisms in the cathepsin S gene with COPD has not been reported previously. In this study, functional polymorphisms in the 5′‐flanking region of the human cathepsin S gene were identified and their association with COPD phenotypes was investigated.

Methods:  Genetic polymorphisms were detected by single strand conformation polymorphism analysis and direct sequencing. Genotypes and haplotypes were determined using amplification refractory mutation systems and single strand conformation polymorphism analysis. A promoter‐reporter assay was used to compare transcriptional activities between the haplotypes on stimulation with IFN‐γ. Haplotype analysis was performed on 204 smoking and 104 non‐smoking Japanese subjects.

Results:  Four novel polymorphisms were detected in the 5′‐flanking region and three major haplotypes were identified. The haplotypes were associated with distinct promoter activities on stimulation with IFN‐γ and there was a trend indicating that higher transcriptional activity was linked to less pulmonary emphysema.

Conclusion:  Novel functional polymorphisms were identified in the cathepsin S gene, which has a possible association with pulmonary emphysema in the Japanese population.
Neutrophil elastase activity in acute lung injury and respiratory distress syndrome
Authors: HASHIMOTO Satoru , OKAYAMA Yoko , SHIME Nobuaki , KIMURA Akio , FUNAKOSHI Yosuke , KAWABATA Kazuhito , ISHIZAKA Akitoshi , AMAYA Fumimasa
Published: April 2008

Background and objective:  Neutrophil elastase (NE) may play a key role in the development of acute lung injury (ALI) or ARDS. NE activity (NEA) was measured in patients with ALI treated with a selective NE inhibitor.

Methods:  NEA and NE‐α1‐antitrypsin (NE‐AT) complex were measured in plasma before, during and after the administration of the selective NE inhibitor, sivelestat, in 32 patients with a diagnosis of ALI or ARDS. NEA index (NEAI) was calculated as NEA/NE‐AT. The sequential organ failure assessment (SOFA) score and the ratio PaO2/fraction of inspired oxygen (FiO2) were measured.

Results:  NEA and NE‐AT was raised in all patients. Sivelestat reduced NEAI and NEA (P < 0.01 for both) but not NE‐AT and NEA, and NEAI returned to pretreatment levels. NEA correlated closely with NE‐AT before, but not after treatment. No relationship was observed between these indices and SOFA score or PaO2/FiO2 ratio.

Conclusions:  Sivelestat reduced NEA and NEAI in patients with ALI or ARDS suggesting NE inhibition. A larger study is needed to determine the relationship of NEA, NE‐AT and NEAI with the outcome of ALI/ARDS.
Effects of spatial aggregation on competition, complementarity and resource use
Authors: MOKANY KAREL , ASH JULIAN , ROXBURGH STEPHEN
Published: April 2008

Abstract The spatial distributions of most species are aggregated to varying degrees. A limited number of studies have examined the effects of spatial aggregation on interspecific and intraspecific interactions, generally finding that spatial aggregation can enhance coexistence between species by reducing the capacity for interspecific competition. Less well studied are the effects of spatial aggregation on complementarity (i.e. differences in resource use strategies) and resource use. Our primary hypothesis was that spatial aggregation reduces the complementarity between species owing to: (i) less interspecific interactions as a result of spatial separation; and (ii) less differences between species as a result of phenotypic plasticity. We further postulate that these negative effects of spatial aggregation on complementarity will reduce resource use by the community. Here we test these hypotheses in a pot experiment in which we applied three levels of spatial aggregation to three sets of two‐species mixtures of herbaceous perennial plant species from native grasslands of south‐eastern Australia. Both root and shoot biomass were significantly affected by spatial aggregation, although the nature of these affects depended upon the species involved, and the relative strengths of interspecificversusintraspecific competition. Complementarity between species in the distribution of their green leaves decreased significantly as spatial aggregation increased for one of the species mixtures, providing some evidence in support of our hypothesis that aggregation reduces complementarity through phenotypic plasticity. Spatial aggregation also altered light interception and use of soil moisture resources, although these effects were dependent on the species involved. We suggest that clear effects of spatial aggregation on complementarity and resource use may be obscured by the idiosyncratic way in which neighbour identity influences plant growth and hence plant size, limiting the ability to generalize, at the community level, any underlying effects of spatial pattern on ecological process.
Woody plant encroachment reduces species richness of herb‐rich woodlands in southern Australia
Authors: PRICE JODI N. , MORGAN JOHN W.
Published: April 2008

Abstract  Woody plants have been increasing in many woodland and savanna ecosystems owing to land use changes in recent decades. We examined the effects of encroachment by the indigenous shrub Leptospermum scoparium (Myrtaceae) on herb‐rich Eucalyptus camaldulensis woodlands in southern Australia. Species richness and compositional patterns were examined under the canopy of L. scoparium and in surrounding open areas to determine the species most susceptible to structural changes. Richness was significantly lower in areas of moderate to high L. scoparium cover (>15%), suggesting that a threshold shrub cover caused major change in this ecosystem. Shrubs were associated with a significant reduction in above‐ground biomass of the ground‐layer flora and a significant shift in community composition. The few species that were positively associated with high L. scoparium cover were also common in the woodland flora; no new species were recorded under the shrub canopy. Important environmental changes associated with L. scoparium cover were decreased light availability and increased litter cover, which were likely a consequence of encroachment. Leptospermum scoparium cover was also associated with greater surface soil moisture, which may be a consequence of increased shading under the shrub canopy or indicate favourable soil conditions for L. scoparium establishment. Reductions in species richness and abundance of the germinable seed bank were found in soil samples taken from under L. scoparium. With ongoing recruitment of L. scoparium and consequent increases in shrub cover, ground‐layer diversity in these species‐rich woodlands should continue to decline over time.
Fruit size preference in the New Zealand pigeon (Hemiphaga novaeseelandiae)
Authors: WOTTON DEBRA M. , LADLEY JENNY J.
Published: April 2008

Abstract  We investigated whether the New Zealand pigeon Hemiphaga novaeseelandiae (Columbidae) exhibits size‐based preferences for fruits. We tested the hypothesis that in small‐fruited species, pigeons would prefer larger fruits, but in larger‐fruited species, this preference would reverse as the pigeons become increasingly limited by their gape size. We collected undispersed fruits and bird‐dispersed seeds of 10 plant species, some over several sites or years (13 datasets in total). We estimated the fruit size of dispersed seeds by fitting regressions of fruit diameter to seed diameter in intact fruits. We were able to predict fruit diameter from seed diameter in 12 of the 13 populations, although the relationship was stronger in single‐seeded species than in multi‐seeded species. Seven of the 12 populations tested showed a significant difference in seed diameter among undispersed and dispersed seeds. However, our results showed no consistent pattern in fruit size preference by the New Zealand pigeon and did not support our hypothesis. The large‐bodied New Zealand pigeon is generally not gape limited and fruit size preferences appear to be independent of mean fruit size.
Male and female effects on fertilization success and offspring viability in the Peron's tree frog,Litoria peronii
Authors: SHERMAN CRAIG D. H. , WAPSTRA ERIK , ULLER TOBIAS , OLSSON MATS
Published: April 2008

Abstract There is increasing theoretical and empirical evidence that genetic compatibility among partners is an important determinant of fertilization success and offspring viability. In amphibians, females often actively choose partners from among a variety of males and polyandry is common. Genetic compatibility among partners may therefore be an important determinant of fertilization success and offspring viability in some amphibians. Amphibians also show some of the highest levels of genetic differentiation among neighbouring populations known in vertebrates, and as such, populations may have evolved different co‐adapted gene complexes. This means that offspring from among‐population crosses may have reduced fitness. It is therefore essential to understand to what extent crossings between and within populations may interfere with successful fertilization and offspring viability. Here, we test whether crossing individuals within and between two different populations of the Australian Peron's tree frog (Litoria peronii) using artificial fertilizations affect fertilization success and offspring viability. Fertilization success per se is strongly influenced by male identity, which is likely to depend at least to some extent on the experimental procedure (e.g. resulting in variation in sperm number per ejaculate), whereas there was no fertilization effect of female identity. More importantly, male and female identity, independently of each other, explained significant variation in offspring viability, whereas no such effect could be linked to population of origin. Thus, our experiments suggest that crossing populations may not always be the most significant factor affecting fertilization success or offspring viability, but may be more influenced by the genetic quality or the genetic compatibility of partners.
Incidence of leaf mining in different vegetation types across rainfall, canopy cover and latitudinal gradients
Authors: SINCLAIR ROBYN J. , HUGHES LESLEY
Published: April 2008

Abstract  Leaf miners are insects whose larval stages live between layers of leaf epidermis, feeding on mesophyll and lower epidermis to create mine‐like cavities. Little is known about the ecology or distribution of leaf miners in Australia. We investigated the incidence of leaf miners in relation to aridity, vegetation types, host plant taxonomy, leaf traits, canopy cover and latitude. We surveyed leaf miners at 15 sites in NSW, eastern Australia, situated along a rainfall gradient from 300 to 1700 mm per annum and a latitudinal gradient of 28°S to 33°S, within four vegetation types (mallee, heath, woodland and rainforest). Leaf mining was recorded from 36 plant species, 89% of which had no previous record of mining. The proportion of mined plant species at each site varied, but there was no significant difference between vegetation types. Leaf mining presence was positively correlated with both total leaf length and leaf thickness. No significant correlations were found between the proportion of mined species at a site and rainfall, latitude or foliar projected cover. We conclude that leaf mining is a widespread type of insect herbivory whose distribution patterns are more likely to be influenced by biotic than abiotic factors.
Repeated seizures lead to altered skilled behaviour and are associated with more highly efficacious excitatory synapses
Authors: Henry Luke C. , Goertzen Crystal D. , Lee Arden , Teskey G. Campbell
Published: April 2008

People with epilepsy have a high incidence of interictal behavioural problems that appear to be related to the location of their seizure focus. This study investigated a novel test of the hypotheses that repeated seizures result in behavioural deficits and altered performance during the interictal state, and that those behaviours are related to the presence of more highly efficacious excitatory synapses. We tested these hypotheses by first repeatedly eliciting seizures with electric current through indwelling electrodes in the corpus callosum at the level of the caudal forelimb area of sensorimotor neocortex in the rat. We then assessed learned skilled behaviours that primarily utilize the forelimbs on tasks that are sensitive to the functional integrity of that structure. We observed both behavioural deficits and altered kinematic performance in rats that experienced repeated neocortical seizures relative to an electrode‐implanted control group. From a separate set of rats, tissue was prepared for quantification of thickness and excitatory synaptic subtypes from neocortical layer V. We observed significantly increased numbers of perforated synapses that make their connections directly onto the dendritic shaft at 3 weeks following the last seizure. Altered reaching behaviours are likely due to neural reorganization in the neocortex including more efficacious synapses.
Bilateral coordination of walking and freezing of gait in Parkinson’s disease
Authors: Plotnik Meir , Giladi Nir , Hausdorff Jeffrey M.
Published: April 2008

Freezing of gait (FOG) in Parkinson's disease (PD) occurs most frequently during turns or step initiation, two tasks that likely demand a high degree of bilateral coordination between the legs. Our objective was to test the hypothesis that impairments in bilateral coordination of stepping are associated with FOG in PD. We compared locomotion features while walking on level ground between patients with PD that experience FOG (PD + FOG; n = 21) and patients with PD that do not (PD − FOG; n = 13). To study bilateral stepping coordination, we defined the stride duration of one foot as a gait cycle or 360°, determined the relative timing of contralateral heel‐strikes and defined this as the phase, ϕ (ideally, ϕ = 180°). The sum of the coefficient of variation of ϕ and the mean absolute difference between ϕ and 180° was defined as the phase coordination index (PCI), representing variability and inaccuracy, respectively, in phase generation. During the ‘Off’ state (= 12 h off anti‐parkinsonian medication), PCI values were higher (poorer coordination) in PD + FOG compared with PD − FOG (P < 0.024). Stride‐to‐stride phase adjustments, Δϕ, were also studied. Both groups scaled their ‘converging’ adjustments (towards 180°) to the same extent, but when generating diverging Δϕ (away from 180°), PD + FOG patients exhibited larger errors compared with PD − FOG patients (P < 0.006). This study demonstrates that patients with PD who experience FOG have distinctive impairments in the bilateral coordination of locomotion. Poor bilateral coordination of walking may predispose to FOG, especially during challenging tasks that demand a high degree of left–right coordination.
Interaction between neuropeptide Y (NPY) and brain‐derived neurotrophic factor in NPY‐mediated neuroprotection against excitotoxicity: a role for microglia
Authors: Xapelli S. , Bernardino L. , Ferreira R. , Grade S. , Silva A. P. , Salgado J. R. , Cavadas C. , Grouzmann E. , Poulsen F. R. , Jakobsen B. , Oliveira C. R. , Zimmer J. , Malva J. O.
Published: April 2008

The neuroprotective effect of neuropeptide Y (NPY) receptor activation was investigated in organotypic mouse hippocampal slice cultures exposed to the glutamate receptor agonist α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA). Exposure of 2‐week‐old slice cultures, derived from 7‐day‐old C57BL/6 mice, to 8 µm AMPA, for 24 h, induced degeneration of CA1 and CA3 pyramidal cells, as measured by cellular uptake of propidium iodide (PI). A significant neuroprotection, with a reduction of PI uptake in CA1 and CA3 pyramidal cell layers, was observed after incubation with a Y2 receptor agonist [NPY(13‐36), 300 nm]. This effect was sensitive to the presence of the selective Y2 receptor antagonist (BIIE0246, 1 µm), but was not affected by addition of TrkB‐Fc or by a neutralizing antibody against brain‐derived neurotrophic factor (BDNF). Moreover, addition of a Y1 receptor antagonist (BIBP3226, 1 µm) or a NPY‐neutralizing antibody helped to disclose a neuroprotective role of endogenous NPY in CA1 region. Cultures exposed to 8 µm AMPA for 24 h, displayed, as measured by an enzyme‐linked immunosorbent assay, a significant increase in BDNF. In such cultures there was an up‐regulation of neuronal TrkB immunoreactivity, as well as the presence of BDNF‐immunoreactive microglial cells at sites of injury. Thus, an increase of AMPA‐receptor mediated neurodegeneration, in the mouse hippocampus, was prevented by neuroprotective pathways activated by NPY receptors (Y1 and Y2), which can be affected by BDNF released by microglia and neurons.
Long‐term potentiation in the nucleus accumbens requires both NR2A‐ and NR2B‐containing N‐methyl‐d‐aspartate receptors
Authors: Schotanus Sietske M. , Chergui Karima
Published: April 2008

N‐methyl‐d‐aspartate (NMDA) receptors play crucial roles in several forms of long‐term changes in the efficacy of glutamatergic synaptic transmission. The suggestion that the NR2A subunit of the NMDA receptor may be selectively involved in the induction of long‐term potentiation (LTP) in the hippocampus and cortex has been challenged. However, the contribution of NR2B in the induction of LTP is not always clearly established. The present study investigates the role of NR2A and NR2B in the induction of LTP in the nucleus accumbens (NAc), a brain region that expresses high levels of NR2B and an NMDA‐dependent form of LTP. We recorded extracellular field excitatory postsynaptic potentials/population spikes in slices of mouse NAc. High‐frequency stimulation of glutamatergic fibers consistently induced LTP of the field excitatory postsynaptic potential/population spike in the NAc. LTP was abolished in the presence of selective antagonists of either NR2B [R‐(R*,S*)‐α‐(4‐hydroxyphenyl)‐β‐methyl‐4‐(phenyl‐methyl)‐1‐piperidine propanol and Ifenprodil] or NR2A ([(R)‐[(S)‐1‐(4‐bromo‐phenyl)‐ethylamino]‐(2,3‐dioxo‐1,2,3,4‐tetrahydroquinoxalin‐5‐yl)‐methyl]‐phosphonic acid) subunits. Recordings performed in a low concentration of Mg2+ ions in the perfusion solution did not reveal a selective involvement of a particular NMDA receptor subunit because either NR2A or NR2B antagonists were able to block LTP. LTP was also abolished in the presence of a low concentration of the non‐subunit‐selective NMDA receptor antagonist dl‐2‐amino‐5‐phosphonopentanoic acid in normal Mg2+ and low Mg2+ in the perfusion solution. These results show that the degree of NMDA receptor activation, and not their subunit composition, determines whether LTP is induced in the NAc.
Balance training and ballistic strength training are associated with task‐specific corticospinal adaptations
Authors: Schubert M. , Beck S. , Taube W. , Amtage F. , Faist M. , Gruber M.
Published: April 2008

The aim of this study was to investigate the role of presumably direct corticospinal pathways in long‐term training of the lower limb in humans. It was hypothesized that corticospinal projections are affected in a training‐specific manner. To assess specificity, balance training was compared to training of explosive strength of the shank muscles and to a nontraining group. Both trainings comprised 16 1‐h sessions within 4 weeks. Before and after training, the maximum rate of force development was monitored to display changes in motor performance. Neurophysiological assessment was performed during rest and two active tasks, each of which was similar to one type of training. Hence, both training groups were tested in a trained and a nontrained task. H‐reflexes in soleus (SOL) muscle were tested in order to detect changes at the spinal level. Corticospinal adaptations were assessed by colliding subthreshold transcranial magnetic stimulation to condition the SOL H‐reflex. The short‐latency facilitation of the conditioned H‐reflex was diminished in the trained task and enhanced in the nontrained task. This was observable in the active state only. On a functional level, training increased the rate of force development suggesting that corticospinal projections play a role in adaptation of leg motor control. In conclusion, long‐term training of shank muscles affected fast corticospinal projections. The significant interaction of task and training indicates context specificity of training effects. The findings suggest reduced motor cortical influence during the trained task but involvement of direct corticospinal control for new leg motor tasks in humans.
Postsynaptic expression of an epidermal growth factor receptor regulates cholinergic synapse formation between identified molluscan neurons
Authors: Van Kesteren Ronald E. , Gagatek Jessica S. , Hagendorf Antje , Gouwenberg Yvonne , Smit August B. , Syed Naweed I.
Published: April 2008

Epidermal growth factor (EGF) family members are conserved in both vertebrates and invertebrates. Recent studies suggest that EGF ligands in invertebrates may have neurotrophic actions that possibly compensate for the apparent absence of neurotrophins in these species. In this study, we have cloned an EGF receptor from the mollusk Lymnaea stagnalis (L‐EGFR), and shown that L‐EGFR is the receptor for a previously identified EGF‐like peptide in Lymnaea, named Lymnaea EGF (L‐EGF). Knock‐down of L‐EGFR expression prevented L‐EGF‐induced excitatory synapse formation between identified cholinergic neuron visceral dorsal 4 (VD4) and its postsynaptic partner left pedal dorsal 1 (LPeD1). Moreover, knock‐down of L‐EGFR also prevented synapse formation induced by Lymnaea brain conditioned medium, suggesting that L‐EGF is the most important, if not the only, brain‐derived factor that promotes excitatory cholinergic synapse formation in Lymnaea. Thus, our data establish canonical EGF/EGFR signaling as an important synaptotrophic mechanism in invertebrates.
Invading populations of an ornamental shrub show rapid life history evolution despite genetic bottlenecks
Authors: Dlugosch Katrina M. , Parker Ingrid M.
Published: April 2008

Human‐mediated species introductions offer opportunities to investigate when and how non‐native species to adapt to novel environments, and whether evolution has the potential to contribute to colonization success. Many long‐established introductions harbour high genetic diversity, raising the possibility that multiple introductions of genetic material catalyze adaptation and/or the evolution of invasiveness. Studies of nascent invasions are rare but crucial for understanding whether genetic diversity facilitates population expansion. We explore variation and evolution in founder populations of the invasive shrubHypericum canariense. We find that these introductions have experienced large reductions in genetic diversity, but that increased growth and a latitudinal cline in flowering phenology have nevertheless evolved. These life history changes are consistent with predictions for invasive plants. Our results highlight the potential for even genetically depauperate founding populations to adapt and evolve invasive patters of spread.
The nature and reality of the aphid clone: genetic variation, adaptation and evolution
Authors: Loxdale Hugh D.
Published: April 2008

1 When aphid clones and clonality are discussed, it is still often said that they are ‘genetically identical’, a statement for which there is no direct evidence, and certainly not for the entire genome. By contrast, there is a growing body of empirical data from the application of high resolution molecular (DNA) markers that aphid asexual lineages rapidly mutate and that, in some documented cases, this variation is selectable, either positively or negatively.

2 Although it is true that, in enclosed conditions (e.g. laboratory or field cage), a so‐called clone as defined as the asexual progeny of a single foundress may be traceable, this is rarely if ever possible in the field without the use of genetic markers, and even then, usually only at a relatively few loci (multilocus genotypes, ‘MLGs’).

3 The continued use of the term clone without qualification of its true nature and the reality of its interesting biology is likely to hamper a proper understanding of the ecology and evolution of these insects (which are interesting in their own right because of their complex life histories, but also because they are important as major pests globally, both by causing direct feeding damage and by transmitting pathogenic plant viruses and thereby leading to huge economic losses in the agricultural, horticultural and forestry industries).

4 In this short review, I provide evidence of what is now known about aphid clonality after the widespread use of molecular markers, comprising information mainly gained within the last 15 years or so.

5 The data demonstrate widespread adaptation and evolution, sometimes involving introgression and hybridization. Because of this new knowledge, our ideas of what constitutes a clone are in need of serious re‐evaluation.
Spatial and temporal dynamics of Myzus persicae clones in fields and suction traps
Authors: Kasprowicz Louise , Malloch Gaynor , Pickup Jon , Fenton Brian
Published: April 2008

1 The population of peach‐potato aphid Myzus persicae in Scotland is comprised almost entirely of long‐term asexual clones.

2 Over a ten year period, M. persicae from Scottish fields and suction traps were analysed with six microsatellite markers.

3 Out of 1497 individuals analysed, 14 clones (denoted A–N) comprised over 98% of the collection.

4 Some clones were particularly abundant but most clones had a widespread distribution on all available plants.

5 Clones E and L had distinct features in their distributions as clone L was geographically totally restricted to the north east of Scotland and clone E showed a marked preference for brassica crops.

6 Clones E and L provide direct evidence of a role for local adaptations in the distribution of M. persicae clones.
Spatial and temporal distribution of Empoasca vitis within a vineyard
Authors: Decante Damien , Van Helden Maarten
Published: April 2008

1 The intra‐plot spatial distribution of the green leafhopper Empoasca vitis (Goethe) (Cicadellidae, Empoascini) was assessed over three successive growing seasons in a Bordeaux vineyard. Weekly measurements of adult trappings and nymphal counts were performed in a 1.7‐ha plot on 130 sampling points.

2 Statistical and geostatistical analyses revealed inconsistent spatial distributions of adults and nymphs in spring, but consistent spatial distributions in summer, which were identical every year.

3 Similarities between spatial distributions of the mobile adults and the sedentary and aggregated nymphs strongly suggest that adults disperse inside the plot to areas preferred for egg deposition.

4 The similarity of summer populations among years suggests that this insects distribution is based on (perennial) differences in plot characteristics.
Histological verification of 11C‐choline‐positron emission/computed tomography‐positive lymph nodes in patients with biochemical failure after treatment for localized prostate cancer
Authors: Schilling David , Schlemmer Heinz P. , Wagner Philipp H. , Böttcher Patrick , Merseburger Axel S. , Aschoff Philip , Bares Roland , Pfannenberg Christa , Ganswindt Ute , Corvin Stefan , Stenzl Arnulf
Published: April 2008

OBJECTIVES

To evaluate the potential of 11C‐choline‐positron emission tomography (PET)/computed tomography (CT) for planning surgery in patients with prostate cancer and prostate‐specific antigen (PSA) relapse after treatment with curative intent.

PATIENTS AND METHODS

We retrospectively reviewed the charts of 10 patients with PSA recurrence after either external beam radiation (two) or radical retropubic prostatectomy (eight) for prostate cancer, and who had a laparoscopic lymphadenectomy for suspicious lymph nodes detected on 11C‐choline‐PET/CT. The histological results and PET/CT findings were compared.

RESULTS

In all, 22 suspicious lymph nodes were found on PET/CT, and 14 on conventional CT or magnetic resonance imaging. Comparing the conventional imaging showed concordance in 13 lymph nodes. Three of the 10 patients had no metastatic lymph node disease on definitive histology. The mean (sd) PSA level for these patients was 1.0 (0.4) ng/mL, whereas that in patients with lymph node metastases was 15.1 (9.2) ng/mL (statistically significant difference, P < 0.05). The positive predictive value was seven of 10. All of the patients initially regressed, with PSA increases after lymphadenectomy. Two of the patients are being managed by watchful waiting, two had radiotherapy of the prostate fossa and two had chemotherapy with docetaxel. Four patients were treated by hormone‐deprivation therapy. After a mean (sd) follow up of 11 (7) months, one patient died, one has PSA progression, but none of those with negative histology has clinical signs of local recurrence.

CONCLUSIONS

11C‐choline‐PET is a valuable tool for detecting recurrent prostate cancer, but the limited positive predictive value should lead to a critical interpretation of the results.