bluuebunny/crossref_metadata_2025 huggingface dataset:
The metabolic syndrome and mortality: the Singapore Cardiovascular Cohort Study
Authors: Lee Jeannette , Heng Derrick , Ma Stefan , Chew Suok‐Kai , Hughes Kenneth , Tai E‐Shyong
Published: July 2008

Objective  This study assesses the effect of the metabolic syndrome on all‐cause and cardiovascular disease (CVD) mortality in healthy Chinese, Malays and Asian Indians in Singapore. The utility of the metabolic syndrome is also compared with the Framingham risk score for prediction of mortality.

Methods  Healthy participants (n = 5699) were grouped by the presence or absence of the metabolic syndrome, and followed up (mean 14·1 years) by data linkage with the National Death Register. Risk of mortality was obtained by Cox's proportional hazards model with adjusted hazard ratios (HRs). Area under receiver operating characteristic (ROC) curves were used to compare the metabolic syndrome and Framingham risk score for prediction of mortality.

Results  During a follow‐up of 80 236 person‐years, there were 382 deaths, of which 128 were due to CVD. Individuals with the metabolic syndrome had an increased risk of mortality for ‘all‐causes’ (males: HR 1·4, 95% confidence intervals (95%CI) 1·1–1·8; and females: HR 1·8, 95%CI 1·3–2·6). There was also an increased risk of mortality due to CVD (males: HR 3·0, 95%CI 1·9–4·8; and females: HR 2·1, 95%CI 1·1–4·0). The area under ROC for Framingham risk score was higher for both all‐cause and CVD mortality than metabolic syndrome.

Conclusions  Although an increased risk of ‘all‐cause’ and CVD mortality due to the metabolic syndrome was found, the Framingham risk function still performed better than the metabolic syndrome in an Asian population. However, the metabolic syndrome should not be disregarded as it is a clinically useful entity for identifying individuals for management of its component CVD risk factors.
Utility of serum tartrate‐resistant acid phosphatase (TRACP5b) as a bone resorption marker in patients with chronic kidney disease: independence from renal dysfunction
Authors: Yamada Shinsuke , Inaba Masaaki , Kurajoh Masafumi , Shidara Kaori , Imanishi Yasuo , Ishimura Eiji , Nishizawa Yoshiki
Published: July 2008

Background  Serum tartrate‐resistant acid phosphatase (TRACP) 5b levels were assessed in predialysis patients with chronic kidney disease (CKD). The aim of the study was to establish the usefulness of a new assay for TRACP5b in assessing bone turnover in these patients.

Methods  Serum concentrations of two bone resorption markers, TRACP5b and N‐terminal cross‐linking telopeptide of type I collagen (NTX); two bone formation markers, bone specific alkaline phosphatase (bone ALP) and intact osteocalcin (OC[1–49]); and PTH were measured in 98 predialysis CKD patients.

Results  Log serum TRACP5b and other bone markers were significantly negatively correlated with glomerular filtration rate (GFR) and positively correlated with log serum PTH, suggesting an increase in serum bone markers with development of secondary hyperparathyroidism. Multiple regression analysis including age, gender, BMI, the presence of diabetes, GFR and log serum PTH showed an association of log serum PTH with log serum TRACP5b and other bone markers. GFR was associated with log serum NTX and log OC[1–49], but not with log serum TRACP5b or log bone ALP. These data show that renal dysfunction does not influence serum TRACP5b and bone ALP, but has an influence on NTX and OC[1–49].

Conclusion  Serum TRACP5b may be a good marker for serum bone resorption in predialysis CKD patients, as it is not affected by renal dysfunction.
Ankle surgery in haemophilia with special emphasis on arthroscopic debridement
Authors: RODRIGUEZ‐MERCHAN E. C.
Published: July 2008

Summary.  Various conservative options are available to treat ankle problems in haemophilia, which achieve a high rate of satisfactory results in the majority of cases. They are usually employed in combination and include the use of patellar tendon bearing (PTB) orthoses and radiosynoviorthesis. The effect of the PTB orthoses is that it allows the patient to walk without weight bearing of the ankle. Radiosynoviorthesis can be performed in cases of haemophilic arthropathy of the ankle, provided there is at least a minimal degree of synovitis within the joint, with a 75% of satisfactory results. If the conservative options fail, surgical intervention can be indicated. Alternatives to total ankle arthroplasty or arthrodesis include arthroscopic debridement, removal of osteophytes of the anterior aspect of the distal tibia and peri‐articular osteotomies to correct angular, rotational or translational malalignment. Ankle arthrodesis is the standard technique for end‐stage ankle arthropathy. Arthroscopic debridement of the ankle with haemophilic arthropathy can offer temporary relief; however, it is important to stress to patients that the degree of improvement is limited. The complication rate in ankle arthroscopy is high compared with other joints, which is especially true for neurological complications and postoperative infections. Orthopaedic procedures are not very frequent in the haemophilic ankle, because the majority of problems can be solved satisfactorily by conservative means (radiosynoviorthesis and PTB orthosis).
Skin biopsy for the diagnosis of peripheral neuropathy
Authors: Lauria G , Lombardi R , Camozzi F , Devigili G
Published: July 2008

Skin biopsy has become an accepted tool for investigating small nerve fibres, which are invisible to conventional neurophysiological tests even though they are affected early on in peripheral neuropathies of varying aetiology. Morphometric analysis of epidermal and dermal nerves has proved to be reliable, reproducible and unaffected by the severity of neuropathy, making skin biopsy useful for diagnosing small fibre neuropathy (SFN) in clinical practice. The possibility of obtaining skin biopsy specimens from different sites of the body, to repeat them within the area of the same sensory nerve, to distinguish between somatic and autonomic nerves and to investigate the expression of nerve‐related proteins has widened the potential applications of this technique to clinical research. Skin biopsy performed using a minimally invasive disposable punch is a safe and painless procedure. Using specific antibodies with bright‐field immunohistochemistry or immunofluorescence technique, it is possible to investigate unmyelinated fibres innervating the epidermis of hairy and glabrous skin, large myelinated fibres supplying specialized corpuscles in glabrous skin, and autonomic fibres innervating sweat glands, blood vessels and arrector pilorum muscles. This review discusses the features of skin innervation in hairy and glabrous skin, the functional properties of skin nerve fibres and their changes in peripheral neuropathies.
SHP2 is up‐regulated in breast cancer cells and in infiltrating ductal carcinoma of the breast, implying its involvement in breast oncogenesis
Authors: Zhou X , Coad J , Ducatman B , Agazie Y M
Published: July 2008

Aims:  To determine whether Src homology phosphotyrosyl phosphatase 2 (SHP2) is up‐regulated in breast cancer and, if so, to determine whether its up‐regulation has any relationship with clinical variables of breast cancer.

Methods and results:  Immunoblotting, immunohistochemistry and immunofluorescence microscopy were used to assess the state of SHP2 expression in breast cancer cells and in infiltrating ductal carcinoma (IDC) of breast. The possible role of SHP2 in breast cancer cell transformation was determined by dominant‐negative expression and anchorage‐independent growth assays. All of the breast cancer cell lines tested and 72% of IDC breast tumours analysed had increased amounts of the SHP2 protein. In support of its positive role, dominant‐negative SHP2 blocked anchorage‐independent growth of breast cancer cells. Furthermore, overexpression of SHP2 seemed to have a positive relationship to HER2 overexpression, nuclear accumulation of hormone receptors, higher tumour grade and lymph node metastasis, but not to age of breast cancer patients.

Conclusion:  SHP2 is a widely overexpressed signalling protein in IDC breast tumours. Given SHP2’s positive role in cell growth, transformation and stem cell survival, the positive relationship of its overexpression to lymph node metastasis, nuclear accumulation of hormone receptors and higher tumour grade suggests that SHP2 promotes breast oncogenesis.
Completing the clinical governance cycle in dietetic gastroenterology outpatients
Authors: Cooper C. , Williams R. , Oxley S. , Burden S.
Published: July 2008

Background:  To overcome high rates of non‐attendance, inappropriate referrals and long waiting times, an audit was undertaken of a dietetic outpatients clinic for gastroenterology patients in 2003 and then repeated in 2007. The aim of the first audit was to identify referral source, types of patient, attendance rates and if dietary advice had a positive outcome. This study aimed evaluated changes since 2003.

Method:  The clinic diary was used to identify patients booked to attend in 2003 and 2007. Information was retrieved from the patient's record on source of referral, types of referral, waiting times, attendance rates and dietary goals achieved. The results were compared to determine if changes had improved service delivery. The data were analyzed in Microsoft Excel (2003) and the attendance rates were compared using chi‐squared statistics.

Results:  There were 92 new patients in 2003 and 69 patients in 2007; data were obtained for n = 77 in 2003 and n = 55 in 2007. There was an increase in referrals from gastroenterologists (n = 31, 55%) in 2007 compared with 2003 (n = 23, 34%). Waiting times improved between the two audits with 44% being seen within 3 months in 2003 compared to 51% in 2007. Attendance rates improved by 30% when the two audits were compared and in both years 2003 and 2007 (p = 0.009), a positive outcome was recorded for the majority of patients who had completed their treatment episodes 78% and 63% respectively.

 Types of patients referred to Gastroenterology clinic

Type of referral
2003
2007

Irritable bowel syndrome
4 (5)
12 (21)

Inflammatory bowel disease
15 (19)
7 (12)

Bariatric surgery
0
11 (20)

Pancreatitis
13 (16)
9 (16)

Gastric surgery
7 (9)
1 (2)

General GI
28 (36)
13 (23)

Non‐gastro
10 (12)
2 (3)

Discussion:  The literature on the audit cycle in dietetic outpatients is limited. The baseline results in 2003 lead to the production of guidelines and the subsequent audit in 2007 demonstrated an improvement in clinical effectiveness. There was incomplete retrieval of records for the 2007 audit that led to missing data.

Conclusion:  Guidelines for the clinic improved appropriateness of referrals and the focus of the clinic. The procedural changes have decreased non‐attendance and improved waiting times for patients. The changes implemented have improved service delivery for the patients and maximised the resources available for a specialist clinic by effectively utilising the skills of a Specialist gastroenterology dietitian.
An retrospective audit of patients with polycystic ovary syndrome: the effects of a reduced glycaemic load diet
Authors: Herriot A. M. , Whitcroft S. , Jeanes Y.
Published: July 2008

Background  Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and chronic anovulation. The aim of this retrospective audit was to determine the patient profile, including anthropometrics, biochemistry and symptoms, and to evaluate the influence of a dietary intervention in women with PCOS.

Methods  Data were collected retrospectively from dietetic and medical records from all PCOS patients (n = 88) who attended a dietetic consultation from July 2004 to July 2006. As standard clinic practice, a reduced glycaemic load diet had been prescribed, with energy reduction in overweight patients. Follow‐up data were available for 59 patients.

Results  Fifty‐eight patients had a body mass index (BMI) ≤ 24.9 kg m−2 and 30 had a BMI ≥ 25 kg m−2. Thirty‐six patients, with a BMI ≤ 24.9 kg m−2, self‐reported central weight gain at their initial appointment. Over two‐thirds of patients self‐reported one or more of the following symptoms: carbohydrate cravings, hypoglycaemia, tiredness and hunger. At the follow‐up appointment, BMI and waist circumference significantly decreased in overweight patients (P < 0.05). Seventy‐one percent of women self‐reported hypoglycaemia initially; this was reduced to 13% at follow‐up (P < 0.01).

Conclusions  The audit indicated a low glycaemic load diet in combination with medication may contribute to an improvement in symptom relief in patients with PCOS.
De novo DNA methylation induced by siRNA targeted to endogenous transcribed sequences is gene‐specific and OsMet1‐independent in rice
Authors: Miki Daisuke , Shimamoto Ko
Published: July 2008

Small interfering RNA (siRNA) is an essential factor for epigenetic modification of the genome. Recent studies have suggested that endogenous siRNAs induce DNA methylation, chromatin modification and chromatin inactivation at homologous sequences. We have shown that siRNAs targeted to promoter regions of endogenous rice genes induce strong DNA methylation of the targeted sequences, but transcriptional gene silencing is rarely observed. Here, an analysis of epigenetic modifications induced by RNAi targeted to transcribed regions of endogenous rice genes shows that the effects of siRNA are gene‐specific, but that they tend to induce higher de novo DNA methylation of CpG dinucleotides than of other cytosines. However, loss of OsMet1 expression by RNAi did not significantly affect levels and patterns of de novo DNA methylation or post‐transcriptional mRNA suppression. We also showed that sequence‐specific de novo DNA methylation extended both 5′ and 3′ of the targeted sequences, but there was no significant extension of siRNA signals either 5′ or 3′. These results suggest that exogenous siRNAs are strong inducers of de novo DNA methylation in transcribed sequences of rice endogenous genes, but are insufficient to induce heterochromatin formation.
The DDF1 transcriptional activator upregulates expression of a gibberellin‐deactivating gene, GA2ox7, under high‐salinity stress in Arabidopsis
Authors: Magome Hiroshi , Yamaguchi Shinjiro , Hanada Atsushi , Kamiya Yuji , Oda Kenji
Published: July 2008

High‐salinity stress affects plant growth and development. We have previously reported that overexpression of the salinity‐responsive DWARF AND DELAYED FLOWERING 1 (DDF1) gene, encoding an AP2 transcription factor of the DREB1/CBF subfamily, causes dwarfism mainly by levels of reducing bioactive gibberellin (GA) in transgenic Arabidopsis. Here, we found that the GA 2‐oxidase 7 gene (GA2ox7), which encodes a C20‐GA deactivation enzyme, is strongly upregulated in DDF1‐overexpressing transgenic plants. A loss‐of‐function mutation of GA2ox7 (ga2ox7‐2) suppressed the dwarf phenotype of DDF1‐overexpressing plants, indicating that their GA deficiency is due to overexpression of GA2ox7. Transient overexpression of DDF1 activated the promoter of GA2ox7 in Arabidopsis leaves. A gel shift assay showed that DDF1 binds DRE‐like motifs (GCCGAC and ATCGAC) in the GA2ox7 promoter. In Arabidopsis under high‐salinity stress, six GA2ox genes, including GA2ox7, were upregulated. Furthermore, the ga2ox7‐2 mutant was less growth retarded than wild‐type Col under high‐salinity stress. These results demonstrate that, under salinity stress, Arabidopsis plants actively reduce endogenous GA levels via the induction of GA 2‐oxidase, with the result that growth is repressed for stress adaptation.
PROCERAencodes a DELLA protein that mediates control of dissected leaf form in tomato
Authors: Jasinski Sophie , Tattersall Alex , Piazza Paolo , Hay Angela , Martinez‐Garcia Jaime F. , Schmitz Gregor , Theres Klaus , McCormick Sheila , Tsiantis Miltos
Published: July 2008

Leaves of seed plants can be described as simple, where the leaf blade is entire, or dissected, where the blade is divided into distinct leaflets. Mechanisms that define leaflet number and position are poorly understood and their elucidation presents an attractive opportunity to understand mechanisms controlling organ shape in plants. In tomato (Solanum lycopersicum), a plant with dissected leaves, KNOTTED1‐like homeodomain proteins (KNOX) are positive regulators of leaflet formation. Conversely, the hormone gibberellin (GA) can antagonise the effects ofKNOXoverexpression and reduce leaflet number, suggesting that GA may be a negative regulator of leaflet formation. However, when and how GA acts on leaf development is unknown. The reduced leaflet number phenotype of the tomato mutantprocera(pro) mimics that of plants to which GA has been applied during leaf development, suggesting that PRO may define a GA signalling component required to promote leaflet formation. Here we show thatPROencodes a DELLA‐type growth repressor that probably mediates GA‐reversible growth restraint. We demonstrate that PRO is required to promote leaflet initiation during early stages of growth of leaf primordia and conversely that reduced GA biosynthesis increases the capability of the tomato leaf to produce leaflets in response to elevated KNOX activity. We propose that, in tomato, DELLA activity regulates leaflet number by defining the correct timing for leaflet initiation.
A role for inositol hexakisphosphate in the maintenance of basal resistance to plant pathogens
Authors: Murphy Alex M. , Otto Bettina , Brearley Charles A. , Carr John P. , Hanke David E.
Published: July 2008

Phytic acid (myo‐inositol hexakisphosphate, InsP6) is an important phosphate store and signal molecule in plants. However, low‐phytate plants are being developed to minimize the negative health effects of dietary InsP6 and pollution caused by undigested InsP6 in animal waste. InsP6 levels were diminished in transgenic potato plants constitutively expressing an antisense gene sequence for myo‐inositol 3‐phosphate synthase (IPS, catalysing the first step in InsP6 biosynthesis) or Escherichia coli polyphosphate kinase. These plants were less resistant to the avirulent pathogen potato virus Y and the virulent pathogen tobacco mosaic virus (TMV). In Arabidopsis thaliana, mutation of the gene for the enzyme catalysing the final step of InsP6 biosynthesis (InsP5 2‐kinase) also diminished InsP6 levels and enhanced susceptibility to TMV and to virulent and avirulent strains of the bacterial pathogen Pseudomonas syringae. Arabidopsis thaliana has three IPS genes (AtIPS1–3). Mutant atips2 plants were depleted in InsP6 and were hypersusceptible to TMV, turnip mosaic virus, cucumber mosaic virus and cauliflower mosaic virus as well as to the fungus Botrytis cinerea and to P. syringae. Mutant atips2 and atipk1 plants were as hypersusceptible to infection as plants unable to accumulate salicylic acid (SA) but their increased susceptibility was not due to reduced levels of SA. In contrast, mutant atips1 plants, which were also depleted in InsP6, were not compromised in resistance to pathogens, suggesting that a specific pool of InsP6 regulates defence against phytopathogens.
ORTH/VIM proteins that regulate DNA methylation are functional ubiquitin E3 ligases
Authors: Kraft Edward , Bostick Magnolia , Jacobsen Steven E. , Callis Judy
Published: July 2008

Appropriate methylation of genomes is essential for gene regulation. Here, we describe the six‐member ORTHRUS (ORTH) gene family of Arabidopsis thaliana that plays a role in DNA methylation in vivo. ORTH1− ORTH5 are predicted to encode proteins that contain one plant homeodomain (PHD), two really interesting new gene (RING) domains, and one set ring associated (SRA) domain, whereas ORTHlike‐1 encodes a protein with only one RING and SRA domain. cDNAs for ORTH1, ORTH2, ORTH5 and ORTHlike‐1 were isolated, and when expressed as glutathione‐S‐transferase (GST) fusion proteins, were capable of promoting ubiquitylation in vitro with the E2 AtUBC11. ORTH1 promotes ubiquitylation when paired with additional AtUBC8 family members. ORTH1 proteins with substitutions in metal–ligand binding residues in each ORTH1 RING domain individually, and ORTH1 truncation derivatives lacking one or both RING domains, were tested for their ability to catalyze ubiquitylation in vitro. In these assays, either ORTH1 RING domain is capable of promoting ubiquitylation. The PHD alone is not active as an E3 ligase, nor is it required for ligase activity. GFP‐ORTH1 and GFP‐ORTH2 are nuclear‐localized in transgenic Arabidopsis plants. Overexpression of ORTH1 or ORTH2 in Arabidopsis leads to an altered flowering time. Inspection of DNA methylation at FWA and Cen180 repeats revealed hypomethylation when ORTH proteins were overexpressed. Once initiated, a late‐flowering phenotype persisted in the absence of the ORTH transgene, consistent with epigenetic effects at FWA. We conclude that ORTH proteins are E3 ligases mediating DNA methylation status in vivo.
The effects of the loss of TIP1;1 and TIP1;2 aquaporins in Arabidopsis thaliana
Authors: Schüssler Manuela Désirée , Alexandersson Erik , Bienert Gerd Patrick , Kichey Thomas , Laursen Kristian Holst , Johanson Urban , Kjellbom Per , Schjoerring Jan Kofod , Jahn Thomas Paul
Published: July 2008

Loss of aquaporin TIP1;1 in Arabidopsis has been suggested to result in early senescence and plant death. This was based on the fact that a partial reduction of TIP1;1 by RNA interference (RNAi) led to gradual phenotypes, ranging from indistinguishable from wild type to lethality, depending on the degree of downregulation of the target messenger, and displaying pleiotropic effects in primary metabolism and cell signalling. A hypothesis was put forward to suggest that TIP1;1, apart from its transport function, may play an essential role in vesicle routing. Here we identify an Arabidopsis transposon insertion line tip1;1‐1 that is completely devoid of TIP1;1 protein, as demonstrated by western blotting and immunolocalization using an isoform‐specific antibody. Strikingly, the complete absence of the protein did not result in any significant effect on metabolism or elemental composition of the plants. Microarray analysis did not indicate increased expression of other aquaporins to compensate for the lack of TIP1;1 in tip1;1‐1. We further developed a double mutant of TIPs in Arabidopsis, lacking both TIP1;1 and its closest paralog TIP1;2. Arabidopsis mutants lacking both TIP1;1 and TIP1;2 showed a minor increase in anthocyanin content, and a reduction in catalase activity, but showed no changes in water status. In contrast to earlier reports, plants lacking TIP1;1 and TIP1;2 aquaporins are alive and thriving. We suggest that RNAi directed towards TIP1;1 may have resulted in off‐target gene silencing, a notion that is potentially interesting for various studies analysing gene function by RNAi.
A study of the killer cell immunoglobulin‐like receptor gene KIR2DS1 in a Caucasoid Brazilian population with psoriasis vulgaris
Authors: Jobim M. , Jobim L. F. J. , Salim P. H. , Cestari T. F. , Toresan R. , Gil B. C. , Jobim M. R. , Wilson T. J. , Kruger M. , Schlottfeldt J. , Schwartsmann G.
Published: July 2008

Psoriasis is a chronic inflammatory skin disease whose pathogenesis and genetic background remain unclear. Considering that previous studies have suggested an association of psoriasis vulgaris (PV) and killer cell immunoglobulin‐like receptors (KIRs), we typed 15 KIR genes and human leukocyte antigen (HLA)‐Cw in 79 Brazilian Caucasoid patients with PV and 110 healthy controls by polymerase chain reaction (PCR) using sequence‐specific oligonucleotides and sequence‐specific primers. We did not observe a relevant increase in the frequency of the activating KIR2DS1 gene in the PV group [KIR2DS1, 46 of 79 cases (58.2%) vs 40 of 110 controls (36.4%)]. However, an association of KIR2DS1 with Cw*0602+ in 26.5% of PV patients was observed, while it was present in only 5.4% of controls. These results suggest that activating KIR2DS1 gene may not confer susceptibility to PV, and an association of KIR2DS1 gene with the HLA‐Cw*0602+ was observed in these patients.
The Milk‐Ejection Reflex in the Sheep: An Anatomical Study on the Afferent Pathway
Authors: Tsingotjidou A. S. , Papadopoulos G. C.
Published: July 2008

The present study is an attempt to reveal the spinal and supra‐spinal organization of the ascending branch of the milk‐ejection reflex in the ewe by means of a tract‐tracing technique. For this purpose, injections of horseradish peroxidase (HRP) were performed into the lateral cervical nucleus (LCN) and into the hypothalamic paraventricular nucleus (PVN). Peroxidase injections into the LCN revealed retrogradely labelled neurons in the medial part of laminae I–III of the ipsilateral L3 and L4 spinal segments, while injections of HRP into the PVN revealed retrogradely labelled cells in the contralateral LCN and the medial cuneate nucleus. Taking into account the results obtained, it is concluded that the transmission of the afferent input from the nipples to the PVN is accomplished by at least two pathways: one employing a single relay station located in the medial cuneate nucleus, and another possessing two relay stations located in the medial part of laminae I–III of the dorsal horn of L3 and L4 spinal segments and in the LCN.
Immunohistochemical Study of 3 β‐Hydroxysteroid Dehydrogenase in Dog’s Perianal Sinus
Authors: Stefanov I. , Vodenicharov A. , Gulubova M.
Published: July 2008

In this study, the localization of 3 β‐hydroxysteroid dehydrogenase (3β‐HSD) activity in the wall of canine perianal sinus (PS) was determined. The 3 β‐HSD activity was found out both in the cytoplasm of cells, situated in the propria and forming clusters adjacently to apocrine glands and in the cytoplasm of some epithelial cells in apocrine cells’ glands. The results obtained about the 3 β‐HSD activity allowed us to propose a role of this enzyme in PS development and possibly, in tumourogenesis.
Projections From the Anterior Interposed Nucleus to the Red Nucleus Diminish With Age in the Mouse
Authors: Olyntho‐Tokunaga H. H. V. , Pinto M. L. , Souccar C. , Schoorlemmer G. H. M. , Lapa R. C. R. S.
Published: July 2008

To analyse the effect of ageing on the projection of the anterior interposed nucleus to the red nucleus, we injected the retrograde tracer fluorogold in the red nucleus of 3‐, 6‐ and 12‐month‐old mice. The number of labelled neurones in the anterior interposed nucleus fell by 9% between 3 and 6 months and by another 9% between 6 and 12 months (all P < 0.001). This suggests that loss of neurones from the cerebellar nuclei starts well before old age.
Potential value of weedy regrowth for rainforest restoration
Authors: Kanowski John , Catterall Carla P. , Neilan Wendy
Published: July 2008

Summary  In subtropical Australia, regrowth forests in former rainforest landscapes are often dominated by the exotic tree, Camphor Laurel (Cinnamomum camphora). In this paper, we report on research into the value of these regrowth stands for rainforest biota. Our initial surveys indicated that Camphor Laurel stands supported a similar number of rainforest animals as restoration plantings, and usually more than timber plantations. Subsequent surveys found that stands of Camphor Laurel supported a high diversity of fruit‐eating birds and had recruited a diverse suite of rainforest plants. More recently, we surveyed stands of Camphor Laurel treated by restoration practitioners using ‘patch’ or ‘selective’ removal of exotic plants. We found that both treatment methods accelerated the recruitment of rainforest plants to Camphor Laurel stands, and that treatment was usually much cheaper than the cost of establishing restoration plantings. Recognition of the value of weedy regrowth for native plants and animals, and the potential utility of manipulating weedy regrowth to achieve cost‐effective restoration, could increase the likelihood of achieving the large‐scale increases in forest cover that will be needed to restore biodiversity and ecosystem services to extensively cleared regions.
Emergency relocation of a Purple Copper Butterfly colony during roadworks: Successes and lessons learned
Authors: Mjadwesch Raymond , Nally Simon
Published: July 2008

Summary  In 2004, the Roads and Traffic Authority (RTA) undertook a road realignment project near Lidsdale in the Central Tablelands of New South Wales. However, the RTA had not detected a population of the threatened Purple Copper Butterfly within the footprint of the project. The RTA responded promptly when notified of the butterflies’ presence by stopping works, and preparing and implementing a butterfly management programme. This programme included modifying the realignment (and reducing the development footprint), supplementary planting of habitat, habitat rehabilitation and translocation of individual caterpillars from within the final footprint area. These actions seem to have safeguarded the population at least in the short term; however, further active management of the site will be needed to ensure its long‐term viability. The project reinforces the importance of thorough predisturbance assessment of a site at the early planning stages, and the results and observations could be particularly informative in planning for introduction, reintroduction and translocation proposals involving the Purple Copper Butterfly.
Contrasting effects of selective lesions of nucleus accumbens core or shell on inhibitory control and amphetamine‐induced impulsive behaviour
Authors: Murphy E. R. , Robinson E. S. J. , Theobald D. E. H. , Dalley J. W. , Robbins T. W.
Published: July 2008

The core and shell subregions of the nucleus accumbens receive differential projections from areas of the medial prefrontal cortex that have dissociable effects on impulsive and perseverative responding. The contributions of these subregions to simple instrumental behaviour, inhibitory control and behavioural flexibility were investigated using a ‘forced choice’ task, various parameter manipulations and an omission schedule version of the task. Post‐training, selective core lesions were achieved with microinjections of quinolinic acid and shell lesions with ibotenic acid. After a series of behavioural task manipulations, rats were re‐stabilized on the standard version of the task and challenged with increasing doses of d‐amphetamine (vehicle, 0.5 or 1.0 mg/kg i.p. 30 min prior to test). Neither core‐ nor shell‐lesioned rats exhibited persistent deficits in simple instrumental behaviour or challenges to behavioural flexibility or inhibitory control. Significant differences between lesion groups were unmasked by d‐amphetamine challenge in the standard version of the forced task. Core lesions potentiated and shell lesions attenuated the dose‐dependent effect of d‐amphetamine on increasing anticipatory responses seen in sham rats. These data imply that the accumbens core and shell subregions do not play major roles in highly‐trained task performance or in challenges to behavioural control, but may have opposed effects following d‐amphetamine treatment. Specifically, they suggest the shell subregion to be necessary for dopaminergic activation driving amphetamine‐induced impulsive behaviour and the core subregion for the normal control of this behaviour via conditioned influences.
Abnormal spatiotemporal processing of emotional facial expressions in childhood autism: dipole source analysis of event‐related potentials
Authors: Wong Teresa K. W. , Fung Peter C. W. , Chua Siew E. , McAlonan Grainne M.
Published: July 2008

Previous studies of face processing in autism suggest abnormalities in anatomical development, functioning and connectivity/coordination of distributed brain systems involved in social cognition, but the spatial sequence and time course of rapid (sub‐second) neural responses to emotional facial expressions have not been examined in detail. Source analysis of high‐density event‐related potentials (ERPs) is an optimal means to examine both the precise temporal profile and spatial location of early electrical brain activity in response to emotionally salient stimuli. Therefore, we recorded 128‐channel ERPs from high‐functioning males with autism (aged 6–10 years), and age‐, sex‐ and IQ‐matched typically developing controls during explicit and implicit processing of emotion from pictures showing happy, angry, fearful, sad and neutral facial expressions. Children with autism showed normal patterns of behavioural and ERP (P1, N170 and P2) responses. However, dipole source analysis revealed that ERP responses relating to face detection (visual cortex) and configural processing of faces (fusiform gyrus), as well as mental state decoding (medial prefrontal lobe), were significantly weaker and/or slower in autism compared with controls during both explicit and implicit emotion‐processing tasks. Slower‐ and larger‐amplitude ERP source activity in the parietal somatosensory cortices possibly reflected more effortful compensatory analytical strategies used by the autism group to process facial gender and emotion. Such aberrant neurophysiological processing of facial emotion observed in children with autism within the first 300 ms of stimulus presentation suggests abnormal cortical specialization within social brain networks, which would likely disrupt the development of normal social‐cognitive skills.
Sleep‐wakefulness effects after microinjections of hypocretin 1 (orexin A) in cholinoceptive areas of the cat oral pontine tegmentum
Authors: Moreno‐Balandrán Elena , Garzón Miguel , Bódalo Cristina , Reinoso‐Suárez Fernando , De Andrés Isabel
Published: July 2008

Hypocretinergic/orexinergic neurons, which are known to be implicated in narcolepsy, project to the pontine tegmentum areas involved in the control of rapid eye movement (REM) sleep. Here, we report the effects on sleep‐wakefulness produced by low‐volume microinjections of hypocretin (Hcrt)1 (20–30 nL, 100, 500 and 1000 μm) and carbachol (20–30 nL, 0.1 m) delivered in two areas of the oral pontine tegmentum of free‐moving cats with electrodes for chronic sleep recordings: in the dorsal oral pontine tegmentum (DOPT) and in the ventral part of the oral pontine reticular nucleus (vRPO). Carbachol in the DOPT produced dissociate polygraphic states, with some but not all REM sleep signs. In contrast, carbachol in the vRPO produced a shift with short latency from wakefulness (W) to REM sleep with all of its polygraphic and behavioral signs. Hcrt‐1 in the DOPT increased W and decreased both slow‐wave sleep (SWS) and REM sleep during the first 3 h post‐drug. The same doses of Hcr‐1 in the vRPO produced a significant suppression of REM sleep without a definitive trend for changes in the other states. Both groups showed significant decreases in the number of transitions from SWS to REM sleep. Thus, Hcrt‐1 produced distinct effects in cholinoceptive areas of the oral pontine tegmentum; in the DOPT it promoted W, suppressed SWS and probably defacilitated REM sleep, and in the vRPO it directly inhibited REM sleep. Hypocretinergic/orexinergic signaling is lost in narcoleptics and this absence would mean that pontine defacilitation/inhibition of REM sleep would also be absent, explaining why these patients can fall directly into REM sleep from W.
Rac1 in cortical projection neurons is selectively required for midline crossing of commissural axonal formation
Authors: Kassai Hidetoshi , Terashima Toshio , Fukaya Masahiro , Nakao Kazuki , Sakahara Mizuho , Watanabe Masahiko , Aiba Atsu
Published: July 2008

Rac1 is a member of Rho family GTPases and regulates multiple cellular functions through actin cytoskeleton reorganization. During cerebral corticogenesis, Rac1 has been assumed to be involved in neuronal migration, neurite formation, polarization and axonal guidance. Here we show the specific role of Rac1, regulating midline crossing of commissural axons during cortical development by using cortex‐restricted Rac1‐knockout mice. In the knockout mice, Rac1 was eliminated from the beginning of corticogenesis exclusively in the dorsal telencephalon where progenitors of cortical projection neurons are located. Cortical lamination was distorted only mildly in the knockout mice, being preserved with six layers of neurons. However, cortex‐restricted Rac1 deletion exhibited striking agenesis of commissural axons including the corpus callosum and anterior commissure without affecting other corticofugal axons including corticospinal and corticothalamic projections. Of note, the commissural axons of the knockout mice were potent in extending their process, but failed to cross the midline. Therefore, these findings indicate that Rac1 specifically controls the midline crossing of the commissural fibers, but not axonal formation of corticospinal or corticothalamic fibers during cortical development.
The top‐down influence of ergogenic placebos on muscle work and fatigue
Authors: Pollo Antonella , Carlino Elisa , Benedetti Fabrizio
Published: July 2008

Placebos have been shown to induce powerful effects in a variety of medical conditions, such as pain and movement disorders, as well as to increase physical performance and endurance in healthy subjects. Here we investigated the effects of an ergogenic placebo on the performance of the quadriceps muscle, which is responsible for the extension of the leg relative to the thigh. In a first experiment, a placebo was administered along with the suggestion that it was caffeine at high dose. This resulted in a significant increase in mean muscle work across subjects, which, however, was not accompanied by a decrease of perceived muscle fatigue. In a second experiment, the placebo caffeine was administered twice in two different sessions. Each time, the weight to be lifted with the quadriceps was reduced surreptitiously so as to make the subjects believe that the ‘ergogenic agent’ was effective. After this conditioning procedure, the load was restored to the original weight, and both muscle work and perceived fatigue assessed after placebo administration. Compared with the first experiment, the placebo effect was larger, with a significant increase in muscle work and decrease in perceived muscle fatigue. Within the context of the role of peripheral and/or central mechanisms in muscle performance, the present findings suggest a central mechanism of top‐down modulation of muscle fatigue. In addition, the difference between the first and second experiment underscores the role of learning in increasing muscle performance with placebos.
It's all relative: ranking the diversity of aquatic bacterial communities
Authors: Shaw Allison K. , Halpern Aaron L. , Beeson Karen , Tran Bao , Venter J. Craig , Martiny Jennifer B. H.
Published: July 2008

The study of microbial diversity patterns is hampered by the enormous diversity of microbial communities and the lack of resources to sample them exhaustively. For many questions about richness and evenness, however, one only needs to know the relative order of diversity among samples rather than total diversity. We used 16S libraries from the Global Ocean Survey to investigate the ability of 10 diversity statistics (including rarefaction, non‐parametric, parametric, curve extrapolation and diversity indices) to assess the relative diversity of six aquatic bacterial communities. Overall, we found that the statistics yielded remarkably similar rankings of the samples for a given sequence similarity cut‐off. This correspondence, despite the different underlying assumptions of the statistics, suggests that diversity statistics are a useful tool for ranking samples of microbial diversity. In addition, sequence similarity cut‐off influenced the diversity ranking of the samples, demonstrating that diversity statistics can also be used to detect differences in phylogenetic structure among microbial communities. Finally, a subsampling analysis suggests that further sequencing from these particular clone libraries would not have substantially changed the richness rankings of the samples.
Colonization of overlaying water by bacteria from dry river sediments
Authors: Fazi Stefano , Amalfitano Stefano , Piccini Claudia , Zoppini Annamaria , Puddu Alberto , Pernthaler Jakob
Published: July 2008

We studied the diversity, community composition and activity of the primary microbial colonizers of the water above freshly re‐wetted sediments from a temporary river. Dried sediments, collected from Mulargia River (Sardinia, Italy), were covered with sterile freshwater in triplicate microcosms, and changes of the planktonic microbial assemblage were monitored over a 48 h period. During the first 9 h bacterial abundance was low (1.5 × 104 cells ml−1); it increased to 3.4 × 106 cells ml−1 after 28 h and did not change thereafter. Approximately 20% of bacteria exhibited DNA de novo synthesis already after 9 h of incubation. Changes of the ratios of 3H‐leucine to 3H‐thymidine incorporation rates indicated a shift of growth patterns during the experiment. Extracellular enzyme activity showed a maximum at 48 h with aminopeptidase activity (430.8 ± 22.6 nmol MCA l−1 h−1) significantly higher than alkaline phosphatase (98.6 ± 4.3 nmol MUF l−1 h−1). The primary microbial colonizers of the overlaying water – as determined by 16S rRNA gene sequence analysis – were related to at least six different phylogenetic lineages of Bacilli and to Alphaproteobacteria (Brevundimonas spp. and Caulobacter spp.). Large bacterial cells affiliated to one clade of Bacillus sp. were rare in the dried sediments, but constituted the majority of the planktonic microbial assemblage and of cells with detectable DNA‐synthesis until 28 h after re‐wetting. Their community contribution decreased in parallel with a rise of flagellated and ciliated protists. Estimates based on cell production rates suggested that the rapidly enriched Bacillus sp. suffered disproportionally high loss rates from selective predation, thus favouring the establishment of a more heterogenic assemblage of microbes (consisting of Proteobacteria, Actinobacteria and Cytophaga‐Flavobacteria). Our results suggest that the primary microbial colonizers of the water above dried sediments are passively released into the plankton and that their high growth potential is counteracted by the activity of bacterivorous protists.
Variations in the mosquito larvicidal activities of toxins from Bacillus thuringiensis ssp. israelensis
Authors: Otieno‐Ayayo Zachariah Ngalo , Zaritsky Arieh , Wirth Margaret C. , Manasherob Robert , Khasdan Vadim , Cahan Rivka , Ben‐Dov Eitan
Published: July 2008

Comparing activities of purified toxins from Bacillus thuringiensis ssp. israelensis against larvae of seven mosquito species (vectors of tropical diseases) that belong to three genera, gleaned from the literature, disclosed highly significant variations in the levels of LC50 as well as in the hierarchy of susceptibilities. Similar toxicity comparisons were performed between nine transgenic Gram‐negative species, four of which are cyanobacterial, expressing various combinations of cry genes, cyt1Aa and p20, against larvae of four mosquito species as potential agents for biological control. Reasons for inconsistencies are listed and discussed. Standard conditions for toxin isolation and presentation to larvae are sought. A set of lyophilized powders prepared identically from six Escherichia coli clones expressing combinations of four genes displayed toxicities against larvae of three mosquito species, with levels that differed between them but with identical hierarchy.
Injectable silicone biomaterial (PTQTM) is more effective than carbon‐coated beads (Durasphere®) in treating passive faecal incontinence – a randomized trial
Authors: Tjandra J. J. , Chan M. K. Y. , Yeh H. C. H.
Published: July 2008

Objective  Both injectable silicone biomaterial (PTQTM) and pyrolytic carbon‐coated beads (Durasphere®) have been shown to be effective in treating passive faecal incontinence due to internal sphincter dysfunction. This is a randomized study to evaluate their relative safety and efficacy.

Method  Forty patients (mean age 59.5 years vs 58.9 years) were randomized to have inter‐sphincteric injection of PTQTM or submucosal injection of Durasphere®. Patients were assessed with anorectal physiology, endoanal ultrasound, a validated incontinence score and quality of life questionnaires.

Results  In the Durasphere® group, complications included rectal pain (5%), erosion through rectal mucosa (10%), and type III hypersensitivity reaction (5%). No complications occurred in the PTQTM group. Compared with PTQTM, Durasphere® group has a more rapid action, with improved continence at 2 weeks after injection. In both groups, faecal continence significantly improved 6 weeks after injection, and continued to improve significantly up to 6 months in both groups (P < 0.0001). At 6 weeks, 6 and 12 months after injection, significantly more PTQTM patients achieved greater than 50% improvement in Wexner’s continence score than Durasphere® patients (respectively, P = 0.01; P < 0.0001; P = 0.001). There was a significant improvement in faecal incontinence quality of life scale and the 12‐month physical health scale of Short Form‐12 health survey in the PTQTM group but not in the Durasphere® group.

Conclusion  In patients with internal sphincter dysfunction, injectable silicone biomaterial was safer and more effective than Durasphere®.
Genetic Influences on Activity Level in Early Childhood: Do Situations Matter?
Authors: Saudino Kimberly J. , Zapfe Jeffrey A.
Published: July 2008

Although genetic influences on individual differences in activity level (AL) are well documented, few studies have considered the etiology of AL from a contextual perspective. In the present study, cross‐situational and context‐specific genetic effects on individual differences in AL at age 2 were examined. The AL of 312 twin pairs (144 monozygotic and 168 dzygotic) was mechanically assessed with actigraphs in the home and in laboratory test and play situations. AL displayed significant genetic variance in all 3 situations. Moreover, actigraph scores significantly correlated across situations. Multivariate genetic model‐fitting analyses found that the observed cross‐situational continuity in AL was due entirely to genetic factors. Situational differences in AL arise from genetic, shared environmental, and nonshared environmental influences.
Investigating the Development of Data Evaluation: The Role of Data Characteristics
Authors: Masnick Amy M. , Morris Bradley J.
Published: July 2008

A crucial skill in scientific and everyday reasoning is the ability to interpret data. The present study examined how data features influence data interpretation. In Experiment 1, one hundred and thirty‐three 9‐year‐olds, 12‐year‐olds, and college students (mean age = 20 years) were shown a series of data sets that varied in the number of observations and the amount of variance between and within observations. Only limited context for the data was provided. In Experiment 2, similar data sets were presented to 101 participants from the same age groups incrementally rather than simultaneously. The results demonstrated that data characteristics affect how children interpret observations, with significant age‐related increases in detecting multiple data characteristics, in using them in combination, and in explicit verbal descriptions of data interpretations.
The Role of General Practitioners in Migraine Management
Authors: Lantéri-Minet M
Published: July 2008

General practitioners (GPs) play a pivotal role in managing migraine and ensuring that patients have a positive first experience when seeking treatment. A large proportion of migraineurs do not consult a GP, preferring to rely on over-the-counter remedies to reduce pain and disability. For those who do consult, receiving a satisfactory outcome at their first consultation is important for ensuring subsequent effective management of their migraine. If patient expectations are not met at their first visit (prescribed treatment is ineffective or GP does not empathize with their suffering), patients may not return for further consultation. There remains a need to improve migraine diagnosis and treatment, and GPs require continuing medical education and neurologist support to ensure that they are providing the best migraine treatments and outcomes. More widespread use of diagnostic tools, standardized management guidelines and individualized treatment regimens will help GPs successfully manage both migraine symptoms and patient expectations.