bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackground  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

SummarySmall 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

SummaryHigh‐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

SummaryLeaves 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

SummaryPhytic 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

SummaryAppropriate 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

SummaryLoss 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

AbstractPsoriasis 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

SummaryThe 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

SummaryIn 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

SummaryTo 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.
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

AbstractThe 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

AbstractPrevious 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.