bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Involvement of the Basolateral Amygdala and Mediodorsal Thalamus in Instrumental Action Selection
Authors: Ostlund Sean B. , Balleine Bernard W.
Published: April 2008

Although it has been shown that the basolateral amygdala (BLA) and the mediodorsal thalamus (MD) are critical for goal-directed instrumental performance, much remains unknown about the respective contributions of these structures to action selection. The current study assessed the effects of post-training BLA and MD lesions on several tests of instrumental action selection. We found that MD damage disrupted the influence of pavlovian cues over action selection but left intact rats' ability to select actions based on either the expected value or the discriminative stimulus properties of the outcome. In contrast, BLA lesions impaired performance on all three tests of action selection. Because both lesion types disrupted the influence of cues that signal reward over instrumental performance, we then investigated the involvement of these structures in pavlovian contingency learning using a task in which the predictive status of one of two cues is degraded by delivering its outcome noncontingently during the intertrial interval. As expected, the sham group selectively suppressed their conditioned approach performance to the cue that no longer signaled its outcome but continued to respond to the control stimulus. In contrast, both lesioned groups were impaired on this task. Interestingly, whereas the MD group displayed a nonspecific reduction in responding to both cues, the BLA group continued to show high levels of responding to both cues as if their performance was completely insensitive to this contingency manipulation. These findings demonstrate that the BLA and MD make important yet distinct contributions to instrumental action selection.
Isoflurane-Induced Caspase-3 Activation Is Dependent on Cytosolic Calcium and Can Be Attenuated by Memantine
Authors: Zhang Guohua , Dong Yuanlin , Zhang Bin , Ichinose Fumito , Wu Xu , Culley Deborah J. , Crosby Gregory , Tanzi Rudolph E. , Xie Zhongcong
Published: April 2008

Increasing evidence indicates that caspase activation and apoptosis are associated with a variety of neurodegenerative disorders, including Alzheimer's disease. We reported that anesthetic isoflurane can induce apoptosis, alter processing of the amyloid precursor protein (APP), and increase amyloid-β protein (Aβ) generation. However, the mechanism by which isoflurane induces apoptosis is primarily unknown. We therefore set out to assess effects of extracellular calcium concentration on isoflurane-induced caspase-3 activation in H4 human neuroglioma cells stably transfected to express human full-length APP (H4-APP cells). In addition, we tested effects of RNA interference (RNAi) silencing of IP3receptor, NMDA receptor, and endoplasmic reticulum (ER) calcium pump, sacro-/ER calcium ATPase (SERCA1). Finally, we examined the effects of the NMDA receptor partial antagonist, memantine, in H4-APP cells and brain tissue of naive mice. EDTA (10 mm), BAPTA (10 μm), and RNAi silencing of IP3receptor, NMDA receptor, or SERCA1 attenuated capase-3 activation. Memantine (4 μm) inhibited isoflurane-induced elevations in cytosolic calcium levels and attenuated isoflurane-induced caspase-3 activation, apoptosis, and cell viability. Memantine (20 mg/kg, i.p.) reduced isoflurane-induced caspase-3 activation in brain tissue of naive mice. These results suggest that disruption of calcium homeostasis underlies isoflurane-induced caspase activation and apoptosis. We also show for the first time that the NMDA receptor partial antagonist, memantine, can prevent isoflurane-induced caspase-3 activation and apoptosisin vivoandin vitro. These findings, indicating that isoflurane-induced caspase activation and apoptosis are dependent on cytosolic calcium levels, should facilitate the provision of safer anesthesia care, especially for Alzheimer's disease and elderly patients.
PET for Sarcomas Other Than Gastrointestinal Stromal Tumors
Authors: Toner Guy C. , Hicks Rodney J.
Published: April 2008

Positron emission tomography (PET) is increasingly used to diagnose, grade, and stage different types of tumors and to assess tumor response to therapy. Metabolic data acquired by fluorine-18-fluorodeoxyglucose (18FDG)-PET may facilitate accurate grading of sarcomas and have prognostic value when combined with other grading methods and various clinical/radiological features. In addition, 18FDG-PET is currently being evaluated in several cancer types for its utility in biopsy guidance. Whole-body 18FDG-PET also appears to be superior to other imaging modalities in detecting bone metastases in certain sarcoma patients. New PET tracers currently being investigated include 18F-fluorothymidine (18F-FLT) and 18F-misonidazole. 18F-FLT can help to determine tumor growth, rather than tumor shrinkage, which could be used to evaluate treatment response in sarcomas. PET imaging offers invaluable information to help maximize the clinical benefit of patients with sarcoma. This article reviews the use of PET in sarcoma management and its potential applications in the near future.
Other Endpoints in Screening Studies for Soft Tissue Sarcomas
Authors: Verweij Jaap
Published: April 2008

Despite extensive research efforts over the past two decades to identify effective agents for the treatment of soft tissue sarcomas, few agents are available, and with modest utility. There is a high unmet medical need to develop novel therapies for the treatment of patients with soft tissue sarcomas. Clinical trials for soft tissue sarcomas should be optimally designed, and it is crucial that they identify and define the desired clinical outcome. Survival is often the ultimate endpoint; however, physiological and biological markers are often used to predict the potential therapeutic benefit of a new agent. These endpoints can be easily measured, but can lead to false-positive results and do not take into account the complicated nature of soft tissue sarcomas. Alternative endpoints that are currently being evaluated include the progression-free survival rate, time to progression, tumor growth rate, and progression arrest rate. This article discusses some of the limitations of current endpoint criteria and potential endpoint criteria that could be used to evaluate treatment options for patients with soft tissue sarcomas.
The Lessons of GIST—PET and PET/CT: A New Paradigm for Imaging
Authors: Van den Abbeele Annick D.
Published: April 2008

Traditional anatomic tumor response criteria are based on uni- or bidimensional changes in tumor size, and do not take into account changes in tumor metabolism, tumor density, or decrease in the number of intratumoral vessels. These changes are, however, all indicative of response to imatinib therapy in patients with gastrointestinal stromal tumor (GIST). In these patients, metabolic responses seen on positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (18FDG) have been shown to be closely related to clinical benefit. Furthermore, these metabolic changes precede by weeks or months significant decrease in tumor size on computed tomography (CT). Conversely, lack of metabolic response on FDG-PET indicates primary resistance to the drug and may help identify patients who would benefit from another therapy, while re-emergence of metabolic activity within tumor sites following a period of therapeutic response indicates secondary resistance to the drug. Newly proposed CT criteria using either no growth in tumor size or a combination of tumor density and size criteria have shown a close correlation with the predictive value results of FDG-PET. Thus, the integration of FDG-PET and CT, as in the combined hybrid PET/CT scanners now available, will not only optimize the evaluation of patients with GIST treated with molecularly targeted drugs, but may ultimately help shorten clinical trials, and accelerate drug development in this disease and other cancers as well.
Association between (AC)n dinucleotide repeat polymorphism at the 5′-end of the aldose reductase gene and diabetic nephropathy: a meta-analysis
Authors: Xu Mingtong , Chen Xiaochao , Yan Li , Cheng Hua , Chen Weiqing
Published: April 2008

Association between the (AC)n dinucleotide repeat polymorphism at the 5′-end of the aldose reductase gene and the occurrence of diabetic nephropathy was conducted. We examined eight studies consisting of ten Caucasian type 1 diabetes mellitus case–control comparisons and eight studies consisting of nine type 2 diabetes mellitus case–control comparisons, which were based on our inclusion criterion and available in the literature. The meta-analysis demonstrated a large heterogeneity among the studies on the type 1 diabetic subjects and a significant association was observed between the (AC)n dinucleotide repeat polymorphism at the 5′-end of the aldose reductase gene and diabetic nephropathy. The Z−2 allele appeared to be a genetic risk factor for susceptibility to diabetic nephropathy with a random effects odds ratio (OR) of 1.40 (95% confidence interval, CI (1.07, 1.84)). The Z+2 allele showed a protective effect on diabetic nephropathy with a random effects OR of 0.77 (95% CI (0.65, 0.91)). The meta-analysis, however, showed no association between the genetic polymorphism and diabetic nephropathy in type 2 diabetic subjects. Neither the risk Z−2 allele nor the protective Z+2 allele in type 1 diabetic subjects appeared to have an effect on nephropathy in type 2 diabetic subjects, while their fixed effects OR was 1.09 (95% CI (0.96, 1.22)) and 0.88 (95% CI (0.67, 1.15)) respectively. The current meta-analysis demonstrated a correlation between the (AC)n dinucleotide repeat polymorphism and the occurrence of diabetic nephropathy in Caucasian type 1 diabetic subjects in contrast to type 2 diabetic subject population in which such an association could not be demonstrated.
Thyroid hormones promote cell differentiation and up-regulate the expression of the seladin-1 gene in in vitro models of human neuronal precursors
Authors: Benvenuti S , Luciani P , Cellai I , Deledda C , Baglioni S , Saccardi R , Urbani S , Francini F , Squecco R , Giuliani C , Vannelli G B , Serio M , Pinchera A , Peri A
Published: April 2008

Thyroid hormones (TH) play an important role in the development of human brain, by regulating the expression of specific genes. Selective Alzheimer's disease indicator-1 (seladin-1) is a recently discovered gene with neuroprotective properties, which has been found to be down-regulated in brain regions affected by Alzheimer's disease. Seladin-1 has anti-apoptotic properties mainly due to the inhibition of the activation of caspase 3. The aim of this study was to determine whether seladin-1 may be regarded as a new mediator of the effects of TH in the developing brain. In order to demonstrate this hypothesis, the effects of TH both on cell differentiation and on the expression of seladin-1 were assessed in two different cell models, i.e. fetal human neuroepithelial cells (FNC) and human mesenchymal stem cells (hMSC), which can be differentiated into neurons. 3,3′,5-Triiodothyronine (T3) determined different biological responses (inhibition of cell adhesion, induction of migration, and increase in the expression of the neuronal marker neurofilament-M and Na+ and Ca2+ channel functionality) in both FNC and hMSC, which express TH receptors. Then, we showed that TH significantly increase the expression levels of seladin-1, and that T3 effectively prevents camptothecin-induced apoptosis. However, in hMSC-derived neurons the expression of seladin-1 was not affected by TH. Our results demonstrated for the first time that seladin-1 is a novel TH-regulated gene in neuronal precursors. In view of its anti-apoptotic activity, it might be hypothesized that one of the functions of the increased seladin-1 levels in the developing brain may be to protect neuronal precursor cells from death.
Expression of glucocorticoid receptor, mineralocorticoid receptor, and 11β-hydroxysteroid dehydrogenase 1 and 2 in the fetal and postnatal ovine hippocampus: ontogeny and effects of prenatal glucocorticoid exposure
Authors: Sloboda Deborah M , Moss Timothy J M , Li Shaofu , Matthews Stephen G , Challis John R G , Newnham John P
Published: April 2008

To determine the expression of glucocorticoid metabolizing and action genes in the hippocampus of fetal, neonatal, and adult sheep. Pregnant ewes (or their fetuses) received intramuscular injections of saline or betamethasone (BETA, 0-5 mg/kg) at 104, 111, 118, and/or 125 days of gestation (dG). Hippocampal tissue was collected prior to (75, 84, and 101 dG), during (109 and 116 dG), or after (121, 132, and 146 dG; 6 and 12 postnatal weeks; 3.5 years of age) saline or BETA injections. Hippocampal glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and 11β-hydroxysteroid dehydrogenase (11βHSD)1 and 11βHSD2 mRNA levels were determined using qRT-PCR. Control animals late in gestation demonstrated a decrease in mRNA encoding GR and 11βHSD1, whereas 11βHSD2 was undetectable, consistent with a damping of the negative feedback influence of circulating or locally produced cortisol on the hypothalamic–pituitary–adrenal (HPA) axis. BETA-administration had transient effects on fetal GR and MR, and early in postnatal life (12 weeks of age) 11βHSD1 mRNA was increased. Hippocampal MR mRNA was elevated in adult offspring exposed to either one or four doses of maternal BETA (P<0.001). Four courses of maternal BETA increased 11βHSD2 (P<0.05) but not 11βHSD1 mRNA levels. Late in gestation a reduction in hippocampal GR and 11βHSD1 mRNA suggests lessening of glucocorticoid negative feedback, facilitating increased preterm HPA activity and parturition. Adult offspring of BETA-treated mothers demonstrated increased MR and 11βHSD2 mRNA, therefore it appears that exposure of fetus to high levels of synthetic glucocorticoids may have long-lasting effects on the hippocampal expression of HPA-related genes into adulthood.
Direct effects of prolactin and dopamine on the gonadotroph response to GnRH
Authors: Henderson Helen L , Townsend Julie , Tortonese Domingo J
Published: April 2008

The intrapituitary mechanisms underlying the inhibitory actions of hyperprolactinaemia on the reproductive axis remain unclear. Previous work on primary pituitary cultures revealed combined suppressive effects of prolactin (PRL) and dopamine on the gonadotrophin response to GnRH. However, whether these effects occur directly at the level of the gonadotroph and are accompanied by changes in gene expression is still unresolved. Here, αT3-1 and LβT2 cells were used to investigate the effects of PRL and dopamine on gonadotrophin synthesis and release in gonadotroph monocultures under basal and GnRH-stimulated conditions. PRL receptor and dopamine receptor mRNA expressions were first determined by RT-PCR in both cell lines. Then, PRL and the dopamine agonist bromocriptine (Br), alone or in combination, were shown to block the maximal α-subunit and LHβ-subunit mRNA responses to a dose-range of GnRH. The LH secretory response was differentially affected by treatments. GnRH dose-dependently stimulated LH release, with a 4–5 fold increase at 10−8 M GnRH. Unexpectedly, PRL or Br stimulated basal LH release, with PRL, but not Br, enhancing the LH secretory response to GnRH. This effect was, however, completely blocked by Br. These results reveal direct effects of PRL and dopamine at the level of the gonadotroph cell, and interactions between these two hormones in the regulation of gonadotrophin secretion. Moreover, uncoupling between LH synthesis and release in both the basal and the GnRH-stimulated responses to PRL and dopamine was clearly apparent.
High periostin expression correlates with aggressiveness in papillary thyroid carcinomas
Authors: Puppin Cinzia , Fabbro Dora , Dima Mariavittoria , Di Loreto Carla , Puxeddu Efisio , Filetti Sebastiano , Russo Diego , Damante Giuseppe
Published: April 2008

Periostin is a mesenchyme-specific gene product, which acts as an adhesion molecule during bone formation and supports osteoblastic cell line attachment and spreading. However, periostin expression is activated in a large variety of epithelial human tumors and correlates with their aggressiveness. Knowledge of expression of periostin in thyroid tumors is still scanty. The aim of the present work was to investigate periostin expression in differentiated neoplasms of the thyroid and to correlate it with several clinical and molecular features of these tumors. Periostin expression was evaluated by quantitative PCR and immunohistochemistry in normal thyroid tissues, papillary thyroid carcinomas (PTCs), follicular thyroid carcinomas (FTCs), and follicular adenomas (FAs). Periostin mRNA levels were also evaluated in several thyroid tumor cell lines. PTCs show mean periostin mRNA levels significantly higher than corresponding normal tissues. In five PTCs, periostin mRNA values were at least 30-fold higher than corresponding normal tissues. Conversely, mean periostin mRNA levels of FTCs and FAs were similar to those of normal tissues. Consistent with mRNA studies, periostin was detectable by immunohistochemistry in cancerous epithelial cells only in several cases of PTCs but not in normal tissue, FTCs, and FAs. In PTCs, periostin mRNA levels positively correlate with extrathyroidal invasion, distant metastasis, and higher grade staging. A negative correlation between periostin and expression of some markers of the thyroid-differentiated phenotype (thyroglobulin, thyrotropin receptor) was also present in the PTCs. These results indicate that an increase in periostin gene expression is present in several PTCs, in which it appears as a marker of aggressiveness. Experiments in thyroid tumor cell lines indicate that high levels of periostin mRNA are due, at least in part, to the increase in periostin promoter activity.
Neuropeptide Y mediates the initial hypothalamic–pituitary–adrenal response to maternal separation in the neonatal mouse
Authors: Schmidt Mathias V , Liebl Claudia , Sterlemann Vera , Ganea Karin , Hartmann Jakob , Harbich Daniela , Alam Stephanie , Müller Marianne B
Published: April 2008

The function of the hypothalamic–pituitary–adrenal (HPA) axis of the neonatal mouse or rat is characterized by a period of quiescence, where mild stimuli are unable to elicit a pronounced increase in circulating corticosterone. A disruption of this period by maternal separation has been shown to result in a variety of long-term consequences, including neuroendocrine and behavioral disturbances. We have recently shown that peripheral metabolic markers like glucose or ghrelin are altered by maternal separation and that these changes precede the effects on corticosterone secretion. In the current study, we investigated whether the initial activation of the HPA axis is mediated via neuropeptide Y (NPY). To test this hypothesis, we studied the effects of an 8 h maternal separation in NPY-deficient mice. In addition, we compared the effect of the genotype with the previously described pharmacological effect of a ghrelin receptor antagonist. We could show that the peripheral response to maternal separation is decreased in NPY heterozygous and homozygous animals. In addition, maternal separation effects on corticotropin releasing hormone and glucocorticoid receptor expression in the brain were prevented in NPY-deficient pups. These effects were similar to a pharmacological ghrelin receptor blockade. We conclude that metabolic signals via an NPY-mediated pathway play a crucial role in activating the stress system of the neonatal mouse.
Vasopressin potentiates corticotropin-releasing hormone-induced insulin release from mouse pancreatic β-cells
Authors: O'Carroll Anne-Marie , Howell Gillian M , Roberts Emma M , Lolait Stephen J
Published: April 2008

Arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH) have both been implicated in modulating insulin secretion from pancreatic β-cells. In the present study, we investigated the insulin-secreting activities of AVP and CRH in wild-type and AVP VIb receptor knockout mice. Both neuropeptides stimulated insulin secretion from isolated mouse pancreatic islets. The response of islets to CRH was increased fourfold by concomitant incubation with a subthreshold dose of AVP that alone did not stimulate insulin secretion. Activation of the endogenously expressed M3 receptor by the cholinergic agonist carbachol also potentiated CRH-induced insulin secretion, indicating that the phenomenon may be pathway specific (i.e. Ca2+-phospholipase C) rather than agonist specific. The protein kinase C (PKC) inhibitors Ro-31-8425 and bisindolylmaleimide I attenuated the potentiating effect of AVP on CRH-stimulated insulin secretion and blocked AVP-stimulated insulin secretion. A possible interaction between the PKC and protein kinase A pathways was also investigated. The phorbol ester phorbol myristate acetate (PMA) stimulated insulin secretion, while the addition of both PMA and CRH enhanced insulin secretion over that measured with either PMA or CRH alone. Additionally, no AVP potentiation of CRH-stimulated insulin secretion was observed upon incubation in Ca2+-free Krebs–Ringer buffer. Taken together, the present study suggests a possible synergism between AVP and CRH to release insulin from pancreatic β-cells that relies at least in part on activation of the PKC signaling pathway and is dependent on extracellular Ca2+. This is the first example of a possible interplay between the AVP and CRH systems outside of the hypothalamic–pituitary–adrenal axis.
Beneficial effects of lipids and prolactin on insulin secretion and β-cell proliferation: a role for lipids in the adaptation of islets to pregnancy
Authors: Brelje T Clark , Bhagroo Nicholas V , Stout Laurence E , Sorenson Robert L
Published: April 2008

To meet the increased demand for insulin during pregnancy, the pancreatic islets undergo adaptive changes including enhanced insulin secretion and β-cell proliferation. These changes peak in mid-pregnancy and return to control levels by parturition. Because lactogens (placental lactogen and/or prolactin) induce this up-regulation and remain elevated throughout gestation, we examined whether lipids alter the effects of prolactin on islets. In response to prolactin, there was a 2.5-fold increase in insulin secretion when compared with control islets. There was also a 2.5-fold increase in insulin secretion in response to palmitate and a fivefold increase when islets were cultured with a combination of prolactin and palmitate. After culture with prolactin and palmitate, acute stimulation with 10 mM glucose for 1 h showed a suppression of insulin release. However, including palmitate in the stimulation media (a condition similar to late pregnancy in vivo) restored a higher rate of insulin release. This suggests that elevated lipids in late pregnancy lead to enhanced insulin secretion that is increasingly dependent on lipids and less sensitive to glucose. β-Cell proliferation was also increased sixfold by prolactin and threefold with palmitate. The combination of both was slightly more than additive (11-fold). Similar experiments with oleate had no effect on insulin secretion. However, oleate stimulated β-cell division by threefold and was synergistic with prolactin (21-fold). These results were repeated in experiments including normal serum. Interestingly, prolactin also blocked the reduction of glucokinase levels observed with fatty acids. Overall, these results suggest that increased lipids during pregnancy likely contribute to the adaptation of islets to pregnancy by further enhancing β-cell division. In addition, the increase in lipids leads to enhanced insulin secretion that is less sensitive to glucose and more dependent on lipids. This provides a potential mechanism for maintaining elevated insulin secretion until parturition while preparing islets for normal glucose sensitivity post partum.
The discontinuance of Boltby reservoir, North Yorkshire, UK
Authors: Walker Jonathan P.
Published: April 2008

Boltby reservoir, North Yorkshire, UK, was completed in 1880 as a means of water supply to the local area. In June 2005 a flood event with a return period in excess of 1 in 10 000 years caused significant damage to the masonry-lined spillway structure. The reservoir had not been used for supply since 2003 and it was subsequently decided to discontinue the reservoir under section 13 of the Reservoirs Act 1975. The discontinuance work consisted of the excavation of a notch in the dam approximately 70 m wide at crest level. A new low-level overflow channel was constructed at the bottom of the notch such that the remaining dam impounds less than 25 000m3 of water. Construction work began in early October 2006 and the discontinuance phase of the scheme was completed in late February 2007. This paper describes the design and construction phase of the discontinuance project including the development of a detailed water level control and contingency plan and a large amount of environmental engineering works.
Discontinuance of Warren dam, Hampshire, UK
Authors: Donovan Katy
Published: April 2008

In terms of reservoir safety, discontinuance has never been, and will never be, an easy option. This paper looks at the issues arising from the proposed discontinuance of a relatively small dam in Havant, Hampshire, UK. This paper will look at the problems, which include the social, health and safety, flood risk and environmental issues faced by the engineer. Warren dam has been subject to a long history of vandalism and has never been used to its full potential, making discontinuance an attractive option to the undertaker.
14th German dam symposium and 7th ICOLD European Club dam symposium, 17–19 September, 2007
Authors: Falkingham John , Kite Peter
Published: April 2008

The 14th German dam symposium was held at Freising, near Munich, over two days, together with a third day visiting Sylvenstein reservoir, Walchensee hydropower station and Munich Technical University's hydraulic engineering laboratory at Obernach. It was attended by almost 500 delegates, about a third of whom were from a total of 28 other countries, including 16 delegates from the UK. The conference was held jointly with the 7th International Commission of Large Dams (ICOLD) European Club.
The Effects of Project Success on Student Academic Performance: A Quasi-Experimental Study
Authors: Shamblen Stephen R. , Ringwalt Chris
Published: April 2008

Project SUCCESS (PS) is a substance use prevention program that targets indicated high school students. We used archival data to explore the program's effects on students' academic achievement and disciplinary problems. It is essential to demonstrate such effects, if prevention curricula are to survive in schools that face multiple competing demands for class time. Using a quasi-experimental design that compared students exposed to the program to those not exposed in five schools, we examined the effects of PS on grades, absenteeism, and disciplinary problems. Using longitudinal analyses that linked individual students' program exposure data to their academic performance, we found that PS had a positive impact on both grades and absenteeism for two years following exposure. We note that these findings are particularly fortuitous, as PS was not designed to affect these outcomes. We recommend that future evaluations of school-based prevention curricula routinely include academic performance.
Evaluation of the Association of IGF2BP2 Variants With Type 2 Diabetes in French Caucasians
Authors: Duesing Konsta , Fatemifar Ghazaleh , Charpentier Guillaume , Marre Michel , Tichet Jean , Hercberg Serge , Balkau Beverley , Froguel Philippe , Gibson Fernando
Published: April 2008

OBJECTIVE—We performed a comprehensive genetic association study of common variation spanning the IGF2BP2 locus in order to replicate the association of the “confirmed” type 2 diabetes susceptibility variants rs4402960 and rs1470579 in the French Caucasian population and to further characterize the susceptibility variants at this novel locus.

RESEARCH DESIGN AND METHODS—We genotyped a total of 21 tagging single nucleotide polymorphisms spanning the IGF2BP2 locus in our type 2 diabetes case-control cohort comprising 3,093 French Caucasian subjects.

RESULTS—IGF2BP2 variants rs4402960 and rs1470579 were not associated with type 2 diabetes in the present study (P = 0.632 and P = 0.896, respectively). Meta-analysis of genotype data from over 34,000 subjects demonstrated that our inability to replicate rs4402960/rs1470579 was consistent with the findings from several previous genome-wide association study (GWAS) datasets that were underpowered to detect this modest association signal (odds ratio [OR] 1.14). We obtained novel evidence that rs9826022, a borderline rare variant (5% minor allele frequency) in the 3′ downstream region, was associated with type 2 diabetes (P = 0.0002; OR 1.53 [95% CI 1.22–1.91]). This result was corroborated by the meta-analysis of 10,542 genotypes from the current study and GWAS datasets using both fixed (P = 9.47 × 10−6; 1.30 [1.16–1.46]) and random effects (P = 0.001; 1.30 [1.11–1.52)] calculations.

CONCLUSIONS—We were unable to replicate the confirmed rs4402960/rs1470579 susceptibility variants but found novel evidence for a rare variant in the 3′ downstream region of IGF2BP2. Further genetic and functional studies are required to identify the etiological IGF2BP2 variants.
Jean-Jacques Rousseau's copy of Albrecht von Haller's Historia stirpium indigenarum Helvetiae inchoata (1768)
Authors: Cook A.
Published: April 2008

Jean-Jacques Rousseau sold his botanical texts to Daniel Malthus (father of Thomas Malthus) about 1775. Two of these are now in the Old Library, Jesus College, Cambridge, but all the rest have long been thought lost. However, a copy of Albrecht von Haller's Historia stirpium indigenarum Helvetiae inchoata (1768) in The Lindley Library, Royal Horticultural Society, London, bears Rousseau's name and seems to have been annotated by him. The volume contains the bookplate of Jane Dalton, a cousin to whom Malthus willed “all [his] Botanical Books in which the Name of Rousseau is written”. Haller was well-known to Rousseau, who, while in exile in the Swiss Jura (1763–1765), studied under one of Haller's collaborators, Abraham Gagnebin. Rousseau cited Haller's entry 762 when describing a species of Seseli to the Duchess of Portland.
The preparation and publication of James Crombie's A monograph of lichens found in Britain (1894), as documented in his letters to William Nylander
Authors: Mitchell M. E.
Published: April 2008

Between 1869 and 1894 James Crombie (c. 1831–1906) contributed substantially to the literature of lichenology; many of his publications concern additions to the British flora, others are reports on collections of exotic material, and several relate to the debate occasioned by the discovery that lichens are composite organisms. Crombie is, however, remembered principally for his descriptive catalogue of the collections in the then British Museum (Natural History), the first part of which was published in 1894 under the title A monograph of lichens found in Britain. In preparing that work – and most of his other publications – Crombie received considerable help from the foremost lichen taxonomist of the day, William Nylander (1822–1899), with whom he began a 25-year correspondence in 1868. Drawing on that correspondence, which comprises almost 150 items, this paper details the long gestation of Crombie's catalogue. Previously unreported biographical information relating to Crombie is also provided.
Bartholomew James Sulivan's discovery of fossil vertebrates in the Tertiary beds of Patagonia
Authors: Brinkman P.
Published: April 2008

While commanding a Royal Navy survey of the Falkland Islands in 1845, Bartholomew James Sulivan discovered and collected fossil mammals at Rio Gallegos, Patagonia. Described the following year by Richard Owen, Sulivan's specimens comprised the first collection taken from what would later be designated the Santa Cruz beds (early-middle Miocene), the most prolific fossil mammal horizon in South America and the oldest discovered by Sulivan's time. Unfortunately, Charles Darwin's conservative estimate of the age of the fossils delayed the full appreciation of Sulivan's discovery. Sulivan was only moderately successful at attracting interest in his discovery among British naturalists. By the time that the first extensive collections of Santa Cruz fossil mammals were made by Argentine paleontologists Carlos and Florentino Ameghino, in the 1890s, Sulivan's pioneering role in the history of South American vertebrate paleontology had been overshadowed and all but forgotten. An examination of Sulivan's experience provides a general model for the process whereby some contributors to science descend from initial fame to lasting obscurity.
George Bentham's Handbook of the British flora: from controversy to cult
Authors: Allen D. E.
Published: April 2008

George Bentham's Handbook of the British flora sold steadily for almost a century from its publication in 1858 to the relatively inexperienced for whom it was explicitly intended, thanks to full descriptions, dichotomous keys and a lengthy exposition of botanical terminology. But in using it as a vehicle for his controversially broad conception of species, and in aggressively dismissing in the preface the validity of much work by those who, unlike him, had long investigated that flora critically, Bentham provoked lasting hostility to the book among the more advanced. The continued buoyancy of its sales after Bentham's death owed less to limited revisions by Sir Joseph Hooker than to the dying-off of its competitors and the addition of W. H. Fitch's line-drawings of every species, the colouring-in of which became popular as a substitute for collecting specimens. The book's aggregate approach in its taxonomy, however, had a divisive effect on the field botany community, a situation ended in 1952 by the Flora of the British Isles of A. R. Clapham, T. G. Tutin and E. F. Warburg and its subsequent associated volumes.
“The great question in agitation”: George Bentham and the origin of species
Authors: Bellon Richard
Published: April 2008

George Bentham initially expressed reservations about Darwin's Origin of species (1859). What most troubled Bentham was the potentially disruptive nature of Darwin's ideas for natural history. Bentham, renowned even among other naturalists for always proceeding with the utmost intellectual caution, decided to ignore Darwin's theory. This reticence disappointed Darwin, who pressured Bentham unsuccessfully to give an assessment of the Origin. Bentham did, however, publicly praise Darwin's work on the fertilisation of orchids as an ideal model for natural history research. Finally, in his 1863 presidential address to the Linnean Society, Bentham directly addressed “the great question in agitation”, evolution. His judicious praise of the Origin would, Darwin was convinced, “do more to shake the unshaken & bring on those leaning to our side, than anything written directly in favour of transmutation.” Bentham's tentative conversion to evolution came only after Darwin's work, particularly on orchids, convinced him that evolution would add “stability” to systematic work. As a result, evolution's influence on systematic botany was largely conservative. It validated, rather than challenged, the method, systems, world view and intellectual authority of established experts like Bentham.
Natural history and the philosophical societies of late Victorian Yorkshire
Authors: Alberti Samuel J. M. M.
Published: April 2008

Natural history, so popular a pursuit in nineteenth-century Britain, was a thriving part of the activities of the literary and philosophical societies that epitomized urban middle-class cultural life. The “lit and phils” are most famous for their museums, but this paper outlines the range of other activities pertaining to natural knowledge that went on within their walls, focusing on the thriving societies in England's largest county, Yorkshire. Foremost among these were regular lectures: this paper discusses the speakers, audience and content, as well as the significance of the architecture of the halls in which they were staged. More exclusive meetings and didactic classes are also examined, as well as their (often extensive) libraries. After a brief examination of the purported decline of the philosophical societies around the turn of the century, a conclusion outlines the importance of science within these voluntary associations both to the provincial middle classes and the emerging professional men of science.
The white dodo of Réunion Island: unravelling a scientific and historical myth
Authors: Hume Julian Pender , Cheke Anthony S.
Published: April 2008

ABSTRACT: The supposed white dodo of Réunion Island (Indian Ocean) arose from a merging of travellers' tales of large whitish birds with some enigmatic paintings of white dodos painted in mid- to late- seventeenth-century Holland. Sub-fossil bone discoveries in the 1970s onwards revealed that the bird which travellers called a solitaire was a large, quasi-flightless ibis, while the Dutch paintings turn out to have been based on a much earlier picture by Roelant Savery of a whitish specimen of a Mauritius dodo (Raphus cucullatus), painted in Prague around 1611. Savery's dodo images impact on this story at various points and are discussed in detail. There are geological reasons for believing dodos, evolving in Mauritius, would have been already flightless before Réunion emerged and hence could not have colonised that more recent volcanic island. No contemporary images are known of the Réunion solitaire (the ibis, Threskiornis solitarius) and no specimens were brought to Europe alive or dead.
An annotated catalogue of the printed illustrations by Franz Bauer (1758–1840)
Authors: Lack H. Walter
Published: April 2008

ABSTRACT: A short biography of Franz Bauer (1758–1840) is given, who was a prolific illustrator in the fields of botany, zoology, human anatomy and pathology. His commissions came mainly from Norbert Boccius, Nikolaus Joseph Jacquin, Sir Joseph Banks and Sir Everard Home. Comparatively late in life Franz Bauer became a scientist in his own right, but published little. An annotated list of the printed illustrations by Franz Bauer is included as well as a synopsis correlating several of them with Home's Lectures on comparative anatomy.
The economy of nature in the botany of Nehemiah Grew (1641–1712)
Authors: Anker P.
Published: April 2008

Historians of natural history often point to the emergence of mathematical and mechanical reasoning in the early-modern period as a pivotal episode in scientifi c understanding of the organic world. This paper visits the natural philosophy of one of the chief supporters of this view of nature, the first curator of plants at The Royal Society, Nehemiah Grew. It sets his work within the material world of patronage, medical and mathematical tools, laboratory life, and his views on human virtues, health and the role of women. The view taken is of Grew as a religiously informed natural philosopher whose understanding of the economy of nature acknowledges the wisdom of the Creator and the possibility of gaining spiritual and bodily health from studying the language of the book of nature. The quest to understand nature's language consisted in tempering human will and arrogance so that one could appreciate the Lord's creative power in the world. As representative of The Royal Society's promotion of empirical and mechanical research, Grew mobilized excitement for natural history and botany with an ethos of showing respect to nature's economy.
Usamaro Takakura (1867–1944), Japanese pioneer nemertean researcher
Authors: Kajihara Hiroshi
Published: April 2008

Usamaro Takakura (1867–1944), a pioneer Japanese specialist on nemerteans (phylum Nemertea), established 14 new species and one new genus, Coeia. This paper gives a brief outline of his life and publications, together with the list of his new taxa, the type materials for which are all lost.
Georges-Louis Leclerc de Buffon's Histoire naturelle in English, 1775–1815
Authors: Loveland Jeff
Published: April 2008

Published in French to considerable acclaim between 1749 and 1767, the 15-volume opening sub-series of Georges-Louis Leclerc de Buffon's Histoire naturelle was first translated into English in near entirety in 1775–1776. Over the next 40 years, two further comprehensive English-language translations were prepared and published in four editions each. This paper describes the three major English translations of Buffon's Histoire naturelle and compares their coverage, order, style, accuracy and footnotes. Supplemented with information from reviews, advertisements and partial translations and adaptations, the history of the large-scale English-language translations of Histoire naturelle provides clues about Buffon's reception in the Anglophone world.
“Behind folding shutters in Whittingehame House”: Alice Blanche Balfour (1850–1936) and amateur natural history
Authors: Opitz Donald L.
Published: April 2008

During the rise of professional biology in the late nineteenth and early twentieth century, individual naturalists continued to develop private collections by modest means and often within their own homes. Despite the increasing opportunities for women to participate in the sciences, the number of women entomologists remained relatively few. The amateur entomological career of Alice Blanche Balfour, the younger sister of Arthur James Balfour, first Earl of Balfour, reveals how a confluence of personal and social factors shaped a gentlewoman's capacity to pursue her interests in natural history. This paper revises earlier images of Alice Balfour by presenting her as an accomplished amateur naturalist who balanced her avocation with the responsibility of managing the daily domestic affairs of estate.
Victorian natural scientists overlooking the Firth of Clyde: a rare, early group-photograph decoded
Authors: Moore P. G.
Published: April 2008

The identities of four eminent nineteenth-century naturalists together in an old photograph on display at the University Marine Biological Station at Millport are revealed as Professor R. A. von Kölliker, Dr W. B. Carpenter FRS, Professor W. Sharpey FRS and Professor J. H. Balfour FRS. Brief biographies are provided. It is suggested that the photograph dates from the British Association for the Advancement of Science's meeting in Glasgow in September 1855. The venue seems likely to have been Carpenter's rented “cottage” on Holy Island, which provided a base for marine biological investigations in the adjacent Lamlash Bay, Arran. The historical significance of this notable early photograph resides in the evidence it confers regarding the relationships between these world-class scientific figures.
Some early drawings by Robert Hooke
Authors: Neri Janice L.
Published: April 2008

Several recently discovered drawings of insects are attributed to Robert Hooke and his collaborators, and their relationship to Hooke's Micrographia is discussed. The annotated drawings reveal a hitherto unknown working relationship between Hooke and several collaborators in making and recording microscopic observations. One of these collaborators is tentatively identified as the London instrument-maker Ralph Greatorex.
A century of Antarctic science; planning and serendipity
Authors: Fogg G. E.
Published: April 2008

The British National Antarctic Expedition planned with discreditable bickering, sailed for the Antarctic in 1901 on the Discovery. The venture was well equipped and commanded by R. F. Scott who, without scientific training himself, was nevertheless remarkably in empathy with his scientists. The expedition was foremost among those dispatched around the same time in establishing basic knowledge of the continent. Followed by the second Scott expedition and those of Shackleton and Mawson, a cadre of able and enthusiastic scientists was established.

The second involvement of the Discovery in Antarctic exploration was planned without quarrels and with unusual understanding of science by a government department, resulting in a massive accumulation of knowledge about the Southern Ocean. United States expeditions began in 1928, introducing modern technology, thereby extending greatly the scope of Antarctic research. The Norwegian-British-Swedish expedition of 1949–1952 put planned science before geographical exploration. The International Geophysical Year of 1957–1958, supported by governments and planned by international committees, achieved great success. Science has flourished in Antarctica with unplanned and serendipitous findings emerging, for example, the structure of the magnetosphere, collection of meteorites by ice movements, the microbial life of the apparently sterile Dry Valleys and the discovery of the ozone “hole”.
The Poles: information for exploration
Authors: Headland R. K.
Published: April 2008

The development of knowledge from exploration and research in both polar regions is indicated, with particular emphasis on international co-ordination of scientific investigation and dissemination of literature. Periods where this was essentially national are contrasted with current circumstances of work in the Arctic and Antarctic where economy and efficiency of effort are particularly important. Historical stages and phases of exploration are distinguished. Most exploration has been governmental but contributions by many private expeditions are also significant.
From natural history to biodiversity: collections of discovery
Authors: Rainbow Philip S.
Published: April 2008

The Natural History Museum, London, houses more than 70,000 jars with more than 5 million specimens of marine animals that constitute the Discovery collections. The Discovery collections are the specimens from the twentieth-century expeditions of British oceanographic ships, a series that began in 1904 with the return of the SY Discovery from the Antarctic. These marine collections are an irreplaceable asset in the history of biological oceanography, spanning a time of changes – change in the use of such collections and dramatic global environmental change. Collections of animals have graduated from being objects of wonder to satisfy curiosity to be essential reference collections for the taxonomy and nomenclature of the world's diversity, underpinning attempts to decipher patterns of marine biodiversity and evolutionary relationships. The Discovery collections offer a record of oceanic life as it was, before the demise of the great whales, before the ozone “hole” and before global warming. The foresight of the collectors of this unique archive can be rewarded by their use as an active research tool, using modern molecular and analytical techniques, and others yet to be imagined.
Southern Ocean circulation
Authors: Cunningham Stuart A.
Published: April 2008

The Discovery Investigations of the 1930s provided a compelling description of the main elements of the Southern Ocean circulation. Over the intervening years, this has been extended to include ideas on ocean dynamics based on physical principles. In the modern description, the Southern Ocean has two main circulations that are intimately linked: a zonal (west-east) circumpolar circulation and a meridional (north-south) overturning circulation. The Antarctic Circumpolar Current transports around 140 million cubic metres per second west to east around Antarctica. This zonal circulation connects the Atlantic, Indian and Pacific Oceans, transferring and blending water masses and properties from one ocean basin to another. For the meridional circulation, a key feature is the ascent of waters from depths of around 2,000 metres north of the Antarctic Circumpolar Current to the surface south of the Current. In so doing, this circulation connects deep ocean layers directly to the atmosphere. The circumpolar zonal currents are not stable: meanders grow and separate, creating eddies and these eddies are critical to the dynamics of the Southern Ocean, linking the zonal circumpolar and meridional circulations. As a result of this connection, a global three-dimensional ocean circulation exists in which the Southern Ocean plays a central role in regulating the Earth's climate.