bluuebunny/crossref_metadata_2025 huggingface dataset:
β‐amyloid inhibition of long‐term potentiation is mediated via tumor necrosis factor
Authors: Wang Qinwen , Wu Jinqun , Rowan Michael J. , Anwyl Roger
Published: November 2005

A number of recent studies have shown that β‐amyloid (Aβ) inhibits the induction of long‐term potentiation (LTP) in the hippocampus. However, little is known about the mechanisms underlying such inhibition of LTP. In the present study, we present evidence that the cytokine tumor necrosis factor (TNF) α has a key role in the Aβ inhibition of LTP. The suppression of LTP by Aβ was absent in mutant mice null for TNF receptor type 1 (TNF‐R1) and was prevented by the inhibitors of TNFα, infliximab and TNF peptide antagonist, and by the inhibitor of TNFα production, thalidomide. In addition, exogenous TNFα inhibited LTP induction, an action mediated via TNF‐R1 as such inhibition was absent in mutant mice null for TNF‐R1. The inhibition of LTP by TNFα involved activation of group I metabotropic glutamate receptor and p38 MAP kinase, identical to that for the Aβ‐mediated inhibition of LTP induction.
Increased discharge threshold after an interictal spike in human focal epilepsy
Authors: de Curtis Marco , Tassi Laura , Lo Russo Giorgio , Mai Roberto , Cossu Massimo , Francione Stefano
Published: November 2005

It is commonly assumed that interictal spikes (ISs) in focal epilepsies set off a period of inhibition that transiently reduces tissue excitability. Post‐spike inhibition was described in experimental models but was never demonstrated in the human epileptic cortex. In the present study post‐spike excitability was retrospectively evaluated on intracerebral stereo‐electroencephalographic recordings performed in the epileptogenic cortex of five patients suffering from drug‐resistant focal epilepsy secondary to Taylor‐type neocortical dysplasias. Patients typically presented with highly periodic interictal spiking activity at 2.33 ± 0.87 Hz (mean ± SD) in the dysplastic region. During the stereo‐electroencephalographic procedure, low‐frequency stimulation at 1 Hz was systematically performed for diagnostic purposes to identify the epileptogenic zone. The probability of evoking an IS during the interspike period in response to 1‐Hz stimuli delivered close to the ictal‐onset zone was examined. Stimuli that occurred early after a spontaneous IS (within 70% of the inter‐IS period) had a very low probability of generating a further IS. On the contrary, stimuli delivered during the late inter‐IS period had the highest probability of evoking a further IS. The generation of stimulus‐evoked ISs is occluded for several hundred milliseconds after the occurrence of a preceding spike discharge. As previously shown in animal models, these findings suggest that, during focal, periodic interictal spiking, human neocortical excitability is phasically controlled by post‐spike inhibition.
Activation and desensitization of neuronal nicotinic receptors modulate glutamatergic transmission on neonatal rat hypoglossal motoneurons
Authors: Quitadamo Costanza , Fabbretti Elsa , Lamanauskas Nerijus , Nistri Andrea
Published: November 2005

In the neonate the muscles of the tongue, which are exclusively innervated by the XII cranial nerves originating from the brainstem nucleus hypoglossus, must contract rhythmically in coincidence with breathing, suckling and swallowing. These motor commands are generated by hypoglossal motoneurons excited by glutamatergic inputs. Because in forebrain areas the efficiency of glutamatergic transmission is modulated by neuronal nicotinic receptors (nAChRs), the role and identity of nAChRs within the nucleus hypoglossus of the neonatal rat were explored using anin vitrobrainstem slice preparation. This area expressed immunoreactivity for α4, α7 and β2 nAChR subunits. Whole‐cell patch‐clamp recording from hypoglossal motoneurons showed lack of spontaneous cholinergic events mediated by nAChRs even in the presence of a cholinesterase inhibitor. However, pharmacological antagonism of α7‐ or β2‐containing receptors depressed glutamatergic currents arising either spontaneously or by electrical stimulation of the reticular formation. Hypoglossal motoneurons expressed functional nAChRs with characteristics of α4β2 and α7 receptor subunits. Such receptors underwent fast desensitization (time constant of 200 ms) with full recovery within 1 min. Low (0.5 µm) concentration of nicotine first facilitated glutamatergic transmission on motoneurons and later depressed it through receptor desensitization. When 0.1 µmnicotine was used, only depression of synaptic transmission occurred, in keeping with the suggestion that nAChRs can be desensitized without prior activation. These results highlight the role of tonic nAChR activity in shaping excitatory inputs to hypoglossal motoneurons, and suggest that nAChR desensitization by ambient nicotine could contribute to disorders of tongue muscle movements.
A daily palatable meal without food deprivation entrains the suprachiasmatic nucleus of rats
Authors: Mendoza Jorge , Angeles‐Castellanos Manuel , Escobar Carolina
Published: November 2005

Food is considered a potent Zeitgeber for peripheral oscillators but not for the suprachiasmatic nucleus (SCN), which is entrained principally by the light–dark cycle. However, when food attains relevant properties in quantity and quality, it can be a potent Zeitgeber even for the SCN. Here we evaluated the entrainment influence of a daily palatable meal, without regular food deprivation, on the circadian rhythm of locomotor activity and the c‐Fos and PER‐1 protein expression in the SCN. Rats fed ad libitum, in constant darkness, received a palatable meal for 6 weeks starting in the middle of the subjective day. Locomotor activity showed entrainment when the offset of activity coincided with the palatable meal‐time. In the SCN, the peak expression of c‐Fos was observed at palatable meal‐time and PER‐1 showed a peak during the onset of subjective night, as predicted according to the behavioural entrained pattern. In addition, c‐Fos and PER‐1 expression in the paraventricular thalamic nucleus (PVT) showed increased expression at palatable meal‐time, while the intergeniculate leaflet did not, suggesting that the PVT may be involved as an input pathway of palatable food‐entrainment to the SCN. These results demonstrate that daily access to a palatable meal can entrain the SCN; several stimuli can be implicated in this process, including motivation and arousal.
Heteromodal connections supporting multisensory integration at low levels of cortical processing in the monkey
Authors: Cappe Céline , Barone Pascal
Published: November 2005

While multisensory integration is thought to occur in higher hierarchical cortical areas, recent studies in man and monkey have revealed plurisensory modulations of activity in areas previously thought to be unimodal. To determine the cortical network involved in multisensory interactions, we performed multiple injections of different retrograde tracers in unimodal auditory (core), somatosensory (1/3b) and visual (V2 and MT) cortical areas of the marmoset. We found three types of heteromodal connections linking unimodal sensory areas. Visuo‐somatosensory projections were observed originating from visual areas [probably the ventral and dorsal fundus of the superior temporal area (FSTv and FSTd), and middle temporal crescent (MTc)] toward areas 1/3b. Somatosensory projections to the auditory cortex were present from S2 and the anterior bank of the lateral sulcus. Finally, a visuo‐auditory projection arises from an area anterior to the superior temporal sulcus (STS) toward the auditory core. Injections in different sensory regions allow us to define the frontal convexity and the temporal opercular caudal cortex as putative polysensory areas. A quantitative analysis of the laminar distribution of projecting neurons showed that heteromodal connections could be either feedback or feedforward. Taken together, our results provide the anatomical pathway for multisensory integration at low levels of information processing in the primate and argue against a strict hierarchical model.
Prominent expression and activity‐dependent nuclear translocation of Ca2+/calmodulin‐dependent protein kinase Iδ in hippocampal neurons
Authors: Sakagami Hiroyuki , Kamata Akifumi , Nishimura Hideki , Kasahara Jiro , Owada Yuji , Takeuchi Yusuke , Watanabe Makoto , Fukunaga Kohji , Kondo Hisatake
Published: November 2005

Multifunctional Ca2+/calmodulin‐dependent protein kinases (CaMKs) including CaMKI, II and IV, are thought to regulate a variety of neuronal functions. Unlike CaMKII, which is regulated by autophosphorylation, CaMKI as well as CaMKIV are activated by CaMKK. In this study, we examined the cellular and subcellular localization of CaMKIδ, a recently identified fourth isoform of CaMKI, in the mature brain.In situhybridization analysis demonstrated wide expression of CaMKIδ mRNA in the adult mouse brain with prominent expression in the hippocampal pyramidal cells. FLAG‐tagged CaMKIδ was localized at the cytoplasm and neurites without nuclear immunoreactivity in approximately 80% of the transfected primary hippocampal neurons. The stimulation with either KCl depolarization or glutamate triggered the nuclear localization of FLAG‐tagged CaMKIδ by two‐fold with a peak at 1 min. In contrast, the catalytically inactive mutants of CaMKIδ remained cytoplasmic without nuclear translocation during KCl depolarization, indicating the requirement of its activation for the nuclear translocation. Furthermore, we showed that immunoprecipitated CaMKIδ could phosphorylate cAMP response element binding protein (CREB)αin vitroand that the over‐expression of CaMKIδ enhanced GAL4‐CREB‐luciferase activity in PC12 cells stimulated by KCl depolarization. Our present study provides the first evidence for the possible involvement of CaMKIδ in nuclear functions through its nuclear translocation in response to stimuli that trigger intracellular Ca2+influx.
Shift from depolarizing to hyperpolarizing glycine action occurs at different perinatal ages in superior olivary complex nuclei
Authors: Löhrke Stefan , Srinivasan Geetha , Oberhofer Martin , Doncheva Ekaterina , Friauf Eckhard
Published: November 2005

The inhibitory transmitters glycine and GABA undergo a developmental shift from depolarizing to hyperpolarizing action (D/H‐shift). To analyse this shift in functionally related nuclei of the rat superior olivary complex (SOC), we employed voltage‐sensitive dye recordings in auditory brainstem slices. Complementarily, we analysed single neurons in gramicidin perforated‐patch recordings. Our results show a differential timing of the D/H‐shift in the four SOC nuclei analysed. In the medial superior olive (MSO), the shift occurred at postnatal day (P) 5–9. In the superior paraolivary nucleus (SPN), it occurred between embryonic day (E) 18 and P1. No D/H‐shift was observed in the medial nucleus of the trapezoid body (MNTB) until P10. This is in line with the finding that most of the patched MNTB neurons displayed glycine‐induced depolarizations between P0–9. While no regional differences regarding the D/H‐shift were found within the MSO, SPN, and MNTB, we observed such differences in the lateral superior olive (LSO). All LSO regions showed a D/H‐shift at P4–5. However, in the high‐frequency regions, hyperpolarizations were large already at P6, yet amplitudes of this size were not present until P8 in the low‐frequency regions, suggesting a delayed development in the latter regions. Our physiological results demonstrate that D/H‐shifts in SOC nuclei are staggered in time and occur over a period of almost two weeks. Membrane‐associated immunoreactivity of the Cl– outward transporter KCC2 was found in every SOC nucleus already at times when glycine was still depolarizing. This implies that the mere presence of KCC2 does not correlate with functional Cl– outward transport.
Fibre‐type composition of rabbit jaw muscles is related to their daily activity
Authors: van Wessel T. , Langenbach G. E. J. , Korfage J. A. M. , Brugman P. , Kawai N. , Tanaka E. , van Eijden T. M. G. J.
Published: November 2005

Skeletal muscles contain a mixture of fibres with different contractile properties, such as maximum force, contraction velocity and fatigability. Muscles adapt to altered functional demands, for example, by changing their fibre‐type composition. This fibre‐type composition can be changed by the frequency, duration and presumably the intensity of activation. The aim of this study was to analyse the relationship between the spontaneous daily muscle activation and fibre‐type composition in rabbit jaw muscles. Using radio‐telemetry combined with electromyography, the daily activity of five jaw muscles was characterized in terms of the total duration of muscle activity (duty time) and the number of activity bursts. Fibre‐type composition of the muscles was classified by analysing the myosin heavy chain content of the fibres. The amount of slow‐type fibres was positively correlated to the duty time and the number of bursts only for activations exceeding 20–30% of the maximum activity per day. Furthermore, cross‐sectional areas of the slow‐type fibres were positively correlated to the duty time for activations exceeding 30% of the maximum activity. The present data indicate that the amount of activation above a threshold (> 30% peak activity) is important for determining the fibre‐type composition and cross‐sectional area of slow‐type fibres of a muscle. Activation above this threshold occurred only around 2% of the time in the jaw muscles, suggesting that contractile properties of muscle fibres are maintained by a relatively small number of powerful contractions per day.
Gene transfer of GLT‐1, a glutamate transporter, into the nucleus accumbens shell attenuates methamphetamine‐ and morphine‐induced conditioned place preference in rats
Authors: Fujio Mayumi , Nakagawa Takayuki , Sekiya Yumiko , Ozawa Tohru , Suzuki Yuichi , Minami Masabumi , Satoh Masamichi , Kaneko Shuji
Published: November 2005

Several lines of evidence have suggested that the glutamatergic system in the nucleus accumbens (NAc) plays an important role in the conditioned rewarding effect of drugs of abuse. In addition, it is recognized that extracellular glutamate is rapidly removed from the synaptic cleft by Na+‐dependent glutamate transporters in neurons and glial cells, thereby maintaining physiological levels of glutamate. We previously reported that activation of glutamate uptake by a glutamate transporter activator attenuated the acquisition of conditioned place preference induced by methamphetamine and morphine in mice. In the present study, we examined the effects of gene transfer of a glial glutamate transporter, GLT‐1, into the NAc shell by recombinant adenoviruses on methamphetamine‐ and morphine‐induced conditioned place preference in rats. Bilateral infusion of the recombinant adenoviruses into the NAc shell efficiently increased GLT‐1 expression surrounding the infusion site, at least during the period 2–8 days after the infusion. In the conditioned place preference paradigm, animals were conditioned with repeated subcutaneous injections of methamphetamine (2 mg/kg) or morphine (3 mg/kg). Intra‐NAc shell overexpression of GLT‐1 before the conditioning significantly attenuated the conditioned place preference induced by methamphetamine or morphine, when compared with control. However, it had no effect on the somatic signs of naloxone‐precipitated morphine withdrawal. These results suggest that GLT‐1 within the NAc shell plays an inhibitory role in the conditioned rewarding effects of methamphetamine and morphine but not the physical dependence on morphine.
An initial investigation of spinal mechanisms underlying pain enhancement induced by fractalkine, a neuronally released chemokine
Authors: Milligan E. , Zapata V. , Schoeniger D. , Chacur M. , Green P. , Poole S. , Martin D. , Maier S. F. , Watkins L. R.
Published: November 2005

Fractalkine is a chemokine that is tethered to the extracellular surface of neurons. Fractalkine can be released, forming a diffusible signal. Spinal fractalkine (CX3CL1) is expressed by sensory afferents and intrinsic neurons, whereas its receptor (CX3CR1) is predominantly expressed by microglia. Pain enhancement occurs in response both to intrathecally administered fractalkine and to spinal fractalkine endogenously released by peripheral neuropathy. The present experiments examine whether fractalkine‐induced pain enhancement is altered by a microglial inhibitor (minocycline) and/or by antagonists/inhibitors of three putative glial products implicated in pain enhancement: interleukin‐1 (IL1), interleukin‐6 (IL6) and nitric oxide (NO). In addition, it extends a prior study that demonstrated that intrathecal fractalkine‐induced mechanical allodynia is blocked by a neutralizing antibody to the rat fractalkine receptor, CX3CR1. Here, intrathecal anti‐CX3CR1 also blocked fractalkine‐induced thermal hyperalgesia. Furthermore, blockade of microglial activation with minocycline prevented both fractalkine‐induced mechanical allodynia (von Frey test) and thermal hyperalgesia (Hargreaves test). Microglial activation appears to lead to the release of IL1, given that pretreatment with IL1 receptor antagonist blocked both fractalkine‐induced mechanical allodynia and thermal hyperalgesia. IL1 is not the only proinflammatory cytokine implicated, as a neutralizing antibody to rat IL6 also blocked fractalkine‐induced pain facilitation. Lastly, NO appears to be importantly involved, as l‐NAME, a broad‐spectrum NO synthase inhibitor, also blocked fractalkine‐induced effects. Taken together, these data support that neuronally released fractalkine enhances pain via activation of spinal cord glia. Thus, fractalkine may be a neuron‐to‐glia signal triggering pain facilitation.
Novelty detector neurons in the mammalian auditory midbrain
Authors: Pérez‐González David , Malmierca Manuel S. , Covey Ellen
Published: November 2005

Novel stimuli in all sensory modalities are highly effective in attracting and focusing attention. Stimulus‐specific adaptation (SSA) and brain activity evoked by novel stimuli have been studied using population measures such as imaging and event‐related potentials, but there have been few studies at the single‐neuron level. In this study we compare SSA across different populations of neurons in the inferior colliculus (IC) of the rat and show that a subclass of neurons with rapid and pronounced SSA respond selectively to novel sounds. These neurons, located in the dorsal and external cortex of the IC, fail to respond to multiple repetitions of a sound but briefly recover their excitability when some stimulus parameter is changed. The finding of neurons that respond selectively to novel stimuli in the mammalian auditory midbrain suggests that they may contribute to a rapid subcortical pathway for directing attention and/or orienting responses to novel sounds.
Corticostriatal functional interactions in Parkinson's disease: a rTMS/[11C]raclopride PET study
Authors: Strafella Antonio P. , Ko Ji Hyun , Grant Joshua , Fraraccio Maria , Monchi Oury
Published: November 2005

Several animal studies have shown that striatal dopamine can be released under direct control of glutamatergic corticostriatal efferents. In Parkinson's disease (PD), abnormalities in corticostriatal interactions are believed to play an important role in the pathophysiology of the disease. Previously, we have reported that, in healthy subjects, repetitive transcranial magnetic stimulation (rTMS) of motor cortex (MC) induces focal dopamine release in the ipsilateral putamen. In the present study, using [11C]raclopride PET, we sought to investigate early PD patients with evidence of unilateral motor symptoms. We measured in the putamen changes in extracellular dopamine concentration following rTMS (intensity, 90% of the resting motor threshold; frequency, 10 Hz) of the left and right MC. The main objective was to identify potential differences in corticostriatal dopamine release between the hemisphere associated with clear contralateral motor symptoms (symptomatic hemisphere) and the presymptomatic stage of the other hemisphere (asymptomatic hemisphere). Repetitive TMS of MC caused a binding reduction in the ipsilateral putamen of both hemispheres. In the symptomatic hemisphere, while the amount of TMS‐induced dopamine release was, as expected, smaller, the size of the significant cluster of change in [11C]raclopride binding was, instead, 61.4% greater than in the asymptomatic hemisphere. This finding of a spatially enlarged area of dopamine release, following cortical stimulation, may represent a possible in vivo expression of a loss of functional segregation of cortical information to the striatum and an indirect evidence of abnormal corticostriatal transmission in early PD. This has potential implications for models of basal ganglia function in PD.
Enhanced expression of brain interferon‐α and serotonin transporter in immunologically induced fatigue in rats
Authors: Katafuchi Toshihiko , Kondo Tetsuya , Take Sachiko , Yoshimura Megumu
Published: November 2005

Immunologically induced fatigue was induced in rats by intraperitoneal injection of a synthetic double‐stranded RNA, polyriboinosinic : polyribocytidylic acid (poly I:C). An injection of poly I:C (3 mg/kg) decreased the daily amounts of spontaneous running wheel activity to ≈ 60% of the preinjection level until day 8. Quantitative analysis of mRNA levels demonstrated that interferon‐α (IFN‐α) and p38 mitogen‐activated protein kinase mRNAs increased in the medial preoptic, paraventricular and ventromedial hypothalamic nuclei and in cortex on both days 1 and 8, while interleukin‐1β and an inhibitor of nuclear factor κB (IκB)‐β mRNAs increased on day 1, but recovered within a week. Serotonin transporter (5‐HTT) mRNA also increased on days 1 and 8 after poly I:C injection in the same brain regions where IFN‐α mRNA increased. The increased 5‐HTT had a functional significance, becausein vivobrain microdialysis revealed that an i.p. injection of poly I:C induced a decrease in the extracellular concentration of 5‐HT in the prefrontal cortex; the decrease was blocked by local perfusion with a nonselective 5‐HT reuptake inhibitor, imipramine. Finally, the poly I:C‐induced fatigue was attenuated by a 5‐HT1Areceptor agonist but not by 5‐HT2, 5‐HT3or dopamine D3agonists. These findings, taken together, suggest that disorders in brain IFN‐α and 5‐HTT expression may be involved in the neuronal mechanisms of the poly I:C‐induced fatigue.
Impaired fear memory and decreased hippocampal neurogenesis following olfactory bulbectomy in rats
Authors: Jaako‐Movits Külli , Zharkovsky Alexander
Published: November 2005

It has been proposed that a decrease in adult hippocampal neurogenesis provides a biological and cellular basis for major depression. The olfactory bulbectomy (OB) in rats is widely accepted as an animal model of depression. In the present study, we investigated the effect of OB on memory formation in the memory tasks related to the hippocampal function and adult hippocampal neurogenesis. OB induced a behavioural syndrome, which was characterized by an increased activity in the open‐field test and impairment in passive avoidance behaviour and contextual fear conditioning. The behavioural changes, following OB, were accompanied by a decrease in the number of proliferating cells in the dentate gyrus. Furthermore, the differentiation of the newly born cells, into mature calbindin‐positive neurons, was also retarded. Stereological analysis revealed a decrease in the total granule neuron numbers within the granule cell layer of the dentate gyrus, without a significant decrease in volume of the dentate gyrus. Although a relationship between altered neurogenesis and behavioural syndrome, induced by OB, is not established yet, our results suggest that decreased neurogenesis might at least partly contribute for behavioural deficits following OB.
Short‐term survival of newborn neurons in the adult olfactory bulb after exposure to a complex odor environment
Authors: Rochefort Christelle , Lledo Pierre‐Marie
Published: November 2005

In the olfactory bulb of adult mice, new neurons are continually integrated into existing neuronal networks. Previous studies have demonstrated that exposure to a complex odor environment increases the incorporation of newborn bulbar neurons without modifying the proliferation rate. Whether this incorporation is transient or leads to the long‐lasting presence of new neurons has not yet been answered. Because a transient increase of new neurons impacts olfactory information processing differently than a long‐lasting increase, we conducted experiments to investigate the time course of survival and cell death of newly generated bulbar neurons following exposure to an enriched olfactory environment. Dividing cells were labeled with bromodeoxyuridine (BrdU) and were counted at several survival time points thereafter. Interestingly, whereas the number of surviving BrdU‐labeled cells was elevated at the time when animals were withdrawn from their enriched housing, this number returned to control level 1 month later. Similarly, when olfactory memory was investigated, we found that the improvement of short‐term memory, induced by enriched odor exposure, lasted less than 1 month. These findings indicate not only that the recruitment of newborn neurons closely followed the degree of environment complexity, but also that olfactory memory is tightly associated with the level of ongoing neurogenesis in the adult olfactory bulb.
Evolution of body size in food webs: does the energetic equivalence rule hold?
Authors: Loeuille Nicolas , Loreau Michel
Published: November 2005

The energetic equivalence rule (EER), which is derived from empirical observations linking population density and body size and from the allometric law linking metabolism and body size, predicts that the amount of energy used by the various species should be independent of body size. Here, we examine this hypothesis using a model that allows entire food webs to emerge from coevolution of interacting species. Body size influences both individual metabolism and interactions among species in the model. Overall, population density does decrease with body size roughly following a power law whose exponent is variable. We discuss this variability in the light of empirical data sets. The emerging relationship between the flux of resources exploited by the various species and their body size follows a decreasing power law, thus contradicting the EER. Our model emphasizes the importance of considering the influence of body size on species interactions in attempting to explain large‐scale patterns related to body size.
In situ probing of Xylella fastidiosa in honeydew of a xylem sap‐feeding insect using 16S rRNA‐targeted fluorescent oligonucleotides
Authors: Rodrigues Jorge L. M. , Silva‐Stenico Maria E. , De Souza Adriane N. , Lopes João R. S. , Tsai Siu M.
Published: November 2005

Xylella fastidiosa is a plant pathogen that threatens a US$ 4.6 billion worldwide wine and citrus industry. Monitoring its presence and distribution in plants and vectors is crucial for designing control strategies, as well as for understanding its ecological role and fate. We developed two fluorescent oligonucleotide probes complementary to different regions of the 16S rRNA gene of X. fastidiosa. The specificity of the newly designed probes S‐S‐X.fas‐0067‐a‐A‐18 and S‐S‐X.fas‐1439‐a‐A‐18 was demonstrated using fluorescence in situ hybridization (FISH) for 12 Xylella isolates, 15 closely related microorganisms and three plant endophytes. These probes were used to detect and quantify X. fastidiosa in plant sap (average value of 2.9 ± 0.3 × 106 cells ml−1) from three different citrus orchards. In a second experiment, cells were quantified in honeydew (2.2 ± 0.2 × 104 cells ml−1) collected from the insect vector Bucephalogonia xanthophis during the acquisition access period on an infected plant. The number of pathogen cells retained or digested by the insect is 10 000 times greater than the estimated minimum value to ensure an efficient transmission. Polymerase chain reaction (PCR) amplification using specific primers with plant sap and honeydew samples, followed by sequencing, confirmed the presence of the plant pathogen. This is the first demonstration of FISH being used for environmental samples, such as plant sap and insect honeydew, to estimate the abundance of a plant pathogen during infection.
Comparison of microbiological results of needle puncture vs. superficial swab in infected diabetic foot ulcer with osteomyelitis
Authors: Kessler L. , Piemont Y. , Ortega F. , Lesens O. , Boeri C. , Averous C. , Meyer R. , Hansmann Y. , Christmann D. , Gaudias J. , Pinget M.
Published: November 2005

Aim  To study prospectively two methods for the bacteriological diagnosis of osteomyelitis related to diabetic foot ulcer: needle puncture performed across normal skin surrounding the foot ulcer and superficial swabbing of the ulcer.

Patients and methods  Diabetic patients with a foot ulcer complicated by bone or joint infection, as detected by X‐ray imaging, were included in the study. Ulcer swabbing and needle puncture were performed in each patient. To reach the tissue nearest the bone surface, needle puncture was guided by X‐ray imaging and the drop of fluid obtained by aspiration was used for both aerobic and anaerobic bacterial culture.

Results  Twenty‐one diabetic patients were included. The mean number of microorganisms isolated by needle puncture was significantly lower compared with that obtained by superficial swabbing: 1.09 vs. 2.04 (P < 0.02). Three bacterial species were isolated by needle puncture only in one patient while three or more bacterial isolates were obtained by superficial swabbing in six patients. No bacterial isolate was detected in five patients by needle puncture and in two patients by superficial swabbing. Staphylococcus aureus accounted for 70% of cases (seven patients) when a single bacterial species was obtained by needle puncture. After needle puncture, no wound complication or infection was observed.

Conclusion  Culture of samples obtained by needle puncture revealed one or two bacterial isolates in two‐thirds of diabetic patients with osteomyelitis following foot ulcer. Given the lack of complications, this invasive diagnostic technique should be considered for deep direct sampling in diabetic patients with osteomyelitis related to foot ulcer when surgical debridement is contraindicated or delayed.
Phytoestrogens and the menopause – do they really help?
Authors: Jefferson A.
Published: November 2005

Summary  Studies have recently questioned the safety of hormone replacement therapy (HRT) during the menopause with regard to an increased risk of breast cancer and heart disease. Most notably the US Women's Health Initiative and British Million Women Study resulted in a considerable media furore which has prompted women, who may previously have been happy to take HRT, to explore alternative approaches to the menopause. It is widely accepted that diet and lifestyle play a large part in symptom relief and evidence is strengthening for the role of phytoestrogens in the relief of hot flushes. It is estimated that three‐quarters of women in the UK experience one or more symptoms of the menopause, and that for one third these symptoms are severe. This article distinguishes the fact from the fiction and provides an overview of the practicalities of a diet and lifestyle to relieve menopausal symptoms.
Postprandial lipaemia – the influence of diet and its link to coronary heart disease
Authors: Berry S. E. E.
Published: November 2005

Summary  Coronary heart disease (CHD) is the leading cause of death worldwide, and dietary fat intake is one of the major environmental risk factors implicated in its causation. In the drive to prevent CHD, much attention has focused on reducing the amount of energy derived from fat in the diet. However, little attention has been given to the amount of fat consumed in an individual meal and its postprandial effects. Postprandial lipaemia is the term used to describe the series of metabolic events that occur following the consumption of a fatty meal. The extent of postprandial lipaemia is indicated by the size or duration of the increase in plasma triacylglycerol (TAG) concentrations. There is evidence to indicate that exaggerated postprandial lipaemia is linked to an increased risk of CHD. There are several mechanisms by which it may influence the pathological processes that result in CHD, including effects on lipoproteins involved in atherosclerosis and acute effects on haemostatic function. The postprandial response to dietary fat is influenced by non‐dietary factors (such as age, gender and activity level) as well as background diet and the amount and type of fat consumed in a meal. This review focuses on the mechanisms linking postprandial lipaemia and CHD risk and the factors affecting the level of postprandial lipaemia.
Folate and colorectal cancer – a review of the current evidence
Authors: Tarr R. , Pufulete M.
Published: November 2005

Summary  Colorectal cancer is the second most common tumour in the United Kingdom. Migration studies suggest that environmental factors, particularly diet, account for the wide variation in worldwide incidence of the disease. Prospective cohort studies have shown that diets low in meat and high in vegetables decrease risk. Folate is thought to account partly for the protection conferred by high intakes of vegetables, since it plays a crucial role in maintaining genomic stability, being required in two important processes, DNA synthesis and methylation. The public health implications of existing evidence supporting a reduction in neural tube defects, ischaemic heart disease and possibly cancer fuel the nationwide folate fortification debate, while ever progressing nutritional genomic technology promises a greater understanding of the mechanisms underlying the relationship between folate and colorectal cancer risk.
Red meat in the diet
Authors: Williamson C. S. , Foster R. K. , Stanner S. A. , Buttriss J. L.
Published: November 2005

Summary  The aim of this paper is to provide an overview of the existing scientific literature on the role of red meat in the diet. It discusses current levels of red meat intake, the nutritional benefits of consuming red meat, dietary and lifestyle factors associated with meat consumption and the effects of red meat intake on health and chronic disease outcomes.
School Nutrition Action Groups and their effect upon secondary school‐aged pupils’ food choices
Authors: Passmore S. , Harris G.
Published: November 2005

Summary  The aim of this intervention was to affect a change in the food choices of adolescents (11–16 years old) at school by giving pupils more control over the food provision in their school through the establishment of the School Nutrition Action Groups. The study compared food selections and pupils’ views of the catering service between 12 schools implementing School Nutrition Action Groups and 12 control schools. Schools were selected to reflect educational achievement, ethnic mix and gender. Pupils completed a baseline and a 2‐year follow‐up questionnaire. In addition, data of the sales of food in the school dining rooms in all schools were collected at baseline and follow‐up. There was a significant increase in the sales of main meals and snack meals in the intervention schools suggesting that School Nutrition Action Groups can be an effective and relevant way of changing food choices in schools.
ANOMALIES, PROBINGS, INSIGHTS: KEN FOREMAN'S ROLE IN THE SAMPLING INFERENCE CONTROVERSY OF THE LATE 20TH CENTURY
Authors: Brewer Ken
Published: November 2005

This paper is based on the author's recollections of work done for and with E.K. Foreman, and later developments of that work. It describes most particularly the author's early intimations of the potential for using prediction models in survey sampling, the reasons why the use of such models, especially for inferential purposes, was so strongly resisted in the second half of the 20th century, the manner in which randomization and prediction inferences can be combined, and some advantages flowing from that combination.
HIERARCHICAL BAYESIAN MODELLING OF SOCIAL VARIATION IN THE AGE DEPENDENCE OF DISABILITY PREVALENCE
Authors: Graham Patrick
Published: November 2005

Motivated by a study of social variation in the relationship of functional limitation prevalence to age, this paper examines methods for modelling social variation in health outcomes. It is argued that, from a Bayesian perspective, modelling the dependence of functional limitation prevalence on age separately for each social group, corresponds to an implausible prior model, in addition to leading to imprecise estimates for some groups. The alternative strategy of fitting a single model, perhaps including some age‐by‐group interactions but omitting higher‐order interactions, requires a strong prior commitment to the absence of such effects. Hierarchical Bayesian modelling is proposed as a compromise between these two analytical approaches. Under all hierarchical Bayes analyses there is strong evidence for an ethnic group difference in limitation prevalence in early‐ to mid‐adulthood among tertiary‐qualified males. In contrast, the single‐model approach largely misses this effect, while the group‐specific analyses exhibit an unrealistically large degree of heterogeneity in gender‐education‐specific ethnicity effects. The sensitivity of posterior inferences to prior specifications is studied.
ESTIMATING PROCESSES OF COUNTS FROM CROSS‐SECTIONAL AGGREGATE DATA, WITH AN APPLICATION TO MULTISTATE LIFE TABLES AND HEALTH EXPECTANCIES
Authors: Heathcote Christopher R. , Puza Borek D.
Published: November 2005

This paper discusses the estimation of time‐dependent probabilities of a finite state‐space discrete‐time process using aggregate cross‐sectional data. A large‐sample version of multistate logistic regression is described and shown to be useful for analysing multistate life tables. The technique is applied to the estimation of disability‐free, severely disabled and other disabled survival curves and health expectancies in Australia, based on data from national health surveys in 1988, 1993 and 1998. A conclusion is that there has been a general upward trend in the future time expected to be spent in a state of disability, the picture being more pessimistic for males than females. For example, during 1988‐1998 the estimated increase in male life expectancy at birth of 2.7 years is decomposed as a decrease of 1.2 years in disability‐free health (life) expectancy and increases of 1.3 and 2.6 years, respectively, in states of severe disability and other disability.
ESTIMATION OF A PROPORTION USING SEVERAL INDEPENDENT SAMPLES OF BINOMIAL MIXTURES
Authors: Wood G.R. , Lai C.D. , Qiao C.G.
Published: November 2005

This paper considers a sequence of independent counts, with each count arising from a mixture of binomial distributions; the mixing distribution is fixed but the number of trials varies from count to count. In this common situation, an estimate of the underlying mean binomial proportion is needed. Two estimators are in general use: the arithmetic average and a weighted average of the observed proportions. Variances of the two estimators are compared and used to decide which estimator is preferred in a given context. The relative merits depend on the distribution of the proportions and the numbers of trials used.
A ROBUST BAYES FACTOR FOR LINEAR MODELS
Authors: Taplin Ross H.
Published: November 2005

This paper proposes a new robust Bayes factor for comparing two linear models. The factor is based on a pseudo‐model for outliers and is more robust to outliers than the Bayes factor based on the variance‐inflation model for outliers. If an observation is considered an outlier for both models this new robust Bayes factor equals the Bayes factor calculated after removing the outlier. If an observation is considered an outlier for one model but not the other then this new robust Bayes factor equals the Bayes factor calculated without the observation, but a penalty is applied to the model considering the observation as an outlier. For moderate outliers where the variance‐inflation model is suitable, the two Bayes factors are similar. The new Bayes factor uses a single robustness parameter to describe a priori belief in the likelihood of outliers. Real and synthetic data illustrate the properties of the new robust Bayes factor and highlight the inferior properties of Bayes factors based on the variance‐inflation model for outliers.
TWO‐STAGE SUPPORT ESTIMATION
Authors: Müller Samuel
Published: November 2005

This paper presents a two‐stage procedure for estimating the conditional support curve of a random variable X, given the information of a random vector X. Quantile estimation is followed by an extremal analysis on the residuals for problems which can be written as regression models. The technique is applied to data from the National Bureau of Economic Research and US Census Bureau's Center for Economic Studies which contain all four‐digit manufacturing industries. Simulation results show that in linear regression models the proposed estimation procedure is more efficient than the extreme linear regression quantile.
ASSESSING AND TESTING FOR THRESHOLD NONLINEARITY IN STOCK RETURNS
Authors: Chen Cathy W.S. , So Mike K.P. , Gerlach Richard H.
Published: November 2005

This paper proposes a test for threshold nonlinearity in a time series with generalized autore‐gressive conditional heteroscedasticity (GARCH) volatility dynamics. This test is used to examine whether financial returns on market indices exhibit asymmetric mean and volatility around a threshold value, using a double‐threshold GARCH model. The test adopts the reversible‐jump Markov chain Monte Carlo idea of Green, proposed in 1995, to calculate the posterior probabilities for a conventional GARCH model and a double‐threshold GARCH model. Posterior evidence favouring the threshold GARCH model indicates threshold nonlinearity with asymmetric behaviour of the mean and volatility. Simulation experiments demonstrate that the test works very well in distinguishing between the conventional GARCH and the double‐threshold GARCH models. In an application to eight international financial market indices, including the G‐7 countries, clear evidence supporting the hypothesis of threshold nonlinearity is discovered, simultaneously indicating an uneven mean‐reverting pattern and volatility asymmetry around a threshold return value.
LARGE AND MODERATE DEVIATIONS PRINCIPLES FOR KERNEL ESTIMATION OF A MULTIVARIATE DENSITY AND ITS PARTIAL DERIVATIVES
Authors: Mokkadem Abdelkader , Pelletier Mariane , Worms Julien
Published: November 2005

This paper studies the large deviations behaviour of the kernel estimator of a probability density f, by considering the case when the kernel takes negative values. It establishes large and moderate deviations principles for the kernel estimators of the partial derivatives of f. The estimators of the derivatives exhibit a quadratic behaviour for both the large and the moderate deviations scales, whereas for the density estimator there is a classical gap between the large deviations and the moderate deviations asymptotics.
EFFICIENT ESTIMATION IN REGRESSION FRAILTY OR TRANSFORMATION MODELS BASED ON AN ALGORITHM
Authors: Vonta Filia
Published: November 2005

This paper considers a regression frailty or transformation model in which the structural parameter is the vector of regression coefficients and the nuisance parameter is a vector of arbitrarily high dimension. It proposes jointly (implicitly) defined parameter estimators which have been proved to be consistent and asymptotically efficient, and develops an algorithmic procedure that provides these estimators. The behaviour of the algorithm is illustrated by analysing simulated and real data.
A WEIGHTED RANK MEASURE OF CORRELATION
Authors: Pinto da Costa Joaquim , Soares Carlos
Published: November 2005

Spearman's rank correlation coefficient is not entirely suitable for measuring the correlation between two rankings in some applications because it treats all ranks equally. In 2000, Blest proposed an alternative measure of correlation that gives more importance to higher ranks but has some drawbacks. This paper proposes a weighted rank measure of correlation that weights the distance between two ranks using a linear function of those ranks, giving more importance to higher ranks than lower ones. It analyses its distribution and provides a table of critical values to test whether a given value of the coefficient is significantly different from zero. The paper also summarizes a number of applications for which the new measure is more suitable than Spearman's.
THE DOGIT ORDERED GENERALIZED EXTREME VALUE MODEL
Authors: Fry Tim R.L. , Harris Mark N.
Published: November 2005

This paper introduces the Dogit ordered generalized extreme value (DOGEV) model, for handling discrete variables that are ordered and heterogeneous. In particular, the DOGEV model can be applied to questionnaire responses on questions allowing a discrete set of ordered possible responses, where there is a preference for particular responses and possibly multiple modes in the data. The DOGEV model combines a model for choice set generation with the ordered generalized extreme value model. The paper illustrates the model using two empirical examples: a model of inflationary expectations and a model for students' evaluations of teaching.
A CHARACTERIZATION OF CONTINUOUS DISTRIBUTIONS VIA REGRESSION ON PAIRS OF RECORD VALUES
Authors: Bairamov I. , Ahsanullah M. , Pakes Anthony G.
Published: November 2005

The exponential type is characterized in terms of the regression of a (possibly non‐linear) function of a record value with its adjacent record values as covariates. Monotone transformations extend this result to more general settings, and these are illustrated with some specific examples.
ON THE COVERAGE PROBABILITY OF CONFIDENCE INTERVALS IN REGRESSION AFTER VARIABLE SELECTION
Authors: Kabaila Paul
Published: November 2005

This paper considers a linear regression model with regression parameter vector β. The parameter of interest is θ= aTβ where a is specified. When, as a first step, a data‐based variable selection (e.g. minimum Akaike information criterion) is used to select a model, it is common statistical practice to then carry out inference about θ, using the same data, based on the (false) assumption that the selected model had been provided a priori. The paper considers a confidence interval for θ with nominal coverage 1 ‐ α constructed on this (false) assumption, and calls this the naive 1 ‐ α confidence interval. The minimum coverage probability of this confidence interval can be calculated for simple variable selection procedures involving only a single variable. However, the kinds of variable selection procedures used in practice are typically much more complicated. For the real‐life data presented in this paper, there are 20 variables each of which is to be either included or not, leading to 220 different models. The coverage probability at any given value of the parameters provides an upper bound on the minimum coverage probability of the naive confidence interval. This paper derives a new Monte Carlo simulation estimator of the coverage probability, which uses conditioning for variance reduction. For these real‐life data, the gain in efficiency of this Monte Carlo simulation due to conditioning ranged from 2 to 6. The paper also presents a simple one‐dimensional search strategy for parameter values at which the coverage probability is relatively small. For these real‐life data, this search leads to parameter values for which the coverage probability of the naive 0.95 confidence interval is 0.79 for variable selection using the Akaike information criterion and 0.70 for variable selection using Bayes information criterion, showing that these confidence intervals are completely inadequate.
A NEW SHORT EXACT GEOMETRIC CONFIDENCE INTERVAL
Authors: Byrne John
Published: November 2005

For discrete distributions, the standard method of producing a two‐sided confidence interval generates an interval that is exact but conservative. This paper proposes a new algorithm to produce a short exact geometric confidence interval with proven properties, and compares the new interval with the standard interval.