bluuebunny/crossref_metadata_2025 huggingface dataset:
Region‐specific reduction of Aβ‐degrading endopeptidase, neprilysin, in mouse hippocampus upon aging
Authors: Iwata Nobuhisa , Takaki Yoshie , Fukami Shinjiro , Tsubuki Satoshi , Saido Takaomi C.
Published: October 2002

Metabolism of amyloid‐β peptide (Aβ) is closely associated with the pathology and etiology of Alzheimer's disease (AD). Neprilysin is the only rate‐limiting catabolic peptidase proven by means of reverse genetics to participate in Aβ metabolism in vivo. The aim of the present study is to assess whether possible spatial changes in neprilysin level in the brain with aging correlate to AD‐vulnerable regions. When neprilysin levels in various brain regions of 10‐, 80‐ and 132‐week‐old mice were evaluated by neprilysin‐dependent endopeptidase activity assay and Western blot‐based quantitative analysis, a clear change in neprilysin level with aging was observed in the hippocampal formation, in which the level was reduced by 20% at 132 weeks, compared to the 10‐week group. Quantitative immunohistochemical analysis confirmed a marked local reduction of neprilysin levels with aging at the outer molecular layer and polymorphic layer of the dentate gyrus, and the stratum lucidum of the hippocampus, where the densities were reduced by 56%, 82% and 83%, respectively, at 132 weeks compared to the 10‐week group. Thus, neprilysin was decreased selectively at the terminal zones and on axons of the lateral perforant path and the mossy fibers. These are the sites that show Aβ pathology in mutant amyloid precursor protein (APP) transgenic mice, and that show synaptic loss in AD. The immunoreactivities to synaptic vesicle protein‐2 and synaptophysin in the stratum lucidum and the dentate gyrus were unchanged, suggesting that a loss or decrease of synapses was not responsible for the decrease in the neprilysin levels. These observations suggest that downregulation of neprilysin is likely to be related to AD pathology and to the Aβ deposition associated with normal aging in humans. © 2002 Wiley‐Liss, Inc.
In vivo conversion of racemized β‐amyloid ([D‐Ser26]Aβ1–40) to truncated and toxic fragments ([D‐Ser26]Aβ25–35/40) and fragment presence in the brains of Alzheimer's patients
Authors: Kubo Takekazu , Nishimura Satoko , Kumagae Yoshihiro , Kaneko Isao
Published: October 2002

The lag between β‐amyloid (Aβ) deposition and neurodegeneration in Alzheimer's disease (AD) suggests that age‐dependent factors are involved in the pathogenesis. Racemization of Ser and Asp in Aβ is a typical age‐dependent modification in AD. We have shown recently that Aβ1–40 racemized at Ser26 ([D‐Ser26]Aβ1–40) is soluble and non‐toxic to neuronal cells, but is easily converted by brain proteases to truncated toxic fragments, [D‐Ser26]Aβ25–35/40. Furthermore, [D‐Ser26]Aβ1–40 in vivo, produced a drastic and synergistic neuronal loss by enhancing the excitotoxicity when co‐injected into rat hippocampus with ibotenic acid, an excitatory amino acid, suggesting an in vivo conversion of non‐toxic [D‐Ser26]Aβ1–40 to toxic fragments including [D‐Ser26]Aβ25–35/40. In this study, we further investigated the mechanism behind the in vivo neuronal loss by [D‐Ser26]Aβ1–40 and ibotenic acid in rats, and also searched for the presence of [D‐Ser26]Aβ25–35/40 antigens in AD brains. Quantitative analyses of the damaged area indicate clearly that non‐toxic [D‐Ser26]Aβ1–40 caused as much neurodegeneration as toxic [D‐Ser26]Aβ25–35/40. MK‐801, an NMDA receptor antagonist, completely inhibited the neurodegeneration. The immunohistochemical analyses using anti‐[D‐Ser26]Aβ25–35/40‐specific antibodies demonstrated the presence of [D‐Ser26]Aβ25–35/40 antigens in senile plaques and in degenerating hippocampal CA1 neurons in AD brains, but not in age‐matched control brains. These results strengthen our hypothesis that soluble [D‐Ser26]Aβ1–40, possibly produced during aging, is released from plaques and converted by proteolysis to toxic [D‐Ser26]Aβ25–35/40, which damage hippocampal CA1 neurons by enhancing excitotoxicity in AD. This may account for the lag between Aβ deposition and neurodegeneration in AD. © 2002 Wiley‐Liss, Inc.
Alzheimer's disease with spastic paresis and cotton wool type plaques
Authors: Tabira Takeshi , Chui De Hua , Nakayama Hiroshi , Kuroda Shigetoshi , Shibuya Makoto
Published: October 2002

We reviewed Alzheimer's cases with spastic paresis and cotton wool type plaques in five Japanese and nine Caucasian cases. Most were early onset familial Alzheimer's disease with presenilin 1 mutations. The cotton wool type plaques were related to extremely high production of Aβ42, due mainly to presenilin 1 mutations and low immune responses. Cotton wool plaques were numerous in the entire central nervous system, including basal ganglia, brainstem and even in spinal cord. Cotton wool type plaques were composed of slightly electron dense synaptic structures, but amyloid fibrils were rarely found. Such a high accumulation of Aβ42 may cause degeneration of the pyramidal tract and basal ganglia from an early stage of Alzheimer's disease. © 2002 Wiley‐Liss, Inc.
β‐secretase as a target for the treatment of Alzheimer's disease
Authors: Citron Martin
Published: October 2002

Finding inhibitors of the first step of the amyloid cascade, Aβ42 generation, is a major goal of Alzheimer's disease drug development. Two target protease activities, β‐and γ‐secretase, were detected more than 10 years ago but progress in this area has been slow because the enzymes were not identified. Using an expression cloning strategy we have identified a novel membrane bound aspartic protease, BACE1, as β‐secretase. The enzyme has been characterized in detail. The X‐ray crystal structure, which is critical for rational inhibitor design, has been solved and shown to be similar to that of other pepsin family members. Our recent knockout studies show that BACE1 is critical for Aβ generation, but the knockout mice show an otherwise normal phenotype, raising the possibility that therapeutic BACE1 inhibition could be accomplished without major mechanism based toxicity. Target‐mediated toxicity of β‐secretase inhibition cannot be ruled out, however, as long as the major substrates of this enzyme are unknown. Although various peptidic β‐secretase inhibitors have been published, the key challenge now is the generation of more drug‐like compounds that could be developed for therapeutic purposes. The focus of this review is progress in the β‐secretase field from the identification of the enzyme in 1999 to the most recent publications. © 2002 Wiley‐Liss, Inc.
Protective effect of dopamine D2 agonists in cortical neurons via the phosphatidylinositol 3 kinase cascade
Authors: Kihara Takeshi , Shimohama Shun , Sawada Hideyuki , Honda Kazuhiro , Nakamizo Tomoki , Kanki Rie , Yamashita Hiroshi , Akaike Akinori
Published: October 2002

Glutamate, one of the excitatory neurotransmitters, contributes to the neuronal death associated with neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, and with ischemia. In Alzheimer's disease brains, there is a decreased number of dopamine D2 receptors, which might cause neuronal dysfunction or death. In the present study, bromocriptine exerted a protective effect against glutamate‐induced cytotoxicity in rat cortical neurons. This neuroprotective effect was mediated via D2 receptors, because it was attenuated by domperidone, a D2 dopaminergic receptor antagonist. Another dopamine D2 agonist, quinpirole, also protected cells against glutamate toxicity. D2 agonists protected cells from calcium influx, nitric oxide, and peroxynitrite toxicity, which are thought to be the mediators of glutamate toxicity. The phosphatidylinositol 3 kinase (PI3K) inhibitor (LY294002) inhibited this neuroprotective effect of bromocriptine, in contrast to the mitogen‐activated protein kinase kinase (MAPKK) inhibitor (PD98059), which did not counter the protective effect. Furthermore, Akt protein kinase, which is an effector of PI3K, was activated by bromocriptine, and the antiapoptotic protein Bcl‐2 was up‐regulated by bromocriptine treatment. These results suggest that D2 dopaminergic receptor activation plays an important role in neuroprotection against glutamate cytotoxicity and that the up‐regulation of Bcl‐2 expression via the PI3K cascade is, at least partially, involved in this effect. © 2002 Wiley‐Liss, Inc.
Age‐related deficits in long‐term potentiation are insensitive to hydrogen peroxide: Coincidence with enhanced autophosphorylation of Ca2+/calmodulin‐dependent protein kinase II
Authors: Watson J.B. , Khorasani H. , Persson A. , Huang K‐P. , Huang F.L. , O'Dell T.J.
Published: October 2002

Reactive oxygen species (ROS) can have deleterious effects for both normal aging and Alzheimer's disease (AD). We examined the hypothesis that synapses undergoing long‐term potentiation (LTP) are preferentially at risk for ROS‐mediated oxidative stress during aging. We observed age‐dependent deficits in LTP induced by a high‐frequency stimulation (HFS) protocol in the CA1 region of hippocampus from C57BL/6 mice. There was a significant difference between LTP measured over 60 min in young (1–2 months) and old (23–26 months) mice. In oxidative stress studies, exogenous H2O2 (580 μM) significantly inhibited LTP in young mice; a similar dose of H2O2 failed to inhibit LTP in slices from adult (2–4 months) or from old mice. The results show that there are significant deficits in LTP in aging mice, but such deficits are insensitive to H2O2. Western immunoblotting studies in young mice show that the relative levels of autophosphorylated α‐Ca2+/calmodulin‐dependent protein kinase II (CaMKII) are unchanged in hippocampal CA1 treated with H2O2 relative to untreated controls. However with aging, there is a significant enhancement in the levels of autophosphorylated CaMKII in H2O2‐treated CA1 of older mice. Phosphorylation of RC3/neurogranin (Ng) by protein kinase C (PKC) is decreased in CA1 in response to H2O2 treatment, irrespective of age. We propose that, during aging, enhanced local release of H2O2 from mitocohondria may induce a compensatory “ceiling” effect at synapses, so that the levels of autophosphorylated αCaMKII are aberrantly saturated, leading to alterations in synaptic plasticity. © 2002 Wiley‐Liss, Inc.
Attenuated transcriptional responses to oxidative stress in the aged rat brain
Authors: Tong LiQi , Toliver‐Kinsky Tracy , Edwards Michael , Rassin David K. , Werrbach‐Perez Karin , Perez‐Polo J. Regino
Published: October 2002

The aged nervous system displays impaired cognitive functions, and these impairments are exacerbated in several neurodegenerative diseases. A role for oxidative stress has been suggested for several of these age‐associated dysfunctions. In addition, recovery from more acute traumatic insults that also generate oxidative stress is impaired in the aged. Here we examine the response of aged rat hippocampi to normobaric hyperoxia treatments and demonstrate an attenuation in the DNA binding activity of the AP‐1 and nuclear factor‐κB transcription factors, which are important components of stress response signal transduction pathways and can determine shifts in cellular commitments to necrosis, apoptosis, or functional recovery in the central nervous system. © 2002 Wiley‐Liss, Inc.
Novel cognitive improving and neuroprotective activities of Polygala tenuifolia Willdenow extract, BT‐11
Authors: Park Cheol Hyoung , Choi Se Hoon , Koo Ja‐Wook , Seo Ji‐Heui , Kim Hye‐Sun , Jeong Sung‐Jin , Suh Yoo‐Hun
Published: October 2002

We carried out this study to search a new active constituent that had cognitive enhancing activity and low side effects from natural source. We found that the extract of dried root of Polygala tenuifolia Willdenow (BT‐11, 10 mg/kg, i.p.) could significantly reverse scopolamine‐induced cognitive impairments in rat, using a passive avoidance and a water maze test. We also investigated the effects of BT‐11 on neurotoxicity induced by glutamate (Glu) and toxic metabolites of amyloid precursor protein (APP) such as amyloid β protein (Aβ) and C‐terminal fragment of APP (CT) in primary cultured neurons of rat. The pretreatment of BT‐11 (0.5, 3, and 5 μg/ml) significantly reduced cell death induced by Glu (1 mM), Aβ (10 μM) and CT105 (10 μM) in a dose‐dependent manner. In addition, BT‐11 inhibited acetylcholinesterase (AChE) activity in a dose‐dependent and non‐competitive manner (IC50 value; 263.7 μg/ml). Our novel findings suggest the possibility that this extract may have some protective effects against neuronal death and cognitive impairments in Alzheimer's disease (AD), or other neurodegenerative diseases related to excitotoxicity and central cholinergic dysfunction. © 2002 Wiley‐Liss, Inc.
Impaired cell cycle control of neuronal precursor cells in the neocortical primordium of presenilin‐1‐deficient mice
Authors: Yuasa Shigeki , Nakajima Mitsunari , Aizawa Hidenori , Sahara Naruhiko , Koizumi Ken‐Ichi , Sakai Tsuyoshi , Usami Mihoko , Kobayashi Shin‐Ichiro , Kuroyanagi Hidehito , Mori Hiroshi , Koseki Haruhiko , Shirasawa Takuji
Published: October 2002

Recent studies have implicated presenilin‐1 (PS‐1) in the processing of the amyloid precursor protein and Notch‐1. We show that PS‐1 has biological effects on differentiation and cell cycle control of neuronal precursor cells in vivo using PS‐1‐deficient mice. The expression of Class III β‐tubulin was upregulated throughout the neocortical primordia of PS‐1‐deficient E14 embryos, especially on the ventricular surface. The increased speed of migration of the immature neurons from the ventricular zone outward in the PS‐1‐deficient neocortical primordia was indicated by an in vivo bromodeoxyuridine (BrdU)‐labeling assay and a DiI‐labeling assay in slice culture. Furthermore, we investigated the cell cycle of neuronal precursor cells in the neocortical ventricular zone using an in vivo cumulative BrdU‐labeling assay. The length of the cell cycle in the neocortical precursor cells of wild‐type mice was 11.4 hr whereas that of the PS‐1‐deficient mice was 15.4 hr. Among all phases of the cell cycle, S‐phase exhibited the most prominent change in length, increasing from 2.4 hr in the wild‐type mice to 7.4 hr in the mutant mice. The distribution of β–catenin was specifically affected in the ventricular zone of the PS‐1‐deficient mice. These findings suggest that PS‐1 is involved in the differentiation and the cell cycle control of neuronal precursor cells in the ventricular proliferating zone of the neocortical primordium. © 2002 Wiley‐Liss, Inc.
4‐Methylcatechol stimulates phosphorylation of Trk family neurotrophin receptors and MAP kinases in cultured rat cortical neurons
Authors: Sometani Ayako , Nomoto Hiroshi , Nitta Atsumi , Furukawa Yoshiko , Furukawa Shoei
Published: October 2002

Effects of 4‐methycatechol (4MC), a potent stimulator of nerve growth factor and brain‐derived neurotrophic factor (BDNF) synthesis, on phosphorylation of cellular molecules in cultured rat cortical neurons were examined. 4MC stimulated tyrosine phosphorylation of various proteins of molecular weight from 10–300 kDa including Trks, which are high‐affinity neurotrophin receptors. Moreover, 4MC enhanced the phosphorylation of serine 133 of mitogen‐activated protein kinase (MAPK/ERK) in a dose‐dependent manner. Pretreatment of cultures with PD98059, a selective inhibitor of MAPK kinase (MEK‐1), inhibited 4MC‐induced phosphorylation of ERKs, demonstrating MEK‐1‐mediated activation. Therefore, it seems that 4MC triggered the phosphorylation of Trks, resulting in the activation of the subsequent MAPK/ERK signal cascade, or perhaps the involvement of BDNF action as 4MC can stimulate neuronal BDNF synthesis. The phosphorylation of MAPK/ERK was unaffected, however, in the presence of cycloheximide, a protein synthesis inhibitor, and K252a, a selective inhibitor of Trks, suggesting that the effect of newly synthesized BDNF was negligible on this event, and that primary sites of 4MC actions are not limited only to Trks. These results suggest that 4MC primarily activates multiple signal transduction molecules such as tyrosine kinases, including Trks. A significant increase in the survival rate of cortical neurons in the presence of 10 or 100 nM 4MC supported this idea, because the concentrations were much lower than those for stimulation of BDNF synthesis. Our results strongly suggest that the neurotrophic actions of 4MC found so far are mediated predominantly by direct activation of some intracellular signals including MAPK/ERK rather than by neurotrophin synthesis. © 2002 Wiley‐Liss, Inc.
Neuroplasticity in Alzheimer's disease
Authors: Teter Bruce , Ashford J. Wesson
Published: October 2002

Ramon y Cajal proclaimed in 1928 that “once development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. In the adult centers the nerve paths are something fixed, ended and immutable. Everything must die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree.” (Ramon y Cajal, 1928). In large part, despite the extensive knowledge gained since then, the latter directive has not yet been achieved by ‘modern’ science. Although we know now that Ramon y Cajal's observation on CNS plasticity is largely true (for lower brain and primary cortical structures), there are mechanisms for recovery from CNS injury. These mechanisms, however, may contribute to the vulnerability to neurodegenerative disease. They may also be exploited therapeutically to help alleviate the suffering from neurodegenerative conditions. Published 2002 Wiley‐Liss, Inc.
Effects of enriched environments with different durations and starting times on learning capacity during aging in rats assessed by a refined procedure of the Hebb‐Williams maze task
Authors: Kobayashi Satoru , Ohashi Yasushi , Ando Susumu
Published: October 2002

Cognitive function as measured by the Hebb‐Williams maze task was examined in Fischer 344 male rats that had been exposed to an enriched environment for periods of variable duration and at different starting ages. In one experiment, rats were exposed to environmental enrichment from weaning until the age of 2.5, 15, or 25 months. The results of 12 problems of the Hebb‐Williams maze task showed that the enriched rearing condition improved the learning ability in all the age groups; however, factor analysis and ANOVA demonstrated that four of the 12 maze problems were not suitable for detecting the effect of age under different environmental conditions. Reanalysis of the results obtained with the other eight maze problems more clearly revealed both the effects of rearing condition and aging. The latter analysis demonstrated that the learning rate of rats reared under enriched conditions was faster than that of rats reared under standard social conditions. Short‐term (3‐month) exposure also had positive effects on cognitive function in both adult (11‐month‐old) and aged (22‐month‐old) animals. The effect of long‐term exposure to an enriched environment starting at weaning was much greater than that of short‐term exposure in aged rats, whereas the effects of both long‐term and short‐term exposure were almost the same in adult rats. These results show that aged animals still have appreciable plasticity in cognitive function, and suggest that environmental stimulation could benefit aging humans as well. © 2002 Wiley‐Liss, Inc.
Animal model of dementia induced by entorhinal synaptic damage and partial restoration of cognitive deficits by BDNF and carnitine
Authors: Ando Susumu , Kobayashi Satoru , Waki Hatsue , Kon Kazuo , Fukui Fumiko , Tadenuma Tomoko , Iwamoto Machiko , Takeda Yasuo , Izumiyama Naotaka , Watanabe Kazutada , Nakamura Hiroaki
Published: October 2002

A rat dementia model with cognitive deficits was generated by synapse‐specific lesions using botulinum neurotoxin (BoNTx) type B in the entorhinal cortex. To detect cognitive deficits, different tasks were needed depending upon the age of the model animals. Impaired learning and memory with lesions were observed in adult rats using the Hebb‐Williams maze, AKON‐1 maze and a continuous alternation task in T‐maze. Cognitive deficits in lesioned aged rats were detected by a continuous alternation and delayed non‐matching‐to‐sample tasks in T‐maze. Adenovirus‐mediated BDNF gene expression enhanced neuronal plasticity, as revealed by behavioral tests and LTP formation. Chronic administration of carnitine over time pre‐ and post‐lesions seemed to partially ameliorate the cognitive deficits caused by the synaptic lesion. The carnitine‐accelerated recovery from synaptic damage was observed by electron microscopy. These results demonstrate that the BoNTx‐lesioned rat can be used as a model for dementia and that cognitive deficits can be alleviated in part by BDNF gene transfer or carnitine administration. © 2002 Wiley‐Liss, Inc.
Golden mean to longevity: Rareness of mitochondrial cytochrome b variants in centenarians but not in patients with Parkinson's disease
Authors: Tanaka Masashi , Fuku Noriyuki , Takeyasu Takeshi , Guo Li‐Jun , Hirose Raita , Kurata Miyuki , Borgeld Harm‐Jan W. , Yamada Yoshiji , Maruyama Wakako , Arai Yasumichi , Hirose Nobuyoshi , Oshida Yoshiharu , Sato Yuzo , Hattori Nobutaka , Mizuno Yoshikuni , Iwata So , Yagi Kunio
Published: October 2002

To test the hypothesis that centenarians are free from deleterious mitochondrial variations, we analyzed amino acid variations in the cytochrome b molecule of 64 Japanese centenarians. Although the frequencies of some variations, such as N260D and G251S, differed significantly between centenarians and patients with Parkinson's disease, the most striking feature of centenarian cytochrome b was the rareness of amino acid variations in contrast to the variety of amino acid replacements in patients with Parkinson's disease. These results suggest that centenarians are genetically hitting the “golden mean” (less variation from the consensus cytochrome b sequence or less mismatch with other subunits). A multiplex detection system for various deleterious variations in combination with genetic tests for longevity‐associated genotypes will be necessary to predict longevity or age‐related diseases. © 2002 Wiley‐Liss, Inc.
Elevated luteinizing hormone expression colocalizes with neurons vulnerable to Alzheimer's disease pathology
Authors: Bowen Richard L. , Smith Mark A. , Harris Peggy L.R. , Kubat Zvezdana , Martins Ralph N. , Castellani Rudolph J. , Perry George , Atwood Craig S.
Published: October 2002

In individuals with Alzheimer's disease (AD), there is a two‐fold elevation in the serum concentrations of the gonadotropins, luteinizing hormone (LH), and follicle stimulating hormone compared to age‐matched controls. Whether this plays a role in disease pathogenesis is unclear. Nonetheless, gonadotropins are known to cross the blood brain barrier and the highest density of gonadotropin receptors in the brain are found within the hippocampus. We report for the first time the localization of LH in the cytoplasm of pyramidal neurons. In addition, we find a significant increase in LH in the cytoplasm of pyramidal neurons and neurofibrillary tangles of AD brain compared to age‐matched control brain. Whereas the functional consequences of increased neuronal LH are unknown, it is notable that LH is primarily localized to those neurons that are known to be vulnerable to Alzheimer's disease‐related neurodegeneration. Elevated serum and cortical neuron levels of LH, coupled with the decline in sex steroid production, could play important roles in the pathogenesis of AD. © 2002 Wiley‐Liss, Inc.
Climatological analysis of wintertime extreme low temperatures in São Paulo City, Brazil: impact of sea‐surface temperature anomalies
Authors: Gonçalves F.L.T. , Silva Dias P.L. , Araújo G.P.
Published: October 2002

A diagnostic climatological study of winter cold temperature extremes in the Metropolitan Area of São Paulo (MASP) is presented. This diagnosis is based on temperature data collected at the Meteorological Station of Parque Estadual das Fontes do Ipiranga (IAG/USP) from 1950 to 2000. The persistence of synoptic and climatological patterns has been studied through principal component (PC) analysis and the results are compared with monthly anomalies in sea‐surface temperature (SST) of the eastern Pacific and South Atlantic. The extreme cold air temperatures, on a monthly basis, have shown no significant change since 1950. On the other hand, the mean monthly air temperatures have shown a slight warming trend, in agreement with the South Atlantic Ocean warming trend. The PC indicates significant loadings of two SST anomaly types: a cold anomaly of the South Atlantic Ocean, and a warm anomaly off the southern Brazilian coast. The latter could also be responsible for some extreme cold events (for daily minimum temperatures) in the MASP, and to a dominant westerly wind direction (southwest to northwest). Both the cold events and the westerly wind direction were evident in such winters as 1953, 1975, 1978, 1981, and 1994. On the other hand, the cold mean monthly temperatures are very well correlated to a broad cold pool anomaly in the South Atlantic at around 25 to 35° S and 15 to 55° W—sometimes narrower (such as in 1979 and 1988), and sometimes broader (such as 1964 and 1990). Where there was a narrowing or a widening, the prevailing wind direction was from the south–southeast. Therefore, the conclusion of these results is that the SST anomalies in the South Atlantic Ocean have a dominant effect on the São Paulo winter temperature climatology. Copyright © 2002 Royal Meteorological Society.
Daily dataset of 20th‐century surface air temperature and precipitation series for the European Climate Assessment
Authors: Klein Tank A. M. G. , Wijngaard J. B. , Können G. P. , Böhm R. , Demarée G. , Gocheva A. , Mileta M. , Pashiardis S. , Hejkrlik L. , Kern‐Hansen C. , Heino R. , Bessemoulin P. , Müller‐Westermeier G. , Tzanakou M. , Szalai S. , Pálsdóttir T. , Fitzgerald D. , Rubin S. , Capaldo M. , Maugeri M. , Leitass A. , Bukantis A. , Aberfeld R. , van Engelen A. F. V. , Forland E. , Mietus M. , Coelho F. , Mares C. , Razuvaev V. , Nieplova E. , Cegnar T. , Antonio López J. , Dahlström B. , Moberg A. , Kirchhofer W. , Ceylan A. , Pachaliuk O. , Alexander L. V. , Petrovic P.
Published: October 2002

We present a dataset of daily resolution climatic time series that has been compiled for the European Climate Assessment (ECA). As of December 2001, this ECA dataset comprises 199 series of minimum, maximum and/or daily mean temperature and 195 series of daily precipitation amount observed at meteorological stations in Europe and the Middle East. Almost all series cover the standard normal period 1961–90, and about 50% extends back to at least 1925. Part of the dataset (90%) is made available for climate research on CDROM and through the Internet (at http://www.knmi.nl/samenw/eca).

A comparison of the ECA dataset with existing gridded datasets, having monthly resolution, shows that correlation coefficients between ECA stations and nearest land grid boxes between 1946 and 1999 are higher than 0.8 for 93% of the temperature series and for 51% of the precipitation series. The overall trends in the ECA dataset are of comparable magnitude to those in the gridded datasets.

The potential of the ECA dataset for climate studies is demonstrated in two examples. In the first example, it is shown that the winter (October–March) warming in Europe in the 1976–99 period is accompanied by a positive trend in the number of warm‐spell days at most stations, but not by a negative trend in the number of cold‐spell days. Instead, the number of cold‐spell days increases over Europe. In the second example, it is shown for winter precipitation between 1946 and 1999 that positive trends in the mean amount per wet day prevail in areas that are getting drier and wetter.

Because of its daily resolution, the ECA dataset enables a variety of empirical climate studies, including detailed analyses of changes in the occurrence of extremes in relation to changes in mean temperature and total precipitation. Copyright © 2002 Royal Meteorological Society.
Luni‐solar tidal influences on climate variability
Authors: Treloar Norman C.
Published: October 2002

A possible exogenous cause of some terrestrial climate variability on time scales of 1 to 100 years is examined. Luni‐solar effects, and especially the coincidences of New Moon with small perigee distance, produce important tidal perturbations. These influences have been resolved in two orthogonal directions, and the variability in the southern oscillation and sea‐surface temperature anomalies may be at least partly understandable as a reflection of these tidal components. The correlation between tidal components and these climate factors is significant. The predictability of tidal effects may make a contribution to improving the accuracy and lead time of climate forecasting. Copyright © 2002 Royal Meteorological Society.
Behaviour of carbon dioxide and water vapour flux densities from a disturbed raised peat bog
Authors: Nieveen Joost P. , Jacobs Adrie F. G.
Published: October 2002

Measurements of carbon dioxide and water vapour flux densities were carried out for a disturbed raised peat bog in the north of the Netherlands during an 18 month continuous experiment. Tussock grass (sp. Molinea caerulae) mainly dominated the vegetation of the bog area. The maximum leaf area index (LAI) of the vegetation reached a numerical value of about 1.7 in mid‐August.

When the LAI is large enough (LAI > 0.2), a mean net uptake of carbon dioxide is observed with a clear daily pattern. The total evapotranspiration consists of a soil, an open water, and a plant transpiration part. When the LAI is large enough (LAI > 0.2), plant transpiration dominates the total evapotranspiration. The mean daily transpiration pattern, however, is not similar to the carbon dioxide uptake pattern.

During the summer months, the daytime carbon dioxide uptake shows a single early morning maximum value followed by a decline in uptake during the rest of the day. The evapotranspiration, however, follows more or less the incoming short‐wave radiation pattern. Effects of the vapour pressure deficit are suggested as a possible cause of this discrepancy. Copyright © 2002 Royal Meteorological Society.
Atmospheric circulation and precipitation in Italy for the last 50 years
Authors: Brunetti Michele , Maugeri Maurizio , Nanni Teresa
Published: October 2002

Daily precipitation series from 75 Italian stations, for the period 1951–95, are clustered into six regions and the average is calculated for each area. For each average series, the seasonal and annual total precipitation and the number of wet days are calculated. The relationship between precipitation and atmospheric circulation is examined using correlation analysis. Atmospheric circulation is represented by five indexes: the well known North Atlantic oscillation index, a blocking frequency index, a Mediterranean oscillation index based on the 500 hPa geopotential record for Algiers, a Western European zonal circulation index (WEZCI) constructed from Madrid + Barcelona and Trondheim + Lund surface pressure records, and a new Mediterranean circulation index (MCI) constructed from Marseille and Jerusalem surface pressure records. All the indexes are calculated using monthly series; then seasonal and yearly averages are obtained. The indexes that show the most interesting correlation with total precipitation and number of wet days are WEZCI and MCI. Trend analysis of the index series gives evidence of a signal connected to a strong increase in winter air pressure in the Mediterranean area starting around 1980. Copyright © 2002 Royal Meteorological Society.
Monthly mean rainfall frequency model for the central Chilean coast: some climatic inferences
Authors: Saavedra N. , Müller E. P. , Foppiano A. J.
Published: October 2002

A simple empirical model giving the annual evolution of monthly mean rainfall frequency for any location along the central Chilean coast is proposed. Model hypotheses are discussed with reference to a climatic scenario, which has been found of value in developing simple empirical climatic models for coastal stations in Chile. Equations giving monthly mean rainfall frequency for any latitude as a function of the latitude of the location of maximum monthly mean pressure in Chile are presented. It is concluded that the proposed model adequately describes the observed annual evolution. Moreover, the model allows qualitative inferences to be made regarding the interaction mechanisms between the main meteorological centres of action on a regional scale, which may prove of value in identifying trends of regional climatic change. Copyright © 2002 Royal Meteorological Society.
Associations between continental‐scale snow cover anomalies and air mass frequencies across eastern North America
Authors: Leathers Daniel J. , Mote Thomas L. , Grundstein Andrew J. , Robinson David A. , Felter Kathleen , Conrad Kathleen , Sedywitz Lauren
Published: October 2002

The spatial extent of snow cover has been shown to affect diverse meteorological variables, including surface air temperatures, atmospheric moisture, longwave and shortwave radiation budgets, and sensible and latent heat fluxes. However, little research has directly addressed the role of snow cover extent in the production and/or maintenance of diverse air mass types. The major hypothesis of this study is that continental‐scale snow cover anomalies should influence air mass frequencies because of their important effects on land‐surface energy budgets. To test this hypothesis, satellite‐derived Northern Hemisphere snow cover data were used in conjunction with a unique air mass classification routine to ascertain the association between air mass frequencies and snow cover anomalies across eastern North America.

Results indicate that continental‐scale snow cover anomalies are strongly associated with changes in the frequency of air masses over eastern North America. However, strong mid‐tropospheric circulation anomalies are often associated with the snow cover and air mass frequency changes, making it difficult to judge the relative importance of the snow cover anomaly to the variations in air mass frequency. During the months of November, December, January and April, circulation patterns are present that would lead to the observed snow cover anomalies and associated air mass frequency changes. Thus, we hypothesize that snow cover anomalies (resulting from the strong circulation anomalies) help to enhance changes in the air mass frequencies of the region. However, during the months of February and March no strong circulation anomalies are apparent, suggesting that during these months snow cover may play a dominant role in air mass frequency variations. Copyright © 2002 Royal Meteorological Society.
Long‐term changes in ozone mini‐hole event frequency over the Northern Hemisphere derived from ground‐based measurements
Authors: Krzyścin Janusz W.
Published: October 2002

Decadal changes of ozone mini‐hole event appearance over the Northern Hemisphere midlatitudes are examined based on daily total ozone data from seven stations having long records (four decades or more) of ozone observations. The various threshold methods for accepting and rejecting the ozone minima as mini‐holes are examined. Mini‐hole event activity is seen to be rather stable when averaged over a decadal time scale if the mini‐holes are selected as large negative departures (exceeding 20%) relative to the moving long‐term total ozone reference. The results are compared with a previous ozone mini‐hole climatology derived from satellite data (TOMS measurements on board the Nimbus‐7 satellite for the period 1978–93). A nonlinear statistical model (MARS), which takes into account various total ozone dynamical proxies (from NCEP–NCAR reanalysis), is used to study dynamical factors responsible for the ozone extremes over Arosa in the period 1950–99. The model explains as much as 95% of the total variance of the ozone extremes. The model–observation differences averaged over the decadal intervals are rather smooth throughout the whole period analysed. It is suggested that the short‐term dynamical processes controlling the appearance of ozone extremes influenced the ozone field in a similar way before and after the onset of abrupt ozone depletion in the early 1980s. The analysis of the ozone profile and the tropopause pressure (from the ozonesondings over Hohenpeissenberg, 1966–99) during mini‐hole events shows ∼60% ozone reduction in the lower stratosphere and an approximately 50 hPa upward shift of the thermal tropopause there. Copyright © 2002 Royal Meteorological Society.
Analysis of recent circulation and thermal advection change in the northern Antarctic Peninsula
Authors: Marshall Gareth J.
Published: October 2002

Changes in circulation at 500 and 850 hPa and horizontal thermal advection between these two levels are examined at Bellingshausen station in the northern Antarctic Peninsula between 1969 and 2000. A synthesis of radiosonde observations and reanalysis data is employed, the latter being ‘corrected’ to remove any bias and trend versus the observations. These data only reveal statistically significant increases in the annual zonal wind component; although the mean direction of the thermal advection is 339° there is no indication of increasing northerlies coincident with the remarkable regional surface warming. Seasonally, the zonal wind is most highly correlated with surface temperature in autumn and winter, the seasons showing the greatest temperature rise. This suggests that the increasing westerlies have played a role in the recent warming, and several authors have postulated that this results from a trend towards the positive phase of the Southern Hemisphere annular mode (SAM). However, a comparison between a regional zonal circulation index derived independently from observations and the reanalysis data used in past studies of the SAM indicates long‐term increases in the latter may be an artefact caused by errors in the early reanalysis data. While observations do indicate an increase in the zonal wind since the late 1970s, coincident with a decline in the strength of the semi‐annual oscillation, there is no clear evidence of circulation changes driving the long‐term Antarctic Peninsula surface warming. Copyright © 2002 Royal Meteorological Society.
Hypothalamic digoxin and hypomagnesemia in human pre‐eclampsic toxemia, cortical venous thrombosis, and postpartum psychosis
Authors: Kurup Ravi Kumar , Kurup Parameswara Achutha
Published: October 2002

The isoprenoid pathway produces three key metabolites—digoxin (membrane sodium‐potassium ATPase inhibitor and regulator of neurotransmitter transport), dolichol (regulates N‐glycosylation of proteins), and ubiquinone (free radical scavenger). The pathway was assessed in patients with pre‐eclampsic toxaemia, cortical venous thrombosis, and postpartum psychosis. It was also studied for comparison in patients with right hemispheric, left hemispheric, and bihemispheric dominance. The results of the study showed that the isoprenoid pathway was upregulated with increased digoxin synthesis in all the three groups of patients. There was also a reduction in red blood cell (RBC) membrane Na+–K+ ATPase activity and serum magnesium levels. There was an increase in serum tryptophan catabolites and reduction in tyrosine catabolites. The serum dolichol and glycoconjugate levels were increased and lysosomal stability reduced with increased plasma lysosomal enzymes in all the three groups. The serum ubiquinone levels were low, and RBC free radical parameters increased. The RBC membrane cholesterol: phospholipid ratio was increased, and glycoconjugate was reduced in the membrane of these patients. This pattern correlated with those in right hemispheric dominance. The isoprenoid pathway and hypothalamic digoxin may thus play a crucial role in the pathogenesis of CVT, PET, and postpartum psychosis. J. Trace Elem. Exp. Med. 15:171–190 2002. © 2002 Wiley‐Liss, Inc.
Milk selenium content is enhanced by modest selenium supplementation in extended lactation
Authors: Dylewski Maggie L. , Picciano Mary Frances
Published: October 2002

Supplemental selenium (Se) as selenate, selenomethionine, or Se‐enriched yeast at 100–200 μg Se/day causes an increase or prevents a decline in human milk selenium content during the first 6 months of lactation. In this study, we evaluated the impact of supplemental Se as sodium selenate at 20 μg/day, an amount that closely approximates the quantity of selenium lost daily via milk secretion. Lactating women (n = 23) provided dietary data and milk and plasma samples at 3 and 6 months postpartum. At 3 months postpartum, all women received a daily vitamin/mineral supplement that furnished 20 μg of Se as sodium selenate for 3 months. Mean Se intake from self‐selected diets was 111 ± 40 μg/day and did not differ between 3 and 6 months. Selenium supplementation increased milk Se from 3 (295 ± 18 nmol/L; 23 ± 7 ng/mL) to 6 months (417 ± 39 nmol/L; 32 ± 14 ng/mL) postpartum (P ≤ 0.01) and corresponding infant Se intakes from 12 μg/day to 20 μg/day. Maternal plasma Se concentration was 1.46 ± 0.42 μmol/L (115 ± 33 ng/mL) at 3 months and 1.76 ± 0.20 μmol/L (155 ± 16 ng/mL) at 6 months postpartum, but this apparent difference was not significantly different. Maternal supplemental Se at 20 μg/day caused a 41% increase in human milk Se and a corresponding 67% increase in infant Se intake. Data show that supplemental Se at or near the quantity secreted daily is sufficient to prevent a decline in human milk Se with advancing lactation. J. Trace Elem. Exp. Med. 15:191–199, 2002. © 2002 Wiley‐Liss, Inc.
Hypothalamic digoxin and hypomagnesemia in relation to the pathogenesis of multiple sclerosis
Authors: Kurup Ravi Kumar , Kurup Parameswara Achutha
Published: October 2002

This study assessed the isoprenoid pathway‐related biochemical cascade in multiple sclerosis, and in this work we discuss the pivotal role of hypothalamic digoxin and membrane sodium‐potassium ATPase inhibition in the pathogenesis of multiple sclerosis. Our results showed that there was an elevation in plasma HMG CoA reductase activity, serum digoxin, and dolichol levels and a reduction in red blood cell (RBC) membrane sodium potassium ATPase activity, serum ubiquinone, and magnesium levels. Serum tryptophan, serotonin, strychnine, nicotine, and quinolinic acid were elevated whereas tyrosine, dopamine, morphine, and noradrenaline were decreased. The total serum glycosaminoglycans, hyaluronic acid, heparin, and heparan sulphate were elevated and levels of chondroitin sulphates and dermatan sulphate were reduced in multiple sclerosis. The serum glycolipids as well as the hexose, fucose, and sialic acid carbohydrate residues of serum glycoproteins were elevated. The activity of glycosaminoglycan degrading enzymes was elevated. The activity of glycohydrolases—beta galactosidase and beta fucosidase—were increased and beta glucosidase reduced in the serum. The RBC membrane glycosaminoglycan, the hexose and fucose carbohydrate residues of glycoproteins, and the cholesterol:phospholipid ratio of the RBC membrane were decreased in multiple sclerosis. Membrane Na+‐K+ ATPase inhibition‐related increased intracellular calcium can produce immune activation via the calcineurin signal transduction system in T cells. Digoxin‐induced altered glycoconjugate metabolism can change the structural integrity of myelin as well as result in immune dysregulation caused by defective presentation of myelin glycoprotein antigens to CD8 cells. Digoxin‐induced defective membrane formation of oligodendrocyte membrane can inhibit remyelination. Digoxin‐related mitochondrial dysfunction can contribute to free radical generation, microglial activation, and oligodendrocyte apoptosis that are important in demyelination. J. Trace Elem. Exp. Med. 15:211–220, 2002. © 2002 Wiley‐Liss, Inc.
Effects of marathon running on the trace minerals chromium, cobalt, nickel, and molybdenum
Authors: Berger Christian E. , Kröner Andreas , Kluger Rainer , Baron Ramon , Steffan Ilse , Engel Alfred
Published: October 2002

There is considerable debate on the effects of endurance stress on concentrations of trace minerals and as to whether athletes, who restrict calories to maintain low body weights, could comprise their trace mineral levels. In a prospective study, the effect of running a marathon course on whole blood levels of chromium, cobalt, nickel, and molybdenum was evaluated. Blood samples of 13 test runners (2 females, 11 males) were obtained twice before, immediately after, and 1 week after running a marathon. The analyses of the concentrations in whole blood were performed using graphite tube atom absorption spectrometry (GFAAS). The chromium level of the samples ranged between 1.3 ng/g and 19.3 ng/g. Mean chromium concentrations were elevated before and immediately after the marathon (4.3–7.4 ng/g) and decreased to an average of 2.7 ng/g after the marathon course. The difference between chromium concentrations obtained immediately after and 1 week after the marathon course was significant. Levels of chromium exhibited a high variability; however, the percentage of concentrations below the detection limit was 0%. Similarly, owing to different individual response to strenuous exercise, concentrations of nickel, molybdenum, and cobalt were highly variable, exceeding normal limits by 47.3%, 25.1%, and 4.6%, respectively. Mean concentrations of nickel, cobalt, and molybdenum ranged from 4.3–22.7 ng/g (Ni), 0.16–2.2 ng/g (Co), and 0.2–0.7 ng/g (Mo); the difference was not significant at any time. The current study was able to show that running a marathon course does not lead to significant changes in the whole blood levels of cobalt, nickel and molybdenum. Chromium levels, however, were significantly decreased immediately after the marathon course, a finding that corresponds well with previous observations of increased mobilization of chromium from body stores and subsequently elevated serum levels. J. Trace Elem. Exp. Med. 15:201–209, 2002. © 2002 Wiley‐Liss, Inc.
Assessing academic department efficiency at a public university
Authors: Moreno Abel A. , Tadepalli Raghu
Published: October 2002

The assessment of public universities has gained importance because of the demands from such state government bodies as the executive and the legislature. Public universities are increasingly being asked to account for how efficiently they have used diminishing state financial resources. Administrators thus have the responsibility of ensuring that the university's financial, human, and physical resources are allocated to academic departments in a manner that enhances the institution's efficiency. In this paper, data envelopment analysis (DEA) is proposed for evaluating the efficiency of academic departments at a public university. DEA provides a single measure of efficiency for each academic unit. It also identifies the causes behind the inefficiencies exhibited by poor performing units, as well as the changes that these units need to make in order to improve their efficiencies. Its usefulness as a planning tool is also discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Beyond profitability: effects of acquisitions on technical efficiency in the Italian pasta industry
Authors: Benfratello Luigi
Published: October 2002

Unlike traditional studies on the impact of ownership changes—which use either profitability measures or stock prices—this paper investigates the impact of acquisitions on acquired firms' technical efficiency. Using a panel of Italian firms in the pasta industry for the 1981–1997 period, I estimate a stochastic production frontier with exogenous factors affecting efficiency in a translog specification with non‐neutral technical progress. The main result is that acquired firms experience, within the 6 years period following the acquisition, an increase in technical efficiency of the order of 10%. This result is statistically significant and proves to be robust with respect to the inclusion of size and calendar year effects as explanatory variables of firms' inefficiency. These findings contribute to the debate on the welfare gains of ownership changes by providing evidence that mergers and acquisitions lead to cost savings, due to the reduction of acquired firms' X‐inefficiency. Copyright © 2002 John Wiley & Sons, Ltd.