bluuebunny/crossref_metadata_2025 huggingface dataset:
Pension system generosity and reform in Algeria, Morocco and Tunisia
Authors: Ben Braham Mehdi
Published: April 2009

Pension systems in the North African countries of Algeria, Morocco and Tunisia are facing a certain number of difficulties. Presenting the characteristics and organizational structure of each, this article identifies the specificities of, as well as the common problems confronting, these countries' pension systems. With reference to authorizing legislation and case simulations, the high level of generosity of the different pension systems is discussed and an analysis presented. In a context of population ageing, it is argued that current levels of generosity cannot be maintained; reform is needed. The article discusses different reform options, the challenges of implementation and the possible macroeconomic impacts of reform.
Does a top‐predator provide an endangered rodent with refuge from an invasive mesopredator?
Authors: Letnic M. , Crowther M. S. , Koch F.
Published: April 2009

In arid environments, ecological refuges are often conceptualised as places where animal species can persist through drought owing to the localised persistence of moisture and nutrients. The mesopredator release hypothesis (MRH) predicts that reduced abundance of top‐order predators results in an increase in the abundance of smaller predators (mesopredators) and consequently has detrimental impacts on the prey of the smaller predators. Thus according to the MRH, the existence of larger predators may provide prey with refuge from predation. In this study, we investigated how the abundance of an endangered rodent Notomys fuscus is affected by Australia's largest predator, the dingo Canis lupus dingo, introduced mesopredators, introduced herbivores, kangaroos and rainfall. Our surveys showed that N. fuscus was more abundant where dingoes occurred. Generalised linear modelling showed that N. fuscus abundance was associated positively with dingo activity and long‐term annual rainfall and negatively with red fox Vulpes vulpes activity. Our results were consistent with the hypothesis that areas with higher rainfall and dingoes provide N. fuscus with refuge from drought and predation by invasive red foxes, respectively. Top‐order predators, such as dingoes, could have an important functional role in broad‐scale biodiversity conservation programmes by reducing the impacts of mesopredators.
Screen‐detected invasive cervical carcinoma and its clinical significance during the introduction of organized screening
Authors: Herbert A , Anshu  , Gregory M , Gupta SS , Singh N
Published: April 2009

Objective  To assess the clinical significance of screen‐detected cancer compared with symptomatic cervical cancer during the introduction of organized screening.

Study design  Screen‐detected and symptomatic cancers were analysed according to International Federation of Obstetrics and Gynecology stage and histological type of cancer and age of women during four 3‐year periods.

Setting  Southampton and South West Hampshire (SSWH).

Population  Women resident in SSWH registered with invasive cervical carcinoma between 1985 and 1996.

Methods  Screen‐detected and symptomatic cancers were defined on the basis of clinical information obtained at the time of diagnosis and recorded together with date of diagnosis, age group, histology and cytology results. Data were held for analysis on an anonymous spreadsheet.

Main outcome measures  Incidence of screen‐detected and symptomatic cancers per 100 000 women; association between route to diagnosis, age group, stage of cancer and screening history during four 3‐year periods.

Results  Of 382 cancers, 256 were symptomatic, 78 screen‐detected fully invasive and 48 screen‐detected microinvasive. Incidence of symptomatic cancers fell from 13.0 to 6.4 per 100 000 total female population (P = 0.0005), and there was a trend towards screen‐detected cancers as a proportion of all cancers (P = 0.002). By the latest period of the study (1994–96), the likelihood of cancers being screen‐detected was strongly associated with younger age groups (P = 0.001). Screen‐detected fully invasive cancers were significantly less likely (P = 0.001) to be diagnosed at stage II or above (16.6%) compared with symptomatic cancers (63.3%). Women with screen‐detected microinvasive cancers were significantly more likely (P < 0.001) to have been screened within 5 years (83.3%) than screen‐detected fully invasive cancers (60.2%) or symptomatic cancers (33.6%).

Conclusion  Screen‐detected cancers were more likely to be diagnosed at an earlier stage, in younger women and in women who had previously been screened and became relatively more frequent as symptomatic cancers declined.
Treating miscarriages: a randomised study of cost‐effectiveness in medical or surgical choice
Authors: Niinimäki M , Karinen P , Hartikainen A‐L , Pouta A
Published: April 2009

Objective  The aim was to carry out a cost effectiveness analysis (CEA) of medical and surgical treatment of miscarriage using quantitative and qualitative indicators.

Design  A prospective study where the data of the clinical course of the treatment and the patients` experiences (pain and satisfaction) were collected from a previous randomised study.

Setting  Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland.

Population  Ninety‐eight eligible women with a diagnosed miscarriage.

Methods  The incremental cost‐effectiveness ratio (ICER) was calculated by using institutional prices (provider’s aspect) of the medical care and the number of patients who experienced pain, dissatisfaction or unsuccessful treatment while treated for the miscarriage.

Main outcome measures  Primary (uncomplicated treatment) and secondary (complications and other unplanned events) costs of the treatments.

Results  Primary costs of the surgical treatment were higher, but the more frequent unplanned events and complications in the medical group brought the costs to the same level. In the medical group, based on the ICER, 12 patients more experienced pain, 7 patients more were dissatisfied with the treatment and 5 patients more had unsuccessful treatment compared with surgically treated patients. In theory, these negative outcomes could have been avoided by investing €1688 more in the surgical treatment.

Conclusions  Medical treatment of miscarriage was not more cost‐effective, when the adverse events were considered. As neither of these two methods was economically superior, the treatment choice should be made on an individual basis by respecting the patient’s choice.
Rescue of Aβ1–42‐induced memory impairment in day‐old chick by facilitation of astrocytic oxidative metabolism: implications for Alzheimer’s disease
Authors: Gibbs Marie E. , Gibbs Zoe , Hertz Leif
Published: April 2009

Administration of small oligomeric β‐amyloid (Aβ)1–42 45 min before one‐trial bead discrimination learning in day‐old chicks abolishes consolidation of learning 30 min post‐training (Gibbs et al. Neurobiol. Aging, in press). Administration of the β3‐adrenergic agonist CL316243, which specifically stimulates astrocytic but not neuronal glucose uptake, rescues Aβ impaired memory. Weakly reinforced training can be consolidated by various metabolic substrates and we have demonstrated neuronal dependence on oxidative metabolism of glucose soon after training versus astrocytic glucose dependence 20 min later. Based on these findings we examined whether different metabolic substrates were able to counteract memory inhibition by Aβ1–42. Although lactate, the medium‐chain fatty acid octanoate, and the ketone body β‐hydroxybutyrate consolidated weakly reinforced training when injected close to learning, none of them were able to salvage Aβ‐impaired memory; at this early time. All three metabolites and the astrocytic‐specific acetate consolidated weak learning and rescued Aβ‐impaired memory when injected 10–20 min post‐training. However, neither glucose nor insulin rescued memory when injected at 20 min. Rescue of memory by providing astrocytes with alternative substrates for oxidative metabolism suggests that Aβ1–42 exerts its amnestic effects specifically by impairing astrocytic glycolysis.
Cerebral oxygen demand for short‐lived and steady‐state events
Authors: Herman Peter , Sanganahalli Basavaraju G. , Blumenfeld Hal , Hyder Fahmeed
Published: April 2009

Because of the importance of oxidative energetics for cerebral function, extraction of oxygen consumption (CMRO2) from blood oxygenation level‐dependent (BOLD) signal using multi‐modal measurements of blood flow (CBF) and volume (CBV) has become an accepted functional magnetic resonance imaging (fMRI) technique. This approach, termed calibrated fMRI, is based on a biophysical model which describes tissue oxygen extraction at steady‐state. A problem encountered for calculating dynamic CMRO2 relates to concerns whether the conventional BOLD model can be applied transiently. In particular, it is unclear whether calculation of CMRO2 differs between short and long stimuli. Linearity was experimentally demonstrated between BOLD‐related components and neural activity, thereby making it possible to use calibrated fMRI in a dynamic manner. We used multi‐modal fMRI and electrophysiology, in α‐chloralose anesthetized rats during forepaw stimulation to show that respective transfer functions (of BOLD, CBV, CBF) generated by deconvolution with neural activity are time invariant, for events in the millisecond to minute range. These results allowed extraction of a significant component of the BOLD signal that can be ascribed to CMRO2 transients. We discuss the importance of minimizing residual signal, represented by the difference between modeled and raw signals, in convolution analysis of multi‐modal signals.
The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer’s disease
Authors: Wang Xinglong , Su Bo , Zheng Ling , Perry George , Smith Mark A. , Zhu Xiongwei
Published: April 2009

Mitochondria play critical roles in neuronal function and almost all aspects of mitochondrial function are altered in Alzheimer neurons. Emerging evidence shows that mitochondria are dynamic organelles that undergo continuous fission and fusion, the balance of which not only controls mitochondrial morphology and number, but also regulates mitochondrial function and distribution. In this review, after a brief overview of the basic mechanisms involved in the regulation of mitochondrial fission and fusion and how mitochondrial dynamics affects mitochondrial function, we will discuss in detail our and others’ recent work demonstrating abnormal mitochondrial morphology and distribution in Alzheimer’s disease (AD) models and how these abnormalities may contribute to mitochondrial and synaptic dysfunction in AD. We propose that abnormal mitochondrial dynamics plays a key role in causing the dysfunction of mitochondria that ultimately damage AD neurons.
Acetate transport and utilization in the rat brain
Authors: Deelchand Dinesh K. , Shestov Alexander A. , Koski Dee M. , Uğurbil Kâmil , Henry Pierre‐Gilles
Published: April 2009

Acetate, a glial‐specific substrate, is an attractive alternative to glucose for the study of neuronal‐glial interactions. The present study investigates the kinetics of acetate uptake and utilization in the rat brainin vivoduring infusion of [2‐13C]acetate using NMR spectroscopy. When plasma acetate concentration was increased, the rate of brain acetate utilization (CMRace) increased progressively and reached close to saturation for plasma acetate concentration > 2–3 mM, whereas brain acetate concentration continued to increase. The Michaelis–Menten constant for brain acetate utilization ( = 0.01 ± 0.14 mM) was much smaller than for acetate transport through the blood–brain barrier (BBB) ( = 4.18 ± 0.83 mM). The maximum transport capacity of acetate through the BBB ( = 0.96 ± 0.18 μmol/g/min) was nearly twofold higher than the maximum rate of brain acetate utilization ( = 0.50 ± 0.08 μmol/g/min). We conclude that, under our experimental conditions, brain acetate utilization is saturated when plasma acetate concentrations increase above 2–3 mM. At such high plasma acetate concentration, the rate‐limiting step for glial acetate metabolism is not the BBB, but occurs after entry of acetate into the brain.
Delayed cerebral oxidative glucose metabolism after traumatic brain injury in young rats
Authors: Scafidi Susanna , O’Brien Janet , Hopkins Irene , Robertson Courtney , Fiskum Gary , McKenna Mary
Published: April 2009

Traumatic brain injury (TBI) results in a cerebral metabolic crisis that contributes to poor neurologic outcome. The aim of this study was to characterize changes in oxidative glucose metabolism in early periods after injury in the brains of immature animals. At 5 h after controlled cortical impact TBI or sham surgery to the left cortex, 21–22 day old rats were injected intraperitoneally with [1,6‐13C]glucose and brains removed 15, 30 and 60 min later and studied by ex vivo 13C‐NMR spectroscopy. Oxidative metabolism, determined by incorporation of 13C into glutamate, glutamine and GABA over 15–60 min, was significantly delayed in both hemispheres of brain from TBI rats. The most striking delay was in labeling of the C4 position of glutamate from neuronal metabolism of glucose in the injured, ipsilateral hemisphere which peaked at 60 min, compared with the contralateral and sham‐operated brains, where metabolism peaked at 30 and 15 min, respectively. Our findings indicate that (i) neuronal‐specific oxidative metabolism of glucose at 5–6 h after TBI is delayed in both injured and contralateral sides compared with sham brain; (ii) labeling from metabolism of glucose via the pyruvate carboxylase pathway in astrocytes was also initially delayed in both sides of TBI brain compared with sham brain; (iii) despite this delayed incorporation, at 6 h after TBI, both sides of the brain showed apparent increased neuronal and glial metabolism, reflecting accumulation of labeled metabolites, suggesting impaired malate aspartate shuttle activity. The presence of delayed metabolism, followed by accumulation of labeled compounds is evidence of severe alterations in homeostasis that could impair mitochondrial metabolism in both ipsilateral and contralateral sides of brain after TBI. However, ongoing oxidative metabolism in mitochondria in injured brain suggests that there is a window of opportunity for therapeutic intervention up to at least 6 h after injury.
Transcranial flavoprotein fluorescence imaging of mouse cortical activity and plasticity
Authors: Tohmi Manavu , Takahashi Kuniyuki , Kubota Yamato , Hishida Ryuichi , Shibuki Katsuei
Published: April 2009

Endogenous fluorescence signals derived from mitochondria reflect activity‐dependent changes in brain metabolism and may be exploited in functional brain imaging. Endogenous flavoprotein fluorescence imaging in mice is especially important because many genetically manipulated strains of mice are available and the transparent skull of mice allows transcranial fluorescence imaging of cortical activities. In the primary sensory areas of mice, cortical activities and experience‐dependent plasticity have been investigated using transcranial fluorescence imaging. Furthermore, differential imaging, based on stimulus specificity of cortical areas, distinguished activities in higher visual areas around the primary visual cortex from those in primary visual cortex. The combination of transcranial fluorescence imaging with the suppression of cortical activities using photobleaching of flavoproteins is expected to aid in elucidating the roles of sensory cortices including higher areas in mice.
GABAergic striatal neurons exhibit caspase‐independent, mitochondrially mediated programmed cell death
Authors: Diwakarla Shanti , Mercer Linda D. , Kardashsyan Liubov , Chu Percy W. Y. , Shin Yea Seul , Lau Chew L. , Hughes Maria L. R. , Nagley Phillip , Beart Philip M.
Published: April 2009

GABAergic striatal neurons are compromised in basal ganglia pathologies and we analysed how insult nature determined their patterns of injury and recruitment of the intrinsic mitochondrial pathway during programmed cell death (PCD). Stressors affecting targets implicated in striatal neurodegeneration [3‐morpholinylsydnoneimine (SIN‐1), 3‐nitropropionic acid (3‐NP), NMDA, 3,5‐dihydroxyphenylglycine (DHPG), and staurosporine (STS)] were compared in cultured GABAergic neurons from murine striatum by analyzing the progression of injury and its correlation with mitochondrial involvement, the redistribution of intermembrane space (IMS) proteins, and patterns of protease activation. Stressors produced PCD exhibiting slow‐onset kinetics with time‐dependent annexin‐V labeling and eventual DNA fragmentation. IMS proteins including cytochromecwere differentially distributed, although stressors except STS produced early redistribution of apoptosis‐inducing factor and Omi, suggestive of early recruitment of both caspase‐dependent and caspase‐independent signaling. In general, Bax mobilization to mitochondria appeared to promote IMS protein redistribution. Caspase 3 activation was prominent after STS, whereas NMDA and SIN‐1 produced mainly calpain activation, and 3‐NP and DHPG elicited a mixed profile of protease activation. PCD and redistribution of IMS proteins in striatal GABAergic neurons were canonical and insult‐dependent, reflecting differential interplay between the caspase cascade and alternate cell death pathways.
Acute changes in intermediary metabolism in cerebellum and contralateral hemisphere following middle cerebral artery occlusion in rat
Authors: Håberg Asta K. , Qu Hong , Sonnewald Ursula
Published: April 2009

Focal ischemia leads to functional deafferentation of regions connected to the ischemic area via fiber tracts. Using i.v. administration of 13C‐labeled glucose and acetate combined with ex vivo13C MR spectroscopy and HPLC of brain extracts we identify the effect of middle cerebral artery occlusion (MCAO) on neurotransmitter synthesis and turnover, and on neuro‐astrocytic interactions in the non‐ischemic cerebellum and in contralesional lateral caudoputamen plus lower parietal cortex (LPC), and upper frontoparietal cortex (UFPCx) in the rat after 30, 60, 120 and 240 min of ischemia. In all regions, there was a significant persisting loss of glutamate, and in LCP and UFPCx also of glutamine, but only in LCP was GABA reduced at all times. Metabolism and blood flow were uncoupled in all regions. In cerebellum, glucose metabolism as well as utilization of intermediates derived from astrocytic tricarboxylic acid cycle activity were significantly decreased at all times in both glutamatergic and GABAergic neurons. In LCP and UFPCx, there were normal or increased enrichment in glutamate and GABA from glucose. Glutamate derived from astrocytic acetate metabolism was increased, but GABA synthesis from acetate was initially impaired. The results showed that both the type of afferent connection, i.e., glutamatergic and/or GABAergic, and local cytoarchitecture, determined the effect MCAO had on metabolic activity in the non‐ischemic regions. In conclusion, it was primarily excitatory input into non‐ischemic regions that was affected by MCAO, perhaps enabling resetting of the excitatory/inhibitory balance, aiding reshaping of the receptive fields and thus facilitating recovery.
Inhibition of the alpha‐ketoglutarate dehydrogenase‐mediated reactive oxygen species generation by lipoic acid
Authors: Ambrus Attila , Tretter László , Adam‐Vizi Vera
Published: April 2009

Dihydrolipoamide dehydrogenase (LADH) is a flavo‐enzyme that serves as a subunit of α‐ketoglutarate dehydrogenase complex (α‐KGDHC). Reactive oxygen species (ROS) generation by α‐KGDHC has been assigned to LADH (E3 subunit) and explained by the diaphorase activity of E3. Dysfunctions of α‐KGDHC and concurrent ROS production have been implicated in neurodegeneration, ischemia‐reperfusion, and other pathological conditions. In this work we investigated the in‐depth details of ROS generation by isolated LADH and α‐KGDHC. We found a parallel generation of superoxide and hydrogen peroxide by the E3 subunit of α‐KGDHC which could be blocked by lipoic acid (LA) acting on a site upstream of the E3 subunit. The pathologically relevant ROS generation (at high NADH/NAD+ ratio and low pH) in the reverse mode of α‐KGDHC could also be inhibited by LA. Our results contradict the previously proposed mechanism for pH‐dependent ROS generation by LADH, showing no disassembling of the E3 functional homodimer at acidic pH using a physiologically relevant method for the examination. It is also suggested that LA could be beneficial in reducing the cell damage related to excessive ROS generation under pathological conditions.
The turnover of the H3 deuterons from (2‐13C) glutamate and (2‐13C) glutamine reveals subcellular trafficking in the brain of partially deuterated rats
Authors: Cerdán Sebastián , Sierra Alejandra , Fonseca Luis L. , Ballesteros Paloma , Rodrigues Tiago B.
Published: April 2009

We investigated by 13C NMR the turnover of the H3 deuterons of (2‐13C) glutamate and (2‐13C) glutamine in the brain of partially deuterated rats. Adult animals (150–200 g) fed ad libitum received 50%2H2O or tap water 9 days before infusing (1‐13C) glucose or (2‐13C) acetate for 5, 10, 15, 30, 60, or 90 min. The brains were then funnel‐frozen and acid extracts were prepared and analyzed by high‐resolution 13C NMR. The deuteration of one or the two H3 hydrogens of (2‐13C) glutamate or glutamine resulted in single (−0.07 ppm) or double (−0.14 ppm) isotopic shifts upfield of the corresponding C2 perprotonated resonance, demonstrating two sequential deuteration steps. The faster monodeuteration generated 3R or 3S (2‐13C, 3‐2H) glutamate or glutamine through the alternate activities of cerebral aconitase or isocitrate dehydrogenase, respectively. The slower process produced bideuterated (2‐13C, 3,3′‐2H2) glutamate or glutamine through the consecutive activity of both enzymes. The kinetics of deuteration was fitted to a Michaelis–Menten model including the apparent Km′ and Vmax′ values for the observed deuterations. Our results revealed different kinetic constants for the alternate and consecutive deuterations, suggesting that these processes were caused by the different cytosolic or mitochondrial isoforms of aconitase and isocitrate dehydrogenase, respectively. The deuterations of (2‐13C) glutamate or glutamine followed also different kinetics from (1‐13C) glucose or (2‐13C) acetate, revealing distinct deuteration environments in the neuronal or glial compartments.
Ischemia activates JNK/c‐Jun/AP‐1 pathway to up‐regulate 14‐3‐3γ in astrocyte
Authors: Dong Yan , Liu Hua Dong , Zhao Rui , Yang Chun Zhang , Chen Xiao Qian , Wang Xin Hong , Lau Lok Ting , Chen Jianguo , Yu Albert Cheung Hoi
Published: April 2009

Ischemia occurs in the brain as the result of stroke and other related injuries and few therapies are effective. If more is understood then potential treatments could be investigated. It was previously reported that 14‐3‐3γ could be up‐regulated by ischemia in astrocyte to protect cells from ischemia‐induced apoptosis. In this study, we attempted to uncover the mechanism responsible for this 14‐3‐3γ up‐regulation in primary culture of astrocytes under ischemic‐like conditions. It was found that in vitro ischemia may activate PI3K/Akt and MAPK signaling pathways. Astrocyte cultures were treated with LY294002 (PI3K inhibitor), U0126 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor). Only SP600125 could inhibit the ischemia‐induced 14‐3‐3γ up‐regulation in astrocytes. At the same time, we observed an ischemia‐induced nuclear translocation of p‐c‐Jun, a major downstream component of JNK. Inhibition of AP‐1 with curcumin also inhibited 14‐3‐3γ up‐regulation indicating that ischemia‐induced up‐regulation of 14‐3‐3γ in astrocyte involves activation of the JNK/p‐c‐Jun/AP‐1 pathway.
Differential gene expression in LPS/IFNγ activated microglia and macrophages: in vitro versus in vivo
Authors: Schmid Christoph D. , Melchior Benoit , Masek Kokoechat , Puntambekar Shweta S. , Danielson Patria E. , Lo David D. , Gregor Sutcliffe J. , Carson Monica J.
Published: April 2009

Two different macrophage populations contribute to CNS neuroinflammation: CNS‐resident microglia and CNS‐infiltrating peripheral macrophages. Markers distinguishing these two populations in tissue sections have not been identified. Therefore, we compared gene expression between LPS (lipopolysaccharide)/interferon (IFN)γ‐treated microglia from neonatal mixed glial cultures and similarly treated peritoneal macrophages. Fifteen molecules were identified by quantative PCR (qPCR) as being enriched from 2‐fold to 250‐fold in cultured neonatal microglia when compared with peritoneal macrophages. Only three of these molecules (C1qA, Trem2, and CXCL14) were found by qPCR to be also enriched in adult microglia isolated from LPS/IFNγ‐injected CNS when compared with infiltrating peripheral macrophages from the same CNS. The discrepancy between the in vitro and in vivo qPCR data sets was primarily because of induced expression of the ‘microglial’ molecules (such as the tolerance associated transcript, Tmem176b) in CNS‐infiltrating macrophages. Bioinformatic analysis of the ∼19000 mRNAs detected by TOGA gene profiling confirmed that LPS/IFNγ‐activated microglia isolated from adult CNS displayed greater similarity in total gene expression to CNS‐infiltrating macrophages than to microglia isolated from unmanipulated healthy adult CNS. In situ hybridization analysis revealed that nearly all microglia expressed high levels of C1qA, while subsets of microglia expressed Trem2 and CXCL14. Expression of C1qA and Trem2 was limited to microglia, while large numbers of GABA+ neurons expressed CXCL14. These data suggest that (i) CNS‐resident microglia are heterogeneous and thus a universal microglia‐specific marker may not exist; (ii) the CNS micro‐environment plays significant roles in determining the phenotypes of both CNS‐resident microglia and CNS‐infiltrating macrophages; (iii) the CNS microenvironment may contribute to immune privilege by inducing macrophage expression of anti‐inflammatory molecules.
The brain‐specific protein, p42IP4(ADAP 1) is localized in mitochondria and involved in regulation of mitochondrial Ca2+
Authors: Galvita Anastasia , Grachev Dmitry , Azarashvili Tamara , Baburina Yulia , Krestinina Olga , Stricker Rolf , Reiser Georg
Published: April 2009

In brain, p42IP4(centaurin‐α1; recently named ADAP 1, which signifies ADP ribosylation factor GTPase activating protein with dual PH domains 1, within the large family of Arf‐GTPase activating proteins) is mainly expressed in neurons. p42IP4operates as a dual receptor recognising two second messengers, the soluble inositol(1,3,4,5)tetrakisphosphate and the lipid phosphatidylinositol(3,4,5)trisphosphate. We show here for the first time that p42IP4is localized in mitochondria, isolated from rat brain and from cells transfected with p42IP4. In rat brain mitochondria we additionally found interaction of p42IP4with 2′, 3′‐cyclic nucleotide 3′‐phosphodiesterase and α‐tubulin by pull‐down binding assay and by immunoprecipitation. In mitochondria from Chinese hamster ovary cells, p42IP4is predominantly associated with the intermembrane space and the inner membrane. This localization of p42IP4indicates that p42IP4might have a still unknown mitochondrial function. We studied whether p42IP4is involved in Ca2+‐induced permeability transition pore opening, which is important in mitochondrial events leading to programmed cell death. We used mouse neuroblastoma cells as a model for the functional studies of p42IP4in mitochondria. In mitochondria isolated from p42IP4‐transfected mouse neuroblastoma cells, over‐expression of p42IP4significantly decreased Ca2+capacity and lag time for Ca2+retention. Thus, we suggest that p42IP4is involved in the regulation of Ca2+transport in mitochondria. We propose that p42IP4promotes Ca2+‐induced permeability transition pore opening and thus destabilizes mitochondria.
A Facility for the Study of Pelvis and Trunk Displacements During Sitting Posture
Authors: Scena S. , Steindler R.
Published: April 2009

Abstract:  Pressure sores are frequent in subjects who are paralysed because of spinal cord injuries and confined to wheelchairs: to prevent sores, these subjects must get used to frequently changing their posture. Useful information to investigate change characteristics may come through studying the behaviour of healthy subjects during long periods of sitting posture: to this aim, in the Department of Biomedical Engineering of Tel Aviv University, markers were applied to the trunks of subjects who were then filmed, while in the Department of Mechanics and Aeronautics of Rome University “La Sapienza” (DMA), angular potentiometers were applied to the base of the spine of subjects sitting on a chair where a pressure map sensor was positioned. In this paper a modification of the potentiometer device is shown: linear potentiometers are also applied to the base of the spine of the subjects; so, in addition to the relations among pelvis centre of pressure (COP) displacements, and trunk rotations, it is possible to find the relations between trunk translations and trunk rotations and between trunk translations and COP displacements; so all the characteristics of the movements of the pelvis and of the trunk at the base of the spine can now be investigated and compared. The results of the tests on 10 healthy DMA students following an established movement sequence are shown: there are particularly significant relations between trunk translations and trunk rotations in the sagittal plane, and between trunk translations and COP displacements in the frontal plane.
Practicalities of participation in urban IWRM: Perspectives of wastewater management in two cities in Sri Lanka and Bangladesh
Authors: Evans Alexandra , Varma Samyuktha
Published: April 2009

As the demand for water in cities increases, the quantity of wastewater being produced is growing at a phenomenal rate. If resources are to be managed effectively, a new paradigm is required for urban wastewater management. This paper reviews the initial findings of a participatory action planning process for managing wastewater for agricultural use. It finds that such processes need considerable facilitation, capacity building and knowledge sharing, but that if a plan can be devised that meets the needs of the stakeholders, even if some compromise is required, then certain stakeholders are likely to take responsibility for specific aspects. This may not meet the entire integrated water resources management (IWRM) vision of the plan but provided the plan is developed in such a way that incremental implementation will be beneficial then this will produce some success and may stimulate further cooperation.
Local IWRM organizations for groundwater regulation: The experiences of the Aquifer Management Councils (COTAS) in Guanajuato, Mexico
Authors: Wester Philippus , Hoogesteger Jaime , Vincent Linden
Published: April 2009

Evidence of groundwater management by aquifer users emerging under Integrated Water Resources Management (IWRM) initiatives is presented, by analyzing the Consejos Técnicos de Aguas (COTAS; Technical Water Councils or Aquifer Management Councils) in the state of Guanajuato, Mexico, established between 1998 and 2000 by the Guanajuato State Water Commission (CEAG). Two contrasting models influenced this attempt to promote user self‐regulation of groundwater extractions: locally autonomous aquifer organizations with powers to regulate groundwater extractions versus aquifer organizations with advisory powers only. The COTAS were conceived as locally autonomous IWRM organizations consisting of all aquifer users that would work together to reduce groundwater over‐extraction and stabilize aquifer levels, at a later stage. CEAG followed an expedient IWRM approach to develop the COTAS, setting achievable targets for their development and explicitly focusing on active stakeholder participation. The article shows that, due to struggles between the state and federal levels, the COTAS have become advisory bodies that have not led to reductions in groundwater extractions. It concludes that achieving user self‐regulation of groundwater extractions requires a fuller delegation of responsibilities to the COTAS which would not be possible without addressing the institutional struggles over water governance at the state and federal levels.
Harvesting of rainwater and brooklets water to increase mountain agricultural productivity: A case study from a dry valley of southwestern China
Authors: Wu Yang , Tang Ya , Huang Chengmin
Published: April 2009

In semi‐arid valleys of southwestern China, seasonal shortage of water is the major contributing factor to low and unstable crop yield. Harvesting of both rainwater and brooklets water in the semi‐arid valleys of Ningnan county of Sichuan Province has brought about considerable economic and environmental change. Brooklet water is collected throughout the year but mainly during the rainy season in a series of ponds while rainwater is harvested in underground tanks constructed on road side or land boundaries with only a small opening above ground to save limited cropland. Increased water availability has promoted cultivation of sugarcane, tobacco, and mulberry, and increased per unit area yield of food crops. Sericulture, sugarcane and tobacco have become three important sources of farmers’ income. The water harvesting has contributed considerably to increased rural income, poverty reduction, reduced soil erosion and improvement in overall environment. Government has played a key role in planning and implementation of water harvesting programmes. Financial support of government and clear ownership of water harvesting facilities are critical for the success of the programme. Application of similar water harvesting techniques in other areas with similar biophysical conditions would contribute to enhancing the rural economy and alleviating poverty.
Gene expression profile of Huh‐7 cells expressing hepatitis C virus genotype 1b or 3a core proteins
Authors: Pazienza Valerio , Clément Sophie , Pugnale Paolo , Conzelmann Stéphanie , Pascarella Stéphanie , Mangia Alessandra , Negro Francesco
Published: April 2009

Background: The liver disease expression in chronic hepatitis C patients is variable and may partially depend on the sequence of the infecting viral genotype.

Aim: To identify some hepatitis C virus (HCV) genotype‐specific virus–host interactions potentially leading to clinically significant consequences.

Methods: We compared the gene expression profile of Huh‐7 cells transiently expressing the core protein of HCV genotype 1b and 3a using microarray technology.

Results: Thirty‐two genes were overexpressed in Huh‐7 transfected with the HCV genotype 1b core protein and 57 genes in cells transfected with the genotype 3a core protein. On the other hand, we found 20 genes downregulated by core 1b and 31 genes by core 3a. These included genes involved in lipid transport and metabolism, cell cycle, immune response and insulin signalling.

Conclusion: The expression of HCV core proteins of different genotypes leads to a specific gene expression profile. This may account for the variable disease expression associated with HCV infection.
Ultrasound‐guided treatments under low acoustic power contrast harmonic imaging for hepatocellular carcinomas undetected by B‐mode ultrasonography
Authors: Maruyama Hitoshi , Takahashi Masanori , Ishibashi Hiroyuki , Okugawa Hidehiro , Okabe Shinichiro , Yoshikawa Masaharu , Yokosuka Osamu
Published: April 2009

Background/Aims: The aim was to examine the efficacy of contrast‐enhanced ultrasound (US) with Sonazoid™ to demonstrate ultrasonically unrecognizable hypervascular hepatocellular carcinoma (HCC) and apply percutaneous US‐guided treatments.

Methods: The subjects of this prospective study were 44 cirrhotic patients with 55 hypervascular lesions (12.7±4.5 mm) found by contrast‐enhanced computed tomography but unrecognized by non‐contrast US. Contrast‐enhanced US was performed to demonstrate these hepatic lesions after an intravenous injection of Sonazoid™ (0.0075 ml/kg). The sonograms in both the early phase (for 1 min after injection) and the late phase (5–10 min after) were taken in the harmonic imaging mode under a low mechanical index (0.24–0.3).

Results: Fifty‐three lesions were demonstrated by contrast‐enhanced US, 52 with positive enhancement in the early phase and 44 with negative enhancement in the late phase. Percutaneous US‐guided treatments were successfully performed for 42 lesions (ethanol injection in 20 and radiofrequency ablation in 22) in 32 patients with reference to contrast‐enhanced US findings. Six patients were treated by transarterial chemoembolization alone because they had more than three lesions in the liver. In the remaining seven lesions in six patients, six were diagnosed as non‐HCC lesions: five with vascular abnormalities such as arterioportal or arteriovenous communication and the other one with benign lesion in alcoholic liver disease. These six lesions and one HCC lesion with severe liver damage were followed up without any treatment.

Conclusions: As the detectability of ultrasonically unrecognizable hypervascular HCC improved by contrast‐enhanced US with Sonazoid™, a wider application of percutaneous US‐guided treatments may be possible.
ABCB4 sequence variations in young adults with cholesterol gallstone disease
Authors: Nakken Karl Esten , Labori Knut Jørgen , Rødningen Olaug K. , Nakken Sigve , Berge Knut E. , Eiklid Kristin , Ræder Morten G.
Published: April 2009

Background and Aims: Mutations in the gene encoding the ABCB4 [adenosine triphosphate (ATP)‐binding cassette, sub‐family B (MDR/TAP), member 4] transporter lower phosphatidylcholine output into bile and contribute to cholesterol gallstone formation by decreasing the solubility of cholesterol in bile. Mutations in ABCB4 have been identified in patients with low phospholipid‐associated cholelithiasis. The aim of the present study was to determine the types and frequencies of ABCB4 mutations in cholecystectomized patients aged <40 years.

Patients and methods: Hundred and four patients (mean age 30.6 years, range 12–39) were included in the study and the ABCB4 gene was sequenced. The frequency of missense mutations found in the patient material was measured in 95 healthy controls. The potential functional implications of the ABCB4 missense variations were assessed by computerized analysis (BLOSUM62 and Grantham substitution matrices, polymorphism phenotyping and sorting intolerant from tolerant).

Results: One patient was heterozygous for a frameshift mutation (c.1399_1400ins10/p.Y467F fsX25). Another patient was heterozygous for a nonsense mutation (c.3136C>T/p.R1046X). These two mutations are considered detrimental to ABCB4 protein function. In addition, six missense mutations were found in the ABCB4 gene, and three of these were only present in patients.

Conclusion: In our study, <2% of young gallstone patients were found to be heterozygous for detrimental ABCB4 mutations. The functional implication of several missense mutations remains to be clarified. Thus, mutations in the ABCB4 gene are a rare cause of gallstone disease.
Radiotracer imaging studies in hepatic encephalopathy: ISHEN practice guidelines
Authors: Berding Georg , Banati Richard B. , Buchert Ralph , Chierichetti Franca , Grover Vijay P. B. , Kato Akinobu , Keiding Susanne , Taylor‐Robinson Simon D.
Published: April 2009

There is lack of consensus on radiotracer usage in hepatic encephalopathy (HE). We have focused our attention on three main areas: (i) radiotracer imaging in animal models of HE, (ii) methodological issues of radiotracer imaging in HE and (iii) radiotracer imaging studies on the pathophysiology and (new) therapies in HE. We suggest the following: 1. Positron emission tomography (PET) and single photon emission computed tomography lend themselves to the study of animal models of HE, but the models that are suitable depend on the specific research question. Magnetic resonance imaging (MRI) may be a useful alternative technique. 2. Owing to the cost of the technique, there is a need for multicentre human PET studies to overcome the problem of underpowered small studies being undertaken in individual research centres. There should be a unified PET protocol with central, anonymised data analysis in one centre, using validated methodology, on behalf of all participating centres. Such studies would be useful for the assessment of early intervention in patients with subtle neuropsychiatric symptoms, or for clarification of the effect of liver transplantation on HE. 3. While radiotracer imaging modalities remain useful research tools for the study of pathogenesis and for the assessment of treatment effects, there is no consensus on the use of imaging in routine clinical practice for diagnosis and prognosis. The most promising objective tools appear to be magnetic resonance spectroscopy (MRS) and volumetric MRI, which can be performed in multiple centres without the difficulties that radiotracer imaging entail.
Quantifying Habitat Requirements of Tree‐Living Species in Fragmented Boreal Forests with Bayesian Methods
Authors: BERGLUND HÅKAN , O'HARA ROBERT B. , JONSSON BENGT GUNNAR
Published: April 2009

Abstract:  Quantitative conservation objectives require detailed consideration of the habitat requirements of target species. Tree‐living bryophytes, lichens, and fungi are a critical and declining biodiversity component of boreal forests. To understand their requirements, Bayesian methods were used to analyze the relationships between the occurrence of individual species and habitat factors at the tree and the stand scale in a naturally fragmented boreal forest landscape. The importance of unexplained between‐stand variation in occurrence of species was estimated, and the ability of derived models to predict species' occurrence was tested. The occurrence of species was affected by quality of individual trees. Furthermore, the relationships between occurrence of species at the tree level and size and shape of stands indicated edge effects, implying that some species were restricted to interior habitats of large, regular stands. Yet for the habitat factors studied, requirements of many species appeared similar. Species occurrence also varied between stands; most of the seemingly suitable trees in some stands were unoccupied. The models captured most variation in species occurrence at tree level. They also successfully accounted for between‐stand variation in species occurrence, thus providing realistic simulations of stand‐level occupancy of species. Important unexplained between‐stand variation in species occurrence warns against a simplified view that only local habitat factors influence species' occurrence. Apparently, similar stands will host populations of different sizes due to historical, spatial, and stochastic factors. Thus, habitat suitability cannot be assessed simply by population sizes, and stands lacking a species may still provide suitable habitat and merit protection.
A Latent Class Model with Hidden Markov Dependence for Array CGH Data
Authors: DeSantis Stacia M. , Houseman E. Andrés , Coull Brent A. , Louis David N. , Mohapatra Gayatry , Betensky Rebecca A.
Published: April 2009

Summary Array CGH is a high‐throughput technique designed to detect genomic alterations linked to the development and progression of cancer. The technique yields fluorescence ratios that characterize DNA copy number change in tumor versus healthy cells. Classification of tumors based on aCGH profiles is of scientific interest but the analysis of these data is complicated by the large number of highly correlated measures. In this article, we develop a supervised Bayesian latent class approach for classification that relies on a hidden Markov model to account for the dependence in the intensity ratios. Supervision means that classification is guided by a clinical endpoint. Posterior inferences are made about class‐specific copy number gains and losses. We demonstrate our technique on a study of brain tumors, for which our approach is capable of identifying subsets of tumors with different genomic profiles, and differentiates classes by survival much better than unsupervised methods.
Using Required Operational Capabilities to Connect Operational and Technical Requirements
Authors: ADAMS KENNETH M. , KOTT KEN
Published: April 2009

One of the fundamental challenges facing an engineering development team is to understand the operational objectives and goals of a system and how it will be applied in real‐world situations. The Navy currently uses Required Operational Capabilities and the Projected Operating Environment (ROC/POE) to define and measure the training needs and operational capabilities for a ship class once it has been introduced into fleet service. We show how the ROC/POE can be used as an upfront engineering tool to translate the CG(X) concept of operations into mission‐based operational needs and objectives, which then drive the system definition, architecture, and design. The analysis of these missions in a holistic fashion will enable the Navy to fully understand the behavior of the ship, control costs, and reduce the risk of failing to meet warfighter needs.
Modeling and Simulation of Notional Future Radar in Non‐Standard Propagation Environments Facilitated by Mesoscale Numerical Weather Prediction Modeling
Authors: MARSHALL ROBERT E. , THORNTON WILLIAM D. , LEFURJAH GEORGE , CASEY TIMOTHY S.
Published: April 2009

Normal near surface radio‐frequency (RF) propagation in the littorals across the land–sea boundary is rare due to the land–sea temperature difference, coastline shape, ground cover, urban density, coastal topography, and soil moisture content. The resulting frequent existence of coastal non‐standard vertical profiles of refractivity and the resulting RF propagation has a profound impact on the performance of Navy ship‐borne radars operating within 100 nm of the shore. In addition, these non‐standard RF propagation conditions are spatio‐temporally inhomogeneous. These spatial and time dependent propagation conditions and the resulting radar engineering implications cannot be revealed by a single vertical profile of refractivity taken near the ship borne radar. The results from single profile analysis techniques provide no spatiotemporal information and may lead to overly conservative radar design. Mesoscale numerical weather prediction (NWP) is a rapidly maturing technology with a strong operational Navy history that can provide a vertical profile of refractivity every 1 km in the battle space and every hour, up to 48 h, in the future. The Sensor Division at NSWCDD has applied mesoscale NWP for the last 2 years to better understand the performance of prototype radar in realistic four‐dimensional (4D) coastal environments. Modern RF parabolic equation models are designed to model specific radar designs and to employ 3D refractivity fields from mesoscale NWP models. This allows for a radar design to be tested in realistic littoral non‐standard atmospheres produced by stable internal boundary layers, sea breeze events, and the more rare sub‐refractive events. Mesoscale NWP is currently qualitative for this purpose, but a research and development program focused on sea testing of prototype radars is described with the purpose of developing a more quantitative mesoscale NWP technology to support radar acquisition, testing, and operations.
Agility and the Combat System
Authors: KOTT KEN , ADAMS KENNETH M. , DOVE RICK
Published: April 2009

As future threats increase in number and capability, the future CG(X) combat system must provide the ability to respond across the spectrum of conflict. In this paper, we present the principles and concepts needed to achieve an agile combat system that can support a wide variety of missions in diverse operating environments.