bluuebunny/crossref_metadata_2025 huggingface dataset:
A kaleidoscope of understandings: spiritual nursing in a multi‐faith society
Authors: MacLaren Jessica
Published: December 2004

Background.  Spirituality is an increasingly discussed topic in nursing. In some parts of the UK there is a policy requirement to establish policies of spiritual health care which are appropriate to a multi‐cultural society. In the nursing literature, spirituality is discussed from religious and secular perspectives which seem impossible to reconcile into a coherent philosophy.

Aims.  To discuss the relationship of spirituality to nursing and to suggest how we can think about spirituality as nurses working in a society of many faiths and cultures.

Discussion.  Spirituality can be thought of in relation to individual patients and nurses. It also has significance for the profession of nursing and for health care as a whole. The difficulty of defining spirituality is discussed, and it is suggested that a definition of ‘spiritual nursing’ may be more achievable. Different concepts of spirituality are compared, including religious and secular spirituality. The relationship between religion and spirituality is seen as potentially problematic, with some religions denying the existence of secular spirituality. Secular spirituality and New Age movements are non‐religious but spiritually influential phenomena. The problem for nursing is how to reconcile the immense variety of approaches to spirituality.

Conclusions.  The concept of spirituality as a meta‐narrative is considered, and a postmodern appreciation of pluralism is employed as a way of embracing different spiritual realities. Spiritual nursing can be an opportunity for nurses to enlarge their understanding of the human condition rather than a narrowly defined concept to be applied within a model of practice.
Epidermolytic hyperkeratosis: a keratin 1 or 10 mutational event
Authors: Lacz Nicole L. , Schwartz Robert A. , Kihiczak George
Published: December 2004

Epidermolytic hyperkeratosis is an unusual type of ichthyosis. This inherited keratinization disorder is characterized clinically by erythema, blistering, and peeling shortly after birth. It may resolve and be replaced with thick scaling. It can lead to life‐threatening complications, such as sepsis. Histologically, there is a hyperkeratosis and vacuolar degeneration. Genetically, this is an autosomal dominant disease with complete penetrance; however, 50% are spontaneous mutations. The clinical phenotype is a result of alterations in the gene(s) for keratin 1 and/or 10. We review this disorder and its therapy, which is mainly symptomatic with emollients and retinoids.
Testing Option Pricing Models with Stochastic Volatility, Random Jumps and Stochastic Interest Rates
Authors: Jiang George J.
Published: December 2004

In this paper, we propose a parsimonious GMM estimation and testing procedure for continuous‐time option pricing models with stochastic volatility, random jump and stochastic interest rate. Statistical tests are performed on both the underlying asset return model and the risk‐neutral option pricing model. Firstly, the underlying asset return models are estimated using GMM with valid statistical tests for model specification. Secondly, the preference related parameters in the risk‐neutral distribution are estimated from observed option prices. Our findings confirm that the implied risk premiums for stochastic volatility, random jump and interest rate are overall positive and varying over time. However, the estimated risk‐neutral processes are not unique, suggesting a segmented option market. In particular, the deep ITM call (or deep OTM put) options are clearly priced with higher risk premiums than the deep OTM call (or deep ITM put) options. Finally, while stochastic volatility tends to better price long‐term options, random jump tends to price the short‐term options better, and option pricing based on multiple risk‐neutral distributions significantly outperforms that based on a single risk‐neutral distribution.
Influencing the national policy process: the role of health consumer groups
Authors: Jones Kathryn , Baggott Rob , Allsop Judith
Published: December 2004

Introduction  Whilst recent research has focused on consumer involvement at local level in the UK, there have been few studies of the representation of user, carer and patients’ interests nationally. This paper concentrates on the role of health consumer groups in representing the collective interests of patients, users and carers in the national policy process.

Methods  The research consisted of (a) a semi‐structured postal questionnaire survey of 123 health consumer groups; (b) semi‐structured interviews with key informants from 39 health consumer groups; and (c) semi‐structured interviews with 31 policy actors.

Results  Health consumer groups were diverse in their origins, scope and structure, and undertook a wide range of activities relating to policy and service provision. Whilst around half the groups described their primary purpose as service provision, over four‐fifths identified influencing policy at national level as ‘very important’ or ‘important’. Health consumer groups had developed relationships with civil servants, ministers, MPs and peers to widen their policy objectives. Key facilitators in the policy process included experiential knowledge, relationships with policy makers and working in alliances with other health consumer groups or other stakeholders. Key barriers included problems relating to the political agenda, problems with the consultation process, lack of resources and working within a context of unequal power relationships.

Conclusion  Health consumer groups are becoming increasingly involved in the health policy process and collectively are becoming an increasingly influential stakeholder. They have a key role to play in ensuring that the patient, user and carer voice is heard in the policy process.
Antagonists for group I mGluRs attenuate excitotoxic neuronal death in cortical cultures
Authors: Strasser Uta , Lobner Doug , Behrens M. Margarita , Canzoniero Lorella M. T. , Choi Dennis W.
Published: December 2004

Activation of ion channel‐linked glutamate receptors, especially N‐methyl‐d‐aspartate (NMDA) receptors, mediates the excitotoxic effects of glutamate upon central neurons. We examined the hypothesis that activation of group I metabotropic glutamate receptors (mGluRs) would increase NMDA receptor‐mediated cortical neuronal death. Addition of the selective group I mGluR agonists, dihydroxyphenylglycine (DHPG) or trans‐azetidine‐2,4‐dicarboxylic acid (t‐ADA) potentiated NMDA‐induced neuronal death, and application of the group I mGluR‐selective antagonist, aminoindan‐1,5‐dicarboxylic acid (AIDA), as well as the non‐selective antagonists methyl‐4‐carboxyphenylglycine (MCPG) or 4‐carboxyphenylglycine (4CPG) reduced NMDA‐ and kainate‐induced neuronal death in murine cortical cultures. The pro‐excitotoxic effect of group I mGluR activation may be mediated largely by enhancement of glutamate release, as DHPG potentiated high potassium‐stimulated glutamate release, and the protective effects of both AIDA and MCPG were abolished when NMDA and alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole proprionic acid (AMPA) receptors were blocked immediately after toxic NMDA receptor overstimulation. The present data support the possibility that antagonizing group I mGluRs may be a useful strategy for attenuating excitotoxic neuronal death in certain disease states.
Endogenous ACh enhances striatal NMDA‐responses via M1‐like muscarinic receptors and PKC activation
Authors: Calabresi Paolo , Centonze Diego , Gubellini Paolo , Pisani Antonio , Bernardi Giorgio
Published: December 2004

Cortical glutamatergic fibres and cholinergic inputs arising from large aspiny interneurons converge on striatal spiny neurons and play a major role in the control of motor activity. We have investigated the interaction between excitatory amino acids and acetylcholine (ACh) on striatal spiny neurons by utilizing intracellular recordings, both in current‐ and in voltage‐clamp mode in rat brain slices. Muscarine (0.3–10 μm) produced a reversible and dose‐dependent increase in the membrane depolarizations/inward currents induced by brief applications of N‐methyl‐d‐aspartate (NMDA), while it did not affect the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)‐induced responses. These concentrations of muscarine did not alter the membrane potential and the current‐voltage relationship of the recorded cells. Neostigmine (0.3–10 μm), an ACh‐esterase inhibitor, mimicked this facilitatory effect. The facilitatory effects of muscarine and neostigmine were antagonized either by scopolamine (3 μm) or by pirenzepine (10–100 nm), an antagonist of M1‐like muscarinic receptors, but not by methoctramine (300 nm), an antagonist of M2‐like muscarinic receptor. Accordingly, these facilitatory effects were mimicked by McN‐A‐343 (1–10 μm), an agonist of M1‐like muscarinic receptors, but not by oxotremorine (300 nm), an agonist of M2‐like receptors. Tetrodotoxin (TTX) did not block the facilitatory effect produced by the activation of muscarinic receptors suggesting that this effect is postsynaptically mediated. The action of neostigmine was prevented either by the intracellular calcium (Ca2+) chelator BAPTA (200 mm) or by preincubating the slices with inhibitors of protein kinase C (PKC) (staurosporine 100 nm or calphostin C 1 μm). McN‐A‐343 did not alter the excitatory post synaptic potentials (EPSPs) evoked by corticostriatal stimulation in the presence of physiological concentration of magnesium (Mg2+ 1.2 mm), while it enhanced the duration of these EPSPs recorded in the absence of external magnesium. Our data show that endogenous striatal ACh exerts a positive modulatory action on NMDA responses via M1‐like muscarinic receptors and PKC activation.
Rhythmic variation in β1‐adrenergic receptor mRNA levels in the rat pineal gland: circadian and developmental regulation
Authors: Pfeffer Martina , Kühn Rebecca , Krug Liselotte , Korf Horst‐Werner , Stehle Jörg H.
Published: December 2004

In the rat pineal gland noradrenaline is released in large quantities from sympathetic nerve endings at the onset of darkness, thereby driving rhythmic melatonin synthesis with elevated levels at night‐time. Upon release, noradrenaline interacts with postsynaptic β1‐adrenergic receptors to activate the cyclic AMP signalling pathway. Well characterized third messengers of this signalling cascade affect cyclic AMP‐inducible genes that are crucially involved in initiation, maintenance and termination of hormone production. Among these third messengers are CREB (cyclic AMP responsive element binding protein) as an activating and ICER (inducible cyclic AMP early repressor) as an inhibitory transcription factor. Because a cyclic AMP‐inducible promoter element is present on the β1‐adrenergic receptor gene, the expression of the receptor itself may be under control of the cyclic AMP‐signalling pathway. By in situ hybridization, Northern blot analysis and RT‐PCR we demonstrate a day/night rhythm in β1‐adrenergic receptor mRNA in the rat pineal gland with elevated levels during the dark period. As this rhythm persists, under constant darkness but is abolished upon removal of the sympathetic innervation, it is truly circadian. A marked day/night difference in the levels of β1‐adrenergic receptor mRNA becomes evident only after postnatal day 10, coinciding with the appearance of a functional cyclic AMP signalling pathway in the rat pineal gland. Furthermore, targeting ICER expression by transfection of pinealocytes with an antisense ICER construct, clearly indicates that the levels of the β1‐adrenergic receptor mRNA are regulated by the cyclic AMP‐signalling pathway in a feedback mechanism.
The neonatal ventral hippocampal lesion model of schizophrenia: effects on dopamine and GABA mRNA markers in the rat midbrain
Authors: Lipska Barbara K. , Lerman Daniel N. , Khaing Zin Z. , Weinberger Daniel R.
Published: December 2004

The neonatal ventral hippocampal lesion in the rat has been used as a model of schizophrenia, a human disorder associated with changes in markers of dopamine and γ‐aminobutyric acid (GABA) circuits in various regions of the brain. We investigated whether alterations in mRNA markers related to the activity of midbrain dopaminergic and GABAergic neurons are associated with this model. We used in situ hybridization histochemistry to assess expression of mRNAs for dopamine transporter (DAT), tyrosine hydroxylase (TH) and glutamate decarboxylase‐67 (GAD67) in the midbrain of adult rats with neonatal and adult ibotenic acid lesions of the ventral hippocampus. Neonatally lesioned rats showed in adulthood significantly reduced expression of DAT mRNA in the substantia nigra and the ventral tegmental area but no changes in the expression of TH and GAD67 mRNAs in these midbrain regions. Adult lesioned rats showed no changes in the expression of any of these genes. As the neonatal ventral hippocampal lesion reproduces many aspects of schizophrenia and is used as an animal model of this disorder, these results suggest that the reduction in DAT mRNA could result from developmental neuropathology in the ventral hippocampus and may thus represent a molecular substrate of the disease process.
Rapid activation of presynaptic nicotinic acetylcholine receptors by nerve‐released transmitter
Authors: Rogers Marc , Sargent Peter B.
Published: December 2004

Nicotine's ability to enhance neurotransmitter release has implicated presynaptic nicotinic acetylcholine receptors (nAChRs) in synaptic modulation, but there are few examples where presynaptic nAChRs are known to be activated by nerve‐released transmitter. We searched for endogenous activation of presynaptic nAChRs in the calyceal nerve terminals of the chick ciliary ganglion by imaging presynaptic calcium transients using dextran‐coupled indicator dyes. The amplitude of Ca2+ signals recorded in individual nerve terminals was frequency dependent over 2–50 Hz. Calcium transients evoked by stimulation of the preganglionic nerve were significantly reduced (≈10–15%) by the nonspecific nAChR antagonist d‐tubocurarine (d‐TC; 100 µm) and the α7‐specific antagonist methyllycaconitine (20–50 nm) but were not affected by 10 µm dihydro‐β‐erythroidine, which should inhibit several non‐α7 nAChRs. Feedback was rapid and did not require a stimulation‐dependent build‐up of transmitter, as d‐TC and MLA reduced the amplitude of the first calcium transient in a 2‐Hz train. Choline is an agonist at α7 nAChRs but is not the sole agonist in this system, as inhibition of acetylcholinesterase by echothiophate failed to reduce calcium transients. These results show that nerve‐released acetylcholine (ACh) feeds back onto presynaptic α7 nAChRs to enhance calcium signals within the terminal. This feedback may help maintain the high rate of transmission at this cholinergic synapse.
Effector‐independent representations of simple and complex imagined finger movements: a combined fMRI and TMS study
Authors: Kuhtz‐Buschbeck J. P. , Mahnkopf C. , Holzknecht C. , Siebner H. , Ulmer S. , Jansen O.
Published: December 2004

Kinesthetic motor imagery and actual execution of movements share a common neural circuitry. Functional magnetic resonance imaging was used in 12 right‐handed volunteers to study brain activity during motor imagery and execution of simple and complex unimanual finger movements of the dominant and the nondominant hand. In the simple task, a flexible object was rhythmically compressed between thumb, index and middle finger. The complex task was a sequential finger‐to‐thumb opposition movement. Premotor, posterior parietal and cerebellar regions were significantly more active during motor imagery of complex movements than during mental rehearsal of the simple task. In 10 of the subjects, we also used transcranial magnetic brain stimulation to examine corticospinal excitability during the same motor imagery tasks. Motor‐evoked potentials increased significantly over values obtained in a reference condition (visual imagery) during imagery of the complex, but not of the simple movement. Imagery of finger movements of either hand activated left dorsal and ventral premotor areas and the supplementary motor cortex regardless of task complexity. The effector‐independent activation of left premotor areas was particularly evident in the simple motor imagery task and suggests a left hemispherical dominance for kinesthetic movement representations in right‐handed subjects.
Convergent responses of Barrington's nucleus neurons to pelvic visceral stimuli in the rat: a juxtacellular labelling study
Authors: Rouzade‐Dominguez Marie‐Laure , Pernar Luise , Beck Sheryl , Valentino Rita J.
Published: December 2004

Barrington's nucleus impacts on bladder and distal colon function and relays pelvic visceral information to the forebrain. This study investigated processing of information from the bladder and the distal colon by Barrington's nucleus in the rat. The responses of individual Barrington's nucleus neurons to bladder and/or colon distention were characterized using extracellular recording and the recorded neurons were identified using juxtacellular labelling. Most neurons within Barrington's nucleus (79%) were activated by bladder distention, consistent with its role as a pontine micturition centre. Although no neurons were selectively responsive to colon distention, the majority of bladder‐responsive neurons (73%) were also activated by colon distention. In a second study, Barrington's nucleus neurons were characterized with respect to their response to colon distention and their immunoreactivity for the stress‐related neuropeptide corticotropin‐releasing factor (CRF). Of 30 labelled neurons in the central part of Barrington's nucleus, 53% were activated by colon distention and 63% of these were CRF‐ir. This is the first report demonstrating that Barrington's nucleus neurons are responsive to colon distention. The results provide evidence for convergence of information from the bladder and the colon onto individual Barrington's nucleus neurons. Taken with evidence that many Barrington's nucleus neurons are synaptically linked to the bladder and colon, the present study suggests a role for these neurons in coordinating peripheral parasympathetic and central responses to both viscera and implicate CRF as a neurotransmitter in this function. Dysfunctions in this circuit may underlie the coexistence of colon and bladder symptoms observed in functional bowel disorders.
HAP1 facilitates effects of mutant huntingtin on inositol 1,4,5‐trisphosphate‐induced Ca2+ release in primary culture of striatal medium spiny neurons
Authors: Tang Tie‐Shan , Tu Huiping , Orban Paul C. , Chan Edmond Y. W. , Hayden Michael R. , Bezprozvanny Ilya
Published: December 2004

Huntington's disease is caused by polyglutamine expansion (exp) in huntingtin (Htt). Htt‐associated protein‐1 (HAP1) was the first identified Htt‐binding partner. The type 1 inositol (1,4,5)‐trisphosphate receptor (InsP3R1) is an intracellular Ca2+ release channel that plays an important role in neuronal function. Recently, we identified a InsP3R1–HAP1A–Htt ternary complex in the brain and demonstrated that Httexp, but not normal Htt, activates InsP3R1 in bilayers and facilitates InsP3R1‐mediated intracellular Ca2+ release in medium spiny striatal neurons [MSN; T.‐S. Tang et al. (2003) Neuron, 39, 227–239]. Here we took advantage of mice with targeted disruption of both HAP1 alleles (HAP1 –/–) to investigate the role of HAP1 in functional interactions between Htt and InsP3R1. We determined that: (i) HAP1 is expressed in the MSN; (ii) HAP1A facilitates functional effects of Htt and Httexp on InsP3R1 in planar lipid bilayers; (iii) HAP1 is required for changes in MSN basal Ca2+ levels resulting from Htt or Httexp overexpression; (iv) HAP1 facilitates potentiation of InsP3R1‐mediated Ca2+ release by Httexp in mouse MSN. Our present results indicate that HAP1 plays an important role in functional interactions between Htt and InsP3R1.
The role of MAP kinases in rapid gene induction after lesioning of the rat sciatic nerve
Authors: Zrouri H. , Le Goascogne C. , Li W. W. , Pierre M. , Courtin F.
Published: December 2004

Lesion of the sciatic nerve caused a rapid activation of p38MAP kinase in the injured nerve adjacent to the site of transection. This activation was detectable 3 min after lesioning, increased during the next 15 min and remained high for several hours. Erk1/2 activation was also observed as early as 15 min after lesioning. Activation of these MAP kinases was seen in both the external sheaths and the endoneurium. The separation of the external sheaths from the endoneurium accelerated the p38MAP kinase activation. To evaluate whether the injury‐activated MAP kinase cascades are implicated in the rapid gene induction observed after nerve lesion, experiments were performed with an ex vivo model. Segments of sciatic nerves were incubated in oxygenated Krebs–Ringer buffer. MAP kinases were activated at 15 min and remained active after 6 h. Induction of mRNA was also observed for nerve growth factor (NGF), interleukin 6 (IL‐6), leukaemia inhibitory factor (LIF) and deiodinases of type 2 (D2) and type 3 (D3). Thus, the ex vivo model mimics events occurring in the animal after nerve section. Finally, nerve segments were incubated in the presence of specific inhibitors of Erk1/2 activation (U0126) and of p38MAP kinase activity (SB203580). U0126 inhibited D3, LIF and to a lesser extent NGF mRNA induction, but did not affect significantly the induction of D2 and IL‐6 mRNAs. SB203580 inhibited the expression of the genes for D3 and LIF. We conclude that MAP kinase cascades, activated by nerve transection, are involved in the rapid gene induction in the nerve.
Trophic cascades: the primacy of trait‐mediated indirect interactions
Authors: Schmitz Oswald J. , Krivan Vlastimil , Ovadia Ofer
Published: December 2004

Trophic cascades are textbook examples of predator indirect effects on ecological systems. Yet there is considerable debate about their nature, strength and overall importance. This debate stems in part from continued uncertainty about the ultimate mechanisms driving cascading effects. We present a synthesis of empirical evidence in support of one possible ultimate mechanism: the foraging‐predation risk trade‐offs undertaken by intermediary species. We show that simple trade‐off behaviour can lead to both positive and negative indirect effects of predators on plant resources and hence can explain considerable contingency on the nature and strength of cascading effects among systems. Thus, predicting the sign and strength of indirect effect simply requires knowledge of habitat and resource use by prey with regard to predators’ presence, habitat use and hunting mode. The synthesis allows us to postulate a hypothesis for new conceptualization of trophic cascades which is to be viewed as an ultimate trade‐off between intervening species. In this context, different predators apply different rules of engagement based on their hunting mode and habitat use. These different rules then determine whether behavioural effects persist or attenuate at the level of the food chain.
Attraction of willow warblers to sawfly‐damaged mountain birches: novel function of inducible plant defences?
Authors: Mäntylä Elina , Klemola Tero , Haukioja Erkki
Published: December 2004

Plants wounded by invertebrate herbivores emit volatile compounds which invertebrate predators and parasitoids can utilize in locating herbivore prey or hosts. We studied the possibility that an analogical phenomenon might operate between plants and avian insectivores. We show that foliar damage by sawfly larvae on the mountain birch led a passerine bird (willow warbler) to prefer intact branches from trees with introduced larvae over intact branches from control trees. Besides olfaction, the UV vision of birds offers a possible mechanism, as some herbivore‐inducible leaf compounds, e.g. surface flavonoids, have UV spectral maxima well within the range of birds’ UV vision.
Integrated regulation in response to aromatic compounds: from signal sensing to attractive behaviour
Authors: Shingler Victoria
Published: December 2004

Deciphering the complex interconnecting bacterial responses to the presence of aromatic compounds is required to gain an integrated understanding of how aromatic catabolic processes function in relation to their genome and environmental context. In addition to the properties of the catabolic enzymes themselves, regulatory responses on at least three different levels are important. At a primary level, aromatic compounds control the activity of specific members of many families of transcriptional regulators to direct the expression of the specialized enzymes for their own catabolism. At a second level, dominant global regulation in response to environmental and physiological cues is incorporated to subvert and couple transcription levels to the energy status of the bacteria. Mediators of these global regulatory responses include the alarmone (p)ppGpp, the DNA‐bending protein IHF and less well‐defined systems that probably sense the energy status through the activity of the electron transport chain. At a third level, aromatic compounds can also impact on catabolic performance by provoking behavioural responses that allow the bacteria to seek out aromatic growth substrates in their environment.
Temporal dynamics and degradation activity of an bacterial inoculum for treating waste metal‐working fluid
Authors: Van Der Gast Christopher J. , Whiteley Andrew S. , Thompson Ian P.
Published: December 2004

In order for established bioreactors to be effective for treating chemically mixed wastes such as metal working fluids (MWF) it is essential that they harbour microbial populations that can maintain sufficient active biomass and degrade each of the chemical constituents present. In this study we investigated the effectiveness of a bacterial consortium composed of four species (Clavibacter michiganensis, Methylobacterium mesophilicum, Rhodococcus erythropolis and Pseudomonas putida), assembled on the basis of their apparent ubiquity in waste MWF, degradation ability and tolerance to fluctuating chemistry of the waste. The temporal dynamics of the inoculum and its effects on the fate of individual chemical components of the waste were studied, by regular sampling, over 400 h. Using a complementary approach of culture with chemotaxonomic (FAME) analysis and applying group specific probes (FISH), the inoculum was found to represent a significant component of the community in bioreactors with and without presence of indigenous MWF populations. In addition, the reduction in the COD by the consortium was approximately 85% of the total pollution load, and 30–40% more effectively than any other treatment (indigenous MWF community alone or activated sludge). Furthermore, all the chemical constituents, including the biocide (a formaldehyde release agent) demonstrated > 60% reduction. Many chemical components of the MWF proved to be recalcitrant in the other treatments. The results of this study confirm that assemblage of an inoculum, based on a comprehensive knowledge of the indigenous microbial community, in the target habitat, is a highly effective way of selecting microbial populations for bioaugmentation of bioreactors.
Isolation and properties of methanesulfonate‐degrading Afipia felis from Antarctica and comparison with other strains of A. felis
Authors: Moosvi S. Azra , Pacheco Catarina C. , McDonald Ian R. , De Marco Paolo , Pearce David A. , Kelly Donovan P. , Wood Ann P.
Published: December 2004

Three novel strains of methylotrophic Afipia felis were isolated from several locations on Signy Island, Antarctica, and a fourth from estuary sediment from the River Douro, Portugal. They were identified as strains of the α‐2 proteobacterium A. felis by 16S rRNA gene sequence  analysis.  Two  strains  tested  were  shown to contain the fdxA gene, diagnostic for A. felis. All strains grew with methanesulfonate (and two strains with dimethylsulfone) as sole carbon substrate. Growth on methanesulfonate required methanesulfonate monooxygenase (MSAMO), using NADH as the reductant and stimulated by reduced flavin nucleotides and Fe(II). Polymerase chain reaction amplification of DNA from an Antarctic strain showed a typical msmA gene for the α‐hydroxylase of MSAMO, and both Antarctic and Portuguese strains contained mxaF, the methanol dehydrogenase large subunit gene. This is the first report of methanesulfonate‐degrading bacteria from the Antarctic and of methylotrophy in Afipia, and the first description of any bacterium able to use both methanesulfonate and dimethylsulfone. In contrast, the type strain of A. felis DSM 7326T was not methylotrophic, but grew in defined mineral medium with a wide range of single simple organic substrates. Free‐living Afipia strains occurring widely in the natural environment may be significant as methylotrophs, degrading C1‐sulfur compounds, including the recalcitrant organosulfur compound methanesulfonate.
Actinide and metal toxicity to prospective bioremediation bacteria
Authors: Ruggiero Christy E. , Boukhalfa Hakim , Forsythe Jennifer H. , Lack Joseph G. , Hersman Larry E. , Neu Mary P.
Published: December 2004

Bacteria may be beneficial for alleviating actinide contaminant migration through processes such as bioaccumulation or metal reduction. However, sites with radioactive contamination often contain multiple additional contaminants, including metals and organic chelators. Bacteria‐based bioremediation requires that the microorganism functions in the presence of the target contaminant, as well as other contaminants. Here, we evaluate the toxicity of actinides, metals and chelators to two different bacteria proposed for use in radionuclide bioremediation, Deinococcus radiodurans and Pseudomonas putida, and the toxicity of Pu(VI) to Shewanella putrefaciens. Growth of D. radiodurans was inhibited at metal concentrations ranging from 1.8 µM Cd(II) to 32 mM Fe(III). Growth of P. putida was inhibited at metal concentrations ranging from 50 µM Ni(II) to 240 mM Fe(III). Actinides inhibited growth at mM concentrations: chelated Pu(IV), U(VI) and Np(V) inhibit D. radiodurans growth at 5.2, 2.5 and 2.1 mM respectively. Chelated U(VI) inhibits P. putida growth at 1.7 mM, while 3.6 mM chelated Pu(IV) inhibits growth only slightly. Pu(VI) inhibits S. putrefaciens growth at 6 mM. These results indicate that actinide toxicity is primarily chemical (not radiological), and that radiation resistance does not ensure radionuclide tolerance. This study also shows that Pu is less toxic than U and that actinides are less toxic than other types of metals, which suggests that actinide toxicity will not impede bioremediation using naturally occurring bacteria.
Tuber magnatum Pico, a species of limited geographical distribution: its genetic diversity inside and outside a truffle ground
Authors: Mello Antonietta , Murat Claude , Vizzini Alfredo , Gavazza Virgilio , Bonfante Paola
Published: December 2004

The aim of this work was to clarify the genetic structure of the ectomycorrhizal fungus, Tuber magnatum Pico, in a natural truffle ground located in north Italy. Ascomata of this population of T. magnatum were collected over a period of up to 5 years. For comparative analysis, T. magnatum fruit bodies of different geographical origin were also considered. We used single locus markers, such as the variable region of ribosomal genes (ITS), the β‐tubulin gene and sequence‐characterized amplified regions (SCAR), as tools to identify single‐nucleotide polymorphisms (SNPs). On the basis of the molecular results, which were indirectly supported by a karyological analysis, a self‐fertilization mechanism is suggested. A SCAR region was polymorphic within the samples of the truffle ground, leading to the identification of two genotypes. In addition, both the SCAR and the ITS proved to be polymorphic among samples coming from different geographical regions, revealing a genetic differentiation in T. magnatum.
Assessing terminal restriction fragment length polymorphism suitability for the description of bacterial community structure and dynamics in hydrocarbon‐polluted marine environments
Authors: Denaro R. , D’Auria G. , Di Marco G. , Genovese M. , Troussellier M. , Yakimov M. M. , Giuliano L.
Published: December 2004

The distribution of bacterial communities terminal restriction fragment length polymorphism (T‐RFLP) fingerprint patterns was evaluated at three proximal hydrocarbon‐contaminated sites located within the harbour of Messina. In order to analyse the short‐term variability of the individual terminal restriction fragment (T‐RF) patterns, water samples were collected at the three sites on three occasions within 3 months (T0, T90 and T91). Four sample sizes, from 50 to 1000 ml for each collected sample, were analysed separately (36 total analysed samples) to evaluate the relationship between the sample size and the bacterial diversity estimates. The dominant T‐RF groups mostly belonged to signatures of putative hydrocarbon‐degrading bacteria, as revealed by the virtual analysis of the obtained bands. In order to test whether significant differences were occurring between the analysed samples, the Kruskal–Wallis non‐parametric test was applied to the T‐RF data set. Neither significant influence of the sample size nor short spatial variability within the three sampled sites was detected for each sampling time. On the contrary, significant temporal changes in the diversity of the bacterial communities were observed. These results were confirmed by the non‐metric multidimensional scales (nMDS) analysis of the whole set of samples, which indicated three main groups corresponding to the three different sampling times. In summary, the T‐RFLP technique, although a polymerase chain reaction‐based method, proved to be a suitable technique for monitoring polluted marine environments, typically characterized by low diversity and high relative abundances of a few dominant groups.
Thermal destruction of dried vegetative yeast cells and dried bacterial spores in a convective hot air flow: strong influence of initial water activity
Authors: Fine Frédéric , Gervais Patrick
Published: December 2004

Thermal treatment of Bacillus subtilis spores and Saccharomyces cerevisiae cells dried on glass beads was performed at various initial water activities (in the range 0.10–0.90). Experiments were carried out at 150°C, 200°C and 250°C for 5–120 s. Significant destruction of up to 107 vegetative cells and up to 105 spores g−1 was achieved, depending upon treatment conditions. This study demonstrated that the initial water activity (aw) value of a sample is very important in the destruction or survival of microorganisms treated with hot air stresses. As described previously, the heat resistance of spores and vegetative cells was strongly enhanced by low initial aw values until an optimal aw value between 0.30 and 0.50, with maximal viability at 0.35 for both S. cerevisiae and B. subtilis. However, our results highlighted for the first time that very low initial aw values (close to 0.10) greatly improved the destruction of spores and vegetative cells. Factors and possible mechanisms involved in the death of vegetative cells and spores are discussed.
The Global Governance of Communicable Diseases: The Case for Vaccine R&D
Authors: ARCHIBUGI DANIELE , BIZZARRI KIM
Published: December 2004

Fighting communicable diseases such HIV/AIDS, tuberculosis (TB, and malaria has become a global endeavor, with international health authorities urging the development of effective vaccines for the eradication of these global pandemics. Yet, despite the acknowledged urgency, and given the feasibility of effective vaccine development, public and private research efforts have failed to address a response adequate to the magnitude of the crisis. Members of the academic community suggest bridging this gap by devising research pull mechanisms capable of stimulating private investments, confident that competition‐based market devices are more effective than public intervention in shaping scientific breakthroughs. With reference to the economics of innovation, the paper argues that, whilst such an approach would lead to a socially suboptimal production of knowledge, direct public intervention in vaccine R&D activities would represent a far more socially desirable policy option. In recognition of the current financial and political fatigue affecting the international community towards communicable disease control, the paper resorts to the theories of global public goods (GPGs) to provide governments, both in the North and in the South, with a powerful rationale for committing to a cooperative approach for vaccine R&D. The paper encourages the creation of a Global Health Research Fund to manage such exercise and proposes enshrining countries’ commitments into an International Health Treaty. The paper ends by providing a number of policy recommendations.
Property Rights and the Control of Strategy: Foreign Ownership Rules and Domestic Firm Globalization in Indian Industry
Authors: CHHIBBER PRADEEP K. , MAJUMDAR SUMIT K.
Published: December 2004

This study examines the influence of foreign ownership levels on domestic firms’ exporting behavior in India. Foreign ownership is categorized according to the control exercisable at different levels of ownership by foreign shareholders. The degree of strategic control a foreign shareholder can possess is determined by the institutional structure of the Indian environment that firms operate in. The results show that, after controlling for a variety of firm and environment‐specific factors, only when property rights devolve unequivocally to foreign owners do domestic firms display the higher export orientation that is consonant with the process of globalization of their operations.
Activity‐Responsive Pacing Produces Long‐Term Heart Rate Variability
Authors: RAJ SATISH R. , ROACH DANIEL E. , KOSHMAN MARY‐LOU , SHELDON ROBERT S.
Published: December 2004

Introduction: Long‐term heart rate variability (HRV) measures, including the standard deviation of means of successive 5‐minute epochs of R‐R interval intervals (SDANN) and the power law slope (β), are important prognostic measures, yet their physiologic basis is unknown. We tested the hypothesis that long‐term HRV arises from physical activity in a randomized cross‐over study in patients with rate‐responsive pacemakers.

Methods and Results: Ten patients with complete heart block and dual‐chamber pacemakers underwent 24‐hour periods of ambulatory ECG in each of three pacing modes: atrially tracked, fixed‐rate, and rate‐responsive pacing. SDANN, ultralow frequency (ULF; frequencies <0.0033 Hz), and β slope were calculated; and high‐frequency power and root mean square of consecutive normal R‐R intervals (rMSSD) were calculated as measures of short‐term HRV, which have autonomic origins. Long‐term HRV measures were similar with atrially tracked and rate‐responsive pacing and were much greater than in fixed‐rate pacing (SDANN P = 0.0001; ULF P = 0.0001; β slope P = 0.0002). Short‐term HRV measures were similarly low in fixed‐rate and rate‐responsive pacing (P = NS) and were significantly lower than with atrially tracked pacing (P = 0.0034).

Conclusion: Rate‐responsive pacing reproduces long‐term, but not short‐term, measures of HRV, suggesting that they may be markers of heart rate responses to patient activity. (J Cardiovasc Electrophysiol, Vol. 15, pp. 179‐183, February 2004)
The significance of platelet‐activating factor and fertility in the male primate: a review
Authors: Roudebush William E. , Massey Joe B. , Elsner Carlene W. , Shapiro Daniel B. , Mitchell‐Leef Dorothy , Kort Hilton I.
Published: December 2004

Abstract:  Since its discovery nearly 30 years ago platelet‐activating factor (PAF) has emerged as one of the more important lipid mediators known. PAF (1‐O‐alkyl‐2‐O‐acetyl‐sn‐glycero‐3‐phosphorylcholine) exists endogenously as a mixture of molecular species with structural variants of the alkyl moiety. PAF is a novel potent signaling phospholipid that has unique pleiotropic biological properties in addition to platelet activation. PAF also plays a significant role in reproduction and is present in the sperm of a number of primate species. PAF content in squirrel monkey sperm is significantly higher during the breeding season than the non‐breeding season. PAF content in rhesus sperm has a significant relationship with sperm motility. PAF content in human sperm has a positive correlation with seminal parameters and pregnancy outcomes. The enzymes (lyso‐PAF‐acetyltransferase and PAF‐acetylhydrolase) necessary for PAF activation and deactivation are present in primate sperm. PAF‐acetylhydrolase may act as a ‘decapacitation factor’. Removal of this enzyme during capacitation promotes PAF synthesis increasing primate motility and fertilization. PAF also plays a significant role in the fertilization process, enhancing the fertilization rates of oocytes. Enhanced embryo development has also been reported in oocytes fertilized with PAF‐treated sperm. Exogenous PAF will also significantly improve primate artificial insemination pregnancy outcomes. PAF antagonists inhibit sperm motility, acrosome reaction, and fertilization thus suggesting the presence of receptors for PAF. The PAF‐receptor is present on primate sperm, with altered transcript levels and distribution patterns on abnormal cells. Whereas, the exact mechanism of PAF in sperm function and reproduction is uncertain, its importance in normal primate fertility is substantial.
Buthionine Sulfoximine Increases the Toxicity of Nifurtimox and Benznidazole toTrypanosoma cruzi
Authors: Faundez Mario , Pino Laura , Letelier Paula , Ortiz Carla , López Rodrigo , Seguel Claudia , Ferreira Jorge , Pavani Mario , Morello Antonio , Maya Juan Diego
Published: December 2004

l-Buthionine (S,R)-sulfoximine (BSO) increased the toxicity of nifurtimox and benznidazole toward the epimastigote, trypomastigote, and amastigote forms ofTrypanosoma cruzi. BSO at 500 μM decreased total glutathione-derived thiols by 70 to 80% in 48 h. In epimastigotes, 500 μM BSO decreased the concentration of nifurtimox needed to inhibit constant growth of the parasites by 50%, from 14.0 to 9.0 μM, and decreased that of benznidazole from 43.6 to 24.1 μM. The survival of epimastigotes or trypomastigotes treated with nifurtimox or benznidazole, as measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) reduction, was significantly decreased by 500 μM BSO. In Vero cells infected with amastigotes, 25 μM BSO was able to potentiate the effect of nifurtimox and benznidazole as measured by the percentage of infected Vero cells multiplied by the average number of intracellular amastigotes (endocytic index). At 0.5 μM nifurtimox, the proportion of Vero cells infected decreased from 27 to 20% and the endocytic index decreased from 2,500 to 980 when 25 μM BSO was added. Similar results were obtained with benznidazole- and BSO-benznidazole-treated cells. This study indicates that potentiation of nifurtimox or benznidazole by BSO could decrease the clinical dose of both drugs and diminish the side effects or the length of therapy.
Effects of Root Extracts of
Fagara zanthoxyloides
on the In Vitro Growth and Stage Distribution of
Plasmodium falciparum
Authors: Kassim Olakunle O. , Loyevsky Mark , Elliott Biaffra , Geall Andrew , Amonoo Henrietta , Gordeuk Victor R.
Published: December 2004

The development of resistance by
Plasmodium falciparum
to conventional drugs poses a threat to malaria control. There is therefore a need to find new, effective, and affordable remedies for malaria, including those derived from plants. This study demonstrates that crude, reverse-phase high-pressure liquid chromatography (RP-HPLC)-semipurified, and RP-HPLC-purified root extracts of
Fagara zanthoxyloides
inhibit the growth of
P. falciparum
in vitro, with 50% inhibitory concentrations (IC
50
s) of 4.90, 1.00, and 0.13 μg/ml, respectively. Roots of
F. zanthoxyloides
, known as chewing sticks, are widely used for tooth cleaning in West Africa. Microscopic examination of Giemsa-stained slides showed a virtual absence of schizonts in ring-stage synchronized cultures treated with crude extracts at concentrations of 30 to 60 μg/ml during 36 to 48 h of incubation. These observations suggest that the active constituent in the extract may be cytotoxic for
P. falciparum
trophozoites, thereby inhibiting their development to the schizont stage. A pure bioreactive fraction was subsequently obtained from the chromatographic separations. When this fraction was mixed with pure fagaronine, the mixture coeluted as a single peak on the analytical RP-HPLC column, suggesting that fagaronine may be the active antimalarial constituent of
Fagara
root extracts. Additional experiments showed that fagaronine also inhibited
P. falciparum
growth, with an IC
50
of 0.018 μg/ml. The results of this study suggest that the antimalarial activity of fagaronine deserves further investigation.
In Vitro Activities of Novel 2-Fluoro-Naphthyridine-Containing Ketolides
Authors: Abbanat Darren , Webb Glenda , Foleno Barbara , Li Y. , Macielag Mark , Montenegro Deborah , Wira Ellyn , Bush Karen
Published: December 2004

In vitro activities of erythromycin A, telithromycin, and two investigational ketolides, JNJ-17155437 and JNJ-17155528, were evaluated against clinical bacterial strains, including selected common respiratory tract pathogens. Against 46 macrolide-susceptible and -resistant
Streptococcus pneumoniae
strains, the MIC
90
(MIC at which 90% of the isolates tested were inhibited) of the investigational ketolides was 0.25 μg/ml, twofold lower than that of telithromycin and at least 64-fold lower than that of erythromycin A. Against
erm
(B)-containing pneumococci, the MIC
90
of all the ketolides was 0.06 μg/ml. The MIC
90
of the investigational ketolides against
mef
(A)-containing pneumococci or pneumococci with both
mef
(A) and
erm
(B) was 0.25 μg/ml, two-and fourfold lower, respectively, than that of telithromycin. In contrast, the MICs of the investigational ketolides against macrolide-resistant
S. pneumoniae
strains with ribosomal mutations were similar to or, in some cases, as much as eightfold higher than those of telithromycin. Against
Haemophilus influenzae
, MICs of all the ketolides were ≤2 μg/ml. Against three
Moraxella catarrhalis
isolates, the MIC of the ketolides was 0.25 μg/ml. The ketolides inhibited in vitro protein synthesis, with 50% inhibitory concentrations ranging from 0.23 to 0.27 μM. In time-kill studies against macrolide-susceptible and
erm
- or
mef
-containing pneumococci, the ketolides were bacteriostatic to slowly bactericidal, with 24-h log
10
decreases ranging from 2.0 to 4.1 CFU. Intervals of postantibiotic effects for the ketolides against macrolide-susceptible and -resistant
S. pneumoniae
were 3.0 to 8.1 h.