bluuebunny/crossref_metadata_2025 huggingface dataset:
Microflora in traditional starter cultures for fermented milk, hurunge, from Inner Mongolia, China
Authors: SHUANGQUAN  , BURENTEGUSI  , YU Bai , MIYAMOTO Taku
Published: March 2006

Microflora were investigated in traditional starter cultures for fermented milk, hurunge, which are used for fermented dairy products by nomadic families in the Inner Mongolia Autonomic Region, China. The acid‐forming bacteria and yeast counts ranged from 1.8 × 105 to 5.3 × 108 c.f.u./g and from 6.1 × 105 to 3.2 × 106 c.f.u./g, respectively. Sixty‐six strains of lactic acid bacteria and 30 strains of yeasts were isolated and identified from three hurunge samples collected from the nomadic families. Lactococcus raffinolactis was the most predominant lactococci isolated from these samples. The other lactococci were Lactococcus lactis ssp. lactis, Lactococcus lactis ssp. cremoris, and Leuconostoc mesenteroides ssp. cremoris. Two major lactobacilli strains, Lactobacillus plantarum and Lactobacillus casei, were identified. In addition, Lactobacillus kefiranofaciens, Lactobacillus acetotolerans, which grew in 11% acetic acid culture medium, and Lactobacillus homohiochii, which grew in the culture medium containing 16% ethanol, were also identified. The isolated yeast strains were identified as Candida kefyr, Saccharomyces cerevisiae, Kluyveromyces marxianus var. lactis, Candida krusei and Candida valida.
An improved understanding of canal hydraulics and flood risk from breach failures
Authors: Dun R. W. A.
Published: March 2006

British Waterways (BW) is the largest navigation authority in the UK, managing a network of 3200 km of inland waterway. Central to this function is the management of a complex water supply system, where water is transferred for resource management, to maintain navigation and for sale to third parties. The navigations also provide land drainage, with 30% of the English and Welsh catchments draining, into the network. Understanding the hydraulic mechanisms present is essential to manage the risks to infrastructure, land, property and personnel. This paper describes studies that have reduced the uncertainty of the hydraulic appraisals of canals. A programme of primary research included site surveys, hydraulic trials and modelling. Hydraulic roughnesses for a range of canal channel types were derived and the impact of structures was quantified. The paper then applies these findings to investigate a recent canal breach. Importantly, in terms of the hydraulic appraisal, pound water levels and flows were automatically monitored throughout the event. The breach was modelled via an innovative dual weir approach. The modelled water level drawdown compared very closely with that measured. In conclusion, this paper illustrates the major steps forward that BW has made in developing the understanding of canal hydraulics and breach failures. This paper is of interest to consultants, researchers and other workers who study canal hydraulics and flood risk throughout the UK and overseas.
Comparison of engineering costs of raw freshwater, reclaimed water and seawater for toilet flushing in Hong Kong
Authors: Tang S. L. , Yue Derek P. T. , Li X. Z.
Published: March 2006

Hong Kong is one of the very few coastal cities in the world that use ‘dual water supply systems’. Dual water supply involves two distribution systems: a freshwater system for potable use and a seawater system for toilet flushing. This study looks into the feasibility, from an engineering cost point of view, of extending seawater supply into districts where potable water is still being used for toilet flushing, including South District of Hong Kong Island, Sai Kung, Northern New Territories and Northwest New Territories. Besides seawater, raw (untreated) freshwater and reclaimed water (treated effluent from local sewage treatment works) are also considered to be used for toilet flushing for these districts. Six cases are developed for comparison by using the lowest net present value of cost criterion. The result shows that using seawater for toilet flushing in these districts has the best engineering economy.
Microbiological risk assessment and management of shallow groundwater sources in Lichinga, Mozambique
Authors: Godfrey S. , Timo F. , Smith M.
Published: March 2006

The principal water target of the Millennium Development Goals (MDG) is to ensure environmental sustainability by halving the proportion of people without access to safe water by 2015. Although great strides have been made in meeting this challenge since the year 2000, the safety of many of these water supplies remains unknown. Acknowledging the weaknesses of current water quality and hydrogeological means of assuring microbial safety, this paper has the objective of developing improved methods for the assessment and management of microbiological water safety based on a ‘risk’ paradigm. This paper provides evidence for the risk assessment of both conventional aquifer pathways and localised (short circuiting) pathways to 25 wells of three well technology types in Mozambique between 2002 and 2005.* Findings from the research outline improve methods of risk assessment and management by demonstrating that (1) the predominant source of contamination was from animal faeces rather than from latrines/septic tanks, (2) short circuiting is a significant risk to shallow groundwater in developing countries, (3) the use of alternative indicator organisms (e.g. enterococci) may improve risk understanding and (4) the World Health Organisation Water Safety Plans are recommended as an appropriate method of risk management.
Stem Cells and Their Niches
Authors: Moore Kateri A. , Lemischka Ihor R.
Published: March 2006

A constellation of intrinsic and extrinsic cellular mechanisms regulates the balance of self-renewal and differentiation in all stem cells. Stem cells, their progeny, and elements of their microenvironment make up an anatomical structure that coordinates normal homeostatic production of functional mature cells. Here we discuss the stem cell niche concept, highlight recent progress, and identify important unanswered questions. We focus on three mammalian stem cell systems where large numbers of mature cells must be continuously produced throughout adult life: intestinal epithelium, epidermal structures, and bone marrow.
Kaposi's Sarcoma-Associated Herpesvirus Fusion-Entry Receptor: Cystine Transporter xCT
Authors: Kaleeba Johnan A. R. , Berger Edward A.
Published: March 2006

Kaposi's sarcoma–associated herpesvirus (KSHV, human herpesvirus 8) is the causative agent of Kaposi's sarcoma and other lymphoproliferative syndromes often associated with HIV/AIDS. Functional complementary DNA selection for a receptor mediating KSHV cell fusion identified xCT, the 12-transmembrane light chain of the human cystine/glutamate exchange transporter system x
–
c
. Expression of recombinant xCT rendered otherwise not susceptible target cells permissive for both KSHV cell fusion and virion entry. Antibodies against xCT blocked KSHV fusion and entry with naturally permissive target cells. KSHV target cell permissiveness correlated closely with endogenous expression of xCT messenger RNA and protein in diverse human and nonhuman cell types.
How Fast Was Wild Wheat Domesticated?
Authors: Tanno Ken-ichi , Willcox George
Published: March 2006

Prehistoric cultivation of wild wheat in the Fertile Crescent led to the selection of mutants with indehiscent (nonshattering) ears, which evolved into modern domestic wheat. Previous estimates suggested that this transformation was rapid, but our analyses of archaeological plant remains demonstrate that indehiscent domesticates were slow to appear, emerging ~9500 years before the present, and that dehiscent (shattering) forms were still common in cultivated fields ~7500 years before the present. Slow domestication implies that after cultivation began, wild cereals may have remained unchanged for a long period, supporting claims that agriculture originated in the Near East ~10,500 years before the present.
Crime Scene Investigation--Permian
Authors: Bush Andrew M.
Published: March 2006

Extinction
. How Life on Earth Nearly Ended 250 Million Years Ago.
By Douglas H. Erwin
. Princeton University Press, Princeton, NJ, 2006. 306 pp. $24.95, £15.95. ISBN 0-691-00524-9.

The author discusses the end-Permian extinction--"the mother of mass extinctions"--and the numerous explanations that have been offered for it.
Energizing Eukaryotes
Authors: Nicholls David G.
Published: March 2006

Power, Sex, Suicide
. Mitochondria and the Meaning of Life.
By Nick Lane
. Oxford University Press, Oxford, 2005. 368 pp. $30, £18.99. ISBN 0-19-280481-2.

The author explores a range of big questions in biology--including eukaryote origins, human evolution, sex, fertility, and death--from the perspective of mitochondria.
Assent in paediatric research: theoretical and practical considerations: Figure 1
Authors: Wendler D S
Published: March 2006

Guidelines around the world require children to provide assent for their participation in most research studies. Yet, little further guidance is provided on how review committees should implement this requirement, including which children are capable of providing assent and when the requirement for assent may be waived on the grounds that the research offers participating children the potential for important clinical benefit. The present paper argues that the assent requirement is supported by the importance of allowing children who are capable to make their own decisions. This suggests children are capable of assent when they become able to understand the research in question. While development varies across individual children, existing data suggest most children develop this ability by approximately age 14. Until instruments are developed to assess the assent capacity of individual children, this age should be used as the threshold for assent. In addition, the importance of protecting children from harm suggests that the sustained dissent of all children, including those who are unable to provide assent, should be respected. While the assent requirement may be waived when research participation offers the potential for important medical benefit that is unavailable outside the research context, analysis suggests that children’s sustained dissent should be respected in all cases.
Empirical research in bioethical journals. A quantitative analysis
Authors: Borry P , Schotsmans P , Dierickx K
Published: March 2006

Objectives:The objective of this research is to analyse the evolution and nature of published empirical research in the fields of medical ethics and bioethics.

Design:Retrospective quantitative study of nine peer reviewed journals in the field of bioethics and medical ethics (Bioethics,Cambridge Quarterly of Healthcare Ethics,Hastings Center Report,Journal of Clinical Ethics,Journal of Medical Ethics,Kennedy Institute of Ethics Journal,Nursing Ethics,Christian Bioethics, andTheoretical Medicine and Bioethics).

Results:In total, 4029 articles published between 1990 and 2003 were retrieved from the journals studied. Over this period, 435 (10.8%) studies used an empirical design. The highest percentage of empirical research articles appeared inNursing Ethics(n=145, 39.5%), followed by theJournal of Medical Ethics(n=128, 16.8%) and theJournal of Clinical Ethics(n=93, 15.4%). These three journals account for 84.1% of all empirical research in bioethics published in this period. The results of the χ2test for two independent samples for the entire dataset indicate that the period 1997–2003 presented a higher number of empirical studies (n=309) than did the period 1990–1996 (n=126). This increase is statistically significant (χ2=49.0264, p<.0001). Most empirical studies employed a quantitative paradigm (64.6%, n=281). The main topic of research was prolongation of life and euthanasia (n=68).

Conclusions:We conclude that the proportion of empirical research in the nine journals increased steadily from 5.4% in 1990 to 15.4% in 2003. It is likely that the importance of empirical methods in medical ethics and bioethics will continue to increase.
Nurses’ views on their involvement in euthanasia: a qualitative study in Flanders (Belgium)
Authors: Dierckx de Casterlé B , Verpoort C , De Bal N , Gastmans C
Published: March 2006

Background:Although nurses worldwide are confronted with euthanasia requests from patients, the views of palliative care nurses on their involvement in euthanasia remain unclear.

Objectives:In depth exploration of the views of palliative care nurses on their involvement in the entire care process surrounding euthanasia.

Design:A qualitative Grounded Theory strategy was used.

Setting and participants:In anticipation of new Belgian legislation on euthanasia, we conducted semistructured interviews with 12 nurses working in a palliative care setting in the province of Vlaams-Brabant (Belgium).

Results:Palliative care nurses believed unanimously that they have an important role in the process of caring for a patient who requests euthanasia, a role that is not limited to assisting the physician when he is administering life terminating drugs. Nurses’ involvement starts when the patient requests euthanasia and ends with supporting the patient’s relatives and healthcare colleagues after the potential life terminating act. Nurses stressed the importance of having an open mind and of using palliative techniques, also offering a contextual understanding of the patient’s request in the decision making process. Concerning the actual act of performing euthanasia, palliative care nurses saw their role primarily as assisting the patient, the patient’s family, and the physician by being present, even if they could not reconcile themselves with actually performing euthanasia.

Conclusions:Based on their professional nursing expertise and unique relationship with the patient, nurses participating as full members of the interdisciplinary expert team are in a key position to provide valuable care to patients requesting euthanasia.
A natural stem cell therapy? How novel findings and biotechnology clarify the ethics of stem cell research
Authors: Patel P
Published: March 2006

The natural replacement of damaged cells by stem cells occurs actively and often in adult tissues, especially rapidly dividing cells such as blood cells. An exciting case in Boston, however, posits a kind of natural stem cell therapy provided to a mother by her fetus—long after the fetus is born. Because there is a profound lack of medical intervention, this therapy seems natural enough and is unlikely to be morally suspect. Nevertheless, we feel morally uncertain when we consider giving this type of therapy to patients who would not naturally receive it. Much has been written about the ethics of stem cell research and therapy; this paper will focus on how recent advances in biotechnology and biological understandings of development narrow the debate. Here, the author briefly reviews current stem cell research practices, revisits the natural stem cell therapy case for moral evaluation, and ultimately demonstrates the importance of permissible stem cell research and therapy, even absent an agreement about the definition of when embryonic life begins.

Although one promising technology, blighted ovum utilisation, uses fertilised but developmentally bankrupt eggs, it is argued that utilisation of unfertilised eggs to derive totipotent stem cells obviates the moral debate over when life begins. There are two existing technologies that fulfil this criterion: somatic cell nuclear transfer and parthenogenic stem cell derivation. Although these technologies are far from therapeutic, concerns over the morality of embryonic stem cell derivation should not hinder their advancement.
The impact of regional culture on intensive care end of life decision making: an Israeli perspective from the ETHICUS study
Authors: Ganz F D , Benbenishty J , Hersch M , Fischer A , Gurman G , Sprung C L
Published: March 2006

Background:Decisions of patients, families, and health care providers about medical care at the end of life depend on many factors, including the societal culture. A pan-European study was conducted to determine the frequency and types of end of life practices in European intensive care units (ICUs), including those in Israel. Several results of the Israeli subsample were different to those of the overall sample.

Objective:The objective of this article was to explore these differences and provide a possible explanation based on the impact of culture on end of life decision making.

Method:All adult patients admitted consecutively to three Israeli ICUs (n = 2778) who died or underwent any limitation of life saving interventions between 1 January 1999 and 30 June 2000 were studied prospectively (n = 363). These patients were compared with a similar sample taken from the larger study (ethics in European intensive care units: ETHICUS) carried out in 37 European ICUs. Patients were followed until discharge, death, or 2 months from the decision to limit therapy. End of life decisions were prospectively organised into one of five mutually exclusive categories: cardiopulmonary resuscitation (CPR), brain death, withholding treatment, withdrawing treatment, and active shortening of the dying process (SDP). The data also included patient characteristics (gender, age, ICU admission diagnosis, chronic disorders, date of hospital admission, date and time of decision to limit therapy, date of hospital discharge, date and time of death in hospital), specific therapies limited, and the method of SDP.

Results:The majority of patients (n = 252, 69%) had treatment withheld, none underwent SDP, 62 received CPR (17%), 31 had brain death (9%), and 18 underwent withdrawal of treatment (5%). The primary reason given for limiting treatment was that the patient was unresponsive to therapy (n = 187). End of life discussions were held with 132 families (36%), the vast majority of which revolved around withholding treatment (91% of the discussions) and the remainder concerned withdrawing treatment (n = 11, 9%).

There was a statistically significant association (χ2= 830.93, df=12, p < 0.0001) between the type of end of life decision and region—that is, the northern region of Europe, the central region, the southern region, and Israel.

Conclusions:Regional culture plays an important part in end of life decision making. Differences relating to end of life decision making exist between regions and these differences can often be attributed to cultural factors. Such cultures not only affect patients and their families but also the health care workers who make and carry out such decisions.
A group randomised trial of two methods for disseminating a smoking cessation programme to public antenatal clinics: effects on patient outcomes
Authors: Campbell E , Walsh R A , Sanson-Fisher R , Burrows S , Stojanovski E
Published: March 2006

Objective:To assess the differential effectiveness of two methods of disseminating a smoking cessation programme to public hospital antenatal clinics.

Design:Group randomised trial.

Setting:22 antenatal clinics in New South Wales, Australia.

Intervention:Clinics were allocated to a simple dissemination (SD) condition (11 clinics) which received a mail-out of programme resources or to an intensive dissemination (ID) condition (11 clinics) which included the mail-out plus feedback, training, and ongoing support with midwife facilitator.

Main outcome measures:Independent cross sectional surveys of women on a second or subsequent visit undertaken pre-dissemination and 18 months after dissemination. Outcomes were: (1) levels of smoking status assessment by clinic staff; (2) proportion of women identifying as having been smokers at their first visit who reported receiving cessation advice; (3) proportion of these women who had quit (self report and expired air carbon monoxide (CO)); and (4) smoking prevalence among all women (self report and CO).

Subjects:5849 women pre-dissemination (2374 SD, 3475 ID) and weighted sample of 5145 women post-dissemination (2302 SD, 2843 ID).

Results:There were no significant differences between the groups on change on any outcome. Change in either group was minimal. In the post-dissemination survey, the cessation proportions were 6.4% (SD) and 10.5% (ID).

Conclusions:Relatively modest strategies for encouraging incorporation of smoking cessation activities into antenatal care were not effective in the long term. Alternative strategies should be implemented and evaluated. The findings reinforce the importance of a whole population approach to tobacco control.
Price and cigarette consumption in Europe
Authors: Gallus S , Schiaffino A , La Vecchia C , Townsend J , Fernandez E
Published: March 2006

Objective:To analyse the variation in demand for tobacco according to price of cigarettes across the European region.

Design:Cross-sectional study.

Setting:All the 52 countries of the European region.

Participants:For each European country, data were collected on annual per adult cigarette consumption (2000), smoking prevalence (most recent), retail price of a pack of local and foreign brand cigarettes (around 2000), the gross domestic product adjusted by purchasing power parities, and the adult population (2000).

Main outcome measure:Price elasticity of demand for cigarettes (that is, the change in cigarette consumption according to a change in tobacco price) across all the European countries, estimated by double-log multiple linear regression.

Results:Controlling for male to female prevalence ratio, price elasticities for consumption were −0.46 (95% confidence interval (CI) −0.74 to −0.17) and −0.74 (95% CI −1.13 to −0.35) for local and foreign brand, respectively. The inverse relation between cigarette price and consumption was stronger in countries not in the European Union (price elasticity for foreign brand cigarettes of −0.8) as compared to European Union countries (price elasticity of −0.4).

Conclusions:The result that, on average, in Europe smoking consumption decreases 5–7% for a 10% increase in the real price of cigarettes strongly supports an inverse association between price and cigarette smoking.
Electrophysiological characterization of murine HL-5 atrial cardiomyocytes
Authors: Xiao Yong-Fu , TenBroek Erica M. , Wilhelm Joshua J. , Iaizzo Paul A. , Sigg Daniel C.
Published: March 2006

HL-5 cells are cultured murine atrial cardiomyocytes and have been used in studies to address important cellular and molecular questions. However, electrophysiological features of HL-5 cells have not been characterized. In this study, we examined such properties using whole cell patch-clamp techniques. Membrane capacitance of the HL-5 cells was from 8 to 62 pF. The resting membrane potential was −57.8 ± 1.4 mV ( n = 51). Intracellular injection of depolarizing currents evoked action potentials (APs) with variable morphologies in 71% of the patched cells. Interestingly, the incidence of successful, current-induced APs positively correlated with the hyperpolarizing degrees of resting membrane potentials ( r = 0.99, P < 0.001). Only a few of the patched cells (4 of 51, 7.8%) exhibited spontaneous APs. The muscarinic agonist carbachol activated the acetylcholine-activated K+current and significantly shortened the duration of APs. Immunostaining confirmed the presence of the muscarinic receptor type 2 in HL-5 cells. The hyperpolarization-activated cation current ( If) was detected in 39% of the patched cells. The voltage to activate 50% of Ifchannels was −73.4 ± 1.2 mV ( n = 12). Voltage-gated Na+, Ca2+, and K+currents were observed in the HL-5 cells with variable incidences. Compared with the adult mouse cardiomyocytes, the HL-5 cells had prolonged APs and small outward K+currents. Our data indicate that HL-5 cells display significant electrophysiological heterogeneity of morphological appearance of APs and expression of functional ion channels. Compared with adult murine cardiomyocytes, HL-5 cells show an immature phenotype of cardiac AP morphology.
Kv2 channels oppose myogenic constriction of rat cerebral arteries
Authors: Amberg Gregory C. , Santana Luis F.
Published: March 2006

By hyperpolarizing arterial smooth muscle, voltage-gated, Ca2+-independent K+ (Kv) channels decrease calcium influx and thus oppose constriction. However, the molecular nature of the Kv channels function in arterial smooth muscle remains controversial. Recent investigations have emphasized a predominant role of Kv1 channels in regulating arterial tone. In this study, we tested the hypothesis Kv2 channels may also significantly regulate tone of rat cerebral arteries. We found that Kv2.1 transcript and protein are present in cerebral arterial smooth muscle. In addition, our analysis indicates that a substantial component (≈50%) of the voltage dependencies and kinetics of Kv currents in voltage-clamped cerebral arterial myocytes is consistent with Kv2 channels. Accordingly, we found that stromatoxin, a specific inhibitor of Kv2 channels, significantly decreased Kv currents in these cells. Furthermore, stromatoxin enhanced myogenic constriction of pressurized arterial segments. We also found that during angiotensin II-induced hypertension, Kv2 channel function was reduced in isolated myocytes and in intact arteries. This suggests that impaired Kv2 channel activity may contribute to arterial dysfunction during hypertension. On the basis of these novel observations, we propose a new model of Kv channel function in arterial smooth muscle in which Kv2 channels (in combination with Kv1 channels) contribute to membrane hyperpolarization and thus oppose constriction.
Distinct requirements for Hfe in basal and induced hepcidin levels in iron overload and inflammation
Authors: Constante Marco , Jiang Wenlei , Wang Dongmei , Raymond Valérie-Ann , Bilodeau Marc , Santos Manuela M.
Published: March 2006

Hepcidin is a negative regulator of iron absorption produced mainly by the liver in response to changes in iron stores and inflammation, and its levels have been shown to regulate the intestinal basolateral iron transporter ferroportin1 ( Fp1). Hereditary hemochromatosis patients and Hfe-deficient mice show inappropriate expression of hepcidin but, in apparent contradiction, still retain the ability to regulate iron absorption in response to alterations of iron metabolism. To further understand the molecular relationships among Hfe, hepcidin, and Fp1, we investigated hepcidin and Fp1 regulation in Hfe-deficient mice ( Hfe−/−and β2m−/−) in response to iron deprivation, iron loading, and acute inflammation. We found that whereas basal hepcidin levels were manifestly dependent on the presence of Hfe and on the mouse background, all Hfe-deficient mice were still able to regulate hepcidin in situations of altered iron homeostasis. In the liver, Fp1 was modulated in opposite directions by iron and LPS, and its regulation in Hfe-deficient mice was similar to that observed in wild-type mice. In addition, we found that iron-deprived mice were able to mount a robust response after LPS challenge and that Toll-like receptor 4 (TLR-4)-deficient mice fail to regulate hepcidin expression in response to LPS. In conclusion, these results suggest that although Hfe is necessary for the establishment of hepcidin basal levels, it is dispensable for hepcidin regulation through both the iron-sensing and inflammatory pathways, and hepatic Fp1 regulation is largely independent of hepcidin and Hfe. The inflammatory pathway overrides the iron-sensing pathway and is TLR-4 dependent.
Experimental colitis modulates the functional properties of NMDA receptors in dorsal root ganglia neurons
Authors: Li Jichang , McRoberts James A. , Ennes Helena S. , Trevisani Marcello , Nicoletti Paola , Mittal Yash , Mayer Emeran A.
Published: March 2006

N-methyl-d-aspartate (NMDA) receptors (NMDARs) on spinal afferent neurons regulate the peripheral and central release of neuropeptides involved in the development of hyperalgesia. We examined the effect of experimental colitis on the molecular and functional properties of NMDARs on these neurons. Lumbosacral dorsal root ganglia (DRG) were collected from adult rats 5 days after the induction of colitis for whole cell patch-clamp recording, Western blot analysis, and quantitative RT-PCR. Compared with neurons from control rats, those taken from animals with colitis had a threefold higher density of NMDA currents in both retrograde-labeled, colon-specific, and unlabeled DRG neurons. Increased current densities were not observed in DRG neurons taken from thoracic spinal levels. There was no significant change in NMDA or glycine affinity or in voltage-dependent Mg2+inhibition; however, there was a 10-fold decrease in sensitivity to the NR2B subunit-selective antagonist ifenprodil. Quantitative RT-PCR and Western blot analysis indicated a 28% increase in the expression of NR2B with little or no change in the other three NR2 subunits. The addition of the Src family tyrosine kinase inhibitor PP2 (10 μM) decreased NMDAR currents in neurons from colitis but not control rats. Conversely, pretreatment of DRG neurons from control animals with 100 μM sodium orthovanadate increased NMDAR currents and decreased ifenprodil sensitivity to levels similar to those observed in neurons from animals with colitis. In conclusion, colonic inflammation upregulates the activity of NMDARs in all DRG neurons within ganglia innervating this tissue through mechanisms involving increased expression and persistent tyrosine phosphorylation.
Geldanamycin prevents hemorrhage-induced ATP loss by overexpressing inducible HSP70 and activating pyruvate dehydrogenase
Authors: Kiang Juliann G. , Bowman Phillip D. , Lu Xinyue , Li Yansong , Ding Xuan Z. , Zhao Baiteng , Juang Yuang-Taung , Atkins James L. , Tsokos George C.
Published: March 2006

Hemorrhage in mice results in decreased ATP levels in the jejunum, lung, kidney, heart, and brain but not in liver tissue lysates, albeit at variable levels and time kinetics. The decreased protein expression and activity of pyruvate dehydrogenase (PDH) accounted for the hemorrhage-induced ATP loss. Treatment with geldanamycin (GA; 1 μg/g body wt), a known inducer of heat shock protein (HSP)70, inhibited the hemorrhage-induced ATP loss in the jejunum, lung, heart, kidney, and brain. GA was found to increase PDH protein, preserve PDH enzymatic activity, and inhibit mucosal injury in jejunum tissues. GA-induced HSP70i was found to form complexes with PDH protein. HSP70 gene transfer into intestinal epithelial cells promoted PDH and ATP levels, whereas HSP70 short interfering RNA limited them. We conclude that agents able to increase the expression of HSP70 and PDH may be of value in reducing pathology resulting from hemorrhage-associated ATP loss.
Immune complexes alter cerebral microvessel permeability: roles of complement and leukocyte adhesion
Authors: Lister Karyn J. , Hickey Michael J.
Published: March 2006

Immune complexes (ICs) are potent inflammatory mediators in peripheral tissues. However, very few studies have examined the ability of ICs to induce inflammatory responses in the brain. Therefore, using preformed ICs or the reverse passive Arthus (RPA) model to localize ICs to the pial microvasculature of mice, we aimed to investigate the ability of ICs to induce an inflammatory response in the cerebral (pial) microvasculature. Application of preformed ICs immediately increased pial microvascular permeability, with a minimal change in leukocyte adhesion in pial postcapillary venules. In contrast, initiation of the RPA response in the pial microvasculature induced changes in cerebral microvascular permeability and increased leukocyte adhesion in pial postcapillary venules. The RPA response induced deposition of C3 in perivascular regions adjacent to sites of IC formation. Depletion of C3 abrogated RPA-induced microvascular permeability and leukocyte adhesion, indicating that the complement pathway was critical for this response. Inhibition of leukocyte adhesion via CD18 blockade also reduced IC-induced microvascular permeability. However, this did not require intercellular adhesion molecule-1, inasmuch as blockade of intercellular adhesion molecule-1 did not alter RPA-induced microvascular permeability and adhesion. These findings demonstrate that ICs are capable of rapidly inducing inflammatory responses in the cerebral microvasculature, with the complement pathway and leukocyte recruitment playing critical roles in microvascular dysfunction.
Evidence for two-pore domain potassium channels in rat cerebral arteries
Authors: Bryan Robert M. , You Junping , Phillips Sharon C. , Andresen Jon J. , Lloyd Eric E. , Rogers Paul A. , Dryer Stuart E. , Marrelli Sean P.
Published: March 2006

Little is known about the presence and function of two-pore domain K+(K2P) channels in vascular smooth muscle cells (VSMCs). Five members of the K2Pchannel family are known to be directly activated by arachidonic acid (AA). The purpose of this study was to determine 1) whether AA-sensitive K2Pchannels are expressed in cerebral VSMCs and 2) whether AA dilates the rat middle cerebral artery (MCA) by increasing K+currents in VSMCs via an atypical K+channel. RT-PCR revealed message for the following AA-sensitive K2Pchannels in rat MCA: tandem of P domains in weak inward rectifier K+(TWIK-2), TWIK-related K+(TREK-1 and TREK-2), TWIK-related AA-stimulated K+(TRAAK), and TWIK-related halothane-inhibited K+(THIK-1) channels. However, in isolated VSMCs, only message for TWIK-2 was found. Western blotting showed that TWIK-2 is present in MCA, and immunohistochemistry further demonstrated its presence in VSMCs. AA (10–100 μM) dilated MCAs through an endothelium-independent mechanism. AA-induced dilation was not affected by inhibition of cyclooxygenase, epoxygenase, or lipoxygenase or inhibition of classical K+channels with 10 mM TEA, 3 mM 4-aminopyridine, 10 μM glibenclamide, or 100 μM Ba2+. AA-induced dilations were blocked by 50 mM K+, indicating involvement of a K+channel. AA (10 μM) increased whole cell K+currents in dispersed cerebral VSMCs. AA-induced currents were not affected by inhibitors of the AA metabolic pathways or blockade of classical K+channels. We conclude that AA dilates the rat MCA and increases K+currents in VSMCs via an atypical K+channel that is likely a member of the K2Pchannel family.
Renal endothelial dysfunction and impaired autoregulation after ischemia-reperfusion injury result from excess nitric oxide
Authors: Guan Zhengrong , Gobé Glenda , Willgoss Desley , Endre Zoltán H.
Published: March 2006

Endothelial dysfunction in ischemic acute renal failure (IARF) has been attributed to both direct endothelial injury and to altered endothelial nitric oxide synthase (eNOS) activity, with either maximal upregulation of eNOS or inhibition of eNOS by excess nitric oxide (NO) derived from iNOS. We investigated renal endothelial dysfunction in kidneys from Sprague-Dawley rats by assessing autoregulation and endothelium-dependent vasorelaxation 24 h after unilateral (U) or bilateral (B) renal artery occlusion for 30 (U30, B30) or 60 min (U60, B60) and in sham-operated controls. Although renal failure was induced in all degrees of ischemia, neither endothelial dysfunction nor altered facilitation of autoregulation by 75 pM angiotensin II was detected in U30, U60, or B30 kidneys. Baseline and angiotensin II-facilitated autoregulation were impaired, methacholine EC50was increased, and endothelium-derived hyperpolarizing factor (EDHF) activity was preserved in B60 kidneys. Increasing angiotensin II concentration restored autoregulation and increased renal vascular resistance (RVR) in B60 kidneys; this facilitated autoregulation, and the increase in RVR was abolished by 100 μM furosemide. Autoregulation was enhanced by Nω-nitro-l-arginine methyl ester. Peri-ischemic inhibition of inducible NOS ameliorated renal failure but did not prevent endothelial dysfunction or impaired autoregulation. There was no significant structural injury to the afferent arterioles with ischemia. These results suggest that tubuloglomerular feedback is preserved in IARF but that excess NO and probably EDHF produce endothelial dysfunction and antagonize autoregulation. The threshold for injury-producing, detectable endothelial dysfunction was higher than for the loss of glomerular filtration rate. Arteriolar endothelial dysfunction after prolonged IARF is predominantly functional rather than structural.
Amino acids as modulators of endothelium-derived nitric oxide
Authors: Kakoki Masao , Kim Hyung-Suk , Edgell Cora-Jean S. , Maeda Nobuyo , Smithies Oliver , Mattson David L.
Published: March 2006

To examine the mechanisms whereby amino acids modulate nitric oxide (NO) production and blood flow in the renal vasculature, chemiluminescence techniques were used to quantify NO in the renal venous effluent of the isolated, perfused rat kidney as different amino acids were added to the perfusate. The addition of 10−4or 10−3M cationic amino acids (l-ornithine, l-lysine, or l-homoarginine) or neutral amino acids (l-glutamine, l-leucine, or l-serine) to the perfusate decreased NO and increased renal vascular resistance. Perfusion with anionic amino acids (l-glutamate or l-aspartate) had no effect on either parameter. The effects of the cationic and neutral amino acids were reversed with 10−3M l-arginine and prevented by deendothelialization or NO synthase inhibition. The effects of the neutral amino acids but not the cationic amino acids were dependent on extracellular sodium. Cationic and neutral amino acids also decreased calcimycin-induced NO, as assessed by DAF-FM-T fluorescence, in cultured EA.hy926 endothelial cells. Inhibition of system y+or y+L by siRNA for the cationic amino acid transporter 1 or the CD98/4F2 heavy chain diminished the NO-depleting effects of these amino acids. Finally, transport studies in cultured cells demonstrated that cationic or neutral amino acids in the extracellular space stimulate efflux of l-arginine out of the cell. Thus the present experiments demonstrate that cationic and neutral amino acids can modulate NO production in endothelial cells by altering cellular l-arginine transport through y+and y+L transport mechanisms.
Ovine bronchial-derived relaxing factor: changes with development and hyperoxic ventilation
Authors: Lakshminrusimha Satyan , Morin Frederick C. , Steinhorn Robin H. , Gugino Sylvia F. , Ryan Rita M. , Kumar Vasanth H. , Russell James A.
Published: March 2006

Recent studies suggest that a bronchial-derived relaxing factor (BrDRF) decreases the contractility of newborn, but not fetal, rat pulmonary arteries (PAs) by a nitric oxide (NO)-mediated mechanism. We studied the effect of an adjacent bronchus on PA contractility to norepinephrine (NE) in late-gestation fetal ( n = 7), neonatal (1 day old, n = 9), ventilated neonatal (24-h ventilation from birth with 100% oxygen, n = 9), and adult sheep ( n = 6) in the presence and absence of the NO synthase inhibitor Nω-nitro-l-arginine (l-NNA). The sheep were anesthetized and killed, and fifth-generation PA rings with and without an attached adjacent bronchus (PA+Br) were contracted in standard tissue baths with NE (10−8–10−6 M). NE contractions were expressed as fraction of KCl (118 mM) contraction and as grams of contraction force. NE contractions were significantly diminished by the presence of an attached bronchus in the neonatal and ventilated neonatal and adult, but not fetal, lambs. Hyperoxic ventilation markedly increased NE contractions in PA and PA+Br. l-NNA significantly enhanced NE contractions in PA+Br in postnatal but not in fetal lambs. Pretreatment with l-NNA abolished the difference between NE contractions in PA and PA+Br in neonatal but not in hyperoxic ventilated neonatal lambs. We conclude that there is a BrDRF that is developmentally regulated and has vascular activity postnatally but not during fetal life. The effect of BrDRF is predominantly mediated by NO in air-breathing neonatal lambs but may involve a second non-NO mediator following hyperoxic ventilation. We speculate that BrDRF may have an important role in postnatal changes in pulmonary arterial reactivity.
Spike-Frequency Adaptation and Intrinsic Properties of an Identified, Looming-Sensitive Neuron
Authors: Gabbiani Fabrizio , Krapp Holger G.
Published: March 2006

We investigated in vivo the characteristics of spike-frequency adaptation and the intrinsic membrane properties of an identified, looming-sensitive interneuron of the locust optic lobe, the lobula giant movement detector (LGMD). The LGMD had an input resistance of 4–5 MΩ, a membrane time constant of about 8 ms, and exhibited inward rectification and rebound spiking after hyperpolarizing current pulses. Responses to depolarizing current pulses revealed the neuron's intrinsic bursting properties and pronounced spike-frequency adaptation. The characteristics of adaptation, including its time course, the attenuation of the firing rate, the mutual dependency of these two variables, and their dependency on injected current, closely followed the predictions of a model first proposed to describe the adaptation of cat visual cortex pyramidal neurons in vivo. Our results thus validate the model in an entirely different context and suggest that it might be applicable to a wide variety of neurons across species. Spike-frequency adaptation is likely to play an important role in tuning the LGMD and in shaping the variability of its responses to visual looming stimuli.
Binaural Response Properties of Low-Frequency Neurons in the Gerbil Dorsal Nucleus of the Lateral Lemniscus
Authors: Siveke Ida , Pecka Michael , Seidl Armin H. , Baudoux Sylvie , Grothe Benedikt
Published: March 2006

Differences in intensity and arrival time of sounds at the two ears, interaural intensity and time differences (IID, ITD), are the chief cues for sound localization. Both cues are initially processed in the superior olivary complex (SOC), which projects to the dorsal nucleus of the lateral lemniscus (DNLL) and the auditory midbrain. Here we present basic response properties of low-frequency (<2 kHz) DNLL neurons and their binaural sensitivity to ITDs and IIDs in the anesthetized gerbil. We found many neurons showing binaural properties similar to those reported for SOC neurons. IID-properties were similar to that of the contralateral lateral superior olive (LSO). A majority of cells had an ITD sensitivity resembling that of either the ipsilateral medial superior olive (MSO) or the contralateral LSO. A smaller number of cells displayed intermediate types of ITD sensitivity. In neurons with MSO-like response ITDs that evoked maximal discharges were mostly outside of the range of ITDs the gerbil naturally experiences. The maxima of the first derivative of their ITD-functions (steepest slope), however, were well within the physiological range of ITDs. This finding is consistent with the concept of a population rather than a place code for ITDs. Moreover, we describe several other binaural properties as well as physiological and anatomical evidence for a small but significant input from the contralateral MSO. The large number of ITD-sensitive low-frequency neurons implicates a substantial role for the DNLL in ITD processing and promotes this nucleus as a suitable model for further studies on ITD-coding.
Dense-Core Secretory Granule Biogenesis
Authors: Kim Taeyoon , Gondré-Lewis Marjorie C. , Arnaoutova Irina , Loh Y. Peng
Published: March 2006

The dense-core secretory granule is a key organelle for secretion of hormones and neuropeptides in endocrine cells and neurons, in response to stimulation. Cholesterol and granins are critical for the assembly of these organelles at the trans-Golgi network, and their biogenesis is regulated quantitatively by posttranscriptional and posttranslational mechanisms.
Cell-Cell Communication Beyond Connexins: The Pannexin Channels
Authors: Barbe Michael T. , Monyer Hannah , Bruzzone Roberto
Published: March 2006

Direct cell-to-cell communication through specialized intercellular channels is a characteristic feature of virtually all multi-cellular organisms. The remarkable functional conservation of cell-to-cell coupling throughout the animal kingdom, however, is not matched at the molecular level of the structural protein components. Thus protostomes (including nematodes and flies) and deuterostomes (including all vertebrates) utilize two unrelated families of gap-junction genes, innexins and connexins, respectively. The recent discovery that pannexins, a novel group of proteins expressed by several organisms, are able to form intercellular channels has started a quest to understand their evolutionary relationship and functional contribution to cell communication in vivo. There are three pannexin genes in mammals, two of which are co-expressed in the developing and adult brain. Of note, pannexin1 can also form Ca2+-activated hemichannels that open at physiological extracellular Ca2+concentrations and exhibit distinct pharmacological properties.
Vasopressin and Pair-Bond Formation: Genes to Brain to Behavior
Authors: Nair Hemanth P. , Young Larry J.
Published: March 2006

Microtine rodents provide an excellent model for the study of the neurobiology of social bonds. In this review, we discuss how the presence of a microsatellite sequence in the prairie vole vasopressin receptor gene may determine vasopressin receptor binding patterns in the brain and how these patterns may in turn affect social behavior.
Congenital Hyperthyroidism: The Fetus as a Patient
Authors: Polak Michel , Legac Isabelle , Vuillard Edith , Guibourdenche Jean , Castanet Mireille , Luton Dominique
Published: March 2006

Congenital hyperthyroidism is less frequent than congenital hypothyroidism but its impact on growth and development can be as dramatic. The immune form of hyperthyroidism that is transmitted from a mother with Graves’ disease to her foetus and then neonate is transient, but cases of persistent congenital hyperthyroidism had also been described, that can now be explained by molecular abnormalities of the thyrotropin receptor. The abundance of published data on the neonatal effects of maternal Graves’ disease contrasts with the paucity of information on fetal effects. Recent studies showed that it is of utmost to scrutinize fetal thyroid by expert ultrasonographist and to have a team work with obstetricians and pediatric endocrinologists in pregnant women with Graves’ disease. This allowed to accurately determine the fetal thyroid status and to adapt the treatment in the mothers successfully. Fetal hyperthyroidism does exist and needs an appropriate aggressive treatment. Clearly the fetus has become our patient!
The Effects of Growth Hormone Treatment on Health-Related Quality of Life in Children
Authors: Sheppard L. , Eiser C. , Davies H.A. , Carney S. , Clarke S.A. , Urquhart T. , Ryder M.J. , Stoner A. , Wright N.P. , Butler G.
Published: March 2006

Background/Aims: The effects of growth hormone deficiency (GHD) on linear growth in children are well documented, but there is less convincing evidence regarding the impact on health-related quality of life (QOL). We examined QOL in children aged 8–16 years with acquired GHD following treatment for malignancy (AGHD) or idiopathic GHD (IGHD) on commencing growth hormone treatment (GHT) over 6 months. We adopted a longitudinal design involving consecutive patients and their families attending clinic over an 18-month period. Mothers and children were invited to complete questionnaires before GHT (T1) and 6 months later (T2). Methods: Mothers of 22 children (AGHD n = 14; IGHD n = 8) completed standardized measures of child QOL and behaviour. Children completed parallel measures of QOL, short-term memory tasks and fitness either in clinic or at the family home. Results: For children with AGHD, QOL was significantly below population norms at T1 and improved over time. For children diagnosed with IGHD, QOL at T1 was below, but comparable with population norms. QOL improved over time, though not significantly. Conclusion: GHT is potentially valuable for improving QOL in children, especially in cases of AGHD. We conclude that benefits of GHT for QOL need to be evaluated independent of different diagnostic groups.