bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Maturation Diets on the Reproductive Output of the White‐striped Cleaner Shrimp, Lysmata amboinensis
Authors: Tziouveli Vasiliki , Hall Mike , Smith Greg
Published: February 2011

Aquaculture production of the cleaner shrimp Lysmata amboinensis, a high‐valued marine ornamental, has been problematic because of prolonged larval development punctuated by periods of mortality. Broodstock maturation diets have been shown to affect fecundity and offspring quality and early survival. The common practice in shrimp culture is the use of fresh frozen foods supplemented with artificial diets. The objective of the study was to identify a suitable maturation diet (natural or artificial) for L. amboinensis. Six diets, comprised of squid, mussel, adult Artemia, a commercial feed, and combinations of the aforementioned, were fed to L. amboinensis for four reproductive cycles. Broodstock fed the squid–mussel diet lost a large proportion of the eggs during incubation, with decreased larval production (P < 0.05). In contrast, broodstock fed Artemia retained the highest proportion of the egg mass; however, hatchability was poor, resulting in low larval numbers per hatch. The Artemia and squid–mussel diets produced significantly fewer larvae than the combination or commercial diets (P < 0.05). In L. amboinensis, a maturation diet consisting of natural feeds alone resulted in poor reproductive performance and partial or complete replacement with an artificial diet was feasible.
Compensatory Growth in Juvenile Freshwater Turtles, Chinemys reevesii, Following Feed Deprivation
Authors: Wang Jie , Niu Cuijuan , Huang Chenxi , Rummer Judie L. , Xie Zhigang
Published: February 2011

The compensatory growth response of juvenile three‐keeled pond turtles, Chinemys reevesii, was investigated by food deprivation for 1–4 wk and then refeeding for 4 wk. After feeding resumed, only turtles that were deprived over 2 wk displayed higher specific growth rates than the continuously fed turtles for 1 wk, but their weights were lower than the control at the end of refeeding, showing a partial compensatory growth pattern. Their feeding rate, rather than the feed conversion efficiency and apparent digestibility of energy, was higher than the control during the compensatory phase, indicating that hyperphagia was responsible for the compensatory growth. As starvation intensified, protein concentrations of deprived turtles increased significantly, whereas the contents of fat tissues decreased sharply. After 4 wk of refeeding, the contents of fat tissues in deprived turtles returned to the control level, whereas protein concentrations did not, indicating that lipid rather than protein was the main fuel utilized during short‐term starvation for juvenile turtles aged over 2 mo.
Effects of Estradiol Valerate on Steroid Hormones and Sex Reversal of Female Rice Field Eel, Monopterus albus (Zuiew)
Authors: Chu Zhangjie , Wu Youxian , Gong Shiyuan , Zhang Guobin , Zhang Lei , Yuan Yongchao , Yuan Hanwen
Published: February 2011

The rice field eel, Monopterus albus (Zuiew), is an important aquaculture fish in many Asian countries. Productivity, however, is limited by low fecundity as a result of sex reversal of female juveniles of this fish. This study was conducted to investigate the effects of estradiol valerate on the sex reversal process of this fish by determining sex changes of initial 2‐yr‐old female eels (26.5 ± 2.6 cm, 21.9 ± 2.1 g) treated with three concentrations of estradiol valerate: 0 mg/kg (Control, Group A), 10 mg/kg (Group B), and 50 mg/kg (Group C). In Group A, sex reversal took place with significantly higher percentage of sex change: about 45% of female eels to intersexes and males. Only about 22% of female eels changed to intersexes and males in Group B, but no sex reversal occurred in Group C during the experimental period. The result also indicated that the gonadal development and the concentrations of serum estradiol (E2) and testosterone (T) varied significantly with different concentrations of dietary estradiol valerate. Serum T significantly reduced but serum E2 significantly increased in Group C compared to the control Group A. The results demonstrated that estradiol valerate affected the secretion of sex steroid hormones in rice field eels and thus inhibited the sex reversal process at a low concentration (10 mg/kg) or stopped the sex reversal process at a high concentration (50 mg/kg) of estradiol valerate. These results suggest that a higher yield of mature female eels could be achieved by treatments with estradiol valerate, thus enhancing the fecundity of this rice field eel.
Clearance of Yellow Pigments Lutein and Zeathanxin in Channel Catfish, Ictalurus punctatus, Reared at Different Water Temperatures
Authors: Li Menghe H. , Robinson Edwin H. , Oberle Daniel F. , Lucas Penelope M. , Peterson Brian C. , Bates Terry D.
Published: February 2011

A study was conducted to determine the clearance time of yellow pigments lutein and zeaxanthin in channel catfish at various temperatures. Fish of initial weight of 13.4 g were stocked into flow‐through aquaria and fed daily with a pigment‐enhanced diet for 11 wk when yellow color became visible in the flesh. All fish were then transferred into tanks in three recirculating systems that were assigned one of the three temperatures (10, 20, and 30 C). During the pigment clearance period, fish were fed a control diet without added pigments daily to satiation for 12 wk. Every 4 wk, fish from three randomly chosen tanks per temperature were euthanized and fillets were analyzed for yellow color intensity (Commission Internationale de I’Eclairage [CIE] b*) and lutein and zeaxanthin concentrations. The b* values of fillets of fish reared at 20 and 30 C decreased linearly as time progressed. There was no significant linear regression of b* value against time for fish raised at 10 C. The rate of pigment clearance was similar for fish reared at 20 and 30 C. Results demonstrate that about 8 wk were needed for catfish to “purge” most of yellow pigment at warm temperatures (20 and 30 C). A longer period of time (> 12 wk) was required at 10 C.
Correspondence
Authors: JARRETT‐KERR MARTIN
Published: February 2011

CORRESPONDENCE
NO MAN IS AN ISLAND
Authors: Wilson Michael
Published: February 2011

Who bends not his eare to any bell, which upon any occasion rings? but who can remove it from that bell, which is passing a peece of himselfe out of this world ? No man is an Iland intire of itselfe; every man is a peece of the continent, a part of the maine; if a clod bee washed away by the Sea, Europe is the lesse, as well as if a Promontorie were, as well as if a Mannor of thy friends or of thine own were; any man's death diminishes me, because I am involved in Mankinde; and therefore never send to know for whom the bell tolls. It tolls for thee.
THE SECULARIZATION DEBATE FORESHADOWED, JERUSALEM 1928
Authors: Gill David M.
Published: February 2011

The significance of the statement made at Jerusalem [regarding secular civilization] can in my opinion hardly be overestimated. Indeed, the twentieth century will have to face a spiritual crisis within Christianity, perhaps more general and more deeply rooted than any other century since the beginning of the Christian era has seen.2
FAITH, FREEDOM AND CULTURAL DIFFERENCE: CUERNAVACA AND CHRISTIAN MISSION
Authors: Fitzpatrick Joseph P.
Published: February 2011

The Centre of Intercultural Documentation and the Institute for Contemporary Latin Studies are located in the city of Cuernavaca in Mexico. The main emphasis of the Institute is to work with Latin Americans in leadership training courses. Summer courses are also held, attended both by Latin Americans and by students from USA and other countries — mostly Roman Catholics — intending to work as missionaries in Latin American countries.

The Institute describes itself as offering “an unusual approach to the understanding of modern man in Latin America, as he experiences the recent and rapid change of all institutions around him”. The Institute accepts as students “both those whose main field of study or research is Latin America and those who seek a new dimension in their understanding of North American social change as contrasted with change in capital‐starved areas of the world”. (Editor's note.)
LATIN AMERICA — AN ECUMENICAL BIRD'S EYE VIEW
Authors: Hayward Victor
Published: February 2011

Please don't skip this introductory paragraph. It is the most important one in the whole of this long survey article — simply because it tells you what it is, and what it isn't. I was appalled to be asked to write this paper. Not only because it was too much like work, but also because I well know that I am no authority on Latin America. Prior to 1970 I had visited this fascinating continent only three times. In September and October of that year I made a quick tour of nine countries in South and Central America and of nine countries or islands in the Caribbean Region (with those of the latter which are English or Dutch‐speaking I shall not deal in this paper). My one advantage was to cover a great deal of ground within a single tour, against the background of similar tours I had already made in all other parts of the world. After visiting each country I wrote an immediate and semi‐confidential report. On the basis of these, my colleagues asked me to write this survey article recording impressions gained largely through this single tour. It is faithful reporting, but inevitably superficial, and may be unintentionally misleading. It is not a mine of information, but a bird's eye view — and the bird not only had an ecumenical bias, but was a bird of passage.
PARTICIPATION IS EVERYTHING
Authors: Mello Manoel de
Published: February 2011

This document is taken from an interview granted to the editor of O Expositor Cristao by Pastor Manoel de Mello. We have omitted the questions and consolidated the answers. Manoel de Mello is a leader of the Brazilian Igreja Evangélica Pentecostal “Brasil para Cristo” — a Pentecostal denomination with about one million members. In São Paulo, Manoel de Mello is building the largest church in the world. It seats 25,000 people, and has many additional halls and rooms for adult education, workshops, etc. De Mello was one of the Pentecostals from Latin America who attended the Fourth Assembly of the World Council of Churches at Uppsala. He also was guest of the Assembly of the Lutheran World Federation at Evian (1970), where — in fact — he was, for part of the time, the only representative of a Brazilian Church.

In the report below he states the reasons why his church has decided to join the WCC. The editors of the news‐service of the Centro Evangélico de Informação (São Paulo) introduce the report with the following noteworthy remark: “With this ecumenical consciousness directed towards renewal, the Pentecostals should become the greatest revolutionary force in Protestant thought in Brazil.” Editor
Book Reviews
Authors: Fallet Marcel
Published: February 2011

Book reviewed in this article:

Ökumene in Schule und Gemeinde, eds.

L'Europe et les Destinées du Proche‐Orient (1815–1848): Unité arabe—Missions chrétiennes—La Question syro‐palestinienne et syro‐libanaise, by J. Hajjar

L'Afrique noire et la crise religieuse de l'Occident, by V. Neckerbrouck

Studia Missionalia, vol. 20, 1971, ed. by Mariasusai Dhavamony

To China with love: The Lives and Times of Protestant Missionaries in China 1860–1900, by Pat Barr

Les Chemins de la Mission aujourd'hui. By Robert Ageneau and Denis Pryen

Prospect and Prophecy. The churches in industrial society. By André Dumas
BUILDING A UNION OF THEIR OWN
Authors: Hartmire Wayne C.
Published: February 2011

Each time a man or woman stands up for justice the heavens sing and the world rejoices. Each time a man or woman stands up for justice and is struck down the heavens weep and the world mourns. Farm workers everywhere are angry and worried but we are not going to fall into the trap that our oppressors have fallen into. We do not need to destroy to win. We are a movement that builds and does not destroy.
WHOSE HUMAN RIGHTS?
Authors: Bonino José Míguez
Published: February 2011

Indians, particularly in Amazonia, are being dispossessed of … their lands … Under these conditions, the “Statute of the Indian” becomes “dead letter” … It is not surprising, therefore, that Indians are led to feel ashamed of their race…

The poor and defenceless are those who fill the jails, where they are frequently tortured, accused of not having identity documents, or arrested in the course of police “razzias”.

“Pastoral Letter to the People of God”

The Episcopal Conference of Brazil, October 25, 1976.
EVANGELISM IN THE SOCIALIST SOCIETY OF CUBA
Authors: Ham Adolfo
Published: February 2011

The Church recognizes that if it is to be the Church of Jesus Christ, sacrificial, fraternal and unconditional love is a necessity; it accepts that the sole reason for its existence is the cause of human dignity and decency always and every where, and makes no proviso about its commitment; without regard to the circumstances in which it may live or the risks it may NII, it participates fully in human redemption (1.C.05).

When the Church lives ita historical reality by placing the human being in the very centre of its interest in Jesus Christ, it is not losing its identity as Body of Christ or as Bride of Christ. On the contrary. Even when most involved in the secular, the Church succeeds in carrying out its indispensable commitment to serve and love Jesus Christ, because in him, at the cost of his self‐sacrifice, God radically and unconditionally involved himself in the secular in his redemptive work of seeking full respect and dignity for all human beings (1.C.08).
LOOKING FOR THE ENERGY OF THE SALT OF THE EARTH
Authors: Isshiki Naotsugu
Published: February 2011

Professor Isshiki, one of Japan's foremost scientists in the energy field, teaches in the prestigious Tokyo Institute of Technology and is an elder in his local congregation (Kyodan). Dr Isshiki developed the safety design for the first Japanese atomic powered ship which, when it was floated several years ago, provoked heated public debate. Fishermen, anxious about the safety aspects, were particularly insensed by the project. Scientists countered with assurances that some of the operational problems which had appeared in the ship's trial run could certainly be ironed out, but popular resistance to the project continued.

The people's resistance stirred deeper questions in Dr Isshiki's mind: What relationship ought there to be between his scientific calling and his faith in Christ? Could these two integral parts of an individual be compartmentalized? Had his participation in this project already shown that compartmentalization in his own thinking? Wasn't one's life a whole, a totality? But could these two things really be mixed? Should he leave his profession and thereby resolve the tension? But if he left his post, the present course of technological development would continue, and he would have no means of influencing it. Were not scientific gifts, such as his, God‐given?

It was out of this ferment that Professor Isshiki undertook his research into new alternative forms of energy which eventually issued in his invention of the CDE engine, a history‐making event, and, for Dr Isshiki, a gift of God.

We asked Dr Isshiki to write something for our readers on the scientific vocation and the responsibilities of a Christian scientist working at this very high technological level. (Editor)
COMPASSION AND SALTPETRE: Reflections on my Life as a Theologian in the Factory
Authors: Hulbert Alastair
Published: February 2011

The following article was written for the French Protestant Industrial Mission by Alastair Hulbert, a young Scots pastor who worked in France from 1972 to 1977 as a member of the Mission Populaire team. First in Roubaix, then in Paris, Alastair and his wife Fiona with their two children experienced every facet of working‐class life. These reflections accordingly take the form of a personal account of a journey; they have the feel and smell of experience, testifying to the difficulties but also to the joys of two English‐speaking team members thrust for five years into an unfamiliar world. Without succumbing to pro‐working‐class snobbery or a taste for martyrdom, Alastair and Fiona Hulbert succeeded in the rare achievement of penetrating deeply at a particular place with no pretence or indulgence towards those with whom and for whom the struggle is waged. In fact, far from selling theology cheap by facile simplifications, this article is a specimen of in situ theological reflection on the motives and conditions of militant action.
Protective effects of glycyrrhizic acid by rectal treatment on a TNBS-induced rat colitis model
Authors: Liu Ying , Xiang Jin , Liu Min , Wang Shi , Lee Robert J , Ding Hong
Published: February 2011

Objectives

The research compared rectal and oral treatments with glycyrrhizic acid for trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.

Methods

Wistar rats were randomly divided into seven groups: one normal and six with colitis, including TNBS, glycyrrhizic acid (2, 10 and 50 mg/kg, rectally treated and 10 mg/kg, orally treated) and sulfasalazine (positive control, 225 mg/kg rectally treated) groups. Colitis was induced by colonic administration of TNBS in 30% ethanol.

Key findings

There were significant pathological changes in colon in TNBS-treated groups, and rectal glycyrrhizic acid significantly attenuated colitis. Myeloperoxidase, tumour necrosis factor-α and interleukin-1β of colon tissue or serum in the rectal glycyrrhizic acid groups were markedly reduced when compared with the TNBS group, and lower than in the orally treated glycyrrhizic acid group. It was further noted that, in vitro, glycyrrhizic acid (up to 100 µg/ml) inhibited interleukin-6 and elevated interleukin-10 production in lipopolysaccharide-activated macrophages, and significantly inhibited proliferation of spleen lymphocytes, suggesting the immunoregulatory function of glycyrrhizic acid.

Conclusions

Rectally administered glycyrrhizic acid has significant protective effects against TNBS-induced colitis in rats, and the rectal route may be a complementary treatment for inflammatory bowel disease.
Expression and functional activity of P-glycoprotein in passaged primary human nasal epithelial cell monolayers cultured by the air–liquid interface method for nasal drug transport study
Authors: Cho Hyun-Jong , Choi Min-Koo , Lin Hongxia , Kim Jung Sun , Chung Suk-Jae , Shim Chang-Koo , Kim Dae-Duk
Published: February 2011

Objectives

P-glycoprotein (P-gp) is an efflux transporter encoded by the multidrug resistance gene (MDR1), which is also known as the human ABCB1 gene (ATP-binding cassette, subfamily-B). The objectives of this study were to investigate the expression of P-gp in passaged primary human nasal epithelial (HNE) cell monolayer, cultured by the air–liquid interface (ALI) method, and to evaluate its feasibility as an in-vitro model for cellular uptake and transport studies of P-gp substrates.

Methods

Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to verify the expression of the MDR1 gene. Transport and cellular uptake studies with P-gp substrate (rhodamine123) and P-gp inhibitors (verapamil and cyclosporin A) were conducted to assess the functional activity of P-gp in HNE cell monolayers cultured by the ALI method.

Key findings

MDR1 gene expression in primary HNE cell monolayers cultured by ALI method was confirmed by RT-PCR. The apparent permeability coefficient (Papp) of the P-gp substrate (rhodamine123) in the basolateral to apical (B to A) direction was 6.9 times higher than that in the apical to basolateral (A to B) direction. B to A transport was saturated at high rhodamine123 concentration, and the treatment of P-gp inhibitors increased cellular uptake of rhodamine123 in a time- and concentration-dependent manner.

Conclusions

These results support the MDR1 gene expression and the functional activity of P-gp in primary HNE cell monolayers cultured by the ALI method.
Ferulsinaic acid attenuation of advanced glycation end products extends the lifespan ofCaenorhabditis elegans
Authors: Sayed Ahmed A R
Published: February 2011

Objectives

Ferulsinaic acid is the first member of a new rearranged class of sesquiterpene coumarins of the genus Ferula. The genus Ferula can be used for the treatment of skin infections, hysteria and for stomach disorders, such as a febrifuge and a carminative agent. The effect of ferulsinaic acid on the lifespan of the nematode Caenorhabditis elegans has been examined. Novel data explaining the effect of ferulsinaic acid on the lifespan of C. elegans and its antioxidant power were obtained.

Methods

C. elegans was cultivated under standard laboratory conditions in absence and presence of different ferulsinaic acid. Also, animals were cultivated under heat and chemical stress conditions in absence and presence of ferulsinaic acid. Life span assay, determination of protein concentration, assay of malondialdehyde and ELISA for determination of AGEs were performed.

Key findings

Under standard laboratory conditions and in presence of ferulsinaic acid (500 nm, 10 µm and 100 µm), mean life span of wild type animals was significantly lengthened in a dose-dependent manner from 18.64 ± 0.19 days (control) to 19 ± 0.19 (P = 0.695), 20.76 ± 0.25 (P = 0.043) and 22.3 ± 0.29 (P = 0.0291), respectively. Interestingly, in C. elegans resistance for heat stress at 35°C and oxidative stress induced by paraquat were significantly improved with ferulsinaic acid. Ferulsinaic acid was found to significantly attenuate both lipid peroxidation and the formation of advanced glycation end products in the wild-type animals under standard laboratory conditions.

Conclusions

Ferulsinaic acid had therapeutic efficacy as an antioxidant with the possibility of its use as an antioxidant drug.
Intestinal enzymatic metabolism of drugs
Authors: Sarti Federica , Barthelmes Jan , Iqbal Javed , Hintzen Fabian , Bernkop-Schnürch Andreas
Published: February 2011

Objectives

The intestinal stability of perorally administered drugs has so far been determined using simulated intestinal fluid containing porcine pancreatin (SIF/P), as human gastrointestinal fluids are in most cases not available. In this study the metabolism of six low molecular mass drugs in SIF/P was compared with that in freshly collected porcine intestinal juice and on excised porcine intestinal mucosa.

Methods

The drugs used were oseltamivir, atazanavir, diloxanide, diltiazem, cephalothin and cefoxitin. Metabolism studies were carried out by incubating each drug in the in-vitro models and by analysing the percentage of unmodified remaining drug at fixed time points.

Key findings

Three drugs showed higher degradation on porcine mucosa compared with that in SIF/P and for five compounds a significantly higher metabolism in collected porcine intestinal juice versus SIF/P was observed. Metabolism of diloxanide furoate in collected intestinal juice, for example, was 40-fold higher compared with SIF/P. Moreover, the involvement of different metabolic pathways in porcine mucosa and intestinal juice was observed for cephalothin, being metabolized to desacetylcephalothin and thienyl-acetylglycine, whereas these metabolites were not found in SIF/P. In addition, diltiazem solution (0.25% m/v) was found to be significantly degraded in intestinal juice whereas its metabolism in SIF/P was negligible.

Conclusions

These findings demonstrated that the use of SIF/P for evaluation of presystemic drug metabolism could be highly misleading. Incubation of drugs in freshly collected porcine intestinal juice will likely lead to the improvement of the mimicry of body conditions to evaluate presystemic drug metabolism.
Encapsulation of vinorelbine into cholesterol-polyethylene glycol coated vesicles: drug loading and pharmacokinetic studies
Authors: Li ChunLei , Cui JingXia , Wang CaiXia , Zhang Lan , Xiu Xian , Li YongFeng , Wei Na , Li YanHui , Zhang Li
Published: February 2011

Objectives

Pegylated liposome formulations of vinorelbine with prolonged circulation half-life (t½) are desirable. However, DSPE-PEG could affect vinorelbine loading into vesicles due to electrostatic interactions. To resolve this problem, chol-PEG was used to prepare pegylated liposomal vinorelbine and the factors affecting drug loading and plasma pharmacokinetics were investigated.

Methods

Vinorelbine was loaded into liposomes using a novel triethylamine 5-sulfosalicylate gradient. The effects of cholesterol and chol-PEG on drug loading were investigated. Pharmacokinetic studies were performed in normal KunMing mice treated with different liposomal vinorelbine formulations. To clarify the effects of chol-PEG on membrane permeability, drug release experiments were performed based on the fluorescence dequenching phenomenon of a fluorescence marker.

Key findings

In contrast to DSPE-PEG, even at high PEG grafting density (∼8.3 mol%), chol-PEG had no effect on vinorelbine loading into HSPC/cholesterol (3 : 1, mass ratio) vesicles. However, for the formulations with low cholesterol content (HSPC/cholesterol 4 : 1), loading efficiency decreased with increasing chol-PEG content. In vivo, the vinorelbine t½ of low cholesterol formulations decreased with increasing chol-PEG content, but for high cholesterol liposomes, the maximum vinorelbine t½ was achieved at ∼3 mol% chol-PEG grafting density. The resulting vinorelbine circulation t½ was ∼9.47 h, which was greater than that of non-pegylated liposomes (∼5.55 h). Drug release experiments revealed that chol-PEG might induce membrane defects and concomitant release of entrapped marker, especially at high chol-PEG density.

Conclusions

Through the investigation of the effects of chol-PEG and cholesterol, an optimum pegylated liposomal vinorelbine formulation with prolonged t½ was achieved. In plasma, the membrane defect induced by chol-PEG may counteract the long circulation characteristics that chol-PEG afforded. When these two opposite effects reached equilibrium, the maximum vinorelbine t½ was achieved.
Anti-inflammatory activity of the non-peptidyl low molecular weight radical scavenger IAC in carrageenan-induced oedema in rats
Authors: Corsi Lorenzo , Zavatti Manuela , Geminiani Elisa , Zanoli Paola , Baraldi Mario
Published: February 2011

Objective

In this research we investigated the anti-inflammatory activity of a non-peptidyl low molecular weight radical scavenger (IAC) in an acute and chronic animal model of inflammation.

Methods

For this purpose the effect of IAC (10, 25, 50 mg/kg) was tested in rats on the associated behavioral responses to subsequent inflammatory and noxious challenges, such as hind paw oedema induced by intra-plantar injection of carrageenan and granuloma induced by subcutaneous implant of a cotton pellet, using indometacin (2.5 mg/kg) as reference drug. Moreover, the serum level of several cytokines was tested in the animal treated (or not) with IAC (50 mg/kg) both in the absence and presence of carrageenan-induced inflammation.

Key findings

IAC showed a significant anti-inflammatory activity in both in acute and chronic models of inflammation. In addition IAC down regulated significantly the serum levels of interleukin (IL) 2 and IL6 whereas it increased the serum concentration of IL1α and glutathione.

Conclusion

Although it remains to be elucidated whether or not the antioxidant property of IAC is directly responsible for the modulation of the tested cytokines, these results suggest IAC to be a possible candidate for a novel anti-inflammatory compound
Preparation of ONO-1301-loaded poly(lactide-co-glycolide) microspheres and their effect on nerve conduction velocity
Authors: Hazekawa Mai , Sakai Yoshiki , Yoshida Miyako , Haraguchi Tamami , Morisaki Tomomi , Uchida Takahiro
Published: February 2011

Objectives

The aim of this study was to prepare poly(lactide-co-glycolide) (PLGA) microspheres containing ONO-1301, a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity, with 10% of drug released in the initial burst and a sustained-release period of about 3 weeks after administration. The effect of PLGA type (molecular weight and the lactide/glycolide (L/G) ratio in PLGA), the preparative conditions and the particle size on the in-vitro release profile were examined. The effect of optimized ONO-1301-loaded PLGA microspheres on delayed nerve condition velocity (NCV) was investigated in streptozotocin (STZ) induced diabetic rats.

Methods

ONO-1301 PLGA microspheres were produced by the oil-in-water emulsion/solvent evaporation method. Drug release from the prepared microspheres was monitored in phosphate buffer solution at 37°C for 4 weeks by high-performance liquid chromatography. The in-vivo study was performed in STZ-induced diabetic rats treated with optimized ONO-1301 PLGA microspheres (10 mg/kg by intramuscular or subcutaneous injection every 3 weeks). NCV was measured in the thigh 4, 8 and 12 weeks after induction.

Key findings

The molecular weights of PLGA, the L/G ratio in PLGA and the particle diameter all affected the length of the sustained release period. Drug release from microspheres containing PLGA 5050 (MW 50 000, L/G 50/50), with an average diameter of about 30 µm, could be sustained for 3 weeks in vitro. In the in-vivo study, delayed NCV was significantly increased by treatment with these ONO-1301 PLGA microspheres once every 3 weeks, in comparison with vehicle only.

Conclusion

Local intramuscular injection of sustained-release ONO-1301 PLGA microspheres improved delayed NCV in STZ-induced diabetic rats.
The interaction of visual, vestibular and extra‐retinal mechanisms in the control of head and gaze during head‐free pursuit
Authors: Ackerley Rochelle , Barnes Graham R.
Published: February 2011

Non‐technical summary  In everyday life, we encounter moving objects and to follow them, we have developed smooth pursuit eye movements. When you rotate your head, the vestibulo‐ocular reflex is activated, which generates compensatory smooth eye movements so your eyes remain focussed on the current object of interest. Previous work has shown that you can overcome this reflex to follow a moving object with your eyes and head together, but this normally requires visual feedback. The current study shows that under certain circumstances, for example when you can anticipate the motion of an object, you can use predictive mechanisms in the brain to supplement your pursuit movements to continue to follow the object if it disappears. We demonstrate that you can sample and store brief visual motion to pursue an unseen moving object. Additionally, you can more accurately follow it with your eyes and head together, compared to just using your eyes.
Cytosolic H+ microdomain developed around AE1 during AE1‐mediated Cl−/HCO3− exchange
Authors: Johnson Danielle E. , Casey Joseph R.
Published: February 2011

Non‐technical summary  Most cellular processes are exquisitely sensitive to pH. Consequently our cells have a range of processes directed to control cellular pH. Plasma membrane transport proteins move acid or base across the plasma membrane to regulate pH precisely. We studied AE1 (also called Band 3) of erythrocytes and kidney cells, which rapidly transports the base, bicarbonate. AE1's high transport rate, combined with the surprisingly slow rates of H+ diffusion in cytosol, led us to wonder whether AE1 changes the pH of its local environment. The key findings were that H+ diffusion through the cytosol occurs at 0.6 μm s−1, and along the inner surface of the plasma membrane at only 0.01 μm s−1. We estimated that the size of the region of altered pH (H+ microdomain) around AE1 is 0.3 μm in diameter. pH‐regulatory transporters, like AE1, have differential effects on their immediate environment, with implications for the regulation of nearby pH‐sensitive proteins.
Desensitization of neurotransmitter‐gated ion channels during high‐frequency stimulation: a comparative study of Cys‐loop, AMPA and purinergic receptors
Authors: Papke David , Gonzalez‐Gutierrez Giovanni , Grosman Claudio
Published: February 2011

Non‐technical summary  During fast synaptic transmission, series of brief pulses of highly concentrated neurotransmitter impinge repetitively on the postsynaptic membrane. The number of neurotransmitter‐gated ion channels (NGICs) that open in response to each neurotransmitter pulse may increase or decrease along such trains of stimuli to an extent that can affect the transmission of action potentials. This ‘short‐term’ plasticity results from transient changes (lasting from milliseconds to minutes) in the properties of the presynaptic terminal, the postsynaptic terminal, or both. In this paper, we studied eight representative members of all three known superfamilies of NGICs to determine the extent to which short‐term plasticity can occur at the postsynaptic‐receptor level. We found that the responsiveness of all tested channels declines appreciably along trains of brief neurotransmitter pulses delivered at physiologically relevant frequencies. We suggest that the role of receptor desensitization in the synaptic control of action‐potential transmission may be more general than previously thought.
BK channel β1 subunits regulate airway contraction secondary to M2 muscarinic acetylcholine receptor mediated depolarization
Authors: Semenov Iurii , Wang Bin , Herlihy Jeremiah T. , Brenner Robert
Published: February 2011

Non‐technical summary  Parasympathetic nerve activation of M3 and M2 muscarinic acetylcholine receptors initiates and modulates calcium release from the sarcoplasmic reticulum to control airway smooth muscle contraction. Here we investigate M2 acetylcholine receptors that also contribute to contraction through depolarization and recruitment of voltage‐dependent calcium channels (VDCCs). We find that the calcium‐ and voltage‐activated potassium channel (BK channel) and its β1 accessory subunit are important proteins that oppose M2‐mediated contraction of airway smooth muscle. BK channels contribute to a negative baseline membrane voltage from which M2‐mediated depolarization only weakly activates VDCCs. The role of BK β1 to oppose M2 signalling is evidenced by a greater than fourfold increase in the contribution of L‐type VDCCs to contraction that otherwise does not occur with M2 receptor antagonist or with β1 containing BK channels. These findings provide a better understanding of how cholinergic second messenger signalling impinges on voltage‐dependent mechanisms and excitation–contraction coupling of smooth muscle.
Insulin acts in the arcuate nucleus to increase lumbar sympathetic nerve activity and baroreflex function in rats
Authors: Cassaglia Priscila A. , Hermes Sam M. , Aicher Sue A. , Brooks Virginia L.
Published: February 2011

Non‐technical summary  Though the pancreatic hormone insulin is known to act in the brain to increase sympathetic nerve activity and baroreflex control of sympathetic nerve activity, its specific site of action had yet to be identified. We show that a region in the hypothalamus, the arcuate nucleus, is the site at which insulin's effects are initiated. This new information may lead to a greater understanding of the role of insulin in the brain in adverse cardiovascular complications, like hypertension and heart attacks, which are associated with insulin‐resistant states, such as obesity and diabetes.
Early activation of mTORC1 signalling in response to mechanical overload is independent of phosphoinositide 3‐kinase/Akt signalling
Authors: Miyazaki Mitsunori , McCarthy John J. , Fedele Mark J. , Esser Karyn A.
Published: February 2011

Non‐technical summary  Hypertrophy of skeletal muscle in response to resistance exercise is associated with significantly elevated rates of protein synthesis. The protein kinase mTORC1 has been shown to be a key signalling hub through which different anabolic factors (i.e. growth factors, nutrients and mechanical strain) contribute to the regulation of protein synthesis. In this study, we use an in vivo model of muscle hypertrophy to delineate the contribution of different input pathways regulating mTORC1. We found that the insulin/insulin like growth factor 1 pathway is not necessary for early activation of mTORC1 signalling but this probably occurs through activation of the ERK/TSC2 pathway. Knowledge of the key upstream pathways that modulate mTORC1 activity in vivo will provide the necessary foundation for the development of new therapeutic strategies for the maintenance of skeletal muscle mass.
The Characteristics of Innovative, Mechanical Products
Authors: Saunders Matthew N. , Seepersad Carolyn C. , Hölttä-Otto Katja
Published: February 2011

Many new products fail upon introduction to the marketplace, but a few products are exceptionally successful, earning innovation awards and other benchmarks of success. To better understand the features of those innovative products, 197 award-winning products are analyzed to identify the characteristics that distinguish those products from the competition. For the analysis, a set of product-level characteristics is identified and organized into categories, which include functionality, architecture, external interactions, user interactions, and cost. Based on their innovation award citations, the products are analyzed with respect to the set of characteristics, and results are tabulated. Several award-winning products are also compared with competitive products on the shelves of major retail stores. On average, award-winning products display multiple characteristics of innovation. Overall, a vast majority (more than two-thirds) of the award-winning products exhibit enhanced user interactions, with a similar percentage displaying enhanced external interactions, compared with approximately one-third of products offering an additional function and approximately half displaying innovative architectures. The award-winning products also exhibit an average of approximately two more characteristics than their competitors on retail shelves, along with significantly higher rates of innovative architecture, external interactions, and user interactions. The analysis concludes with a discussion of the implications of these findings for engineering design methods.
Heat and Mass Transfer Caused by a Laminar Channel Flow Equipped With a Synthetic Jet Array
Authors: Trávníček Zdeněk , Dančová Petra , Kordík Jozef , Vít Tomáš , Pavelka Miroslav
Published: February 2011

Low Reynolds number laminar channel flow is used in various heat/mass transfer applications such as cooling and mixing. A low Reynolds number implies a low intensity of heat/mass transfer processes since they rely only on the gradient diffusion. To enhance these processes, an active flow control by means of synthetic (zero-net-mass-flux) jets is proposed. The present study is experimental, in which a Reynolds number range of 200–500 is investigated. Measurement has been performed mainly in air as the working fluid by means of hot-wire anemometry and the naphthalene sublimation technique. Particle image velocimetry (PIV) experiments in water are also discussed. The experiments have been performed in macroscale at the channel cross sections (20×100) mm and (40×200) mm in air and water, respectively. The results show that the low Reynolds number channel flow can be influenced by an array of synthetic jets. The effect of synthetic jets on the heat transfer enhancement is quantified. The stagnation Nusselt number is enhanced by 10–30 times in comparison with the nonactuated channel flow. The results indicate that the present arrangement can be a useful tool for heat transfer enhancement in various applications, e.g., cooling and mixing.
Simulation and Experimental Research on Chatter Suppression Using Chaotic Spindle Speed Variation
Authors: Fansen Kong , Peng Liu , Xingang Zhao
Published: February 2011

A method for varying the spindle speed using chaotic signal to suppress chatter in machining is developed. The effects of spindle speed variation on cutting chatter control between using chaotic and sinusoidal signals were analyzed by simulation and experimental methods. Various chaotic codes are used in the chatter suppression process, and it is found that LORENZ-1 code results in the smallest machine noise.
Gα
q
and Phospholipase C-β: Turn On, Turn Off, and Do It Fast
Authors: Ross Elliott M.
Published: February 2011

A crystal structure illuminates reciprocal regulation between a G protein and its effector.
Making It Short and Sweet
Authors: Adler Elizabeth M.
Published: February 2011

O
-linked β-
N
-acetylglucosamine transferase cleaves HCF-1, as well as glycosylating it, in a process necessary for its functional activation.
Limiting Inflammatory Signaling with EPO
Authors: Gough Nancy R.
Published: February 2011

Erythropoietin inhibits NF-κB activation in macrophages and thus limits proinflammatory signaling.
Wearing the Same Cap
Authors: Gough Nancy R.
Published: February 2011

Some viruses evade detection by encoding enzymes that modify the structures of their coding RNAs to match those of their hosts.
Time for a Pause
Authors: Hurtley Stella M.
Published: February 2011

A peptide-mediated translational pause facilitates the unconventional splicing of a messenger RNA on the endoplasmic reticulum.
Not So Different After All
Authors: VanHook Annalisa M.
Published: February 2011

Dissociation of a plant receptor kinase inhibitor from its substrate is mediated by tyrosine phosphorylation.
Variation in Transit
Authors: Stern Peter R.
Published: February 2011

The waveform of an action potential can be physiologically modified while it travels along the axon.
Development of Tetravalent, Bispecific CCR5 Antibodies with Antiviral Activity against CCR5 Monoclonal Antibody-Resistant HIV-1 Strains
Authors: Schanzer Jürgen , Jekle Andreas , Nezu Junichi , Lochner Adriane , Croasdale Rebecca , Dioszegi Marianna , Zhang Jun , Hoffmann Eike , Dormeyer Wilma , Stracke Jan , Schäfer Wolfgang , Ji Changhua , Heilek Gabrielle , Cammack Nick , Brandt Michael , Umana Pablo , Brinkmann Ulrich
Published: February 2011

In this study, we describe novel tetravalent, bispecific antibody derivatives that bind two different epitopes on the HIV coreceptor CCR5. The basic protein formats that we applied were derived from Morrison-type bispecific antibodies: whole IgGs to which we connected single-chain antibodies (scFvs) via (Gly
4
Ser)

n

sequences at either the C or N terminus of the light chain or heavy chain. By design optimization, including disulfide stabilization of scFvs or introduction of 30-amino-acid linkers, stable molecules could be obtained in amounts that were within the same range as or no less than 4-fold lower than those observed with monoclonal antibodies in transient expression assays. In contrast to monospecific CCR5 antibodies, bispecific antibody derivatives block two alternative docking sites of CCR5-tropic HIV strains on the CCR5 coreceptor. Consequently, these molecules showed 18- to 57-fold increased antiviral activities compared to the parent antibodies. Most importantly, one prototypic tetravalent CCR5 antibody had antiviral activity against virus strains resistant to the single parental antibodies. In summary, physical linkage of two CCR5 antibodies targeting different epitopes on the HIV coreceptor CCR5 resulted in tetravalent, bispecific antibodies with enhanced antiviral potency against wild-type and CCR5 antibody-resistant HIV-1 strains.
Evaluations of Shorter Exposures of Contact Lens Cleaning Solutions against Fusarium oxysporum Species Complex and Fusarium solani Species Complex To Simulate Inappropriate Usage
Authors: Ramani Rama , Chaturvedi Vishnu
Published: February 2011

An outbreak of
Fusarium
keratitis in contact lens users resulted in withdrawal of ReNu with MoistureLoc solution, although the exact cause of the outbreak remains enigmatic. We evaluated current and discontinued multipurpose cleaning solutions (MPSs; MoistureLoc, Equate, MultiPlus, and OptiFree Express) against plankton- and biofilm-derived cells of
Fusarium oxysporum
species complex (FOSC) and
F. solani
species complex (FSSC). The methods included a traditional assay based on CFU counts and a novel flow cytometry (FC) assay based on percent cell subpopulation (PCS) stained with two fluorochromes (Sytox Red and 5-chloromethylfluorescein diacetate). The tests were done with the respective manufacturers' recommended cleaning regimens (240 to 360 min) and under shorter exposures (15 to 60 min) to simulate inappropriate usage by the customers. FC assay measured PCS, which was available rapidly, in 5 to 7 h, whereas 24 to 48 h was needed for CFU counts, and there was good correlation between the two methods (
r
2
= 0.97). FC assays allowed identification of injured fungal cells, which are likely to be missed with growth assays. In general, a time- and inoculum-dependent survival pattern was seen for both FOSC and FSSC cells, and biofilm-derived cells were more resistant than plankton-derived cells. MultiPlus and Equate produced 100% sterilization of fungi even under shorter exposures. However, biofilm FOSC and FSSC cells survived for up to 4 h in MoistureLoc solution and up to 6 h in OptiFree Express solution under shorter exposure times. This finding was enigmatic, as OptiFree Express is not associated with any outbreak of
Fusarium
keratitis. This study provides additional support for possible roles that improper lens cleaning regimens and fungal biofilms could play as predisposing factors for
Fusarium
keratitis.
The Marine Sponge-Derived Polyketide Endoperoxide Plakortide F Acid Mediates Its Antifungal Activity by Interfering with Calcium Homeostasis
Authors: Xu Tao , Feng Qin , Jacob Melissa R. , Avula Bharathi , Mask Melanie M. , Baerson Scott R. , Tripathi Siddharth K. , Mohammed Rabab , Hamann Mark T. , Khan Ikhlas A. , Walker Larry A. , Clark Alice M. , Agarwal Ameeta K.
Published: February 2011

Plakortide F acid (PFA), a marine-derived polyketide endoperoxide, exhibits strong inhibitory activity against the opportunistic fungal pathogens
Candida albicans
,
Cryptococcus neoformans
, and
Aspergillus fumigatus
. In the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model organism
Saccharomyces cerevisiae
to investigate the mechanism of action of this compound. PFA elicited a transcriptome response indicative of a Ca
2+
imbalance, affecting the expression of genes known to be responsive to altered cellular calcium levels. Several additional lines of evidence obtained supported a role for Ca
2+
in PFA's activity. First, mutants lacking calcineurin and various Ca
2+
transporters, including pumps (Pmr1 and Pmc1) and channels (Cch1 and Mid1), showed increased sensitivity to PFA. In addition, the calcineurin inhibitors FK506 and cyclosporine strongly enhanced PFA activity in wild-type cells. Furthermore, PFA activated the transcription of a
lacZ
reporter gene driven by the calcineurin-dependent response element. Finally, elemental analysis indicated a significant increase in intracellular calcium levels in PFA-treated cells. Collectively, our results demonstrate that PFA mediates its antifungal activity by perturbing Ca
2+
homeostasis, thus representing a potentially novel mechanism distinct from that of currently used antifungal agents.
Benzimidazole Analogs Inhibit Human Herpesvirus 6
Authors: Prichard Mark N. , Frederick Samuel L. , Daily Shannon , Borysko Katherine Z. , Townsend Leroy B. , Drach John C. , Kern Earl R.
Published: February 2011

Several benzimidazole nucleoside analogs, including 1H-β-
d
-ribofuranosyl-2-bromo-5,6-dichlorobenzimidazole (BDCRB) and 1H-β-
l
-ribofuranosyl-2-isopropylamino-5,6-dichlorobenzimidazole (maribavir [MBV]), inhibit the replication of human cytomegalovirus. Neither analog inhibited the related betaherpesvirus human herpesvirus 6 (HHV-6). Additional analogs of these compounds were evaluated against both variants of HHV-6, and two
l
-analogs of BDCRB had good antiviral activity against HHV-6A, as well as more modest inhibition of HHV-6B replication.