bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of 4‐methylumbelliferone on cell‐free synthesis of hyaluronic acid
Authors: Nakamura Toshiya , Funahashi Masaru , Takagaki Keiichi , Munakata Hidekazu , Endo Masahiko , Tanaka Kanji , Saito Yoshiharu
Published: July 2007

Human skin fibroblasts were cultured in the presence of 0.5 mM 4‐methylumbelliferone for 12 h, and cell‐free synthesis of hyaluronic acid was performed using membrane‐rich fraction from the cells. The preincubation of the cells with 4‐methylumbelliferone reduced hyaluronic acid synthesis to 15% of that of non‐preincubated cells, although its chain length was not changed. On the other hand, without preincubation of the cells with 4‐methylumbelliferone, hyaluronic acid synthesis was not changed even when 4‐methylumbelliferone was added directly to the reaction mixture. These results suggest that 4‐methylumbelliferone represses the expression of hyaluronic acid synthase on the cell surface.
Adenosine deaminase activity in serum and pleural effusions of tuberculous and non‐tuberculous patients
Authors: Al‐Shammary F. J.
Published: July 2007

In a retrospective study Adenosine deaminase (ADA) was assayed in 86 serum samples and 12 pleural fluid samples of patients with pulmonary tuberculosis. Serum and pleural fluid ADA levels were also examined in a group of 38 non‐tuberculous patients with pleural effusion. Highly significant increases in both serum and pleural fluid ADA levels were noted in tuberculous patients when compared to both control enzyme cut‐off values and non‐tuberculous pleural effusion patients. Negative Ziehl‐Nielsen staining for acid fast bacilli and Purified Protein Derivative skin test results were obtained in 32.3% and 11.1% of the examined patients respectively. All these patients showed significantly elevated serum or pleural fluid ADA levels. It is hereby suggested that serum and pleural fluid ADA levels can in conjtmction with other tests, serve as a marker in patients of pulmonary tuberculosis.
The irradiation of hepatocytes with He‐Ne laser causes an increase of cytosolic free calcium concentration and an increase of cell membrane potential, correlated with it, both increases taking place in an oscillatory manner
Authors: Vacca R. A. , Moro L. , Petragallo V. A. , Greco M. , Fontana F. , Passarella S.
Published: July 2007

Isolated hepatocytes were irradiated with Helium‐Neon laser (fluence: 0.24 Joules x cm‐2, fluence rate: 12 mW x cm‐2 and changes of both cytosolic free Ca2+ concentration and cell membrane potential were checked by measuring fura‐2 and bis‐oxonol fluorescence respectively. Irradiation resulted in an enhancement in cytosolic free Ca2+ concentration that requires the presence of Ca2+ in the phase outside hepatocytes; consistently an increase in cell membrane potential was measured correlated with it. Interestingly, the rate of increase of both cytosolic free Ca2+ concentration and cell membrane potential shows special time dependent features similar to those peculiar of oscillatory processes.
Transfer of cholesterol from macrophages to lymphocytes in culture
Authors: de Bittencourt Paulo Homem , Curi Rui
Published: July 2007

A major feature of macrophage metabolism is its capacity to produce and export cholesterol. Several reports have shown that the manipulation of lymphocyte cholesterol content elicits important changes in lymphocyte proliferation. These findings lead to an inquiry as to whether macrophage‐derived cholesterol released into the lymphocyte surroundings may be transferred to the latter thus affecting lymphocyte function. In this study, cholesterol transfer from macrophages to lymphocytes was examined in vitro using rat cells in culture. The findings indicate that there may be a significant transfer of cholesterol from [4‐14C]cholesterol labeled resident peritoneal macrophages to mesenteric lymph node resting lymphocytes (up to 173.9±2.7 pmol/107 lymphocytes/107 macrophages when co‐cultivated for 48 h), in a lipoprotein‐dependent manner. This represents the mass transfer of ca. 17 nmoles of cholesterol molecules per 107 lymphocytes from 107 macrophages (calculated on the basis of specific radioactivity incorporated into macrophages after the pre‐labelling period), which suggests that macrophages are capable of replacing the whole lymphocyte cholesterol pool every 21 h. Moreover, an 111%‐increase in the total cholesterol content of lymphocytes was found after co‐cultivation with macrophages for 48 h. When compared to peritoneal cells, monocytes/macrophages obtained from circulating blood leukocytes presented a much higher cholesterol transfer capacity to lymphocytes (3.06±0.10 nmol/107 lymphocytes/107 macrophages co‐cultivated for 24h). Interestingly, inflammatory macrophages dramatically reduced their cholesterol transfer ability (by up to 91%, as compared to resident macrophages). Cholesterol transfer may involve a humoral influence, since it is not only observed when cells are co‐cultivated in a single‐well chamber system (cells in direct contact), but also in a two‐compartment system (where cells can communicate but not by direct contact). Co‐cultivation with macrophages decreased the basal incorporation of [2‐14C]thymidine into lymphocyte DNA and the addition of cholesterol to lymphocyte culture media also impaired the lymphocyte proliferative response to the mitogens concanavalin A (Con A) and bacterial lipopolysaccharide (LPS). The above results suggest that macrophages may transfer cholesterol to lymphocytes (from both lymph nodes and blood), thus regulating lymphocyte function by raising the intracellular cholesterol content and suppressing lymphocyte proliferative activity. If this is so, a modulatory role for the transfer of cholesterol in both physiological (e.g. immune response) and pathological conditions (e.g. atherosclerosis) may be postulated. This hypothesis is currently under investigation in our laboratory.
Menadione toxicity in Saccharomyces cerevisiae cells: Activation by conjugation with glutathione
Authors: Ządzinski Roland , Fortuniak Anna , Bartosz Grzegorz , Bilinski Tomasz , Grey Martin
Published: July 2007

Menadione (2‐methyl‐1,4‐naphthoquinone) has been used extensively as an oxidant stressor at the cellular level. However, the mechanism of cytotoxicity of this compound still remains controversial. This study deals with the role of intracellular glutathione in the resistance of the yeast Saccharomyces cerevisiae to menadione. Incubation with 0.5 mM menadione resulted in a decrease of total glutathione concentration in yeast cells, intracellular formation of menadione S‐glutathione conjugate and export of the conjugate from cells. GSH‐deficient mutants showed lower stimulation of superoxide and hydrogen peroxide production upon exposure to menadione and were more resistant to menadione than wild‐type isogenic strains. These results indicate that in yeast cells the formation of S‐glutathione conjugate is a major pathway of menadione metabolism and that this reaction leads to redox activation of menadione but permits its removal from the cells.
Heat stress affects the glucocorticoid receptor interaction with heat shock protein Hsp70 in the rat liver
Authors: Cvoro Aleksandra , Dundjerski Jadranka , Trajkovic Divna , Matic Gordana
Published: July 2007

The association of glucocorticoid hormones receptor (GR) with heat shock protein Hsp70 in the liver cytosol of rats exposed to 41°C whole body hyperthermic stress was examined by quantitative immunoblotting of the two proteins within immunopurified untransformed GR multiprotein complexes. The presence of Hsp70 in the rat liver GR heterocomplexes was confirmed, and 2‐fold increase in the Hsp70 relative to the steroid binding protein content within the complexes was recorded 2 and 12 h after the stress. This increase exceeded the stress‐induced elevation in the total cytoplasmic Hsp70 level, but could not be seen 24 h after the stress, when cytoplasmic Hsp70 returned to basal level. The results suggest that hyperthermic stress alters the composition of the rat liver untransformed GR heterocomplexes increasing the Hsp70 share.
Cys25‐nitrosylation inactivates papain
Authors: Venturini Giorgio , Fioravanti Emanuela , Colasanti Marco , Persichini Tiziana , Ascenzi Paolo
Published: July 2007

Nitric oxide (NO) may modulate the catalytic activity of cysteine proteases. In the present study, the inhibitory effect of NO, released by the NO‐donors (±)‐(E)‐4‐ethyl‐2‐[(E)‐hydroxyimino]‐5‐nitro‐3‐hexenamide and nitroprusside, on papain action is reported. Papain inactivation via NO‐mediated nitrosylation of the Cys25 catalytic residue represents a molecular model for cysteine protease inhibition.
Changes of nuclear membrane fluidity during rat liver regeneration
Authors: Tomassoni Maria‐Letizia , Albi Elisabetta , Magani Mariapia Viola
Published: July 2007

We have previously shown that the nuclear membrane fluidity is affected by lipid composition changes and that is very high, particularly in the hydrophobic core. The aim of this work is to study the modifications of nuclear membrane fluidity in relation to the cell cycle. Since compensatory hepatic growth is an informative and well characterised model for natural cell proliferation, the nuclear membrane fluidity, detected by two fluorescent probes, was studied at various regenerating times, ranging from 0 to 30 hours after partial hepatectomy. At 18 hours after partial hepatectomy the nuclear membrane fluidity increased and at 30 hours the higher values of hydrophobic core fluidity were observed. The behaviour of fluidity was related to the nuclear membrane neutral‐sphingomyelinase activity and, then, to the content of sphingomyelin. Therefore, the significant changes of the nuclear membrane fluidity and of the neutral‐sphingomyelinase activity found during rat liver regeneration suggested a their likely role in signal transduction pathways implying cell regeneration.
Oxidized Lipoproteins in Blood Plasma: Possible Marker of Atherosclerosis Progression
Authors: Moriel Patricia , Okawabata Fabio S. , Abdalla Dulcineia S. P.
Published: July 2007

Oxidized lipoproteins and antioxidants were detected during the course of hypercholesterolemia development in cholesterol‐fed rabbits. Lipid peroxides in blood plasma and very‐low‐, low‐, and high‐density lipoproteins (beta‐VLDL, LDL, and HDL) were increased during the course of hypercholesterolemia. The content of phospholipid peroxides increased in beta‐VLDL and LDL in parallel to that of cholesterol, whereas the amount of alpha‐tocopherol was decreased either in lipoproteins or blood plasma. Ascorbate and urate concentrations were also decreased. Lipid peroxides were positively correlated with volume and area of atherosclerotic lesions, suggesting a relation between the concentrations of lipid peroxides in blood plasma and the progression of atheromatous lesions.
Copper‐Dependent Oxidative Stress and Neurodegeneration
Authors: Rotilio G. , Carr` M. T. , Rossi L. , Ciriolo M. R.
Published: July 2007

Copper is an essential trace element, but its redox reactivity leads to risks of damage to cell and tissues. These are well exemplified by several forms of neurodegenerative diseases, either arising as inherited disorders of copper metabolism, such as Menkes' and Wilson's disease, or as conformational diseases such as Alzheimer's disease and prion diseases. This review will cover some aspects of the involvement of copper‐mediated oxidative stress in degenerative processes in the central nervous system, with special focus on the familial form of amyotrophic lateral sclerosis (FALS). Furthermore, a possible role of copper reactivity in inducing critical steps in the apoptotic pathways leading to neurodegeneration is envisaged.
Mitochondrial Production of Hydrogen Peroxide Regulation by Nitric Oxide and the Role of Ubisemiquinone
Authors: Boveris Alberto , Cadenas Enrique
Published: July 2007

Mitochondria are considered the major cellular site for hydrogen peroxide production, a process that is kinetically controlled by the availability of oxygen and nitric oxide to cytochrome oxidase and of ADP to F1‐ATPase. The multisite regulation of mi1 tochondrial respiration and energy‐transducing pathways support a critical regulatory role of mitochondrion in cell signaling pathways. The cellular steady‐state levels of hydrogen peroxide and the role of mitochondria in maintaining these levels are reviewed.
In Vitro Binding Analysis of Hepatitis B Virus preS‐derived Putative Helper T‐cell Epitopes to MHC Class II Molecules Using Stable HLA‐DRB1*0405/‐DRA*0101 Transfected Cells
Authors: Kim Jung‐hwan , Park Jung‐hyun , Lee Yun‐Jung , Cho Eun‐wie , Bae Yong‐soo , Kim Kil Lyong
Published: July 2007

In designing epitope‐based vaccines, the inclusion of a helper T‐lymphocyte (HTL) epitope is necessary to elicit both humoral and cellular immune responses. Whereas the preS region of the hepatitis B virus (HBV) surface antigen is well‐known to raise protective immunity, the epitopes for activating HTLs are poorly characterized. In an attempt to identify such epitopes, the HBV‐preS region was screened for peptide sequences with HLA‐DR4 binding motifs, and putative HTL candidate peptides were synthesized in a biotinylated form. Using L929 mouse fibroblasts stably transfected with HLA‐DRB1*0405 and HLA‐DRA*0101 cDNA, specific binding of the peptides was then detected using fluorescence‐conjugated streptavidin. The cell‐surface expression of HLA‐DR molecules on transfectants was confirmed by confocal microscopy, and quantitative analysis of candidate peptide binding was performed by fluorescence activated cell sorting. Among eight preS‐derived peptides, three candidate peptides?namely preS1(23‐33), preS1(62‐72), and preS1(76‐86)?showed good binding characteristics to HLA‐DR4 molecules, among which the preS1(23‐33) epitope was regarded as the most promising HTL epitope. Further studies with these candidate HTL stimulatory peptides will show their ability to activate the human immune system against HBV.
A shell element for finite strain analyses: hyperelastic material models
Authors: Toscano Rita G. , Dvorkin Eduardo N.
Published: July 2007

Purpose

This paper aims to develop a simple and efficient shell element for large strains hyper‐elastic analyses.

Design/methodology/approach

Based on the classical MITC4 shell element formulation a 3D shell element with finite strain kinematics is developed. The new quadrilateral shell element has five dof per node and two global dof to model the thickness stretching. The shell element is implemented for hyperelastic material models and the application of different hyperelastic constitutive relations is discussed.

Findings

The results obtained considering three of the hyperelastic material models available in the literature are quite different when the developed strains are relatively high; this indicates that, for analyzing actual engineering examples, experimental data should be used to decide on the most suitable constitutive relation.

Originality/value

The 3D version of the MITC4 element was developed.
Human capital value creation practices of software and service exporter firms in India
Authors: Murthy Vijaya , Abeysekera Indra
Published: July 2007

Purpose

The purpose of this study is to explore the human capital (HC) value creation practices of knowledge‐based software and service exporter industry in India.

Design/methodology/approach

The study used HC disclosure attributes as a tool to the contents of the annual reports for the year 2003‐2004, to evaluate the type and amount of HC disclosed by the software firms. The study also conducted semi‐structured interviews with the heads of human resources (HR) of 14 software firms to obtain a greater understanding of the similarities between reporting and managed HC practices.

Findings

The study identified most reported and least reported attributes of HC using content analysis and explained their reporting of value creation using interviews and resource‐based view. The findings suggest that the HC reporting practices were consistent with interview findings. The frequency of HC attributes reported followed the extent of the management's perception of HC value creation to the firm.

Research limitations/implications

The limitations of the study are: first, it is a cross‐sectional study; second, the findings may be applicable exclusively to the software and service industry in India and cannot be generalised to other industries in India or software industry in other countries; third, the assertions by the HR heads are assumed to faithfully reflect the firm's HC practices; fourth, the study assumes that annual reports are the primary documents available to public (stakeholders) requiring information on the firms.

Originality/value

This study provides an insight into the HC reporting practices of the nascent software and service exporter industry in India that is experiencing an economic boom that is positively influenced by the information technology software industry. This study throws light on the utilization of HC for value creation by the top software firms. This may help countries having tie‐up with Indian firms to understand the value creation process of these firms to sustain growth. The study would enable other software firms to understand HC reporting practices of the industry, and could use a framework that is similar to the framework used in this study.
Does cannabis use predict the first incidence of mood and anxiety disorders in the adult population?
Authors: Van Laar Margriet , Van Dorsselaer Saskia , Monshouwer Karin , De Graaf Ron
Published: July 2007

Aims  To investigate whether cannabis use predicted the first incidence of mood and anxiety disorders in adults during a 3‐year follow‐up period.

Design and participants  Data were derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a prospective study in the adult population of 18–64 years. The analysis was carried out on 3881 people who had no life‐time mood disorders and on 3854 people who had no life‐time anxiety disorders at baseline.

Measurements  Life‐time cannabis use and DSM‐III‐R mood and anxiety disorders, assessed with the Composite International Diagnostic Interview (CIDI).

Findings  After adjustment for strong confounders, any use of cannabis at baseline predicted a modest increase in the risk of a first major depression (odds ratio 1.62; 95% confidence interval 1.06–2.48) and a stronger increase in the risk of a first bipolar disorder (odds ratio 4.98; 95% confidence interval 1.80–13.81). The risk of ‘any mood disorder’ was elevated for weekly and almost daily users but not for less frequent use patterns. However, dose–response relationships were less clear for major depression and bipolar disorder separately. None of the associations between cannabis use and anxiety disorders remained significant after adjustment for confounders.

Conclusions  The associations between cannabis use and the first incidence of depression and bipolar disorder, which remained significant after adjustment for strong confounders, warrant research into the underlying mechanisms.
Importance of 5‐hydroxytryptamine receptors on intestinal afferents in the regulation of visceral sensitivity
Authors: Greenwood‐van Meerveld B.
Published: July 2007

Abstract  Serotonin (5‐HT) plays an important role as a signalling molecule in the gastrointestinal (GI) tract. The regulation of GI sensitivity via 5‐HT is mediated by specific 5‐HT receptor subytypes on intrinsic and extrinsic afferents. This review discusses visceral afferent hypersensitivity in irritable bowel syndrome (IBS) and the importance of 5HT3, 5HT4, and 5HT2B receptor‐mediated mechanisms in the regulation of visceral sensitivity.
No association of the ‐105 promoter polymorphism of the selenoprotein S encoding gene SEPS1 with cerebrovascular disease
Authors: Hyrenbach S. , Pezzini A. , Del Zotto E. , Giossi A. , Lichy C. , Kloss M. , Werner I. , Padovani A. , Brandt T. , Grond‐Ginsbach C.
Published: July 2007

A common pro‐inflammatory promoter variant of the selenoprotein S encoding gene (SEPS1) was studied in young stroke patients from Italy and Germany and in healthy control subjects. The ‐105A‐allele was found in 56 of 205 (27.3%) patients with ischemic stroke IS because of a spontaneous cervical artery dissection (CAD), and in 69 of 295 (23.4%) patients <50 years with IS of non‐CAD origin. The SEPS ‐105A promoter variant was detected in 87 of 393 healthy control subjects (22.1%) and in 11 of 55 CAD patients without IS (20%). The non‐significant differences of SEPS1 allele frequencies between disease groups and healthy controls suggest that the SEPS1 ‐105A allele is not a major‐risk factor for stroke.
Influence of residual milk‐clotting enzyme and proteolysis on melting properties of soft cheese
Authors: CANDIOTI M C , ALONSO M J , HYNES E
Published: July 2007

In this work, we assessed the influence of coagulant residual activity and primary proteolysis on Cremoso Argentino cheese melting properties. For that purpose, we made Cremoso soft cheeses using different amounts of coagulant, and also obtained samples in which milk‐clotting enzyme was inactivated. Primary proteolysis correlated with residual activity of coagulant in early stages of cheese ripening; however, it was similar in all cheeses after 30 days. The hydrolysis of caseins did not significantly affect the melting ability of the cheeses, expressed as the area increase after heating samples under standardized conditions. Samples with similar proximate composition showed some changes in meltability; those seemed related to pH evolution during ripening.
Tyrosine metabolism in pigment‐forming Yarrowia lipolytica strains isolated from English and European speciality mould‐ripened cheese exhibiting a brown discolouration defect
Authors: WILLIAMS ALAN G , WITHERS SUSAN E
Published: July 2007

Yarrowia lipolytica s4fd was isolated from a UK‐manufactured speciality mould‐ripened cheese as the causative micro‐organism of a brown surface discolouration spoilage defect. Comparative studies utilizing Y. lipolytica isolates indicated that inter‐strain variations in pigment accumulation were attributable to differences in tyrosine uptake and metabolism to homogentisic acid. The range and activity profiles of proteolytic enzymes involved in tyrosine release and turnover in isolates that differed in pigment formation were, however, similar. Homogentisic acid formation was affected by physiological parameters, and approaches that may be developed by the cheesemaker to prevent spoilage losses associated with the development of the brown discolouration defect are discussed.
Temporal Dynamics and Impact of Manure Storage on Antibiotic Resistance Patterns and Population Structure of
Escherichia coli
Isolates from a Commercial Swine Farm
Authors: Duriez Patrick , Topp Edward
Published: July 2007

Many confined-livestock farms store their wastes for several months prior to use as a fertilizer. Storing manure for extended periods could significantly bias the composition of enteric bacterial populations subsequently released into the environment. Here, we compared populations of
Escherichia coli
isolated from fresh feces and from the manure-holding tank (stored manure) of a commercial swine farm, each sampled monthly for 6 months. The 4,668 confirmed
E. coli
isolates were evaluated for resistance to amikacin, ampicillin, cephalothin, chloramphenicol, kanamycin, nalidixic acid, streptomycin, sulfamethoxazole, tetracycline, trimethoprim, and trimethoprim plus sulfamethoxazole. A subset of 1,687 isolates was fingerprinted by repetitive extragenic palindromic PCR (rep-PCR) with the BOXA1R primer to evaluate the diversity and the population structure of the collection. The population in the stored manure was generally more diverse than that in the fresh feces. Half of the genotypes detected in the stored manure were never detected in the fresh fecal material, and only 16% were detected only in the fresh feces. But the majority of the isolates (84%) were assigned to the 34% of genotypes shared between the two environments. The structure of the
E. coli
population showed important monthly variations both in the extent and distribution of the diversity of the observed genotypes. The frequency of detection of resistance to specific antibiotics was not significantly different between the two collections and varied importantly between monthly samples. Resistance to multiple antibiotics was much more temporally dynamic in the fresh feces than in the stored manure. There was no relationship between the distribution of rep-PCR fingerprints and the distribution of antibiotic resistance profiles, suggesting that specific antibiotic resistance determinants were dynamically distributed within the population.
NADP(H) Phosphatase Activities of Archaeal Inositol Monophosphatase and Eubacterial 3′-Phosphoadenosine 5′-Phosphate Phosphatase
Authors: Fukuda Chikako , Kawai Shigeyuki , Murata Kousaku
Published: July 2007

NADP(H) phosphatase has not been identified in eubacteria and eukaryotes. In archaea, MJ0917 of hyperthermophilic
Methanococcus jannaschii
is a fusion protein comprising NAD kinase and an inositol monophosphatase homologue that exhibits high NADP(H) phosphatase activity (S. Kawai, C. Fukuda, T. Mukai, and K. Murata, J. Biol. Chem. 280:39200-39207, 2005). In this study, we showed that the other archaeal inositol monophosphatases, MJ0109 of
M. jannaschii
and AF2372 of hyperthermophilic
Archaeoglobus fulgidus
, exhibit NADP(H) phosphatase activity in addition to the already-known inositol monophosphatase and fructose-1,6-bisphosphatase activities. Kinetic values for NADP
+
and NADPH of MJ0109 and AF2372 were comparable to those for inositol monophosphate and fructose-1,6-bisphosphate. This implies that the physiological role of the two enzymes is that of an NADP(H) phosphatase. Further, the two enzymes showed inositol polyphosphate 1-phosphatase activity but not 3′-phosphoadenosine 5′-phosphate phosphatase activity. The inositol polyphosphate 1-phosphatase activity of archaeal inositol monophosphatase was considered to be compatible with the similar tertiary structures of inositol monophosphatase, fructose-1,6-bisphosphatase, inositol polyphosphate 1-phosphatase, and 3′-phosphoadenosine 5′-phosphate phosphatase. Based on this fact, we found that 3′-phosphoadenosine 5′-phosphate phosphatase (CysQ) of
Escherichia coli
exhibited NADP(H) phosphatase and fructose-1,6-bisphosphatase activities, although inositol monophosphatase (SuhB) and fructose-1,6-bisphosphatase (Fbp) of
E. coli
did not exhibit any NADP(H) phosphatase activity. However, the kinetic values of CysQ and the known phenotype of the
cysQ
mutant indicated that CysQ functions physiologically as 3′-phosphoadenosine 5′-phosphate phosphatase rather than as NADP(H) phosphatase.
G-Protein Control of the Ribosome-Associated Stress Response Protein SpoT
Authors: Jiang Mengxi , Sullivan Susan M. , Wout Patrice K. , Maddock Janine R.
Published: July 2007

The bacterial response to stress is controlled by two proteins, RelA and SpoT. RelA generates the alarmone (p)ppGpp under amino acid starvation, whereas SpoT is responsible for (p)ppGpp hydrolysis and for synthesis of (p)ppGpp under a variety of cellular stress conditions. It is widely accepted that RelA is associated with translating ribosomes. The cellular location of SpoT, however, has been controversial. SpoT physically interacts with the ribosome-associated GTPase CgtA, and we show here that, under an optimized salt condition, SpoT is also associated with a pre-50S particle. Analysis ofspoTandcgtAmutants and strains overexpressing CgtA suggests that the ribosome associations of SpoT and CgtA are mutually independent. The steady-state level of (p)ppGpp is increased in acgtAmutant, but the accumulation of (p)ppGpp during amino acid starvation is not affected, providing strong evidence that CgtA regulates the (p)ppGpp level during exponential growth but not during the stringent response. We show that CgtA is not associated with pre-50S particles during amino acid starvation, indicating that under these conditions in which (p)ppGpp accumulates, CgtA is not bound either to the pre-50S particle or to SpoT. We propose that, in addition to its role as a 50S assembly factor, CgtA promotes SpoT (p)ppGpp degradation activity on the ribosome and that the loss of CgtA from the ribosome is necessary for maximal (p)ppGpp accumulation under stress conditions. Intriguingly, we found that in the absence ofspoTandrelA,cgtAis still an essential gene inEscherichia coli.
Control of DegP-Dependent Degradation of
c
-Type Cytochromes by Heme and the Cytochrome
c
Maturation System in
Escherichia coli
Authors: Gao Tao , O'Brian Mark R.
Published: July 2007

c
-type cytochromes are located partially or completely in the periplasm of gram-negative bacteria, and the heme prosthetic group is covalently bound to the protein. The cytochrome
c
maturation (Ccm) multiprotein system is required for transport of heme to the periplasm and its covalent linkage to the peptide. Other cytochromes and hemoglobins contain a noncovalently bound heme and do not require accessory proteins for assembly. Here we show that
Bradyrhizobium japonicum
cytochrome
c
550
polypeptide accumulation in
Escherichia coli
was heme dependent, with very low levels found in heme-deficient cells. However, apoproteins of the periplasmic
E. coli
cytochrome
b
562
or the cytosolic
Vitreoscilla
hemoglobin (Vhb) accumulated independently of the heme status. Mutation of the heme-binding cysteines of cytochrome
c
550
or the absence of Ccm also resulted in a low apoprotein level. These levels were restored in a
degP
mutant strain, showing that apocytochrome
c
550
is degraded by the periplasmic protease DegP. Introduction of the cytochrome
c
heme-binding motif CXXCH into cytochrome
b
562
(
c-b
562
) resulted in a
c
-type cytochrome covalently bound to heme in a Ccm-dependent manner. This variant polypeptide was stable in heme-deficient cells but was degraded by DegP in the absence of Ccm. Furthermore, a Vhb variant containing a periplasmic signal peptide and a CXXCH motif did not form a
c
-type cytochrome, but accumulation was Ccm dependent nonetheless. The data show that the cytochrome
c
heme-binding motif is an instability element and that stabilization by Ccm does not require ligation of the heme moiety to the protein.
Nitric oxide-dependent inhibition of alveolar fluid clearance in hydrostatic lung edema
Authors: Kaestle Stephanie M. , Reich Christian A. , Yin Ning , Habazettl Helmut , Weimann Jorg , Kuebler Wolfgang M.
Published: July 2007

Formation of cardiogenic pulmonary edema in acute left heart failure is traditionally attributed to increased fluid filtration from pulmonary capillaries and subsequent alveolar flooding. Here, we demonstrate that hydrostatic edema formation at moderately elevated vascular pressures is predominantly caused by an inhibition of alveolar fluid reabsorption, which is mediated by endothelial-derived nitric oxide (NO). In isolated rat lungs, we quantified fluid fluxes into and out of the alveolar space and endothelial NO production by a two-compartmental double-indicator dilution technique and in situ fluorescence imaging, respectively. Elevation of hydrostatic pressure induced Ca2+-dependent endothelial NO production and caused a net fluid shift into the alveolar space, which was predominantly attributable to impaired fluid reabsorption. Inhibition of NO production or soluble guanylate cyclase reconstituted alveolar fluid reabsorption, whereas fluid clearance was blocked by exogenous NO donors or cGMP analogs. In isolated mouse lungs, hydrostatic edema formation was attenuated by NO synthase inhibition. Similarly, edema formation was decreased in isolated mouse lungs of endothelial NO synthase-deficient mice. Chronic heart failure results in endothelial dysfunction and preservation of alveolar fluid reabsorption. These findings identify impaired alveolar fluid clearance as an important mechanism in the pathogenesis of hydrostatic lung edema. This effect is mediated by endothelial-derived NO acting as an intercompartmental signaling molecule at the alveolo-capillary barrier.
Low specificity of metal ion binding in the metal ion core of a folded RNA
Authors: Travers Kevin J. , Boyd Nathan , Herschlag Daniel
Published: July 2007

The structure and activity of nucleic acids depend on their interactions with metal ions. Fundamental to these interactions is the degree of specificity observed between the metal ions and nucleic acids, and a complete description of nucleic acid folding requires that we understand the nature of the interactions with metal ions, including specificity. The prior demonstration that high concentrations of monovalent cations prevent nonspecific association of divalent ions with nucleic acids provides a novel and powerful means to examine site-specific metal ion binding isolated from complicating effects of the ion atmosphere. Using these high monovalent cation solution conditions we have monitored the affinity of a series of divalent metal ions for two site-specific metal ion binding sites in the P4-P6 domain of the Tetrahymena group I intron ribozyme. The metal ion core of this highly structured RNA binds two divalent metal ions under these conditions. Despite multiple metal ion–RNA interactions observed in the X-ray crystallographic structure of P4-P6 RNA at the metal ion binding sites, these sites exhibit low specificity among Mn2+, Mg2+, Ca2+, Ni2+, and Zn2+. Nevertheless, the largest divalent metal ions tested, Sr2+ and Ba2+, were excluded from binding, exhibiting affinities at least two orders of magnitude weaker than observed for the other metal ions. Thus, a picture emerges of two metal ion binding sites, each with a high tolerance for metal ions with different properties but also with limits to accommodation. These limits presumably arise from steric or electrostatic features of the metal ion binding sites.
Claims provisions in liability insurance
Authors: Lemaire Jean
Published: July 2007

The settlement delay for very large claims in liability insurance may extend to quite a few years; a delay often years in automobile third‐party liability is by no means an exception. The companies consequently have to set aside huge amounts as provisions for outstanding claims. As the total provision may attain 100 times the underwriting profit, an underestimation of this provision of a few per cent could mean short‐term bankruptcy for the company. A precise forecast of those outstanding liabilities is therefore of crucial importance

Owing to the special nature of the information set (a triangular array of cumulative payments, called the‘run‐off triangle’), actuaries have in the past neglected the time series analysis approach and devised their own forecasting models. Those methods are reviewed, and illustrated by a real‐life example. Two new autoregressive methods are proposed.
The implementation of forecasting models
Authors: Schultz Randall L.
Published: July 2007

The use of forecasting models can help managers make better decisions, a fact that motivates this study. Findings from research on the implementation of operations research/management science are generalized to include forecasting models. The similarity between forecasting and other models allows conclusions to be drawn about managing forecasting model implementation: these include better management support, closer links to management performance, improved user–preparer relationships, more goal congruence, minimized perception of change and an appropriate configuration of the forecasting system to user needs, style, resources and environment.
Strategic issues in development management: Learning from successful experience. Part I
Authors: Conyers Diana , Kaul Mohan
Published: July 2007

This paper draws general conclusions from a set of case‐studies presented at two Round Tables organized by the Commonwealth Secretariat. The paper is in two Parts. Part I, published here, deals with the choice of criteria for determining the success of local development initiatives. The approach adopted at the two Round Tables was judgemental. However, an attempt is made to measure ‘success’ more systematically by defining development and classifying the indicators that might be used to measure the achievement of such development as quantifiable, partly quantifiable and qualitative. A set of hypotheses concerning the factors contributing to the success of local development projects was put forward at the Warwick meeting and amended in Livingstone. Part I of the paper classifies the factors contributing to success into four groups: the project environment, the basic character of the project, the mode of project initiation, and project organization and management. Three environmental factors are emphasized: the political environment, local leadership and the history of self‐reliance. Three basic characteristics of a project are of particular importance: the level of beneficiary involvement, the use made of local resources, and the prevailing ‘organizational culture’. Two aspects of project initiation are particularly important: the source of a project and its scale. Five major organizational factors are stressed: the clarity of project goals; flexibility and responsiveness to needs; autonomy and accountability; a ‘learning process’ approach to project planning and management; and human resource development. Part II will discuss the broader implications of these factors in the local, national and international contexts.
Understanding administrative bottlenecks
Authors: Werlin Herbert
Published: July 2007

While the administrative bottlenecks presented in this Special Issue appear obvious, perceptions of them are confused with unanswerable questions of organization, policy, procedure, and technology. This leads to contradictory conclusions and the so‐called ‘mysteries of development’. To separate out what we can generalize about from what we cannot, a ‘political software’ approach is suggested, using the common sense steps that a serious, enlightened, and experienced businessperson might take in facilitating a development project. Combining these steps or requirements into ‘the theory of political elasticity’, we can see why violations of them lead to the bottlenecks illustrated in this issue. While reform is difficult, the effort must be made, encouraged by examples of success. The World Bank can play a useful role, if it can insist and build upon the borrower's commitment to reform and use a learning process approach.
Monitoring and evaluating (M&E): The South Asian experience
Authors: Ahmed Viqar , Bamberger Michael
Published: July 2007

According to a 1987 monitoring and evaluation (M&E) conference in Pakistan, South Asian M&E efforts have been undermined by organizational confusion, overcentralization, neglect of evaluation, weakness of data, and inadequate training, among other problems. Studies from India, Pakistan, and Nepal, among other South Asian countries, indicate the impact of these problems. In reducing the problems, efforts should be made to make the collection and use of M&E data less threatening, more practical, and more relevant to the intended beneficiaries of development projects.

This article summarizes material presented in Ahmed, V. and Bamberger, M. (1989). Monitoring and Evaluating Development Projects: the South Asian Experience. The World Bank ED1 Seminar Series, Washington D.C.
Environment and development: Concepts and practices in transition
Authors: Atkinson Adrian
Published: July 2007

This article starts by sketching the shape of the institutions and mechanisms which currently aim to protect the environment in developing countries. The form these have taken is largely based upon the environmental institutions created in the United States in the early 1970s, under the influence of the outburst of environmental concern at that time. The sudden reemergence of environmental concern at the top of the political agenda in the 1980s is attributable in significant measure to the ‘Green Movement’, that has evolved out of the concerns originally expressed in the early 1970s. The new institutions and mechanisms have, however, failed to check environmental deterioration in many developing countries; it is necessary to focus on the macroframework determining development priorities and practices if environmental problems are to be adequately addressed. The root of the problem is not merely institutional, or even macroeconomic, but is primarily cultural, stemming more specifically from the imposition of European cultural values. The environmental crisis is not restricted to developing countries and is unlikely to be solved without considerably more far‐reaching initiatives than we have seen so far. According to the literature of the Green Movement, the process of the ‘greening of development’ is far from completed in the creation of current environmental agencies and management mechanisms.
Civil service reform and retraining in transitional economies: Strategic issues and options
Authors: Collins Paul
Published: July 2007

Centrally planned and erstwhile centrally‐planned economies in Africa, Asia, Europe and Latin America are variously reforming their systems of production and exchange, sometimes in response to a breakdown in or declining performance of existing models and sometimes in consequence of the need to meet the challenges of a changing global economic environment. The developments that are taking place pose great challenges for governments in managing the process of transition as well as for donors in supporting the bold endeavours of the former. State institutions are also undergoing change, usually as a consequence of the economic reforms underway. This article reviews the experience of Eastern Europe, CIS and selected countries in other regions in three critical areas: policy making capacities and coordination, civil service legislation and reform and civil service training and retraining. Lessons are drawn from international technical cooperation projects being undertaken by both bilateral and multilateral donors in a variety of national contexts.
Institution‐building issues in South Africa
Authors: Horwitz Frank
Published: July 2007

This article discusses structural and labour‐market factors associated with institution building in South Africa. It pays particular attention to the role of management development in institution building in the public sector. Two case studies that address the question of organizational restructuring following moves towards commercialization of some public sector organizations are discussed.
Managing organizations in the third world: A case study of management control in a Bangladeshi jute mill
Authors: Hoque Zahirul , Siddiquee Noore Alam , Hopper Trevor
Published: July 2007

This article reports on a study of the operation of management control systems in a large nationalized jute mill of Bangladesh. The study seeks to describe how ‘control’ operated in practice and to explain why the systems of control worked in these ways. Investigations revealed a number of significant factors. First, the organization operated in both competitive and regulated environments; it had little authority over its operational activities and, head office and the sponsoring ministry were prominent in organizational planning and control. Second, the accounting system in the mill was mainly a response to external legitimacy (e.g. stewardship and tax matters). Third, although budgeting was perceived as part of the formal structure of control, it was not a dominant mode of control in the organization; the budgeting system was created to comply with head office and state requirements. Fourthly, the mill managers used a variety of social/informal control and mechanisms to cope with the complexity and uncertainty around the mill's operations. This study reinforces the conclusions of other research claiming that the wider social, economic, political and institutional contexts govern the ways management control operates in an organization.
Financing growth in the 1990s: New challenges for OECS countries
Authors: Simmonds Keith C.
Published: July 2007

This article argues that the world as we know it is becoming increasingly integrated and that the traditional providers of foreign assistance for infrastructure and other purposes, are about to increase the demand that poorer nations like the OECS countries must do more for themselves during the process of social development. The article admits that poorer countries like the OECS have developed revenue raising structures that facilitate indigenous development but the post‐Cold War reality intensifies the need for countries like the OECS to do more for themselves than ever before. The reasons for this occurrence have been stated largely as being attributed to financial, economic, attitudinal changes in major industrial countries, particularly in North America. These changes suggest difficult limes for industrial countries in the future and are likely to have serious impacts on countries like the Organization of Eastern Caribbean States (OECS).

The article offers a specific approach to dealing with this anticipated demand from donor countries to do more for themselves. The author advocates the following: (1) expand the existing revenue structure of the OECS countries to include specific revenue instruments to finance new growth and development in these countries; (2) broaden the concept and practice of ‘pay‐as‐you‐go’ to ‘pay‐as‐you‐grow;’ (3) require new growth to pay its own way or at a minimum, to shoulder a large proportion of the cost; (4) let those who primarily benefit from new growth pay for it. ‘Impact’ or ‘development’ fees have been suggested to be a new method of financing growth, particularly in countries that are experiencing new levels of growth. The author argues that this method will not be unusual to developers‐foreign investors from North America, or OECS nationals who may be returning temporarily or otherwise to their home country. This discussion on pay‐as‐you‐grow, it is hoped, will contribute to the growing literature on Caribbean public finance.
Civil service reform in Uganda: Lessons learned
Authors: Langseth Petter
Published: July 2007

This article presents the Civil Service Reform Programme (CSRP) in Uganda. It outlines the context in which the CSRP is being implemented and establishes the link between the CSRP and other reform programmes, particularly constitutional decentralization, liberalization/privatization and army demobilization. It also analyses the progress made so far, given certain obstacles, and attempts to assess and make some suggestions for the road ahead. The issues of civil service reform go beyond addressing the need for pay reform and improving organizational structure. While these are important pieces of the puzzle, they cannot stand alone. Issues of greater participation, transparency and accountability in decision making—all of which strangthen democratization—are also at stake. The aim of these reforms is to enable the state to function more rationally and effectively, as the duties it performs—as well as the country's needs—become more complex and varied. The overarching theme is to develop the state's own capacity in order to create sustainable reforms in the quest for long‐term development. The close of the cold war has brought many changes. In recent years, for example, the international donor community has paid increasing attention to reform issues. It has called on recipient governments to participate in the design and implementation of these programmes. In recipient countries, the movement toward decentralization, privatization and commercialization of many government functions has increased the range of opportunities available to citizens. It has also brought demands for greater responsiveness on the part of the government and parastatal agencies. Moreover, in an era of dwindling aid budgets, donors are now seeking better value for their money, and they are less willing to excuse widespread graft and corruption on geopolitical grounds.