bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Wild Hosts ofSweet potato feathery mottle virusShow Spatial Differences in Virus Incidence and Virus-Like Diseases in Uganda
Authors: Tugume A. K. , Mukasa S. B. , Valkonen J. P. T.
Published: May 2008

Sweet potato feathery mottle virus (SPFMV, genus Potyvirus) is globally the most common pathogen of sweetpotato. An East African strain of SPFMV incites the severe ‘sweetpotato virus disease’ in plants co-infected with Sweet potato chlorotic stunt virus and threatens subsistence sweetpotato production in East Africa; however, little is known about its natural hosts and ecology. In all, 2,864 wild plants growing in sweetpotato fields or in their close proximity in Uganda were observed for virus-like symptoms and tested for SPFMV in two surveys (2004 and 2007). SPFMV was detected at different incidence in 22 Ipomoea spp., Hewittia sublobata, and Lepistemon owariensis, of which 19 species are new hosts for SPFMV. Among the SPFMV-positive plants, ≈60% displayed virus-like symptoms. Although SPFMV incidence was similar in annual and perennial species, virus-like diseases were more common in annuals than perennials. Virus-like diseases and SPFMV were more common in the eastern agroecological zone than the western, central, and northern zones, which contrasted with known incidence of SPFMV in sweetpotato crops. The data on a large number of new natural hosts of SPFMV detected in this study provide novel insights into the ecology of SPFMV in East Africa.
A Test of Taxonomic Predictivity: Resistance to Early Blight in Wild Relatives of Cultivated Potato
Authors: Jansky S. H. , Simon R. , Spooner D. M.
Published: May 2008

Host plant resistance offers an attractive method of control for early blight (caused by the foliar fungus Alternaria solani), a widespread disease that appears annually in potato crops worldwide. We tested the assumed ability of taxonomy to predict the presence of early blight resistance genes in wild Solanum species for which resistance was observed in related species. We also tested associations to ploidy, crossing group, breeding system, and geography. As in a prior study of Sclerotinia sclerotiorum (white mold) resistance, tremendous variation for resistance to early blight was found to occur within and among species. There was no discernable relationship between the distribution of resistant phenotypes and taxonomic series (based on an intuitive interpretation of morphological data), clade (based on a cladistic analysis of plastid DNA data), ploidy, breeding system, geographic distance, or climate parameters. Species and individual accessions with high proportions of early blight resistant plants were identified, but high levels of inter- and intra-accession variability were observed. Consequently, the designation of species or accessions as resistant or susceptible must take this variation into account. This study calls into question the assumption that taxonomic or geographic data can be used to predict sources of early blight resistance in wild Solanum species.
Characterization of Mutations in the Iron-Sulphur Subunit of Succinate Dehydrogenase Correlating with Boscalid Resistance in Alternaria alternata from California Pistachio
Authors: Avenot H. F. , Sellam A. , Karaoglanidis G. , Michailides T. J.
Published: May 2008

Thirty-eight isolates of Alternaria alternata from pistachio orchards with a history of Pristine (pyraclostrobin + boscalid) applications and displaying high levels of resistance to boscalid fungicide (mean EC50 values >500 μg/ml) were identified following mycelial growth tests. A cross-resistance study revealed that the same isolates were also resistant to carboxin, a known inhibitor of succinate dehydrogenase (Sdh). To determine the genetic basis of boscalid resistance in A. alternata the entire iron sulphur gene (AaSdhB) was isolated from a fungicide-sensitive isolate. The deduced amino-acid sequence showed high similarity with iron sulphur proteins (Ip) from other organisms. Comparison of AaSdhB full sequences from sensitive and resistant isolates revealed that a highly conserved histidine residue (codon CAC in sensitive isolates) was converted to either tyrosine (codon TAC, type I mutants) or arginine (codon CGC, type II mutants) at position 277. In other fungal species this residue is involved in carboxamide resistance. In this study, 10 and 5 mutants were of type I and type II respectively, while 23 other resistant isolates (type III mutants) had no mutation in the histidine codon. The point mutation detected in type I mutants was used to design a pair of allele-specific polymerase chain reaction (PCR) primers to facilitate rapid detection. A PCR-restriction fragment length polymorphism (RFLP) assay in which amplified gene fragments were digested with AciI was successfully employed for the diagnosis of type II mutants. The relevance of these modifications in A. alternata AaSdhB sequence in conferring boscalid resistance is discussed.
Mapping global sensitivity of cellular network dynamics: sensitivity heat maps and a global summation law
Authors: Rand D.A
Published: May 2008

The dynamical systems arising from gene regulatory, signalling and metabolic networks are strongly nonlinear, have high-dimensional state spaces and depend on large numbers of parameters. Understanding the relation between the structure and the function for such systems is a considerable challenge. We need tools to identify key points of regulation, illuminate such issues as robustness and control and aid in the design of experiments. Here, I tackle this by developing new techniques for sensitivity analysis. In particular, I show how to globally analyse the sensitivity of a complex system by means of two new graphical objects: the sensitivity heat map and the parameter sensitivity spectrum. The approach to sensitivity analysis is global in the sense that it studies the variation in the whole of the model's solution rather than focusing on output variables one at a time, as in classical sensitivity analysis. This viewpoint relies on the discovery of local geometric rigidity for such systems, the mathematical insight that makes a practicable approach to such problems feasible for highly complex systems. In addition, we demonstrate a new summation theorem that substantially generalizes previous results for oscillatory and other dynamical phenomena. This theorem can be interpreted as a mathematical law stating the need for a balance between fragility and robustness in such systems.
Kindlin-2 controls bidirectional signaling of integrins
Authors: Montanez Eloi , Ussar Siegfried , Schifferer Martina , Bösl Michael , Zent Roy , Moser Markus , Fässler Reinhard
Published: May 2008

Control of integrin activation is required for cell adhesion and ligand-induced signaling. Here we report that loss of the focal adhesion protein Kindlin-2 in mice results in peri-implantation lethality caused by severe detachment of the endoderm and epiblast from the basement membrane. We found that Kindlin-2-deficient cells were unable to activate their integrins and that Kindlin-2 is required for talin-induced integrin activation. Furthermore, we demonstrate that Kindlin-2 is required for integrin outside-in signaling to enable firm adhesion and spreading. Our findings provide evidence that Kindlin-2 is a novel and essential element of bidirectional integrin signaling.
Cross-species de novo identification of cis-regulatory modules with GibbsModule: Application to gene regulation in embryonic stem cells
Authors: Xie Dan , Cai Jun , Chia Na-Yu , Ng Huck H. , Zhong Sheng
Published: May 2008

We introduce the GibbsModule algorithm for de novo detection of cis-regulatory motifs and modules in eukaryote genomes. GibbsModule models the coexpressed genes within one species as sharing a core cis-regulatory motif and each homologous gene group as sharing a homologous cis-regulatory module (CRM), characterized by a similar composition of motifs. Without using a predetermined alignment result, GibbsModule iteratively updates the core motif shared by coexpressed genes and traces the homologous CRMs that contain the core motif. GibbsModule achieved substantial improvements in both precision and recall as compared with peer algorithms on a number of synthetic and real data sets. Applying GibbsModule to analyze the binding regions of the Krüppel-like factor (KLF) transcription factor in embryonic stem cells (ESCs), we discovered a motif that differs from a previously published KLF motif identified by a SELEX experiment, but the new motif is consistent with mutagenesis analysis. The SOX2 motif was found to be a collaborating motif to the KLF motif in ESCs. We used quantitative chromatin immunoprecipitation (ChIP) analysis to test whether GibbsModule could distinguish functional and nonfunctional binding sites. All seven tested binding sites in GibbsModule-predicted CRMs had higher ChIP signals as compared with the other seven tested binding sites located outside of predicted CRMs. GibbsModule is available at http://biocomp.bioen.uiuc.edu/GibbsModule.
The use of molecular markers of bone turnover in the management of patients with metastatic bone disease
Authors: Seibel Markus J.
Published: May 2008

Biochemical markers of bone turnover are widely used in clinical practice. These indices have been shown to be associated with the occurrence, prognosis and therapeutic response of malignant bone lesions. For example, markers of bone resorption are often elevated in patients with established bone metastases and while this may point to a role of these markers in the diagnostic workup of cancer patients, the available evidence does not permit any final conclusions as to the accuracy and validity of the presently used markers in the early diagnosis of bone metastases. Many bone turnover markers appear to respond to antiresorptive and antineoplastic therapies, and recent evidence from prospective trials suggests that the aim of bisphosphonate therapy should be to normalize rates of bone remodelling to optimize therapeutic and prognostic outcomes. However, it remains unknown whether the use of bone markers in the routine clinical setting has any defined beneficial effects on overall outcome in cancer patients. Clearly, bone turnover markers have insufficient diagnostic or prognostic value to be used in isolation; however, the combination of these markers with other diagnostic techniques may improve clinical assessment of patients with bone‐seeking cancers. This article reviews the available evidence (as of August 2007) on the clinical use of bone turnover markers in the management of patients with metastatic bone disease.
Prevalence of metabolic syndrome (MS) in children and adolescents with varying degrees of obesity
Authors: Calcaterra V. , Klersy C. , Muratori T. , Telli S. , Caramagna C. , Scaglia F. , Cisternino M. , Larizza D.
Published: May 2008

Objective  Childhood obesity is increasingly common and is associated with health problems; in particular, obesity plays a central role in the metabolic syndrome (MS). We estimated the prevalence of MS in Caucasian children and adolescents with varying degrees of obesity.

Patients and methods  We studied 191 obese [body mass index (BMI) > 97th percentile] children and adolescents. Obesity was stratified on the basis of a threshold BMI z‐score and subjects were classified as moderately (z‐score 2–2·5) or severely obese (z‐score > 2·5). Seventy‐six, nonobese subjects were recruited into a comparison group. Thirty‐one of them were of normal weight (BMI < 75th percentile) and 45 overweight (BMI 75th–97th percentile).

Patients were classified as having MS if they met three or more of the following criteria for age and sex: BMI > 97th percentile, triglyceride levels > 95th percentile, high density lipoprotein (HDL) cholesterol level < 5th percentile, systolic or diastolic blood pressure > 95th percentile and impaired glucose tolerance (blood glucose level: 7·8–11·1 mmol/l at 2 h). Insulin resistance was calculated using the homeostasis model assessment for insulin resistance (HOMA‐IR) and impaired insulin sensitivity was defined as a HOMA‐IR ≥ 2·5 in prepubertal patients and HOMA‐IR > 4 in pubertal subjects.

Results  The overall prevalence of MS was 13·9% and was present in 12·0% of moderately obese and 31·1% of severely obese subjects; no overweight or normal weight subjects met the criteria for MS. The rate of the MS increased progressively with increasing BMI categories (P < 0·001). Severely obese patients had a threefold increased risk with respect to moderately obese patients.

Conclusions  The prevalence of the MS is higher in obese as opposed to nonobese subjects and increases with severity of obesity.
Differential responses of circulating amylin to high‐fat vs. high‐carbohydrate meal in healthy men
Authors: Eller Lindsay K. , Ainslie Philip N. , Poulin Marc J. , Reimer Raylene A.
Published: May 2008

Objective  The success of an amylin analogue in weight loss trials has generated interest in amylin as a physiological satiety signal. Little is known about how plasma amylin responds to macronutrients. This study examined the effects of a high‐carbohydrate meal (CHO), a high‐fat meal (FAT) or a continued fast (FAST) on amylin concentrations and correlations among other satiety hormones and measures of appetite.

Design/patients  In a randomized, crossover design, 10 healthy males consumed a meal high in carbohydrate or fat or continued fasted.

Measurements  Blood samples and subjective hunger scores were obtained at baseline and 30, 90 and 210 min postprandial.

Results  After CHO, amylin, insulin and C‐peptide were greater and des‐acyl ghrelin lower compared to FAT (P < 0·001). Area under the curve (AUC) was greater for amylin and insulin and lower for des‐acyl ghrelin following CHO. Subjective satiety and fullness were higher for CHO and FAT than FAST at 30 and 90 min but only for CHO at 210 min (P < 0·01). Hunger and desire to eat were lower for CHO and FAT than FAST at 30 and 90 min but only for CHO at 210 min (P < 0·005). Amylin was negatively correlated to hunger, desire to eat, and nausea and positively related to satiety and insulin. Des‐acyl ghrelin was negatively associated with C‐peptide, insulin and GLP‐1 and satiety.

Conclusions  CHO enhances amylin and suppresses des‐acyl ghrelin to a greater extent than FAT in healthy men. The mechanisms responsible for these changes and their implications in the physiology of satiety remain to be elucidated.
Asymmetrical thermal constraints on the parapatric species boundaries of two widespread generalist butterflies
Authors: MERCADER R. J. , SCRIBER J. M.
Published: May 2008

Abstract 1. The sibling species Papilio glaucus and Papilio canadensis meet in a narrow hybrid zone believed to be maintained by temperature thresholds acting independently on both species. The present study tests if this assertion is true for the cold‐adapted species, P. canadensis, which is presumed to be limited by the effect of high temperatures in late summer and/or autumn on pupal survival.

2. Three experiments were conducted examining the effects of: (i) short periods of high temperature stress in autumn, (ii) prolonged warm temperatures in autumn, and (iii) temperatures simulating warmer winters/longer springs upon the survival of P. canadensis and P. glaucus.

3. Results indicated that short periods of high temperatures did not induce the high mortality rates required to be the key factor limiting the range of P. canadensis. However, P. canadensis did exhibit a considerably lower tolerance to high temperature extremes, prolonged warm temperatures in autumn, and conditions simulating shorter/warmer winters than P. glaucus.

4. Differences in temperature tolerance throughout the pupal stage are likely to be a significant factor in maintaining the southern range limit of P. canadensis. Further warming as may occur during climate change, particularly in winter and spring, will likely affect the dynamics of southerly populations of P. canadensis.
Study comparing the double kissing (DK) crush with classical crush for the treatment of coronary bifurcation lesions: the DKCRUSH‐1 Bifurcation Study with drug‐eluting stents
Authors: Chen S. L. , Zhang J. J. , Ye F. , Chen Y. D. , Patel T. , Kawajiri K. , Lee M. , Kwan T. W. , Mintz G. , Tan H. C.
Published: May 2008

Background  Classical crush has a lower rate of final kissing balloon inflation (FKBI) immediately after percutaneous coronary intervention (PCI). The double kissing (DK) crush technique has the potential to increase the FKBI rate, and no prospective studies on the comparison of classical with DK crush techniques have been reported.

Materials and methods  Three hundred and eleven patients with true bifurcation lesions were randomly divided into classical (n = 156) and DK crush (n = 155) groups. Clinical and angiographic details at follow‐up at 8 months were indexed. The primary end point was major adverse cardiac events (MACE) including myocardial infarction, cardiac death and target lesion revascularization (TLR) at 8 months.

Results  FKBI was 76% in the classical crush group and 100% in the DK group (P < 0·001). The incidence of stent thrombosis was 3·2% in the classical crush group (5·1% in without‐ and 1·7% in with‐FKBI) and 1·3% in the DK crush group. Cumulative 8 month MACE was 24·4% in the classical crush group and 11·4% in the DK crush group (P = 0·02). The TLR‐free survival rate was 75·4% in the classical crush group and 89·5% in the DK crush group (P = 0·002).

Conclusions  DK crush technique has the potential of increasing FKBI rate and reducing stent thrombosis, with a further reduction of TLR and cumulative MACE rate at 8 months.
Prevention of colonic fibrosis byBoswelliaandScutellariaextracts in rats with colitis induced by 2,4,5‐trinitrobenzene sulphonic acid
Authors: Latella G. , Sferra R. , Vetuschi A. , Zanninelli G. , D’Angelo A. , Catitti V. , Caprilli R. , Gaudio E.
Published: May 2008

Background Currently, no effective preventive measures or medical therapies are available for intestinal fibrosis and, thus, surgery remains the only available strategy in the management of fibrostenotic enteropathies, especially Crohn's disease. The aim of this study was to evaluate the efficacy of a combined therapy of anti‐inflammatoryBoswelliaand antifibroticScutellariaextracts on the development of colonic fibrosis in rats.

Materials and methods Chronic colonic inflammation‐associated fibrosis was induced in rats by intracolonic administration of 2,4,5‐trinitrobenzene sulphonic acid (TNBS). Sixty‐four healthy male Sprague‐Dawley rats were assigned to five groups: 8 controls, 14 TNBS, 14 TNBS orally treated withBoswelliaextracts (50 mg kg−1 day−1), 14 TNBS orally treated withScutellariaextracts (150 mg kg−1 day−1), and 14 TNBS orally treated with bothBoswellia(50 mg kg−1 day−1) andScutellariaextracts (150 mg kg−1 day−1). The colon was removed after 21 days of treatment and assessed by macroscopic, histological, morphometric and immunohistochemical analyses. For immunohistochemical analysis, alpha‐smooth muscle actin (α‐SMA), collagen types I–III, connective tissue growth factor (CTGF), transforming growth factor‐beta1 (TGF‐β1), Smad3, Smad7 and CD3 antibodies were used.

Results Combined oral administration ofBoswelliaandScutellariasignificantly improved the course and macroscopic findings of TNBS‐induced chronic colitis assessed by disease activity index, colon weight, length, adhesions, strictures, dilatation, thickness, oedema, ulcerations and extension of damage. The histological severity of the colonic fibrosis was also notably improved by the treatment and associated with a significant reduction in the colonic expression of α‐SMA, collagen I–III, CTGF, TGF‐β1, Smad3, and Smad7.

Conclusions These data demonstrate that the prophylactic administration of anti‐inflammatoryBoswelliaand antifibroticScutellariaextracts is effective in preventing colonic fibrosis in TNBS‐induced colitis. Their antifibrotic mechanism of action seems to be mediated by the inhibition of TGF‐β1/Smad3 pathway.
Hypomagnesaemia and risk for metabolic glucose disorders: a 10‐year follow‐up study
Authors: Guerrero‐Romero F. , Rascón‐Pacheco R. A. , Rodríguez‐Morán M. , De La Peña J. Escobedo , Wacher N.
Published: May 2008

Background   Although several lines of evidence suggest that hypomagnesaemia is a risk factor for developing type 2 diabetes, there are no studies regarding the association between hypomagnesaemia and the risk for developing impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Our objective was to examine the association between serum magnesium levels and the risk for developing IFG, IGT and type 2 diabetes.

Materials and methods   A total of 1122 individuals (20–65 years of age) were enrolled between 1996 and 1997, and 817 individuals re‐examined about 10 years later. New‐onset IFG (5·6–7·0 mmol L−1 fasting glucose), IGT (7·8–11·1 mmol L−1 glucose 2‐h postload), and type 2 diabetes were determined from the number of subjects who had these conditions at the second examination without evidence that they were present at the first one. The relative risk of new‐onset metabolic glucose disorders and diabetes (dependent variables) was computed using Poisson regression model adjusted for age, sex, family history of diabetes, waist circumference and homeostasis model assessment for insulin resistance index. Serum magnesium levels of < 0·74 mmol L−1 (independent variable) defined the exposed group.

Results  At baseline, 420 (51·4%) individuals had hypomagnesaemia. New‐onset IFG and IGT was identified in 276 (33·8%) individuals. The relative risk for IFG, IGT and IFG + IGT was 1·11 (95% confidence interval, 0·5–5·1), 1·38 (95% confidence interval, 1·1–6·3) and 1·49 (95% confidence interval, 1·1–4·9), respectively. New‐onset diabetes was identified in 78 (9·5%) individuals (relative risk 2·54; 95% confidence interval, 1·1–4·1).

Conclusions  Hypomagnesaemia is independently associated with the development of IGT, IFG + IGT and type 2 diabetes, but not with the development of IFG.
Efficacy of interferon in immunocompromised HCV patients after liver transplantation or with HIV co‐infection
Authors: Reiberger T. , Rasoul‐Rockenschaub S. , Rieger A. , Ferenci P. , Gangl A. , Peck‐Radosavljevic M.
Published: May 2008

Background Interferon (IFN)‐based antiviral therapy is increasingly used in immunocompromised patients with chronic hepatitis C after orthotopic liver transplantation (OLT) and HIV–HCV co‐infection. Differences in early viral kinetics have not been compared in these patients.

Materials and methods We retrospectively analysed 76 patients (31 OLT, 20 HIV–HCV and 25 HCV control patients) undergoing IFN sensitivity testing before starting antiviral therapy with pegylated IFN‐α2a (180 µg week−1) plus ribavirin (0·8–1·2 g day−1) for 48 weeks. We compared baseline parameters, response to IFN and treatment outcome between the groups and assessed the influence of specific calcineurin inhibitors in OLT patients and immune status in HIV–HCV patients on treatment response.

Results Viral loads pretherapy were higher in OLT compared to nontransplanted HCV controls (P = 0·003). The same trend was present in HIV–HCV (P = 0·09). The log‐drop after test dose was less in OLT compared to HCV (P = 0·02), while no significant difference was found between HIV–HCV and HCV. In HIV–HCV patients viral load log‐drop correlated significantly with CD4+cell counts (P = 0·001). No difference in viral load pretherapy, log‐drop and treatment outcome was noted between different calcineurin inhibitors in OLT patients. Sustained virological response rates were 28% in OLT, 50% in HIV–HCV and 56% in HCV patients.

Conclusions Immunosuppression results in high HCV viral loads. Initial efficacy of IFN is significantly impaired in OLT patients, but not in HIV–HCV with largely preserved CD4+cell counts. Sustained virological response rates of 28% in OLT patients are suboptimal, but encouraging results are shown for HIV–HCV patients with relatively high CD4+cell counts.
Fat overload aggravates oxidative stress in patients with the metabolic syndrome
Authors: Cardona F. , Túnez I. , Tasset I. , Montilla P. , Collantes E. , Tinahones F. J.
Published: May 2008

Background  Patients with the metabolic syndrome have greater levels of oxidative stress. However, as the response of markers of this stress to a fat overload is unknown, we evaluated certain markers of oxidative stress in these patients.

Material and methods  The study population comprised 93 subjects (70 men and 23 women): 13 healthy people (controls) with a mean age of 48·81 ± 9·01 years and 80 patients with the metabolic syndrome (mean age, 43·25 ± 11·55 years), according to the Adult Treatment Panel III criteria. All the participants were given a 60 g fat overload (Supracal). Three hours later the following biomarkers of oxidative stress were measured: lipid peroxidation products, protein carbonyl groups, reduced glutathione, glutathione peroxidase (GSH‐Px), catalase, superoxide dismutase, glutathione reductase (GSH‐Road) and glutathione S‐transferase. The levels of oxidized glutathione (GSSG) were calculated.

Results  Compared with the controls, the patients showed greater baseline oxidative stress, higher levels of lipid peroxidation products and oxidized glutathione, and lower levels of reduced glutathione, glutathione peroxidase activity, glutathione reductase and glutathione transferase. This stress was more intense after the subjects received a fat overload, more so in the patients who experienced a greater reduction in GSHpx and GSHrd antioxidant activity and a greater increase in the levels of carbonylated proteins and lipoperoxides than the controls.

Conclusions  Patients with the metabolic syndrome have greater oxidative stress than healthy people. The variation in markers of this stress after a fat overload was even more pronounced in the patients.
A model of plant strategies in fluvial hydrosystems
Authors: BORNETTE G. , TABACCHI E. , HUPP C. , PUIJALON S. , ROSTAN J. C.
Published: May 2008

1. We propose a model of plant strategies in temperate fluvial hydrosystems that considers the hydraulic and geomorphic features that control plant recruitment, establishment and growth in river floodplains.

2. The model describes first how the disturbance gradient and the grain‐size of the river bed load affect the relative proportion of erosion and deposition processes, and how the frequency of flood disturbance affects the intensity of such processes.

3. Secondly, the model predicts plant strategies according to direct and indirect effects of floods (disturbances through erosion versus deposition processes, and associated nutrient excess or limitation).

4. The relevance of the model as a prediction tool is discussed. Some proposals are made to validate the model, and traits are proposed that should be considered in future research for improving the predicting value of the model.
Genetic homogeneity among breeding grounds and nursery areas of an exploited Lake Malawi cichlid fish
Authors: GENNER MARTIN J. , NICHOLS PAUL , SHAW PAUL W. , CARVALHO GARY R. , ROBINSON ROSANNA L. , TURNER GEORGE F.
Published: May 2008

1. Nursery areas are commonly recognized as important habitats for the management and conservation of fish stocks. Here we report the use of nursery areas by an exploited offshore cichlid in Lake Malawi, Rhamphochromis longiceps.

2. Like all haplochromine cichlids that have been studied, the species is a maternal mouthbrooder that broods eggs for several weeks following spawning. We found evidence that during this brooding period females migrate from open water to release juveniles in three shallow peripheral waterbodies (Chia Lagoon, Unaka Lagoon, Lake Malombe). However, it was unclear whether there is geographical population structuring within the species, which could indicate stock differences in their use of these nursery habitats, or if the lake contains a genetically panmictic population that employs nursery habitats opportunistically.

3. To investigate spatial and temporal population structuring within the lake we genotyped populations at seven microsatellite DNA loci. Overall, we found no significant spatial structuring among juveniles from the peripheral lagoons or among breeding males within the main lake body. Moreover, we found no evidence of temporal structuring among males on the breeding grounds within Lake Malawi or females entering Chia lagoon. Together, these results suggest that Lake Malawi contains a genetically homogeneous population of R. longiceps.

4. At present we know little of the distribution of juvenile R. longiceps elsewhere in the Lake Malawi basin, but their absence from surveyed rocky and sandy littoral habitats makes it possible that the species is dependent upon a small number of nearshore nursery areas, including these lagoons. As such, conservation of lagoon habitats and monitoring of exploited fish stocks within them may be important for effective preservation of biodiversity within the catchment.
Quality of life in haemophilia
Authors: GRINGERI A. , VON MACKENSEN S.
Published: May 2008

Summary.  There is a growing interest in patient‐reported outcomes as measures for evaluating the benefits of new and existing treatments. Health‐related quality of life (HRQoL) is one of these patient‐reported outcomes and represents the individual experience and perception of illness/health together with the psychosocial response to disease‐related and treatment‐related symptoms. Generic and disease‐specific HRQoL questionnaires enable us to assess and quantify the multi‐dimensional perception of well‐being, namely the physical components and the psychological (emotional, mental, social and behavioural) components of patient’s well‐being and functioning. These instruments should be standardized and validated and they should prove to be reliable, valid, specific and sensitive in a similar manner to instruments created for objective parameters. HRQoL assessment can help us to evaluate the benefits of new treatments from the perspective of patient’s values and expectations. It can also help to evaluate the quality of care provided, in order to be able to improve it at a local and national level. Moreover, HRQoL assessment can be routinely assessed to monitor improvement and progress or deterioration and decline from the global point of view of each single patient, integrating the otherwise limited angle of objective signs and instrumental or lab parameters.
Diagnosis of factor VIII deficiency
Authors: VERBRUGGEN B. , MEIJER P. , NOVáKOVA I. , VAN HEERDE W.
Published: May 2008

Summary. The correct diagnosis of factor VIII deficiency and the assessment of severity of the disease are essential for a patient‐tailored treatment strategy. An optimal diagnostic procedure comprises sensitive and specific screening methods and factor VIII activity assays. Different screening reagents show variable characteristics and receiver operator characteristic curves are presented showing the relation between sensitivity and specificity of eleven activated partial thromboplastin time reagents. The details of the three methods for factor VIII activity assay, one‐stage and two‐stage assay and chromogenic assays, are discussed. The chromogenic assay seems to be more sensitive than the one‐stage assay with regard to the detection of severe haemophilia. Discrepant results obtained with one‐stage and two‐stage assays are reviewed and discussed.
Animal models of bleeding and tissue repair
Authors: HOFFMAN M.
Published: May 2008

Summary.  While a number of animal models have been developed for human haemophilia, it has been difficult to develop reproducible measures of bleeding in these models. They have also not been extensively utilized to study the complications of haemophilia beyond blood loss. Poor haemostatic function also leads to local haematomas, joint damage and poor wound healing. Some of the abnormalities related to bleeding are because of the deleterious effects of iron deposition in the tissues. Evidence from mouse skin wound and joint haemorrhage models suggests that bleeding and iron deposition initiate a vicious cycle of inflammation, angiogenesis and renewed bleeding. However, there is much yet to be learned about the effects of bleeding on tissue responses, including validating the results of animal studies in clinical trials.
Prophylaxis for severe haemophilia: clinical challenges in the absence as well as in the presence of inhibitors
Authors: FISCHER K. , VALENTINO L. , LJUNG R. , BLANCHETTE V.
Published: May 2008

Summary.  Prophylaxis is defined as the regular administration of clotting factor concentrates to prevent bleeding. Extensive data from observational studies and a recent randomized controlled trial (have established that early prophylactic treatment prevents bleeds and arthropathy in boys with severe haemophilia. The initiation of prophylaxis in young children remains challenging. To prevent arthropathy, prophylaxis should be started early, before the onset of joint damage. Alternative strategies of starting include starting before the age of 2 years, or starting before the third joint bleed. Dose and frequency vary between the original Swedish regime of 20–40 IU kg−1 three times per week and lower dosed and step up regimes starting with 50 IU kg−1 once weekly and rapidly increasing dose and frequency in case of bleeds. In the second decade, most patients on prophylaxis learn self‐infusion. Self‐management warrants confirmation of adequate knowledge of the disease. Increasing self‐management concurring with major physical and psychological changes may cause reduced adherence. The challenge is to promote adherence and continue to prevent bleeds during this important period of rapid growth. The third decade of life often represents a change in lifestyle. Patients may get a job and periods of physical activity may be more confined. About two thirds of patients experiment with discontinuing prophylaxis in their early twenties, and 20–30% with mild bleeding patterns switch to on‐demand treatment for prolonged periods or even permanently. The challenge is to optimize efficiency by individualizing prophylactic dose and frequency according to lifestyle and bleeding pattern.

Inhibitors may develop in up to 30% of patients with severe haemophilia. Especially those with high titre inhibitors are at increased risk of developing target joints and severe arthropathy. The use of prophylactic treatment with bypassing agents in inhibitor patients is increasing. Early studies report in a significant reduction of bleeds, including intracranial bleeds, and improvement in quality of life. Data on results of primary prophylaxis in patients with inhibitors to prevent arthropathy are not yet available.
Regulation of Initiation of Meiosis in Fetal Gonads
Authors: Byskov Anne Grete
Published: May 2008

Undifferentiated 11 day old fetal mouse gonads were cultured for 7 days in media in which tissues of fetal mouse testis or rete testis had grown. The rete testis medium contained a substance, which triggers the male germ cells to enter meiosis. The medium from the testis blocked meiosis in the female germ cells. It is proposed that a meiosis inducing substance. MIS, and a meiosis preventing substance, MPS, are present within the differentiating fetal testis, and that the two substances participate in the control of germ cell behaviour.
Inhibin: Evidence for Its Existence, Methods of Bioassay and Nature of the Active Material
Authors: Davies R. V. , Main S. J. , Setchell B. P.
Published: May 2008

Results are presented on the changes in serum FSH, LH and testosterone levels and in testis weight after efferent duct ligation, X‐irradiation or heating the testes, or injections of antiserum to testosterone. These results can only be explained by the existence of a feed‐back substance “inhibin”, which is produced by the seminiferous tubules and which regulates the secretion of FSH by the pituitary. Several bioassay methods have been developed for the detection of inhibin‐like activity and have been used to follow the purification of this activity, mainly from ram rete testis fluid proteins. The active material exhibits an apparent heterogeneity, with apparent molecular weights of 90 000, 20 000 and < 5000.
Studies on Purification of Inhibin from Ovine Testicular Secretions Using an In Vitro Bioassay
Authors: Baker H. W. G. , Burger H. G. , de Kretser D. M. , Eddie L. W. , Higginson R. E. , Hudson B. , Lee V. W. K.
Published: May 2008

An in vitro bioassay based upon inhibition of follicle stimulating hormone (FSH) secretion by rat pituitary cells in culture was used to investigate preliminary steps in the purification of inhibin from ovine rete testis fluid (RTF) and testicular lymph (OTL). Since androgens also suppress gonadotrophin levels in this assay, steroids were removed from test substances. Charcoal adsorption and ethanol precipitation were found to be unsatisfactory because of large losses of inhibin activity. Using RTF protein as the starting material a two‐fold purification was achieved by precipitation with 50% ammonium sulphate. Chromatography of the ammonium sulphate precipitate on DEAE Sephadex resulted in further purification and separation of inhibin from testosterone.
Plasma Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) Suppression in the Cryptorchid Ram by a Non‐Steroid Factor (Inhibin) from Ram Rete Testis Fluid
Authors: Blanc M. R. , Cahoreau C. , Courot M. , Dacheux J. L. , Hochereau‐de‐Reviers M. Th. , Pisselet Cl.
Published: May 2008

Cryptorchid rams were bled every 15 or 30 min for 25 h. 20 ml of charcoal treated RTF were injected at the 5th and at the 6th h after the beginning of sampling. Human serum albumin or γ‐globulin were injected similarly as controls. FSH, LH, testosterone and prolactin were measured by radioimmunoassay. A non‐steroid factor from RTF suppresses the secretion of both FSH and LH but with different kinetics. FSH is progressively lowered after the first injection and a plateau (30% of depletion) is observed about 8 h after the first injection and lasts for about 7 h. RTF injections result in the suppression of LH peaks for 3 to 5 h starting at the first two h after treatment.
Factors Affecting Blood Levels of Androgen Binding Protein in the Rat
Authors: Gunsalus Glen L. , Musto Neal A. , Bardin C. Wayne
Published: May 2008

The factors which determine the levels of androgen binding protein (ABP) in blood were studied. Serum ABP concentrations are high at 18 days of age and decline, after formation of the blood‐testis barrier, to levels found in adults. Secretion of ABP into the epididymis was markedly decreased in Hre rats and animals with Sertoli cell enriched testis, but the serum concentrations were normal. Serum ABP concentrations increase following obstruction of the efferent ducts and decrease following hemicastration. Testosterone treatment of chronically hypophysectomized rats resulted in an increase in testicular and serum ABP concentrations but no change in epididymal levels. By contrast, treatment with testosterone and FSH caused an increase in the epididymal content many‐fold greater than that observed in plasma. These observations are consistent with the hypothesis that release of ABP into blood is controlled by factors which are independent of transport to the epididymis.
Quantitation of Spermatogenesis by Flow Cytometric DNA Measurements
Authors: Clausen O. P. F. , Purvis K. , Hansson V.
Published: May 2008

Suspensions of testicular cells from rats, mice and humans have been subjected to flow cytometry (FCM) after staining with the fluorochromes ethidium bromide and mitramycin. The resulting DNA distribution patterns give valuable information about the relative quantities of cells with haploid, S‐phase, diploid and tetraploid DNA content in the testis.

In the present study we show some examples of how FCM can be used to monitor meiosis, and to get a quantitative assessment of spermatogenesis in animals and humans.
Inhibition of Sperm Maturation Through Intervention of the Carnitine System
Authors: Bøhmer Thomas , Johansen Liv
Published: May 2008

Carnitine, acetylcarnitine and carnitine acetyltransferase (E.C.2.2.1.7) are present in 6–120 fold higher concentrations in human spermatozoa than in seminal plasma. Carnitine uptake by epididymal tissue in vitro in the rat is most active in the same segments of epididymis where the highest concentrations of carnitine are found in man. Radiolabelled carnitine is not taken up by mature human spermatozoa. Carnitine suppresses oxygen uptake in bovine ejaculated spermatozoa but not in human ejaculated or in rat or bovine epididymal spermatozoa. These findings indicate that the epididymis contributes to the accumulation of carnitine in caput spermatozoa and that carnitine may not be primarily responsible for the quiescent state of the spermatozoa in the cauda epididymis.

Extensive changes in carnitine uptake in the epididymis can be encouraged by a hormonal treatment which has no effect on the carnitine uptake by the heart. This raises the possibility of interference with the carnitine balance in the epididymis without effecting the pattern of carnitine uptake in other tissues.
Electrolyte and Water Transport in Rat Epididymis; Its Possible Role in Sperm Maturation
Authors: Wong P. Y. D. , Au C. L. , Ngai H. K.
Published: May 2008

Electrolyte and water transport in different regions of the rat epididymis has been studied using a microperfusion technique. The caput and proximal corpus epididymides were found to absorb NaCl and water and secrete K+ at a lower rate than the cauda epididymidis. The secretion rate of protein was the same in both regions. In the caput and proximal corpus, reabsorption of chloride was hypertonic. Reabsorption of sodium could not account for water reabsorption. In contrast, water reabsorption in the cauda epididymidis was dependent upon the intraluminal sodium ions. Amiloride inhibited both the Na+ and water reabsorption in this region. It was concluded that in the proximal regions of the rat epididymidis, water reabsorption may be secondary to an active transport of chloride, whereas in the cauda, a net transepithelial transport of sodium ions is the driving force for water reabsorption.

Transport of electrolytes and water across the perfused rat cauda epididymidis has also been studied under various experimental conditions. Treatment of rats with alpha‐chlorohydrin (9 mg/kg/day) for 7 days inhibited the rate of sodium and water reabsorption without affecting the secretion of proteins. Ligation of the testicular efferent duct or the corpus epididymidis had no significant effect on the transport functions of the cauda epididymidis. When cyproterone acetate (10 mg/rat/day) was injected into male rats, the rate of sodium and water reabsorption was reduced. This effect was accompanied by a loss of sperm motility. It is concluded that the transport functions of the cauda do not require the normal flow of testicular fluid, but may depend on the supply of circulating androgen in the blood. Alpha‐chlorohydrin and cyproterone acetate may affect sperm maturation by disrupting the normal milieu of the epididymal duct.
Male Contraception: Clinical Assessment of Chronic Administration of Testosterone Enanthate
Authors: Swerdloff Ronald S. , Palacios Anselmo , McClure R. Dale , Campfield L. Arthur , Brosman Stanley A.
Published: May 2008

Testosterone enanthate (TE) was administered im to 39 normal adult men (age 21–39) to assess its efficacy as a suppressor of spermatogeneis and to determine possible adverse effects. 17 subject (Group A) received TE (200 mg/week) for 16 to 20 weeks. 16/17 lowered sperm counts (SC) to < 5 million/cc; 11/17 to < 300 000; and 10/17 became azoospermic. Group B received TE (200 mg/weeks); in 10/22 SC were < 5 million/cc at 16 weeks; 9/22 to < 300 000; and 5/22 azoospermic; when those with SC > 5 million/cc were switched to weekly treatment (additional 3–16 weeks), 9/12 lowered SC to < 5 million/cc. Overall, 19/22 of Group B attained this level. Serum LH and FSH were decreased on both regimens. These effects were dose‐related. Mean serum testosterone was elevated above control (64%) in Group A, but remained at basal levels 2 weeks after TE injection in Group B. Decreasing the frequency of TE (3 or 4 weeks) resulted in a rebound of FSH and LH above baseline and increased SC. After discontinuing treatment, sperm counts and hormonal measurements returned to normal. Modest increase in body weight, red cell mass, oiliness of skin and mild acne were seen in some subjects. Liver function tests, glucose tolerance, blood lipids and renal function were unchanged.
Testosterone and Testosterone Binding Globulin (TeBG) in Young Men during Prolonged Stress
Authors: Aakvaag A. , Bentdal Ø. , Quigstad K. , Walstad P. , Rønningen H. , Fonnum F.
Published: May 2008

The effect of prolonged physical and psychological stress on the testicular function was studied in 8 students (age 22–25 years) of the Norwegian Academy of War during a combat course of 5 days' duration. The average urinary excretion of free cortisol and 17‐ketogenic steroids was 81 and 129% higher than the respective control values one week after the course. Plasma cortisol levels increased from 21.7 μg/100 ml at 8 a. m. before the course to 24.6 (P < 0.05), and serum HGH rose from undetectable levels, < 0.08 ng/ml, to an average value of 12.9 ng/ml ± 3.7 (SD) at 8 a. m. during the course.

A marked suppressive effect on plasma testosterone levels from 5.6 ng/ml ± 1.4 to 0.9 ± 0.5, and no adjustment to stress was observed over a 5 day period. TeBG increased gradually from 26.9 nmol/l ± 9.9 to 52.7 ± 17.7 on day 6, followed by a slow decrease without reaching control values on day 12, suggesting that the decreased plasma testosterone levels probably reflect reduced production and not increased metabolism of testosterone. LH fluctuated during the course, but was significantly higher in the morning immediately following the end of the course than at the start (P < 0.02). It is postulated that the effect of stress on the plasma testosterone levels is mediated via an action both on the hypothalamus‐pituitary level and on the testis.
Effect of Long Term Treatment with Gonadotrophic Hormones on In Vitro Metabolism of [3H]Progesterone in Human Testicular Tissue
Authors: Berg A. Å:son , Kjessler B.
Published: May 2008

Gonadotrophic hormones appear to influence the preferred pathways for intratesticular androgen biosynthesis. Individuals with low levels of gonadotrophin in the peripheral circulation, as e. g. prepubertal boys and a hypophysectomized adult male, have previously been shown to metabolize [3H]progesterone in vitro mainly to 20α‐dihydroprogesterone (20α‐DH‐P) and less to 17α‐hydroxyprogesterone (17α‐OH‐P), i. e. an “immature metabolic pattern” (Berg et al. 1976; Kjessler & Berg 1976b).

With physiologically increasing amounts of circulating gonadotrophins the preferred metabolic pathway in vitro shifts in favour of 17α‐OH‐P, i. e. a “mature metabolic pattern”. Such an alteration in the preferred in vitro metabolic pattern of [3H]progesterone has also been obtained by exogenous administration of gonadotrophins to a 47, XYY‐male with an initially immature metabolic pattern (Berg & Kjessler 1976).

We have sequentially analysed the metabolism of [3H]progesterone in vitro in testicular incubates derived from a chromosomally normal male before and after 16 weeks of substitution therapy with gonadotrophic hormones.

The patient originally displayed an “immature” pattern of progesterone metabolites, i. e. the ratio 20α‐DH‐P/17é‐OH‐P was 3.04. After treatment with human menopausal gonadotrophins and hCG, the metabolic activity in total had increased, and the ratio 20é‐DH‐P/17é‐OH‐P had switched to 0.39.

These results confirm and extend the concept that gonadotrophic hormones may have a regulatory function on androgen biosynthesis by stimulating the oxidative metabolic pathway from progesterone to biologically active androgens via 17α‐hydroxyprogesterone.
The Occurrence of Sperm Agglutinating Antibodies Before and After Testicular Biopsy
Authors: Norén S. , Friberg J.
Published: May 2008

Bilateral testicular biopsy was performed in 30 infertile men with azoospermia or with less than 30 mill. spermatozoa per ml. Blood serum was analysed for sperm‐agglutinating antibodies prior to the operation and during six months post‐operatively. Out of 26 subjects, with no sperm‐agglutinating antibodies in the blood, only one had a weak and transitory agglutinating activity post‐operatively.