bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond corals and fish: the effects of climate change on noncoral benthic invertebrates of tropical reefs
Authors: PRZESLAWSKI RACHEL , AHYONG SHANE , BYRNE MARIA , WÖRHEIDE GERT , HUTCHINGS PAT
Published: October 2008

Climate change is threatening tropical reefs across the world, with most scientists agreeing that the current changes in climate conditions are occurring at a much faster rate than in the past and are potentially beyond the capacity of reefs to adapt and recover. Current research in tropical ecosystems focuses largely on corals and fishes, although other benthic marine invertebrates provide crucial services to reef systems, with roles in nutrient cycling, water quality regulation, and herbivory. We review available information on the effects of environmental conditions associated with climate change on noncoral tropical benthic invertebrates, including inferences from modern and fossil records. Increasing sea surface temperatures may decrease survivorship and increase the developmental rate, as well as alter the timing of gonad development, spawning, and food availability. The broad latitudinal distribution and associated temperature ranges of several pantropical taxa suggest that some reef communities may have an in‐built adaptive capacity. Tropical benthic invertebrates will also show species‐specific sublethal and lethal responses to sea‐level rise, ocean acidification, physical disturbance, runoff, turbidity, sedimentation, and changes in ocean circulation. In order to accurately predict a species' response to these stressors, we must consider the magnitude and duration of exposure to each stressor, as well as the physiology, mobility, and habitat requirements of the species. Stressors will not act independently, and many organisms will be exposed to multiple stressors concurrently, including anthropogenic stressors. Environmental changes associated with climate change are linked to larger ecological processes, including changes in larval dispersal and recruitment success, shifts in community structure and range extensions, and the establishment and spread of invasive species. Loss of some species will trigger economic losses and negative effects on ecosystem function. Our review is intended to create a framework with which to predict the vulnerability of benthic invertebrates to the stressors associated with climate change, as well as their adaptive capacity. We anticipate that this review will assist scientists, managers, and policy‐makers to better develop and implement regional research and management strategies, based on observed and predicted changes in environmental conditions.
Rituximab as a single agent in the management of adult patients with haemophilia A and inhibitors: marked reduction in inhibitor level and clinical improvement in bleeding but failure to eradicate the inhibitor
Authors: ALEEM A. , SAIDU A. , ABDULKARIM H. , AL‐DIAB A. R. , AL‐SAGHEER A. , QAYUM A. , AL‐MOMEN A. K.
Published: October 2008

Summary.  Management of patients with severe haemophilia A who develop inhibitors is difficult and expensive. Standard treatment of this complication is immune tolerance induction (ITI) therapy, but is successful in only 60–80% of the patients. Failure of ITI results in a higher risk of morbidity and mortality. We used rituximab, an anti‐CD20 antibody, in three patients with severe haemophilia A and inhibitors. Two patients with high‐titre inhibitors had marked reduction in the inhibitor level; the third patient with low‐titre inhibitor had a disappearance of the inhibitor. All patients improved clinically, with fewer bleeding episodes and a better quality of life. Inhibitor level increased with time in these patients, but the clinical benefit continued in two patients with high‐titre inhibitors initially, after a follow‐up of 48 and 22 months. One of the patients with concomitant human immunodeficiency virus (HIV) infection and a very low CD4 lymphocyte count developed severe truncal herpes zoster after the third weekly dose of rituximab. Caution is required in such patients, and we recommend avoiding rituximab use in HIV‐infected patients with very low CD4 lymphocyte count. In conclusion, rituximab is useful in reducing the inhibitor level with clinical benefit in patients with severe haemophilia A and inhibitors, but it cannot eradicate the inhibitors for long periods with the currently used protocol of up to five doses.
Cardiac surgery in patients with haemophilia
Authors: TANG M. , WIERUP P. , TERP K. , INGERSLEV J. , SØRENSEN B.
Published: October 2008

Abstract.  Today the populations of haemophilia patients in many countries have a higher life expectancy than previously known, and age‐related disorders such as arterial disease are expected to become more prevalent, calling for surgical intervention. Cardiac surgery constitutes a major haemostatic challenge because of sternotomy, the need of total heparinization, extracorporal circulation, mild hypothermia and cardiac arrest. To evaluate our current experience and results with cardiac surgery in patients with haemophilia the present case series report on six patients with haemophilia A (Severe = 1, Moderate = 1, Mild = 4) undergoing cardiac surgery (coronary artery bypass grafting; CABG = 2, aortic valve replacement = 1, CABG + aortic valve replacement = 2, ventricular resection + mitral valve reconstruction = 1). The present paper provides detailed information on the haemostatic treatment regimens adopted (factor concentrate dosages, timing and duration) and postoperative thromboprophylaxis (dosing and duration of low molecular weight heparin). Moreover, we present data on concomitant disorders (hypertension, hypercholesterolaemia, atrial fibrillation and diabetes), left ventricle ejection fraction (30–60%), type of anaesthesia, total amount of heparin (34 500–53 500 IU) and duration of extracorporeal circulation (80–115 min). Clinical outcomes included: re‐operation because of bleeding (none), transfusion requirements, peri‐ and postoperative blood loss and complications and postoperative development of inhibitors (none). Clinical outcomes were compared with a control group of patients (n = 5993) without haemophilia and we found no difference in postoperative morbidity. Adopting meticulously supervised haemostatic treatment regimens, we have successfully performed major cardiac surgery in patients with haemophilia A. The clinical outcome as well as the severity and incidence of postoperative complications were similar to patients without haemophilia.
Familial multiple coagulation factor deficiencies – chance associations and distinct clinical disorders
Authors: ROBSON P. J. , MUMFORD A. D.
Published: October 2008

Summary.  The familial multiple coagulation factor deficiencies (FMCFDs) are a group of rare haemostatic disorders of genetic origin in which there is reduced plasma activity of more than one coagulation factor. FMCFDs may arise from co‐incidental inheritance of separate coagulation factor deficiencies or from a single genetic or cytogenetic defect. All the FMCFDs present significant challenges in diagnosis and management yet there is little systematic evidence with which to guide clinical practice. This review summarizes the historical literature that describes the FMCFDs and introduces a refined classification of these disorders. The clinical and laboratory characteristics of the most common FMCFDs are considered in detail.
Assay discrepancy in mild haemophilia A: entire population study in a National Haemophilia Centre
Authors: POULSEN A. L. , PEDERSEN L. H. , HVAS A.‐M. , POULSEN L. H. , THYKJÆR H. , INGERSLEV J.
Published: October 2008

Summary.  Assay discrepancy in mild haemophilia, here defined by a significantly higher factor VIII (FVIII):C response by the one‐stage procoagulant assay as compared with a two‐stage enzymatic method, has repeatedly been reported in literature. The purpose of this study was to determine the overall prevalence of this phenomenon amongst mild haemophilia families from a population of 2.95 million inhabitants in the Western Danish region. Information was collected retrospectively through a thorough search of archives of the National Haemophilia Centre in Aarhus. We identified 109 patients with mild haemophilia A amongst whom 92 were eligible to enter the study. These represent a total of 53 unrelated families. Our data illustrate that this assay discrepancy pattern is found quite frequently amongst our mild haemophilia A families. While the ratio of FVIII:C chromogenic/FVIII:C clot values was quite consistent amongst patients belonging to same family pattern, ratios in the entire cohort of families ranged from 0.18 to 1.00. Selecting a cut‐off level for the FVIII:C chromogenic/FVIII:C clot ratios at 0.7, 0.6 and 0.5, respectively, we found that 38 (72%), 27 (51%) and 19 (36%) of families, respectively, displayed this assay discrepancy. In 10 patients, the FVIII:C chromogenic level was inside the category of moderate haemophilia at >0.01–<0.05 IU mL−1, pointing to a class‐shift in the biochemical phenotype. In conclusion, our data illustrate a substantial prevalence of the assay discrepancy phenomenon amongst mild haemophilia A patients in our geographical area.
Treatment and prevention of acute bleedings in von Willebrand disease – efficacy and safety of Wilate®, a new generation von Willebrand factor/factor VIII concentrate
Authors: BERNTORP E. , WINDYGA J. ,   THE EUROPEAN WILATE STUDY GROUP
Published: October 2008

Summary.  For many patients with von Willebrand disease (VWD), the replacement therapy with von Willebrand factor (VWF)/factor VIII (FVIII) concentrates is the treatment of choice. To evaluate clinical efficacy, safety and tolerability of Wilate®, an albumin‐free VWF/FVIII concentrate with a ratio of the two haemostatic moieties of approximately 1 to 1, a prospective clinical programme has been designed. The dataset on the treatment and prevention of bleedings is derived from 44 patients (20 males and 24 females) of all VWD types. Thousand and ninety five bleeding episodes were treated with an overall efficacy rating of excellent or good in 96%. The median dose per treatment day was 26 IU FVIII:C per kg. Eighty‐one per cent of bleeds were stopped within 1 or 2 days. Gastrointestinal (GI) bleeds needed higher doses (mean 44 IU kg−1) and longer treatment (mean 4 days). Efficacy and dosing data from eight children of 12 or less years of age did not differ significantly from the overall study population. Nineteen patients, including six children, were treated prophylactically for more than 3 months (mean 14.8, range 3–46) with a mean prophylactic dose of 27.4 IU kg−1 and a mean frequency of 1.9 infusions per week. A drop of bleeding frequency from a mean of 4.5 to 1.4 bleeds per month was observed. The overall tolerability was very good. Adverse drug reactions were rare and were mild or moderate in their intensity. The large prospective clinical dataset shows that Wilate® is efficacious and safe in the treatment and prevention of haemorrhages in all VWD types in both adult and paediatric patients.
Central venous access devices for paediatric patients with haemophilia: a single‐institution experience
Authors: TITAPIWATANAKUN R. , MOIR C. , PRUTHI R. K. , STAVLO P. L. , SCHMIDT K. A. , RODRIGUEZ V.
Published: October 2008

Summary.  Use of a central venous access device (CVAD) can facilitate early introduction of home‐based infusion of factor concentrate for long‐term prophylaxis or immune tolerance therapy in children with bleeding disorders. The aim was to review outcomes associated with use of CVAD. Retrospective review of paediatric patients with bleeding disorders was observed at the Mayo Clinic Comprehensive Hemophilia Center. Thirty‐seven CVAD were placed in 18 patients (haemophilia A [n = 15], type 3 von Willebrand disease [n = 2] and haemophilia B [n = 1]). Follow‐up was for 45 952 CVAD days, and median time that CVAD remained in place was 1361 days per device. Factor VIII (FVIII) inhibitors were present in 4 of the 15 patients. Ten CVAD‐related infections occurred (median, 672 days; range, 72–1941 days), of which six were in one patient with FVIII inhibitors. Overall infection rate was 0.22 (95% confidence interval [CI], 0.10–0.40) per 1000 CVAD days, with 0.11 infections in patients without FVIII inhibitors compared with a pooled incidence of 0.66 (95% CI, 0.44–0.97) reported in the literature. Indications for removal of 27 CVAD were blockage, change to peripheral venous access, catheter displacement, infection, leak in the port septum, short catheter and skin erosion. No clinically apparent thrombosis or sequelae of thrombosis were observed. Infection is the most common complication associated with CVAD use and is increased in patients who have inhibitors. The low rate of clinically apparent thrombosis reflects our practice of not screening for thrombosis. The low infection rate reflects our practice of using and reinforcing the aseptic technique.
Photoperiod and Testosterone Interact to Drive Seasonal Changes in Kisspeptin Expression in Siberian Hamsters (Phodopus sungorus)
Authors: Greives T. J. , Humber S. A. , Goldstein A. N. , Scotti M.‐A. L. , Demas G. E. , Kriegsfeld L. J.
Published: October 2008

Kisspeptin, a neuropeptide product of the KiSS‐1 gene, has recently been implicated in the regulation of seasonal breeding in a number of species, including Siberian hamsters. In this species, kisspeptin expression is reduced in the anteroventral periventricular nucleus (AVPV) following exposure to inhibitory day lengths, and exogenous kisspeptin activates the reproductive neuroendocrine axis of reproductively quiescent animals. Because sex steroids can impact kisspeptin expression, it is unclear whether changes in kisspeptin occur in direct response to photoperiodic cues or secondarily in response to changes in sex steroid concentrations resulting from the transition to reproductive quiescence. The present study aimed to assess the relative contributions of photoperiod and testosterone in regulating kisspeptin expression in Siberian hamsters. Animals housed in long or short day lengths for 8 weeks were either castrated or received sham surgeries. Half of the hamsters in each photoperiod were given testosterone to mimic long‐day sex steroid concentrations. The results obtained indicate that kisspeptin neurones in the AVPV and arcuate nuclei were influenced by both photoperiod and testosterone. In the AVPV, removal of testosterone or exposure to inhibitory day lengths led to a marked reduction in kisspeptin‐immunoreactive cells, and testosterone treatment increased cell numbers across conditions. Importantly, long‐day castrates exhibited significantly more kisspeptin cells than short‐day castrates or intact short‐day animals with empty capsules, suggesting the influences of photoperiod, independent of gonadal steroids. In general, the opposite pattern emerged for the arcuate nuclei. Collectively, these data suggest a role for both gonadal‐dependent and independent (i.e. photoperiodic) mechanisms regulating seasonal changes in kisspeptin expression in Siberian hamsters.
Meniere’s Attacks Occur in the Inner Ear with Excessive Vasopressin Type‐2 Receptors
Authors: Kitahara T. , Doi K. , Maekawa C. , Kizawa K. , Horii A. , Kubo T. , Kiyama H.
Published: October 2008

Meniere’s disease is peculiar to humans and is characterised by episodic vertigo, fluctuating hearing loss and tinnitus, and attacks of the affliction occurring under conditions of stress. Its pathology was first revealed to be inner ear hydrops through temporal bone studies in 1938. Although subsequently proposed as a disorder of water metabolism in the inner ear, its pathogenesis remains unsolved. The present study aimed to assess the link between the inner ear pathology in Meniere’s disease and vasopressin, an anti‐diuretic stress hormone with a potential role in inner ear fluid homeostasis. Blood samples were obtained from Meniere’s disease patients in the morning, before any surgical treatment, to examine plasma vasopressin (pAVP) levels, and then from inner ear tissue during surgical treatment, to examine vasopressin type‐2 receptor (V2R) in the endolymphatic sac. pAVP and the relative V2R mRNA expression in the endolymphatic sac were examined using a real‐time polymerase chain reaction. Relative cAMP activity in the endolymphatic sac was also examined using tissue culture and cAMP assay. Both pAVP (1.6‐fold versus controls; P = 0.048) and inner ear V2R mRNA expression (41.5‐fold versus controls; P = 0.022) were significantly higher in Meniere’s patients. cAMP activity was basally up‐regulated (2.1‐fold versus controls) and cAMP sensitivity to vasopressin application was largely elevated (4.9‐fold versus controls) in Meniere’s patients. We conclude that, in the pathogenesis of inner ear hydrops, resulting in Meniere’s attacks, elevation of pAVP levels (probably as a result of stress) may present as a matter of consequence, but susceptibility of the V2R‐overexpressed and cAMP‐hypersensitised inner ear to pAVP elevation might be essential as the basis of this disease. Further experimental and clinical studies are needed to better clarify the relationship between Meniere’s disease and stress.
Antagonists of the Protein Kinase A and Mitogen‐Activated Protein Kinase Systems and of the Progestin Receptor Block the Ability of Vaginocervical/Flank‐Perineal Stimulation to Induce Female Rat Sexual Behaviour
Authors: González‐Flores O. , Etgen A. M. , Komisaruk B. K. , Gómora‐Arrati P. , Macias‐Jimenez A. , Lima‐Hernández F. J. , Garcia‐Juárez M. , Beyer C.
Published: October 2008

Brief vaginocervical stimulation using a glass rod (VCS) combined with manual flank‐perineal stimulation (FS) rapidly (within 5 min) induced both receptive and proceptive behavioural responses to males in ovariectomised, oestrogen‐primed rats. This receptive‐proceptive response to males, resulting from a single brief (5‐s duration) instance of manual VCS + FS, declined markedly within 4 h. However, the decline was prevented if the females were mounted by males immediately after the manual VCS + FS and 2 h later. We tested the participation of the cAMP‐dependent protein kinase A system and the mitogen‐activated protein kinase (MAPK) system in the response to VCS + FS by infusing either 100 ng of Rp‐adenosine 3′,5′‐cyclic monophosphorothiate triethylamonium salt (a protein kinase A blocker) or 3.3 μg of PD98059 (a MAPK blocker) i.c.v. 15 min prior to VCS + FS. Both inhibitors blocked the ability of VCS + FS to induce the proceptive‐receptive responses to males at all testing intervals. In experiment 2, systemic administration of 5 mg of RU486 1 h before VCS + FS also blocked the ability of VCS + FS to induce the proceptive‐receptive responses to males. The present findings suggest that both VCS + FS and mating stimuli provided by males release neurotransmitters and neuromodulators that trigger the protein kinase A and the MAPK signalling systems, which interact with the progestin receptor to rapidly (within 5 min) induce proceptive‐receptive behaviour in females.
In Three Brain Regions Central to Maternal Behaviour, Neither Male Nor Female Phodopus Dwarf Hamsters Show Changes in Oestrogen Receptor Alpha Distribution with Mating or Parenthood
Authors: Timonin M. E. , Cushing B. S. , Wynne‐Edwards K. E.
Published: October 2008

Oestrogen receptor (ER)α immunoreactivity in three brain regions relevant to maternal behaviour (medial preoptic area, bed nucleus of the stria terminalis and medial amygdala) was measured in two species of dwarf hamster that both mate during a postpartum oestrous but differ in expression of paternal behaviour. Male and female Phodopus campbelli and Phodopus sungorus were sampled as sexually naïve adults, following mating to satiety, and as new parents. In all brain regions, females expressed higher levels of ERα than males. Species did not have an effect on ERα distribution except in the medial amygdala, where P. sungorus females had higher expression levels than all other groups. Behavioural status was not associated with altered ERα expression. These results were not expected for females and suggest that a primary activational role for oestrogen, acting through ERα in these regions, does not generalise to maternal behaviour in Phodopus. In males, these results are consistent with previous manipulations of the ERα ligand, oestrogen, and suggest that paternal behaviour in P. campbelli is likely to be regulated by developmental effects of oestrogen on the brain during early life (similar to Microtus ochrogaster), rather than through activation by oestrogen at the time of fatherhood (similar to Peromyscus californicus).
Arginine Vasotocin Neuronal Phenotypes among Congeneric Territorial and Shoaling Reef Butterflyfishes: Species, Sex and Reproductive Season Comparisons
Authors: Dewan A. K. , Maruska K. P. , Tricas T. C.
Published: October 2008

Arginine vasotocin (AVT) and the homologous arginine vasopressin (AVP) neuropeptides are involved in the control of aggression, spacing behaviour and mating systems in vertebrates, but the function of AVT in the regulation of social behaviour among closely‐related fish species needs further clarification. We used immunocytochemical techniques to test whether AVT neurones show species, sex or seasonal differences in two sympatric butterflyfish sister species: the territorial monogamous multiband butterflyfish, Chaetodon multicinctus, and the shoaling polygamous milletseed butterflyfish, Chaetodon miliaris. The territorial species had larger AVT‐immunoreactive (‐ir) somata within the preoptic area, and higher AVT fibre densities within but not limited to the ventral telencephalon, medial and dorsal nucleus of the dorsal telencephalon, torus semicircularis, and tectum compared to the shoaling nonterritorial species. Furthermore, AVT‐ir somata size and number did not differ among sexes or spawning periods in the territorial species, and showed only limited variation within the shoaling species. The distinct difference in AVT neuronal characteristics among species is likely to be independent of body size differences, and the lack of sex and seasonal variability is consistent with their divergent but stable social and mating systems. These phenotypic differences among species may be related to the influence of AVT on social spacing, aggression or monogamy, as reported for other fish, avian and mammalian models. The present study provides the first evidence for variation in vasotocin neural organisation in two congeneric and sympatric fish species with different social systems.
How big is the financial burden of hepatitis B to society? A cost‐of‐illness study of hepatitis B infection in Singapore
Authors: Ong S. C. , Lim S. G. , Li S. C.
Published: October 2008

Summary.  Hepatitis B virus (HBV) infection is the most common cause of chronic viral liver disease in Singapore. Nevertheless, very little data exist on the financial burden of HBV infection to the society as a whole. The aim of this study was therefore to assess the direct and indirect cost of HBV infection in a cost‐of‐illness analysis. The combined data from the direct and indirect cost with the estimated prevalence for different disease stages of HBV infection would represent the annual financial burden of HBV infection to the Singaporean society as a whole. The estimated total annual cost of chronic HBV infection and its associated complications in Singapore was US$279 million (range US$34–941 million when allowing various assumptions as tested by the sensitivity analyses), with 58% or US$161 million attributable to direct cost. Based on the base‐case estimation, total direct cost alone is equivalent to 12% of the national healthcare expenditure for 2003. The total cost incurred by chronic hepatitis B patients represents the biggest cost component, followed by decompensated cirrhosis (DC) patients. The ratio of direct to indirect costs based on the base‐case estimation increased with disease severity, with the highest ratio obtained for the post‐liver transplants (40.2:1), followed by hepatocellular carcinoma (7.4:1) and DC patients (2.7:1). The results of this study suggest that the management of HBV infection poses more than a medical challenge as it is a sizeable economic burden from both the payer and societal perspectives.
Hepatitis C virus replicons: dinosaurs still in business?
Authors: Woerz I. , Lohmann V. , Bartenschlager R.
Published: October 2008

Summary. Since the molecular cloning of the hepatitis C virus (HCV) genome for the first time in 1989, there has been tremendous progress in our understanding of the multiple facets of the replication cycle of this virus. Key to this progress has been the development of systems to propagate the virus in cell culture, which turned out to be a notoriously difficult task. A major breakthrough has been the construction of subgenomic replicons that self‐amplify in cultured human hepatoma cells. These RNAs recapitulate the intracellular steps of the HCV replication cycle and have been instrumental to decipher details of the RNA amplification steps including the identification of key host cell factors. However, reproduction of the complete viral replication cycle only became possible with the advent of a particular molecular HCV clone designated JFH‐1 that replicates to very high levels and supports the production of infectious virus particles. The availability of this new culture system raises the question, whether the use of replicons is still justified. In this review, we will discuss the pros and cons of both systems.
Genotypes on the move: some things old and some things new shape the genetics of colonization during species invasions
Authors: DLUGOSCH KATRINA M. , HAYS CYNTHIA G.
Published: October 2008

When we set a species loose outside of its historical range, we create opportunities to test fundamental questions about how populations establish, adapt, disperse, and ultimately define range boundaries. A particularly controversial issue here is how genetic variation among and within populations contributes to the dynamics of species distributions. In this issue of Molecular Ecology, Rosenthal and colleagues (2008) seize an opportunity to examine how multiple introductions create genetically distinct establishment events and how these are incorporated into invasive spread. Their findings suggest that a particular recombinant lineage of Brachypodium sylvaticum may be responsible for most of the recent expansion of this invader, highlighting the potential importance of genetic novelty and historical context for colonization success.
Transcriptional and biochemical signatures of divergence in natural populations of two species of New Zealand alpinePachycladon
Authors: VOELCKEL C. , HEENAN P. B. , JANSSEN B. , REICHELT M. , FORD K. , HOFMANN R. , LOCKHART P. J.
Published: October 2008

New Zealand is diverse in alpine and subalpine environments, a consequence of Late Tertiary tectonic and climatic change. However, few studies have sought to evaluate the importance of these environments as abiotic drivers in the diversification of plant species. Of particular interest is the Late Tertiary radiation ofPachycladon, an endemic New Zealand genus of alpine cress. Here we report observations on genome‐wide levels of differential expression measured in the habitats of two closely related species ofPachycladonwith distinct altitudinal preferences. UsingArabidopsismicroarrays, we have identified 310 predominantly hormone‐ and stress‐response genes up‐regulated inPachycladon fastigiataand 324 genes up‐regulated inPachycladon enysii. Expression patterns for glucosinolate biosynthesis and hydrolysis genes (MAM1, MAM‐I, MAM‐D, AOP2, ESP, ESM1) as well as flavonoid biosynthesis genes (F3’H, FLS, FAH1) were found to be species specific. Predicted differences in flavonoid contents were partly confirmed by high performance liquid chromatography analysis. Differences in glucosinolate profiles and glucosinolate hydrolysis products obtained by high performance liquid chromatography and gas chromatography–mass spectrometry analysis, respectively, also supported inferences from expression analyses. Five glucosinolate chemotypes were matched to knownArabidopsisecotypes, and the potential adaptive significance of these chemotypes has been discussed. Our findings, in contrast to expectations for evolution of the New Zealand flora, suggest that biotic drivers, such as plant–herbivore interactions, are likely to be as important as abiotic drivers in the diversification ofPachycladon.
Regional oesophageal sensitivity to acid and weakly acidic reflux in patients with non‐erosive reflux disease
Authors: Emerenziani S. , Ribolsi M. , Sifrim D. , Blondeau K. , Cicala M.
Published: October 2008

Abstract  The mechanisms underlying symptoms in non‐erosive reflux disease (NERD) remain to be elucidated. Non‐erosive reflux disease patients appear to be more sensitive to intraluminal stimula than erosive patients, the proximal oesophagus being the most sensitive. In order to assess regional oesophageal changes in reflux acidity and sensitivity to reflux, according either to the acidity or the composition of the refluxate, combined multiple pH and multiple pH‐impedance (pH‐MII) was performed in 16 NERD patients. According to multiple pH‐metry, 29% and 12% of reflux events reached the middle and proximal oesophagus respectively, and 35% and 19% according to conventional pH‐MII (P < 0.05). The per‐individual analysis confirmed the difference between the two techniques. According to combined distal and proximal pH‐MII, approximately 30% of distal acid reflux became weakly acidic at the proximal oesophagus. In all patients, the frequency of symptomatic refluxes, both acid and weakly acidic, was significantly higher at the proximal, compared with distal oesophagus (25 ± 8%vs 11 ± 2% for acid reflux and 27 ± 8%vs 8 ± 2% for weakly acidic reflux; P < 0.05). Compared with multiple pH‐metry, pH‐MII shows a higher sensitivity in the detection of proximal reflux. As approximately 30% of acid reflux becomes weakly acidic along the oesophageal body, to better characterize proximal reflux, in clinical practice, combined proximal pH‐impedance monitoring should be used. In NERD patients, the proximal oesophagus seems to be more sensitive to both acid and weakly acidic reflux.
Endogenous IL‐10 Regulates Sepsis‐induced Thymic Apoptosis and Improves Survival in Septic IL‐10 Null Mice
Authors: Tschoeke S. K. , Oberholzer C. , LaFace D. , Hutchins B. , Moldawer L. L. , Oberholzer A.
Published: October 2008

Recent studies have shown that increased lymphocyte apoptosis contributes to sepsis‐induced mortality. Furthermore, studies have demonstrated that IL‐10 can suppress lymphocyte apoptosis, in part, by upregulating Bcl‐2 expression and interfering with activation induced cell death. We have previously shown that intrathymic delivery of IL‐10 with an adenoviral vector in wild‐type mice significantly improves outcome to sepsis. Presently, we investigated the role of endogenous IL‐10 expression on thymocyte apoptosis and outcome in IL‐10 null mice subject to induction of generalized polymicrobial peritonitis via cecal ligation and puncture. Compared to wild‐type C57BL/6 mice, IL‐10 null mice demonstrated increased mortality and enhanced lymphocyte apoptosis. Intrathymic injection with an adenoviral vector expressing human IL‐10 prior to cecal ligation and puncture in IL‐10 null mice significantly improved outcome and decreased thymic caspase‐3 activity. Furthermore, plasma concentrations of IL‐6 were also significantly reduced in IL‐10 null mice treated with the IL‐10 expressing adenovirus. In contrast, injection of a control adenovirus did not improve outcome in IL‐10 null mice, nor was caspase‐3 activity reduced. Thus, local thymic expression of IL‐10 not only improves outcome but also reduces local tissue apoptosis and caspase‐3 activity, and appears to attenuate the systemic proinflammatory cytokine response.
Optically stimulated luminescence dating as a tool for calculating sedimentation rates in Chinese loess: comparisons with grain‐size records
Authors: STEVENS THOMAS , LU HUAYU
Published: October 2008

Understanding loess sedimentation rates is crucial for constraining past atmospheric dust dynamics, regional climatic change and local depositional environments. However, the derivation of loess sedimentation rates is complicated by the lack of available methods for independent calculation; this limits interpretation of the environmental changes revealed by the loess record. In particular, while the Quaternary/Neogene Chinese loess and Red Clay sequences have the potential to provide detailed records of past sedimentation and climate change, there is great uncertainty concerning: (i) the influences on sediment grain‐size and accumulation; and (ii) their relationship through time and across the depositional region. This uncertainty has led to the widespread use of assumptions concerning the relationship between sedimentation rate and grain‐size in order to derive age models and climate reconstructions. To address this uncertainty, detailed independent age models, based on optically stimulated luminescence dating, undertaken at 10 to 40 cm intervals at five sections across the Loess Plateau in China, have been used to calculate sedimentation rates and make comparisons with grain‐size changes over the late Pleistocene and Holocene. The results demonstrate that sedimentation rates are site specific, extremely variable over millennial timescales and that this variation is often not reflected in grain‐size changes. In the central part of the Loess Plateau, the relationship between grain‐size and sedimentation rate appears most complex, suggesting an interplay between local conditions at source and sink and a changing emplacement mechanism. This observation further undermines the common use of loess sedimentation age models that rely on a derived relationship between grain‐size and sedimentation rate from a type section. The results also highlight the difficulty in assigning specific environmental causes to sedimentation rate changes and, to a lesser extent, grain‐size shifts.
Synsedimentary brecciation in the Eifelian (Middle Devonian) Baltic Basin: sudden catastrophe or diagenetic collapse?
Authors: Tänavsuu‐Milkeviciene Kati , Plink‐Björklund Piret , Kirsimäe Kalle
Published: October 2008

The Eifelian sedimentary record in the epeiric Baltic Basin contains an extensive brecciated interval known as the Narva Breccia. During recent decades, the origin of this breccia has been attributed to (1) palaeoseismicity, (2) extraterrestrial impact event or (3) diagenetic collapse. Our studies show the presence of two different breccia types that form 11 stratigraphic horizons and contain several laterally and stratigraphically unrelated breccias. The occurrence of Type‐1 and Type‐2 breccias, together with carbonate sabkha and carbonate inter‐ to supratidal tidal flat deposits on the basin margins, indicates synsedimentary brecciation formed in a sabkha environment. Type‐2 breccia could also originate from wave‐cycling loading.
Thermochronological evidence for Mesozoic–Tertiary tectonic evolution in the eastern Sardinia
Authors: Zattin M. , Massari F. , Dieni I.
Published: October 2008

Apatite fission‐track analyses on samples from eastern Sardinia document a complex tectonic history, whose reconstruction is problematic because of the reactivation of faults and structures at different times from Jurassic to Miocene. The oldest ages (150–154 Ma) have been detected on the southern margin of the Gulf of Orosei and are related to the extensional tectonics that characterize the European passive margin during Early and Middle Jurassic times. Thermal modelling of these data allows reconstruction of the burial history of the Mesozoic basin and estimation of a sedimentary thickness of 2000 m. Part of these sediments was eroded during the following uplift, documented by mid‐Cretaceous fission‐track ages. A further exhumation episode of Eocene age has been revealed by fission‐track data on granite samples, and has been inferred to be related to the Alpine orogenic phase. This tectonic episode caused the exhumation of crustal blocks bound by faults that were finally reactivated during the Late Oligocene–Early Miocene.
The high‐resolution gravimetric geoid of North Iberia: NIBGEO
Authors: Corchete V.
Published: October 2008

The gravimetric geoid computed in the northern part of Iberia, is presented in this paper. This computation has been performed considering two study windows fitted to the areas with higher density of gravity data, to reduce the computation errors associated to the scarcity of gravity data, as much as possible. The bad influence of a bathymetry with poorer resolution than the topography is also reduced considering the smallest marine area possible. Moreover, the computation of this gravimetric model is based on the most recent geopotential model: EIGEN‐GL04C (obtained in 2006). The method used in the computation of the new gravimetric geoid has been the Stokes integral in convolution form. The terrain correction has been applied to the gridded gravity anomalies, to obtain the corresponding reduced anomalies. Also the indirect effect has been taken into account. Thus, a new geoid model has been calculated and it is provided as a data grid in the Geodetic Reference System of 1980, distributed for the northern part of Iberia from 40 to 44 degrees of latitude and −10 to 4 degrees of longitude, on a 161 × 561 regular grid with a mesh size of 1.5′ × 1.5′. This new geoid and the previous geoid Iberian Gravimetric Geoid 2005, are compared with the geoid undulations measured for eight points of the European Vertical Reference Network (EUVN) on Iberia. The new geoid shows an improvement in precision and reliability, fitting the geoidal heights of these EUVN points with more accuracy than the previous geoid. Moreover, this new geoid has a smaller standard deviation (12.6 cm) than that obtained by any previous geoid developed for the Iberian area up to date. This geoid obtained for the northern part of Iberia will complement the previously obtained geoid for South Spain and the Gibraltar Strait area; both geoids jointly will give a complete picture of the geoid for Spain and the Gibraltar Strait area. This new model will be useful for orthometric height determination by GPS over this study area, because it will allow orthometric height determination in the mountains and remote areas, in which levelling has many logistic problems. This new model contributes to our knowledge of the geoid, but the surrounding areas must be better known to constrain the lithospheric and mantle models.
OsGSR1 is involved in crosstalk between gibberellins and brassinosteroids in rice
Authors: Wang Li , Wang Zhen , Xu Yunyuan , Joo Se‐Hwan , Kim Seong‐Ki , Xue Zhen , Xu Zhihong , Wang Zhiyong , Chong Kang
Published: October 2008

Gibberellins (GAs) and brassinosteroids (BRs), two growth‐promoting phytohormones, regulate many common physiological processes. Their interactions at the molecular level remain unclear. Here, we demonstrate that OsGSR1, a member of the GAST (GA‐stimulated transcript) gene family, is induced by GA and repressed by BR. RNA interference (RNAi) transgenic rice plants with reduced OsGSR1 expression show phenotypes similar to plants deficient in BR, including short primary roots, erect leaves and reduced fertility. The OsGSR1 RNAi transgenic rice shows a reduced level of endogenous BR, and the dwarf phenotype could be rescued by the application of brassinolide. The yeast two‐hybrid assay revealed that OsGSR1 interacts with DIM/DWF1, an enzyme that catalyzes the conversion from 24‐methylenecholesterol to campesterol in BR biosynthesis. These results suggest that OsGSR1 activates BR synthesis by directly regulating a BR biosynthetic enzyme at the post‐translational level. Furthermore, OsGSR1 RNAi plants show a reduced sensitivity to GA treatment, an increased expression of the GA biosynthetic gene OsGA20ox2, which is feedback inhibited by GA signaling, and an elevated level of endogenous GA: together, these suggest that OsGSR1 is a positive regulator of GA signaling. These results demonstrate that OsGSR1 plays important roles in both BR and GA pathways, and also mediates an interaction between the two signaling pathways.
The essential gene EMB1611 maintains shoot apical meristem function during Arabidopsis development
Authors: Leasure Colin D. , Fiume Elisa , Fletcher Jennifer C.
Published: October 2008

The Arabidopsis thaliana genome contains hundreds of genes essential for seed development. Because null mutations in these genes cause embryo lethality, their specific molecular and developmental functions are largely unknown. Here, we identify a role for EMB1611/MEE22, an essential gene in Arabidopsis, in shoot apical meristem maintenance. EMB1611 encodes a large, novel protein with N‐terminal coiled‐coil regions and two putative transmembrane domains. We show that the partial loss‐of‐function emb1611‐2 mutation causes a range of pleiotropic developmental phenotypes, most dramatically a progressive loss of shoot apical meristem function that causes premature meristem termination. emb1611‐2 plants display disorganization of the shoot meristem cell layers early in development, and an associated stem cell fate change to an organogenic identity. Genetic and molecular analysis indicates that EMB1611 is required for maintenance of the CLV‐WUS stem cell regulatory pathway in the shoot meristem, but also has WUS‐independent activity. In addition, emb1611‐2 plants have reduced shoot and root growth, and their rosette leaves form trichomes with extra branches, a defect we associate with an increase in endoreduplication. Our data indicate that EMB1611 functions to maintain cells, particularly those in the shoot meristem, roots and developing rosette leaves, in a proliferative or uncommitted state.
The major histocompatibility complex class Ib molecule HLA‐E at the interface between innate and adaptive immunity
Authors: Sullivan L. C. , Clements C. S. , Rossjohn J. , Brooks A. G.
Published: October 2008

The non‐classical major histocompatibility complex (MHC) class I molecule human leucocyte antigen (HLA)‐E is the least polymorphic of all the MHC class I molecules and acts as a ligand for receptors of both the innate and the adaptive immune systems. The recognition of self‐peptides complexed to HLA‐E by the CD94‐NKG2A receptor expressed by natural killer (NK) cells represents a crucial checkpoint for immune surveillance by NK cells. However, HLA‐E can also be recognised by the T‐cell receptor expressed by αβ CD8 T cells and therefore can play a role in the adaptive immune response to invading pathogens. The recent resolution of HLA‐E in complex with both innate and adaptive ligands has provided insight into the dual role of this molecule in immunity.
Impact of cytokine gene polymorphisms on graft‐vs‐host disease
Authors: Markey K. A. , MacDonald K. P. A. , Hill G. R.
Published: October 2008

Allogeneic hematopoietic stem cell transplantation (SCT) remains the only available curative therapy for hematological malignancy. It does, however, result in significant morbidity and mortality, predominantly as a consequence of infections, leukemic relapse and graft‐vs‐host disease (GVHD). While differences in human leukocyte antigen (HLA) molecules between donor and host make a crucial contribution to the alloreactivity driving the donor–antihost response, the cytokine milieu consisting of molecules that both promote and regulate the alloresponse after transplantation is also critical. As such, genetic studies correlating donor and/or host cytokine polymorphisms with disease outcomes have provided useful insight into disease pathogenesis, often confirming effects that have been dissected in animal models of the disease. It is now clear that the polymorphic expression of key cytokines (particularly tumor necrosis factor and interleukin 10) has a demonstrable effect on disease outcome and overall transplant‐related mortality. Consideration of the role of genetic polymorphisms in GVHD severity and procedural mortality associated with SCT will lead to improvements in patient outcome such that the addition of non‐HLA genetic typing of potential donors will allow optimization of donor selection for a given recipient. This review provides a discussion of the current state of the literature regarding polymorphic expression of the key GVHD cytokines and their capacity to predict clinical disease outcome.
Evidence for cattle major histocompatibility complex (BoLA) class II DQA1 gene heterozygote advantage against clinical mastitis caused by Streptococci and Escherichia species
Authors: Takeshima S. , Matsumoto Y. , Chen J. , Yoshida T. , Mukoyama H. , Aida Y.
Published: October 2008

Mastitis is an inflammatory response of the mammary gland to irritation, injury, or infectious agents and is a major problem in the dairy industry. We genotyped bovine major histocompatibility complex (BoLA)‐DRB3 and BoLA‐DQA1 genes in 120 Holstein cattle with clinical mastitis and 85 randomly selected Holstein cattle in Japan by polymerase chain reaction–sequence‐based typing. The mastitis cattle were divided into four groups according to the bacterial species that caused the mastitis (Staphylococcus aureus, Streptococci, Escherichia, and coagulase‐negative staphylococci). The BoLA‐DRB3 and BoLA‐DQA1 heterozygosity of each group was compared with that of the control cattle, while the expected heterozygosities based on Hardy–Weinberg proportions and the observed heterozygosities for each locus were compared for each group. The Escherichia‐induced and Streptococci‐induced mastitis groups showed significant differences between their expected and observed heterozygosities with regard to their BoLA‐DQA1 genes. No differences were observed for any group with regard to the BoLA‐DRB3 genes. We then found that two BoLA‐DQA1 alleles promoted susceptibility to Streptococci‐induced mastitis, namely BoLA‐DQA1*0101 and BoLA‐DQA1*10012 and that the homozygous BoLA‐DQA1*0101/0101 and BoLA‐DQA1*10011/10011 genotypes promoted susceptibility to mastitis caused by Streptococci and Escherichia, respectively. This is the first report showing that heterozygosity of the BoLA‐DQA1 gene is associated with resistance to mastitis progression.
Alleles and intron polymorphism of KIR3DL1 shown by combination of allele group‐specific primers and sequencing
Authors: Sun J. Y. , Oki A. , Senitzer D.
Published: October 2008

Allelic polymorphism of killer immunoglobulin‐like receptor (KIR) genes may affect receptor expression as well as function. We used a combination of allele group‐specific primers and DNA sequencing techniques to verify our KIR genotyping primers in polymerase chain reaction and identified three KIR3DL1 alleles. By sequencing some introns of 3DL1 in 18 genomic DNA samples, we found that a 4‐bp insert in intron 1 of 3DL1*002 exists in multiple alleles, but that a 2‐bp deletion in intron 7 is unique to 3DL1*01501 and that a 19‐bp insert in intron 1 seems specific to the CEPH family 1416. Our data suggest that extensive KIR gene polymorphisms are ubiquitous as well as quite complex.
HLA‐A polymorphisms in four ethnic groups from Guinea‐Bissau (West Africa) inferred from sequence‐based typing
Authors: Spínola C. , Bruges‐Armas J. , Brehm A. , Spínola H.
Published: October 2008

Human leukocyte antigen (HLA)‐A locus polymorphisms were examined at high‐resolution level, using sequence‐based typing, in the four most representative Guinea‐Bissau (Northwest Africa) ethnic groups: Balanta, Bijagós, Fula and Papel. Despite the Fula group having significant differences when compared with the other three ethnic groups, all four groups most likely received a genetic input from non sub‐Saharans. The Bijagós and Papel groups showed similarities to neighboring populations from Mali and Senegal. The Balanta, despite their oral tradition of an East Africa origin, show affinities to Cameroon populations, highly influenced by Bantu migrations. These results are congruent with historical sources and other genetic studies that support the finding that the Guinea‐Bissau genetic pool was influenced by several migrations from North Africa, Sahara and East Africa.