bluuebunny/crossref_metadata_2025 huggingface dataset:
Linear ubiquitin fusion to Rps31 and its subsequent cleavage are required for the efficient production and functional integrity of 40S ribosomal subunits
Authors: Lacombe Thierry , García‐Gómez Juan J. , De La Cruz Jesús , Roser Daniela , Hurt Ed , Linder Patrick , Kressler Dieter
Published: February 2009

The post‐translational modifier ubiquitin is generated exclusively by proteolytic cleavage of precursor proteins. In Saccharomyces cerevisiae, cleavage of the linear precursor proteins releases ubiquitin and the C‐terminally fused ribosomal proteins Rpl40 (Ubi1/2 precursor) and Rps31 (Ubi3 precursor), which are part of mature 60S and 40S ribosomal subunits respectively. In this study, we analysed the effects of ubi3 mutations that interfere with cleavage of the ubiquitin–Rps31 fusion protein. Strikingly, the lethal ubi3+P77 mutation, which abolished cleavage almost completely, led to a rapid G1 cell cycle arrest upon genetic depletion of wild‐type UBI3. Under these conditions, the otherwise unstable Ubi3+P77 protein was efficiently assembled into translation‐competent 40S ribosomal subunits. In contrast to the cleavage‐affecting mutations, deletion of the ubiquitin moiety from UBI3 led to a decrease in 40S ribosomal subunits and to the incorporation of the 20S pre‐rRNA into polyribosomes. Altogether, our findings provide additional evidence that the initial presence of the ubiquitin moiety of Ubi3 contributes to the efficient production of 40S ribosomal subunits and they suggest that ubiquitin release is a prerequisite for their functional integrity.
The targeting of the oxysterol‐binding protein ORP3a to the endoplasmic reticulum relies on the plant VAP33 homolog PVA12
Authors: Saravanan Ramu S. , Slabaugh Erin , Singh Vijay R. , Lapidus Lisa J. , Haas Thomas , Brandizzi Federica
Published: February 2009

In plants, sterols play fundamental roles as membrane constituents in the biosynthesis of steroid hormones, and act as precursors for cell wall deposition. Sterols are synthesized in the endoplasmic reticulum (ER), but mainly accumulate in the plasma membrane. How sterols are trafficked in plant cells is largely unknown. In non‐plant systems, oxysterol‐binding proteins have been involved in sterol trafficking and homeostasis. There are at least twelve homologs of oxysterol‐binding proteins in the Arabidopsis genome, but the biology of these proteins remains for the most part obscure. Here, we report our analysis of the targeting requirements and the sterol‐binding properties of a small Arabidopsis oxysterol‐binding protein, ORP3a. We have determined that ORP3a is a bona fide sterol‐binding protein with sitosterol‐binding properties. Live‐cell imaging analyses revealed that ORP3a is localized at the ER, and that binding to this organelle depends on a direct interaction with PVA12, a member of the largely uncharacterized VAP33 family of plant proteins. Molecular modeling analyses and site‐directed mutagenesis led to the identification of a novel protein domain that is responsible for the PVA12–ORP3a interaction. Disruption of the integrity of this domain caused redistribution of ORP3a to the Golgi apparatus, suggesting that ORP3a may cycle between the ER and the Golgi. These results represent new insights into the biology of sterol‐binding proteins in plant cells, and elucidate a hitherto unknown relationship between members of oxysterol‐binding protein and VAP33 families of plant proteins in the early plant secretory pathway.
Lung transplantation in patients with scleroderma: case series, review of the literature, and criteria for transplantation
Authors: Shitrit David , Amital Anat , Peled Nir , Raviv Yael , Medalion Benjamin , Saute Milton , Kramer Mordechai R.
Published: February 2009

Abstract:  Backgrounds:  The use of lung transplantation (LTX) to treat respiratory failure because of scleroderma is controversial. We present our experience, review the current literature, and suggest specific criteria for LTX in scleroderma. Of the 174 patients who underwent LTX at our center, seven (4%) had scleroderma‐associated respiratory failure.

Patients and methods:  A MEDLINE search of the English literature was performed for studies of LTX in patients with scleroderma between 1986 and 2006. A Kaplan–Meier survival curve was calculated over the time of the studies.

Results:  The MEDLINE search yielded one large review and four small case series. The small case series were included in the review. The review and our series yield a total of 54 patients. Mean patient age was 47.1 yr; 59.3% were female. Pre‐operative lung data were available for 24 patients: 22 (92%) had pulmonary fibrosis and 17 (71%) had pulmonary hypertension. Most patients (69%) underwent single‐lung transplantation. Mean forced expiratory volume at one s after LTX was 67% (range 56–87%). There was no difference in infection and rejection rates between the patients with scleroderma and other LTX recipients. The two‐ and five‐yr survival rates were 72% and 55%, respectively.

Conclusions:  LTX is a valid option in well‐selected patients with scleroderma and pulmonary fibrosis, yielding good pulmonary function and acceptable morbidity and mortality.
Calcineurin inhibitor effects on glucose metabolism and endothelial function following renal transplantation
Authors: Åsberg Anders , Midtvedt Karsten , Voytovich Monica H. , Line Pål‐Dag , Narverud Janicke , Reisæter Anna V. , Mørkrid Lars , Jenssen Trond , Hartmann Anders
Published: February 2009

Abstract: Background:  Calcineurin inhibitors (CNI) are involved in the development of post‐transplant diabetes mellitus (PTDM). Changes in insulin secretion and sensitivity contribute to the development of PTDM and are associated with endothelial function.

Methods:  In a pre‐defined substudy of a previously published randomized trial in renal transplant recipients we compared the effect of CNI treatment (n = 23) with complete CNI‐avoidance (n = 21) on insulin secretion and sensitivity (oral glucose tolerance test) as well as endothelial function (laser Doppler flowmetry), 10 wk and 12 months following transplantation.

Results:  Insulin sensitivity differed 10 wk post‐transplant and was significantly better after 12 months in patients never treated with CNI drugs [0.091 (0.050) vs. 0.083 (0.036) μmol/kg/min/pmol/L, p = 0.043]. Insulin secretion tended to be higher in CNI treated patients at both time points (p = 0.068). Endothelial function was not significantly different at week 10 [540 (205) vs. 227 (565) arbitary units × minutes, p = 0.35] or month 12 [510 (620) vs. 243 (242), p = 0.33].

Conclusions:  Findings in the present study indicate that long‐term CNI treatment negatively affects glucose metabolism and this may contribute to the increased risk for premature cardiovascular disease in CNI treated renal transplant recipients. Further studies to elucidate this hypothesis are, however, needed.
Promoter deletion analysis elucidates the role of cis elements and 5'UTR intron in spatiotemporal regulation of AtPht1;4 expression in Arabidopsis
Authors: Karthikeyan Athikkattuvalasu S. , Ballachanda Devaiah N. , Raghothama Kashchandra G.
Published: February 2009

The high‐affinity phosphate transporter AtPht1;4 (Arabidopsis phosphate transporter1;4) is not only induced in response to inorganic phosphate (Pi) starvation but also preferentially expressed in the roots of Arabidopsis. In this study, we carried out AtPht1;4 promoter deletion analysis to identify regions that control the Pi responsiveness and spatiotemporal expression of the gene. Expression cassettes with truncated promoter fragments cloned to GUS (β‐glucuronidase) coding sequence were developed. Full‐length promoter (‐2327) and truncations up to ‐1436 (from the translational start) showed normal expression of GUS in various parts of the plants. The Pi responsiveness and inducibility of the reporter gene remained unaltered. However, deletion of the promoter region containing the first PHR1‐binding site (P1BS) motif (‐1350) abolished the AtPht1;4 expression in roots but not in aerial parts. A 164‐bp region immediately upstream of the transcription start site appears to be sufficient for the basal expression of the gene. Interestingly, the 5'UTR (5′ untranslated region) intron exhibited weak promoter activity as evidenced by its ability to drive the expression of AtPht1;4 in stipules and reproductive organs. Further analyses showed that the 5'UTR intron is essential for AtPht1;4 expression in root tips besides enhancing the level of expression in roots during Pi starvation. However, expression of AtPht1;4 in aerial parts of the plant was not influenced by the intron. Together these results suggest that expression of AtPht1;4 in the roots and aerial parts is regulated by independent mechanisms.
Effects of Temperature on the Alkaloid Content of Seeds of Lupinus angustifolius Cultivars
Authors: Jansen G. , Jürgens H.‐U. , Ordon F.
Published: February 2009

Three experiments were conducted to investigate the effects of high temperatures during seed filling on the alkaloid content of narrow‐leaf lupin cultivars. Six cultivars of Lupinus angustifolius were grown in field experiments under different weather conditions in four subsequent years. A high content of alkaloids was found in the seeds harvested in 2006, in which the growing season was characterized by high ambient temperatures during seed filling. A second experiment was performed in the green house at different temperatures (10, 20 and 30 °C) using one cultivar in 2006. This experiment confirmed the results of the field experiments as higher temperatures resulted in a higher alkaloid content of the seeds. In a third temperature stress experiment, three cultivars were grown under long day conditions at day/night temperatures of 30 °C/16 °C and 20 °C/16 °C in growth chambers in comparison with an outdoor control at mean temperatures of 15.5 °C. Like in the other experiments, the seed alkaloid content increased with rising temperature. From these results, it may be concluded that the seed alkaloid content is strongly influenced by the temperature during initiation of flowering up to pod ripening. This has to be taken into account e.g. in trials for cultivar release in which the alkaloid content is a knock‐out criterion.
Effect of Phosphorus Deficiency on Reflectance and Chlorophyll Fluorescence of Cotyledons of Oilseed Rape (Brassica napus L.)
Authors: Yaryura P. , Cordon G. , Leon M. , Kerber N. , Pucheu N. , Rubio G. , García A. , Lagorio M. G.
Published: February 2009

The spectroscopic changes in reflectance and fluorescence caused by phosphorus (P) starvation in Brassica napus L. young plants were evaluated. P deficiency produced an important decrease in reflectance values between 500 and 650 nm for both intact leaves and cotyledons. Furthermore, cotyledons under P deficiency showed a Chl‐F ratio in the red/far‐red region (Fred/Ffar‐red) lower than that of non‐stressed plants (1.91 and 2.89 respectively). As minimal differences in Fred/Ffar‐red were detected in leaves, P deficiencies may be better perceived by measuring changes in Chl‐F emission in cotyledons than in leaves. Stressed cotyledons also showed different emission spectra in the blue green (maxima at 470 and 560 nm) from those of non‐stressed cotyledons. The results are explained in terms of higher anthocyanin and chlorophyll contents and of damage to photosystem II. We evaluate that measuring variations in fluorescence and reflectance data may be useful to detect early damages induced by P stress.
The influence of light availability and predatory behavior of the decapod crustacean Nephrops norvegicus on the activity rhythms of continental margin prey decapods
Authors: Aguzzi Jacopo , Bahamon Nixon , Marotta Leonardo
Published: February 2009

The day–night cycle is one of the strongest geophysical cycles modulating species’ behavioral rhythms. However, in deep‐water continental margins, where light intensity decreases over depth, interspecific competition may alter behavioral responses to day–night cycles. The burrowing decapod crustacean Nephrops norvegicus is a large‐size predator in benthic communities, exerting despotic territorial behavior. In this study, we analysed how the effect of light intensity cycles on decapod behavioral rhythms is reduced as one moves from shelves to slopes. In the Western Mediterranean, the predatory behavior and interspecific competition for substrate use of Nephrops increases moving from the shelf (100–110 m) to the slope (400–430 m). Vector fitting and generalized additive models were used to assess the effect of light intensity and behavioral rhythms of N. norvegicus on the temporal variation of prey decapods co‐occurring in trawl tow catches carried out on the shelf and the slope during October 1999 and June 2000. The combination of diel variations in light intensity and N. norvegicus abundance influences the activity rhythms of prey decapods in a depth‐ and seasonal‐dependent manner. Light modulation is stronger on the shelf and weaker on the slope, where Nephrops population size is greater. Although present regression analysis does not necessarily imply a direct cause–effect relationship between rhythms of predators and prey, we suggest that Nephrops alters the temporal patterning in the behavior of its prey on the slope, where light intensity is reduced. This alteration is stronger in endobenthic species than in benthopelagic species; the former rely on bottom substrate for the expression of behavioral rhythms, experiencing stronger interspecific competitions with Nephrops at time of activity.
Growth dynamics and bioactivity variation of the Mediterranean demosponges Agelas oroides (Agelasida, Agelasidae) and Petrosia ficiformis (Haplosclerida, Petrosiidae)
Authors: Ferretti Cristina , Vacca Simone , De Ciucis Chiara , Marengo Barbara , Duckworth Alan R. , Manconi Renata , Pronzato Roberto , Domenicotti Cinzia
Published: February 2009

Growth dynamics and bioactivity variation of the Mediterranean demosponges Agelas oroides and Petrosia ficiformis were investigated over 15 months at Paraggi and Colombara within the Marine Reserve of Portofino Promontory (Mediterranean Sea, Ligurian Sea, Italy). For both species, growth rates varied between individuals and were unaffected by initial sponge size. The two species showed a different trend in growth pattern: A. oroides did not vary significantly between seasons, sites and depths; in contrast, some individuals of P. ficiformis showed a seasonal pattern, shrinking during winter as water temperature decreased and growing during summer when water temperature increased. Differences in growth between the two species may result from different reproductive cycles, food availability, species‐specific thermophily and patterns of spatial competition. Moreover, spatial competition probably induced sponges to produce bioactive secondary molecules. Spatial and temporal variation of bioactivity of both species was examined for the first time by studying its effect on human neuroblastoma cells. The bioactivity of A. oroides extracts differed significantly between seasons, sites and depths, whereas the cytotoxicity of P. ficiformis differed significantly between seasons and depths (differences for sites were not determined). These results suggest the possible influence of environmental factors on bioactive metabolite biosynthesis.
Correlation of restriction fragment length polymorphism genotyping with internal transcribed spacer sequence, randomly amplified polymorphic DNA and multilocus sequence groupings for Candida parapsilosis
Authors: Van Asbeck Eveline C. , Clemons Karl V. , Markham Angela N. , Stevens David A.
Published: February 2009

Epidemiological studies of Candida parapsilosis have been performed by molecular methods. To compare two prominent methods, 29 isolates, typed by multilocus sequence typing (MLST), were typed by restriction fragment length polymorphism (RFLP). Of the 19 proposed Candida parapsilosis sensu stricto isolates [group I by internally transcribed spacer (ITS1) sequence], the most commonly encountered species, 17 were RFLP type VII‐1. The species Candida orthopsilosis (eight isolates) and Candida metapsilosis (two isolates) consisted of five and one other RFLP types, respectively; none were VII‐1. None of the non‐VII‐1 types were in more than one ITS group. VII‐1 is the most common RFLP type (176/203 in continuing studies), and C. parapsilosis sensu stricto is similarly dominant in other studies, and cannot be subtyped by RFLP or MLST. RFLP subtype VII‐1 and C. parapsilosis sensu stricto appear to be nearly identical; C. orthopsilosis, which can be subtyped by MLST, can also be subtyped by RFLP. C. metapsilosis appears rarely.
The parent‐reported prevalence and management of peanut and nut allergy in school children in the Australian Capital Territory
Authors: Kljakovic Marjan , Gatenby Paul , Hawkins Carolyn , Attewell Robyn G , Ciszek Karen , Kratochvil Gitta , Moreira Alayne , Ponsonby Anne‐Louise
Published: February 2009

Aim:  To describe parent‐reported prevalence and management of peanut and nut allergy in school entrant children.

Method:  A population‐based, cross‐sectional study in the Australian National Capital.

Results:  Out of 3851 children, parents reported 127 had a strong allergic reaction to peanuts and 19 to other nuts ever. Nut allergy ever prevalence was 3.8% (95% confidence interval 3.2–4.4%), and of peanut allergy ever 3.3% (2.8–3.9%).

Children with nut allergy were more likely to have a general practitioner (odds ratio 2.64, 1.16–6.03), hay fever (3.78, 2.67–5.36), eczema (4.54, 3.15–6.56) and wheeze in the last 12 months (3.19, 2.22–4.59) and have been breastfed (2.68, 1.26–5.77) than those who did not.

At follow up of 109 children with parent‐reported allergy (75% response), 70% had diagnostic test‐confirmed sensitisation, 32% had been prescribed an adrenalin autoinjector (6% had used one) and 46% were not eating peanut. Increasing severity of reported symptoms following consumption of peanut was associated with an increasing likelihood of recommended management. Based on parent report, the projected estimated diagnostic test‐confirmed prevalence of peanut sensitisation was 2.4% (1.9%, 3.0%) for the entire sample.

Conclusion:  Among a highly representative sample of children at school entry, 1 in 30 parents reported their child to have a strong allergic reaction to nuts and over 1 in 50 are estimated to have diagnostic test‐confirmed peanut sensitisation, based on parent report.
Do no more harm: The psychological stress of the medical examination for alleged child sexual abuse
Authors: Marks Susan , Lamb Robyn , Tzioumi Dimitra
Published: February 2009

Aim:  Currently, there is some controversy that the medical examination following allegations of child sexual abuse may further traumatise the child. Access for children to appropriate care may be hindered if decisions about referral are influenced by personal beliefs, rather than by recognition of the potential health and psychological benefits of the assessment. We aimed to study the expectations and emotional responses of children and their parents to the medical examination.

Methods:  We conducted a prospective quantitative and qualitative study at the Children's Hospital at Westmead. Participants completed questionnaires pre‐examination and post‐examination, including Children's Anxiety and Pain Scales. Clinicians recorded a Genital Examination Distress Scale and a questionnaire about potentially prognostic variables.

Results:  Parents found the medical examination significantly less stressful than they had anticipated. They highlighted the importance of being involved in the process, the child's reaction, staff attitudes and the doctor's explanations. Although most parents expected that the medical would be stressful for their child, this did not correlate with the children's reports of feeling scared beforehand. Increased parental and child distress were significantly associated with the child being 12 years or older. The type of abuse was not significantly linked to any of the parent or child self‐reports.

Conclusion:  Our findings indicate that the medical examination is not as stressful as expected and support the recommendation that timely medical assessment by appropriately trained professionals should be offered for all children following allegations of sexual abuse.
Role of NAD(P)H oxidase in transforming growth factor‐β1‐induced monocyte chemoattractant protein‐1 and interleukin‐6 expression in rat renal tubular epithelial cells
Authors: ZHANG HAIYAN , JIANG ZONGPEI , CHANG JIE , LI XIAOYAN , ZHU HENGMEI , LAN HUI Y , ZHOU SHU‐FENG , YU XUEQING
Published: February 2009

Aim:  This study investigated the role of NAD(P)H oxidase in transforming growth factor‐β1 (TGF‐β1)‐induced reactive oxygen species (ROS) generation, monocyte chemoattractant protein‐1 (MCP‐1), and interleukin‐6 (IL‐6) expression in rat renal tubular epithelial NRK‐52E cells.

Methods:  The cells were treated with 10 ng/mL TGF‐β1, either in the presence or absence of the NAD(P)H oxidase inhibitor, diphenyleneiodonium (DPI), or short hairpin RNA (shRNA) suppressing p67phox expression. Expression of NAD(P)H oxidase subunits, MCP‐1, and IL‐6 at the mRNA levels was detected by reverse transcription polymerase chain reaction, while expression of NAD(P)H oxidase subunit p67phox protein was analyzed by western blot and MCP‐1 by enzyme‐linked immunosorbent assay. The cellular ROS generation was visualized using 2′,7′‐dichlorodihydrofluorescein diacetate by confocal microscopy.

Results:  Compared to control, TGF‐β1 upregulated NAD(P)H oxidase subunit p67phox mRNA by 3.59‐fold (P < 0.01), but had no effect on p22phox, gp91phox and p47phox NAD(P)H subunits. TGF‐β1 was also able to significantly increase intracellular ROS (P < 0.05), MCP‐1 (P < 0.01) and IL‐6 (P < 0.05) expression in NRK‐52E cells. Further studies showed that generation of ROS and upregulation of MCP‐1 and IL‐6 by TGF‐β1 were significantly blocked by addition of DPI or shRNA‐p67phox (P < 0.01), suggesting that these effects were NAD(P)H oxidase‐dependent.

Conclusion:  TGF‐β1 differentially regulates the expression of NAD(P)H oxidase subunits and mediates MCP‐1 and IL‐6 expression in rat renal tubular cells via the NAD(P)H oxidase/p67phox‐dependent mechanism.
Effect of N‐acetylcysteine on the early expression of inflammatory markers in the retina and plasma of diabetic rats
Authors: Tsai Gina Y , Cui Jing Z , Syed Husnain , Xia Zhengyuan , Ozerdem Ugur , McNeill John H , Matsubara Joanne A
Published: February 2009

Abstract

Purpose:  The aim of this study is to investigate markers of inflammation and oxidative stress in an early model of diabetic retinopathy, correlate retinal and plasma results and evaluate the influence of treatment by N‐acetylcysteine (NAC), a free radical scavenger.

Methods:  Four groups were studied: control (C), streptozotocin (STZ)‐induced diabetic rats (D), STZ rats following 8 weeks of NAC (DT), and control rats following 8 weeks of NAC (CT). Plasma levels of free 15‐F2t‐isoprostane (15‐F‐2t‐IsoP), superoxide dismutase (SOD) and tumour necrosis factor‐alpha (TNF‐α) were obtained. Primary antibodies against macrophages (ED‐1), microglia (Ox‐42), pericytes (NG‐2), endothelial and perivascular cells (IB‐4), haem oxygenase 1 (HO‐1) and vascular endothelial growth factor (VEGF) were used.

Results:  Expression of NG‐2 was robust in C, CT, DT, and mild in D. The intensity of IB‐4 was higher in D and DT compared with the C and CT. Ox‐42 and ED‐1 expression was higher in the D than in the DT, C or CT. Expression of VEGF and HO‐1 was non‐specific across the four groups. Plasma levels of 15‐F‐2t‐IsoP and TNF‐α were higher in the D as compared with the C, CT and DT. SOD levels were lower in the D when compared with the C, CT and D.

Conclusions:  Macrophage/microglia activation, pericyte loss and endothelial/perivascular cell changes occur early in the pathogenesis of DR. These changes are associated with an increase in plasma markers of oxidative stress and inflammation and are minimized by treatment with NAC. The results suggest that therapies that reduce free radicals will help minimize the early events in diabetic retinopathy in the STZ model.
Enhanced recovery in colorectal resections: a systematic review and meta‐analysis1
Authors: Walter C. J. , Collin J. , Dumville J. C. , Drew P. J. , Monson J. R.
Published: February 2009

Objective  The study aimed to produce a comprehensive up‐to‐date meta‐analysis exploring the safety and efficacy of enhanced recovery (ER) programmes after colorectal resection.

Method  Key‐word and MESH‐heading searches of MEDLINE, EMBASE and the Cochrane Databases from 1966 to February 2007 were used to identify all available randomized and clinical controlled studies. Two independent reviewers assessed studies for inclusion and exclusion based on methodological quality criteria prior to undertaking data extraction. Summary estimates of treatment effects using a fixed effect model were produced with RevMan 1.0.2, using weighted means for length‐of‐stay data and relative risks of morbidity, mortality and readmission rates.

Results  Analysis of four papers including 376 patients demonstrated primary and total length‐of‐stays (primary + readmission length‐of‐stay) to be significantly reduced (P < 0.001) with ER programmes [weighted mean differences of −3.64 days (95% confidence interval, 95% CI −4.98 to −2.29) and −3.75 days (95% CI−5.11 to −2.40)]. Analysis of controlled clinical trial data showed morbidity rates to be reduced and readmission rates increased. These trends were not seen amongst the randomized controlled trial data. There were no differences in mortality rates.

Conclusion  Enhanced recovery programmes after colorectal resections reduce length‐of‐stay and may reduce 30 days morbidity and increase 30 days readmission without increasing mortality.
Differences in ano‐neorectal physiology of ileoanal and coloanal reconstructions for restorative proctectomy
Authors: Rink A. D. , Kneist W. , Radinski I. , Guinot‐Barona A. , Lang H. , Vestweber K.‐H.
Published: February 2009

Objective  Restorative proctectomy with straight coloanal anastomosis (CAA) and restorative proctocolectomy with ilealpouch‐anal anastomosis (IPAA) are options for maintaining bowel integrity after rectal resection. The aim of this study was to compare clinical function and anorectal physiology in patients treated with CAA and IPAA.

Method  Three‐dimensional vector‐manometry and neorectal volumetry were performed in straight CAA [53 patients (34 male)] and IPAA [61 patients (39 male)] for ulcerative colitis. Function was assessed using a 14 day incontinence diary.

Results  Function was similar in both groups, but neorectal compliance and threshold volumes for sensation, urge and maximum tolerated volume (MTV) were significantly higher after IPAA than after CAA. Mean pressure, vector volume and sphincter symmetry at rest were significant determinants of continence in both groups but squeeze pressure did not correlate significantly with function in either group. Threshold volume, MTV, and compliance were significantly correlated with frequency of defecation in patients with IPAA but not with CAA.

Conclusion  A strong consistent resting anal sphincter pressure is one determinant of continence after both IPAA and CAA. Squeeze pressures do not influence the functional result. In IPAA but not CAA, the neorectum has a reservoir function which correlates with the postoperative frequency of defaecation.
A minimal model of the variability of marine ecosystems
Authors: Mullon Christian , Fréon Pierre , Cury Philippe , Shannon Lynne , Roy Claude
Published: February 2009

In marine ecology, population abundance time series often reveal patterns, such as decadal pseudo‐cycles, on scales that make them difficult to mathematically characterize by means of conventional models based on functional responses. We propose here a simple non‐deterministic model based on three strong ecological constraints, without any use of functional responses or external factors: (i) mass balance constraints between flows and biomass, (ii) a satiation constraint relating inflows and biomass and (iii) an inertia principle restricting the variation of populations of a given species according to its lifespan. This model reproduces in a robust manner observed patterns of variability and can be used to question the relevance of other modelling approaches of ecosystem dynamics with regard to determinism, constraints and stochasticity. Referring to a non‐deterministic model without any functional relationships and environmental or anthropogenic forcing can help in avoiding misleading advice based on the belief that we can explain the causes of observed patterns, which may simply result from basic structural constraints within which the ecosystem functions.
Vulnerability of national economies to the impacts of climate change on fisheries
Authors: Allison Edward H. , Perry Allison L. , Badjeck Marie‐Caroline , Neil Adger W. , Brown Katrina , Conway Declan , Halls Ashley S. , Pilling Graham M. , Reynolds John D. , Andrew Neil L. , Dulvy Nicholas K.
Published: February 2009

Anthropogenic global warming has significantly influenced physical and biological processes at global and regional scales. The observed and anticipated changes in global climate present significant opportunities and challenges for societies and economies. We compare the vulnerability of 132 national economies to potential climate change impacts on their capture fisheries using an indicator‐based approach. Countries in Central and Western Africa (e.g. Malawi, Guinea, Senegal, and Uganda), Peru and Colombia in north‐western South America, and four tropical Asian countries (Bangladesh, Cambodia, Pakistan, and Yemen) were identified as most vulnerable. This vulnerability was due to the combined effect of predicted warming, the relative importance of fisheries to national economies and diets, and limited societal capacity to adapt to potential impacts and opportunities. Many vulnerable countries were also among the world’s least developed countries whose inhabitants are among the world’s poorest and twice as reliant on fish, which provides 27% of dietary protein compared to 13% in less vulnerable countries. These countries also produce 20% of the world’s fish exports and are in greatest need of adaptation planning to maintain or enhance the contribution that fisheries can make to poverty reduction. Although the precise impacts and direction of climate‐driven change for particular fish stocks and fisheries are uncertain, our analysis suggests they are likely to lead to either increased economic hardship or missed opportunities for development in countries that depend upon fisheries but lack the capacity to adapt.
Risk factors for the presence of non‐rhesus D red blood cell antibodies in pregnancy*
Authors: Koelewijn JM , Vrijkotte TGM , de Haas M , van der Schoot CE , Bonsel GJ
Published: February 2009

Objective  To identify risk factors for the presence of non‐rhesus D (RhD) red blood cell (RBC) antibodies in pregnancy. To generate evidence for subgroup RBC antibody screening and for primary prevention by extended matching of transfusions in women <45 years.

Design  Case–control study.

Setting  Nationwide evaluation of screening programme for non‐RhD RBC antibodies.

Population  Cases: consecutive pregnancies (n = 900) with non‐RhD immunisation identified from 1 September 2002 to 1 June 2003 and 1 October 2003 to 1 July 2004; controls (n= 968): matched for obstetric caregiver and gestational age.

Methods  Data collection from the medical records and/or from the respondents by a structured phone interview.

Main outcome measures  Significant risk factors for non‐RhD immunisation in multivariate analysis.

Results  Significant independent risk factors: history of RBC transfusion (OR 16.7; 95% CI: 11.4–24.6), parity (para‐1 versus para‐0: OR 1.3; 95% CI: 1.0–1.7; para‐2 versus para‐0: OR 1.4; 95% CI: 1.0–2.0; para >2 versus para‐0: OR 3.2; 95% CI: 1.8–5.8), haematological disease (OR 2.1; 95% CI: 1.0–4.2), history of major surgery (OR 1.4; 95% CI: 1.1–1.8). For the clinically most important antibodies, anti‐K, anti‐c and other Rh‐nonD‐antibodies RBC transfusion was the most important risk factor, especially for anti‐K (OR 96.4; 95%‐CI: 56.6–164.1); 83% of the K‐sensitised women had a history of RBC transfusion. Pregnancy‐related risk factors were a prior male child (OR 1.7; 95% CI: 1.2–2.3) and caesarean section (OR 1.7; 95% CI: 1.1–2.7).

Conclusions  RBC transfusion is by far the most important independent risk factor for non‐RhD immunisation in pregnancy, followed by parity, major surgery and haematological disease. Pregnancy‐related risk factors are a prior male child and caesarean section. Subgroup screening for RBC antibodies, with exclusion of RhD‐positive para‐0 without clinical risk factors, is to be considered. This approach will be equally sensitive in detecting severe Haemolytic Disease of the Fetus and Newborn compared with the present RBC antibody screening programme without preselection. Primary prevention by extending preventive matching of transfusions in women younger than 45 will prevent more than 50% of pregnancy immunisations.
Occurrence of placental abruption in relatives
Authors: Rasmussen S , Irgens LM
Published: February 2009

Objective  The aim of this study was to assess the recurrence of placental abruption by severity, comparing the risk in a woman with that of recurrence in her sister and in the partner of her brother.

Design  Prospective observational study.

Setting  General population.

Population  Population‐based study based on records of pregnancies from the Medical Birth Registry of Norway; 377 902 sisters with 767 395 pregnancies, 168 142 families incorporating 2–10 sisters, and 346 385 brothers with 717 604 pregnancies in their partners were identified.

Methods  Placental abruption with preterm birth, birthweight below 2500 g or perinatal death was defined as severe, other cases as mild. Because of the nested family data structure, multilevel multivariate regression was used.

Main outcome measures  Placental abruption (severe and mild).

Results  Adjusted odds ratios of recurrence of mild and severe abruption were 6.5 (1.7%) and 11.5 (3.8%), respectively, compared with risks of 0.2 and 0.3% in the total population. After a severe abruption, odds ratios in her sisters were 1.7–2.1, whereas mild abruption produced no increased recurrence in sisters. The estimated heritability between sisters of severe abruption was 16%. No excess rate of abruption was observed between sisters and brothers’ partners, between brothers’ partners, or from brothers’ partners to sisters. The odds ratios for a third abruption after a second abruption and a second severe abruption were 38.7 (19%) and 50.1 (24%), respectively.

Conclusions  The recurrence risk of placental abruption in the same woman was higher after severe than mild abruption. Severe abruption was associated with a two‐fold risk in sisters. Pregnancies following a second abruption should be considered very high risk.
Managed Care Quality of Care and Plan Choice in New York SCHIP
Authors: Liu Hangsheng , Phelps Charles E. , Veazie Peter J. , Dick Andrew W. , Klein Jonathan D. , Shone Laura P. , Noyes Katia , Szilagyi Peter G.
Published: February 2009

Objective. To examine whether low‐income parents of children enrolled in the New York State Children's Health Insurance Program (SCHIP) choose managed care plans with better quality of care.

Data Sources. 2001 New York SCHIP evaluation data; 2001 New York State Managed Care Plan Performance Report; 2000 New York State Managed Care Enrollment Report.

Study Design. Each market was defined as a county. A final sample of 2,325 new enrollees was analyzed after excluding those in markets with only one SCHIP plan. Plan quality was measured using seven Consumer Assessment of Health Plans Survey (CAHPS) and three Health Plan Employer Data and Information Set (HEDIS) scores. A conditional logit model was applied with plan and individual/family characteristics as covariates.

Principle Findings. There were 30 plans in the 45 defined markets. The choice probability increased 2.5 percentage points for each unit increase in the average CAHPS score, and the association was significantly larger in children with special health care needs. However, HEDIS did not show any statistically significant association with plan choice.

Conclusions. Low‐income parents do choose managed care plans with higher CAHPS scores for their newly enrolled children, suggesting that overall quality could improve over time because of the dynamics of enrollment.
Investigation of the different adrenoceptor targets of nebivolol enantiomers in rat thoracic aorta
Authors: Tran Quang T , Rozec B , Audigane L , Gauthier C
Published: February 2009

Background and purpose: Nebivolol is a highly selective β1‐adrenoceptor antagonist with β3‐adrenoceptor agonist properties and is a racemate mixture of D‐ and L‐enantiomers. However, the cellular mechanisms of the effects of each enantiomer are not yet clear and are a matter for debate. The aim of the present experiments was to determine the adrenoceptors involved in the vascular effects of D‐ and L‐enantiomers of nebivolol in rat thoracic aorta.

Experimental approach: Responses to nebivolol enantiomers were evaluated in rings of thoracic aorta from male Sprague‐Dawley rats.

Key results: D‐nebivolol (0.1–10 µmol·L−1), but not L‐nebivolol, significantly shifted to the right the concentration‐response curve to phenylephrine, an α1‐adrenoceptor agonist, in a concentration‐dependent manner. For the following experiments, aortic rings were constricted with endothelin 1 and now both enantiomers produced an endothelium‐dependent relaxation of the rings involving the nitric oxide pathway. This relaxation was not modified by 1 µmol·L−1CGP 20,712A (β1‐adrenoceptor antagonist), but significantly blunted by 7 µmol·L−1L‐74,8337 (β3‐adrenoceptor antagonist). However, only the vasorelaxation induced by D‐nebivolol was significantly reduced by 1 µmol·L−1ICI 118,551 (β2‐adrenoceptor antagonist).

Conclusions and implications: Our results suggest that the nebivolol enantiomers act on different targets. D‐nebivolol induced vasorelaxation by activating β2‐ and β3‐adrenoceptors and antagonizing α1‐adrenoceptors. L‐nebivolol induced vasorelaxation by activating only β3‐adrenoceptors in our model. Our results emphasize that nebivolol is a β1‐adrenoceptor antagonist with several important pharmacological differences from other β1‐adrenoceptor antagonists.

Mandarin translation of abstract
Mild hypothermia does not affect liver regeneration after partial hepatectomy in mice
Authors: Arab Juan Pablo , Pizarro Margarita , Solis Nancy , Sun Hongdan , Thevananther Sundararajah , Arrese Marco
Published: February 2009

Background: The use of mild hypothermia has been suggested to be therapeutically useful in treating acute liver failure. It is not known if hypothermia influences liver regeneration.

Aim: To assess the effect of hypothermia on liver regeneration in mice.

Methods: After partial (70%) hepatectomy (PHx), C57BL6/J mice were randomly assigned to either a hypothermic group or a normothermic group. Controlled mild hypothermia was maintained for up to 3 h after surgery. In addition, assessment of liver mass restitution was examined by studying the induction of key cell cycle proteins (cyclin A, D1 and E) and hepatocyte proliferation [assessment of proliferating cell nuclear antigen (PCNA) protein expression] by Western blotting and DNA synthesis by measuring 5‐bromo‐2‐deoxyuridine (BrdU) incorporation by immunohistochemical techniques 45 h after PHx.

Results: Partial hepatectomy induced a vigorous proliferative response in the remnant livers of both groups of mice (normothermic and hypothermic groups), as evidenced by the induction of key cyclins, PCNA and incorporation of BrdU after PHx. The liver/body weight ratio and both cyclin and PCNA protein expression as well as BrdU incorporation did not differ between the regenerating livers of hypothermic and normothermic groups.

Conclusion: Mild hypothermia does not influence liver regeneration in mice.
Viral suppression correlates with dendritic cell restoration in chronic hepatitis B patients with autologous cytokine‐induced killer cell transfusion
Authors: Shi Ming , Fu Junliang , Shi Feng , Zhang Bin , Tang Zirong , Zhang Zheng , Zhang Hui , Jin Lei , Chen Liming , Wang Huifeng , Akbar Sheikh Mohammad Fazle , Wang Fu‐Sheng
Published: February 2009

Background: Myeloid and plasmacytoid dendritic cells (mDCs, pDCs) are functionally impaired in patients with chronic hepatitis B (CHB). Adoptive immunotherapy can suppress hepatitis B virus (HBV) replication in CHB patients, but whether it can restore the functionality of mDCs and pDCs remains unknown.

Methods: Autologous cytokine‐induced killer (CIK) cells obtained from 14 CHB patients were transfused back to patients, case by case, to observe the effect of CIK‐cell treatment on the frequency and functionality of mDCs and pDCs in CHB patients during a 24‐week follow‐up investigation.

Results: Seven virological responders exhibited a sustained decrease in HBV load after CIK‐cell transfusion; another seven non‐virological responders showed only sustained high levels of HBV load during the 24‐week period following CIK‐cell transfusion. The rate of hepatitis B e antigen loss or seroconversion was also higher in virological responders than in non‐virological responders. Importantly, we found that the frequency and cytokine‐producing capacity of mDCs and pDCs increased significantly in virological responders, but not in non‐virological responders. In addition, these patients exhibited a close correlation between restoration DC subsets and a decrease in HBV DNA load, rather than a change in the alanine aminotransferase level.

Conclusion: Cytokine‐induced killer‐cell treatment reduced HBV DNA load in some CHB patients; the efficiency at least partially correlates with the restoration of frequency and functionality of mDCs and pDCs.
Increased hepatic expression is a major determinant of serum alanine aminotransferase elevation in mice with nonalcoholic steatohepatitis
Authors: Liu Rui , Pan Xiaomin , Whitington Peter F.
Published: February 2009

Background:Serum alanine aminotransferase (ALT) is a biomarker for hepatitis of various aetiologies including fatty liver disease. Increased serum ALT is thought to be related to its increased release from dying hepatocytes.

Aim:We sought to understand the mechanisms by which serum ALT is elevated in a mouse model of experimental fatty liver disease where hepatocyte death is minimal.

Methods:To induce fatty liver disease, female A/J mice were fed a methionine‐choline deficient (MCD) diet for up to 12 weeks. Serum and liver ALT expression and hepatic inflammation, necrosis and apoptosis were assessed and expressed relative to their expressions in control‐diet‐fed mice.

Results:Feeding mice the MCD diet produced hepatic steatosis with minimal hepatic inflammation or necrosis. Liver cell apoptosis was not significantly increased by MCD diet treatment. Conversely, serum ALT activity was approximately four‐fold increased at 12 weeks of diet treatment, and ALT protein expressions in serum were correspondingly increased: ALT1 1.7‐fold and ALT2 1.9‐fold at 12 weeks. The expressions of ALT1 and ALT2 protein in liver increased over 2–12 weeks of MCD treatment. At 12 weeks, liver ALT1 protein was 2.27±0.31‐fold increased and ALT2 protein 4.72±0.48‐fold increased relative to their expressions in the mice fed a diet replete with methionine and choline. Liver ALT mRNA expressions were correspondingly increased: ALT1 mRNA 2.58‐fold and ALT2 mRNA 4.97‐fold at 12 weeks. Linear regression analysis showed a strong correlation between serum and liver tissue expressions for both ALT1 and ALT2.

Conclusions:These findings suggest that induction of hepatic expression significantly contributes to increased serum ALT in this model of experimental fatty liver disease, whereas cell death appears not to.
Prognosis following non‐surgical second treatment in patients with recurrent hepatocellular carcinoma after percutaneous ablation therapy
Authors: Morimoto Manabu , Numata Kazushi , Nozaki Akito , Tanaka Katsuaki
Published: February 2009

Objective: The aims of this study were to identify prognostic factors in patients who received a non‐surgical second treatment for the development of recurrent hepatocellular carcinoma (HCC) after an initial percutaneous ablation therapy.

Methods: We retrospectively studied 147 patients with HCC who had received an initially successful percutaneous ablation therapy. The patients were followed up using computed tomography and/or ultrasound every 3 months and a second treatment was performed for subsequent recurrent tumours.

Results: The 3‐ and 5‐year survival rates of the 147 patients were 90 and 65% respectively. During a mean follow‐up period of 33 months, local or distant tumour recurrences developed in 77 of the 147 patients, and the 3‐ and 5‐year survival rates after a second treatment in these 77 patients were 73 and 44% respectively. Forty‐six of the 77 patients with up to three recurrent tumours received percutaneous ablation therapy for the second treatment, and the remaining 31 patients with more than three (multiple) recurrent tumours received transcatheter arterial chemoembolization for their second treatment. A multivariate analysis revealed the serum α‐fetoprotein level at the time of the appearance of the recurrent HCC (<100 ng/ml vs ≥100 ng/ml, P=0.009) and the number of recurrent tumours (up to three vs more than three, P=0.009) to be independent prognostic factors after the second treatment.

Conclusions: The serum α‐fetoprotein level and recurrent tumour number were prognostic factors following the second treatment in patients with recurrent HCC who had received an initially successful ablation therapy.
The Test‐Taking Strategy Intervention for College Students with Learning Disabilities
Authors: Holzer Mary LaFrance , Madaus Joseph W. , Bray Melissa A. , Kehle Thomas J.
Published: February 2009

Limited research exists related to empirically validated strategies to assist college students with learning disabilities (LD). Given that students with LD demonstrate both fewer test‐taking skills and higher levels of test anxiety than their peers without LD, and poor test‐taking skills contribute to higher levels of test anxiety, such research is critical. The present study examines the effectiveness of the test‐taking strategy on test performance (timed/untimed), degree of strategy usage, and time on test‐taking task, with a sample of university students with LD. This strategy has been successful with adolescents with LD, but has not been studied with postsecondary populations. Results of a multiple baseline design suggested that the strategy was an effective intervention for these students. Implications are discussed.
Nuclear lamins: key regulators of nuclear structure and activities
Authors: Prokocimer Miron , Davidovich Maya , Nissim‐Rafinia Malka , Wiesel‐Motiuk Naama , Bar Daniel Z. , Barkan Rachel , Meshorer Eran , Gruenbaum Yosef
Published: February 2009

The lamin molecule

The supramolecular assembly of lamins

Lamin‐binding proteins

Lamins and aging

Lamins and stem cells

Lamins and cancer

Lamin and viruses

The nuclear lamina is a proteinaceous structure located underneath the inner nuclear membrane (INM), where it associates with the peripheral chromatin. It contains lamins and lamin‐associated proteins, including many integral proteins of the INM, chromatin modifying proteins, transcriptional repressors and structural proteins. A fraction of lamins is also present in the nucleoplasm, where it forms stable complexes and is associated with specific nucleoplasmic proteins. The lamins and their associated proteins are required for most nuclear activities, mitosis and for linking the nucleoplasm to all major cytoskeletal networks in the cytoplasm. Mutations in nuclear lamins and their associated proteins cause about 20 different diseases that are collectively called laminopathies’. This review concentrates mainly on lamins, their structure and their roles in DNA replication, chromatin organization, adult stem cell differentiation, aging, tumorogenesis and the lamin mutations leading to laminopathic diseases.